You are on page 1of 332

DRUG ALLERGY

Daniel Vervloet Michel Pradal Michel Castelain

Daniel Vervloet, Michel Pradal, Michel Castelain Department of Pneumology and Allergy Department of Dermatology Hopital Sainte Marguerite Université de la Méditerrannée Marseille FRANCE

DRUG ALLERGY

-1-

© Daniel Vervloet/Michel Pradal/Michel Castelain ISBN 91-973440-0-1
-2-

TABLE OF CONTENTS
PREFACE .................................................................................. 5 INTRODUCTION ..................................................................... 6 I. II. III. IV. V. VI. DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE ......................................................... 7 ANALGESICS AND ANTI-INFLAMMATORY DRUGS .......................................................................... 37 ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS .......................................................................... 53 CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS ........................................................... 105 DRUGS USED IN CARDIOLOGY ............................ 151 DYES, PRESERVATIVES, ANTISEPTICS ................ 163

VII. PRODUCTS USED IN DIALYSIS ............................. 185 VIII. DIAGNOSTIC AGENTS............................................. 195 IX. X. XI. ENZYMES ................................................................... 209 HORMONES ............................................................... 217 SERA AND VACCINES ............................................. 239

XII. VITAMINS................................................................... 263 XIII. MISCELLANEOUS .................................................... 273 INDEX................................................................................... 306
-3-

-4-

we published a second edition. Seven years after this second edition. Each drug has its own metabolites and mechanisms. we thought it would be useful to publish an updated version enriched with up-to-date knowledge and recent references. Daniel Vervloet -5- . in the hope that this work might be a practical help to allergists facing difficulties in making etiologic diagnoses of drug allergies. in 1992. this time in English. To achieve this. and I thank Pharmacia & Upjohn for its material support. Two years later.PREFACE The first version of this work was originally the thesis that Dr Michel Pradal submitted for his Doctorate of Medicine in 1987. this first version was published in French in 1990. I asked dermatologist and allergist Doctor Michel Castelain to join Doctor Pradal and myself and enrich this work particularly in regard to delayed allergic reactions which often show skin reactions. and received positive reviews among the French allergist community. there is but one general rule: “there are no general rules”. These difficulties reside in the fact that where drug allergy is concerned. and the diagnostic tools must be adapted to the type of reaction caused by the drug in question and to the mechanisms involved. Thanks to Pharmacia & Upjohn Diagnostics Division. I hope that all the information found here will be useful in the day-to-day practice of allergology.

14. This book was written as a practical guide to allergy diagnosis management and the main drugs responsible. in vitro). In a Swiss drug monitoring program. but several remain obscure and this lack of knowledge accounts for the difficulties in differentiating allergy from other side effects. Numerous mechanisms have been implicated. We have tried to specify the main clinical manifestations and risk factors for each of them. where possible.9% appeared to be allergic.7% of the study group reported reliable histories of systemic drug reactions. 5. known mechanisms and management. -6- . Others have stated that allergic drug reactions account for 510% of adverse drug reactions. risk factors. In a French study of 2067 adults aged from 20 to 67 visiting a health-care center for check-up examination. as well as the diagnostic methods (in vivo and. and management strategy for diagnosis and prevention.4 -5. about 17% of hospitalized patients showed adverse drug reactions.INTRODUCTION Estimations of incidence figures for drug allergy show a variation. assessing the incidence.

I DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE -7- .

Amides (group II): aromatic: articaine. propoxycaine. piperocaine. dibucaine. thiophenic: alphacaine Amides are by far the most used today. tetracaine. mepivacaine. procaine. CLINICAL MANIFESTATIONS Reactions unrelated to drugs: — psychomotor: hyperventilation. RISK FACTORS Long term topical application of anesthetic drugs (contact dermatitis). adrenergic — sympathetic stimulation — operative trauma Toxic responses in normal subjects: — central nervous system effects — cardiovascular effects -8- . True allergic reactions are exceedingly rare (less than than 1% of all reactions). vaso-vagal.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE LOCAL ANESTHETICS These drugs anesthetize the area to which they are applied by blocking nerve conduction and preventing depolarization of cell membranes. lidocaine. bupivacaine. cocaine. prilocaine. etidocaine. chlorprocaine. INCIDENCE 2 to 3% of local anesthesias (faints). There are two main families of local anesthetics: Benzoic acid ester group (group I): benzocaine.

Fixed drug eruptions: extremely rare (lidocaine. analgesics. phlebectasias treatment). mepivacaine). Delayed-type hypersensitivity (contact allergy) is more frequent due to the increasing use of topical preparations containing local anaesthetics of the amide group. Few case reports with type I clinical manifestations and positive intradermal skin-tests with 1/10 000 to 1/100 concentrations. but not to the local anesthetic itself: — associated drugs: epinephrine. delayed-type hypersensitivity was reported mainly with esters which are much less commonly used nowadays. -9- . angioedema are exceptional. Type I allergic reactions: anaphylactic shock. The role of preservatives (parabens. No specific IgE found MECHANISMS No absolute demonstration of IgE-mediated reactions.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE Reactions due to either adjuvants or injection. Patch-tests are useful in the diagnosis of type IV manifestations (contact dermatitis) to esters and amides. antibiotics. sulfites) remains controversial. Several of these cases have been reported in chronically treated patients with topical applications of Emla cream (lidocaine + prilocaine). — traumatic subcutaneous emphysema. DIAGNOSTIC METHODS Cutaneous testing Prick-tests are mostly negative. Type IV reactions: contact dermatitis (esters and amides). urticaria. Cross-reactivity among amides is not always encountered. Cases of contact allergy to lidocaïne have been also reported (antihemorroidal cream. sulfites. Historically. Intradermal skin-tests: false positive at 1/10 and pure concentration. parabens.

Kaufmann R. • • • • .J. 1° prick 2° S. Clin. de las Heras M.4): 379-95. Lahoz C.C 5° S.5 ml 1 ml 2 ml undiluted undiluted undiluted undiluted undiluted Alternative therapies: — preservative-free preparations — be aware of cross-reactivity between esters (frequent) and amides (less frequent) — antihistamines (diphenhydramine) may be used as anesthetics — general analgesia (N2O) — hypnosis REFERENCES • • Fisher M. Allergy. ”Alleged allergy to local anaesthetics”.B. “Accidents resulting from local anesthetics. 1991 . 97 (4): 933-7 Wasserfallen J.J. Clin.T.. Figueredo E. True or false allergy ?”. “Adverse reactions to local anesthetics: analysis of 197 cases”. J. Allergy.C 0. “Allergic reaction caused by local anesthetic agents belonging to the amide group”. Lluch M. 99 (3): 427-8 Eggleston S. Immunol.C. 50: 162-5 Sindel L.Allergy. Fernandez M.C 3° S. Frey P.M. 1997 . 1996 .10 - . Care. 1995 .8): 851-7 Gall H. de Shazo R. 30 (7. 25 (6): 611-4 Cuesta-Herranz J. Umpierrez A. Rev.. Anaesth. Immunol. Kalveram C. J.D. ”Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics”. Ann. Clin.C 4° S. Intensive.Allergy. “Understanding allergic reactions to local anesthetics”.W. Pharmacother. Lush L. 1996 . 1997 .M. Bowey C.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MANAGEMENT Challenge test remains the ”gold standard” in local anesthetic reactions. 9 (3.1 ml 0. Many suggested dosing protocols exist: for example (at 15 minute intervals).

INCIDENCE Reported incidence ranges from 1/7000 to 0/23000. MANAGEMENT Avoidance. Respiratory (bronchospasm) and digestive symptoms are unusual. No deaths have been reported. CLINICAL MANIFESTATIONS Essentially cutaneous. Symptoms are usually delayed (a few minutes after injection). urticaria.11 - . 0. rash. MECHANISMS Non specific histamine-release. mucosal (pruritus.2% in dentistry. DIAGNOSTIC METHODS None. edema) and cardiovascular.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE HYPNOTICS BARBITURATES METHOHEXITAL Methohexital is a barbiturate derivative used for brief surgical procedures. .

R. Possible delayed reactions. generalized erythema. THIOPENTAL Frequently used hypnotic. INCIDENCE 1/23000 to 1/29000 administrations. “Acute allergic reaction associated with methohexital anesthesia: report of six cases” J.D. O’Day R. Scientific results of 4379 administrations. Haematological: haemolytic anemia. Deaths rarely reported. “Adverse reaction to methohexitone and gallamine”. 5: complications”. 1972 . barbiturate anesthetic. Surg. . “Severe histamine-mediated reaction to rectally administered methohexital”. 30: 906-9. fixed drug eruption. Dent. 1981 .L.. Anaesthesia. RISK FACTORS Previous exposure (94%).M. 36 (1): 40-4 Driggs R. angioedema. Cutaneous: flush. Sedat.12 - . “Methohexitone in dentistry. Thompson I.L. 1982 . 11 (2): 51-7 Harrison G.A.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE REFERENCES • • • • Liu L. Anaesth. Liu P.. Moss J. Anesthesiology. 1984 . 61 (1): 95-7 McDonald D. Female gender (gender ratio 3/1) CLINICAL MANIFESTATIONS General: anaphylactic shock Respiratory: bronchospasm. Oral.

Fr.M.A. encompassing and including the attached hetero atom. Harle D. 12 (2): 173-81 Baldo B. MECHANISMS Immediate hypersensitivity: Usually IgE-mediated. BA Baldo ed. 1991 ...A.Reanim. which specificity is confirmed by hapten inhibition studies. Possible involvement of non-specific histamine release. . Smal M. Harle D. Allergenic determinants: pentyl and ethyl groups attached to position 5 on the pyrimidine ring nucleus and the secondary region of the ring. In: Molecular approaches to the study of allergens. Karger. Halasi S. Wajon P.M. 1993 . Fisher M. Ann. Monographs in allergy.A.A. Harle D.A.G. Detection of thiopentone-reactive IgE antibodies by the RAST method . 16: 493-8. Fisher M. 1990.M. Rev.Anaesth.13 - . Can. au thiopental et aux opiacés”.28. Dilution 1/1000 to 1/10 of 2. Allergy.5% thiopental. ”Fixed drug eruption associated with anaesthesia”. 42 (7): 628-30 Baldo B. “Drug allergenic determinants (pp 11-51)”. Clin. Fisher M. Baldo B. Vol.Anesth.G. Basel. 1995 .A. REFERENCES • • • • • Bremang J.G. MANAGEMENT Avoidance. ”Detection of thiopentone reactive IgE antibodies following anaphylactoid reactions during anaesthesia”. “Allergy to thiopentone” Clin. 1986 . Allergy. Baldo B.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE DIAGNOSTIC METHODS Cutaneous testing Prick-tests or intradermal tests. 9 (3-4): 295-308. “Diagnostic de l’allergie IgE dépendante aux curares.J.

Martin A. Watkins J. DIAGNOSTIC METHODS No in vivo or in vitro diagnostic method currently available.L. Few cardiovascular and respiratory effects. MECHANISMS Etomidate is a poor histamine releaser. 42 (3): 323-4. 1988 . 1983 . INCIDENCE Exceedingly rare.J.R. “Anaphylactoid reaction following the use of etomidate” . an “immunologically safe” anaesthetic agent”. CLINICAL MANIFESTATIONS Essentially cutaneous and gastrointestinal. 38 (S): 34-8 . Anaesthesia. “Angioneurotic edema following etomidate/lignocaine”. MANAGEMENT Avoidance. 1987 . “Etomidate. Tolhurst-Cleaver C.. Anaesthesia.14 - . REFERENCES • • • Fazackerley E. Anaesthesia.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE NON-BARBITURATES ETOMIDATE Short-acting general anesthetic. 43 (1): 953-4.J. Bricker S. Watkins J.

Cutaneous: rash.15 - . MANAGEMENT Avoidance..Anesth. 1990 .007% to 0. 47: 624-7 PROPANIDID Short-acting general anesthetic used especially for tooth extractions. Breuil K.Fr. ”Allergie à la kétamine” . Ann. Swider M. CLINICAL MANIFESTATIONS General: anaphylactic shock. INCIDENCE Very high: 1 out of 500 to 1 out of 700 anesthesias.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE KETAMINE INCIDENCE Exceedingly rare. J. DIAGNOSTIC METHODS Cutaneous testing Intradermal skin-tests: 0.05 ml of Ketalar 5% or ketamine base 1/ 100 and 1/10 positive in one patient. “Reaction to ketamine: anaphylactoid or anaphylactic ? “ Br. urticaria. REFERENCES • • Karayan J.T.13%. Anaesth. MECHANISMS Probable IgE-mediated hypersensitivity. 1975 . 9 (4): 396-7 Mathieu A. .Reanim.. Lacoste L. Severe reactions: 0. Respiratory: laryngospasm. Goudsouzian N.

Christmas J. MANAGEMENT Prohibited in many countries since 1983.L. 39: 470-3. 32 (5): 252-3. Dermatological: various delayed reactions. 1984 . Rev. ”Reaccion anafilactica a la propanidida”.. Anesthesiol Reanim. diarrhea. Herrera J. Respiratory: bronchospasm. de las Mulas M. which activates the classical or alternative complement pathway. REFERENCES • • Guerrero J. 1985 . Digestive: nausea. glycerol) used in anesthesia. Non-specific histamine release. Malagon F.2% of peroperative anaphylactic shocks in France. vomiting.. releasing C3a anaphylatoxin and leukocyte migration.C. INCIDENCE 1/60 000 1.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE CLINICAL MANIFESTATIONS General: anaphylactic shock.P. . Blood histamine measurement at the time of the accident. Avoidance. MECHANISMS Responsibility of solvent: cremophor E.16 - . Anaesthesia. DIAGNOSTIC METHODS Complement assay at the time of the accident (difficult). “Immune reaction to propanidid”. PROPOFOL Propofol (2-6 diisopropylphenol) is an alkyl phenol in a lipid vehicle (soybean oil. egg lecithin. Trevilla J.M. Esp.

MANAGEMENT Do not use propofol in muscle relaxant-allergic patients. Cutaneous: urticaria. ”Anaphylactoid reaction to propofol”.Fr. angioedema. Ann.. Positive in most patients with anaphylactic reactions. Konieczko K. 1992 .C. erythema. Do not use atracurium with propofol (high frequency of anaphylactoid reactions). Intradermal skin-tests from 1 µg/ml to 100 µg/ml (1/1000 to 1/ 10). Ocular: conjunctival chemosis. Allergy to muscle relaxants. 77 (2): 384-6 .17 - . DIAGNOSTIC METHODS Cutaneous testing Skin prick-tests. 1994 . Anaesthesia. facial edema.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE RISK FACTORS Previous drug allergy.A.Anesth. MECHANISMS IgE-mediated hypersensitivity in most cases. “Anaphylaxis due to propofol”. Respiratory: bronchospasm.Reanim. Specific IgE (RIA): positive in 10/14 propofol allergic patients. Association with atracurium.. Propofol contains 2 isopropyl group that may act as the epitopes. Anesthesiology. 47 (10): 864-5 de Leon-Casasola O. Avoidance. Leukocyte-specific histamine release: positive in 3/5 propofol allergic patients. CLINICAL MANIFESTATIONS General: anaphylactic shock. ”Utilisation du Diprivan* chez le patient allergique” .P. Lema M.J. 1992 . REFERENCES • • • Laxenaire M. Weiss A. 13 (4): 498-502 Mc Hale S.

Anesthesiology. “Anaphylactoid reactions following propofol-atracurium sequence (letter . Gueant J.H.A.18 - . 77 (2): 275-80 Mc Leskey C. macular and maculopapular eruptions. “Lifethreatening anaphylactoid reactions to propofol (Diprivan*)” . INCIDENCE Very low. Moneret-Vautrin D. morphine monomethyl ether) belongs to the opiod group.J..L. scarlatiniform rashes. 1990 . Can. pseudoscarlet fever. . fixed drug eruption (occupational dermatitis from codeine has been reported). erythema multiforme. comment)”.Anaesth. angioedema. 37 (8): 946-7 MORPHINOMIMETICS CODEINE Codeine (methylmorphine. Mata-Bermejo E. urticaria. The main indication of codeine is as a cough suppressant. Cutaneous: pruritus. 1992 . erythema nodosum. RISK FACTORS Intravenous use in children. CLINICAL MANIFESTATIONS General: arterial hypotension (intravenous route).DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE • • Laxenaire M.C. Respiratory: bronchospasm.

A. Dermatitis. Fernandez L. Garrett C. (fixed drug erup tion). 32 (2): 120 de Groot A. Garcia-Abujeta J.F. codeine phosphate 0. Anaesthesia.P. rash). Marshall A. “Generalized dermatitis due to codeine”. . A report of 3 cases”. “Adverse reactions to intravenous codeine phosphate in children. urticaria). The risk of cross-sensitivity is higher with morphine congeners than with phenylpiperidine or methadone-type agents.G. 14 (4): 209-14. ganglionar blockade and histamine release could explain hypotension. 1995 .001% to 0. MANAGEMENT Avoid intravenous use in children. Conemans J. Jerez J. Dermatitis.19 - .L.J. 1996 .1% aq. REFERENCES • • • • Gonzalo-Garijo M.C. MECHANISMS Non immunological histamine release (pruritus. 38 (1): 40-3. 1986 .033% aq. Oral challenge tests (fixed drug eruption). Contact. 1983 .C. (urticarial rash).. Delayed-type hypersensitivity (urticaria.O. Revenga-Arranz F. Shanahan E. Maquiera E. “Allergic urticarial rash from oral codeine”.Dermatol. Llaca H.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE DIAGNOSTIC METHODS Cutaneous testing Skin patch-tests: codeine phosphate 0. 135 (3): 498-9 Rodriguez F. Contact. ”Fixed drug eruption due to codeine (letter)”.. Br. . Vasomotor depression.

Pharm. Clin. RISK FACTORS Previous sensitization to another phenylpiperidine drug. 33 (1): 75-8. Hirshman C. Soc.. angioedema. Respiratory: bronchospasm. Anderson L.20 - .A. used exclusively in anesthesia. 1992 .DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE FENTANYL Major morphinomimetic analgesic. 1986 . “Diffuse rash associated with transdermal fentanyl”. Mc Millan J.5 ng/ml to 5 ng/ml (2 cases reported)..A. MECHANISMS Fentanyl does not induce non-specific histamine-release. J. Hanifin J.M. . “Anaphylactic reaction during anaesthesia associated with positive intradermal skin test to fentanyl”.J. 11 (3): 222 Bennett M. Ebertz J. diffuse rash (transdermal fentanyl).C. REFERENCES • • Stoukides C. Stegman M. Can. CLINICAL MANIFESTATIONS General: anaphylactic shock. DIAGNOSTIC METHODS Cutaneous testing Intradermal skin-tests positive from 0. IgE-mediated hypersensitivity (positive skin-tests).K. Cutaneous: urticaria. Anaesth.M. INCIDENCE Extremely rare. MANAGEMENT Avoidance.

1982 .DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE • Pevny I.C.21 - . 1978 . “Hypersensitivity to meperidine”. Non-specific histamine release (meperidine is one of the strongest histamine-releasers of all anaesthetic agents).. Kripke B. Danhauser I.E. CLINICAL MANIFESTATIONS General: anaphylactic shock. Levy J. Rockoff M.A. Analg.H. 1987 . MANAGEMENT Avoidance. “Histamine release by 4 narcotics: a double blind study in humans”. Bloom B. MECHANISMS IgE-mediated hypersensitivity.P. “Anaphylaxis to meperidine”. 66: 723-30. 61 (3): 301-3 Waisbren B. Immediate skin-tests may be positive (do not exceed a concentration of 1/100000).J. Anaesthesist. Anesth. Flacke W. 1981 . Cutaneous: flush. 30: 400-4 MEPERIDINE . INCIDENCE Very low. DIAGNOSTIC METHODS Specific IgE (RAST): positive in a few cases of anaphylaxis.. JAMA..PETHIDINE Narcotic analgesic frequently used for analgesia and general anesthesia (induction). Van Etton A. REFERENCES • • • Flacke J.W. Analg.A. 239 (14): 1395 . wheezing. Respiratory: cough. ”Anaphylaktisher schock wahrend der narkose mit positivem hauttest auf fentanyl und alloferin”. urticaria. Anesth.

1989 . with a hydroxyl group at C6 and a methyl substituent attached to the N-atom. Dick W. DIAGNOSTIC METHODS Cutaneous testing Intradermal skin-tests: positive 1/100 000 (solution of 10 mg/ ml) Specific IgE (RIA morphine-sepharose) positive in a patient. Case report: implication of IgE antibodies that react with morphine and codeine and identification of an allergic determinant”. 31: 463-5 • . historically chief among the opioids . INCIDENCE Extremely rare. Baldo B.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MORPHINE Morphine.22 - .M. CLINICAL MANIFESTATIONS General: anaphylactic shock. Cross-reactivity with codeine and other opioids may occur. REFERENCES • Harle D.J. Cutaneous: urticaria. Respiratory: bronchospasm. MANAGEMENT Avoidance. cancer).G. is widely used as an analgesic in various clinical situations (postoperative period. Anesthesiology. IgE-mediated hypersensitivity: the morphine allergenic determinant comprises the cyclohexenyl ring. Coroneos N. ”Anaphylaxis following administration of papaveretum. Anesthesist.. MECHANISMS Nonspecific histamine release .A. Fisher M. . 1982 . “Anaphylactoide reaktion nach intravenöser injektion von morphinum hydrochloricum”. 71 (4): 489-94 Rossi R.

Digestive: diarrhea. “Hemodynamics. Anesthesiology. CLINICAL MANIFESTATIONS General: collapse.e. 55: 329-31 MUSCLE RELAXANTS Family of agents widely used in general anesthesia to achieve muscle relaxation. Previous allergic reactions to muscle relaxants. RISK FACTORS Use of muscle relaxants with a “flexible chain”. cardiac arrest.R. High diagnostic performance if conducted with proper concentrations. Respiratory: bronchospasm. Muscle relaxants account for 60 to 70% of all allergic reactions occurring during general anesthesia. Pancuronium. Female gender (80% of cases).23 - . Rocuronium. Mivacurium. Vecuronium. Haematological: disseminated intravascular coagulation. plasma histamine and catecholamine concentrations during an anaphylactoid reaction to morphine” . No involvement of atopy. 10% of these reactions are fatal. Dermatological and mucosal: flush. arrhythmia. Atracurium. diffuse erythema. i. for intradermal skin testing: . Cisatracurium INCIDENCE One anaphylactic shock out of every 10000 general anesthesias. 1981 . Suxamethonium. DIAGNOSTIC METHODS Intradermal skin tests or prick tests (using undiluted muscle relaxants). tachycardia. angioedema.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE • Fahmy N. diffuse urticaria.

DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE ≤100 µg/ml for suxamethonium. Specific histamine release. ≤100 µg/ml for rocuronium ≤2 µg/ml for mivacurium ≤400 µg/ml for vecuronium. ≤200 µg/ml for cisatracurium Subjects remain positive for several years (up to 30 years). ”Flexible” molecules with simple carbon chains (Suxamethonium) can stimulate sensitized cells more strongly than rigid molecules (Pancuronium). antiseptics. The rigidity of the chain linking quaternary ammoniums plays a triggering role in allergic reactions. Some reactions are not based on an IgE mechanism. ≤10 µg/ml for atracurium. Leukocytes from subjects with a history of anaphylactic accidentsbrought into contact with increasing concentrations of muscle relaxants in vitro. Role of quaternary ammonium ion determinants. ≤200 µg/ml for pancuronium. cosmetics. . MANAGEMENT Use safer muscle relaxants such as Pancuronium rather than Suxamethonium. release histamine which can be measured (dose-dependent response). but on a nonspecific histamine release effect. antibiotics. Mediator release from target cells. and soaps with a quaternary ammonium ion structure).24 - . Histamine release from basophils involves IgE antibodies. MECHANISMS Immediate IgE-mediated hypersensitivity: detection of IgE specific to muscle relaxants (quaternary ammonium ion determinants) accounting for cross reactions between different curarizing anesthetics and reactions upon first contact with a muscle relaxant (antihypertensors. Detection of anticurare and antisuxamethonium IgE antibodies by RAST methods.

Alazia M. Rev. Pradal M. Patients with a history of anaphylactic reactions: Conduct preoperative skin-tests with all muscle relaxants. 1996 . Clin. “Is systematic preoperative screening for muscle relaxants and latex allergy advisable ?”. 50: 374-7 Birnbaum J. Didier J. Sansarricq M. Ann. “Prick-tests in the diagnosis of anaphylaxis to general anaesthetics”. J. 1995 . Clin.. in press Nicklas R.25 - . Anesth. “Anaphylaxis during general anesthesia. (good negative precitive value). “ Substances responsables des chocs anaphylactiques peranesthesiques”. Br. 15: 1211-8 Porri F. Gouin F. Vervloet D. No preventive treatment can avoid anaphylactic reactions REFERENCES • Porri F. Clin. 1991 . 1998 . Clin. 1991 . 1987 . the intraoperative period and postoperative period”. J. “Nonspecific histaminereleasing properties of general anesthetic drugs”. Allergy.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE Systematic screening-tests in a general population are not advisable due to the poor positive predictive value of the tests. Lanteaume A. Fr. (Frequent cross-reactivity between 2 or more muscle relaxants) — If skin-tests are positive. Allergy. Allergy.A. 9 (3-4): 269-80 Leynadier F. Rud C.M. the agents may be administered . Guilloux L.. Mazzarella B. Exp. 9 (3-4): 281-93 Marone G. Dry J.. Stellato C. Allergy. Didelot R. Vervloet D. Allergy. Vervloet D. do not use the offending muscle relaxants. 101: S512-6 Laxenaire M. — If skin-tests are negative. Lemiere C. Mastronardi P. Anaesth.C et le groupe d’étude des réactions anaphylactoïdes peranesthesiques. “Allergy to muscle relaxants”. Rev. Charpin D. 59: 683-9 • • • • • • . 1998 . Immunol. ”Prevalence of muscle relaxants sensitivity in a general population: implications for a preoperative screening”. Birnbaum J. Charpin D..

MECHANISMS Unknown. propylene glycol. The most common offending molecules are diazepam and flunitrazepam. was used as the solvent (not in France). CLINICAL MANIFESTATIONS General: anaphylactic shock. widely used against seizures and as a muscle relaxant. angioedema. sodium benzoate). . bronchospasm. Major role of solvents (chromophor E. Cutaneous: urticaria. purpura. Respiratory: dyspnea. DIAGNOSTIC METHODS Cutaneous testing Usually negative. flush..DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE BENZODIAZEPINES DIAZEPAM Leading benzodiazepine.26 - . Positive reintroduction test (with caution) if necessary. INCIDENCE Low in France but one injection out of 1000 when cremophor E. polymorphous erythema.L. collapse. In one case patch-test positive. hives. In one case prick-test positive with solvent. Renal: allergic interstitial nephropathy.L.

Manoury B. Non-specific histamine release.R. DIAGNOSTIC METHODS None. “Complement-mediated reactions to diazepam with cremophor as solvent (Stesolid M. Gillon J. 1980 .DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE Other hypothesis: Immediate IgE-mediated hypersensitivity: Prausnitz-Kustner test positive in one case. Complement activation. The active metabolite common to all benzodiazepines is desmethyldiazepam. . REFERENCES • • Daumal M. Br. Pila Y. which appears to be an antigenic molecule and accounts for cross reactivity among different benzodiazepines. INCIDENCE Extremely rare.27 - . MANAGEMENT Manifestations are usually observed when cremophor E. Anaesth.. (rôle du diazépam et de la succinylcholine”). 52: 77-9 . J.C. Respiratory: bronchospasm. rash. Cutaneous: angioedema. MIDAZOLAM Midazolam hydrochloride is a short-acting imidazobenzodiazepine used in anesthesiology. 32 (4): 313-5. Stoffersen E.S. 1984 . Huttel M. CLINICAL MANIFESTATIONS General: anaphylactic shock.)” . Guilbert J. is used as a solvent (not used in France).L. Line B. ”Syndrome de detresse respiratoire aigue après choc anaphylactique.M. Schou Olesen A. Cahiers d’Anesthésiologie.

. Yokota K. REFERENCES • • Fujita Y. 1992 .28 - .. “Midazolam-induced angioedema and bronchoconstriction”. Cutaneous: angioedema (swollen tongue). INCIDENCE Exceptional. Crit.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MECHANISMS Unknown. Elstad M. 20 (2): 307-8 NEUROLEPTICS DROPERIDOL Droperidol is a neuroleptic drug (butyrophenone class) frequently used postoperatively as an antiemetic and a sedative.E. 79 (4): 811-2 Yakel D. Whittaker S. ”Anaphylactoid reaction to midazolam” . Ishikawa H. Anesth. Care. Diagnostic methods Cutaneous testing Intradermal skin-tests (1/1000) positive in 2 patients. Respiratory: bronchospasm.L Jr.R. . CLINICAL MANIFESTATIONS General: anaphylactic shock. MANAGEMENT Avoidance. erythema of face and torso. RISK FACTORS Phenothiazine hypersensitivity. 1994 . Res. Analgesia.

Intensive. Care.J. Med. 1996 . 3 (6): 440-2 . Murray G. Increase in serum histamine due to inhibition of histamine-Nmethyltransferase. Deaths reported. Michel A. 1984 .. Ann. Pruneta R. . MANAGEMENT Avoidance. They are produced by Leuconostoc mesenteroides. Reanim. “Deux cas d’anaphylaxie au droperidol” . Saban Y. ”Angio-oedema with droperidol”. 1/70000 grade III/ IV with hapten inhibition. Intesive. Klingelberger C. Ann. glucose polymers. Anaesth. INCIDENCE 1/2000 grade III /IV without hapten inhibition .. Care. 1985 .P.F.29 - . thromboembolic prevention and as distention and irrigating fluids for various endoscopic procedures. Pourcher N. Emerg. “Angioedema associated with droperidol administration”. “Tongue-swelling with droperidol”. PLASMA SUBSTITUTES DEXTRANS Dextrans. Anesthesiology. REFERENCES • • • • • Palombaro J. Fr. 21 (3): 375 Clark R.E. 21 (6): 898 Moss J. Occelli G. Anaesth. Anesth. 27 (3): 379-81 Corke P. “Droperidol inhibits histamine N-methyl transferase”.J. Maestracci P.M. Henry D.M.M.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MECHANISMS IgE-mediated hypersensitivity (positive cutaneous tests. 1993 . 63: A303. Verburg K.. one case with positive Prausnitz-Kustner test). 1993 . are used as plasma expanders.

flushing. joint pains.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE RISK FACTORS Atopy (grade I and II reactions). DIAGNOSTIC METHODS Cutaneous testing (usually negative). Grade I: skin manifestations (urticaria. MECHANISMS The majority of adverse reactions are mild anaphylactoid. When dextran is infused into a patient with high titer of dextran-reactive antibodies. oliguria. immunecomplexes are generated and lead to the release of mediators. . macular rash. Respiratory: dyspnea. vomiting. Dextran reactive antibodies (passive hemagglutination). High levels of dextran-reactive antibodies (grade III and IV reactions). back pain. mild fever. Classification of dextran-induced adverse reactions. caused by naturally occurring IgG class dextran-reactive antibodies . Cutaneous: general itching. bronchospasm. angioedema.30 - . Grade II: mild to moderate hypotension. The severe reactions are immunogenic (immune-complex mediated) anaphylactic reactions. urticaria. Grade IV: cardiac and/or respiratory arrest. Grade V: death. erythema). FEVER. Other: nausea. flush. Clinical manifestations GENERAL: ANAPHYLACTIC SHOCK. increased clotting time. pulmonary edema. Grade III: severe hypotension. gastrointestinal disturbances. shock. tightness of chest. wheezing. convulsions. Dextran specific IgG and IgM (ELISA): the presence of a high level of specific IgG antibodies is a major risk factor. nonimmunogenic reactions. coughing.

9 (3-4): 397-414 GELATINS Gelatins are used as plasma expanders in emergency situations. Fluid gelatins are produced by hydrolysis of collagen and chemical modification: . ”Prevention of dextran anaphylaxis. Hedin H. 6 (4): 167-71 Ljungstrom K. 7 (1): 71-3 Ring J. 18 neonatal deaths and 7 cases of neurological impairment have been reported in France..P. Ten years experience with hapten dextran”. Int.G. “Safety of dextran in relation to other colloids-ten years’ experience with hapten inhibition”. This leads to a 35-fold reduction of severe (grade III/IV/V) reactions to clinical dextran. Allergy.. C.M. 20: 206-10 Barbier P. Saf. “Anaphylactic reactions to high molecular weight dextran during hysteroscopic surgery”. 95 (2): 633-4 Huhn A. 1997 .A. dextrans should be avoided and replaced by gelatins or crystalloid solutions due to the risk to the fetus of anaphylactic shock in the mother (antidextran IgG cross the placental membrane). Arch. If more than 15 minutes have passed following the injection before starting the infusion. Infusionsther. Clin. Clin. Allergy. J.. “Probable grade IV dextran-induced anaphylactic reaction despite hapten inhibition”. “Fetal risks with dextrans during delivery”. 1992 .G. Drug. 1993 .R. Coureau C. Jonville A.J. Ljungstrom K. Allergy. 1995 . Immunol.31 - . Transfusionsmed. another dose of dextran 1 should be given. 1995 . 20 ml of Promit (dextran 1 (15%)) must be injected prior to infusion of clinical dextrans. 1991 .DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MANAGEMENT Hapten inhibition. “Anaphylactoid reactions to intravenous solutions used for volume substitution”. REFERENCES • • • • • • Hedin H. 113 (1-3): 358-9 Bircher A. Immunol. Concerning preloading in pregnant women prior to epidural analgesia. Rev. Berglund A. Autret E..N.

146% to 0. flush. instant pudding. . Male gender. Respiratory: bronchospasm. arterial hypotension. V death.048% of serious manifestations).852% administrations (0. INCIDENCE Gelatins linked to urea: 0. sweets/foods such as liquorice. ENT: sneezing. Oxypolygelatins: 0. III same + vomiting.066% to 0.617% of administrations. juices). corned beef. instant whipped cream.338 % of administrations (0. fruit yogurt.016% of serious manifestations). CLINICAL MANIFESTATIONS General: anaphylactic shock Cutaneous: urticaria +++. diarrhea + bronchospasm + cyanosis + shock IV same + respiratory arrest + cardiac arrest. Classification of allergic reactions: I urticaria.32 - . Drug allergy.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE — succinylation (modified fluid gelatin). — cross-linking with glyoxal and subsequent degradation by oxidation and heating (oxypolygelatin). — cross-linking with hexamethylene diisocyanate (urea linked gelatin). Modified fluid gelatins: 0. RISK FACTORS Gelatin allergy (gummy bears. brawn. marshmallows. II same + nausea +dyspnea + tachycardia.

1994 . 13 (3): 301-10 Duffy B. “Anaphylactic reactions to modified fluid gelatins”. Ann. 1994 . mécanismes.33 - . Allergy. ”Cardiac arrest following Haemaccel”. 19 (1): 77-80 Vervloet D. 22 (1): 90-2 Ring J. Charpentier C. 1991 . 1983 . facteur de risque. Intensive. Allergy.N. Dugue P. Fuller W..L. Rev. Kleinhans D. Senft M. MANAGEMENT Antihistamines H1 and H2 are useful in prevention of minor cutaneous reactions. ”Réactions anaphylactoïdes aux substituts colloidaux du plasma: incidence.. 1989 . Histamine-release by blood basophils.Anesth. 71: 535-40 • • • • . Anaesth. Avoidance of gelatins. MECHANISMS Direct histamine-release (urea linked gelatins by excess of diisocyanate) IgE-mediated hypersensitivity. Allergy. Feldman L. “IgE-mediated allergic reactions to fruit gums and investigation of cross-reactivity between gelatin and modified gelatincontaining products”. “Anaphylactoid reactions to intravenous solutions used for volume substitution”. Harding J. Exp. Care. Charpin J. Clin.Reanim. Immunol. Enquête prospective multicentrique française”.Fr.R.C.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE DIAGNOSTIC METHODS Cutaneous testing Intradermal skin-tests: positive from 1/1000 to 1/10 in a few patients with anaphylactic shock Specific IgE (UniCAP ®/Pharmacia CAP System™). Clin. J. REFERENCES • Laxenaire M. Clin.L. Peake S.. Wahl R. 9(3-4): 397-414. Arnaud A.

IgG. pruritus: beginning 1 to 3 weeks after HES infusion .085% (grade I to IV) 0. Intradermal skin-tests 0. IgA (ELISA) IgM are found 1/1004 in patients following administration of starch with no clinical significance. Pruritus: direct stimulation of cutaneous nerves by HES deposits in macrophages and endothelial cells. DIAGNOSTIC METHODS Cutaneous testing Skin prick-tests. related to the type (concentration and molecular weight of HES ) and total infusion dose .058% to 0. pentastarch (250 000 D) hetastarch (480 000 D) INCIDENCE 0. Cutaneous: rash. 6 months after anaphylactic shock. Anti-HES IgM. . lasted 6 weeks to 6 months . IgA. IgM. One patient with high titers of IgG. Complement activation. urticaria.05 ml Hetastarch 1/10 and pure: seldom positive.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE HYDROXYETHYLSTARCH (HES) Hydroxyethylstarch or hetastarch is a synthetic colloid derived from amylopectin used as plasma substitute.34 - .006% (grade III/IV) Pruritus: 10 to 40% CLINICAL MANIFESTATIONS General: anaphylactic shock. MECHANISMS Poor histamine-releaser. Non IgE-HES specific antibodies.

Niklas M. 1990 . “Persistent erythema and pruritus.. Kraft B.Anesth. 1995 . Feldman L. Enquête prospective multicentrique française”. Br... 1994 . Popple A. Lancet. “Reactions anaphylactoïdes aux substituts colloidaux du plasma: incidence. Schimetta W. 346 (8966): 49-50 Laxenaire M. 13 (3): 301-310 Cullen M.H. Kaufmann R. Anaesthesia.Fr. Ann. .DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE MANAGEMENT Avoidance. 1996 . Lauterjung L. 1998 . 45 (12): 1041-42 • MANNITOL Mannitol is a hexahydric alcohol closely related to the hexose sugars . Gerlach E. REFERENCES • • • • • Dieterich H. INCIDENCE Very low. Singer M. Polz W. 1996 . which has been used in a variety of clinical situations for its osmotic diuretic qualities (chemotherapy. CLINICAL MANIFESTATIONS General: anaphylactic shock.W. ”Hydroxyethylstarch antibodies in humans: incidence and clinical relevance”. 134 (2): 353-7 Kreimeier U. facteurs de risque. “Clinical and pathophysiological aspects of hydroxyethylstarch-induced pruritus: evaluation of 96 cases”. Boehncke W. Peter K.Dermatol. cerebral edema).D. “Anaphylaxis due to hydroxyethylstarch reactive antibodies”. Anesth. Sirtl C. 192 (3): 222-6 Cox N. Schultz K.. following the use of a hydroxyethylstarch plasma expander”. Analg. Dermatology.J. RISK FACTORS Atopy. Messmer K. Charpentier C. “Severe anaphylactoid reaction to hydroxyethylstarch”.C.J. mecanismes. Peter K.H. Laubenthal H.Reanim. 86 (5): 1123-6 Gall H. with a confluent histiocytic skin infiltrate.35 - . Christ F. Fewer than 10 cases reported.J. Kraft D.

1985 .Y. Can. 1992 . Drug. DIAGNOSTIC METHODS Cutaneous testing. Pharm. “Immediate hypersensitivity to mannitol: a potential cause of apparent hypersensitivity to cisplatin”.P. Lichtenstein L. specific histamine-release. “In vitro basophil histamine-release induced by mannitol in a patient with mannitol-induced anaphylactoid reaction” . 69 (5): 562-3 Mc Neill I. Keogh J. 47 (1): 61-2 Ackland S.1): 578-83 Lamb J. “Anaphylactoid reaction to mannitol”. J. bronchospasm. No specific IgE. Intell. Kagey-Sobotka A. 1979 . pruritus.R. Respiratory: sneezing. Immunol. 26 (5): 435-6 . MECHANISMS Hyperosmolar solutes are capable of inducing non-cytotoxic basophil histamine release.36 - . Cancer. Specific histamine-release (RIA method) positive in a patient with anaphylactic shock. Clin. chest tight-ness. Anaesth.... Rep. J. Wuthrich B. Soc. periorbital edema. 1985 . ”Peranaesthetic anaphylactoid shock due to mannitol”. “Hypersensitivity reaction to mannitol”. Allergy.A. Treat. REFERENCES • • • • • Schmid P.M. Allergy. MANAGEMENT Avoidance. 1984 . rash.DRUGS USED FOR ANESTHESIA AND INTENSIVE CARE Cutaneous: urticaria. Clin. Intradermal skin-tests positive at 1/100. IgE-mediated hypersensitivity: positive cutaneous tests.D. 19 (7-8): 552-3 Findlay S.L. 73 (5.. Hillcoat B.

37 - .ANALGESICS AND ANTI-INFLAMMATORY DRUGS II ANALGESICS AND ANTIINFLAMMATORY DRUGS .

MECHANISMS Acetaminophen possesses a weak cycloxygenase inhibitor action. but does exist. . (30%) . Specific acetaminophen allergy is probably exceptional. Rhinoconjunctivitis. CLINICAL MANIFESTATIONS Urticaria (61% of reactions). maculopapular exanthemas. (30%): positive in 3 patients with delayed manifestations. 250 mg. Patch-tests: paracetamol syrup in pet. Aspirin-sensitive patients may react to high doses (> 650 mg) of acetaminophen. (30%). INCIDENCE Uncommon in non-aspirin sensitive patients. which suggests cycloxygenase inhibition. DIAGNOSTIC METHODS Cutaneous testing. fixed drug eruption. pure paracetamol powder in pet. pruritus. Anaphylactic shock Bronchospasm. acute generalized exanthematous pustulosis. pigmentary purpura.ANALGESICS AND ANTI-INFLAMMATORY DRUGS ACETAMINOPHEN Acetaminophen is a widely used analgesic and antipyretic.38 - . angioedema. 750 mg) at 30 minute intervals. Skin prick-tests: one positive case reported following generalized urticaria. 100 mg. paracetamol suppository in pet. 500 mg. Specific IgE: one case reported following generalized urticaria. Type I hypersensitivity to paracetamol is rare. Oral challenge (50 mg. exfoliative dermatitis.

Dermatology. Munoz M. Ann. 1992 .. Allergy. “Adverse reactions to acetaminophen. 1996 . Use oral provocation challenge to ascertain that analgesic substitutes are safe . Laso M. 96: 480-5 Leung R. “Acetaminophen anaphylaxis with aspirin and sodium salicylate sensitivity: a case report”. Christiansen S..A. One case of aseptic pustular eruption due to paracetamol with worsening of lesions.”Paracetamol anaphylaxis” . Asthma.. “Delayed hypersensitivity reaction to paracetamol (acetaminophen)”. Allergy.D.. Huyghens L. “Acute generalized exanthematous pustulosis induced by paracetamol. Suys E. Pipeleers-Marichal M. REFERENCES • • • • Mendizabal S. J. Clin. (appearance of toxic epidermal necrolysis) and severe hemodynamic disturbances following intravenous use of propacetamol hydrochloride. Immunol. 1998 .ANALGESICS AND ANTI-INFLAMMATORY DRUGS MANAGEMENT Cross reactivity between acetaminophen and other NSAIDs is conflictual (0 to 34%).D.J. van Strubarq A. Gaspar A.L. 77: 473-4 Settipane R. Mathison D. “Prevalence of cross sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects”. Immunol. 1995 .C. 1996 . Allergy. 193 (4): 338-41 Ibanez M.E. Exp. J. Schrank P. Asthma.S. Carvalho F.I. Diez Gomez M. 51 (2): 121-3 Schwarz N. Ham Pong A. Clin.39 - .. Low frequency has been reported when acetaminophen challenge doses of 650 mg or less are administered (0 to 6 %). Simon R. 1996 .C. Pinto J. Allergy. A case with severe hemodynamic disturbances” .S.A.T.R. “Paracetamol sensitivity without aspirin intolerance”.T. ASA and NSAIDs in children: what alternatives?”. Roseeuw D. Stevenson D.P. Immunol. Martinez E. 99: 151-2 de Coninck A. 18 (5): 313-8 Ownby D. Allergy. Plomley R.A. Nogueira J. Alonso E. Allergy. 22 (9): 831-3 • • • • . “Acetaminophen-induced urticaria and tolerance of ibuprofen in an eight year-old child”.A. Avoid high doses of acetaminophen (>1000 mg) in aspirin-sensitive asthmatic patients.P. Allergy. 1997 .A.M. Clin. 53 (4): 457-8 de Almeida M. 1997 .L. Czarny D.L. Proc..

Double blind placebo-controlled challenge.ANALGESICS AND ANTI-INFLAMMATORY DRUGS ANTHRALINIC ACID DERIVATIVES Group of NSAIDs including glafenine. and the fenamates (mefenamic acid. DIAGNOSTIC METHODS Cutaneous testing. etofenamic and meclofenamic acids).1 to 1 mg/ ml and meclofenamate 0. Urticaria. . One case of positive intradermal skin test with glafenine 0. hepatitis. floctafenine. antrafenine. blood dyscrasias.1 to 1 mg/ ml. 14 cases of allergy requiring hospital admission in the Netherlands in 1981. Basophil histamine release: positive in 16% of patients with glafenine intolerance.6/100 000 treatments.4/100 000 courses.40 - . RISK FACTORS Intolerance to other NSAIDs.3/100 000 treatments. Bronchospasm. CLINICAL MANIFESTATIONS Anaphylactic shock. Floctafenine: 0. Renal failure. flufenamic. INCIDENCE (CONFLICTUAL) Glafenine: 1/2000 to 3. Antrafenine: 1. Leukocyte migration test: positive in 50% of patients with glafenine intolerance. angioedema.

Ann. Albengres E. 1991 .H.. “Bilan d’une enquête nationale prospective sur les effets indésirables de la glafenine.H. Clin.R. “Anaphylaxis to glafenine (letter)”. 71 (6): 515-8 Stricker B. Davila I. “Hypersensitivity reactions to anthralinic acid derivatives”. 1993 . Ascertain other NSAID tolerance. “Glafenine-associated anaphylaxi as a cause of hospital admission in the Netherlands”.H. et de la floctafenine”. Pharmacol. Therapie. Losada E. 336 (8720): 943-4 Cheymol G.R. 40 (4): 367-71 Stricker B. Quirce S. 1990 .. INCIDENCE Aspirin induced asthma — asthmatic adults: 10% . Cuevas M. de Groot R. Intolerance: similar mechanisms to other NSAIDs. Bruneel M.ANALGESICS AND ANTI-INFLAMMATORY DRUGS MECHANISMS (UNCERTAIN) IgE-mediated hypersensitivity: one case reported with positive skin tests in a patient specifically allergic to anthralinic derivatives but tolerating aspirin and other NSAIDs. Allergy. de la Hoz B.41 - . de Groot R. Biour M. Lancet. Wilson J. Hamel J.D. 40: 45-50 ASPIRIN AND NON STEROID ANTI-INFLAMMATORY DRUGS (NSAIDs) Aspirin and NSAIDs are widely used drugs in the field of pain and inflammatory disorders.H. J. REFERENCES • • • • Fernandez-Rivas M. Wilson J. 1985 . de l’antrafenine. MANAGEMENT Avoidance of glafenine and related molecules (withdrawn in numerous countries). Eur.

azapropazone. intolerance to multiple NSAIDs not structurally related). angioedema. then asthma. piroxicam.42 - . Drugs involved: naproxen. usually severe and corticodependant. NSAIDs sensitivity and oral anaphylaxis from aeroallergens (mites). Cutaneous: chronic urticaria (in free patients and in patients with chronic urticaria). HLA DQW2 (controversial). Classic triad: rhinitis with nasal polyps. Respiratory: hypersensitivity. ibuprofen. photodermatitis (naproxen. diclofenac). Lyell’s syndrome (fenbrufen. cytopenia. sulindac. oxyphenylbutazone. RISK FACTORS Female gender (urticaria). indomethacin. purpura (phenylbutazone. CLINICAL MANIFESTATIONS General: anaphylactoid reaction. atopy. pneumonitis (fever.5% — normal individuals: 0. pulmonary infiltrates): most reactions occur in patients with inflammatory arthritis. Atopy (localized periorbital edema). . phenylbutazone. (zomepirac.ANALGESICS AND ANTI-INFLAMMATORY DRUGS Aspirin induced urticaria — chronic urticaria: 21 to 30% (mean 23%) — rhinitis and asthma: 1. decrease of incidence of DPB1 0401 in both aspirin-tolerant and aspirin-sensitive asthmatics. asthma and ASA sensitivity. benoxaprofen). tiaprofenic acid. indomethacin. Haematological: eosinophilia. diclofenac. tolmetine.3%. derivatives). Rhinoconjunctivitis/asthma: chronic eosinophilic rhinosinusitis with or without nasal polyps and secondary purulent infection of the paranasal sinuses . piroxicam. salicylate. cough. New triad: atopy. isolated periorbital edema (younger subjects. piroxicam).

Day 2: 100 mg . Day 3: 325 mg . 360 mg). Day 1: placebo. Rhinosinusitis/asthma.ANALGESICS AND ANTI-INFLAMMATORY DRUGS DIAGNOSTIC METHODS Cutaneous testing. Controlled oral challenges: gold standard in the diagnostic of NSAID hypersensitivity. Usually ineffective and negative . Urticaria (aspirin). 90 mg. 650 mg Urticarial responses are measured by skin scores recorded every 2 hours. . soluble in water (ASA-Lysine: 11. No severe bronchoconstriction. 45 mg . No reaction. 22. Asthma only: FEV1 decrease > or = 20% Rhinitis: naso-ocular reaction only. 180 mg.25 mg. Specific antibodies to salicyloyl and O-methylsalicyloyl (RASTRAST inhibition). Oral challenge (single blind or double blind) Day 1 Day 2 Day 3 8 H00 AM 11H00 AM 2H00 PM placebo placebo placebo ASA 3 or 30 mg ASA 60 mg ASA 100 mg 150 mg 325 mg 650 mg Classical response (86%): FEV1 decrease > 20% + naso-ocular reaction. one case of positive cutaneous test with aspirin polylysine 2 mg/ ml in a patient with urticaria. 200 mg. Bronchial inhalation challenge with Lysine-ASA. Mild asthma: FEV1 decrease 15 to 20% combined with naso-ocular reaction. Lysine-acetylsalicylate conjugate.5 mg. IgE antibodies against platelet antigens. Easier to perform .43 - . available as a powder. Specific IgE (controversial).

since they release free radicals of O2 and cytocidal mediators in response to NSAIDs. LTE4) which are potent bronchoconstrictors. zomepirac 80 to 100%. Piroxicam 10 mg. Clonixin 50 mg. Sensitivity to aspirin-like drugs in ASA-sensitive patients. 20 mg at 120 minute intervals. MECHANISMS Leukotriene C4. 250 mg. 250 mg at 60 minute intervals. an elevated count of eosinophils. 125 mg at 60 minute intervals. at 60 minute intervals. 400 mg. — prostaglandin synthetase inhibitors: indomethacin 100%. 1000 m at 60 minute intervals. Metabolites of arachidonic acid (LTC4. Paracetamol 100 mg.ANALGESICS AND ANTI-INFLAMMATORY DRUGS Other drugs (single-blind. Salsalate 500 mg. Administration of aspirin shifts the metabolism of arachidonic acid towards the 5-lipooxygenase pathway with synthesis of leukotriene sulfidopeptides (LTC4. Diclofenac 25 mg. naproxen 100%. 500 mg.44 - . mefenamic acid 60%. Leukotriene over-production is related to marked eosinophilic infiltration of the mucosa. 25 mg. ibuprofen 97%. 50 mg at 120 minute intervals. phenylbutazone 42% . LTD4. LTD4. fenoprofen 100%. LTE4) may be detected in urine and bronchial and nasal fluid following aspirin challenge. 500 mg. Isonixin 100 mg. at 60 minute intervals. Platelets have been implicated in the pathogenesis of asthma intolerance. at 60 minute intervals. Diflunisal 100 mg. and higher levels of ECP compared to aspirintolerant asthmatic patients. placebo-controlled drug challenge). Mefenamic acid 50 mg. 125 mg. Platelets from ASA-sensitive patients become cytotoxic in the presence of ASA. histamine and tryptase are released from cells in ASA-sensitive asthmatics following ASA challenge. Ketoprofen 10 mg. Studies performed in patients suffering from asthma due to aspirin intolerance have demonstrated higher levels of IL5. 50 mg at 120 minute intervals.

a new NSAID. Avoidance. suprofen. Asthmatics with normal sinus X-rays or CT scans of the sinuses. is safe in ASA-intolerant patients. Long-term desensitization does not appear feasible for patients with ASA/NSAIDs-induced urticaria. and asthmatics with clear evidence of IgE-mediated allergy are at low risk of ASA sensitivity.ANALGESICS AND ANTI-INFLAMMATORY DRUGS — no prostaglandin synthetase inhibitors: sodium salicylate < 1%. Desensitization. Aspirin desensitization is accompanied by a reduced aspirininduced production of sulfido peptide leukotrienes (LTE4). Imidazole salicylate. ASA desensitization may be considered in patients with: — uncontrolled respiratory inflammation despite appropriate treatment (local and systemic corticosteroids). Hypersensitivity pneumonitis. and diclofenac in asthmatic patients with ASA sensitivity due to the risk of bronchospasm. salicylate < 1%. RHINOSINUSITIS/ASTHMA. Avoidance of ASA/NSAIDs. .8 to 98% of NSAID-intolerant patients. — patients with arthritis or recurrent arterial thromboembolic diseases. choline salicylate < 1%. which inhibits Tx A2 synthesis without interfering with cyclooxygenase pathway. Avoidance of all NSAIDs.45 - . Do not administer topical ophtalmic ketorolac. flurbiprofen. propoxyphene < 1% MANAGEMENT URTICARIA. — patients requiring frequent sinus surgery. Use of systemic corticosteroids. Nimesulide (4 nitro-2 phenoxymethane-sulfon-anilide) is an NSAID-inhibiting cox2 and is well-tolerated in 90 to 100% of asthmatics and 92.

R. Care.A. (Middleton E. Nizankowska E. 1992 . Castillo R.X.ANALGESICS AND ANTI-INFLAMMATORY DRUGS REFERENCES • Szczeklik A.2): S34-6 Stevenson D.T. Schmitz-Schumann M. Li H.M. 7 (3): 160-8 Quiralte J. Med. Christie P.D. Carrillo T. Invest. Allergol. Barker J. Respir. “The atopy trait in hypersensitivity to non steroidal anti-inflammatory drugs”.H..46 - . Simon R. “The effect of aspirin desensitization on urinary leukotriene E4 concentrations in aspirin-sensitive asthma”. Sousa A. Med. Respir.H. “Mechanism of aspirin sensitivity”. Clin. Mo L. Allergy. Delgado J. Bell G. Cmiel A. Oates J.M. Care. Am. Following intravenous injection. Zhao J.A. Allergy. Pfister R. J..E. Mastalerz L. Immunol.S.R. 1996 . 145 (2. St Louis CV Mosby 1992 • • • • • • • PROPACETAMOL Propacetamol (N. It is composed of an acetaminophen molecule coupled to a vector: diethylglycine.N-diethyl glycidyl ester of acetaminophen) is a soluble bioprecursor of acetaminophen. eds) page 174765. Am. Dworski R. Nizankowska E. J. Crit. “Sensitivity to aspirin and non steroidal antiinflammatory drugs”. it is a prodrug widely used for its analgesic and antipyretic properties. 1997 . “Intolerance to non steroidal inflammatory drugs: results of controlled drug challenges in 98 patients”. Lee P. 1996 .H. propacetamol is readily hydrolized into acetaminophen 2 and N. J. Rev. 153 (1): 90-6 Bochenek G. Blanco C. “Drug allergy: identification and characterization of IgE-reactivities to aspirin and related compounds”. Respir. Allergy. Crit. 158: 1168-72 Zhu D. 1995 . Immunol.E. 98 (3): 678-85 Nasser S. Szczeklik A.. Reed C.L. Lee T. Am. 151 (5): 1326-30 Lee T. Sheller J. Respir. 1998 . Crit.N-diethylglycine 3). 51: 16-23 Nasser S. Med. Am. Clin. A very effective and well tolerated analgesic. J.R. Prokop A. . 1996 . Dis. “Inflammatory cell populations in bronchial biopsies from aspirin-sensitive asthmatic subjects”. In. Care. Patel M. “Salmeterol prevents aspirin-induced attacks of asthma and interferes with eicosanoïd metabolism”. J.

Barbaud A. especially in cases where allergic history enhances the risk of occupational sensitization. 346: 902 . are positive in patients with contact dermatitis to propacetamol.ANALGESICS AND ANTI-INFLAMMATORY DRUGS INCIDENCE Several cases of occupational contact dermatitis have been reported in nurses handling propacetamol . “Occupational allergy to propacetamol”. but negative with solvent. MECHANISMS Patch-tests with N.N-diethylglycine. and occasionally on the face. This strongly suggests that propacetamol acts as an activated form of N. “Mechanism of allergic contact dermatitis from propacetamol: sensitization to activated N.N-diethylglycine phenyl ester (activated form of N. Contact Dermatitis. 38: 185-8 Barbaud A.47 - . REFERENCES • • Berl V. intensive care units. Lancet. Lepoitevin J. CLINICAL MANIFESTATIONS Chronic eczema with vesiculous flares on the back of the hands sometimes extending to wrists. 1998 . Schmutz J. Trechot P. acetaminophen and diethylglycine.N.L.P. So acetaminophen allergy has never been observed in propacetamol-allergic patients. 1995 .diethylglycine) in 10% pet. Patch-tests with propacetamol are positive . oncology). transferring this part of the molecule to nucleophilic residues of proteins. MANAGEMENT The wearing of gloves for preparing propacetamol is mandatory.N-diethylglycine” . Bertrand O. DIAGNOSTIC METHODS Cutaneous testing. RISK FACTORS Nurses frequently handling propacetamol (surgery. forearms.

2. MECHANISMS IgE-mediated hypersensitivity: positive skin tests + specific IgE . Toxic epidermal necrolysis . Fixed drug eruption. Bronchospasm (intolerance). Amidophenazone.5 . Erythema multiforme. INCIDENCE Metamizol: from 0. urticaria). Contraindicated if anaphylactic shock. angioedema (allergy). Allergy contact dermatitis. Sometimes useful in patients with asthma or urticaria.3 . CLINICAL MANIFESTATIONS Anaphylactic shock. DIAGNOSTIC METHODS Cutaneous testing.01% in most patients with allergic symptoms (anaphylactic shock. Metamizol.ANALGESICS AND ANTI-INFLAMMATORY DRUGS PYRAZOLINE DRUGS OR PYRAZOLONES Clinical use of this family of analgesics was sharply curtailed due to its potentially fatal bone marrow toxicity (agranulocytosis). Oral challenge.one found in 17/19 pyrazolone sensitive patients. Intolerance: similar mechanisms to other NSAIDs.phenyl . Intradermal skin-tests: positive at 0.pyrazoline . . Specific IgE (RAST) for 1 . Urticaria.001 to 0.dimethyl . especially in patients with anaphylactic shock or urticaria. Propylphenazone. Maculopapular eruption.48 - . Phenazone.13% to 2.4% of cutaneous reactions. Allergic vasculitis .3 .

Schlaak M. Arylpropionic derivatives (ketoprofen). Becker W. The first national pharmacovigilance inquiry (1993-95) in France reported 260 cases of local intolerance to topical NSAIDs among 11 million units sold.phenyl .5 . Agents. “Detection of IgE antibodies specific for 1 .dimethyl . Schulz K. Drugs. REFERENCES • Zhu D.pyrazoline . “Analgesics. 19: 303-11 Szczeklik A. J. 1986 . Actions.3 .one by RAST*: a serological diagnostic method for sensitivity to pyrazoline drugs”. 1986 . Summertime.. Allergy.. RISK FACTORS Sun exposure. Immunol. 1992 .3 . Suppl.2.49 - . Schubeler K.M. 10 (2): 95-101 Voigtlander V. 32 (s4): 14863 • · TOPICAL NON STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDs) Widely used in the treatment of various eczemas. Avoid all NSAIDs in cases of intolerance. INCIDENCE Difficult to evaluate. Pac.H. . French contact dermatitis group (GERDA) recently reported 62 observations. Asian. ascertain safe other NSAIDs. allergy and asthma” .ANALGESICS AND ANTI-INFLAMMATORY DRUGS MANAGEMENT In patients with specific pyrazolone allergy. “Adverse dermatological reaction to pyrazolones” .

ANALGESICS AND ANTI-INFLAMMATORY DRUGS CLINICAL MANIFESTATIONS Contact dermatitis. Bottlaender A. If there is photosensitivity to ketoprofen or tiaprofenic acid. DIAGNOSTIC METHODS Cutaneous testing. avoid fenofibrate and benzophenones. Oral challenge may be dangerous and should be avoided. fenoprofen. Cross-sensitivity exists between NSAIDs of the same family. Contact Dermatitis.J. REFERENCES • le Coz C. Heid E. Photo allergy is due to the benzophenone moiety of ketoprofen. flurbiprofen. Alminoprofen.50 - .N. Oral administration of NSAIDs following cutaneous sensitization may lead to severe generalized eruption. contact erythema multiforme. The mean duration of application is 13 days . MANAGEMENT Avoidance of causative family Use of NSAIDs of other families if mandatory.J. or thiophene-phenylketone moiety of tiaprofenic acid but not to the arylpropionic function. UVB and total light). 38: 245-52 . 1998 . MECHANISMS Delayed contact hypersensitivity and virtual photocontact sensitivity (preponderance of UVA). Grosshans E. ibuprofen or naproxen may be tolerated in such cases. Patch-tests and photopatch-tests (UVA. “Photocontact dermatitis from ketoprofen and tiaprofenic acid: cross-reactivity study in 12 consecutive patients”. eruption may be prolonged (mean duration 25 days) with frequent regional or generalized extension. Cribier B. photocontact dermatitis. Santinelli F. Scrivener J.

Baudot S. “Photosensibilisation de contact au ketoprofene.. Litoux P. Derm. 5 observations. La lettre du GERDA.” . Venereol.51 - . Ann. 1997 . 124: 523-6 Milpied B. Dutartre H. Milpied-Homsi B. “Réseau Revidal et AINS topiques: un an d’expérience”.ANALGESICS AND ANTI-INFLAMMATORY DRUGS • • Bastien M. 1997 . 14: 50-4 .

- 52 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

III ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

- 53 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

ACYCLOVIR
Acyclovir is a structural analogue of guanosine which inhibits viral DNA-polymerase and is widely used as an antiviral drug in herpes and herpes-zoster infections.

INCIDENCE
Rare.

RISK FACTORS
AIDS. Repeated topical use .

CLINICAL MANIFESTATIONS
Topical use: contact dermatitis. Systemic administration: generalized eczema, vesicular eruption, phlebitis, urticaria.

DIAGNOSTIC METHODS
Cutaneous testing. Patch-tests with acyclovir 5% in water or pet. must be read at 30 min, 48 and 72 or 96 hours. Some cases of sensitization are due to vehicle constituents (propylene glycol).

MECHANISMS
Delayed contact dermatitis.

MANAGEMENT
Avoidance of acyclovir (topical and systemic) and valacyclovir.

REFERENCES
• • Montoro J, Basomba A, “Fixed drug eruption due to acyclovir”, Contact Dermatitis, 1997 ; 36: 225-31 Goday J, Aguirre A, Gil-Ibarra N, Ezaguirre X, “Allergic contact dermatitis from acyclovir”, Contact Dermatitis, 1991 ; 24: 380-1

- 54 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

ALLYLAMINES
New class of antifungal agents (terbinafine).

INCIDENCE
Severe cutaneous side-effects: 1/100000.

CLINICAL MANIFESTATIONS
Rashes, urticaria, erythema multiforme (2 to 5 weeks after starting treatment), Stevens-Johnson’s syndrome and toxic epidermal necrolysis (5 to 8 days after the first intake). All cases were regressive within 4 to 18 days after stopping terbinafine.

DIAGNOSTIC METHODS
Patch-tests with 1% terbinafine are negative in Lyell’s syndrome.

MECHANISMS
Unknown.

MANAGEMENT
Avoidance.

REFERENCES
• • Mc Gregor J.M, Rustin M.H.A, “Terbinafine and erythema multiforme”, Br.J.Dermatol., 1994 ; 131: 587-8 Carstens J, Wendelboe P, Sogaard H, Thestrup-Pedersen K, “Toxic epidermal necrolysis and erythema multiforme following therapy with terbinafine”, Acta. Derm. Venereol., 1994 ; 74: 391-2

AMINOGLYCOSIDES
Aminoglycosides are broad-based heterosides with a broadspectrum antibiotic action.

- 55 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

Streptidine group. Streptomycin, dihydrostreptomycin, hydroxystreptomycin, manosidostreptomycin. Desoxystreptamine group. 1,3 substitution (trisaccharide): kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin. 1,2 substitution (tetrasaccharide): paramomycin, neomycin.

INCIDENCE
High for neomycin and streptomycin: >2% of treatments. Occasional for gentamicin and amikacin: 0.1 to 2% of treatments. Uncommon for kanamycin: 0.1 to 0.5% of treatments.

CLINICAL MANIFESTATIONS
General: anaphylactic shock uncommon, fever (11% with longterm streptomycin), serum sickness. Cutaneous: urticaria, rash (11% with streptomycin; 0.8% with gentamicin; 0.6% with tobramycin), contact dermatitis (3 to 10% with streptomycin), exfoliative dermatitis. Haematological: eosinophilia, immunological blood dyscrasia.

DIAGNOSTIC METHODS
Cutaneous testing. Skin prick-tests: one case positive with systemic reaction in a patient with anaphylactic shock following topical use of framycetin (framycetin sulfate 10 mg/ ml). Patch-tests: * positive in 12% of patients treated with streptomycin. * positive in patients presenting contact dermatitis, rash, fever. * positive with neomycin in 10 to 35% of patients with leg ulcers. The presence of antibodies against specific aminosides has rarely been demonstrated. — antistreptomycin IgG antibodies in association with hemolytic anemia (direct and indirect Coombs); — antierythrocyte antibodies (neomycin, gentamicin, kanamycin).
- 56 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

MECHANISMS
IgE-mediated hypersensitivity (rare). Cell-mediated delayed hypersensitivity for contact dermatitis (neomycin) ; neomycin is the antibiotic with the highest contact sensitizing power. Sensitization tends to occur on altered skin (leg ulcers) and with long-term application.

MANAGEMENT
Avoid use of offending antibiotics for leg ulcers. The use of neomycin should be avoided in dermatology. Cross sensitivity between aminosides has been documented (neomycin-framycetin: 93% ; neomycin-ribostamycin 73% ; neomycin-kanamycin 60% ; neomycin-gentamycin 46% ; neomycin-tobramycin 40%).

REFERENCES
• • • • • Assier-Bonnet H, Revuz J, “La néomycine topique, risques et bénéfices. Plaidoyer pour un retrait” , Ann. Dermatol. Venereol., 1997 ; 124: 721-5 Proebstle T.M, Jugert F.K, Merk H.F, Gall N, “Severe anaphylactic reaction to topical administration of framycetin”, J. Allergy. Clin. Immunol., 1995 ; 96 (3): 429-30 Samsoen M, Metz R, Melchior E, Foussereau J, “Allergie croisée entre les antibiotiques aminosides”, Ann. Dermatol. Venereol., 1979 ; 106 (8-9): 683-9 Chung C.W, Carson T.R, “Cross sensitivity of common aminoglycoside antibiotics”, Arch. Dermatol., 1976 ; 112: 1101-7. Rippen R.P, “Anaphylactic reaction after Chymacort® ointment”. Br. Med. J., 1966 ; 1: 1172.

STREPTOMYCIN
Streptomycin is a chemical complex substance, being composed of a central hexose (streptidine) linked to an amine-substituted disaccharide. Widely used in the past (tuberculosis), its use has declined drastically but is now routinely added to cell culture media (PHA-LAK) and to Ham’s F-10 medium, which is used for in vitro fertilization.
- 57 -

0. Linana J.58 - .J. positive in patients with contact dermatitis. MANAGEMENT Desensitization (3 hours) beginning with 1 mg intravenously. Skin prick-tests (1 to 10 mg/ ml).F. Dermatitis. REFERENCES • • Perez R. 1996 . Carretero P. Patch-tests with streptomycin in 2% pet. Allergy. Specific IgE (RAST. 0. “Anaphylaxis induced by streptomycin in cell media”. Rodriguez-Serna M. Contact. Intradermal skin-tests (1 mg/ ml). MECHANISMS High molecular mass impurities (streptomycin polymers) related to some reactions aminogroups of streptomycin are the allergens involved in immediate-type allergies.01 µg/ml). ELISA) few cases with positive results Histamine-release test: one case with dose-dependent release following stimulation with streptomycin (1 . 35 (6): 374-5 . ANTIVIRAL. Blanco J. serum sickness.1 . Marcos M. ANTIFUNGAL DRUGS INCIDENCE High in the past (> 2% of treatments). Juste S. Navarro J. exfoliative dermatitis. “Allergic contact dermatitis from streptomycin in a cattle breed”. Alonso L. Cutaneous: urticaria. DIAGNOSTIC METHODS Cutaneous testing. haemolytic anemia. 1996 . 51 (2): 135-6 Gauchia R. Drug re-challenge. fever. rash. Silvestre J. Ahaga A. contact dermatitis. Haematological: eosinophilia. CLINICAL MANIFESTATIONS General: anaphylactic shock.ANTIBIOTICS. Garces M.

RISK FACTORS AIDS.A.ANTIBIOTICS. Ann. ANTIVIRAL. 1984 . Bock S. MECHANISMS Unknown. . 49 (5): 388-9 Tinkelman D. Kuwert C.. Ambisome has proved effective in the treatment of fungal infections including candida. Ring J. which is well tolerated. 1994 . “Anaphylaxis presumed to be caused by beef containing streptomycin”. DIAGNOSTIC METHODS None..G. Allergy. 53 (3): 243-4 AMPHOTERICIN B Liposomal preparations of amphotericin B have the advantage of lower toxicity compared with conventional preparations. erythema. INCIDENCE 3/187 in transplant recipients. aspergillus and cryptococcus. CLINICAL MANIFESTATIONS Anaphylactic shock. Segnini-Torres M. MANAGEMENT Anaphylaxis to ambisome does not preclude subsequent use of amphotericin B. Allergy. ANTIFUNGAL DRUGS • • Abeck D. “Streptomycininduced anaphylactic reaction during in vitro fertilization (IVF)”. fever. One case of fatal cardiac arrest. Rash. The lipid content of the drug is suspected to be the culprit. edema. Bronchospasm. Przybilla B.59 - .

skin. Lancet. 1996 . “A randomized double-blind study of AmBisome (liposomal amphotericin B) in prophylaxis of invasive fungal infections in bone marrow transplant recipients”. . Pharmacother. cryptococcal meningitis and as prophylaxis for cryptococcal infections in HIV patients.R. Malcolm G. fixed drug eruptions. ANTIVIRAL. Ljungman P. toxic epidermal necrolysis.M. 1994 .60 - . Bone Marrow Transplant. oral and vaginal mucosa . 1993 . Ann. Ringden O.S. Sundberg B. . “Allergic reactions and other rare side effects of liposomal amphotericin”. 344 (8923): 682 Tollemar J.S. angioedema. 344 (8930): 1156-7 Laing R.J. Stevens-Johnson’s syndrome. CLINICAL MANIFESTATIONS Anaphylactic shock. Leen C.J. Vazquez P. Remberger M. 30 (9): 10367 Ringden O. Andersson S. “Anaphylactic reactions to liposomal amphotericin”.. Milne L. 12: 577-81 AZOLE DERIVATIVES FLUCONAZOLE Fluconazole is a triazole antifungal agent used in the treatment of infections of the nails. INCIDENCE Probably very low.W. Andström E.ANTIBIOTICS. Steers A. maculopapular eruptions. Tyden G.P. Lopez-Herce J.D. “Anaphylactic reaction to liposomal amphotericin B in children (letter)”. 1994 .. Svahn B. Rashes. Lancet.L. Tollemar J. ANTIFUNGAL DRUGS REFERENCES • • • • Torre I. systemic candidiasis.

One case with positive skin-prick tests 1/10. Peralta F. MANAGEMENT Cross-reactivity with other azole derivatives is likely. MECHANISMS Unknown. MECHANISMS Unknown. REFERENCES • • Craig T. coccidiodomycosis. Allergy.M. Immunol. INCIDENCE Probably low. CLINICAL MANIFESTATIONS Erythematous rash. “Desensitization for fluconazole hypersensitivity”. Pletscher M. ANTIVIRAL.J. candidosis and aspergillosis. Clin. 302 (6788): 1341 ITRACONAZOLE Triazole antifungal agent used for treatment of histoplasmosis. Desensitization (orally): 0.61 - . Boggavarapu J. Drug re-challenge. paracoccidiodomycosis. “Anaphylactic reaction after oral fluconazole”. 1991 . sporotrichosis. Pavic N. ANTIFUNGAL DRUGS DIAGNOSTIC METHODS Cutaneous testing .2 mg to 400 mg in 15 days. . 1996 .ANTIBIOTICS. Maculopapular rash. DIAGNOSTIC METHODS Skin-prick tests: negative. B.J. 98 (4): 845-6 Neuhaus G. J.

Histamine release test was positive in the same patient. rash. Stapleton J. No specific IgE found. facial angioedema. . ANTIFUNGAL DRUGS MANAGEMENT Desensitization. 1 mg to 200 mg over 4 hours. J. also effective in the treatment of dermatophytosis and superficial mycosis. 1994 .ANTIBIOTICS. 200 mg positive in the same patient following a cumulative dose of 75 mg. Clin. Skin-prick tests with 1. 40 mg/ ml positive with a concentration of 10 mg/ ml in a patient with allergic reaction to ketoconazole. Clin. Casale T. 100 mg. ANTIVIRAL. urticaria. Spelman D.B. J. 50 mg. 94 (2.1): 270-1 KETOCONAZOLE Ketoconazole is a synthetic imidazole-derivative antifungal agent used in the treatment of systemic and subcutaneous mycosis. 99 (2): 269 Bittleman D. comment)”. Czarny D. 1997 . Immunol. CLINICAL MANIFESTATIONS Anaphylactic shock. Allergy. Immunol. REFERENCES • • Douglas R. “Desensitization to itraconazole (letter. “Report of successful desensitization to itraconazole (see comments)”. 10. Oral challenge: 25 mg. INCIDENCE Very low (4 cases published).62 - . 20. Allergy.B. DIAGNOSTIC METHODS Cutaneous testing.. Pruritus. O’Hehir R.

73 (4): 326-8 METRONIDAZOLE Nitroimidazole derivative used for the treatment of anaerobic infections and trichomonas infections. MANAGEMENT Avoidance.75% metronidazole vaginal gel applied to the vaginal mucosa induced wheals of 6 x 6 mm in one patient and 2. Cross-reactivity with other azole derivatives is possible. . Florido-Lopez F. Lavarenne J. 1994 ..ANTIBIOTICS. Therapie. ANTIFUNGAL DRUGS MECHANISMS IgE-mediated hypersensitivity is likely. 1996 . CLINICAL MANIFESTATIONS Fever. Bronchospasm.5 x 5 mm in another with severe allergic reactions to metronidazole. Marin-Pozo J. ANTIVIRAL. REFERENCES • • Beal M.. INCIDENCE Uncommon.F. Simmonnet F. 51 (5): 604-5 Gonzalez-Delgado P. “Reaction anaphylactique au ketoconazole”. Saenz de San Pedro B. Cuevas-Agusti M. Boch C. Ann. maculopapular rash. Urticaria. Zenut M. Allergy. but not demonstrated .”Hypersensitivity to ketoconazole”. MECHANISMS IgE-mediated hypersensitivity is likely in some cases. Bernard C.63 - . pustulosis.5 mg of 0. DIAGNOSTIC METHODS 1. fixed drug eruption. serum sickness.

Two different protocols have been published: — 0. 500 mg. REFERENCES • • • Pearlman M. “An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reactions to metronidazole”. 2 g orally (3 h).. Allergy Clin..ANTIBIOTICS. Clinical manifestations Usually severe: anaphylactic shock with hypotension (80%) pruritus. swelling of the tongue and face urticaria Contact dermatitis. ANTIFUNGAL DRUGS MANAGEMENT Cross-reactivity between metronidazole and tinidazole (fixed drug eruption). 28 (3): 325-6 Kurohara M. ANTIVIRAL. 174 (3): 934-6 Knowles S. Kwong F. 1994 . Solomon W. Gynecol. 1991 .K. Pharmacother.64 - . 88 (2): 279-80 BACITRACIN Antibiotic polypeptide complex produced by Bacillus subtilis widely used as topical antibacterial medication. Desensitization. burns). Obstet. Lebherz T. flush. Klaustermeyer W. Ernst S. Ann.D.B.L.. RISK FACTORS Compromised skin barrier (leg ulcers.B. Am. excoriated dermatitis. INCIDENCE Immediate allergy is infrequent (10 cases reported) Contact dermatitis is common. Shear N. J. Immunol.H. then 250 mg. J. Chhoudhury T. 1996 .0025 mg to 1 000 mg in 8 steps (orally) — 5 µg to 125 mg intravenously (3h40). . “Metronidazole hypersensitivity and oral desensitization”. Yashar C. “Medronidazole hypersensitivity”.

D. Shear N. Analg.. “Anaphylaxis to topical bacitracin”. ANTIVIRAL. 34 (8): 572-3 Eedy D. 1997 . Skin prick-tests positive in a few cases of anaphylaxis (intradermal skin-tests may be dangerous).L.P. “Anaphylactic reactions to topical antibiotic combinations”.A.ANTIBIOTICS. although IgE antibodies have not been disclosed by other methods. MANAGEMENT Avoidance. MECHANISMS Strong evidence of IgE-mediated hypersensitivity including positive immediate skin tests. Positive patch-tests in contact dermatitis. Mc Millan J. Dermatol. Schedewie H. 1990 . 52: 870-1 Knowles S. It comprises a nitrobenzene ring linked to propanol. Postgrad. Campine J.R. “Anaphylaxis from bacitracin and polymyxin B (polysporin) ointment”. 71 (4): 430-3 CHLORAMPHENICOL Antibiotic produced by Streptomyces venezuelae. Allergy. INCIDENCE Uncommon. 1995 . “Near-fatal anaphylaxis to topical bacitracin ointment”. positive Prausnitz-Küstner tests. Clin.J.. “Intraoperative anaphylactic shock after bacitracin irrigation”. Immunol. with an amide group binding to a derivative of dichloroacetamide acid. Bingham E.1): 136-7 Dyck E.. 66 (780): 858-9 Sprung J. Vadas P.. Med. 101 (1.K. Woodmansee D. Anesth. Patterson R.H. Int. J. Allergy.65 - . 1990 . J. ANTIFUNGAL DRUGS DIAGNOSTIC METHODS Cutaneous testing. . J. REFERENCES • • • • • Lin F.C. 1998 .

Antibodies against chloramphenicol have been found. aplastic anemia. ANTIVIRAL. Dermatitis. anaphylactic shock. REFERENCES • Le Coz C. Haematological: aplastic anemia. fever. ANTIFUNGAL DRUGS RISK FACTORS Allergy to penicillin. The dichloroacetamide ring is probably the major antigenic determinant. Severe infection.66 - . maculopapular rash. Santinelli F. Positive scratch and patch test reported in some cases involving cutaneous manifestations (patch-tests with chloramphenicol 1% in pet). Contact. Cross-sensitivity between chloramphenicol and synthetic derivatives is likely. MANAGEMENT Avoidance. CLINICAL MANIFESTATIONS Topical use of chloramphenicol may lead to: contact dermatitis. Previous exposure to phenicols. 38: 108-9 . angioedema.J. MECHANISMS Unknown. Respiratory: bronchospasm. with no obvious clinical manifestation.ANTIBIOTICS. “Facial contact dermatitis from chloramphenicol with cross-sensitivity to thiamphenicol”. 1998 .. contact dermatitis. DIAGNOSTIC METHODS Cutaneous testing. Cutaneous: urticaria. General: anaphylactic shock.

“Anaphylaxis due to chloramphenicol”. Alvarez M. “Widespread ocular use of topical chloramphenicol: is there justifiable concern regarding idiosyncratic aplastic anaemia?”. Med.J. Mc Entire J. INCIDENCE Up to 10% of patients treated develop rashes at the end of the first week. 1991 .. Shapiro D. Br.M. ANTIVIRAL. CLINDAMYCIN Clindamycin is a semi-synthetic derivative of lincomycin active against most gram-positive and anaerobic bacteria. J. 51 (1): 67-9 Mc Ghee C. . Stevens-Johnson syndrome. 80 (2): 182-4 Liphshitz I.C. 288 (1): 43–5. maculopapular eruptions. DIAGNOSTIC METHODS Cutaneous testing. Ophtalmol.A.N. or during the second week of therapy. Munoz-Bellido F. Fonseca J.H... lip or palpebral edema. Hamory B. Dermatol. 1984 . Clindamycin together with pyrimethamine has been used as alternative treatment for toxoplasmic encephalitis in AIDS patients. Bellido J.A. 58% of patients treated with pyrimethamine/clindamycin have cutaneous reactions after an averageof 13 days.. Allergy. Loewenstein A. Anastas C. pruritus. Sci. Am. 1985 . 75 (1): 64 Schewach-Millet M. “Allergic contact dermatitis to chloramphenicol”. Funk E. leukocytoclastic angeitis.E. Cutaneous: contact dermatitis (very rare). J. Respiratory: bronchospasm. “Urticaria and angioedema due to topically applied chloramphenicol ointment”. Arch. J.L. “Anaphylactic reaction following application of chloramphenicol eye ointment”. Skin prick-tests (150 mg/ ml): negative..ANTIBIOTICS. Br. Palchick B.J. 121: 587.67 - . 1996 . 1996 . ANTIFUNGAL DRUGS • • • • • Moyano J. Ophtalmol. CLINICAL MANIFESTATIONS General: anaphylactic shock.

20 mg. 600 mg Day 7: 600 mg. 40 mg Day 3: 80 mg. ANTIFUNGAL DRUGS Intradermal skin-tests: negative. 40 mg. Gentilini M. 21 (3): 656-8 Marcos C. or aq. Iglesias A. Feo F.. Rogeaux O. 600 mg. Katlama C. Luna I. 1995 . 600 mg. Gomez E. No specific IgE found. 80 mg. Detection of hemagglutinating antibodies which specificity has been confirmed by inhibition of hemagglutination. REFERENCES • • Garcia R. “Clindamycin desensitization in an AIDS patient”.68 - . AIDS. Dermatitis. in AIDS patients with toxoplasmic encephalitis). 1995 . Bricaire F. 80 mg Day 4: 150 mg. ANTIVIRAL. Martinez-Vazquez C.A. Galindo P. MECHANISMS Residual impurities from the manufacturing process. Day 1: 20 mg. 35 (2): 116-7 Caumes E. MANAGEMENT Desensitization (orally. Bocquet H. Patch-tests (clindamycin phosphate 1% pet.ANTIBIOTICS. Sopena B. 300 mg. 9 (10): 1201-2 Vidal C. Clin. 600 mg Discontinuation of the treatment 9% to 14% due to adverse effects. “Hypersensitivity to clindamycin”. 25 (3): 317 • • . de la Fuente J. 1996 . 600 mg. “Adverse cutaneous reactions to pyrimethamine/sulfadiazine and pyrimethamine/clindamycin in patients with AIDS and toxoplasmic encephalitis”. Infect. 1991 . Fernandez F. Contact. Saez A. 300 mg Day 6: 600 mg. I. “Delayed allergic reactions to amoxycillin and clindamycin”. Rodriguez M. D.): positive in patients with contact dermatitis. 150 mg Day 5: 300 mg. C. 150 mg. 20 mg Day 2: 40 mg. Gonzalez R. Guermonprez G. P. Dis.

it is also part of the treatment for Pneumocystis carinii pneumonitis in HIV patients. ANTIFUNGAL DRUGS DAPSONE Diaminodiphenylsulfone is traditionally used in the treatment of leprosy and dermatitis herpetiformis. RISK FACTORS HIV patients. MECHANISMS Hypersensitivity to dapsone may be caused by metabolites of dapsone-forming haptens. N-acetylation is mediated by Nacetyltranferase type 2 showing a bimodal pattern of activity. hepatitis. rash (erythema. 21 cases of sulfone syndrome due to dapsone reported up to 1994. 2C6 and 2C11.3%). maculopapular eruption.ANTIBIOTICS. 40% haemolytic anemia. eosinophilia. lymphocytosis. High doses. CLINICAL MANIFESTATIONS Dapsone hypersensitivity syndrome (occurring 2 . hepatosplenomegaly. ANTIVIRAL. INCIDENCE Unknown. Dapsone N-hydroxylation is mediated by human lever microsomal enzymes P4503A4.69 - . DIAGNOSTIC METHODS Low complement levels. 1949: 2% of patients treated with dapsone for leprosy. slow and fast acetylation. Usual dose 50 to 300 mg/day: 85% rash. arthralgias. haemolytic anemia. exfoliative dermatitis). This . lymphadenopathy.8 weeks of starting therapy): fever. Mortality: 11%. with formation of antidapsone antibodies. Dapsone is metabolized primarily via two pathways: N-acetylation and N-hydroxylation (oxidation). probably low (0.

“Dapsone therapy causing sulfone syndrome and lethal hepatic failure in an HIV-infected patient” . ANTIFUNGAL DRUGS pathway is thought to be the initial step in the formation of toxic intermediate metabolites (nitrosamines) that can induce haemolytic anemia. Br.H.J. 1994 . J. J. Delfau-Larue M. Dermatol.2): 346-9 Bocquet H. Jurado R. Robinson J.E. Med.. INCIDENCE Cutaneous reactions: 0. Drug fever: 0. Shear N.70 - . 122 (8): 514-6 Chalasani P.H. replace with clofazimine (50 mg/day). Ann. Venereol. Baffoe-Bonnie H.Dermatol.L.. “Dapsone hypersensitivity syndrome”. For the treatment of dermatitis herpetiformis. Acad. 137 (4): 657-8 Prussick R. On withdrawing dapsone. For the treatment of leprosy. 1995 .5%. “Are dapsone hypersensitivity reactions dose-related?”. 25 mg/day in children. Am.ANTIBIOTICS. Side effects other than ocular toxicity are rare. 35 (2. 61 (4): 391-2 ETHAMBUTOL Ethambutol was widely used in the treatment of tuberculosis. 1990 . Revuz J.C. Clone T circulant transitoire”. patients usually recover within 2-8 weeks. Lepr. Bourgault-Villada I. Dermatol. Wechsler J. 1996 . “The dapsone hypersensitivity syndrome occurring in a patient with dermatitis herpetiformis” . MANAGEMENT Use 50 mg/day in adults. ANTIVIRAL. 1997 . Roujeau J.. “Syndrome d’hypersensibilité à la dapsone. REFERENCES • • • • • Mc Kenna K.. South. replace with another sulfonamide (sulfapyridine).. 87 (11): 1145-6 de Soldenhoff R. Rev.3%. Corticosteroids (no controlled study). .

“Ethambutol-induced neutropenia and eosinophilia”. Eur.C. 50 mg. Borish L. 32 mg. 1994 .. ANTIVIRAL. Gribnau F. 16 mg. 200 mg at 45 minutes intervals. 8 (5): 866-8 Matz J. O’Bar P.F.1): 815-7 Wong C.S Jr. 149 (3. 0. thrombocytopenia. purpura.W. 100 mg. Respir. 1981 .W. Tubercle. Med. Arch. Cutaneous: pruritus.. “Hypersensitivity to ethambutol”. Wong C. 1 mg. Chest. Choi H. MANAGEMENT Desensitization if absolutely necessary: 0.L.R. then 400 mg 3H30 later. 4 mg..C. toxic epidermal necrolysis. J. “Ethambutol-induced pulmonary infiltrates with eosinophilia and skin involvement”.1 mg . 2 mg. Haematological: eosinophilia.F. 106: 1638-9 Pegram P. 1995 . J.J. 62 (3): 215-7 . “Oral desensitization to rifampin and ethambutol in mycobacterial disease”.71 - . Care Med. Routes J. 1981 . Majoor C. Yew W. maculoerythematous rash.W. 141 (12): 1677-8 Kerremans A. then 400 mg x 3 the next day. Am.M.D. 8 mg . Yew W. “Ethambutol-induced toxic epidermal necrolysis”. Respiratory: dyspnea. neutropenia.5 mg. REFERENCES • • • • • Wong P.. DIAGNOSTIC METHODS Drug re-challenge is usually positive in the cases of fever or maculopapular rash.ANTIBIOTICS. MECHANISMS Unknown. pulmonary infiltrates. Rosenwasser L.Y. ANTIFUNGAL DRUGS CLINICAL MANIFESTATIONS General: fever. Crit. Intern. Respir. 1994 . Mountz J.

“Rapid oral desensitization to isoniazid and rifampin”. Patch-tests: isoniazid 2% in dis. 80 (4): 578-82. water (contact dermatitis).D. Respiratory: lung infiltrates. contact dermatitis (occupational in nurses and manufactories). Specific IgE . flu-like syndrome.ANTIBIOTICS. 1993 . MECHANISMS IgE-mediated hypersensitivity in a few cases. DIAGNOSTIC METHODS Cutaneous testing. Contact Dermatitis.. Bielory L.06 to 6 mg/ ml. Start with 0.72 - . MANAGEMENT Desensitization is possible and effective. 98: 1518-9 Asai S. INCIDENCE 5% of patients. “Systemic contact dermatitis from isoniazid”. J. Malasky C. Fujiwara K. Malek T. Chest. ANTIFUNGAL DRUGS ISONIAZID Isoniazid is a major antituberculosis drug. Shimoda T.L. Allergy Clin. Intradermal skin-tests: 0. maculopapular or urticarial rash. Salvador M. Cutaneous: morbilliform. 1987 . Immunol. REFERENCES • • • Meseguer J. Hara K. 1990 . Delayed hypersensitivity (contact dermatitis). . 28 (2): 110-1 Holland C. CLINICAL MANIFESTATIONS General: fever. Sastre A. Ogunkoya A. ANTIVIRAL. interstitial pneumonia.1 mg and go to 150 mg in 17 hours. “Occupational asthma caused by isonicotinic acid hydrazide (INH) inhalation”.

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

• •

Fujiwara K, Saita T, Shimoda T, Asai S, Hara K, “Isonicotinic acid hydrazide as an antigen”, J. Allergy. Clin. Immunol., 1987 ; 80 (4): 582-5 Gabrail N, “Severe febrile reaction to isoniazid”, Chest, 1987 ; 91: 620-1.

MACROLIDES
Widely used class of antibodies which act by inhibiting bacterial protein synthesis.

INCIDENCE
Uncommon (0.5 to 2.3% of treatments) for skin reactions. Exceptional for anaphylaxis and acute respiratory failure.

RISK FACTORS
Penicillin allergy. Lupus erythematosus.

CLINICAL MANIFESTATIONS
Anaphylaxis. Asthma (spiramycin ++). Fixed drug eruption (erythromycin), urticaria, maculopapular rash, vasculitis (rare), contact dermatitis. Urticaria, vasculitis, fixed drug eruption and thrombocytopenic purpura recently described with clarithromycin.

DIAGNOSTIC METHODS
Cutaneous testing: usually negative with erythromycin. One case with positive skin prick-tests (erythromycin lactobionate 10 mg/ ml) Positive patch-tests in fixed drug eruption (skin lesions). Specific IgE: usually negative. One case with erythromycin specific IgE (sepharose radioimmunoassay).

- 73 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

Leukocyte histamine release. Drug re-challenge.

MECHANISMS
IgE-mediated hypersensitivity in few patients.

MANAGEMENT
Avoidance. Cross-reactivity among macrolides has not been demonstrated.

REFERENCES
• • • • Rosina P, Chieregato C, Schena D, “Fixed drug eruption from clarithromycin” , Contact. Dermatitis., 1998 ; 38: 105-22 Jorro G, Morales C, Braso J.V, Pelaez A, “Anaphylaxis to erythromycin” , Ann. Allergy. Asthma. Immunol., 1996 ; 77: 456-8 Pascual C, Crespo J.F, Quiralte J, Lopez C, Wheeler G, Martin-Esteban M, “In vitro detection of specific IgE antibodies to erythromycin”, J. Allergy. Clin. Immunol., 1995 ; 95 (3): 668-71 Igea J.M, Quirce S, De la Hoz B, Fraj J, Pola J, Diez-Gomez M.L, “Adverse cutaneous reactions due to macrolides”, Ann. Allergy., 1991 ; 66: 216–8.

PENICILLIN AND OTHER BETA-LACTAMS
β-lactams: bactericidal antibiotics that act on bacteria during their growth phase by inhibiting the formation of specific peptide bonds on the bacterial wall. Penicillins: natural or semi-synthetic antibiotics with a core structure consisting of a β-lactam fused to a thiazolidine (6 amino penicillanic acid) differing simply in regard to their lateral fixed chain on the 6 amino function. Cephalosporins: antibiotics with a core structure consisting of a β-lactam fused to a 1.3-thiazine ring system.

- 74 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

Some anaphylactic reactions to cephalosporins are due to antibodies directed against specific side chains in these molecules rather than the β-lactam ring.

INCIDENCE
Penicillins: 1/1 000 administrations, i.e. 0.7 to 10% of treatments. Responsible for 75% of anaphylactic deaths in the USA. Urticaria: 4.5% of treatments. Systemic reactions: 2% of treatments. Anaphylactic shock: 0.2% of treatments. Mortality: 0.02% of treatments. Cephalosporins: 1.1 to 3% cutaneous reactions.

RISK FACTORS
Atopy not implicated. Sensitivity to moulds not implicated. Intravenous administration. Mean age, 20 to 49 years. Prior history of penicillin reaction (risk x 6).

CLINICAL MANIFESTATIONS
Immediate (< 1 h): anaphylactic shock, urticaria, angioedema, laryngospasm, bronchospasm (especially with benzylpenicillin). Accelerated (1 to 72 h): mainly urticaria. — cutaneous: maculopapular rash, pruritis, erythema multiforme, bullous erythema, erythrodermia (especially with amino penicillin) — serum sickness — hematological: hemolytic anemia, neutropenia, thrombocytopenia — renal: acute interstitial nephropathy. Late (> 72 h): maculopapular rash, contact dermatitis

DIAGNOSTIC METHODS
Cutaneous testing.

- 75 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

Scratch, prick or intradermal skin tests with: — Polylysine penicilloyl (main component): P. P. L. 6 10-5 M. — Variable amounts of minor components (M. D. M.): benzylpenicillin, benzylpenicilloic acid, benzylpenilloate, benzylpenicilloylamine or benzylpenicilloate salt (now standardized on lyophilized form). Begin with the polylysine penicilloyl prick-test. If negative do the intradermal test with polylysine penicilloyl. If negative do the prick test with minor component mixture, and if this is negative do the intradermal test with minor component mixture. Results: wheal: — 0—3 mm: — 3—5 mm: — 5—10 mm: — > 10 mm: negative test undetermined test positive test strongly positive test

In case of anaphylactic shock, begin the test with M. D. M. at diluted concentrations (1/100 and 1/10). The reported incidence of positive skin-tests for detection of IgE sensitization in patients with suspected previous history of allergy to penicillin is less than 20%. Risk of anaphylactic reactions to penicillin is < 3% if skin tests for major and minor determinants are negative. For drugs other than penicillin G, conduct empirical skin tests using 0.25 mg/ ml; 2.5 mg/ ml; 25 mg/ ml for prick tests, and if negative 2.5 mg/ ml and 25 mg/ ml for intradermal injection. N.B.: A patch test may be positive in patients with contact dermatitis to aminopenicillin. Specific IgE: RAST and ELISA for the major determinant of the most common penicillins are available. However, there are no tests for IgE antibodies to minor determinants.

MECHANISMS
The metabolites of benzyl penicillin are haptens and can lead to the formation of antibodies by conjugating with a carrier to form a complete antigen (serum or tissue protein).
- 76 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

Reactions to penicillin may be caused by consuming milk or meat from cows treated with penicillin. Pregnant or nursing mothers treated with penicillin may induce reactions in fetuses or babies. Also occupational exposure, skin tests (theoretical). IMMEDIATE IGE HYPERSENSITIVITY Detection of IgE antibodies against major components (especially in accelerate reactions). Detection of IgE antibodies against minor components (especially in immediate reactions). Detection of IgE antibodies against side chains in some patients allergic to cephalosporins. IgE-mediated reactions are responsible for anaphylactic shock, angioedema as well as some forms of urticaria. CYTOTOXIC MECHANISMS Detection of IgG antibodies against erythrocytes and neutrophils. This mechanism is responsible for hemolytic anemia and leukoneutropenia. HYPERSENSITIVITY DUE TO IMMUNE COMPLEXES Implicated in serum sickness as well as in some forms of urticaria and maculopapular rash. DELAYED CELL-MEDIATED HYPERSENSITIVITY Responsible for contact dermatitis and some form of maculopapular rash. Two particular problems: — Ampicillin rash (5 to 8% of patients treated). Nonimmunological mechanism: the amine function of aminopenicillins causes changes in leukocyte function (especially lymphocytes), particularly if there is a concurrent disease (viral infection, chronic lymphoid leukemia). — Cross sensitivity between penicillin and cephalosporins: 8 to 10% risk of allergy to cephalosporins in patients allergic to penicillin.

- 77 -

ANTIBIOTICS, ANTIVIRAL, ANTIFUNGAL DRUGS

MANAGEMENT
Patients with a positive history of penicillin allergy and negative skin-tests for major and minor determinants have a risk of < 3%. Patients with a positive history and a positive skin-test response to penicillin have a 50% or greater risk of repeat reaction after administration of penicillin. Patients with a positive history of penicillin allergy but with negative skin-tests to major and minor determinants may receive a cephalosporin at no greater risk than the general population. Patients with a positive history of penicillin allergy and positive skin-tests to penicillin determinants have a 5-10% risk of clinical reactions to cephalosporins. An alternative antibiotic class should be proposed or provocation-desensitization with the cephalosporin if needed. The negative predictive value of skin-tests with cephalosporins is unknown. Example of penicillin desensitization: 0 min: 100 U orally (penicillin V) 15 min: 200 U orally 30 min: 400 U orally 45 min: 800 U orally 1 h: 1 600 U orally 1 h 15: 3 200 U orally 1 h 30: 6400 U orally 1 h 45: 12800 U orally 2 h: 25000 U orally 2 h 15: 50000 U orally 2 h 30: 100000 U orally 2 h 45: 200000 U orally 3 h: 400000 U orally 3 h 15: 200000 U subcutaneous (penicillin G) 3 h 30: 400000 U subcutaneous 3 h 45: 800000 U subcutaneous 4 h: 1 000000 U intramuscular

- 78 -

Garcia J. 1987 . ANTIFUNGAL DRUGS REFERENCES • • • • • Nicklas R. “Tests for immunological drug reactions”. Sullivan T. Rev.2): 543-625 Adkinson N. 1997 . J. 1992: 717-22 Blanca M. Cutaneous reactions: morbilliform eruptions 15%. 20: 475-81 Redelmeier D. “Allergy to penicillin with good tolerance to other penicillins. 79 (3): 523-32. Intern. Avila M.79 - .W. Immunol. Int.R. Vega J. Med.. Clin. theintravenous form of the drug is seldom used. Carmona M. 37: 29-35 Bernstein I.J.F Jr. In: Rose NR. Asthma. 75 (6.M.107: 204-15. J. generalized urticaria. Goodman E.J. 1998 . 1990 . Arch. Vervloet D. Terado S. ANTIVIRAL. CLINICAL MANIFESTATIONS Cutaneous: morbilliform eruptions. Saxon J. “Acute and chronic desensitization of penicillin allergic patients using oral penicillin”. Manual of clinical laboratory immunology.. 1995 . for reasons of efficacy and toxicity. Earl H. 150: 1939-45.S.A.ANTIBIOTICS. “Allergie aux penicillines”. 4th ed. erythroderma. de Marco EC ed. “Practice parameters for allergy diagnostic testing”. Juarez C. Ann. 1990 . facial rash.N. Sox H.L. Med. • • • PENTAMIDINE Aerosolized pentamidine is widely used for pneumocystis carinii pneumonitis in AIDS patients. Ann. “The role of skin testing for penicillin allergy”. Miranda A. Immunol. Lumry W. Washington: American society of microbiology. INCIDENCE Bronchospasm: 10 to 29%.. Study of the incidence in patients allergic to betalactams”. Gross G. Storms W. Clin. contact urticaria ( nurses)..J. “Bêta-lactam antibiotics”.. Immunol. Exp. Allergol. .L.A. Allergy Clin. Allergy.C Jr. Stark B. Conversely. Allergy. 101: S498-501 Birnbaum J. fr. 1987 .J. Allergy. “Immediate hypersensitivity reactions to b-lactam antibiotics” .

ANTIBIOTICS. In patients with hypersensitivity to systemic pentamidine. MECHANISMS Non specific histamine release (documented with intravenous pentamidine). ANTIVIRAL. hypersensitivity pneumonitis. some cases of bronchospasm). DIAGNOSTIC METHODS Cutaneous testing.006 0. Irritative effect (bronchospasm). MANAGEMENT Use premedication with nebulized albuterol and/ or cromolyn sodium prior to aerosolized pentamidine. cautious administration of aerosolized pentamidine is safe when the following protocol is applied: Dilution of 300 mg of pentamidine isethionate in 20 ml of sterile water (15 mg/ ml). Dilution 1/10 000 1/1 000 1/100 1/10 Full strength Volume inhaled 4 4 4 4 20 . Intravenous test dose is dangerous (2 deaths reported). Skin-prick tests positive with 3 mg/ ml pentamidine isethionate in contact urticaria and some cases of bronchospasm. IgE-mediated hypersensitivity (contact urticaria. Intradermal skin-tests: false positive with 0. laryngeal edema.015 and 0. Slow intravenous administration (decreases non specific histamine release).80 - Pentamidine (mg) 0. ANTIFUNGAL DRUGS Respiratory: bronchospasm (aerosolized pentamidine).15 mg/ ml pentamidine.06 0. Other: conjunctivitis. tongue swelling.6 6 300 .

L. Intern..81 - . “Contact urticaria from pentamidine isethionate” . “Adverse reactions to trimethoprim-sulphamethoxazole in patients with the acquired immunodefiency syndrome”.96: 65-97 Belsito D. O’Sullivan M. Presse. “Bronchospasme de mécanisme allergique a l’isethionate de pentamidine en aérosol”.M.. Vincent D.G. RISK FACTORS Unknown. Allergy. “Prophylaxis of AIDS-related Pneumocystis carinii pneumonia with aerosolized pentamidine in a patient with hypersensitivity to systemic pentamidine”.. 22 (11): 554 Baum C.V. Clin. AIDS. DIAGNOSTIC METHODS None. Ann.M. Med. Simon G. ANTIVIRAL. 1995 . Mills J. CLINICAL MANIFESTATIONS Urticaria. Tightness of the chest. 1993 . .. Difficulty swallowing. 1984 . Immunol. 29 (3): 158-9 Pradalier A. Girard P. Bouée S. 1992 . MECHANISMS Unknown. Dermatitis. Wofsy C. “Pathogenesis and management of HIV-associated drug hypersensitivity”. 1993 .ANTIBIOTICS.A. Med. Contact.A. ANTIFUNGAL DRUGS REFERENCES • • • • Carr A. 90 (2): 268-9 Gordin F. Clin. 100: 495-9 • PRAZIQUANTEL Praziquantel is an isoquinolin drug widely used as trematodicide.B. Rev. Sonnabend J. Cooper D. INCIDENCE Exceptional (one case published). J.

ANTIBIOTICS. positive in one patient with a pruriginous rash. Premedication with hydroxyzine.. dexamethasone and prednisone 6 hours prior to administration of praziquantel: 18 mg x 6 then 180 mg x 3. Clin. Increasing by 50 to 100% every 30 minutes up to the total dose. ANTIVIRAL. ANTIFUNGAL DRUGS MANAGEMENT Desensitization. . INCIDENCE Uncommon. J. CLINICAL MANIFESTATIONS Mainly cutaneous: flushing. 90: 5-867 PYRAZINAMIDE Synthetic pyrazine analogue of nicotinamide used in the treatment of tuberculosis.82 - . MECHANISMS. 1992 . MANAGEMENT Desensitization if absolutely necessary: starting dose 5 mg. DIAGNOSTIC METHODS Cutaneous testing Patch-tests: pyrazinamide 1% eth. “A clinical approach to a patient with praziquantel hypersensitivity”. urticaria. rash. Allergy. and 10% eth. then 360 mg x 3 (at 15 minute intervals). Immunol. REFERENCES • Huang S.W. Undetermined.

Trotta R. Contact Dermatitis. 1988 . ANTIFUNGAL DRUGS REFERENCES • • • Shorr A. Patch-tests (quinine 1% pet). fixed drug eruption. fever. Chest . Thrombocytopenia is more frequent (1/1000 to 1/3500). rash. Diaz-Perez J. 109 (3): 855-6 Goday J. 22 (3): 181-2 Soyez F. Intradermal skin-tests: positive 1/1000 in one case of anaphylaxis. QUININE Quinine is the main alkaloid derived from cinchona bark. It is used in medicine mainly as an antimalarial drug but also as an antipyretic and analgesic easily available in many over-the-counter preparations (treatment of leg cramps). fr. DIAGNOSTIC METHODS Cutaneous testing. CLINICAL MANIFESTATIONS Anaphylactic shock. ANTIVIRAL. 28: 1. . 1990 . 1996 . Aguirre A. INCIDENCE Anaphylaxis is uncommon.ANTIBIOTICS. “ A positive patch test in a pyrazinamide drug eruption”. Allergol. Photo-patch tests. Agranulocytosis. contact dermatitis (hair lotions). lichenoid photosensitivity. “Réaction inhabituelle au pirilène”. Philip-Joet F.. disseminated intravascular coagulation.F. Surpas P. Eczematous eruption (photoallergic). allergic vasculitis. Rev.83 - . Arnaud A.F.L. “Pyrazinamide hypersensitivity”. Vestri R. thrombocytopenia. hemolytic uremic syndrome.

Med. Intern. “Hypersensibilité immédiate à la quinine”. Ann.. 119: 243-4 Ljunggren B. Quinine dependent erythrocyte antibodies (antiglobulin test).B. ANTIFUNGAL DRUGS Serologic methods Quinine dependent neutrophil antibodies IgG. Campbell A. Quinine dependent platelet antibodies IgG..84 - . Hindsen M. anemia.F. 119: 215-7 Aster R.H. 1992 . “Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine” . 1985 . Warning of quinine potential harmful effects should be printed on all over the counter preparations and on bottles of tonic-water. Senft M. agglutination).ANTIBIOTICS. Stronsek D. leukopenia. Ann.. 1993 . Delayed cell-mediated hypersensitivity: contact dermatitis. MANAGEMENT Cross-sensitivity between quinine and quinidine (photoallergy) Quinine should be available one prescription only. Contact.H. . ANTIVIRAL. “Quinine sensitivity: a new cause of the hemolytic uremic syndrome”. Vervloet D. coagulopathy and renal failure associated with multiple quinine-dependent antibodies”. IgM (immunofluorescence. Presse Med. 1993 .C. 14 (17): 967-9. Charpin J. 26: 1-4 Pin I. Dermatitis. Cytotoxicity: thrombocytopenia. Med. Intern. IgM (immunofluorescence). “Recurrent pancytopenia. Dor P. REFERENCES • • • • Maguire R. MECHANISMS IgE-mediated hypersensitivity: few cases with positive cutaneous tests and specific IgE. Oral provocation test: positive in one case of anaphylaxis. Specific IgE Positive RAST and RAST-inhibition in one case of anaphylaxis. Isaksson M.

. RISK FACTORS AIDS. Norfloxacin. Glafenine. New quinolones are used in various systemic infections. In France 43 cases of anaphylaxis to quinolones were transmitted to pharmacovigilance in 1992 (first generation quinolones were almost always involved). Enoxacin. Nitroxolin). ANTIFUNGAL DRUGS QUINOLONES Synthetic antibiotics first generation quinolones were used for treatment of urinary tract infections because of their rapid excretion by kidney. Female gender. pruritus. Cutaneous: maculopapular or bullous exanthema.ANTIBIOTICS. INCIDENCE 18 to 23/10 million days of treatment. Sun exposure (photosensitivity). First generation: Nalidixic acid. neuropsychiatric manifestations. Ciprofloxacin. fever. Tiliquinol. Past exposure to quinolones or related compounds (Chloroquine. arthralgias. Pipemidic acid.85 - . fixed drug eruption and rarely Stevens-Johnson or Lyell’s disease (enoxacin. Flumequin Second generation: Pefloxacin. sparfoxacin and lomefloxacin are wellknown to cause photosensitivity). Ofloxacin. ANTIVIRAL. Oxolinic acid. Differentiate from other side effects: gastrointestinal disturbance. CLINICAL MANIFESTATIONS General: anaphylactic shock. Lomefloxacin Third generation: Sparfloxacin. angioedema.

Ciprofloxacin 0. Diez M. Immunol. MECHANISMS Unknown. A propos de huit observations”. Rutishauser M.86 - . Specific IgE: none.Clin. Skin. 1995 . 96: 1001-2 Davila I. Cross-reactivity between first and second generation quinolones +++. Allergy. 48: 388-90 RIFAMPICIN Rifampicin is a semi-synthetic broad-spectrum antibiotic very effective against mycobacteria.. Pauli G. 1997 . 37 (1): 15-9 Lantner RR. Charpentier C. MANAGEMENT Eviction (all quinolones). Lazaro M. “L’allergie aux quinolones. REFERENCES • • • • • Kimura M. 52: 1246-8 Arboit F. . Fr. Dermatitis. Kawada A. ANTIFUNGAL DRUGS DIAGNOSTIC METHODS Cutaneous testing.L. . “Photosensitivity induced by lomefloxacin with crosssensitivity to ciprofloxacin and fleroxacin”. 1998 .ANTIBIOTICS.. Quirce S. and Staphylococci.prick tests and intradermal tests give false positive results. If absolutely necessary: desensitization.J. Fraj J. 1997 . ANTIVIRAL. J. Bessot J. Allergy. Photo-patch tests with lomefloxacin are usually negative and crosssensitivity with other quinolones is rarely reported. “Oral “desensitization” of maculopapular exanthema from ciprofloxacin”. “Ciprofloxacin desensitization in a patient with cystic fibrosis”. Contact. de La Hoz B.. 38: 180 Bircher A. Brucella.C. Allergy 1993 . “Cross reactivity between quinolones.05 mg to 150 mg (3H). Report of three cases”. Rev. Allergol. Deblay F. Challenge test: 11 cases published. Dietemann A.

RISK FACTORS AIDS. ANTIVIRAL. renal failure. DIAGNOSTIC METHODS Cutaneous testing. Haematological: thrombocytopenia.1 to 4%) . ANTIFUNGAL DRUGS INCIDENCE Anaphylactic shock is rare (6/30 000 reports of possible allergic reactions to rifampicin). acute haemolytic anemia. urticaria. Specific IgE (RAST) Circulating rifampicin dependent antibodies. . facial swelling. Flu-like syndrome: rare when administered in daily regimens (0.87 - . erythema. Intradermal skin-tests: 1/1000 to 1/10 (intravenous rifampicin 60 mg/ ml): positive in a few cases of anaphylactic shock. frequent in intermittent or discontinuous regimens (20%). Renal: renal failure. maculopapular rash. antiglobulin test) Circulating immune complexes. Haemolytic complement titers MECHANISMS Possible IgE-mediated hypersensitivity: anaphylactic shock with immediate positive skin-tests. Stevens-Johnson’s syndrome. CLINICAL MANIFESTATIONS General: anaphylactic shock. vasculitis.ANTIBIOTICS. thrombocytopenic purpura). red man syndrome. Respiratory: shortness of breath. Cutaneous: pruritus. complement binding test. Intermittent treatment (flu-like syndrome. especially when intermittent therapy is used (Coombs test. bronchospasm. serum sickness. haemolytic anemia.

thrombocytopenia). MANAGEMENT Desensitization (contra-indicated if severe manifestations: renal failure. Respir. 1994 .ANTIBIOTICS. Nessi R.. Am. Type III hypersensitivity: serum sickness.5 mg . ANTIVIRAL. Fowst G. 32 mg . Care. J. Ogunkoya A. REFERENCES • • • • • Matz J. J.J.. ANTIFUNGAL DRUGS Type II hypersensitivity: blood dyscrasias. “Serum sickness-like illness associated with rifampicin”. “Rapid oral desensitization to isoniazid and rifampin”.M. Ann. 97 (4): 403-4 Holland C. 2 mg . Borish . 98: 1518-9. INCIDENCE Uncommon. . 73 (2): 123-5 Cnudde F. 4 mg . Respir. — 0.1 mg to 300 mg within 17 hours.88 - . Ferreira A. 150 mg at 45 minutes intervals. Cuevas M. “Oral desensitization to rifampin and ethambutol in mycobacterial disease”. Rosenwasser L.1 mg . Med.L.C. Dis.. Routes J. Suppl. Crit. 149 (3. then 300 mg x 2 next day. J.J. 1994 . comment”. 1973 . Malasky C. Scand. 1990 . 2 protocols: — 0. Chest. 50 mg: 100 mg . Am. 0. Domenichini E. Widely used by surgeons for local application. Bielory L. 8 mg . 16 mg . then 300 mg 3H30 later. 1 mg . Med. 84: 15-19 RIFAMYCIN SV Semi-synthetic antibiotic derived from Rifamycin B. Allergy. 1994 .1): 815-7 Parra F. Perez-Elias M. “Allergic reactions during rifampicin treatment: a review of published cases”.M. Leynadier F. “The diagnosis of allergy to rifampicin confirmed by skin-test: letter .

Allergologie. Jeannin P. ANTIVIRAL. Facon A. Tille-Leblond I. Clin. MECHANISMS IgE-mediated allergy.ANTIBIOTICS. Porri F. Possible cross-reactivity with Rifampicine and Rifabutine. Tonnel A. “Anaphylactic reaction to local administration of Rifamycin” (abstract). Specific IgE: detected in at least one case. 16: 284-5 . Immunol.B. 95: 1-7 Piazza I. 1999 in press Cardot E. Pommier G.J. J. DIAGNOSTIC METHODS Cutaneous testing. “Anaphylactic reaction to rifamycin SV: presence of specific IgE antibodies”. 1995 . Bonerandi J.J. MANAGEMENT Avoidance. 1987 . 12 (s): 96 Grob J. Intradermal tests 50 µg/ml to 5000 µg/ml (positive in 4/4 patients with anaphylaxis). “Contact urticaria from Rifamycin”. Contact urticaria.M.. Prick-tests 50µg/ml. Allergy. Dermatitis. J. Collet-Vilette A. Breuil K.89 - . Vervloet D. “Anaphylactic reaction to local administration of Rifamycin SV”. Allergy. REFERENCES • • • • Magnan A. Venemalm L. Contact. Immunol. Anaphylactic reactions. Antiparasite cytotoxicity by platelets (positive in 4/4 patients with anaphylaxis). Clin. ANTIFUNGAL DRUGS CLINICAL MANIFESTATIONS Contact dermatitis. Patte F. 1989 . Histamine release (positive in 2/3 patients with anaphylaxis). Robaglia A.

90 - . ANTIVIRAL. Venous stasis Leg ulcers. 1996 . INCIDENCE 25 cases of contact dermatitis have been reported. MANAGEMENT Avoidance. 34: 159 . “Contact dermatitis from sodium fusidate”. Pelletier N.ANTIBIOTICS. RISK FACTORS Atopic dermatitis. CLINICAL MANIFESTATIONS Contact eczema. REFERENCES • Giordano-Labadie F. Contact Dermatitis. or in 0. Bazex J. DIAGNOSTIC METHODS Patch-tests with sodium fusidate in 1 to 2% in pet.1% propylene glycol. ANTIFUNGAL DRUGS SODIUM FUSIDATE Sodium fusidate is a sodium salt of fusidic acid widely used for the treatment of cutaneous infections with Staphylococcus aureus. MECHANISMS Type IV delayed hypersensitivity.

Idiosyncratic or hypersensitivity toxicity: 1° Sulfonamide allergy (rare). Occurring 7-12 days after starting treatment. Duration and dose of therapy. INCIDENCE General population: 3 to 5%. Anaphylactic shock. 2° Sulfonamide hypersensitivity reactions (AIDS). Intrinsic toxicity: renal toxicity. renal tubular acidosis. RISK FACTORS (uncertain) Degree of immunodeficiency (CD4+<200/mm3). AIDS patients treated with high-dose cotrimoxazole: 44 to 83%. ANTIVIRAL.91 - . Urticaria. hypoglycemia. ANTIFUNGAL DRUGS SULFAMETHOXAZOLETRIMETHOPRIM (SMX-TMP) Both components of cotrimoxazole act as antifolate drugs by inhibiting the biosynthesis of tetrahydrofolic acid. Slow acetylator phenotype. rash. Coexisting viral infection. CLINICAL MANIFESTATIONS Differentiate: Pharmacologic toxicity: blood dyscrasias associated with folate deficiency. Atopic diathesis. methaemoglobinaemia. . Bronchospasm. Cotrimoxazole is widely used in AIDS patients with Pneumocystis carinii pneumonia. goitrogenic effects. nausea and vomiting. Severe. life threatening idiosyncratic toxicity: 1/10000. keratoconjunctivitis sicca. headache and neurological disturbances.ANTIBIOTICS.

specific IgE. uveitis. SMX-HA auto-oxidizes to the more reactive nitroso metabolites with production of superoxide anion radicals.ANTIBIOTICS. The SMX-HA metabolic is believed to be critical in the pathogenesis of many of the SMX adverse effects. Inhibition of skin-test reactivity with a monovalent inhibitor. Fever. Other cutaneous manifestations: erythema nodosum. serum sickness. most prominent on the body and upper limbs. 27% positive in 44 patients with histories of allergic reaction to sulfamethoxazole. leukocytosis. erythema multiforme. Skin-prick tests with SMX-poly-L-tyrosine up to 1 mg/ ml. Anicteric hepatitis. ANTIVIRAL.92 - . SMX is either acetylated or hydroxylated at the N4 position to form: N4 acetyl SMX (45-70%) and N4 hydroxyl SMX (2-5%): SMX-HA. . Specific IgE anti -SMX (RAST and RAST inhibition). myocarditis. positive skin-tests. ANTIFUNGAL DRUGS Cutaneous rash: erythematous. The major determinant is N4-sulfonamidyl group 2° Sulfonamide hypersensitivity reactions in AIDS patients. eosinophilia. lupus erythematosus. Acute interstitial pneumonitis. pruritis. Intradermal skin-tests with SMX-poly-L-tyrosine 0. maculopapular. SMX is oxidized to SMX-HA by the cytochrome P450 and by myeloperoxidase-dependent oxidation in neutrophils and macrophages/ monocytes.03 mg/ ml. toxic epidermal necrolysis. DIAGNOSTIC METHODS (in immediate type I reactions) Cutaneous testing. MECHANISMS 1° IgE-mediated hypersensitivity (rare). Aseptic meningitis.

ANTIVIRAL. pruritic or non-pruritic. . there are 3 possibilities: 1° Treatment throughout the duration of hypersensitivity. Slow acetylator phenotype is associated with a susceptibility to sulfonamide hypersensitivity reactions. Glutathione protects against the toxicity of SMX-HA to isolated peripheral blood mononuclear cells by preventing its oxidation to nitroso SMX. 3° Desensitization. 2° Re-challenge A history of cutaneous rash is not a contra-indication to retreatment. high incidence of hypersensitivity reactions to sulfonamides in AIDS patients is probably multifactorial: highdose regimens. This binding is inhibited by acetylation. ANTIFUNGAL DRUGS Nitroso-SMX reacts with glutathione to form an unstable semimercaptal which is reduced back to SMX-HA in the presence of excess glutathione. since only 20 to 66% cutaneous reactions occur on re-challenge. Faced with hypersensitivity reaction to cotrimoxazole in AIDS patients. There is no evident cross-reactivity between sulfonamide antimicrobials and sulfamide diuretics (furosemide. fever) may be treatedsymptomatically with antihistamines and may resolve.ANTIBIOTICS. hypoglycemics (tolbutanol. The rash (general exanthema. The nitroso SMX which covalently binds to proteins is the ultimate toxic metabolite.93 - . In summary. There is no correlation between presence of anti-SMX-antibodies (IgG) and occurrence of adverse reaction. chlorothiazide. altered immunological responses. chlorpropanol) or antihypertensives (diazoxide). MANAGEMENT Cross-sensitivity between SMX-TMP and sulfadiazine is frequent. acetazolamide) . reaction with glutathione or reduction back to SMX-HA and SMX. except thrombocytopenia. altered pathways of drug metabolism.

Katlama C. Clin. Life-threatening reactions may occur during desensitization.. Sullivan T. 88 (5): 784-92 • . 94 (6.V.P. Allergy. 1995 . Bricaire F. Clin.8 8-1. AIDS. Sullivan T. Dermatol. REFERENCES Caumes E.A. Trepanier L. “Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins” . ANTIVIRAL. Guermonprez G. Adverse Drug. “Efficacy and safety of desensitization with sulfamethoxazole and trimethoprim in 48 previously hypersensitive patients infected with human immunodeficiency virus”.96: 65-97 ·• Meekins C. Spielberg S. 133 (4): 465-9 • Cribb A. dose progression and success rate (33 to 96%). 1997 . ANTIFUNGAL DRUGS Numerous studies.J. 1991 . involving no more than 45 patients differed greatly with regard to the inclusion criteria.S. Immunol. Arch. “Detection of human IgE to sulfamethoxazole by skin-testing with sulfamethoxazoyl-poly-L-tyrosine”.ANTIBIOTICS. 15 (1): 9-50 • Carr A. Lee B. J.S.E. 1994 . Rev. React. Clin.. Cooper D.A. Toxicol.94 - . Immunol. For example: Hours D1 9 AM 11 AM 1 PM 5 PM 9 AM 3 PM 9 PM 9 AM Dose of SMX-TMP (mg) 4-0. Lecomte C.L.J. Allergy.6 20-4 40-8 80-16 160-32 200-40 400-80 D2 D3 Risk factor of desensitization failure: female sex. duration of the protocol. “Pathogenesis and management of HIV-associated drug hypersensitivity”.. Rev. “Adverse reactions to sulfonamide and sulfonamide-trimethoprim antimicrobials: clinical syndromes and pathogenesis”.1): 1017-24 · Gruchalla R. J. Gruchalla R. 1996 ..

ANTIFUNGAL DRUGS SULPHADIAZINE Sulphadiazine combined with pyrimethamine is the most effective first-line treatment of cerebral toxoplasmosis in AIDS patients (sulphadiazine 1-1. MECHANISMS See sulfamethoxazole-trimethoprim. x 6 weeks + pyrimethamine 100-200 mg loading dose. INCIDENCE High. Stevens-Johnson’s syndrome.Oral route in 5 days +/.ANTIBIOTICS.5 g q 6 hours p. 2 mg/ ml. MANAGEMENT Alternative therapy Replace sulphadiazine with clindamycin. itching. x 6 weeks + leucovorin 10-20 mg / day p. Skin-prick tests (1 mg/ ml. No specific histamine release. thrombocytopenia (12%). facial angioedema.).o. conjunctivitis. CLINICAL MANIFESTATIONS General: fever (10%).o. Cutaneous: rash (19%): maculoerythematous or morbilliform . 5 mg/ ml) are negative. ANTIVIRAL.o.95 - . but no accurate findings. Haematological: leukopenia (40%). then 50-75 mg / day p.corticosteroids . clarithromycin or atovaquone Desensitization: 2 different protocols have been published: 1°. DIAGNOSTIC METHODS Cutaneous testing. RISK FACTORS AIDS. azithromycin.

infections.S. “Sulphadiazine desensitization in patients with AIDS and cerebral toxoplasmosis”. 10 (6): 439-54 Tenant-Flowers M. Boyle M.96 - . chlortetracycline. Perez Elias M. Carlin E. Cuevas M.A. J. “Therapeutic approaches for AIDSrelated toxoplasmosis”. Main J. Weston R. In dermatological practice.5 g/6 hours Day 5: 750 mg and 750 mg Day 10: 2 g/6 hours Success rate: 100% REFERENCES • • • • Behbahani R. “Management of sulfadiazine allergy in patients with acquired immunodeficiency syndrome”.Oral route in 10 days without corticosteroids Day 1: 5 mg and 10 mg Day 6: 1 g and 1 g Day 2: 20 mg and 40 mg Day 7: 1 g/8 hours Day 3: 80 mg and 160 mg Day 8: 1g/6 hours Day 4: 250 mg and 500 mg Day 9: 1. Davila Ruiz I. Clin. they are commonly used in the treatment of acne and rosacea.. ANTIFUNGAL DRUGS Day 1: 10 µg to 200 µg Day 2: 300 µg to 8 mg Day 3: 15 mg to 500 mg Day 4: 500 mg: 1 x 4 / day Day 5: 500 mg: 2 x 4 / day Success rate: 62% 2°. Fraj Lazaro J. 1994 . Drug. Fernandez-Rivas M. 88 (1): 137-8 TETRACYCLINE GROUP The tetracycline antibiotics are a group of broad spectrum protein synthesis inhibiting compounds used in the treatment of Gram+ and Gram . Saf. Moshfeghi M. Cooper D. ANTIVIRAL. Harkness J.J. oxytetracycline . Allergy. Penny R. Natural tetracyclines: basic tetracycline. Pharmacother. 29 (7-8): 760-8 Peters B. Ann.J. AIDS. Baxter J.. 1991 . Immunol.L. Quirce Gancedo S. Alvarez Cuesta E.D. 1995 . Sweeney J. “Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection”..J. Marriott D.J. Carey D. Weber J. Puyana Ruiz J. Loveless S. 5 (3): 311-5 de la Hoz Caballer B. 1991 ..ANTIBIOTICS. Cuesta Herranz J.

Renal: acute interstitial nephritis. ANTIVIRAL. Intradermal skin-tests: positive in one patient with anaphylaxis. Migration inhibitory factor (MIF) + mast cell degranulation test positive in 4/15 patients. Re-challenge with minocycline or tetracycline is not recommended in patients with severe reactions. Cutaneous: pruritus.ANTIBIOTICS. arthritis. photosensitivity.97 - . Haematological: autoimmune hemolytic anemia. leukopenia. CLINICAL MANIFESTATIONS General: anaphylactic shock. Hemagglutinating antibodies positive in patients with Lyell’s syndrome . erythema multiforme. fixed drug eruption. bronchospasm. Hepatic: hepatitis. . fever. rash. Patch-tests (chlortetracycline hydrochloride 0. 3 distinct syndromes have been reported: — hypersensitivity syndrome reaction (HSR): fever. DIAGNOSTIC METHODS Cutaneous testing. angioedema. exanthema — drug induced lupus (DIL) . rash. Stevens-Johnson’s syndrome. arthralgia and/or lymphadenopathy. arthralgia. contact dermatitis. minocycline INCIDENCE Uncommon. urticaria. serum sickness. Deaths reported. occurring 2 to 4 weeks after the start of therapy — serum sickness like reaction (SSLR): fever.5% in pet). Respiratory: pneumonitis. urticaria. ANTIFUNGAL DRUGS Semi-synthetic tetracyclines: doxycycline. thrombocytopenia. internal organ involvement. Lyell’s syndrome.

. MANAGEMENT Cross-sensitivity between tetracycline/doxycycline and minocycline concerning fixed drug eruptions is not constant. Dermatol. 7: 285-90 TRIMETHOPRIM Trimethoprim (2. Das A. Knowles S. J. 1996 . Dermatol. 133 (10): 1224-30 Knowles S.ANTIBIOTICS.E. 11 (5. 1984 . “Tetracycline asthma: a case report”.1): 900-2 Menon M. Acad.H. 1996 .. thereby causing direct cell damage.. Dermatol. Allergy.R.H. Am. Amir J. 1977 .5'-trimethoxybenzyl) pyrimidine) is a synthetic folate antagonist anti-infective agent used for the treatment of urinary tract infections and for Pneumocystis pneumonia in AIDS patients. 1997 .S. Patients who experienced a serious adverse event while receiving one of the tetracycline antibiotics must avoid all tetracyclines until more information is available. Varsano I. Clin. Arch. “Serum-sickness-like reaction associated with minocycline therapy in adolescents”. Shear N. 132 (8): 934-9 Harel L. “Comparative safety of tetracycline. Patients receiving long-term minocycline therapy should have an antinuclear antibody test and assessment of hepatic transaminase levels only if symptoms develop during their course of treatment. Livni E. ANTIFUNGAL DRUGS MECHANISMS The potential reactive metabolites generated by minocycline may bind to tissue macromolecules.K.4-diamino-5-(3'.. Shapiro L.P. Arch. “Lack of cross-sensitivity between tetracycline. minocycline and doxycycline”. Shear N. or they may act as haptens.98 - .4'. ANTIVIRAL. Pharmacother. Ann. REFERENCES • • • • • Shapiro L. .E. 30: 481-3 Bargman H. doxycycline and minocycline with regard to fixed drug sensitivity to tetracycline”. “Serious adverse reactions induced by minocycline and review of the literature”. Straussberg R..R.

pruritus. Vega A. Bronchospasm. ANTIVIRAL. Immunol. specific IgE) 3 different IgE antibody binding determinants: — 3-4 dimethoxybenzyl group. Rash. MANAGEMENT Avoidance. facial angioedema. Allergy. fixed drug eruption. REFERENCES • • • Pham N. ANTIFUNGAL DRUGS INCIDENCE High. 97 (1. Baldo B. general urticaria. Allergy. Skin-prick tests with trimethoprim 10 mg/ ml in glycerol. CLINICAL MANIFESTATIONS Anaphylactic shock. — entire TMP molecule.T. Specific IgE RAST TMP-HSA + RAST inhibition (TMP-HSA coupled to bisoxirane-activated sepharose or nitrocellulose paper disks). Clin. hypersensitivity pneumonitis. 26: 1155-60 Cabanas R. “Anaphylaxis to trimethoprim”. 17: 209-16 .A. J. Clin. Manfredi M.A. Martin-Esteban M. — 2-4 diamino-5-(3'. “An immunoassay for the detection of IgE antibodies to trimethoprim in the sera of allergic patients”.1): 137-8 Harle D.A. 1987 . Smal M. “Fine structural specificity differences of trimethoprim allergenic determinants”. 1996 . Exp. Clin. DIAGNOSTIC METHODS Cutaneous testing. Pascual C.4'-dimethoxy-benzyl) pyrimidine group. Caballero M. Allergy. Baldo B. Zerboni R. 1996 .A. MECHANISMS IgE-mediated hypersensitivity (positive cutaneous tests.99 - .ANTIBIOTICS.G. Van Nunen S.H..

Stevens-Johnson’s syndrome.1 µg/ml. Skin-prick tests are usually negative. ANTIVIRAL. fever. ANTIFUNGAL DRUGS VANCOMYCIN Preferred antimicrobial agent for the treatment of methicillineresistant Staphylococcus aureus . CLINICAL MANIFESTATIONS “Red man syndrome”: flushing. DIAGNOSTIC METHODS Cutaneous testing. Vancomycin is a complex tricyclic glycopeptide obtained from the nocardia species Amycolatopsis orientalis.ANTIBIOTICS. Duration > 7 days: risk factor for delayed reactions. RISK FACTORS Association with narcotics. Linear IgA bullous dermatosis. pruritus. Occurring 8 to 55 days after the start of treatment. erythema multiforme. INCIDENCE Adults: 5 to 14%. hypotension (occurs in 50% to 90% of normal volunteers infused with 1 g of vancomycin over one hour).02 ml at 0. Age < 40 years: risk factor for infusion-related and delayed reactions. Delayed cutaneous eruptions: maculopapular rashes. Intradermal skin-tests: few cases published positive with 0. . interstitial nephritis.6 to 35%.100 - . fever. Often associated with eosinophilia. toxic epidermal necrolysis. exfoliative dermatitis. hypoxia and eosinophilia (inhaled vancomycin used in decontamination of the respiratory tract for allogenic bone marrow transplantation). One case with dyspnea. Children: 1.

101 - . Antimicrob.ANTIBIOTICS. 1997 . Turnidge J. Pretreatment with an antihistamine (hydroxyzine 50 mg 2 hours before a vancomycin dose). “Vancomycin anaphylaxis and successful desensitization”. or direct inotropic myocardial depression.M. ANTIVIRAL. Myocardial dysfunction is secondary to endogenous myocardial histamine release.D. Chemother. Slowing infusion rate (no faster than 10 mg/ min). 17 (6): 1341-44 Korman P.E. Allergy. Reisman R. One case published of specific histamine release and crossreactivity between vancomycin and teicoplanin.. “Delayed hypersensitivity reaction to vancomycin”. Hypotension is linked to peripheral vasodilatation following histamine release. 1997 . “Risk factors for adverse cutaneous reactions associated with intravenous vancomycin” . DESENSITIZATION Rush: 0. MANAGEMENT PREVENTION OF THE “RED MAN SYNDROME”: Decreasing vancomycin doses.. 73 (5): 402-4 . IgE-mediated hypersensitivity reactions do exist in a few cases. REFERENCES • • • Marik P. Fast: 0. Middleton E Jr. 39 (3): 371-81 Anne S. Ferris N. Cross-reactivity between vancomycin and teicoplanin remains controversial. Pharmacotherapy. ANTIFUNGAL DRUGS Basophil histamine release test.5 mg/500 ml// 4 hours to 1 000 mg/250 ml// 4 hours in 13 days. 1994 . Grayson M.0001 mg/ ml infusion to 10 mg/ ml infusion in 100 minutes with pretreatment (antihistamines).. MECHANISMS “Red man syndrome” is due to histamine release into the blood by vancomycin with no antibody or complement involvement. Ann. J.E.L.

Clin. Marks D. Mc Lean J. ANTIFUNGAL DRUGS • Wong J. Possible production of toxic metabolites (like sulfonamides). RISK FACTORS Unknown. Allergy.T.1): 189-94 ZIDOVUDINE Dideoxynucleoside analog of thymidine. “vancomycin hypersensitivity: synergism with narcotics and “desensitization” by a rapid continuous intravenous protocol”. 1994 ..J. Bloch K.E.R. MANAGEMENT Desensitization. J. — 0. Bronchospasm. acting as a virostatic drug against HIV by interfering with viral reverse transcriptase. CLINICAL MANIFESTATIONS Erythroderma. INCIDENCE Few cases of zidovudine allergy have been published. Leukocytoclastic vasculitis. 94 (2. Urticaria. Maculopapular rash. MECHANISMS Unknown.ANTIBIOTICS.A.008 mg to 1 200 mg (37 days) — 10 mg to 500 mg (10 days) The protective effect of corticosteroids is controversial. 2 protocols have been published. ANTIVIRAL. DIAGNOSTIC METHODS No in vitro or in vivo tests are available. Fever. Ripple R. .102 - . Immunol.

103 - .. 91 (2): 683-85 Mc Kinley G.F. Lancet. “Zidovudine-related erythroderma and successful desensitization: a case report”. “Allergy and desensitization to zidovudine in patients with acquired immunodeficiency syndrome (AIDS)”. 1993 .H. Allergy. Pellon L.S.. Clin. 98: 234-5 Carr A. Rodriguez F.A.. Grieco M. Immunol. “Urticarial reaction to zidovudine”.F.ANTIBIOTICS. J. 1990 . Allergy. Clin. Penny R. Jerez J. 336: 384 . ANTIFUNGAL DRUGS REFERENCES • • • Duque D. 1996 . Maquiera E. de la Puente J. Immunol. Mazza D. Cooper D. J. ANTIVIRAL.

ANTIBIOTICS.104 - . ANTIVIRAL. ANTIFUNGAL DRUGS .

105 - .CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS IV CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS .

Cutaneous biopsy (toxic epidermal necrolysis). Cross-reactivity between alkylating agents is exceptional. Cutaneous: toxic epidermal necrolysis. pharyngitis. MANAGEMENT Avoidance. INCIDENCE Uncommon. CLINICAL MANIFESTATIONS General: fever. Pulmonary: interstitial pneumonitis (14 cases up to 1994). stomatitis. urticaria. Patch-tests: chlorambucil mixed in vaseline 5% and 10% positive in 2 cases of toxic epidermal necrolysis. Hematological: immune hemolytic anemia (antibody able to bind complement to erythrocytes only in the presence of chlorambucil). maculopapular erythema. MECHANISMS Unproven.106 - . . DIAGNOSTIC METHODS Cutaneous testing. but type III allergic reaction is likely (immune complex deposition). Re-challenge test is often positive but harmful. conjunctivitis.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS ALKYLATING AGENTS CHLORAMBUCIL Chlorambucil is an alkylating agent widely used in the treatment of lymphoproliferative diseases.

Aust. “Allergic reaction with immune hemolytic anemia resulting from chlorambucil”. Chest. 17 (6): 600-2 CYCLOPHOSPHAMIDE Nitrogen mustard derivative widely used in the treatment of various malignancies and auto-immune disorders. Couderc L. “Unusual reaction to chlorambucil: a case report”. 1989. Ozcanu A. Israel-Biet D. Hocker G. Neubauer A. “Chlorambucil . “Chlorambucil allergy. ifosfamide. Gargovich A. Torino F. ”Severe adverse skin reaction to chlorambucil in a patient with chronic lymphocytic leukemia”. INCIDENCE Low. 1987.A.Z. and cyclophosphamide metabolites: 4 hydroperoxycyclophosphamide and phosphoramide mustard. 105 (2): 634-6 Pietrantonio F.. Thomson D. 8 (5): 468-9 Crestani B. Frija J.. cyclophosphamide metabolites 1 µg/ml to 10 mg/ ml.N. Hematol.107 - . Clauvel J.bronchospasm (+++). 1990. Anticancer. J. CLINICAL MANIFESTATIONS (higher with intravenous than oral route) Urticaria (+++) immediate or delayed.a series of three cases”.P. Am. 32 (3): 230-1 Hitchins R. 54 (3): 109-11 Thompson-Moya L. Ozcan C. Fewer than 25 cases reported. DIAGNOSTIC METHODS Cutaneous testing with cyclophosphamide.. Heuft H. Harputluoglu M.associated pneumonitis”. 1994. Prick-tests and intradermal tests: cyclophosphamide and ifosfamide 1 mg/ ml and 10 mg/ ml. Moriconi L. Turhan O. N. Angioedema.G. Lett. Romano A. Martin T...J. 1997. Anaphylactic shock +/. Herrmann R. Karincaoglu Y. Cancer. Jaccard A. . Drugs.B. Med. J.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • • • Aydogdu I. Vasculitis.

Arthritis. Condemi J. 97: 26-33 Knysak D. Allergy Clin. MECHANISMS Possible IgE-mediated allergy. ifosfamide).G. MANAGEMENT Avoidance. 1985... Cyclophosphamide is a low molecular weight compound able to form an immunogenic complex with a carrier protein. Looney R. 76 (4): 591–4. Clin. J.A.J.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS A few cases with positive skin-tests to cyclophosphamide. • • • . Mc Cune W. Colvin M. Immunol. Immunol.P. 37 (7): 1101-4 Cromar B. “Hypersensitivity reaction to a metabolite of cyclophosphamide”. “Allergic reactions to cyclophosphamide: delayed clinical expression associated with positive immediate skin-tests to drug metabolites in five patients”. Saidi P. chlorambucil. “Immediate hypersensitivity reaction to cyclophosphamide” . “Validity of skin tests to cyclophosphamide and metabolites”.108 - .J. 1996.R. Phosphoramide mustard contains the bischlorethylamine group common to the nitrogen mustards leading to potential crossreactivity with other nitrogen mustards (melphalan. Rheum.C.. Sheehan M. REFERENCES • Popescu N. Colvin M. 1994. Leddy J. No specific IgE.B.H. Kouides P. 1991. or metabolites.A. Allergy Clin. ifosfamide. J. Use of an other nitrogen mustard (ifosfamide) is sometimes possible under strict medical supervision. J.J.E.A. Immunol. Fox D. Mc Lean J.A.W. Allergy. Loughner J. Kesarwala H. 88: 965-7 Kim H. Solomon W. Casale T..J.

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

MECHLORETHAMINE
Antimitotic alkylating agent known as nitrogen mustard administered intravenously in the treatment of hematological disorders and applied topically in the treatment of mycosis fungoids and severe psoriasis.

INCIDENCE
Frequent when applied topically. Uncommon when administered intravenously.

CLINICAL MANIFESTATIONS
General: anaphylactic shock. Respiratory: dyspnea. Cutaneous: pruritus, urticaria, angioedema, bullous reactions, contact dermatitis (topical use), erythema multiforme.

DIAGNOSTIC METHODS
Cutaneous testing: prick-tests and patch-tests positive in patients with reactions to topical mechlorethamine.

MECHANISMS
Unknown for immediate reactions. Cell-mediated hypersensitivity for contact dermatitis.

MANAGEMENT
Desensitization in patients with mycosis fungoids. — topical desensitization: from 0.01 mg/100 ml to 20 mg/ 100 ml — intravenous desensitization.

Not always successful. REFERENCES
• Pariser D.M, Childers R.C, Kechijian P, Halprin K.M, Taylor J.R, “Intravenous desensitization to mechlorethamine in patients with psoriasis”, Arch. Dermatol., 1976; 112 (8): 1113-4

- 109 -

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

Constantine V.S, Fuks Z.Y, Farber E.M, “Mechlorethamine desensitization in therapy for mycosis fungoids. Topical desensitization to mechlorethamine (nitrogen mustard) contact hypersensitivity”, Arch. Dermatol., 1975; 111 (4): 484-8

MELPHALAN
Nitrogen mustard class cytostatic alkylating agent, used as a first line drug in the treatment of multiple myeloma.

INCIDENCE
2.4% (intravenous route). Uncommon when administered orally (0.3%). No deaths reported.

RISK FACTORS
IgA multiple myeloma (55% of cases). Intravenous route.

CLINICAL MANIFESTATIONS (at least 2 prior doses, up to 28 previous doses) General: anaphylactic shock. Cutaneous: urticaria, angioedema, rash, pruritus. Respiratory: interstitial pneumonitis. DIAGNOSTIC METHODS
Leukocyte migration inhibition test: one positive test in a case of interstitial pneumonitis.

MECHANISMS
Alkylation reaction may occur in vivo, and altered proteins may serve as new antigens capable of stimulating antibodies to the hapten-protein complex.

- 110 -

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

MANAGEMENT
Avoidance of the intravenous route. Some reactive patients may be switched to oral melphalan with no further reaction.

Cross reactivity with other alkylating agents is exceptional (cyclophosphamide). REFERENCES
• • • • Weiss R.B, “Hypersensitivity reactions” , Semin.Oncol., 1992; 19 (5): 458-77 Liote H, Gauthier J.F, Prier A, Gauthier-Rahman S, Kaplan G, Akoun G, “Pneumopathie interstitielle, aigüe, réversible, induite par le melphalan”, Rev. Mal. Respir., 1989; 6 (5): 461-4 Lawrence B.V, “Anaphylaxis due to oral melphalan” , Cancer, Treat. Rep., 1980; 64 (4-5): 731-2 Cornwell G.G. III, Pajak T.F, Mc Intyre O.R, “Hypersensitivity reactions to IV melphalan during treatment of multiple myeloma: Cancer and Leukemia Group B experience”, Cancer. Treat. Rep., 1979; 63 (3): 399-403

AMINOGLUTETHIMIDE
Estrogen biosynthesis inhibitor, producing a “medical adrenalectomy” in patients with breast cancer.

INCIDENCE
Common (>20%).

RISK FACTORS
Associated radiotherapy.

CLINICAL MANIFESTATIONS
General: anaphylactic shock, fever. Cutaneous: maculopapular rash, oral ulcerations, capillaritis.

- 111 -

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

DIAGNOSTIC METHODS
No in vivo or in vitro method is currently available for diagnosis, other than challenge by reintroduction.

MECHANISMS
Undetermined.

MANAGEMENT
Avoidance. Corticosteroid therapy may be useful.

REFERENCES
• • • Vanek N, Hortobagyi G.N, Buzdar A.U, “Radiotherapy enhances the toxicity of aminoglutethimide”, Med. Pediatr. Oncol., 1990; 18 (2): 162-4 Zambetti M, Brambilla C, Tancini G, Bonadonna G, “Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments”, Tumori., 1987; 73 (4): 369-73 Leloire O, Forzy G, Derreumaux L.L, Cordonnier D, Vincent G, “Reaction anaphylactique sévère à l’aminoglutéthimide (lettre)”, Presse. Med., 1986; 15 (1): 34

- 112 -

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

ANTHRACYCLINE ANTIBIOTICS
DAUNORUBICIN
Antimitotic antibiotic used to treat hematological disorders.

INCIDENCE
Uncommon (1 to 2%). No deaths reported.

CLINICAL MANIFESTATIONS
General: fever; anaphylactic shock. Cutaneous: rash; urticaria, angioedema.

DIAGNOSTIC METHODS
No in vivo or in vitro method is currently available for diagnosis.

MECHANISMS
Unknown.

MANAGEMENT
Avoidance. Possible cross reactivity with doxorubicin.

REFERENCES
• • • Ma D, Isbister J.P, “Cytotoxic-induced fulminant hyperpyrexia”, Cancer, 1980; 45: 2249–51. Crowther D, Powles R.L, Bateman C.J.T, Beard M.E.J, Gauchi C.L, Wrigley P.F.M, Malpas J.S, Hamilton-Fairley G, Bodley-Scott R., “Management of adult acute myelogenous leukaemia”, Br. Med. J., 1973; 1: 131–7. Freeman A.I, “Clinical note: allergic reaction to daunomycin (NSC-82151)”, Cancer. Chemother. Rep., 1970; 54: 475-6

- 113 -

CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS

DOXORUBICIN
Doxorubicin is an anthracycline antibiotic isolated from cultures of Streptomyces peucetius It is used in the treatment of hematological malignancies and solid and soft tissue tumors. Pegylated liposomal doxorubicin may be less cardiotoxic than free doxorubicin but mucositis is increased.

INCIDENCE
Uncommon: urticaria 1/160 to 3%. One death reported.

RISK FACTORS
Clindamycin allergy? Intravenous route.

CLINICAL MANIFESTATIONS
General: anaphylactic shock. Cutaneous: pruritus, urticaria, rash, flush, flare reaction: erythema, pruritus, urticaria localized or adjacent to the site of infusion, handfoot syndrome (palmar-plantar dysesthesia). E.N.T.: nasal congestion. Respiratory: bronchospasm.

DIAGNOSTIC METHODS
Drug re-challenge.

MECHANISMS
Direct degranulation of mast cells or circulating basophils without antibody mediation. Activation of alternate complement-activity pathway.

MANAGEMENT
The use of pegylated liposomal doxorubicin (PLD) increases the frequency (7 to 9%) of hypersensitivity reactions in the first cycles of treatment (flushing, shortness of breath, facial swelling,

- 114 -

18 (5): 402-3 L-ASPARAGINASE Polypeptide of bacterial origin (E. hypotension). Intell.115 - . Sharifi R. Drugs. 1990. Intramuscular route: 6 to 18%. Intravenous route: 15 to 33%. prophylactic administration of antihistamines may be useful. Non-association with prednisone and vincristine. REFERENCES • • • • • Alberts D. 112 (2): 150 Lee M. Ann. give an other effective intravesical agent — if the reaction is mild and self-limiting. Sherlock S. coli) widely used in the treatment of acute lymphoblastic leukemia in children and adults.. 54 (S4): 30-5 Arena F. 18 (10): 808-11 Collins J. Med. Drug. Deaths reported. Wilson J. Concerning use of intravesical doxorubicin: — if the reaction is severe.P.A. . Prior exposure months or years previously. Urol. “Doxorubicin-induced hypersensitivity reactions”. Pharm. Hiatus of 1 month or more between two courses.. Intell.J. Pharm. RISK FACTORS Intravenous use. “Safety aspects of pegylated liposomal doxorubicin in patients with cancer”. Drug.S. “Hypersensitivity reaction to doxorubicin” . INCIDENCE Highest of all antimitotic agents.. Garcia D. 1984. 1987.P. “Doxorubicin hypersensitivity and clindamycin (letter)”. Clin.. “Generalized hypersensitivity reaction to intravesical thiotepa and doxorubicin” . chills. 138 (1): 143-4 Solimando D. Intern.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS headache.A Jr. Clin. back pain. 1984. J. 1997. tightness in the chest and throat.

L-asparaginase-specific IgG antibodies bind and activate the complement system. Complement activation induced by formation of immune complexes of L-asparaginase and specific IgM and IgG class antibodies. angioedema. Leukotriene production by bone marrow-derived mast cells. urticaria. Premedication (epinephrine). MECHANISMS IgE-mediated hypersensitivity: a few cases. Specific IgM and IgG (microtiter solid-phase radioimmunoassay). Specific IgE. Complement activation (C3d).CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS CLINICAL MANIFESTATIONS General: anaphylactic shock. Cutaneous: pruritus. Ineffective (false positive and negative). rash. but hypersensitivity reactions to L-asparaginase do not impact on the remission duration in adults with acute lymphoblastic leukemia. bronchospasm.116 - . Use of alternative formulations: — L-asparaginase derived from Erwinia chrysantemia: fewer anaphylactic reactions and no cross-reactivity with Escherichia coli L-asparaginase — Polyethyleneglycol-L-asparaginase: lower immunogenicity. Increased specific IgE antibodies found in patients in whom Lasparaginase infusions are followed by allergic reactions. DIAGNOSTIC METHODS Cutaneous testing. Respiratory: laryngospasm. MANAGEMENT Avoidance. High titers of IgG3 or IgG4 anti L-asparaginase may predict Lasparaginase allergy. .

. Clin. Hori H. 75 (5): 1176-81 Fabry U. Res. J.D Jr.H. Voute P.K. 1985. Kawasaki H.year -old child with myelogenous leukemia).2 U/hour over 4. Leukemia. Allergy.. Komada Y.117 - . 101 (4. “Anaphylaxis to Lasparaginase during treatment for acute lymphoblastic leukemia in children. Wahn V. Immunol. Umemoto M. Cancer. 101 (3): 429-31 Ettinger L. .F. Pediatr. Meyer C. “Hypersensitivity reactions to Escherichia Coli derived polyethylene glycolated-asparaginase associated with subsequent immediate skin-test reactivity to E. Wray B. Jurgens H. Fretzin M. Sakurai M. Schiffer C.2 hours to 1200 U/hour over 3. Jurgens H.1): 571-12 Stone H. Evidence of a complement activated mechanism”.derived granulocyte colony stimulating factor”.A. J. From 1. Dodge R.C.A. Allergy.. Clin. 1995. REFERENCES • • • Larson R. Immunol. Halpern S. 1998. This immunosuppressive agent has become the mainstay of therapy for rheumatological and dermatological conditions. INCIDENCE Hypersensitivity reactions to azathioprine: more than 50 patients reported (up to 1998) in English medical literature. “An openlabel multicenter study of polyethyleneglycol-L-asparaginase for the treatment of acute lymphoblastic leukemia”.L. 1998. 12 (5): 660-5 Bonno M.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Desensitization (in a 2 .A. Coli . “Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia”. Davis P.B. . 19 (4): 400-8 • • AZATHIOPRINE Azathioprine is an imidazole analogue of 6-mercaptopurine.J. Kurtzberg J. “Rapid desensitization for L-asparaginase hypersensitivity”. Korholz D. 1998. and inflammatory bowel diseases.8 hours. Dipiro C. Gobel U.

Recurrence of symptoms with drug re-challenge (to be performed with extreme caution). erythema nodosum. Respiratory: dyspnea (5/49). petechiae. erythema multiforme. tachycardia (2/49). Musculoskeletal: arthralgia (7/49). DIAGNOSTIC METHODS No antibodies to azathioprine or its metabolites have been found. myalgia (6/49). maculopapular eruption (3/49). purpura. rhabdomyolysis (1/49). MECHANISMS Unknown. acute interstitial nephritis (1/49).CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS RISK FACTORS Presence of fever. Concomitant use of corticosteroids (hypotension). hypotension (4/49). jaundice (3/49). hepatitis (3/49). meningismus (3/49). Renal: oliguria (3/49).118 - . seizure (1/49). especially if the initial dose of the medication elicits a febrile or systemic response. gastrointestinal symptoms. pancreatitis (3/49). CLINICAL MANIFESTATIONS (within 4 weeks of initiation of the treatment) General: fever (38/49). pneumonitis (3/49). or exacerbation of the underlying disease upon initiation of the drug are risk factors for a hypersensitivity reaction. . vomiting (21/49). cough (1/49). Gastrointestinal: nausea (21/49). Cutaneous: urticaria (8/49). Neurological: headache (7/49). diarrhea (10/ 49). Role of the imidazole side-chain? MANAGEMENT Avoidance. peripheral neuropathy (2/49).

91 (5): 471-4 Jones J.M. Acad. Postgrad. CLINICAL MANIFESTATIONS General: fever. Byrd R.. 1986. INCIDENCE Fever: 20 to 25% of patients. DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis.. Ossorio M.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • Fields C. J.W. Cutaneous: pruritus. Fulminant reactions: 1 to 8% of patients.A. South.1): 795-6 Rosenthal E. J. fibrosis. 1998. “ Azathioprine-induced shock in dermatology patients”. hypotension. Deaths reported. “Azathioprine shock”.L. RISK FACTORS Lymphoma (for fulminant reactions). Robinson J. toxic epidermal necrolysis. “Hypersensitivity reaction to azathioprine”. 29 (5. angioedema.119 - . Dermatol. flagellate dermatitis. Am. Roy T. 1993. erythematous rash. Intravenous administration. Ashworth J. Bleomycin inhibits cell cleavage by blocking the uptake of thymidine by DNA and leading to weakening and break-up of DNA chains. Med.J. . J. Respiratory: eosinophilic pneumonia. 62 (729): 677-8 BLEOMYCIN Cytostatic agent produced by a strain of Streptomyces verticillus. Med..P Jr.

CLINICAL MANIFESTATIONS Cutaneous (main manifestations): bullous eruptions. Intern. REFERENCES • Haerslev T. 52 (1): 45-6 • Yousem S. 88 (1): 103-6 •· Khansur T. “Sudden onset of adverse effects due to low-dosage bleomycin indicates an idiosyncratic reaction”. Arch. Lifson J. 1984. 144 (11): 2267 BUSULFAN Alkylating agent able to act selectively against the myeloid cell line used in the treatment of chronic leukemia.. Little B. pulmonary fibrosis.120 - . Med.V. Colby T. Respiratory: interstitial pneumonia (often severe).. polycythemia vera. INCIDENCE Uncommon. Joergensen M. Chest. Tavassoli M.D. MANAGEMENT Antihistamines and corticosteroids are sometimes effective.A. .. “Chemotherapy-induced eosinophilic pneumonia. Avnstorp C. Relation to bleomycin”. MECHANISMS Undetermined. “Fulminant and fatal angioedema caused by bleomycin treatment”.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MECHANISMS Non immunological mechanisms are likely. urticaria. 1993. and thrombocythemia. DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis. Cutis. 1985.

1978. . 1985.T. INCIDENCE 23 cases of hypersensitivity have been reported (17 in patients.) contained in the intravenous solution (not in oral form) has been implicated. “Allopurinol-type” rash due to busulphan” . Manoharan A. In the 17 patients reported: 5/17 no previous exposure. Provocation challenge: oral or intravenous. Lancet.N. CLINICAL MANIFESTATIONS General: anaphylactic shock. 12/17 previous exposure to cyclosporine or cremophor EL (15 intravenous route.L. periorbital edema. pruritus. Cutaneous: erythematous skin rash (generalized or mainly on face and trunk). 2 oral route). DIAGNOSTIC METHODS Cutaneous testing is seldom performed: 2/17 patients had positive skin-tests.. Interne. Respiratory: dyspnea. Ann.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MANAGEMENT Avoidance. MECHANISMS The organic solvent (cremophor E.121 - .J. E. Med. bronchospasm.(Paris). REFERENCES • • Akoun G. urticaria. 136 (8): 671-6 Leyden M. 5 in normal volunteers). “Pulmonary changes caused by cytostatic drugs”. 2 (8093): 797 CYCLOSPORINE Cyclosporine is a potent immunosuppressive agent used to prevent rejection of transplanted organs. Mayaud C. Milleron B.: laryngospasm.

— During the first ten minutes of the first and second cyclosporine infusions.5 mg/ ml with 5% dextrose or 0. Tubing used for the infusion must not contain PVC.122 - . The soft. Complement activation. — cyclosporine should be diluted to 0. no specific IgE found). glass bottles or polypropylene syringes. corn oil-based gelatin capsule appears to be the safest formulation of cyclosporine.9% saline or 5% dextrose.9% sodium chloride. — oral soft gelatin capsule: Sandimmune (diluent: polyoxyethylated glycolysed glycerides) — oral solution microemulsion: Neoral (diluent: polyoxyl 40 hydrogenated castor oil) — oral soft gelatin capsule microemulsion: Neoral (diluent: polyoxyl 40 hydrogenated castor oil). the infusion must be mixed thoroughly by shaking or swirling the bottle. MANAGEMENT Use alternative formulations of cyclosporine: — oral solution (cyclosporine 100 mg/ ml): Sandimmune (diluent: polyoxyethylated oleic glycerides). If high-dose intravenous cyclosporine is used: — cyclosporine solutions are incompatible with polyvinyl chloride (PVC) plastics and must be prepared in non-PVC plastic bags. — high-dose cyclosporine should not be administered to the patient unless the patient has received appropriate corticosteroid and antihistamine premedication . supervision by medical personnel with proper resuscitation skills is advisable. . After adding cyclosporine to the carrier fluid.5 to 2. — the tubing system must be primed with 0. The infusion fluid must appear homogenous. Direct histamine release.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS IgE-mediated hypersensitivity (positive skin-tests.

Chan H.G.. 31: 1287-91 Boehnke-Michaud L. Palmar-plantar syndrome: rare.123 - . myalgia. .L. maculopapular rash. diaphoresis. “Mechanism of anaphylactoid reactions: improper preparation of high-dose intravenous cyclosporine leads to bolus infusion of cremophor EL and cyclosporine”. Toxic conjunctivitis: uncommon. hypotension. 1995. arthralgia. 1998. Palmar-Plantar erythema: +/. Asthma. Liau-Chu M. Neutrophilic eccrine hidradenitis: uncommon. 13 (10): 2508-16 • • CYTARABINE Antimitotic antimetabolite agent. rigors. Pharmacother. chest pain. 1997. Allergy. Van Delenn R.W.G. “Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of cremophor EL”.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • Volcheck G. Doyle J. Koren G. J. CLINICAL MANIFESTATIONS Type I reactions: dyspnea. Ann.generalized erythematous maculopapular rashes. Cytarabine syndrome: fever. “Methods for preventing reactions secondary to cremophor EL”. It is used in the treatment of acute leukemia and some solid tumors. Theis J.. urticaria.G. 1997. 80 (2): 159-63 Liau-Chu M. 31: 1402-4 Theis J. “Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review”. Greenberg M. Cytarabine syndrome: up to 21% of treated patients in some reports. Immunol.W. Pharmacother.S. INCIDENCE Type I reactions: uncommon. Ann. Clin. This hydrosoluble pyrimidic nucleoside-resembling cytidin inhibits desoxycytidin synthesis by a competitive mechanism. conjunctivitis. fever. hypotension. Koren G.. Ann. angioedema..W. Oncol.

REFERENCES • • Blanca M.002% cytarabine up to 200 mg of cytarabine in 500 cc of saline. Adults (1 case): starting with 10 ml of 0. Desensitization. A few cases of positive intradermal skin-tests at a concentration of 4 µg/ml. Pretreatment with corticosteroids is sometimes helpful. erythematous.L.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Neutrophilic eccrine hidradenitis: tender. Giron M. Prick-tests are negative. detection of IgE antibodies and passive cutaneous anaphylaxis. toxic conjunctivitis. MANAGEMENT Type I reactions. DIAGNOSTIC METHODS Type I reactions. “Hypersensitivity reactions” Sem.T.”Successful administration of cytarabine after a previous anaphylactic reaction” . MECHANISMS Type I reactions: IgE-mediated hypersensitivity is suggested by immediately positive intradermal skin tests. Children (1 case): 200 µg to 45 mg in 13 hours. 52: 1009-1011 Weiss R.1997. Cutaneous testing. Cytarabine syndrome.B.1992. indurated lesions (trunk + upper extremities). Specific histamine release. Oncology. Martinez-Valverde A.124 - . Other reactions. Corzo J. Torres M. Presence of specific IgE antibodies: in some patients with anaphylactic shock. Allergy. neutrophilic eccrine hidradenitis: direct toxicity is likely. 19 (5): 458-77 .

Arch. King M.J. . Hepatic: allergic hepatitis (allergic hepatic veno-occlusive disorder: Budd-Chiari syndrome). Child. More common for photosensitivity and hepatitis. 140: 425-8 DACARBAZINE Dacarbazine (DTIC) is an imidazole carboxamide used in the treatment of malignant melanoma. Wehde S.D.125 - . DIAGNOSTIC METHODS None. J.T. pruritus. localized skin reaction. Ped. Howell S. 1987. Am. MECHANISMS Unknown. “Anaphylactic shock due to cytarabine in a leukemic child”. Med. 1980. Pfeifle C.I. CLINICAL MANIFESTATIONS General: anaphylactic shock (one case). 141: 1000-1 Markman M. sarcomas. Hodgkin’s disease and neuroblastoma. Crum E.. Intern. Med. Cutaneous: photosensitivity.E. INCIDENCE Anaphylactic shock: one case.”Anaphylactic reaction to cytarabine: in vitro evidence that the immune response is IgEmediated”. erythema.B. Oncol. “Cytarabine induced anaphylaxis demonstration of antibody and successful desensitization”. MANAGEMENT Avoidance. Forman W. Nasserman S. Dis.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS • • • Berkowitz F.B.L.. 12: 201–3 Rassiga A. 1984. Schwartz H. edema. Ngwenya E.

Photodermatology. “Anaphylactic shock due to dacarbazine”. Cancer Treat. DIAGNOSTIC METHODS Recurrence of hypersensitivity reactions with drug re-challenge (3/3). Rao S. Child. No protocols for prophylactic premedication have been yet published. Rep.J. Am. Balizet L. 1987. MANAGEMENT Avoidance.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • • Serrano G. Dis. urticaria. 1982. 1989.B. Arch.T. Respiratory: bronchospasm. MECHANISMS The solvent: N. Miller S. “Unusual local cutaneous reaction to dacarbazine”.N-dimethylacetamide could be involved in hypersensitivity reactions. 71 (2): 219-20 Koehn G.G. Dermatol. Mastrangelo M.. .P.J. “Allergy-induced hepatic toxicity associated with dacarbazine”. CLINICAL MANIFESTATIONS (occurring after several courses of diaziquone) General: anaphylactic shock. 142 (9): 918 Mc Clay E. 118 (12): 1018-9 DIAZIQUONE Diaziquone is an aziridinylbenzoquinone alkylating agent used in various carcinomas. Cutaneous: pruritus. Pollio L. “Dacarbazine induced photosensitivity” . Lusch C. 1988. J.. INCIDENCE 1 to 2%.126 - . Aliaga A. 6: 140-1 Abhyankar S. Febrer I.

R. Pharmacol. Weiselberg L. 1982.B. High incidence in children with Hodgkin’s disease. DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis.. RISK FACTORS Intravenous route. “Anaphylactoid reactions to AZQ”. 1984. 68 (10): 1215-7 Budman D. small cell lung carcinoma and malignant lymphoma. chest tightness.J. active against a number of tumors: germ cell neoplasms.J. Vinciguerra V. Treat. hypertension (rare). O’Dwyer P.127 - . “Hypersensitivity reactions”. INCIDENCE 93 cases reported up to 1996. exanthema. CLINICAL MANIFESTATIONS Hypotension.. Schulman P. fever. bronchospasm. “Anaphylactic reactions to diaziquone”. Hoth D.G. tachycardia.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • Weiss R. . chills.Oncol.F. facial flushing. dyspnea. Semin. 8 (3): 317 EPIDOPHYLLOTOXINS ETOPOSIDE Semi-synthetic derivative of podophyllotoxin. cyanosis. Urticaria is uncommon. 19 (5): 45877 Posada J. 1992. Cancer Chemother. Degnan T. 3 deaths.. Rep. Cancer.

Crist W. Continuing administration without modification (65% successful) Premedication with antihistamines and/ or corticosteroids. ten Bokkel Huinink W.A.M.. Weinstein H. “Hypersensitivity reactions to epidophyllotoxins in children with acute lymphoblastic leukemia”. J. Cancer.M. 1988.W. Schornagel J.H. 1996. 67: 1070-5 Eschalier A. Crone M.H. Rupp C. Link M..128 - . 1993. “Acute hypersensitivity reactions to etoposide in a VEPA regimen for Hodgkin’s disease”.L..H. Ann. INCIDENCE 2 to 11%. MANAGEMENT Lowering of the infusion rate.J. Pharmacol. Pui C. “Hypersensitivity reactions to etoposide”. . Marina N. Pharmacother. Tarbell N. Beijnen J. 30 (4): 367-71 Hudson M. Wilimas J.J.P.M. Rodriguez M. Kun L. Burtin C. Greenwald C. Renoux M. Oncol. 41% of children with acute lymphoblastic leukemia treated with intensive multiagent chemotherapy.M. 21: 246-50 • • TENIPOSIDE Semisynthetic derivative of podophyllotoxin which interacts with type II topoisomerase to induce DNA cross-links and double-strand breaks. Rodman J. Cancer Chemother. Chapuy E. 1991. Humphrey W.Donaldson S. 11 (6): 1080-4 Kellie S. The role of polysorbate 80 (Tween 80) used as an excipient in the parenteral formulation is doubtful. REFERENCES • • Hoetelmans R. “Study of histamine release induced by acute administration of anti tumor agents in dogs”.S.J.H.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MECHANISMS Non specific histamine release. Lavarenne J. Clin.E. Fairclough D.

“Hypersensitivity reactions to teniposide (VM-26): an analysis ”.L.L.M. Fairclough D. Carstensen H. 1 (8634): 394 Nolte H. MANAGEMENT Premedication with diphenydramine +/. Oncol. sweating. Pediatr. “Anaphylactic reactions to teniposide”.. 1991. urticaria. Rivera G. 1988. King S.E.J.J.H. .A. Hematol. 4 (8): 1262-9 . “Hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia”. CLINICAL MANIFESTATIONS (often on the first dose) General: hypotension. oliguria. Lancet. Nunn A.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS RISK FACTORS Children with neuroblastoma or brain tumors. J. Cancer.. Am.K. Respiratory: chest pain. Crone M. High doses (children): 1500 to 2000 mg/ m2. intravascular hemolysis.. Martin J. Etoposide does not usually cross-react. 1986. Fortner C. Oncol. Leyland-Jones B. One case with IgG 1 antibody to teniposide. 10 (4): 308-12 O’Dwyer P.H. 1989. Hertz H. REFERENCES • • • • Kellie S. Cutaneous: flushing. palor.corticosteroids is useful.J. Pui C. 67 (4): 1070-5 Siddall S. angioedema.J. wheezing. MECHANISMS Cremophor EL is thought to be the culprit (see cremophor EL). Crist W. Clin. DIAGNOSTIC METHODS In vitro histamine release from basophil leukocytes: non-specific histamine release. Rodman J.129 - . “VM-26 (teniposide)-induced hypersensitivity and degranulation of basophils in children”. fever. J.

INCIDENCE Unknown. RISK FACTORS Seborrheic dermatitis (palmar-plantar dermatitis). phototoxicity and photosensitization. Probable direct cytotoxic effect of 5 FU (palmar-plantar dermatitis). Palmar-plantar dermatitis. DIAGNOSTIC METHODS Cutaneous testing: one case with intradermal test positive (anaphylactic shock). 35: 124-5 . Pujol R. MECHANISMS IgE-mediated hypersensitivity (one case of anaphylactic shock). Contact eczema by topical application. Dermatitis. Iterative long-term topical applications. Randazzo L. Contact. pigmentation abnormalities. 1996. REFERENCES • Nadal C. Marchello E.5-1% 5-FU in pet. No specific IgE found. Angioedema. “Systemic contact dermatitis from 5-Fluorouracil”.130 - . CLINICAL MANIFESTATIONS Anaphylactic shock (4 cases reported). Alomar A. MANAGEMENT Avoidance. Topical 5-FU is widely used for the treatment of actinic keratosis and warts in some countries.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS 5-FLUOROURACIL Pyrimidine analogue used for the treatment of several types of malignancies. Patch-tests and photopatch-tests with 0.M..

58: 862-4 de Beer R. Fever: 15 cases published (up to 1997). Respiratory: alveolitis (rare). Treat. basal layer degeneration. fixed drug eruption (rare). “Anaphylactic reaction following i. 1986.v administration of 5-fluorouracil (letter)”. CLINICAL MANIFESTATIONS General: fever.S. Kabakow B. flattening of the dermoepidermal junction. Rep. Cancer. “Allergic reactions to 5-fluorouracil infusion”.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS • • • Milla Santos A. 1986. oral or leg ulceration. Sanchiz Medina F. “Anaphylactoid reactions associated with intravenous administration of 5-fluorouracil”. ulcerative lichen planus-like dermatitis. 70 (11): 1346 Sridhar K.Y. hyperpigmentation of skin and nails. disappearing rapidly after discontinuation. Med.. DIAGNOSTIC METHODS Skin biopsy: epidermal thickening. 1979. 79: 1750-1 HYDROXYUREA Antimetabolite acting primarily on cells in S phase.131 - . It is used in patients with myeloproliferative disorders. Cancer. MECHANISMS Cutaneous reactions: Lichenoid hypersensitivity reaction? Hydroxyurea toxicity on the basal layer of the epidermis? . N. cutaneous atrophy. State. colloid body formation... INCIDENCE Cutaneous manifestations: 10 to 35% of patients. appearing within the first few weeks after first exposure. Cutaneous: generalized dryness and scaling (xerosis). J. dermatomyositis-like eruption (dorsal hands).

CLINICAL MANIFESTATIONS General: anaphylactic shock. 1995. Skin prick-test: with methotrexate 10 mg/ ml.. 1994. angioedema. Cutaneous: pruritus. “Hydroxyurea induced dermatomyositis-like eruption” .M.. 133 (3): 455-9 Lossos I. Perrin P. Matzner Y.H. Stiegelis W. 1997. cutaneous vasculitis.M. Porneuf M. Australas. Dermatol. 35 (2): 61-4 METHOTREXATE Folic acid antagonist used in the treatment of several neoplasms and inflammatory disorders.I. Br. 51 (3): 114-8 Senet P. bronchospasm..F. Respiratory: acute pneumonitis. J. Marsden A.132 - . hemolytic anemia. J.. Neth. Ann. One positive case (anaphylactic shock). “Fever caused by hydroxyurea: a report of three cases and review of the literature”. Bull R. Sucec P. J. REFERENCES • • • • van der Klooster J. DIAGNOSTIC METHODS Cutaneous testing. “Hydroxyurea-induced fever: case report and review of the literature”. agranulocytosis. “Cutaneous manifestations of long-term hydroxyurea therapy”. Aractingi S.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MANAGEMENT Hydroxyurea can be continued if necessary with no worsening of cutaneous lesions. Duterque M. Hematological: pancytopenia. INCIDENCE Anaphylactic shock: fewer than 20 cases reported. Med. Pharmacother. severe epidermal toxicity.S. 1995. urticaria. Hagenbeek A. 29 (2): 132-3 Kelly R. . Dermatol.

Clin.G. REFERENCES • • • • Alkins S. re-challenge may be considered. Irwin L. cutaneous vasculitis. Lopez-Serrano C.R. Drug induced lymphocyte stimulation test (DLST): positive in 2 cases of pancytopenia.1 mg up to 25 mg in 60 hours).133 - . Ann.Allergy. 94 (2.B. Most of the time (92%) there are recurrent symptoms despite premedication.1 ml of 25 mg/ ml solution of methotrexate. 77 (10): 2123-6 Vega A. Ward F. No specific histamine release shown. urticaria. Martinez-Alzamora F. Pascual C. MANAGEMENT If no alternative therapy exists and there is a non life-threatening hypersensitivity reaction. Cantor R. 1994.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Intradermal test: 0. One case positive complicated by syndromic reaction (anaphylactic shock).K..A. “Anaphylaxis to methotrexate: a possible IgEmediated mechanism”. “Anaphylactoid reactions to methotrexate” . Desensitization is sometimes used (one successful case beginning with 0.T. Allergy. Rep. IgG3 antibody in a case of hemolytic anemia. Immunol. angioedema. Cohn J. Cancer. Lopez-Casana J. Type II reactions: hemolytic anemia. “Anaphylactic reaction to high dose methotrexate” .B. No specific IgE found. 70 (5): 384-5 Gluck-Kuyt I.E. Morgan S. Byrd J. J. 1979. and one case of agranulocytosis. 1993. Cancer. Treat. “Systemic anaphylaxis from low dose methotrexate” . Weiss R. 1996.. Type III reactions: acute pneumonitis..1): 268-70 Cohn J. Fellin F. Cabanas R. Contreras J. 63: 797-8 . MECHANISMS Type I reactions: anaphylaxis.

DIAGNOSTIC METHODS Cutaneous testing.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MITOMYCIN Antitumor antibiotic derived from Streptomyces caespitosus. the genitals. bleomycin or doxorubicin. Respiratory: interstitial lung disease.6% in water or in petrolatum) positive in patients with contact allergy. Skin tests: one immediately positive intradermal skin test reported in a patient who presented an immediate reaction. and feet. mediated transvesically. Patch-tests (concentration ranging from 0. MANAGEMENT Avoidance. widely used for treatment and prevention of superficial bladder cancer (intravesical instillation). MECHANISMS Presence of CD I + has been shown in bladder epithelium. RISK FACTORS Association with vincristine. CLINICAL MANIFESTATIONS Cutaneous: vesicular dermatitis of the hands. Topical corticosteroids may be useful.06% to 0. . Eczematous eruptions are type IV hypersensitivity reactions.134 - . INCIDENCE Cutaneous side-effect: 9% of patients treated with intravesical instillations. More diffuse reactions involving the trunk.

Br. 126 (5): 596-7 MITOXANTRONE Mitoxantrone (DHAD) has been synthesized by systematic substitution on the basic anthraquinone nucleus. CLINICAL MANIFESTATIONS General: anaphylactic shock. Spencer M. 24 (3): 201-9 Colver G.C.A. facial edema. Cutaneous: rashes (vesicular and erythematous). 1981.. DIAGNOSTIC METHODS Skin biopsy: leukocytoclastic vasculitis in a case of erythematous vesicular rash. Inglis J. Tolley D. 1991. . Conemans J. “Side effects associated with intravesical mitomycin”. INCIDENCE Less than 1%..A. Herrod H.S.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • de Groot A. 1990. Hunter J.135 - . “Systemic allergic contact dermatitis from intravesical instillation of the antitumor antibiotic mitomycin C”. Dermatitis. J. Contact. J. Soloway M. Dermatol. Mc Vittie E. It is used in the treatment of refractory cancers (advanced breast cancer).J. Urol. “Dermatitis due to intravesical mitomycin C: a delayed-type hypersensitivity reaction ?”.M. 122 (2): 217-24 Nissenkorn I.B.. MANAGEMENT Avoidance.A. MECHANISMS Unknown.

chronic lymphocytic leukemia). Treat.L. Respiratory: cough.T. Rep. Roberts J.C. . and widely used as antineoplastic agent (lymphoid malignancies. fever.B. “Allergic reactions to mitoxantrone”. Cutaneous: pruritus. Hematological: eosinophilia.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • Taylor W. “Phase II trial of mitoxantrone”. Garnick M. Cancer. flushing. MECHANISMS Concomitant administration of allopurinol to prevent hyperuricemia secondary to tumor lysis could enhance pentostatin toxicity. CLINICAL MANIFESTATIONS General: anaphylactic shock.B. pulmonary infiltrates. Recurrence of reactions with drug re-challenge.5 to 1 %. Pentostatin is formulated using mannitol and sodium hydroxide. spleen. cerebral cortex (autopsy).136 - . rash. 1982. DIAGNOSTIC METHODS Hypersensitivity vasculitis involving arteries and veins in the heart. INCIDENCE 0. 66 (11): 1929-31 PENTOSTATIN Pentostatin (2'-deoxycoformycin) is an antibiotic produced by culture broths of Streptomyces antibioticus. RISK FACTORS Concomitant use of allopurinol. 1 (8495): 1439 Anderson K.M. Harris A. Cantwell B. edema.I. dryness of the chest and limbs. 1986. Cohen G. Lancet. mycosis fungoids.

10 of 150 children with brain tumors.137 - .L. INCIDENCE Unusual (< 8% of patients). urticaria. REFERENCES • • O’Dwyer P. Am. 1989. DeConti R. RISK FACTORS Occupational exposure to platinum salts(?) CLINICAL MANIFESTATIONS General: anaphylactic shock. bronchospasm. “ Hypersensitivity vasculitis associated with 2-deoxycoformycin and allopurinol therapy”. J. Grem J. Eisenhauer E. King S.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MANAGEMENT Avoidance of systematic use of allopurinol. 1989. diffuse erythema. Ginsburg R.. cyanosis.J. Chemother. Respiratory: dyspnea.A.C. 23 (3): 173-5 Steinmetz J. Hoth D.. Pharmacol. Increase with the number of courses in adults (6% at cycle 6 to 67% by cycle 10) with ovarian carcinoma. Cancer. . 86 (4): 498-9 PLATINUM COMPOUNDS CARBOPLATIN Mainstay therapy in ovarian and testicular carcinoma but also in brain tumors in children (pilocytic astrocytoma). “Hypersensitivity reactions to deoxycoformycin”.F. Med. Digestive: vomiting. Cutaneous: pruritus.

In adults: “rush” protocol (4 hours): 350 mg/ m2 carboplatin in 100 ml aqueous dextrose solution (D5W) 0.1 ml .7.10 . No specific IgE found.0.1 .4 .1 . Direct histamine release.5 . Then: 100 mg/ hr for one hour then remainder of the dose at 200 mg/ hr. “slow” protocol: 0.5 . The remainder of the dose over one hour. diphenydramine 30 minute before and ranitidine 30 minute before.138 - . Desensitization. MECHANISMS IgE-mediated hypersensitivity in some cases (platinum is a tetravalent inorganic molecule that readily complexes with proteins to form antigens).5 . Many protocols have been reported: In children: “rush” protocol: Premedication with prednisolone 12 h and 1 h before.2. MANAGEMENT Pre-treatment with corticosteroids and antihistamines (sometimes ineffective in preventing IgE-mediated reactions).25 and 50 mg of carboplatin infused at 1 mg/ min every 15 minutes.2 . Then: 1 .0.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS DIAGNOSTIC METHODS Cutaneous testing Intradermal skin-tests positive at 0. .5 . The remainder of the dose at 200 mg/ hr.5 .1 mg/ ml and 1 mg/ ml in a few patients.10 ml diluted in 100 ml D5W over one hour each.1 ml .2 .10 and 15 mg at 1 mg/ min every 15 minutes.3 .

A new platinum chemotherapeutic agent”. Intraperitoneal use: if large doses and high infusion time ratio (>2.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS “slow” protocol (81 hours): 0. Fishman A. Confino-Cohen R.. 1996. “A modified prolonged desensitization protocol in carboplatin allergy”. 355 mg carboplatin / 500 ml over 50 hours. Most active agent in germ-cell tumors and osteogenic carcinoma. Friedman H.139 - . Clin. “Successful desensitization to carboplatin in patients with systemic hypersensitivity reactions”.F. Immunol. actinomycin. 90: 681-3 CISPLATIN Cytostatic agent able to inhibit DNA synthesis selectively and specifically. 1992. Beyth Y.4 mg carboplatin / 150 ml over 1. 26 (2): 105-10 Goldberg A.5 hour. Oncol.H. INCIDENCE Common in the 1970’s studies: 6 to 14% (six or more doses of cisplatin).S. J.2). 98: 841-3 Windom H. RISK FACTORS Concurrent use of other drugs (bleomycin. Immunol. 1996. “Anaphylaxis to carboplatin. 40 mg carboplatin / 150 ml over 15 hours. Allergy. cyclophosphamide). Far less frequent in the 1980’s: only 3 or 4 cisplatin courses in testicular carcinoma.I. Med. 4 mg carboplatin / 150 ml over 15 hours. Mac-Guire W. and common use of diphenydramine and dexamethasone in emesis prevention.. J. REFERENCES • • • Broome C. Intravesical use: incidence 10 to 25% (especially if > 8 courses). Adkinson Jr N.B. Schiff R.G. Allergy. Altaras M. Pediatr. Clin. .. Hamilton R. vinblastine.

. iproplatin and DACPP) is likely.01 mg/ ml.L. MANAGEMENT Pretreatment with corticosteroids and antihistamines (sometimes ineffective in preventing IgE-mediated reactions).T. Ann..R. Soper J. 0. DIAGNOSTIC METHODS Cutaneous testing.140 - .1 mg/ ml Intradermal-test: 0. One case with positive histamine release test. Hematological: hemolytic anemia (or false positive direct antiglobulin test). Kessler J. Cross-reactivity with other platin derivatives (carboplatin. After premedication with hydroxyzine and methylprednisolone. REFERENCES • Hebert M. rash.”Anaphylactoid reactions with intraperitoneal cisplatin”. 0. 29: 260-3 . Pharmacother. Histamine release. urticaria. Direct release of vasoactive substances.D. Respiratory: dyspnea.001 mg/ ml. 0. gradual increase of doses from 1 mg to 80 mg at 30 min intervals. flush.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Occupational exposure to platinum salts(?). bronchospasm. MECHANISMS IgE-mediated hypersensitivity in some cases (cisplatin acts as a hapten bound to serum proteins). Desensitization: a few cases reported. Cutaneous (most common): pruritus. Few patients positive to I. Blivin J. 1995.. Oleson J.E. CLINICAL MANIFESTATIONS General: anaphylactic shock (deaths reported). Prick-test: 0.1 mg/ ml.1 mg/ ml. Digestive: vomiting.

CLINICAL MANIFESTATIONS General: fever. Altaras M. especially when anticonvulsant therapy is used. fixed drugeruption.. 1986. Ann..P:) chez un malade allergique”.D.. toxic epidermal necrolysis.B. “Desensibilisation spécifique au cis-dichloro-diamino-platinum (D.141 - . “Anaphylaxis to cisplatin: diagnosis and value of pretreatment in prevention of recurrent allergic reactions”. Allergy. Confino-Cohen R.. Bousquet J.. RISK FACTORS Brain tumors. Michel F. DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis other than re-challenge (which is hazardous: life-threatening pneumonitis published). Piquemal M.L.A. . Respiratory: cough. MECHANISMS Classical complement pathway activation is possible. INCIDENCE Severe allergic reactions: 2%.M. severe toxic effects: 2%.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS • • Goldberg A. Med. Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital. Cutaneous: pruritus. Menardo J. Beyth Y. 73: 271-2 Ter-Schiphorst C. Mekori Y. Presse. urticaria. pleural effusion. 15 (26): 1242. PROCARBAZINE Cytostatic agent derived from methylhydralazine. 1994. Bataille A. Mainly used in the treatment of lymphoma and brain tumors. Much higher (25%) in patients with brain tumors. acute pulmonary infiltrates. lifethreatening allergic reactions: 1% in Hodgkin’s disease. dyspnea. angioedema. maculopapular rash (+++).

7%. Allergy. Pharmacol. pruritus.3%. the new chemotherapeutic agent (taxoids) derived from the needles of the European yew (Taxus baccata). INCIDENCE Cutaneous manifestations (erythema. and procarbazine chemotherapy in the treatment of glioma”. Hurteau T.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MANAGEMENT Avoidance. 1997. Grade III: 6. Coyle T. Use non enzyme-inducing anticonvulsants. Opelz G. 13 (3): 244-6 Glovsky M. 1992. Clin.8%. 57 (2): 134-40 • • TAXANES DOCETAXEL Docetaxel. Ancalmo N. Braunwald J. macular eruptions. dry skin. Immunol. J. 62 (2): 225-9 Coyle T. swelling. Grade III: 2.. grade IV: 1. Clin. “Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors”. Ther. burning.. “Hypersensitivity reactions to procarbazine with mechlorethamine..N. Graziano S. Cancer. Clin.F. Winfield J. 1990. REFERENCES • • Lehmann D. “Delayed life-threatening pneumonitis secondary to procarbazine” . Bushunow P. Oncol. vincristine. . urticaria and low serum complement activity”. Fever: 35. 1976. J. 69 (10): 2532-40 Brooks B. Am. Grinton S. “Hypersensitivity to procarbazine associated with angioedema.2%.B.E. Wright J. breast and non small cells lung cancer. Alvarez S. Newman N. Alenty A. grade IV: 0. desquamation): 64.142 - .8%. Corticosteroids are useful in the management of respiratory manifestations.E.4%.F. Hendler M. shows significant antitumor activity in phase II trials of ovarian.J Jr.

focal vacuolar alteration or plain perivascular lymphocytic inflammation. before the administration of docetaxel. twice daily for 3 days. followed by dexamethasone 8 mg p.7%. Respiratory: dyspnea. fever. 7 hours. rash. clemastine 1 mg 13 hours. angioedema.6%. bronchospasm. flushing.3 % (usually occurring in the first or second course). urticaria. CLINICAL MANIFESTATIONS General: hypotension.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Hypersensitivity reactions: 31. general urticaria or angioedema. Severe: hypotension. grade IV: 0. MECHANISMS Non-specific release of vasoactive mediators following mast-cell degranulation is likely. 1 hour before the administration of docetaxel. chills. chills. pruritus. flushing. Oral pretreatment 12 hours and 3 hours before infusion of docetaxel with 32 mg of methyprednisolone. 7 hours.7%). 1 hour. MANAGEMENT The usefulness of premedication with antihistamines and corticosteroids is controversial. fever. Mild: pruritus. Grade III: 6. solitary erythematous to edematous plaque in the infusionarm proximal to the site of infusion. Cutaneous: erythrodysesthesia. dyspnea.143 - . . bronchospasm. DIAGNOSTIC METHODS Skin biopsy (erythrodysesthesia): epidermal dysmaturation with necrotic keratinocytes or sparse superficial perivascular lymphocytic infiltration with eosinophils. Classical prophylactic medication: dexamethasone 8 mg 13 hours.o. 10 mg of cetirizine and 1 mg of ketotifen limits the development of acute hypersensitivity reactions (28% -> 7.

Mc Collough M.144 - . “Acute cutaneous reactions to docetaxel. Prove A. “Docetaxel”. 7 (1): 104 Cortes J. INCIDENCE Severe reactions: 2%. and improves the condition in most patients. a new chemotherapeutic agent”.L. van Oosterom A. Ann. “Successful docetaxel re-challenge with cromoglycate after major sensitivity reactions”. Skin toxicity is not prevented by corticosteroids and antihistamines. dyspnea (81%).W. ten Bokkel Huinink W. Dirix L.E. Oncol. Pazdur R. 4 (7): 610-11 PACLITAXEL A member of a new class of antineoplastic agents (taxanes). Oncol. Vonck I. Rodenhuis S.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS Sodium cromoglycate (400 mg orally x 4 daily) could be an alternative to corticosteroids and conventional antihistamines in the treatment of taxoid-induced acute hypersensitivity reactions. Ann. Pneumonitis (in previously irradiated patients). CLINICAL MANIFESTATIONS Bronchospasm.D. Kuhn J.. Kaye S. Keeling J. Oncol. REFERENCES • • • • Westermann A.C. 131 (2): 202-6 Schrijvers D. Clinically active in ovarian. 1995. J. Arch. Hypersensitivity reactions: > 10%.. Wanders J.. Cook G. 1993.. Burris H. erythematous rash (74%). Angioedema (19%). Hypotension (41%). 1996. isolated from the bark of Taxus brevifolia. . Urticaria. paclitaxel is a natural diterpene product.H.A. Clin. 1995. Von Hoff D. Dermatol. breast and non-small lung cancer. 13 (10): 2643-55 Zimmermann G.M. Treatment with an ointment of glycerin and chlorhexidine is simple. Irvin R. “Coping with toxicities of docetaxel (Taxotere)”.

MECHANISMS The vehicle (cremophor EL + ethanol) is likely to be responsible.V + 300 mg cimetidine or 50 mg ranitidine I.M. . then continuous infusion. and 50 mg I. Numerous prophylactic regimens have been published: 1° 20 mg dexamethasone orally 12 hours and 6 hours before paclitaxel.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS DIAGNOSTIC METHODS Basophil histamine release: non IgE-mediated response.V just before treatment + 50 mg diphenhydramine orally 12 hours and 6 hours before paclitaxel. MANAGEMENT Premedication is effective. 8 ml) to 1 ml undiluted solution. and 300 mg cimetidine I. 2° 5 to 20 mg dexamethasone I. 2.V + 50 mg diphenhydramine I. 4.V one hour before paclitaxel. Desensitization: 1/100000 (1.145 - . Clinical efficacy needs to be established.V 30 minutes before paclitaxel.V just before paclitaxel + 50 mg orphenadrine I. 3° 20 mg dexamethasone I. Alternative formulations of paclitaxel: — polyethylene glycol (decreases the antitumor activity of taxol) — cyclodextrins (renal and hemolytic toxicity) — polyvinylpyrrolidone nanoparticles (improvement in antitumor efficacy) — phospholipid suspensions: liposomes (increased efficacy) — prodrugs.V just before treatment + 25 mg ephedrine sulfate orally one hour before paclitaxel (if possible). and 20 mg I.

W. Kloth D. INCIDENCE 3% of intravesical infusions. Ozols R. Cancer. J. 1996. 1996.M.K. “Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity reactions”.A. J. Tognoni A.R Jr. “Complement activation by cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study”.J. Maksymiuk A. 8 (7): 1263-8 THIOTEPA Alkylating agent acting upon synthesis of desoxyribonucleoproteins. Trump D. RISK FACTORS Bladder instillation. Cancer Treat. Nuijen B.F. 8 (6): 611-4 Meerum-Terwogt J. Used in the treatment of ovarian. breast cancer and bladder tumors (intravesical instillation). 7 (9): 978-9 Weiss R. Donehower R.. Cutaneous: pruritus.. “Alternative formulations of paclitaxel”. Immunol. 88 (7): 463-5 Gennari A. Lichtenstein L.D. Ozols R.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS REFERENCES • • • • • • • Szebeni J. 1997.146 - . Natl. King E. Oncol..M. Ann. Smolinski S.F. 90 (4): 300-6 Bookman M.D.H. Ann.R.E. 1996. Inst.M. Alving C. angioedema.B. “Rapid intravenous premedication with dexamethasone prevents hypersensitivity reactions to paclitaxel (letter). Rev. 1990. Beijnen J.. Kover P. Natl. 23 (2): 87-95 Essayan D. 1997.F. “Successful parenteral desensitization to paclitaxel”.C. J. “Hypersensitivity reactions from taxol”.. .M. Oncol.. Allergy. Ten Bokkel Huinink W. 97: 42-6 Boehm D.W. Ohnuma T. 1998.D. J. Cancer. Leyland-Jones B.A. Clin. Baker J. Wiernik P. Salvadori B. “Paclitaxel premedication regimens (letter)”. Conte P.H. Inst. Kagey-Sobotka A. Colarusso P. urticaria. Van Echo D. Gralla R.L. Muggia F. Von Hoff D. Oncol. CLINICAL MANIFESTATIONS General: fever.J. Clin.

Soroff H. Cancer. 138 (1): 143–4. INCIDENCE Exceptional for anaphylaxis. 1985. Kim A. Deaths reported. Gonder M. “Combined thiotepa and mitomycin C instillation therapy for low-grade superficial bladder tumor”. 55 (8): 1654-8 VINCA ALKALOIDS VINBLASTINE – VINCRISTINE – VINDESINE Plant alkaloids frequently used in current chemotherapy protocols. localized epidermal necrolysis Respiratory: acute respiratory failure (vinblastine).147 - .CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis. CLINICAL MANIFESTATIONS General: anaphylactic shock (vincristine). REFERENCES • • Lee M.N. 1987. MANAGEMENT Avoid use. More common for bronchospasm. pleural effusion. RISK FACTORS Associated treatment with mitomycin (respiratory manifestations). Urol. Hu K. Sharifi R.. J. Cutaneous: erythrodermia. Khan A.S. . “Generalized hypersensitivity reaction to intravesical thiotepa and doxorubicin”. bronchospasm.

Soc. “Acute bronchospasm after vinca alkaloids in patients previously treated with mitomycin”..J. Proc.T. 1993. Le Caer H. Vervloet D. “Fatal acute respiratory failure following vinblastine and mitomycin administration for breast cancer” . ANCILLARY DRUGS 5 HYDROXYTRYPTAMINE 3 RECEPTOR ANTAGONISTS Granisetron.P. Ballen K.148 - . Kris M. MANAGEMENT Avoidance. Rev. Sci. Kleisbauer J. Mal. Martello O.T. 23 (11): 961 Luedke D. 10: 268-71 Rivera M. Cancer. Gupta G.G.K.A. Reed G. Clin. 295 (6): 558-60 Bhardwaj B. Med.1988.K.. Weiss S. Am. Gralla R. J. Meet Am. 1985. 9: A1246. McLaughlin T. Kalra S. “Bronchospasme aigu du à l’association alcaloïde de la pervenchemitomycine”. Indian Pediatr. Daughaday C. 1984. Ann. 310 (6): 389. . ondansetron and tropisetron are used for prevention of nausea and vomiting associated with cancer chemotherapy. “Incidence and syndrome of acute shortness of breath following vinca alkaloids in patients receiving mitomycin”. “Mitomycin C and Vindesine associated pulmonary toxicity with variable clinical expression”. 1986. Premedication with corticosteroids may be useful. J.. 1990. “Fatal anaphylaxis following intravenous vincristine (letter)”.W. White D. New Eng. Pradal M. Oncol. 55: 542–5 Dyke R. MECHANISMS Undetermined.P. Harrison B. Montcharmont D. Med. Luedke S..CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS DIAGNOSTIC METHODS No in vivo or in vitro method is currently available for diagnosis. REFERENCES • • • • • • Thomas P. Resp. Pulmonary function tests show obstructive patterns.

Anaphylactic reactions. “Anaphylactoid reactions associated with ondansetron”. Rashes. 1994. de Bruijn K.. DIAGNOSTIC METHODS Drug re-challenge: positive. MANAGEMENT Avoidance of all 5 HT 3 receptor antagonists due to effects of drug class. Ann. Facial edema. RISK FACTORS Previous reaction with another 5 HT 3 receptor antagonist.K.L. MECHANISMS Unknown. Ondansetron: 24 cases (FDA 1994). gastrointestinal symptoms).CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS INCIDENCE Uncommon. Arrhythmias. Chest pain. Lancet.. Tropisetron: 11 cases. Kwok K. 347: 1484-5 Kataja V. REFERENCES • • • Frigerio C. Buchwalder P. 28 (9): 1029-30 . “Hypersensitivity reactions associated with 5 hydroxytryptamine 3 receptor antagonists: a class effect ?”. Spertini F. CLINICAL MANIFESTATIONS Differentiate from non-allergic side-effects (headache. 1996. Lancet. “Ondansetron: reasons to be restrictive”. Bronchospasm. Pharmacother. 1996. 347: 584-5 Kossey J.149 - .M.A.

“Allergic reactions to mesna (letter) (see comments)”. MANAGEMENT Benefits of mesna outweigh the risk of allergic reactions.150 - . Clin. 338 (8768): 705-6 Seidel A.R. 1991. MECHANISMS Unknown.. Fever.H. 1991. Haga H. 338 (8763): 381-2 Pratt C.M. Meyer W. Intell. Corticosteroids may be useful.. INCIDENCE Severe reactions: 3/83. “Mesna-induced urticaria”.J. DIAGNOSTIC METHODS 2 cases with delayed type patch-tests reactions. REFERENCES • • • D’Cruz D. Lancet.B. Hughes G. a thiol compound is used to prevent hemorrhagic cystitis.T. Urticaria. Kässer U. All reactions: 4/31. Drug. comment)”. 1988. 22: 914 . Lemmel E.M. Sandlund J. Andrassy K. “Allergic reactions to mesna (letter. No specific IgE found. CLINICAL MANIFESTATIONS Macular pruriginous rash. complication of cyclophosphamide treatment.CHEMOTHERAPY DRUGS AND IMMUNOSUPPRESSORS MESNA Mesna (2 -mercaptoethane sulphonate). Ritz E. Pharm. Cain A.. Lancet.

DRUGS USED IN CARDIOLOGY V DRUGS USED IN CARDIOLOGY .151 - .

— uncontrolled retrospective studies: 6 . post-nasal drip. dry. .152 - . Idiopathic angioedema (angioedema). non smokers (cough). Dyspnea and wheezing: ten times less frequent than cough in reports of adverse respiratory reaction.3 to 6%. Cutaneous. Rash: 1. CLINICAL MANIFESTATIONS Respiratory. Pre-existing cough may be exacerbated. disappearing on average 3-6 days after drug withdrawal. Black Americans. INCIDENCE Cough: mean 15%. Average time of onset: one week. Worse in supine posi tion and at night. — nasal congestion.DRUGS USED IN CARDIOLOGY ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACE) The ACE inhibitors appear to be an attractive choice for managing hypertension and congestive heart failure at all stages.15%. Hong-Kong Chinese (cough). for as long as the drug is taken. Asthma is not a risk factor for cough. tickling. RISK FACTORS Women (cough). — controlled studies: 20%. Angioedema 1/1000 to 7/1000. sinusitis — hypersensitivity pneumonitis — cough: non productive.3%. — post-marketing surveillance: 1 .

often transitory. lips. PGE directly stimulates unmyelinated afferent vagal C fibers. Enalapril: 1/1000 during the first week. Often after first dose or within the first few days of treatment. Positive in 30% of patients with cutaneous manifestations. Patch tests: pure captopril in vaseline 0. Higher incidence with captopril is related to excessively high doses (600 to 1200 mg/ day) in the first studies. Drug re-challenge. Captopril increases plasma levels of prostaglandins.1/1/10 mg/ ml.1%. DIAGNOSTIC METHODS Cutaneous testing (anaphylactic or cutaneous reactions) Intradermal: 0. lasting for only a few hours or days and rarely a cause of discontinuation of treatment. Usually occurring within the first four weeks of therapy. MECHANISMS Cough. Angioedema: evolving face. tongue. Accumulation of bradykinin which stimulates the release of tachykinins including substance P and neurokinin A.DRUGS USED IN CARDIOLOGY Rash: maculopapular eruption predominantly occurring on the arms and upper torso. The rash is sometimes specific to a particular ACE inhibitor. the initial chemical mediator of the cough reflex in the lung. Check results after 15 minutes.05 ml of pure captopril: 0.153 - . May be associated with respiratory distress. Respiratory function tests: bronchial hyperresponsiveness to histamine or metacholine is sometimes found in patients who develop cough with ACE inhibitors. Positive in 60% of patients with cutaneous manifestations. 1 and 10% applied to the patient’s back. Skin biopsy: vasculitis with leukocyte infiltration in patients with cutaneous lesions. accompanied by pruritus. . Check results after 48 and 72 hours. but more often within the first few days.

In addition. Substance P is metabolized by ACE in tissues. MANAGEMENT Use another antihypertensive agent (especially if skin-tests are positive: high predictive value) lozartan (angiotensine 2 antagonist) which does not induce cough. which is effective in the treatment of cough induced by ACE inhibitors. “Thromboxane A2 synthetase inhibition suppresses cough induced by angiotensin converting enzyme inhibitors”. 1997. Nakashima M.154 - . Other drugs are now available: ozagrel (thromboxane A2 synthetase inhibitor). but a few cases of angioedema. Pulmonary accumulation of bradykinin may be a mediator of ACE inhibitor-induced coughing. Life Sci. and ACE inhibitors have previously been shown to decrease its metabolism. Sodium cromoglycate reduces cough scores of 50% by its inhibitor effect on the tachykinin-induced activation of C fibers. Bradykinin is known to activate afferent sensory C fibers via type J receptors which cause coughing. REFERENCES • Umemura K. Conversely bradykinin could increase the formation of prostaglandins and leukotrienes.DRUGS USED IN CARDIOLOGY Tachykinin stimulates the C fibers whose activation causes cough. including lung and skin.. a decrease in bradykinin degradation increases the synthesis of bradykinin and/ or related kinines. Saruta T. The mechanism of ACE inhibitor-induced coughing may involve substance P mediated airway priming but the final triggering of the ACE inhibitor-induced cough is unlikely to be due to this peptide. Thromboxane A2 is implicated in ACE induced cough. 60 (18): 1583-8 . Substance P is important in neurogenic inflammation and has a functional relationship via C fibers with mast cells in various tissues. Angioedema. Inhibition of ACE and/ or related enzymes in the kinine-kallikrein system blocks bradykinin metabolism.

Intradermal skin-tests at 1/100 are positive in a few cases. neck. 308 (6920): 18-21 Parish R. J. CLINICAL MANIFESTATIONS General: anaphylactic shock. “Putative mechanisms of cough after treatment with angiotensin converting enzyme inhibitors”.J. “Higher incidence of discontinuation of angiotensin converting enzyme inhibitors due to cough in black subjects”.. Drug Safety. Hedner T..C. Lindholm L.. Samuelsson O. . 60 (5): 582-8 Semple P. B. Clin. INCIDENCE Uncommon for anaphylactic shock. The Prausnitz-Küstner test is positive in a few cases.J. Miller L. enalapril and lisinopril. Andren L. 1992. “Dyspnoea.. A controlled retrospective cohort study”. 1995. Pharmacol.F. asthma and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors”. Ther.J. “Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril. Hypertens. DIAGNOSTIC METHODS Cutaneous testing. 1994. 1996. MECHANISMS Positive results of skin tests and Prausnitz-Küstner test suggest an IgE-mediated mechanism. An update”. Clin. 39 (3): 265-70 Lunde H. 13 (S3): S17-21 Wood R. Wiholm B.DRUGS USED IN CARDIOLOGY • • • • • Elliott W. chest). Cutaneous: erythematous rashes (face. Lötvall J. 1995.E.155 - . Specific IgE has not been detected. Pharmacol. Br.M. Suppl. 7 (1): 14-31 ATROPINE Atropine is a widely used premedication drug for the prevention of vagal bradycardia and especially in strabismus surgery. J. “Adverse effects of angiotensin converting enzyme (ACE) inhibitors.

Gancedo V. Anaesthesia. Giralt P. Strabismus surgery may be performed with hyoscine or glycopyrronium after skin tests. Anaesthesia. Arino J. Beta-blockers and local allergic effect. but the rate is probably much lower with cardioselective beta-blockers. Three problems: Beta-blockers and asthma. 1978. 13 deaths and 200 major reactions to timolol maleate eye drops have been reported in asthmatics in the USA. 43 (11): 955-7. Saez de Eguilaz J. as well as for local treatment of glaucoma.A.W. 50: 866. Beta-blockers and anaphylactic shock. Martinez-Bourio R. Dundee J. 44 (7): 290-1 Aguilera L. Mirakhur R. Cid C. Beta-blockers and anaphylactic shock: unknown. Rev.K. REFERENCES • • • Moyano P.. Bronchoconstriction also occasionally occurs in patients with chronic bronchitis.. Br. the local allergic effect has recently been recognized. “Anaphylactic reaction after atropine”.. .L. Reanim.156 - . Beta-blockers in eye-drops are widely used for the treatment of glaucoma. Esp. 1988. Ricos M. “Hypersensitivity to atropine”.J. Anestesiol.DRUGS USED IN CARDIOLOGY MANAGEMENT Avoidance. J. Ribas M. Arizaga A. BETA-BLOCKERS Family of drugs widely used to treat arterial hypertension and angina. INCIDENCE One 40 or 80 mg tablet of propranolol can induce bronchoconstriction in 50% of asthmatics. “Anestesia en dos casos de alergia a la atropina en la cirurgia del estrabismo”. 1997.

Anaphylactic shock to beta-blockers is characterized by bradycardia. MECHANISMS The mechanism underlying the ability of beta-blockers to produce bronchoconstriction remains unclear. if necessary determined by quantitative measurement of cardioselectivity: Clinical surveillance and spirometry at the time of administration.157 - . Beta-blockers and anaphylactic shock: beta-blockers inhibits the production of cyclic AMP (by reducing intracellular levels) and lower the threshold of mediator release by mastocytes and basophils. respiratory arrest. contact conjunctivitis with beta-blockers containing eye-drops. In contact allergy. MANAGEMENT Beta-blockers and asthma: — If a beta-blocker must be administered to an asthmatic pa tient. Beta-blockers and eczema: patch-tests 0. Administration in hospital: Day 1: Day 2: 1/10th of the dose. apnea in children. despite collapse and poor response to epinephrine. Beta-blockers decrease endogenous adrenaline secretion by blocking beta-2-receptors at synapses. This may be due to a common aldehyde after primary metabolism. DIAGNOSTIC METHODS Beta-blockers and asthma: clinical signs and spirometric data. Eczema of the eyelids.5% aq. Beta-blockers and anaphylactic shock: clinical signs. . dyspnea. and inhibit beta 1 effects of exogenous and endogenous adrenaline on the heart.DRUGS USED IN CARDIOLOGY CLINICAL MANIFESTATIONS Asthma. most of them cross-react. bronchospasm. beta-blockers have a very close structure. or pure eye-drops. 1/5th of the dose. use a selective beta 1 agent.

P. Herman D. 124: 322-4 Tattersfield A. either discontinue beta-blockers 48 hours before surgery. e. 30. Iseman M.158 - . “Allergie de contact aux bloqueurs des collyres: allergie croisée ?” . Bazeix J.. A propos de 14 observations” . dopamine. pulse and arterial blood pressure) at start then at 15. “Accidents anaphylactiques chez des patients traités par bêtabloquants. 41: 139-42. Preventive treatment: Skin-test and desensitization under beta-blockers is prohibited.E. Ann. 60 and 120 minutes. Rev. Fernandez E. The risk of recurrence is high if another local betablocker is used. to timolol: instillation of one drop of timolol collyre at 0. Beta-blockers and contact eczema with eye-drops: avoidance. full dose.50% in each eye followed by second instillation 20 minutes later. —The best agent available at the present time is a beta 1 selective product: betaxolol. For anesthesia. 1997. Dermatol.g.M. • . Nataf P. Pharmacol. 1986. — If beta-blocker eye drops must be administered to an asthmatic patient. Am. Cardiovasc. Thérapie. Cherniack R.D.S. need for blood volume expansion (6 to 7 l). Calix I. Gerber M. “The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects” . clinical surveillance (chest auscultation. Beta-blockers and anaphylactic shock: Curative treatment: refractory to adrenaline. or perform an isoprenalin test during surgery (seldom done). use of isoprenaline. REFERENCES • • • Giordano-Labadie F. Dis. 8 (S 4). Respir.L. J. 133: 264-8. 1986. Dunn T. 35-9. Benitah E. or glucagon. Venereol.. “Beta adrenoreceptor antagonists and respiratory disease”. first test tolerance..J. perform spirometry at the same time. 1986. Lepoittevin J. Shen A.DRUGS USED IN CARDIOLOGY Day 3: Day 4: 1/2 of the dose.

no difference was found in the proportion of serious cutaneous adverse events between the three drugs. However. The number of diltiazem-induced cutaneous events was significantly higher than those induced by either nifedipine or verapamil.2) days after initiation of the treatment. benzothiazepines.4 (+/. non-thrombocytopenic purpura. urticarial vasculitis. CLINICAL MANIFESTATIONS Cutaneous: acute generalized exanthematous pustulosis (AGEP): 5 cases . 151 (48%) were cutaneous.2.159 - .DRUGS USED IN CARDIOLOGY CALCIUM CHANNEL BLOCKERS Widely used in the treatment of arterial hypertension. DIAGNOSTIC METHODS Cutaneous testing.8) days after discontinuation. StevensJohnson’s syndrome. photosensitivity. hypersensitivity syndrome reaction (1-17 days after initiation of therapy). maculopapular rashes. one patient with non thrombocytopenic purpura due to nifedipine had a similar eruption with diltiazem. dihydropyridines. Serious cutaneous reactions: erythema multiforme. There are 3 groups of calcium channel blockers: phenylalkylamines.Occurring 8. Conversely. another one with pruritic exanthema after diltiazem had a recurrence after amlodipine. and clearing 10 (+/-1. toxic epidermal necrolysis. . INCIDENCE Of the 315 cases of possible diltiazem-induced adverse reactions that were reported by the Health Protection Branch. Patch-test or intradermal skin tests: sometimes positive in diltiazeminduced cutaneous reactions. Similarly nifedipine-reactive patients have usually tolerated diltiazem. Less severe reactions: fixed drug eruptions. Drug re-challenge with nifedipine or verapamil in diltiazem reactor patients is rarely positive.

1994. 1989.. Respiratory: acute pulmonary edema. Intern. “Cutaneous adverse reactions associated with calcium channel blockers”. J. vasculitis.K.A.. requires careful monitoring. Cutaneous: pruritus. Arch.DRUGS USED IN CARDIOLOGY MECHANISMS The mechanism of adverse reactions from diltiazem and other calcium channel blockers is unknown. Am. 38: 201-6 Baker B. Acad. lichenoid eruption.G. REFERENCES • • • Knowles S. 1998. 0. “The spectrum of cutaneous reactions associated with diltiazem: three cases and a review of the literature”. Dermatol.. it is likely that the pathophysiology differs with each reaction. Stevens Johnson’s syndrome. periorbital edema. INCIDENCE Exceedingly rare for anaphylactic reactions. Pharmacother. Khalsa J. vesiculo-bullous eruption. . Shear N. Digestive: pancreatitis. urticaria. Med. Ann. CLINICAL MANIFESTATIONS General: anaphylactic shock. Cacchione J.5% for mild cutaneous reactions. eczematous rash. Gupta A. Because the spectrum of cutaneous reactions is extensive. 149: 829-32 FUROSEMIDE Furosemide or chloro-4-furfurylamino-2-sulfamoyl-5-benzoic acid is a widely used Henle’s loop diuretic. hepatitis. MANAGEMENT In case of calcium inhibitor allergy the use of a such treatment. “Cross-sensitivity between diltiazem and amlodipine”. even from another group. 28: 118-9 Stern R.160 - .H.

M. Med.. MECHANISMS Type I suspected on a basis of immediate positive skin tests. “Anaphylaxis to intravenous furosemide”. MANAGEMENT Avoidance. J.DRUGS USED IN CARDIOLOGY DIAGNOSTIC METHODS Cutaneous testing. Guillaume C. Med. Intradermal at 1%: positive for furosemide as well as for chlorothiazide. “Comparison of adverse reactions to bumetamide and furosemide”. Vedrinne J.. “Absence d’allergie croisée entre furosemide et bumetanide”. Motin J. Godard J.C.161 - . Immunol. Hansbrough J. 1987. Wedner H. 21: 615-9 . Bui-Xuan B.H. 1987. Dan.. Patte F. 1989. Vandel B.J. No cross reactivity between furosemide and sulfonamides. Allergy Clin. “Adverse reactions in the skin from antihypertensive drugs”.D. 80 ( 4): 538-41 Thestrup-Pedersen K. Rev. “Allergie de mécanisme non-immediat au furosemide”. REFERENCES • • • • • Gratadour P. Type III suspected in pancreatitis and hepatitis. bumetanide and sulfamethoxazoletrimethoprim. Bumetanide may be used as replacement therapy in furosemide induced vasculitis. Bull. Pineau-Drouin D. 19 (32): 1504 Breuil K. Prick-tests: negative. 29 (3): 150-1. J. Meurice J. 1981. 1990. fr.R... Presse. Pharmacol. Clin. Chaplin D. Allergol. 34 (S1): 3-5 Tuzel I. One case with delayed positivity (10th hour).

Anaphylactic shock: one case reported. Ring J. CLINICAL MANIFESTATIONS General: anaphylactic shock Cutaneous: urticaria.DRUGS USED IN CARDIOLOGY PRAZOSIN Prazosin is a derivative of quinazoline.3% of subjects treated. angioedema. MECHANISMS Undetermined. No specific IgE found. Lancet. 86 (1 B): 91-3 Ruzicka T.. 1989. MANAGEMENT Avoidance. Am. “Hypersensitivity to prazosin”. . “Prazosin in hypertensive patients with chronic bronchitis and asthma: a brief report”. REFERENCES • • Chodosh S. Tuck J.162 - . 1983. DIAGNOSTIC METHODS Cutaneous testing: prick tests are very hazardous (one collapse reported). Med. Respiratory: bronchospasm. 1 (8322): 473-4. INCIDENCE Urticaria: 0. Pizzuto D. J. It is an antihypertensive drug that produces vasodilatation by blocking post-synaptic alpha receptors.

163 - . PRESERVATIVES. ANTISEPTICS . ANTISEPTICS VI DYES. PRESERVATIVES.DYES.

Cutaneous: pruritus. triamcinolone acetonide). MANAGEMENT Avoidance is extremely difficult due to the extensive use of carboxymethylcellulose (drugs and foods).164 - . Scratch-tests: positive with the drug and carboxymethylcellulose.DYES. latex. corticosteroids). angioedema. urticaria. . Intradermal skin-tests: 1/100000 to 1/10000. ANTISEPTICS CARBOXYMETHYL-CELLULOSE Carboxymethylcellulose sodium is a highly viscous material used in pharmaceutical preparations as a suspending agent to promote dissolution of compounds with poor water solubility (barium enema. Specific histamine release: 2 cases. Described with barium enema (differentiate from other ingredients: methylparaben. Specific IgE: one case. MECHANISMS IgE-mediated hypersensitivity. Respiratory: bronchospasm. carrageenan) and corticosteroids (cortivazol. prednisolone acetate. CLINICAL MANIFESTATIONS General: anaphylactic shock. DIAGNOSTIC METHODS Cutaneous testing Skin-prick tests: 1%. PRESERVATIVES. INCIDENCE Infrequent.

4 with cyanosis. “Anaphylaxie à la carboxymethylcellulose: à propos de deux cas de chocs à des corticoïdes injectables”. J. N..L. Asthma. 1997.DYES. INCIDENCE 50 cases reported between 1967 and 1984: 22 with hypotension.165 - . Allergy. Anaphylactic reactions have been reported after urinary catheterization.. Jones R. Fujii T. Cutaneous: pruritus. Saeki K. PRESERVATIVES. photosensitive dermatitis. Respiratory: bronchospasm. Nakaya N. Moneret-Vautrin D. Henmi K. Yamagata M. Yunginger J. 9 with anaphylactic shock. Immunol. Dunn W. (Paris). Engl. RISK FACTORS For anaphylactic reactions: contact dermatitis to chlorhexidine. 1995. occupational asthma. mycobacteria. Allerg.W. contact dermatitis. Nishibori M. and placement of a central venous catheter. 24 (9): 333-5 • CHLORHEXIDINE Biguanide antiseptic and disinfectant active against a broad spectrum of bacteria. Kanny G. erythema. CLINICAL MANIFESTATIONS General: anaphylactic shock. Hunt L. Ann.F. Gueant J. . Immunol.. “Anaphylaxis from the carboxymethylcellulose component of barium sulfate suspension”.W. viruses and fungi.A. topical application of a dressing on a burn. 13 with dyspnea. fixed drug eruption. “Anaphylaxis induced by the carboxymethylcellulose component of injectable triamcinolone acetonide suspension (Kenalog)”.L. Hosoi S. 1992. 337 (18): 1275-7 Patterson D. disinfection of a drain insertion site. ANTISEPTICS REFERENCES • • Muroi N. urticaria.T. 74 (2): 163-6 Beaudouin E. Med.

101 (1. 70 (4): 451-2 Okano M. Stevens W. Craenen A.05%. Kanda N. Do not use chlorhexidine gluconate on mucosa. Urol..005% to 0. Kitano Y. Hamasaki J. Sato K.0002% to 0. Histamine release test. MANAGEMENT Avoidance in allergic patients. Hata S. J. ANTISEPTICS DIAGNOSTIC METHODS Cutaneous testing. Yoshimoto Y. 1998.1): 128-9 Oda T. Anesthesiology.J.. PRESERVATIVES. “ Severe allergic reaction to intraurethral preparation containing chlorhexidine”. Specific IgE (RAST). Okada N. Intradermal skin-tests: 0. Bridts C. MECHANISMS IgE-mediated hypersensitivity.prick tests: 0. Matthieu L.02 ml at 0. Immunol. . 87 (5): 1242-4 Ramselaar C. Mikami K. Bijleveld R. Allergy. Br. Arch. Aoki T.DYES. Hama R. “Contact allergic dermatitis and life-threatening anaphylaxis to chlorhexidine”. Dermatol. “Anaphylactic shock induced by an antiseptic-coated central venous catheter”. Skin.T. Nomura M.166 - . J. Use at lowest bactericidal concentration (0.G.H. 125: 50-2. Tashiro M. 1992.. REFERENCES • • • • Ebo D. Positive in anaphylaxis cases. 1989. Clin. Patch-tests 1%: positive in contact dermatitis. “Anaphylactic symptoms due to chlorhexidine gluconate”. 1997.G.05%) on wound surfaces.002% concentrations.

antiseptic and anesthetic properties used in many externally applied products as well as in drugs (vasopressin.S. 21 (2): 211-2 Hofman H. One positive result was reported in a patient with a maculopapular eruption. Cutaneous: pruritus. oxytocin). MANAGEMENT Avoid use of drugs containing this preservative. CLINICAL MANIFESTATIONS General: anaphylactic shock. One death reported. “Anaphylactic shock from chlorobutanolpreserved oxytocin”. Bowles B.J.C. Intravenous challenge with chlorobutanol was positive in a patient 5 minutes after 1 ml of 1/1000 chlorobutanol solution.M.5%.M. ANTISEPTICS CHLOROBUTANOL Preservative with hypnotic. DIAGNOSTIC METHODS Cutaneous testing. — Intradermal skin-tests using chlorobutanol at 0. Care. 1985.J. Goerz G. 1986. Anaesthesia. Contact Dermatitis. PRESERVATIVES. 40: 655-6 . Pumphrey R. Russell W. MECHANISMS Undetermined. heparin. Plewig G. “Anaphylactoid reaction to Syntocinon*”.DYES. — One positive scratch test in a patient with anaphylactic shock. 15 (4): 241-2 Slater R.167 - . INCIDENCE Uncommon. .H. R. Anaesth. sedative. REFERENCES • • • Maycock E. maculopapular eruption. “Anaphylactoid reaction to oxytocin in pregnancy”. 1993. Intensive.

Non IgE-mediated hypersensitivity (IgG 4). Rosenfeld J. and high viscosity. Respiratory: bronchospasm.L. “Hypersensitivity to chlorobutanol in DDAVP solution”. Yamaji T. polyoxyethylated castor oil used to dissolve water insoluble drugs. Cutaneous: urticaria. MECHANISMS IgE-mediated hypersensitivity (few cases). Lancet. Greater specific gravity than water. Complement activation (+++). Katayama S. TAXOL (paclitaxel).DYES. DAKTARIN (miconazole). DIAGNOSTIC METHODS Cutaneous testing. Non specific histamine release. A few cases with positive intradermal tests with cremophor 0. CREMOPHOR E. Non ionic surfactant. Lancet. KONAKION (vitamin K1).L.B. CLINICAL MANIFESTATIONS General: anaphylactic shock. Pitlik S. ANTISEPTICS • • Itabashi A. INCIDENCE Adverse reactions have been described with numerous drugs.Perry G. EPONTOL (propanidid): withdrawn from the market. .2 mg/ml to 20 mg/ml. 1982. 1981 1 (8212):149. STESOLID MR (diazepam): reformulated without cremophor E. DIPRIVAN (propofol). VUMON (teniposide). SANDIMMUNE (cyclosporine). “Hypersensitivity reaction to chlorbutol-preserved heparin”.168 - . ALTHESIN (alphaxalone). PRESERVATIVES. generalized erythema. No specific IgE found. DIDEMNIN B (didemnin B): currently in use. 1 (8263): 108 Dux S.

is soluble in water. Ann. Cutaneous: chronic urticaria. 50 (6): 571-3 Dorr R.B. Respiratory: asthma.J. Ann. serum sickness. Locker S. PRESERVATIVES. This could be extrapolated to other drugs containing cremophor E. Vergnaud M. Corry R.T. 1998.A. INCIDENCE Uncommon. “The hemodynamic effects of cremophor E.L .169 - . It belongs to the azoic-class of coloring agents.. Transplantation. “Reactions anaphylactoides à une solution polyvitaminée injectable contenant un cremophore”. Allergy. “Pharmacology and toxicology of cremophor E. Pharmacother. Ames S. ANTISEPTICS MANAGEMENT Avoid use as excipient if possible. Ann.. REFERENCES • • • Volcheck G. .C. Immunol. binds strongly to serum proteins in vitro and presents little toxicity while supplying a high level of iodine.T.L”. Piquet M. and avoidance of polyvinylchlorure in the set-up.L”. CLINICAL MANIFESTATIONS General: anaphylactic shock.W.D. angioedema. Bricard H. Therapie. E. 51 (4): 847-50 • • ERYTHROSINE Erythrosine is a tetraiodofluoresceine-resembling eosine used as a food and drug colorant.DYES.N. 1997. . Jennings W. 80 (2): 159-63 Michaud L. Van Dellen R. In the case of intravenous cyclosporine: proper mixing during the preparation of the infusion.G. 28 (5 s): S11-14 Bowers V. Pharmacother. photosensitization.L diluent”. Asthma. “Methods for preventing reactions secondary to cremophor E. Mosquet B. 1994. 1995.: chronic rhinitis. Esse-Comlan A. Laroche D. 1991.. “Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review”.. Divanon F. 31 (11): 1402-4 Mounier P.

Girard J.P. followed by reintroduction of the coloring agent in capsule form gives clear and irrefutable results. an elimination diet of several weeks. 1985. ANTISEPTICS DIAGNOSTIC METHODS Cutaneous testing. . Aminophylline is a complex of 2 theophylline molecules to one ethylenediamine molecule. Precipitating antibodies in patients with serum sickness. Immune complex-mediated hypersensitivity has been implicated in patients with serum sickness.. Allergol. 1 (25) 7-11. Re-challenge with surveillance of target organ: MECHANISMS Immediate IgE-mediated hypersensitivity is involved in most cases (immediate positive skin tests.DYES. ETHYLENEDIAMINE Ethylenediamine is used as a binding agent (creams.5 mg/ml give positive results in 35 to 70% of patients with immediate or delayed reactions to erythrosine.170 - . eye drops. Etude du rôle des mécanismes d’hypersensibilité”. Intradermal skin-test using an aqueous solution at a concentration of 1. Detection of IgE antibodies by RAST is successful in 70% of patients with immediate reactions. Bodmer R. detection of specific IgE antibodies). aminophylline. REFERENCES • Vesely B. PRESERVATIVES. Rev. enema) conferring greater solubility and reducing the alkalinity of the drug. Guerin B. “Manifestations cliniques à l’erythrosine. fr. MANAGEMENT Value of challenge tests in conjunction with RAST and skin test. For cutaneous manifestations.

headache. MECHANISMS Possible IgE-mediated hypersensitivity in few cases Type IV cellular reaction. erythroderma. exfoliative dermatitis. to ethanolamine group antihistamines (clemastine. Patch-tests: aminophylline 1% pet. General: anaphylactic shock. . Acetylation is one of the major metabolic pathways for ethylenediamine. Intradermal skin-tests: aminophylline 1%. fever. occupational asthma in exposed subjects to ethylenediamine vapors. carbinoxamine. urticaria. Sensitization to ethylenediamine is particularly common with topical drugs. MANAGEMENT Ethylenediamine-sensitive patients can develop allergy to piperazine (antihelminthic agent). maculopapular rash. periorbital edema. ethylenediamine 1% pet.1% and 1%.171 - . Cutaneous: pruritus. Specific histamine-release positive in one case. but delays of 6 to 8 hours have also been reported. contact dermatitis (occupational in pharmacists). Respiratory: bronchospasm. CLINICAL MANIFESTATIONS (allergic reaction may occur with intravenous aminophylline and oral formulations or suppositories) Manifestations usually appear 24 to 48 hours after intake of the drug.DYES. myalgia. DIAGNOSTIC METHODS Cutaneous testing. diphenhydramine. ethylenediamine 0. No specific IgE found. angioedema. . PRESERVATIVES. ANTISEPTICS INCIDENCE Ethylenediamine sensitivity: 13% in patients with contact dermatitis.

Rev.DYES. Contact.: laryngeal edema. 1993. 1981.I. Dermatitis. Contact. 39 (8):600-3. Elias J.A.A. . 31 (3): 198-9 Eedy D. Cuevas M. Cole P. Gibb W. antazoline phosphate). “Hypersensitivity reactions to ethylenediamine in aminophylline”. Ann.. Respir.172 - . MERCURY ANTISEPTICS Widely used antiseptics: mercurochrome. Delayed cutaneous reactions are common. Levinson A. Use an ethylenediamine-free theophylline. Cutaneous: acute urticaria. to triethanolamine containing creams and to ethylenediamine antihistamines (tripelennamine hydrochloride. 28 (1): 48-9 de la Hoz B. INCIDENCE Systemic reactions are uncommon. Allergy. “Immediate adverse reaction to aminophylline” . Citron K. facial edema. Respiratory: bronchospasm. REFERENCES • • • • • Urbani C. “Angioneurotic oedema following piperazine ingestion in an ethylenediamine-sensitive subject”. ANTISEPTICS hydroxyzine). Thorax. Perez C. “Urticarial reaction to ethylenediamine in aminophylline following mesotherapy”..M. “ Generalized allergic reactions to aminophylline”. E. 71 (5): 452-4 Thompson P.J. 123 (5): 550-2. Dis. Salazar F. PRESERVATIVES. Am. thiomersal. CLINICAL MANIFESTATIONS General: anaphylactic shock. Lazaro M. phenylmercuric acetate.E.N.J. Tejedor M.G.T.R. 1994. 1984. 1993. contact dermatitis. Dermatitis.

Dermatol. Torres. 3% of delayed cutaneous manifestations. MANAGEMENT Avoid use. PARABENS These methyl. INCIDENCE 0. propyl. 1985. 118. “Ocular inflammation in patients using soft contact lenses”. 54. and butyl esters of hydroxybenzoic acid have bacteriostatic and fungicide properties and are the most widely used preservatives in food. 230–232. antihepatitis B). In addition to products for external use. One positive Prausnitz-Küstner test has been reported. Rietschel. “Anaphylactic hypersensitivity to mercurochrome (merbrominum). ANTISEPTICS DIAGNOSTIC METHODS — Prick and intradermal tests with mercury chloride. 1982. 147–148.9% of drug allergies. . mercurochrome. — Patch-test may be positive in patients with contact dermatitis (thiomersal). mercury nitrate. cosmetics and medications (more than 300 pharmaceutical categories). phenylmercury acetate. MECHANISMS IgE-mediated hypersensitivity may be implicated in immediate reactions. ethyl. Allergy. thiomersal.173 - . thiosalicylic acid.DYES. Arch. S. some vaccines also contain mercury antiseptics (antituberculosis. 0. PRESERVATIVES. REFERENCES • • A. “Ann. Results may be positive following an acute reaction.8% of chronic dermatitis (skin tests).. Cell-mediated hypersensitivity in patients with contact dermatitis.

and butylparaben in order to avoid false negatives. Insidious chronic dermatitis is frequent especially if corticosteroids are associated. propyl and butyl para-hydroxybenzoates. DIAGNOSTIC METHODS Cutaneous testing. PRESERVATIVES. pruritus. propylparaben. Previous sensitization by substances with a para-amine function. Cross-sensitivity may occur between parabens and molecules possessing a free amine group in the para position ( benzocaine. . ethyl. MECHANISMS IgE-mediated hypersensitivity is suggested by the following findings: positive Prausnitz-Küstner tests reported in several cases. Localization on the face or the neck. Parabens mix belongs to the European patchtests standard series and contains 3% of methyl. ANTISEPTICS RISK FACTORS Damaged skin (leg ulcer.DYES. angioedema. immediately positive intradermal skin tests. CLINICAL MANIFESTATIONS After topical use: contact eczema After oral use: Eczema-like eruptions. pruritus. Cell-mediated hypersensitivity is responsible for contact dermatitis. — Respiratory: dyspnea. stasis dermatitis). urticaria. — Intradermal skin-tests should be performed with a 5% concentration of methylparaben. — Cutaneous: erythema. — Patch-tests are often positive in patients with contact dermatitis. After systemic administration. ethylparaben. worsening of ongoing asthma. bronchospasm. However. urticaria.174 - . A few positive results have been reported in patients with immediate reactions. IgE antibodies have never been detected.

“The parabens: paradoxical preservatives” Cutis. Manassero J. PRESERVATIVES. Cassuto D.E.T. JAMA. 51 (6): 405-6 Chichmanian R.M. oral.175 - . 237: 1594-5. “Paraben allergy”. 437-8 Fisher A. Spreux A. hydroxyl compounds has been documented. ANTISEPTICS para-phenylendiamine and sulfonamides). 1995. Frosch P. 1985. 40: 365-7. “Multiple sources of allergic contact dermatitis from parabens” . MANAGEMENT Avoidance is difficult. 1993. 1977.G. Cross reactivity between p. Contact. “Textbook of contact dermatitis”. The only difference between such products and parabens is the presence of a hydroxy instead of an amine group in the para position. Menne T. Rôle d’un excipient”. contact dermatitis.DYES. 36 (5): 269-70 Rycroft R. CLINICAL MANIFESTATIONS General: anaphylactic shock Cutaneous: urticaria. “Manifestations allergiques multiples.J. Fuscaldo J. Thérapie. REFERENCES • • • • • Verhaeghe I. Dooms-Goossens A. amine and p.J. Nagel J. POVIDONE Povidone or polyvinyl pyrrolidone is a polymer with a molecular weight ranging from 10000 to 700000. 1997. INCIDENCE Rare. Respiratory: asthma (hair spray). and parenteral pharmaceutical products. 2nd Ed. Mignot G.Springer-Verlag Berlin. Fireman P. comparable to plasma proteins and used as excipient in topical.A. Dermatitis. .

Histamine release test. MANAGEMENT Avoidance. IgE-mediated hypersensitivity. Mata E. responsable d’un accident à un produit iodé de contraste: à propos d’un cas d’asthme après hysterosalpingographie”.N. Povidone 10 has been shown to be a potent activator of suppressor T-cells. 1996. Ann. (Paris). Proteau J. Allerg. “Anaphylactic shock following povidone”. Pharmacother. 1989.A. E. Pneumol. INCIDENCE Rare. Capron F. Pages M. Trechot M.G..A. Clin. 21: 196-9 Ameille J. Rev. “Pathologie respiratoire induite par l’inhalation de laque capillaire”. whereas povidone 40 and 60 are able to activate B-cells. 30 (1): 37-40 Moneret-Vautrin D. “Allergie probable à la polyvidone. Duran Quintana J.176 - . PRESERVATIVES. MECHANISMS Non specific histamine release. Basophil degranulation test.. REFERENCES • • Gonzalo Garijo M. Maiquez Asuero P. Immunol. Gerard H. ANTISEPTICS Ocular: conjunctivitis (intraocular lenses). 1985. DIAGNOSTIC METHODS Cutaneous testing. Rochemaure J. Provocation challenge.A. .DYES. Bobadilla Gonzalez P.T: rhinorrhea. 41: 325-30 • POVIDONE IODINE Povidone iodine is widely used as an antiseptic.

Macotela E. 1990.DYES. Contact Dermatitis.G. SO2: sulfurous anhydride.H. 8 (1): 107-9 Ancona A. Patch-tests: positive with Betadine solution. 20% in pet. Betadine ointment. Suarez de la Torre R. Na2S 2O 5: sodium metabisulfite. Betadine scrub 2% in water. negative with potassium iodide 5. PRESERVATIVES. NaHSO 3: sodium bisulfite. van der Berg W. Na2SO3: sodium sulfite.. povidone iodine 10% in pet. ANTISEPTICS CLINICAL MANIFESTATIONS Cutaneous: contact eczema. K2S2O5: potassium metabisulfite. DIAGNOSTIC METHODS Cutaneous testing.177 - . 10.W. negative with iodine tincture (open test). MANAGEMENT Avoidance. “Allergic contact dermatitis from povidone-iodine”. “Sensitization to povidone-iodine”. MECHANISMS Type IV hypersensitivity. 15. INCIDENCE < 2% in the general population. 4 to 8% of asthmatics are sulfites sensitive 1. 13: 66-8 SULFITES Sulfites are used in the pharmaceutical and food industry for their antioxidizing and antibacterial properties. Clin.H. Dermatol.7% of positive sodium metabisulfite patch-tests in patients with eczematous dermatitis . REFERENCES • • van Ketel W. 1985.

50. PRESERVATIVES. Patch-tests with sodium metabisulfite 1% in petrolatum are used in the diagnosis of contact allergy. contact dermatitis. dried fruits. candies. lidocaine. angioedema.5% citric acid positive in 20% of steroid-dependent asthmatic children.DYES. MODE OF EXPOSURE Food: preservative in dried food (e. ANTISEPTICS The majority of sulfite reactions are dietary.100 mg dissolved in 20 ml of 0. rhinorrhea. delayed skin-tests with sulfite solution 2% are usually negative. Laryngeal edema. doxycycline) Anaphylactic shock. Challenge tests. bleaching agent in codfish filets. Asthma (steroid-dependent chronic asthma). Skin-prick tests (1 to 10 mg/ml).178 - . Drug: at least 1000 sulfite-containing drugs in USA (aminoglycosides. fish). Subcutaneous challenge tests (do not exceed 10 mg): not always positive in sulfite-sensitive individuals. Oral challenge tests: 5. shrimps.10. Urticaria.25. cider. wine. CLINICAL MANIFESTATIONS (reported with: novocaine. fruit and vegetable juice. local anesthetics with epinephrine. 3% of total reactions are attributed to drugs. DIAGNOSTIC METHODS Cutaneous testing. gentamicin. antifungal creams).g. beer. vitamin B injection preparations. RISK FACTORS Aspirin intolerance? Steroid dependent asthma. vegetables. fresh grapes. nasal pruritus. periorbital edema. metoclopramide. Inhalation challenge tests. corticosteroids. intradermal skin-tests (5 mg/ml). .

25 (8): 680-1 Vena G. Contact Dermatitis. 1993. 31 (3): 172-5 Lodi A. Clin. A propos de 9 patients. Toxicol. but false negative results are frequent. MANAGEMENT Cyanocobalamin is effective in preventing clinical sulfite reactions. Investig. Marotel C.G. Immunol. Drugs: see the drug listing. “Aspects cliniques et diagnostic de l’intolérance aux sulfites. or use detection band.C “ Review of parenteral sulfite reactions”. 1992. Allergol. “Contact allergy to sodium sulfite contained in an antifungal preparation”. Contact Dermatitis.L.. L’Her P.179 - . Vaylet F. Torro I. a detection band can be used. Martorell A. Angelini G. If not. “Sulfite contact allergy”.. J. 1992. “Sulfite sensitivity ”. positive transfer-tests. Chiarelli G. 1994. Rev.Allergy. ANTISEPTICS MECHANISMS Several hypotheses: — IgE-mediated hypersensitivity (positive skin-tests. 2 (1): 36-8 Smolinske S. Natali F. Clin.DYES. 1995. 1996.Exp. Pneumol. J. Crosti C.”. Clin. Carlos-Cerda J. Alvarez V. 52 (6): 363-71 Peroni D. Boner A. Foti C. no specific IgE found) — Inhalation of sulfur dioxide (bronchoconstriction) — Direct nervous stimulation by SO2 — Direct membrane toxicity — Sulfite oxidase deficiency — Delayed contact sensitivity in contact eczema. REFERENCES • • • • • • Miltgen J. 29 (2): 97 Sanz J..A.L. “Intolerance to sodium metabisulfite in children with steroid-dependent asthma”. Mancini L. Clin. PRESERVATIVES. Avoid use: Foods: easy if the presence of sulfites is indicated on the package label. 30 (4): 597-606 . Toxicol.

antihistamines. E. .1 to 6 subjects /1 000.5. steroids. fixed drug eruption. Consequently.180 - .25 and 50 mg at 30 minute intervals. no avoidance of tartrazine in aspirin-allergic patients unless an adverse reaction has been observed in challenge tests. Asthma: tartrazine 0. bronchodilators and antidepressants (imipramine. Respiratory: bronchospasm.: rhinitis. amitriptyline).DYES. INCIDENCE 0. CLINICAL MANIFESTATIONS General: anaphylactic shock. allergic vasculitis. No cross reaction has been demonstrated between tartrazine and aspirin with regard to respiratory symptoms.N. perform oral challenge. ANTISEPTICS TARTRAZINE Tartrazine is an azo dye used in many foods an drugs including antibiotics. Reappearance of symptoms is sufficient proof of tartrazine hypersensitivity. In obscure cases.1 mg to 50 mg at 30 minute intervals. Cutaneous: urticaria (acute and chronic). re-challenge with tartrazine. angioedema. MECHANISMS Direct histamine release? MANAGEMENT Tartrazine free diet and avoidance of all drugs containing tartrazine. PRESERVATIVES. DIAGNOSTIC METHODS The oral challenge with tartrazine is a only reliable method of accurate diagnosis: Urticaria: tartrazine 1. desipramine. If symptoms improve. contact dermatitis.T.

“Fixed drug eruption to tartrazine”. Austral. influenza.R. J. — Immunoglobulins: RhoD for example. 1997. 1990. and active against fungi and yeast.A. or thiomersal. — Vaccines: diphtheria. 38 (4): 212-4 Dipalma J. J. tick-borne encephalitis.. Lumry W. Varigos G.C. It is bacteriostatic against Gram+ and – bacteria. 1986. “Adverse reactions to tartrazine”. “Tartrazine sensitivity”. histoplas min. 10% of patients with positive patch-tests to thimerosal show adverse reactions to thimerosal containing vaccines.R.001 to 0. 42 (5): 1347-50 Stevenson D.181 - . J. hyposensitization therapy . staphylococcus. 22 (3): 139-43. PRESERVATIVES. or merthiolate (sodiumethylmercurithiosalicylate) has been used as a preservative in vaccines and topical medication for years. — Extracts and diluents for: intracutaneous allergy tests. meningococcus A. Asthma.1%).DYES. 78: 182-91. 1985. Fam.A. THIMEROSAL Thimerosal. Dermatol. mumps. Simon R. tetanus. Am. “Clinical spectrum of adverse reactions to tartrazine”. intracutaneous testing for candida. pertussis. ANTISEPTICS REFERENCES • • • • Orchard D.. Mathison D. Immunol.D. sal monella. mumps.. Collins-Williams C. Allergy Clin.A. RISK FACTORS Young adults (greater exposure to vaccines containing thimerosal?) CLINICAL MANIFESTATIONS Possible sources of thimerosal (0. Physician. coccidioidin. hepatitis B. INCIDENCE 1 to 25% of positive patch-tests to thimerosal in patients with contact allergy.

but negative to other mercurials — positive to thimerosal and some other mercurials. skin — Storing and cleaning solutions for soft contact lenses. PRESERVATIVES.05% in pet. toothpastes. . ethylmercurychloride 0. Contact urticaria. but negative to mercurials and thiosalicylic acid — positive to thimerosal and thiosalicylic acid.1% in pet. Asthma (one case). Persistent local reactions to vaccines.182 - . (0. pesticides. Contact dermatitis.1% is irritant) thiosalicylic acid 0. mouthwashes. — Disinfectant for skin and mucous membranes — Cosmetic creams and lotions. but negative to thiosalicylic acid. generalized exanthematic eruptions. There is a cross-reactivity between thiosalicylate and a degraded photoproduct of (sensitization to thimerosal with photosensitivity to piroxicam). ENT area. MECHANISMS The ethylmercury radical appears to be the allergenic determinant.DYES. Acute laryngeal obstruction (throat spray). Generalized urticaria. ANTISEPTICS — Blood and plasma products — Topical medications: eyes. DIAGNOSTIC METHODS Patch-tests with: thimerosal 0. Keratoconjunctivitis (contact lens wearers). Prolonged external otitis (topical ear treatment).05% in pet 3 groups of patients are to be considered — positive to thimerosal. The high frequency of patch-test reactions to thimerosal is due to sensitization by thimerosal containing vaccines.

E. “Sensitivity to thimerosal and photosensitivity to piroxicam”. Dermatitis. J. Gonçalo S. REFERENCES • • • • • Luka R. Freitas J.P. “Vaccination despite thimerosal sensitivity”. 24: 6-10 . Dermatitis. 1996. Oppenheimer J. Clin. Dermatitis. “Hypersensitivity to thimerosal: the sensitizing moiety”. 24 (3): 187-92 Aberer W. Rossi J. 1994. Miller N. Contact. Themido R. Contact. PRESERVATIVES. Contact. 1997.L. 34: 201-3 van’tVeen A.J. Dermatitis. van Joost T. Menezes-Brandao F. Figueiredo A. “Delayed hypersensitivity to thimerosal in Rho (D) immunoglobulin”.. 1991.6%) of hydrogen peroxide. A history of ocular sensitivity to thimerosal does not preclude hepatitis B vaccine administration. 1991. 100 (1): 138-9 Gonçalo M. Replace thimerosal in soft contact lenses care with sterile singleunit preservative-free saline with thermal disinfection or use special preservative-free care system containing only a low concentration (0. “Sensitization to thimerosal (merthiolate) is still present today”.J. Contact. 31 (5): 293-8 Cirne de Castro J. A positive patch-test with thimerosal should often be regarded as an accidental finding with no clinical relevance. Immunol. Bielory L.DYES. Allergy.183 - . ANTISEPTICS MANAGEMENT Hypersensitivity to thimerosal does not imply true mercury allergy.

DYES. PRESERVATIVES. ANTISEPTICS .184 - .

PRODUCTS USED IN DIALYSIS VII PRODUCTS USED IN DIALYSIS .185 - .

Respiratory: dyspnea. MANAGEMENT Use of reused dialyzers lower complement activation.PRODUCTS USED IN DIALYSIS CUPRAMMONIUM CELLULOSE HEMODIALYZERS Dialyzers prepared with raw cellulose.3/year/1000 patients. Cutaneous: pruritus. copper. Atopy (more rapid onset and more pronounced complement activation). hypotension. and other chemical products. vomiting.186 - . CLINICAL MANIFESTATIONS First-use syndrome: chest and back pain. Digestive: nausea. nausea. INCIDENCE 3. Previous exposure to the same type of hemodialyzer. abdominal cramps. Insufficient rinsing before dialysis. First-use syndrome: 3 to 5% of dialysed patients. edema. MECHANISMS Complement activation via the alternative pathway. Ethyleneoxide has an increased allergenicity after contact with cuprammonium cellulose dialyzers. wheezing. vomiting. shortness of breath. urticaria. abdominal pain. . General: hypotension. RISK FACTORS Use of new cellulose. ammoniac.

187 - . “Severe hypersensitivity reaction during hemodialysis”. it is used in association with both CO2 (90%) and fluoric hydrocarbons. Breillatt J. 4/100000 hemodialysis sessions with hollow-fiber dialysers. 4 (7): 646-52 Daugirdas J. Allergy. Walb D. Roxe D.2 out of 1000000 dialyzers sold. Hakim R. Abdelhamid S.T.H. Lee S. “Complement activation and hypersensitivity reactions to dialysis membranes”. J.M. Ing T. Baur X. 52: 282. ethylene oxide sterilizes at a temperature of 40° and a humidity of 40% within 4 hours. Asthma.M. Fiegel P.M. In such conditions. 145: 489-94. Since it is a highly inflammable gas. Med.. 1984. Bhat K. 1989. Ann. Dial.B. Immunol. Arch. 311: 1178-82 ETHYLENE OXIDE Ethylene oxide is a gas capable of killing microorganisms by the alkylation of the sulfur-containing proteins. Shinaberger J. 1997. Transplant. Lazarus J. Lozano J. Med. It is used to sterilize various medical instruments and supplies that would not tolerate sterilization by heat..PRODUCTS USED IN DIALYSIS REFERENCES • • • • • Kraske G. Ann. 78 (2): 217-20 Rockel A.B.. Port F. “Anaphylactic reaction on subsequent exposure to cuprophan hollow-fiber dialyzer: a case report”. N. “Severe anaphylactoid reactions to cuprammonium cellulose hemodialyzers”. 1985.K.. . Thiel C. RISK FACTORS Atopy. Allergy.K. INCIDENCE Severe but non-fatal reactions: 4. Frequent exposure (spina-bifida).M. Nephrol.K. “Allergy to dialysis materials”. Klinke B. Intern. Hertel J. Klaustemeyer W. Engl. Use of cuprammonium cellulose dialyzers. 1984.

MANAGEMENT Sterilization by heat is not possible. DIAGNOSTIC METHODS Cutaneous testing with ETO-HSA. Skin prick-tests: 1 mg/ ml then. In Japan. Other: local intra-articular reactions (reconstructive knee surgery).02 ml ETO-HSA 10 µg/ml. ENT: rhinitis. Intradermal skin-tests: 0. 100µg/ml.188 - . Respiratory: bronchospasm. Rinsing of the blood compartment and all lines of a cuprammonium cellulose dialyzer with 2 liters of sterile saline. Correlation between ETO-specific IgE and allergic symptoms during dialysis. MECHANISMS The quantity of ETO remaining in the dialyzer after washing can interact with human albumin and induce the formation of allergens with a cross-linking agent. Negative predictive value: 96%. Frequent reuse of compatible membranes (cheaper and safer). RAST). the use of steam or gamma radiation made adverse reactions to ethylene oxide disappear. Specific IgE (ELISA. sterile shunt malfunction. 1mg/ ml. angioedema. flushing. Rinsing of the dialysate compartment with 10 liters of dialysate. itching.PRODUCTS USED IN DIALYSIS CLINICAL MANIFESTATIONS General: anaphylactic shock Cutaneous: urticaria. Catheters should be washed in a physiologic solution then left in a well-ventilated place in order to remove all trace of the ethylene oxide used (not always feasible). Positive predictive value: 80%. .

J. “The role of ethylene oxide allergy in sterile shunt malfunctions”.T. 96:486-8 Pittman T.T. Thiel C. Contact dermatitis is frequent. “Ethylene oxide allergy in dialysis patients”. Allergy. Transplant.H. Knutsen A.M. Mueller K. Kiburz J. 12 (7): 1461-3 Pittman T. Abdelhamid S.R.B. Exposure to formaldehyde gas at work and in the home (insulation with urea-formol foam) can lead to the development of asthma. Immunol. 78 (2): 217-20 Purello D’Ambrosio F. Nephrol. Klinke B. Wiggins C. Immunol.PRODUCTS USED IN DIALYSIS REFERENCES • • • • • Kraske G.. 4 (7): 646-52 • FORMALDEHYDE The simple formaldehyde molecule is a highly sensitizing molecule that is the underlying cause of contact dermatitis in many patients. Immunol. Walb D. It is also used for sterilization. 1997. Krock J. Nephrol.R. 1994. Allergy. Gangemi S. J. “Ethylene oxide allergy in children with spina bifida”. “A comparison of cutaneous testing and ELISA testing for assessing reactivity to ethylene oxide-human serum albumin in hemodialysis patients with anaphylactic reactions”. J. Shinaberger J. Roberts M.189 - .A. 8 (1): 41-5 Grammer L. Gabriel K. Clin. Dial. Ann. 1997. . 1991.. 87: 674-6 Röckel A. Cuzzocrea S.. Allergy. Fitzsimons R. as an antibiotic additive in grooming products (toothpaste. Transplant. certain allergoids). 1995. notably of dialyzers.. Dial. Klaustermeyer W. INCIDENCE Anaphylactic shock is uncommon (hemodialysis and dentistry). RISK FACTORS Previous exposure to formaldehyde.F. Santoro D. Rathore M.K.. “Severe hypersensitivity reaction during hemodialysis”. Ivanovich P. Baur X. shampoo. Clin.. Br.C. Ricciardi L. Roxe D. Neurosurg. “Allergy to dialysis materials”. soaps) and in certain medications (antihepatitis B vaccine. Bellinghieri G. 1989. Wiliams D. Asthma. Bagnato G. Patterson R. Fiegel P. Savica V. Steinhardt G. Hertel J.

angioedema.N. DIAGNOSTIC METHODS Cutaneous testing. Perform an intradermal test with antihepatitis B vaccine in patients presenting contact dermatitis to formaldehyde (risk of generalized urticaria or eczema). maculopapular rash on the face and in the mouth (dentistry).190 - . MECHANISMS IgE-mediated hypersensitivity (anaphylactic shock). MANAGEMENT Avoid using dialysis membranes sterilized with formaldehyde in patients with previous allergic skin reactions to formaldehyde.1 and 1% are often positive in subjects presenting immediate reactions. E.T.PRODUCTS USED IN DIALYSIS CLINICAL MANIFESTATIONS Differentiate from irritation syndrome (ocular. General: anaphylactic shock. nasal. . — patch-tests using a formaldehyde solution at 1% are often positive in subjects with contact dermatitis (high doses are irritating and should not be used). Respiratory: bronchospasm. Cutaneous: urticaria. — prick-tests using formaldehyde solutions at 0.: rhinorrhea. Specific IgE antibodies against formaldehyde can often be detected by RAST or ELISA in subjects with immediate manifestations. Type III: IgG antibodies against formaldehyde/serum albumin conjugates have been detected in patients exposed through the respiratory or parenteral route. bronchial). Cell-mediated hypersensitivity (contact dermatitis). polymorphous erythema. Results should be read immediately (20 minutes). contact dermatitis.

50 (3): 274-6 Bousquet J. cutaneous and immunologic effects”. “ Allergy to formaldehyde and ethyleneoxide”. Allergy Clin. cardiac arrest. The typical treatment regimen consists of 10 doses of 100 mg of iron dextran injected during hemodialysis treatment. Cutaneous: itching. Haglmuller T. J. dyspepsia. INCIDENCE 0. Allergy. 0.B.191 - . “Formaldehyde: an analysis of its respiratory. IRON DEXTRAN Intravenous iron dextran is used in the treatment of anemia in patients with end-stage renal disease when oral iron therapy fails to maintain adequate iron reserves. Respiratory: chest pain. RISK FACTORS History of drug allergy (OR: 2. Clin..1% of dextran injections (in non uremic patients). 1986. swelling. wheezing.P.4). 9: 357-70. Allergy.5). History of multiple drug allergy (OR: 5. 1991. CLINICAL MANIFESTATIONS Immediate General: hypotension.PRODUCTS USED IN DIALYSIS REFERENCES • • · • Wantke F.J Jr. Larsson P. “Anaphylactic shock caused by formaldehyde in a patient undergoing long term hemodialysis”. Allergy. Digestive: nausea. Montanaro A. Jarisch R. flushing. 77 (4): 594-7. Gotz M. 4.. 1991. Bousquet J. “Anaphylaxis after dental treatment with a formaldehyde-containing tooth-filling material”. diarrhea. Bardana E. Ann.6% of patients (non uremic). Michel F. 66 (6): 441-52 Maurice F. Rivory J. . dyspnea. Hemmer W. Rev. Immunol. 1995.7% in uremic patients.

W. Glasco G. J. 1996. 1994. 28 (4): 529-34 Monaghan M. Maesaka J. 87 (10): 1010-2 Novey HS. complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients”. Bradsher R. may last for 3 to 7 days) Lymphadenopathy. 1992. In one case.M. The same mechanisms could be involved as were reported concerning dextrans used as plasma expanders. Lim V. “The safety of intravenous iron dextran in hemodialysis patients” . hapten inhibition and desensitization: Day 1: 50 mg/ 100 ml rate: 20 ml/ h Day 2: 100 mg/ 250 ml rate: 40 ml/ h 24 hours later 200 mg/ 250 ml rate: 50 ml/h6 hours later Day 3: 400 mg then 500 mg 24 hours later 500 mg then 250 mg REFERENCES • • • • Fishbane S. Am. Olsen K. “Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis”. Pahl M. Ungureanu V.K. Med. “Dextran antibodies.D.W. Allergy. Stewart W. Ann. MECHANISMS Poorly studied. 72 (3): 224-8 Fleming L. DIAGNOSTIC METHODS No specific reports concerning iron dextran.K. Dis. Transplant.J. 7: 35-9 .D. Vaziri N. “Safe administration of iron dextran to a patient who reacted to the test dose” . Haydik I. Dial. ephedrine. Kaupke C. 1994.. Kidney.192 - . fever. but only 40% of all anaphylactoid reactions occur with the test dose.. Parratt D.. J. St John G. MANAGEMENT A test dose of 25 mg of iron dextran is commonly recommended. Wish J.PRODUCTS USED IN DIALYSIS Delayed (4 to 48 hours after iron administration. headache.. arthralgia. myalgia. Nephrol.S. South. iron dextran was administered to a patient who reacted to the test dose after premedication with corticosteroids. antihistamines.

angioedema. Hypersensitivity during hemodialysis can sometimes be due to the membrane.M. itching. This does not occur in . abdominal cramps. J.H. CLINICAL MANIFESTATIONS (onset within 20 minutes after starting dialysis) Major criteria: dyspnea.193 - . burning/ heat sensation at the access site or throughout the body. Minor criteria: urticaria. RISK FACTORS Concomitant use of ACE inhibitors.A. MECHANISMS Contact of plasma with negatively charged AN 69 membrane initiates the contact phase of coagulation and leads to the activation of the Hageman factor and conversion of prekallikrein to kallikrein.L. Block M.D. “Intravenous iron dextran in clinical medicine”.PRODUCTS USED IN DIALYSIS • Hamstra R. 243: 1726-31 POLYACRYLONITRILE AN 69 MEMBRANE Hemodialysis is a safe procedure. rhinorrhea. Normally kininogen is almost completely cleared by the kininases during its passage in the lung circulation. INCIDENCE Unknown. 1980. DIAGNOSTIC METHODS Increased bradykinin in samples obtained from afferent blood line of patients. which cleaves bradykinin from the high molecular weight kininogen. lacrimation. Schocket A.A.

Vanherweghem J. Dial.PRODUCTS USED IN DIALYSIS patients with ACE inhibitors. 45: 1497-1503 . MANAGEMENT Avoidance of the association of AN 69 membrane with ACE inhibitors. 11 (S2): 112-5 Verresen L. 1996. 1994. Vanrenterghem Y. leading to bradykinin accumulation and development of anaphylactoid reactions. REFERENCES • • Tielemans C. Transplant.Int. Goldman M. “Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN 69 membranes”. Lemke H.. Nevertheless. Nephrol. “Acute hemodialysis membrane-associated reactions”.D. Gastaldello K. Fink E. Kidney. anaphylactoid reactions have been reported with AN 69 membranes without ACE inhibitor association.L.194 - .

DIAGNOSTIC AGENTS VIII DIAGNOSTIC AGENTS .195 - .

6%. INCIDENCE All adverse reactions: (IV administration): 0.6 to 16.T. hives: 0. E. Non-specific histamine release? MANAGEMENT Premedication may be useful (controversial). itching. Anaphylaxis: 0 to 0.DIAGNOSTIC AGENTS FLUORESCEIN Angiography using fluorescein is a valuable tool for the ophthalmologist in investigating vascular disease in general. RISK FACTORS Previous reaction during fluorescein angiogram. and chorioretinitis in particular. However this useful method is not free from risk.1%. Desensitization (0. angioedema. urticaria.: sneezing (early symptom of allergy).2% (deaths reported). Black females (urticaria in one study). No specific IgE found. Cutaneous: pruritus. A positive prick-test with 10% fluorescein solution could predict anaphylactoid reaction to intravenous injection of fluorescein. Flushing.1 ml 1/1 000 to 1 ml pure) is poorly used.5 to 0.9%. (oral administration): 0.N. False positive in intradermal skin-tests.196 - . CLINICAL MANIFESTATIONS General: anaphylactic shock Respiratory: bronchospasm. DIAGNOSTIC METHODS Cutaneous testing. Mechanisms Unknown. .

1991. Allergy. 65 (7): 465-71 Rohr A. 90 (3. Clin. Ganka.J.L. laryngeal edema. Gakkai. Bressler S. “Adverse reactions during retinal fluorescein angiography”. Respiratory distress.M.P. 1992. 98 (7): 1139-42 • • • GASTROINTESTINAL CONTRAST MEDIA Significant anaphylactoid reactions to gastrointestinal contrast media are rare. Optom. One case with allergy to fish. DIAGNOSTIC METHODS None. Torii Y. chest tightness. Schachat A. J. 100 (4): 313-7 Jennings B. “Frequency of adverse systemic reactions after fluorescein angiography. Ando F.T. RISK FACTORS Unknown.S.A.DIAGNOSTIC AGENTS REFERENCES • Matsuura M. Results of a prospective study”. J. “Prophylaxis against fluorescein-induced anaphylactoid reactions”.G.. Nippon.E Jr. CLINICAL MANIFESTATIONS Anaphylactic shock. Ophtalmology. Assoc.. Am.E. Kyogane I. Immunol. . Matsuura M. Bressler N. peanuts (barium preparation). Zasshi.1): 407-8 Kwiterovich K. stridor. Murphy R. Pappano J.5 million procedures.197 - . bronchospasm. “Usefulness of the prick-test for anaphylactoid reaction in intravenous fluorescein administration (article in Japanese)”. 1996.B. 1994. Mathews D. INCIDENCE One severe anaphylactoid reaction/ 2. Fine S.. Fukumoto K. Maguire M..

. J.07%.DIAGNOSTIC AGENTS MECHANISMS Numerous components of the gastrointestinal media may be involved: — Ancillary supplies (latex) — Barium sulfate (unlikely) — Water-soluble gastrointestinal agents: gastrografin (sodium and meglumine diatrizoate solution). Indocyanine green is a tricarbocyanine organic dye with less than 5% of iodine (for stabilization). Am. 168 (4): 957-8 Miller S. 168 (4): 962-4 INDOCYANINE GREEN Used in the diagnosis and management of choroidal vasculature affections. Roentgenol.05% to 0. Kesack C. J.D. REFERENCES • • • Seymour P..H.C. Roentgenol. Am. 1997. “Anaphylactic shock during a routine upper gastrointestinal series”. hypaque (sodium diatrizoate solution).198 - . J. “Anaphylactoid reaction after oral administration of diatrizoate meglumine and diatrizoate sodium solution”. . Increased gastrointestinal permeability has sometimes been demonstrated. 1997. One death reported during cardiac catheterization with indocyanine green. 168 (4): 959-61 Skucas J. if a subsequent examination is necessary. MANAGEMENT Avoidance of the same agent. INCIDENCE 0. “Anaphylactoid reactions with gastrointestinal contrast media (comment)”. Am. Roentgenol. 1997.

“Adverse reactions due to indocyanine green”. Myles R. Am. Gradoudas E. Hayashi K.DIAGNOSTIC AGENTS CLINICAL MANIFESTATIONS Anaphylactic shock Pruritus. Cathet.A. Ophtalmol. 1989. DIAGNOSTIC METHODS None.P. J. Cardiovasc. Ophtalmol. Ophtalmology. Radiographic contrast media can be divided into 4 categories: . Arend O. Capone A Jr.W. Yannuzzi L.. Gilman J. 114: 638-9 Benya R. Miki P.. REFERENCES • • • • • Olsen T.199 - . Arch. Reactions from intravascular injection are usually mild and self-treated. 1992.I. 1994. Brundage B. 114 (1): 97 Hope-Ross M. Lim J. “Survey of complications of indocyanine green angiography in Japan”. Reim M.A. “Severe anaphylactic reaction after indocyanine green fluorescence angiography”. Diagn. or to the dye itself.. Quintana J. MECHANISMS Anaphylaxis may be related to the iodine additive. Am. Schulte K. 1996. “Anaphylactic shock following indocyanine green angiography (letter)”. 17: 231 IODINATED CONTRAST MEDIA Iodinated radiographic contrast media are widely used. Ophtalmol. Wheezing.. 118: 749-53 Wolf S. A case report and review of the literature”.. J.S. 1994. MANAGEMENT Avoidance. 101: 529-33 Obana A. “Adverse reactions to indocyanine green.

5 to 15% with non-ionic monomers. iothalamate.5. iopamidol. highest carboxyl group toxicity) Diatrizoate. previous adverse reaction to contrast media. Non ionic monomers (same osmotoxicity as ionic dimers.11% — Severe: 0 to 0. Non ionic dimers (lowest osmotoxicity.04 to 0. 5 hydroxyl groups: iopentol.2% — Severe: 0. ioversol. LOCM: 0 to 1/168363.04 to 0. 9 hydroxyl groups: iodixanol. metrizoate. . iopromide. allergy.66% — Moderate: 0. ioxythalamate. iomeprol. INCIDENCE Acute reaction rates: High osmolarity contrast media (HOCM): — Mild: 2.22 to 1.016%. Ionic dimers (lower osmotoxicity: ratio 3. No significant association with immediate reactions.5 to 12.58 to 3. no carboxyl group toxicity).13% — Moderate: 0. 12 hydroxyl groups: iotrolan. Delayed reactions: 5 to 30% with ionic monomers.DIAGNOSTIC AGENTS Ionic monomers (highest osmotoxicity: ratio 1.4% Low osmolarity contrast media — Mild: 0. 6 hydroxyl groups: iohexol. no carboxyl group toxicity). May be over estimated due to false delayed adverse reactions resulting from clinical methodology (questionnaire). Death HOCM: 1/10931 to 1/117000. iodamide. ioxitol. 4 hydroxyl groups: metrizamide. Risk of repeated reaction: 17 to 35%.200 - . lower carboxyl group toxicity) Ioxaglate.

— Food or medication allergies: relative risk of any reaction: 1. rigors. — Beta-adrenergic blockers: relative risk 2. urticaria (limited). .5 relative risk of severe reaction: 5.9 relative risk of severe reaction: 4.201 - . hypotension). Minor reactions Pruritus. cardiogenic shock. Severe reactions Cardiovascular shock. erythema: no treatment. Moderate reactions Urticaria (diffuse). myocardial infarction.8 times higher risk of developing an adverse reaction to intravascular injection of contrast media. dizziness.DIAGNOSTIC AGENTS RISK FACTORS — Asthma: relative risk of any reaction: 1. cardiac arrest: hospitalization.2 — Previous contrast reaction: relative risk of any reaction: 3.2 to 2.9 — Atopy — Concomitant use of interleukin 2 increases incidence and severity of delayed reactions (fever. laryngeal edema. cardiac rupture. cardiac tamponade.6 to 3 relative risk of severe reaction: 2.4 A patient with peak expiratory flow less than 400 l/ min 10 minutes before injection runs a 3.3 to 6.1 to 8. respiratory arrest. flushing. chills.3 to 3.5 to 10. bronchospasm: treatment. angioedema. hypovolemia. sepsis or other drug intolerance.7 — Female gender is associated with greater risk of anaphylactoid reactions and severe anaphylactoid reactions — Cardiac diseases — Sea-food allergy or povidone-iodine allergy are not risk factors. CLINICAL MANIFESTATIONS Differentiate from other cardiac or non cardiac manifestations: vasovagal response.

osmotoxicity and iontoxicity of contrast media influence cell membranes of blood cells. abdominal pain. nausea.DIAGNOSTIC AGENTS Differentiate from non-idiosyncratic manifestations: warmth.202 - . MECHANISMS Not fully known. platelets. contrast-induced renal failure. Antigen-antibody interaction. but hyperosmolarity is crucial. . vomiting. MANAGEMENT Universal premedication with corticosteroids Methylprednisolone 32 mg 12 h and 2 h before injection of conventional ionic contrast media decreases the frequency of all reactions from 9% to 6. fibrinolytic. The chemotoxicity. if any is exceptional. or kinin system leading to activation and creation of bradykinin. The role of 2 mercaptobenzothiazole (MBT) used in the manufacture of rubber and present in disposable plastic syringes has seldom been advocated. upper respiratory tract congestion. leukotrienes.4% and of severe reactions requiring treatment from 2% to 1. Flu-like syndrome: fatigue. DIAGNOSTIC METHODS A few reports state that anaphylactoid reactions could be IgEmediated: one case with positive intradermal reaction to meglumine and sodium diatrizoate (1/100) and positive human basophil degranulation test (HBDT). diarrhea. nausea. endothelial cells and mast cells leading to release of vasoactive substances (histamine. fever. dizziness. anaphylatoxins.2%. prostaglandines) and structural changes in molecules of the complement. coagulation. Delayed reactions (at least 30 minutes after contrast media injection). weakness. vomiting. headache. metallic taste in the mouth. chills. rash.

Use a low osmolarity RCM. Choice of agent and management of complications”.Discontinue beta-blockers if possible REFERENCES •· Cohan R.Use a pre-treatment protocol.Diphenydramine: 50 mg intramuscular 1 hour before the procedure. 2°.H.o 12 hours before intravenous injection of the ionic dimer ioxaglate decreases the rate of reactions from 12. Am. Emergency pre-treatment in previous reactors Intravenous hydrocortisone 100-250 mg q 4 hours until completion of the procedure. 1°+2°+3°: 0.5% to 1% in low-risk patients. 7 hours and 1 hour before the procedure.R.H.m. 4°.Have emergency equipment available..v. Hydroxyzine 100 mg p.Evaluate the necessity of a procedure requiring RCM. In patients at risk of anaphylactoid reactions to radiographic contrast media 1°. 1 hour before the procedure. Ellis J.Administration of a LOCM to patients with prior severe anaphylactoid reactions to HOCM. North. Pre-testing with an intravenous injection of a small amount of contrast media is not useful in predicting severe reactions to ionic or non-ionic contrast media. Urol.Ephedrine: 25 mg p.. Invest. i.Prednisone: 50 mg 13 hours. 2°.DIAGNOSTIC AGENTS Patients with history of prior reactions to contrast media 1°. Iopamidol causes fewer allergic-type adverse events but more flushing than ioxaglate in patients with asthma or atopic disease.203 - . “Iodinated contrast material in uroradiology. 4°. 24 (3): 471-91 • Simon M. 3°. Clin. i. “Allergic-type adverse reactions to low-osmolarity contrast media in patients with a history of allergy or asthma”.o. 1995. 3°.7% reactions 1°+2°+3°+4°: 0% reaction Use of anti H2 histamine is optional and controversial. Diphenydramine p. Radiol. 30 (5): 285-90 . 1997. 5°.o 1 hour before the procedure (optional).

P. Eng. Smith S.M.F. Soyer P.. Adverse reactions 2.09%. “The etiology of contrast medium reactions”. 1991. 1995.7%. 87 (4): 867-72 • Katayama H. N.C. Takashima T. J.. Allergy. Clin. J.. Invest. A report from the Japanese committee on the safety of contrast media”. Seez P. “Adverse reactions to ionic and non ionic contrast media. anaphylactic shock: 3/million. Adverse reactions in patients with a history of reaction to MR imaging contrast agent: 21.4% (rash: 0. 1990. Matsuura K. Immunol. Yamagushi K. urticaria: 0. Adverse reactions in allergic patients: 3. Allergy. 175: 621-8 • Lasser E. Billardon M. 184 (2): 383-4 • Greenberger P.7%.A.C. . 1992.. et al. Berry C. 95 (4): 813-7 • Almen T.DIAGNOSTIC AGENTS Lang D.3% Adverse reactions to iodinated contrast agent: 6. Radiology. Patterson R.204 - .07%. Radiology.3% Deaths reported..B.J. Adverse reactions in asthmatic patients: 3.T. “Pretreatment with corticosteroids to alleviate reactions to intravascular contrast material”. 29 (S1): S37-45 •· Bertrand P. INCIDENCE Gadopentetate dimeglumine. 1987. Alpern M. Radiol. Gadopentetate dimeglumine.B. Kozuka T.M. gadoterate meglumine.R. Med.. “The prevention of immediate generalized reactions to radiocontrast media in high-risk patients” . 1994. Rouleau P.J. J. gadoteridol. “Gender risk for anaphylactoid reaction to radiographic contrast media”. Talner L. Immunol. Alison D. Clin. “Comparative randomized double-blind study of hydroxyzine versus placebo as premedication before injection of iodinated contrast media”. Visintainer P. 317: 245-9 • PARAMAGNETIC CONTRAST AGENTS Gadolinium chelates used as contrast agents for magnetic resonance (MR) imaging are considered to be relatively safe.

Rapid injection is not an adverse reaction risk factor.L. Gross C.C.. urticaria. “Life-threatening anaphylactoid reaction after intravenous gadoteridol administration in a patient who had previously received gadopentetate dimeglumine”. Radiol..C. Dinger J. Radiol. Gifford L.A.H. “In vitro histamine release induced by magnetic resonance imaging and iodinated contrast media”. Lazarus S. allergy. MANAGEMENT No premedication data published. Invest.. CLINICAL MANIFESTATIONS Anaphylactic shock Bronchospasm. facial and lingual edema. Lasser T. Radiology.B.M. 15 (3): 523-4 •· Shellock F. Am.P. Clauss W. previous reaction to iodinated contrast agent. Itskovich E.A. J. Brasch R. “Tolerance data of Gd-DTPA: a review”.L.J. Mink J. Neuroradiol. the same mechanisms as iodinated contrast agents could be involved.P. 13 (1): 15-20 . 28 (4): 308-12 • Niendorf H.C. Alhassan A. 1991. REFERENCES • Nelson K. MECHANISMS Paramagnetic contrast agents are ionic or non-ionic.. Anzai L. Lauber-Huber C.DIAGNOSTIC AGENTS RISK FACTORS Asthma. “Adverse reaction to intravenous gadoteridol (see comments)”. Pruritus. Haustein J. Although not yet fully understood. “Clinical safety of gadopentetate dimeglumine”. J. 1993. previous reaction to MR imaging contrast agent.205 - . 1995.G. maculopapular exanthema. DIAGNOSTIC METHODS None. 196 (2): 439-43 • Witte R.. Cornelius I. Eur. Radiology. 189 (1): 151-2 • Baxter A. 1994. 1993. Hahn H.

2. RISK FACTORS Exposure to tryphenylmethane dyes: textile industry. 0.7% were positive to a prick-test. INCIDENCE 0.1 to 2.3% were positive to a patch-test. prick. plaque-disclosing agents in dentistry. No deaths reported. cosmetics. Cutaneous: pruritus. pharmaceutical plants. . CLINICAL MANIFESTATIONS General: anaphylactic shock. urticaria.5% of lymphography procedures. About 30 allergic reactions and 25 cases of anaphylactic shock have been reported. IgE antibodies have never been detected by RAST.206 - . food processing plants.DIAGNOSTIC AGENTS PATENT BLUE DYE Patent blue is an aniline dye (alphazurin 2 G) used to stain the lymphatic channels prior performing lymphangiography. In the course of routine preliminary testing: 0.14 to 3. DIAGNOSTIC METHODS Cutaneous testing. Histamine release from leukocytes incubated with patent blue. contact dermatitis. angioedema.5% of patients were positive to an intradermal skin-test. farms. Scratch. print shops. Respiratory: bronchospasm. and especially intradermal skin tests. Positive results are often observed in patients presenting immediate generalized reactions. using 1/100000 to 1/100 dilutions.

If absolutely necessary : perform lymphangiography without visualization of lymphatic vessels . 35 (3): 739-46 Kalimo K. use Evans blue (but contact dermatitis has been reported). “Allergy to dyes used in lymphangiography” . Sorbette F. Therapie. 1989. Phlébologie. Indirect histamine release with activation of the alternative complement pathway. Jansen C. 1982. 1985. “Sensitivity to patent blue dye during skin-prick testing and lymphography. 141 (2): 365-7 . Lymphangiography is seldom performed nowadays. REFERENCES • • • • Belhaouari M. Chevallier H. 1981.L.H.. A retrospective and prospective study” . Radiology. Kormano M. “Accidents “au bleu patenté” observés durant la lymphographie”.207 - . Carl H. Mécanismes. fréquence et traitement”. MANAGEMENT Predictive skin testing does not detect latent patent blue sensitivity in all cases. “Les accidents allergiques au blue patent violet. Non-specific histamine release. 12 (1): 54-5 Dubost J. 44 (5): 377-8 Pevny I. Contact Dermatitis. Marty M.T.DIAGNOSTIC AGENTS MECHANISMS Possible IgE-mediated hypersensitivity in some cases. Vitry A.

208 - .DIAGNOSTIC AGENTS .

209 - .ENZYMES IX ENZYMES .

CLINICAL MANIFESTATIONS General: anaphylactic shock. Between 1964 and 1993: 26 cases have been reported (3 deaths). Cutaneous: localized or generalized urticaria. DIAGNOSTIC METHODS Cutaneous testing. Respiratory: bronchospasm. It is used in cardiac surgical procedures. purified from cattle lungs.1% to 5. 50% of all patients still show measurable levels of IgG antiaprotinin. Skin-prick tests. RISK FACTORS Interval of less than 200 days between two aprotinin exposures. platelet preservation. It decreases blood loss and transfusion requirements (30 to 40%) by its antifibrinolytic effect. IgE and IgG antiaprotinin are found in 55% of patients with allergic reactions and 32% of non-reactors. . anti-inflammatory effect and possible preventive action on CNS injury.8% if re-exposure. clinical value is not clearly established. INCIDENCE 0. Specific IgE and IgG After 48 months. Thus. then intradermal skin tests from 1/1000 to 1/10: a few cases with positive skin tests after an allergic reaction. 2.210 - .ENZYMES APROTININ Aprotinin is a naturally occurring polybasic polypeptide serine protease inhibitor.5% of allergic reactions. especially 35 days to 2 months.

03 mg/kg + cimetidine 5 mg/kg) in cases of known or possible previous exposure. Shida T. Brenet O. 63 (1): 242-4 Cottineau C. 1993. ”Immunological studies on patients who received aprotinin therapy”. Avoidance of re-exposure within the first 6 months after the previous exposure to aprotinin.L. REFERENCES • • Dobkowski W.. Surg. Drug.A. Moreau X. 34 (9): 899–904. Test dose of 10000 KIU of aprotinin in all patients with aprotinin treatment. 1998. ”A risk-benefit assessment of aprotinin in cardiac surgical procedures”. Wendel H. ”Anaphylactic shock after aprotinin re-exposure: time course of aprotininspecific antibodies”. 1997. Spath P.S. Surg. Ziemer G. 12 (6): 590-3 Yanagihara Y. Thorac. Richter J. Fr. Use predictive skin-tests in patients with previous exposure or beefallergic.B.. Ann.. 1997.211 - .M..M. 1985. 113 (1): 194-201 Scheule A. Non-specific histamine release. ”Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight re-exposures to aprotinin in heart operations”. Haberle L. Reanim. MANAGEMENT Do not use aprotinin in non-cardiovascular surgery Delay the first bolus injection of aprotinin until the surgeon is ready to begin cardiopulmonary bypass. Jurmann M.P. • • • . Eckstein F.ENZYMES MECHANISMS IgE-mediated hypersensitivity. 18 (1): 21-41 Dietrich W. H1/H2 blockade (clemastine 0. Drouet M. Arerugi. ”Choc anaphylactique lors de l’utilisation de l’aprotinine à fortes doses en chirurgie cardiaque”. Other antifibrinolytics are available (tranexamic acid).J. Anesth. De Brux J. Murkin J. Ann. J. Delhumeau A. Cardiovasc. Thorac. Ebell A. Saf.

44 to 2% of chemonucleolysis procedures.8). urticaria. papain and chymopapain exhibit cross-reactivity (chymopapain is the major active component of papain). Occupational: inhalation of airborne papain and bromelain.3). It is extracted from a fraction of non-crystallized latex from a tropical tree: Carica papaya. Chymopapain is more soluble and has greater proteolytic activity than papain. Exposure to papain (O. fatal anaphylactic shock. beverages containing exotic fruits. pineapple (bromelain). serum sickness. detergents. 9 to 17% after a second injection. Drugs containing papain: digestive aids. meat tenderizer containing papain. MODES OF SENSITIZATION TO PAPAIN Food: Papaya in any form. yogurt).R 7. contact lens cleaning solutions.212 - . Delayed (up to 2 weeks after chemonucleolysis): urticaria. Incidence of severe anaphylactic reactions: 0. beer. Since 1965 it has been used to treat herniated discs (chemonucleolysis).45% at the first injection. angioedema. various mixed foods (appetizer mixes. pruritus. angioedema. ointments containing papain.ENZYMES CHYMOPAPAIN Chymopapain is a proteolytic enzyme with a molecular weight of 27 000 D. CLINICAL MANIFESTATIONS Immediate (within 30 minutes after injection of the test dose or total dose): discomfort.R 13. Coca-Cola. ENT solutions.18% to 0. Because they have the same antigenic determinants. INCIDENCE Incidence: 0. RISK FACTORS Atopy (O. antiinflammatory drugs. 8 deaths reported before 1974. . 7 deaths from 1982 to 1991.

and in all patients before second chemonucleolysis: predictive skin prick-tests. Feldmann L. 24 (5): 471-6 . This is suggested by previous history.ENZYMES DIAGNOSTIC METHODS Cutaneous testing. REFERENCES • Moneret-Vautrin D.Exp. The choice of anesthesia remains controversial. Skin prick-tests: chymopapain 1 mg/ml to 10 mg/ml (one case of anaphylaxis during cutaneous testing)..A. Baumann A. Kanny G. MANAGEMENT In high risk patients (atopy and/ or exposure to papain) before first chemonucleolysis. local anesthesia is advocated. Specific IgE (UniCAP®/Pharmacia CAP System™). Roland J. Excellent negative predictive value. “Incidence and risk factors for latent sensitization to chymopapain: predictive skin-prick tests in 700 candidates for chemonucleolysis”. MECHANISMS IgE-mediated hypersensitivity is responsible for most reactions. while in France general anesthesia is usually performed. Activation of the alternate complement route by the enzyme or activation of the normal complement route by chymopapain specific IgG immune complexes. If the skin test is negative: chemonucleolysis. Pere P. Autoimmune responses against proteoglycans derived from mucopolysaccharide protein complexes which are produced in great quantity during the 24 hours after injection into the disc. Non-specific histamine release. 1994. Clin.213 - . if the skin test is positive: surgery. In America. and detection of IgE antibodies. immediately positive skin tests. Surgery is indicated in patients with a history of allergic reaction during previous chemonucleolysis.Allergy.

R. rhinorrhea.4% of allergic reactions to streptokinase. Gutt L. Schofield S. Clin. Schatz M. Zeiger R. myalgias. antithrombotic use (4 years). Orthop. Schafer M. periorbital swelling. Clin. Patterson R. Delayed reactions: fever. Bernstein D. ARDS.L. Roberts M. arterial thrombosis and embolism. GUSTO-1 trial: 5. arthralgias. deep venous thrombosis. INCIDENCE ISIS-2 trial: 4. ISIS-3 trial: 3.J. Dolovich J.C. . Rash.J. “Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing”. “Safety of chemonucleolysis. 293: 122-34 Grammer L. sneezing.6% of allergic reactions to streptokinase. 1993. renal abnormalities.. CLINICAL MANIFESTATIONS Anaphylactic shock.7% of allergic reactions to streptokinase (0..H.ENZYMES • • Nordby E. cutaneous eruptions. Orthop. Adverse effects reported in the United States.214 - . Wright P.. 1988. 234: 12-15. Shaughnessy J. 1982-1991”. RISK FACTORS Previous exposure to streptokinase: topical (6 months).6% anaphylaxis). Clinical uses of streptokinase include the treatment of acute myocardial infarction. Bernstein I. Bronchospasm. Once bonded with plasminogen the streptokinaseplasminogen complex cleaves arginine 560 on free plasminogen molecules from free plasma.. Cogen F. STREPTOKINASE Streptokinase is a 47000 D protein produced by Beta hemolytic streptococci.

Human albumin. antibody titers. If positive do not use streptokinase. Serologic methods. Intradermal skin tests: 0. Antistreptokinase IgE. IgM (ELISA). glomerulonephritis. and clinical outcome requires further studies. Lymphocyte transformation test (one case). The biologic efficacy of streptokinase is not compromised by an allergic reaction. .02 ml of 3 IU and 10 IU streptokinase. Antistreptokinase IgG (fluorimetric assay. Some cases positive in patients with anaphylaxis. IgG. Type III hypersensitivity: serum sickness. Precipitating antibodies . and sodium glutamate are contained in streptokinase preparations. Hydrocortisone and antihistamines appear to have no protective effect against hypotensive reactions. a negative skin-tests is predictive of safe administration of streptokinase. MANAGEMENT Use alteplase or urokinase in patients previously exposed to streptokinase. The presence of antistreptokinase antibodies in high titers may lead to a lower rate of coronary reperfusion if streptokinase is reused. MECHANISMS Complement activation. phosphate buffers. vasculitis.215 - .ENZYMES DIAGNOSTIC METHODS Cutaneous testing. fibrinplate assay). Perform an intradermal skin-test with 100 IU of streptokinase before intravenous use. IgE-mediated hypersensitivity: positive skin-tests. The precise relation between streptokinase allergy. specific IgE. Skin-prick tests with streptokinase 300 000 IU/ml.

“Identification of patients at risk for anaphylaxis due to streptokinase”. Stockley R. Red T. Clin. Med. 1995.. 1993. “The significance of anti-streptokinase antibodies” . Heart. J. 13 (2): 76-80 • Lynch M. Exp. REFERENCES Tsang T. • ..J. Califf R. Patterson R.M. “Hypersensitivity reactions to streptokinase in patients with high pre-treatment anti-streptokinase antibody and neutralization titres (see comments)”. 79 (9): 1232-5 •· Jennings K. Cho S.W. Immunol.ENZYMES Rapid enzyme immunoassay of antistreptokinase antibodies in human plasma (in 30 minutes) should allow the best thrombolytic therapy for the patient.S.. 1994. Davidson R.S.216 - . Cardiol. 1997. Mc Kenzie A. Pentecost B. Am. B. Jennings K. Davison R. 312 (7028): 393-4 • Lee H.A. Drug Safe.S. Mc Grath K. Intern. 1986. Arch.M.L. Yule S. 1996. “How safe is the re-administration of streptokinase ?”. “Antibodies to streptokinase (editorial)”.A.J. Lee K.C.L. Littler W. Kaplan K.. 96 (3): 427-31 • Lee H. Cross S. 146 (2): 305–7. Ross A.. Stebbins A. Eur. J.L. Armstrong P.S. “Incidence and impact on outcome of streptokinase allergy in the GUSTO-1 trial”. 14 (12): 1640-3 • Dykewicz M.M.

HORMONES X HORMONES .217 - .

HORMONES ADENOCORTICOTROPHIC HORMONE (ACTH) – TETRACOSACTRIN ACTH is used for routine laboratory evaluation of adrenocortical function. For many practitioners. West’s syndrome.218 - . Much lower with tetracosactrin (synthetic ACTH peptide). . CLINICAL MANIFESTATIONS General: anaphylactic shock. Intradermal skin-tests: ACTH 0. Challenge is hazardous. tetracosactrin 100 µg/ ml. urticaria. This may be due to the absence of the terminal 15 AA chain in tetracosactrin. MECHANISMS IgE-mediated hypersensitivity: — Tetracosactrin is less allergenic than ACTH.1 U/ ml. ACTH is the product of choice for patients with multiple sclerosis. tetracosactrin 1 µg/ ml. DIAGNOSTIC METHODS Cutaneous testing. one case using RAST and ELISA. Cutaneous: angioedema. Skin-prick tests: ACTH 10 U/ ml. INCIDENCE Formerly common when natural ACTH was used. Respiratory: bronchospasm. Deaths reported. maculopapular erythema. Detection of IgE antibodies against ACTH has been reported in many cases and against corticotrophin. ulcerative colitis and tumoral cerebral edema.

secondary and quaternary antigenic determinants depends on their spatial configuration in the molecule. for the treatment of Paget’s disease. 51 (5): 1175-9 Sonneville A. hypercalcemia. REFERENCES • • Lee T. desensitization can be used: 0. synthetic salmon and synthetic human calcitonin. 79 (6): 964-88. This may explain the different cutaneous reactions to A. Takaya Y. Patterson R. Three types of calcitonin are used. 1980. MANAGEMENT If tetracosactrin is absolutely necessary. Metab. .. Clin. i. natural porcine. • CALCITONIN Cacitonin is a 32 amino acid polypeptide synthesized by the parafollicular cells of the thyroid.10 mg intravenously then 0. fr. Hashimoto K.A. Grammer L. “Hypersensibilité immédiate au tetracosapeptide”.T. — This may also explain the high incidence of allergic reactions with depot tetracosactrin whose quaternary structure is alte red by the presence of zinc atom.H. Yunoki S.. 17 (1): 43-6. J. Muh J. “Evaluation and management of corticotrophin allergy”. Allergol. Shaughnessy M.. “Anaphylactic shock after synthetic adrenocorticotrophin-(1-18) in a patient with isolated adrenocorticotrophin and beta-lipotropin deficiency”. hyperparathyroidism.40 mg intravenously during 4 hours.e. Allergy Clin. Sabbah A. These injections should be administered at 20-minute intervals.C. It inhibits bone resorbtion and increases urinary calcium and phosphor output.Baudouin J.A.HORMONES — Effect of the primary. and osteoporosis. Immunol.M. 1977.P.C. and tetracosactrin. J. Endocrinol. Garrigue M. Takahara J. Ofuji T.01 mg intravenously then 0. 1987.219 - . Rev.01 mg subcutaneously then 0.

angioedema. MECHANISMS Immediate IgE hypersensitivity. CLINICAL MANIFESTATIONS General: anaphylactic shock. Tafforeau M. Cutaneous: pruritus. Dubois L. Allergy Clin.220 - . 1991.. DIAGNOSTIC METHODS Skin tests: scratch and intradermal (1/1000 and 1/100) were positive in one patient presenting anaphylactic shock with porcine calcitonin. Rev. Vervloet D.HORMONES INCIDENCE Reported incidence varies from 6% to less than 1/30000.. urticaria. Negative skin-tests do not exclude allergic manifestations induced by calcitonin. Birnbaum J. 42 (9): 435-41 Cuskey J. 28 (3): 248–9. Caprari M. Allergol. rash. MANAGEMENT Avoidance. . du Buske L. Immunol. fr. “Schock anafillattico da calcitonina. Charpin J. 1994. J. Descrizione di un caso e revisione della letteratura”. 87 (1): A359. “Induction of urticaria and angioedema by synthetic salmon calcitonin”. “Réaction anaphylactique à la calcitonine”. Pala M. Respiratory: bronchospasm.. Minerva Cardioangiol. In vitro tests: detection of IgE against porcine calcitonin (RAST) was positive in one case. Pirson F. Use other types of calcitonin (synthetic salmon or human calcitonin). 1988. REFERENCES • • • Piccone U.

HORMONES CORTICOSTEROIDS Glucocorticoids are steroids with 21 carbon atoms. dexamethasone (9%). Paradoxically. prednisolone (11%). methylprednisolone (31%). perinasal dermatitis. pentacyclic carbure. prednisone (3%). . RISK FACTORS Female gender. exanthematous rashes with focal bullae and purpura. urticaria. Atopic background (controversial). INCIDENCE Uncommon for systemic reactions: fewer than one hundred cases reported since 1957 (10 deaths published after methylprednisolone pulse therapy). Age 30 to 60 years. Generalized delayed systemic reactions: generalized dermatitis. although widely used for inflammatory and allergic manifestations. angioedema. Immediate: anaphylactic shock.8% prevalence in patients attending clinics for patch testing (corticosteroid contact dermatitis will be explored in the next chapter). Allergic contact dermatitis: worsening or lack of response of dermatitis to treatment.2 to 4. they can cause allergic symptoms.221 - . worsening of perennial rhinitis. They are derived from sterane. Intravenous administration. Chronic dermatitis requiring topical therapy over an extended period (for corticosteroid contact allergy). CLINICAL MANIFESTATIONS Drugs involved: hydrocortisone (46%). bronchospasm. Common for contact dermatitis: 0. Aspirin intolerance (for bronchospasm due to hydrocortisone).

MANAGEMENT Do not use hydrocortisone in patients with aspirin intolerance. Specific IgE antibodies: one case (methylprednisolone). MECHANISMS Unclear. Possible role of steroid salts (hydrocortisone esters). sulfites. Preservatives and excipients have been implicated: parabens. perform desensitization to hydrocortisone starting with 15 µg and ending with 100 mg in 46 days. Skin-tests with the excipient may be positive (carboxymethylcellulose).HORMONES DIAGNOSTIC METHODS Cutaneous testing. carboxymethylcellulose. Intradermal skin-tests: positive in 50% of the cases with immediate hypersensitivity. Skin-prick tests: sometimes positive. In patients with aspirin intolerance. Possible role of contaminants and metabolites. prostacycline) which play an important role in bronchodilatation. Patch-tests: budesonide (1% eth) + tixocortol pivalate (1% pet) positive in 91. Most cases involve a non-allergic mechanism.3% of corticosteroid contact allergic subjects. hydrocortisone inhibits arachidonic acid release by phospholipids and thus deprives the airways of the cycloxygeneation products (PGE2. . When possible. If use is absolutely necessary.222 - . IgE-mediated hypersensitivity: one case report. Challenge tests may be useful but hazardous. administer orally rather than intravenously.

4% to 6. J. Jung R. budesonide) — C: betamethasone. Browning M.4% of positive patch-tests to different topical corticosteroids in populations with contact dermatitis.H. . 1995. 33 (3): 149-51 Clee M. INCIDENCE 0. carbonates. Diaz-Pena J. desoxymethasone. 1997. 1995. RISK FACTORS Long term application of topical corticosteroids (leg ulcers.A. There are 4 chemical/structural classes of corticosteroids. Therapie. de Las Heras M. Allergy. “Screening for corticosteroid contact hypersensitivity”.. betamethasone-vale rate. Contact. 32 (4): 193-8 Reveilleau-Richard S.T. 97: 1169-71 Whitmore S. Contact. Allergy Clin. 1996.D. Clark R. psoriasis.K. — A: hydrocortisone.6%) in a multicentre European study. Martin-Barroso J. “Anaphylaxis to dexamethasone” .M. “Anaphylaxis to 6-alpha-methylprednisolone in an eight-yearold child”. “Delayed systemic allergic reactions to corticosteroids” . lichen planus). Lluch-Bernal M. fluocortolone — D: esters: hydrocortisone-17-butyrate. Ferguson J.. Cuesta-Herranz J. dexamethasone. Beck M. Umpierrez A. “Hypersensibilités aux glucocorticoïdes: reflexions à partir d’un échantillon de cas rapportés dans la litterature”. “Glucocorticoïd hypersensitivity in an asthmatic patient: presentation and treatment”. 52: 877 Moreno-Ancillo A. Wilkinson S.A. prednisolone.E. Dermatitis. desonide.. Castot A. 189/7238 patients (2.. Navarre C. betamethasone-dipropionate. 40 (6): 477-8 TOPICAL CORTICOSTEROIDS Widely used drugs in dermatology. Thorax. Allergy to hydrocortisone has been reported for the first time in 1959. .M. carboxylates.HORMONES REFERENCES • • • • • • Figueredo E. Dermatitis. tixocortol pivalate — B: acetonides (triamcinolone. Immunol.C. Martin-Munoz F.A. 50 (5): 439-46 Boffa M. 1985. atopic dermatitis. Sastre J. Ojeda J. 1995.J.223 - .

urticaria. . Patch-tests must be read at 48 and 96 hours. — Anaphylaxis.224 - . MECHANISMS Delayed contact hypersensitivity. psoriasis) — Reactivation of eczema following oral. followed by hydrocortisone17-butyrate (1%). hydrocortisone-17-butyrate are the best candidates. a repeated open application test with the corticosteroid preparation or a serial dilution of patch testing may be useful. angioedema following parenteral ad ministration of a corticosteroid.4%). leg ulcers. Interpretation of the tests is often difficult due to vasoconstriction or vasodilatation effects. tixocortol pivalate. DIAGNOSTIC METHODS Cutaneous testing. In dubious cases. budesonide and tixocortol pivalate give the highest positive patch-tests (1. but also at day 7 or 10 (delayed reactions due to the anti-inflammatory effects of the topical corticosteroids). Clobetasol propionate and betamethasone valerate have the lowest frequency. Cross-reactivity between corticosteroids may be found in patch testing but is not always clinically relevant. parenteral or intraarticular administration of a corticosteroid.HORMONES CLINICAL MANIFESTATIONS The diagnosis of topical corticosteroid allergy is often difficult due to the anti-inflammatory action on cutaneous lesions and their delayed appearance. Among the corticosteroids. — Increased eczema despite well-conducted topical treatment — Eczematization of chronic dermatosis (seborrheic dermatitis. MANAGEMENT Avoidance. Topical corticosteroids should be included in standard patch testing: budesonide.

Derm.. Bruynzeel D. Dooms-Goossens A. . “Identification of cross-reaction patterns in contact dermatitis from topical corticosteroids”. polycystic ovary disease. Frosch P. Leuprorelin (leuprolide).M. Gonadorelin. Dermatol. Buserelin. Hannuksela M.P. Wilkinson J. Brandao F. CLINICAL MANIFESTATIONS General: anaphylactic shock. Cutaneous: flush. pruritus. bronchospasm. precocious puberty. Burrows D.. Contact. RISK FACTORS Route of administration (constant infusion > intermittent use)..225 - . Goserelin. 1995.M. 33: 40-4 Lepoittevin J. Dooms-Goossens A. Camarasa J. Menne T. 1989. and prostate cancer. Br. 131: 31-7 Coopman F.HORMONES REFERENCES • • Pons-Guiraud A. urticaria. General reactions are rare. Drieghe J. “Allergie aux dermocorticoïdes”.D.E. Nafarelin.E. “Corticosteroid contact allergy: an ECDRG multicentre study”. Lahti A. Dermatitis. Wahlberg J. Degreef H. Lachapelle J. J. Arch. Ducombs G. Peau. local erythema. INCIDENCE Local reactions: 0 to 13%. Length of treatment. vasculitis (sometimes delayed) Respiratory: sneeze. 1996. Objectif. 121: 27-34 • • GNRH ANALOGUES These drugs are used to induce ovulation and in treatment of endometriosis. “Studies in patients with corticosteroid contact allergy: understanding cross-reactivity among different steroids”. 1996. Tripterolin. 4: 433-5 Dooms-Goossens A. Andersen K.

Fertil. “Case report: systemic hypersensitivity reaction to goserelin acetate” . Non-specific histamine release.. specific IgE). Raj M. Specific IgG (RIA): controversial role. 48 (3): 500-2. “Immunoglobulin-mediated hypersensitivity in response to long-term treatment with gonadorelin hydrochloride (Factrel) in a female patient”. MANAGEMENT Avoidance of all GnRHs.226 - . Stevenson D.. Skin-prick tests positive in various concentrations for gonadorelin. Karadsheh A. • . Halevy S. Obstet. J. 1996.2): 943-6 Foster W. Jarrell J. Yung-Lai E.H. 52 (3): 217-8 Letterie G. Kumar P. Biol. Gynecol. Type III reaction (one case). MECHANISMS IgE-mediated hypersensitivity (immediate positive skin tests.G. Eur. Steril. 78 (5. 160 (4): 979-83 Mac Leod T. MIF one case positive with triptorelin Skin-biopsy: one case of allergic vasculitis with triptorelin. leuprorelin.J. “Recurrent anaphylaxis to a depot form of GnRH analogue”. 1991. Med. Sci. Obstet.L.H. buserilin. Grunwald M.G.HORMONES DIAGNOSTIC METHODS Cutaneous testing. REFERENCES • • • • Raj S.L. Shah A.V. 1987. 1989. Am. J.J. Gynecol. Reprod. Specific IgE (RAST): a few cases published. 312 (4): 187-90 Amichai B.. Eisen A.. 1993. Guillot R. Gynecol.F. “Allergic vasculitis induced by Decapeptyl*: confirmation by macrophage migration inhibition factor (MIF) test”. Obstet. Am. Dolovich J.S. goserilin. J. “Anaphylactic reaction to synthetic luteinizing hormone-releasing hormone”. Sussman G..

occurring to 2 to 4 days after heparin administration (platelet sequestration?). CLINICAL MANIFESTATIONS I Heparin associated thrombocytopenia (HAT). RISK FACTORS Female gender and obesity (delayed allergic skin reactions). INCIDENCE Heparin associated thrombocytopenia: 1 to 5% of patients receiving unfractioned heparin for at last 5 days. Heparin is widely used in surgery (cardiopulmonary bypass) and in medicine to treat deep venous thrombosis and pulmonary embolism. II Immediate hypersensitivity reactions. developing 6 to 12 days after start of heparin therapy and often complicated by venous and arterial thromboembolic events (immunological mechanism). — Type II: severe (often < 50000 platelets/ mm3). — Anaphylactic shock — Bronchospasm — Urticaria — Rhinitis. conjunctivitis . Skin-necrosis: uncommon.HORMONES HEPARIN Heparin is a highly acidic. anionic. — Type I: moderate and transient decline in platelet count. Type I manifestations: exceptional.227 - . sulfated mucopolysaccharide obtained from beef lung or beef and porcine intestinal mucosa and is highly antigenic.

eczematous lesion after superficial injection. MECHANISMS Platelets of patients with peripheral arterial disease are hypersensitive to heparin in vitro and in vivo. With or without thrombocytopenia. — 57 cases described (1996) with unfractioned heparins — 10 cases described (1996) with low weight molecular heparins Infiltrative plaque after deep injection. DIAGNOSTIC METHODS I Thrombocytopenia. Subcutaneous injection of 0. Patch-tests are often negative in delayed allergic skin-reactions. Low molecular weight heparins show in vitro and in vivo crossreactivity with unfractioned heparin.228 - . Heparin-induced platelet activation test (HIPA) Stagnation point flow adhesioaggregometry (SPAA) These techniques must be performed to confirm the responsibility of heparin in thrombocytopenia (IgG antibodies) and also with the substitutes: low molecular weight heparins or heparinoid before using them. IV Delayed allergic skin-reactions. 5 to 9 days after beginning of the treatment. Skin-biopsies show type III histologic lesions in skin-necrosis and type IV histologic lesions in delayed allergic skin-lesions. indurated erythema occurring at the injection sites with subsequent skin-necrosis. 4 days. It must be read at 30 minutes. occurring 10 days after initiation of therapy. Sensitization to heparin may occur with other polysulfated glycosaminoglycans. Prick-tests and intradermal skin-tests are sometimes positive in immediate cutaneous reactions (urticaria).1 ml. and must only be used after immunological exclusion of cross-reactivity. 2 days. or pure heparin is often the better test. . II Cutaneous reactions.HORMONES III Skin-necrosis.

Reactions to preservatives (chlorocresol. Immediate discontinuation of heparin. numerous alternatives exist: — use bovine lung heparin. chlorbutanol) were reported in the Seventies. Heparin allergy. Substitution with low molecular weight heparin or heparinoid (danaparoid sodium). Type IV: delayed skin reactions.HORMONES Type I: immediate reactions (urticaria). Type III: skin-necrosis. hirudin. D3: 5000 IU /1000 ml saline/24 hours. Type II: thrombocytopenia. if in vitro aggregation test is negative. argatro ban. — use iloprost in cardiopulmonary by-pass or dialysed patients — DESENSITIZATION is possible (2 cases reported). I Intravenous desensitization: D1: 100 IU/1000 ml saline/24 hours. In a patient with history indicating possible heparin allergy. Use warfarin or coumadin therapy. if there is a reaction to porcine gut heparin (one case) — use low molecular weight heparin or heparinoids (beware of cross-reactivity) — use thrombin inhibitors: ancrod (thrombin-like enzyme extracted from the venom of Malayan pit viper). D2: 1000 IU/1000 ml saline/24 hours.229 - . MANAGEMENT Thrombocytopenia. Vena cava filters are sometimes useful (pulmonary embolism). Then 5000 IU subcutaneously twice daily until surgery. . and if no other possibilities.

C D3: 500 IU I.HORMONES II Subcutaneous and intravenous desensitization: D1: 50 IU S.E. Dermatol. Varano C. Thromb. Surber C. 81 (6): 641-9 Bircher A. Br. “Rush desensitization in heparin hypersensitivity: a case report”. Townsend G. Bowen T. al-Momen A.. Schweiberer L. Steckmeier B. Thromb. Schiavino D. “Successful heparin desensitization after heparin-induced anaphylactic shock”. Schiavello R. “Platelets of patients with peripheral arterial disease are hypersensitive to heparin”. Ann.6): 523-6 Patriarca G. 1997.C After 40 minutes: 500 IU S. Anlauf M.R.B.H..C After 40 minutes: 250 IU S.V REFERENCES • Tholl U. “Delayed hypersensitivity to one low-molecular-weight heparin with tolerance of other low-molecularweight heparins”. Overdick K. J. 1995. Fayed D. Res.C D2: 500 IU S.Y. Dial.V After 40 minutes: 3000 IU I. 1994. The prevalence .. 1996. Pharmacother. Lasser R.J.A. Transplant. Berry B. 49 (4): 292-4 • • • • • INSULIN Immunological responses to insulin are responsible for 2 principal syndromes: insulin allergy and insulin resistance.V After 40 minutes: 1500 IU I. Schinco G.C After 40 minutes: 1500 IU S.. “Enoxaparin for unstable angina and ancrod for cardiac surgery following heparin allergy”.E. Rossi M. 1995.C After 40 minutes: 3000 IU S. 30 (5): 476-80 Reininger C. Fais G. Greinacher A.230 - .K. Allam A.V D4 5000 IU I. 1996. “Life-threatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparininduced thrombocytopenia”. Graf J.K. Greinacher A. Allergy. Itin P. 132 (3): 461-3 al-Eryani A.. Res.. Nephrol. 79 (5.F. Tsakiris D. 12 (12): 27505 Smith R.

II/ Systemic. . — Delayed (tuberculin-like): onset at 12 hours. protamine). 4). Anaphylactic shock. insulin pumps. periorbital edema. peaks at 12 hours. Bronchospasm. species (bovine > pork > human). Insulin factors: purity. — Immediate (within minutes of injection): pain + itching accompanied by erythema and swelling < 1 hour. peaks at 24-48 hours. Individual factors: age. interrupted insulin therapy. induration with erythema and pruritus. physical properties (pH). Previous allergies (controversial). RISK FACTORS Atopy (controversial) . Mode of insulin administration: SC > IV. CLINICAL MANIFESTATIONS I/ Local (2-3% in patients treated with highly purified pork or human insulin).231 - . INCIDENCE Historically: 50% of patients using impure insulin preparation. generalized lymphadenopathy. retarding agents (Zn. General urticaria. immunological background (HLA DR 2. 3. Less than 1% of de novo human insulin treated patients.HORMONES of insulin allergy has decreased considerably since human recombinant insulins became available. angioedema. Immunological insulin resistance. presence of insulin antibodies. induration with pruritus. — Biphasic (immediate + late phase response): starting at 4 hours and persisting 1-3 days. Serum sickness. — Intermediate (Arthus reaction): onset at 4-8 hours.

Protamine-specific IgE (UniCAP®/Pharmacia CAP System™) are positive in a few patients with allergy to insulins containing protamine . High titers of IgE are frequently present in systemic insulin allergy. Intradermal skin-tests: 0. urticaria). Antigenic characteristics.02 to 0. — Differences in primary amino acid sequence from human insulin — Altered tertiary structure — Dimer and aggregate formations . Type III reactions (antigen-antibody initiated complement fixation. Type IV reactions: rare. leukocyte attraction and inflammatory response): Arthus. Cutaneous testing allows assessment of the less immunogenic insulin. Skin-prick tests: insulins 40 UI/ ml. immunological insulin resistance). Specific IgE (RAST. adenopathies. ELISA) Low concentrations of IgE anti-insulin are present in the serum of many patients treated with insulin and do not correlate with allergic reactions.232 - . protamine sulfate 10 mg/ ml . This requires a quantitative assay of the insulin binding capacity of the serum (if greater than 5 U/l of plasma = insulin resistance) MECHANISMS IgE-mediated hypersensitivity (local reactions: immediate or biphasic. general reactions: anaphylactic shock. serum sickness.05 ml of different insulins (5 U/ ml).HORMONES DIAGNOSTIC METHODS Cutaneous testing (40% of patients receiving insulin without clinical allergy develop positive immediate skin-tests to the insulin used for treatment). Specific IgG (ELISA) High titers of insulin IgG antibodies are found in patients with insulin resistance.

A1920-21. peptides. Allergy occurs more often with bovine insulin than with porcine insulin therapy. Reassure the patient.A positions A1. The insulin molecule has well-identified immunogenic epitopes which map at A. present in NPH insulin and protamine-zinc insulin as the cause of generalized allergic reactions to insulin (clinically: absence of previous local reactions.HORMONES — Non-insulin protein contaminants (proinsulin. refractory period of weeks or months between reactions). A6. Differences in amino acid sequences of the various exogenous is one of the major contributors to exogenous insulin allergy. MANAGEMENT I/ Local reactions. preservatives. Porcine and bovine insulins differ from human insulin by 1 and 3 amino acids. B-3 and B-30. A few papers reported allergy to protamine.233 - . switch to a more purified form of insulin. Antigenicity of human semi-synthetic insulin is probably due to a tertiary structure change and to shared antigen determinants with pork and beef insulins. Insulin syringes and insulin vial stoppers containing latex and may lead to allergic reactions in patients with diabetes. buffers). microbial contaminants) — Non-protein additives (zinc. desensitize to the least reactive regular insulin preparation. glucagon. protamine. If insulin treatment is absolutely necessary and skin-tests are positive. use antihistamines. A chain loop (A8-A11). . Different from contact allergy due to glue components in infusion sets of insulin pumps: epoxyresin. severity of reactions. II/ Generalized reactions. Most cases of allergy to human insulin have histories of animal insulin exposure. use several injection sites.

1997..S. 1994. Diabetes Care. “Immunogenicity and allergenic potential of animal and human insulins”.C. “Insulin allergy and insulin resistance”. Curr. Kim H. Allergy. Ther. . Kahn C.02 ml (0. Carrillo T. de Kalbermatten N. 6: 500-4 Blanco C. LISPRO (analog of human insulin) with reversed position of amino acids lysine 28 and proline 29 on the insulin Beta chain. “ Anaphylaxis to subcutaneous neutral protamine Hagedorn insulin with simultaneous sensitization to protamine and insulin”. remains in a monomeric state and has lowest immunogenicity.1): 117-25 Schernthaner G. 1996. Yoo T. 16 Suppl 3: 155-65 • • • .05 U/ ml) ID to 0. 5: 461-4 Dykewicz M. Graf I.E. 51 (6): 421-4 Goldfine A. Metab. Garcia I. Curr. Castillo R. Aubry M. 93 (1. Allergy. “Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin”.increase insulin dose 5 Uq 12 h until control is achieved. Orfan N. de Pablos P. “Desensitization-resistant insulin allergy”.08 ml (50 U/ ml).R. “Insulin allergy and insulin resistance”.. then follow with double dose SC q 4 h until control is established.continue NPH or lente insulin q12 h If the patient is medically unstable: rapid desensitization protocol. REFERENCES • • • • Frigerio C. Quiralte J. 20 (9): 1357-9 Lebovitz H. 52 (2): 238-9 Kumar D.W.. It has been successfully used in allergy to other insulins and in immunemediated insulin resistance cases. Gaillard R. Clin. Gomez F. Endocrinol. J.B. for example: 0. Spertini F. Diabetes Care. Delgado J.234 - . 1994.J. 1993. Metab. Immunol. Ther.. Allergy. Endocrinol. “Lispro analog for treatment of generalized allergy to human insulin”. Lieberman P. 1997. Dayer E. 1997.HORMONES If the patient is medically stable: give 1/2 dose of insulin.

Previous protamine exposure. In patients with no prior exposure to SC protamine insulin preparations. Urticaria. INCIDENCE 2. Seroconversion is associated with male gender and insulin-dependent mellitus. Systemic hypotension +/. It is purified commercially from salmon milt.pulmonary vasoconstriction.235 - . these patients may be at increased risk on subsequent exposure. Anaphylactic shock. the presence of IgG to protamine leads to a relative risk of 25. Pulmonary vasoconstriction: 1. Vasectomy and fish allergy are not risk factors. rash.6% of insulin diabetic patients with NPH insulin or PZ insulin have reactions to intravenously administered protamine versus 0. the presence of IgG to protamine leads to a relative risk of 38.4% of non diabetic patients.76% to 0.9% to 26.HORMONES PROTAMINE Strongly alkaline polycationic molecule used to neutralize the anticoagulant effect of heparin or to slow the absorption of insulin. . CLINICAL MANIFESTATIONS. Bronchospasm. Insulin dependent diabetic patients treated with NPH or PZI: the presence of IgE to protamine leads to a relative risk of 95 if protamine is used.2% RISK FACTORS Single-dose intravenous protamine results in protamine specific IgE or IgG antibody production in 28% of patients.

Hirshman C. Baumgartner W. causing pulmonary arterial pressure elevation. Skin-prick tests positive at 10 mg/ ml in one patient with NPH insulin allergy. Inhibition of serum carboxypeptidase. aprotinin). Solid phase immunoassay (IgE. Shampaine E. Allergy. Use of adjuncts to promote hemostasis (antifibrinolytics. Intradermal skin-tests with 1 µg/ ml and 10 µg/ ml protamine give false positive results. Protamine specific antibody assays. RAST (IgE. “Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies”. Augmentation in thromboxane A2 and 6 ketoprotaglandin F1 alpha. C4a. C5a). IgG). ELISA (IgE.L. J. Direct non-immunological histamine release.HORMONES DIAGNOSTIC METHODS Cutaneous testing (controversial).M. IgG). Clin. IgG): false positive results.236 - .F Jr. Adkinson N. Complement activation (by heparin-protamine complexes or by interaction with protamine-antiprotamine IgG antibody complexes leading to generation of C3a.P. Immunol. Use of hexadimethrine in place of protamine. Potentiation of IgE-mediated histamine release.A. Hamilton R. Frank S. MECHANISMS IgE or IgG-mediated hypersensitivity (with or without complement activation unrelated to rate of administration). 97 (4): 991-7 .A. MANAGEMENT Use of ancrod or hirudin instead of heparin.G.. 1996. Premedication with antihistamines and steroids reduces the severity of an allergic reaction (controversial) REFERENCES • Nyhan D.

Freeland C.. 9 (3-4): 339–55 Vincent G. Cardiovasc. 1991. Orfan N. (patch-tests).HORMONES • • • • Horrow J. eye drops with neosynephrine. 93 (1. Diagn.S. “Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamineinsulin preparations”. eczema (oral absorption of pseudoephedrine). 23 (3): 164-8 PSEUDOEPHEDRINE Many drugs contain cathecholamine derivatives (local anesthetics. J.. “Allergy to protamine”. Allergy Clin. 82 (2): 386-9 Dykewicz M. Adkinson N. Anesth.J. . Pharo G.W..237 - . “Neither skin-tests nor serum enzyme-linked immunosorbent assay tests provide specificity for protamine allergy”. Allergy. Acute conjunctivitis with eczema of the eyelids (neosynephrine containing eye drops). Immunol. Clin.C. Delayed contact hypersensitivity is more frequent.S. Cathet. nasal vasoconstrictives).F Jr.H. Levit L. Rev. Prick-tests and patch-tests with pseudoephedrine 1%. “Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin”. INCIDENCE Low. CLINICAL MANIFESTATIONS Urticaria. fixed drug eruption.M. Yoo T. 1991. 1996. DIAGNOSTIC METHODS Cutaneous testing.1): 117-25 Weiss M.E. Menlove R. Kim H. 5% in water or pet. scarlatin-like rash. Analg. MECHANISMS Immediate hypersensitivity is exceptional. Lieberman P. Janowski M. Mechanism is unknown in toxic shock syndrome and in most rashes. 1994.

Contact.J. J.HORMONES MANAGEMENT Avoidance. 5: 235-6 Tomb R. Cross-reactivity may exist among cathecholamine derivatives. Morales C. 1991. Immunol.B. Dermatitis. Duffill M. “Recurrent pseudo-scarlatina and allergy to pseudoephedrine hydrochloride”. Dermatol. — epinephrine and phenylephrine do not seem to cross-react with the first group. 38: 41-3 Rochina A. with corresponding T-cell hyperresponsiveness in vitro”.. 24: 86-8 Taylor B. Allergol. Rueff F. “Severe allergic contact blepharoconjunctivitis from phenylephrine in eye drops.. REFERENCES • • • • Thomas P. These molecules have a very close structure and can cross-react. “Adverse reaction to pseudoephedrine”. 1988.. Br. Espinassouze F. Pelaez A.T. Invest. Pryzbilla B.238 - . 1995. Dermatitis. 118: 827-9 . pseudoephedrine and norephedrine derived from a molecular structure of phenyl propanolamine type. Braso J.V. Thus sensitization to pseudoephedrine does not contra-indicate the use of eye drops containing neosynephrine and the use of epinephrine containing local anesthetics. “Systemic contact dermatitis from pseudoephedrine”. J. 1998. Lepoittevin J.R. There are 2 types of derivatives: — ephedrine. Burches E. Contact. Foussereau J. Heid E.

SERA AND VACCINES XI SERA AND VACCINES .239 - .

CLINICAL MANIFESTATIONS Anaphylactic shock Bronchospasm. or murine species. Skin prick-tests with dilutions to 1/1000 to pure have a better predictive value. and bone marrow graft rejection. MECHANISMS IgE-mediated hypersensitivity (immediate reactions). cardiac. rabbit. Cutaneous eruptions. . Circulating immune complexes (serum sickness). RISK FACTORS Allergy to horses. INCIDENCE Anaphylaxis < 1% of treatments.S. murine).240 - . MANAGEMENT Skin prick-tests must be performed in all patients treated with heterologous antisera. DIAGNOSTIC METHODS Skin tests must be performed before use of antithymocyte globulins in order to detect at-risk patients. A.R. Several commercial preparations from different animal serums exist (horse. Intradermal skin tests give false positive results. periorbital edema.D. rabbits.SERA AND VACCINES ANTITHYMOCYTE GLOBULINS Antithymocyte globulins are the preferred treatment for patients with aplastic anemia and in prevention and treatment of renal. kidney.

5 000 µg/ ml at ten minutes intervals then 0. 500 µg/ ml. 300 µg/ ml. Transplantation.L. 5 000 µg/ ml at ten minutes intervals then 0.S. Sullivan T.5% . Brentjens J. 79 (1): 237 ANTIVENOMS Antivenoms are prepared from immunized animal sera. — desensitization may be performed: 0. Allergy. Scorpion: 8% with centuroides sculpturatus antivenom. Immunol. 3 000 µg/ ml. Carrington D. Jiang C. spider and scorpion envenomation. INCIDENCE Snake: 3 to 54%. REFERENCES • • • Bielory L. JAMA. 2 mg/ min intravenous for ten minutes each with the therapeutic dose of ATG at 15 mg/kg constantly infused over 24 hours. 1988. Spider: 0. J. Nienhuis A.5 ml subcutaneous 50 µg/ ml. “Reactions to antilymphocyte globulins”.02 ml intradermal 5µg/ ml. ”Antilymphocyte globulin hypersensitivity in bone marrow failure patients”.W. 1.. . 43 (2): 309-12 Gartner J. “Acute serum sickness with glomerulonephritis induced by antithymocyte globulins”. 260 (21): 3164-7 Cunningham E. Kaliner M. Clin. 50µg/ ml. 1 000 µg/ ml. Wright R. 1 mg/ min.SERA AND VACCINES For patients with positive skin prick-tests: — use a preparation from other mammalian origin (horse <— > rabbit). 1987.241 - .7 to 2.5 mg/ min. Venuto R. They constitute the specific treatment for snake. Chi Y. Earl H. Young N. 100 µg/ ml. quinquestriatus venom.6% with L.A. 1987.

pruritus. Pre-treatment with antihistamine and epinephrine. —If positive. perform intradermal skin tests.SERA AND VACCINES RISK FACTORS Allergy to animal serum or dander (horse. Delayed: serum sickness. 32 (2): 165-71 . the risk of immediate reaction is high —Negative results do not absolutely rule out the possibility of a reaction. with centuroides sculpturatus antivenom specificity is 98%. and slow intravenous injection of the antivenom at a 1/1000 or 1/10000 dilution are good precautions. Toxicol. vomiting. REFERENCES • • Ismail M. DIAGNOSTIC METHODS Cutaneous testing: its usefulness is controversial. diarrhea. Toxicon. abdominal pain.242 - . MANAGEMENT In high risk patients. sensitivity 68%. “Response to specific centuroides sculpturatus antivenom in 151 cases of scorpion stings”. CLINICAL MANIFESTATIONS Immediate: anaphylactic shock. 1994. J. urticaria. Clark R. urticaria. Nevertheless. MECHANISMS IgE-mediated hypersensitivity. 1994. bronchospasm. Bloom M. “The treatment of the scorpion envenoming syndrome: the Saudi experience with serotherapy”. 32 (9): 1019-26 Gateau T. Complement activation by antivenom or impurities. Rapid desensitization has been recommended. polyadenopathy . rash. False positive and negative seem to be high. goat). Clin. Circulating immune complexes (serum sickness). arthralgias.

1987. Ann. Assoc. CLINICAL MANIFESTATIONS Differentiate from lymphadenitis or generalized granulomatosis.. Med. Anaphylaxis. “Antivenoms”. Fewer than ten cases in neonates or infants have been reported. Emerg. Singhthong P. Med. J. 35 (3): 250-1 Malasit P. “Prediction. Pustular vasculitis. Chanthavanich P. “Venomous snakebite in a patient allergic to horse serum”. 292: 17–20. Dermatomyositis (conflictual). Lupus vulgaris +/. J. 1983. 1986 . Otten EJ. Acute febrile neutrophilic dermatosis (Sweet’s syndrome). Erythema multiforme. J...243 - . Supich C. DIAGNOSTIC METHODS Dextran reactive antibodies: in a few cases where high titers of DRA were found in a maternal blood sample or child’s blood sample. Br. Lovering KE. “Rapid desensitization in antivenom hypersensitivity”. Phys. Mackimm D. 1979. Other indications are intralesional treatment in superficial bladder cancer. BCG VACCINE BCG Vaccine is widely used throughout the world to prevent tuberculosis.Viravan C. . 12: 624–7. 671–4. Urticaria. INCIDENCE Quite uncommon.SERA AND VACCINES • • • • Varma T. Warrell DA. Mongkolsapaya J. Austr. Med. prevention and mechanisms of early (anaphylactic) antivenom reactions in victims of snake bites” .urticarial vasculitis. Ind. Sutherland SK.

Gunthard J. Berglund A. Mougeolle JM. Staehlin J. Compr. INCIDENCE 9% of injections (immediate manifestations: 5%. Dermatol. “Reactions immunoallergiques cutanées dues aux vaccins”. Halter C. One method of management is injection of an equine botulinal antitoxin.9% of cases. Eur.244 - . Vénéréol.Guérin (BCG) immunotherapy in superficial bladder cancer”. CLINICAL MANIFESTATIONS Anaphylactic shock (occurs even with small amounts of serum): 1. “Complications of bacillus Calmette . Dextran 1 should be used in the vaccines. 1995.SERA AND VACCINES MECHANISMS Concerning the neonatal anaphylactic reactions reported after BCG vaccination. Ann. 1991. Therapy. Lancet. Urticaria: 2. “Hypersensitivity of dextran in BCG vaccine”. 1994.6% of cases.122: 129-38 Sosnowski JT. REFERENCES • • • • Rudin C. J. Fine PEM. Pediatr. Moreno C. 1995. passively acquired maternal dextran antibodies reacted with the 100 KD dextran which is a component of the BCG vaccine. MANAGEMENT Use BCG vaccine without dextran (sodium glutamate). “Anaphylactoïd reaction to BCG vaccine containing high molecular weight dextran”. Schmutz JL. . delayed manifestations: 4%).20 (12): 695-701 Pönnighaus JM. instead of high molecular weight (100 KD) dextran.154 (11): 941-2 Barbaud A.337: 1039 BOTULINAL ANTITOXIN Botulism is a paralyzing illness caused by the action of neurotoxins produced by Clostridium botulinum.

69: 567–70. Am. The role of immune complexes is likely in cases involving serum sickness. Inject less than 40 ml of botulinal antitoxin so as to minimize serum sickness. REFERENCES • Black RE. but IgE antibodies have never been demonstrated.7% of cases. . MECHANISMS IgE-mediated hypersensitivity probably underlies anaphylactic manifestations. Generalized erythema.245 - . BOVINE SERUM ALBUMIN Bovine serum albumin is a powerful immunogen able to produce allergic reactions. DIAGNOSTIC METHODS Cutaneous testing Intradermal skin tests may be positive in patients presenting anaphylactic shock. Med. MANAGEMENT No effective prevention for immediate manifestations.SERA AND VACCINES Serum sickness (injections exceeding 40 ml): 3. 1980. Gunn RA. “Hypersensitivity reactions associated with botulinal antitoxin”. However. J. It is used during bone marrow transplantation and in vitro fertilization. the false negative rate is high (50%) and this test does not rule out the possibility of generalized reactions. laryngeal edema: 0. Using botulinal immune globulin obtained from hyperimmunized human donors will be beneficial.7% of cases..

Specific IgE: IgE anti BSA (ELISA / RAST). Urticaria. fever.SERA AND VACCINES INCIDENCE Serum sickness: 1% to 15% (in 32 patients with in vitro fertilization). Specific IgG (ELISA) in serum sickness-like reactions. and positive to fetal calf serum (containing bovine serum albumin). MECHANISMS IgE-mediated hypersensitivity: positive skin tests and specific IgE against BSA.246 - . 8 to 12 days after procedure). Rhinoconjunctivitis. angioedema. Skin prick-tests: positive with BSA in 1% distilled water. Sensitization to BSA may develop following natural contact (eating meat. RISK FACTORS Atopy. .1 and 1 mg/ ml are positive in immediate and late responses. Intradermal skin tests with BSA 0. CLINICAL MANIFESTATIONS Anaphylactic shock. exposure to animal epithelia. Serum sickness (maculopapular eruption. drinking cow’s milk. arthralgias. Bronchospasm. dander or saliva containing serum albumin cross-reactive with BSA) Serum sickness-like reactions: IgG 1 mediated sensitization to BSA MANAGEMENT Preoperative skin prick tests or RAST with the insemination medium is recommended. DIAGNOSTIC METHODS Cutaneous testing.

Allergy. Stern A. Serum sickness.247 - . Inv. Allergol. Boulard P.4 (5): 246-9 Moneret-Vautrin DA. Wal JM. equine rabies immunoglobulin (ERIG) is more readily available than human rabies immunoglobulin (HRIG). 83: 871-5 EQUINE RABIES IMMUNOGLOBULINS In developing countries. Immunol. Immunol. Allergy Clin.50: 179-83 Morales C. Clin. “Bovine serum albumin immunization. Allergy. Bulpitt K. Bronchospasm. CLINICAL MANIFESTATIONS Anaphylactic shock. “Severe anaphylactic reaction to bovine serum albumin at the first attempt of artificial insemination”. Pellicer A. Pelaez A.6%. Johansson SGO. An apparent reaction to self mediated by IgE antibodies to bovine serum albumin”. J. Champlin RE.SERA AND VACCINES Concerning bone marrow infusion. 1989. Serum sickness: 1-1. Gerard H. Saxon A. Modern ammonium-sulfate-precipitated ERIG products are safe and effective. REFERENCES • • • • Wüthrich B. 1991. Generalized urticaria . “Anaphylaxis to infusion of autologous bone marrow. 1994. “Serum sickness due to bovine serum albumin sensitization during in vitro fertilization”. . Ruiz A. INCIDENCE Anaphylaxis: 1/35 000. J. Braso JV. A new risk of allergy during protocols for in vivo fertilization”. 1995. autologous plasma or serum is now used instead of BSA. Guillet-Rossof F. 46: 228-34 Macy E.

248 - .02 ml of 1/100 ERIG). Arthus phenomenon. Clin. eczema exacerbation. — General reactions: arthralgias. 1995.21 (3): 660-2 HEPATITIS B VACCINE Recombinant DNA techniques have permitted the development of vaccines to the hepatitis B virus prepared by cloning and expressing the Hbs antigen in yeast or CHO cells. Type III hypersensitivity reactions (serum sickness). Infect. “Value of skin testing for predicting reactions to equine rabies immunoglobulin”. generalized urticaria. . REFERENCES • Tantawichien T. Siakasem A. RISK FACTORS Contact sensitization to formaldehyde or thiomersal. erythema nodosum. erythema multiforme (2/200 000). Yeast allergy. MECHANISMS Type I hypersensitivity reactions (anaphylaxis). Jaijaroensup W. Sitprija V. myalgias. thrombocytopenic purpura. or if wheal is 5-10 mm in diameter with a flare > 20 mm. do not use ERIG. CLINICAL MANIFESTATIONS — Local reactions: local urticaria or aluminum granuloma. Wilde H. INCIDENCE Less than 1%.SERA AND VACCINES DIAGNOSTIC METHODS AND MANAGEMENT Intradermal skin test must be performed before administration of ERIG (0. pruritus (1/122 500). If wheal is > 10 mm in diameter with or without flare. False positives have been reported. Yountong C. Benjavongkulchai M. Dis. Chareowai S.

Helminiak C. Schmutz JL.618 persons”. Lancet. 1995. i: 903 Ring J. Patch tests: thiomersal 0. Mougeolle JM. REFERENCES • • • • • • Lear JT. aluminum chloride 0. formaldehyde 2%. “Adverse reaction to the recombinant hepatitis B vaccine” . Lancet. Scadding GK. aluminum chloride 0. Wainwright D. Bulkow L.249 - . use vaccine containing a different preservative .88 (5): 821-2 Brightman CAJ. Wainwright R. Lancet. latex. Gervais F. Shuster J. Immunol. latex or formaldehyde. English JSC. 1986. “Reactions immunoallergiques cutanées dues aux vaccins”. “Exacerbation of eczema by formalin-containing hepatitis B vaccine in formaldehyde allergic patient”. Trimble D. aluminum chloride.5%.SERA AND VACCINES DIAGNOSTIC METHODS Cutaneous testing.i: 522-3 . saccharomyces cerevesiae. 1995. Venereol. Dermatol. thiomersal 0.5%. “Yeast derived hepatitis B vaccine and yeast hypersensitivity”.1%.122: 129-38 Mac Mahon B. “Frequency of adverse reactions to hepatitis B vaccine in 43. J.345: 1249 Barbaud A. Newkirk M. use a glass syringe and remove the rubber bung.1%. Intradermal skin tests: full vaccine 1/100. Ann. Dumbreck LA. Brostoff J. “Anaphylaxis after hepatitis B vaccination”. MECHANISMS Aluminum hydroxide. Allergy. thiomersal. Am. formalin. Latchman Y. Clin. 1989. Med. Prick tests: full vaccine 1/10. 1992. MANAGEMENT If revaccination is necessary. J. In patients with latex allergy. yeast or latex are responsible for the few reported allergic reactions to the hepatitis B vaccine. saccharomyces cerevesiae. 1991. Specific IgE: saccharomyces cerevesiae.92: 196-9 Hudson TJ. Few cases with positive tests to thiomersal.

Serum sickness is more frequent. Cutaneous: cutaneous eruptions.5 ml at 1:10.250 - . Renal: glomerulonephritis. but negative if the product is left to stand for 4 to 8 hours at room temperature. DIAGNOSTIC METHODS Skin tests must be performed before injection in order to detect IgE antibodies and ascertain the risk of anaphylactic reaction. It is used for prophylactic and curative treatment of kidney graft rejection. CLINICAL MANIFESTATIONS General: anaphylactic shock.SERA AND VACCINES HETEROLOGOUS SERA Antilymphocyte globulin is a gammaglobulin prepared by injection of human lymphocytes into various animals (e. perform: — prick test at 1:10 — intradermal injection of 0. serum sickness (most common). Respiratory: adult respiratory distress syndrome. . RISK FACTORS Detection of IgE antibodies against hair from the animals providing the serum. A 20-minute intervals. horses) and then purifying the IgG against human lymphocytes from the serum.02 ml at 1:1 000 or 1:100 — intravenous injection of 0. These tests are often positive with fresh antilymphocyte globulin. periorbital edema. INCIDENCE Anaphylaxis is uncommon.g. Murin monoclonal antibodies are used against tumor antigens in oncology.

C. Y. HUMAN SERUM ALBUMIN Used as a plasma expander. Transplantation. J. Carrington. in plasma exchange and for pulmonary perfusion scan (technetium 99 m labeled human albumin microspheres). Gartner. “Acute serum sickness with glomerulonephritis induced by antithymocyte globulins”. Brentjens. H. Venuto. Cunningham. If necessary. the rest can be administered by slow infusion. 359–387. D. Sullivan. T. J.251 - . Gifford. but the risk of fatal anaphylactic shock remains. desensitization may be performed in patients with positive skin tests. “Serum therapy and immunoprophylaxis”. Boston G. J. Jiang. Start with an intravenous injection of 0.) Clinical Allergy and Immunology. Serum sickness is probable between the 10 and 14th day following desensitization. If a reaction occurs. REFERENCES • • • J. resume treatment at half the dose that caused the reaction. 237. 1987. 43. K. Treat with corticosteroids.1 ml at 1:1000 and then double the dose every 15 to 20 minutes. 309–312. “Reactions to anti-lymphocyteglobulin (ALG)”.. When 1 ml of pure serum is reached. Hall Co. 1984. Earl. 79 (1). . MANAGEMENT Use aged antilymphocyte globulins in patients with negative reactions to the aged products. Immunol.. E. L. Circulating immune complexes underlie serum sickness (IgE antibodies).SERA AND VACCINES MECHANISMS IgE-mediated hypersensitivity underlies immediate reactions. In Altman (ed. Chi. 1987. Allergy Clin. R. 2.

Straughn MA. Hoff RG.252 - . MANAGEMENT Avoidance. urticaria. One third of reactions are life-threatening. IgG anti IgA in IgA-defective patients. Lobel CA.5% and 5%. 85–8. Getz P.. undialyzed and ultracentrifuged HSA 0. Schwartz E. Fruge BC. Complement activation. Ann. Specific IgE (ELISA). 1985. Fadel HE. Allergy 1988.012%. Transfusion. 61 (2). DIAGNOSTIC METHODS Cutaneous testing Intradermal skin tests with undiluted human serum albumin leads to false positive results. 25: 435-6 . Pruritus. Bronchospasm.SERA AND VACCINES INCIDENCE 0. Some authors reported positive skin tests with dialysed. “Anaphylaxis to human serum albumin”. REFERENCES • • Stafford CT. CLINICAL MANIFESTATIONS Anaphylactic shock. MECHANISMS IgE-mediated hypersensitivity is suggested by immediately positive cutaneous tests and evidence of specific IgE. Moffitt JE. Edelman BB. Albumin aggregates (high molecular weight aggregates and some denatured albumin-globulin complexes may form during preparation of albumin solution). “Uneventful plasma exchange with albumin replacement in a patient with a previous anaphylactoid reaction to albumin”.

flushing. Common variable hypogammaglobulinaemia. Severe: anaphylactic shock. INCIDENCE 2 to 6% (rate related). Anti IgA antibodies are found more frequently in patients with combined IgA and IgG2 subclass deficiencies.253 - . and in 20 to 60% of patients with selective IgA deficiency. “Anaphylactoid reaction to human albumin microspheres”. CLINICAL MANIFESTATIONS Occurring one the first or second infusion. Mild: headache. Multiple blood or plasma infusions. Med. nausea. J. muscle pain. Moderate: chest tightness. IgE anti IgA (ELISA) have been reported in patients with anaphylactic shock and IgA deficiency. IgA antibodies are class-specific. abdominal pain. low backache. RISK FACTORS Selective IgA deficiency. DIAGNOSTIC METHODS IgG anti IgA antibodies are detected in a 22% of patients with common variable immunodeficiency. . subclass-specific. antiisoallotypic. antiallotypic. chills. 16 (3): 236-7 INTRAVENOUS IMMUNOGLOBULINS Polyvalent immunoglobulins are used in the treatment of congenital or acquired immunodeficiencies and in the management of some immune disorders.SERA AND VACCINES • Littenberg RL. Nucl. mild wheezing. or of limited specificity. 1975.

Lavi S. Roifman CM. New Eng.6/million doses (life-threatening anaphylactic reactions). 8 (2): 139-44 MEASLES VACCINE Measles vaccine is an attenuated live virus vaccine cultured on chick embryo fibroblasts.254 - . Buckley RH. Wells JV. Drug. Med. 9 (4): 254-62 Burks AW. REFERENCES • • • • Misbah SA. Intensive. Much controversy exists concerning its use in egg-allergic children. “Anaphylactic reactions after gammaglobulin administration in patients with hypogammaglobulinemia”. Lederman HM. Sampson HA. Am. 314 (9): 560–4. J. 1986. Use IgA-depleted intravenous immunoglobulins preparations in patients with high titers of anti IgA antibodies. Presence of IgG or IgE anti IgA in patients with absolute absence of IgA. Care. Anaesth. J.. Gelfand EW.SERA AND VACCINES MECHANISMS Formation of immune complexes between antibodies in intravenous immunoglobulins and microbial antigens in the recipient with subsequent complement activation. Med. “Corticosteroids for prevention of adverse reactions to intravenous immune serum globulin infusion in hypogammaglobulinemic patients”. INCIDENCE < 71. MANAGEMENT Prophylactic use of hydrocortisone and an antihistamine is advisable (first and second infusion). 1980. Safety. King MA.. “Adverse effects of intravenous immunoglobulins”. .. 1993. 81: 443–6. Chapel HM. 1986. “Adverse reactions to human plasma proteins”.

wheezing. Specific IgE to gelatin (immunoblotting. urticaria. whereas 43 non egg-allergic children showed immediate reactions after the immunization. MECHANISMS IgE-mediated hypersensitivity due to the presence of minute quantities of ovalbumin ( 37 to 260 pg). Up to now (1997). . cough. 1326 egg-allergic children who received the Schwarz strain measles vaccine suffered no allergic reactions. DIAGNOSTIC METHODS Cutaneous testing (controversial): patients with or without allergy may have positive skin test reactions to the vaccine and still be safely immunized. fluorimetric ELISA).255 - . Gelatins: numerous papers show a strong relationship between systemic immediate-type allergic reactions to vaccine and the presence of specific IgE to gelatins. Gelatin specific cell mediated immunity: in vitro lymphocyte proliferation assay. Non-immediate mild skin eruptions (several to 48 hours after vaccination).SERA AND VACCINES RISK FACTORS Allergic reactions to food gelatin. UniCAP®/Pharmacia CAP System™. Neomycin: few cases (controversial). Egg allergy: controversial CLINICAL MANIFESTATIONS Anaphylactic shock. MANAGEMENT (CONTROVERSIAL) Measles vaccine containing the Edmoston-Zagreb strain (grown in human diploid cells) has lower immunogenicity than the Schwarz strain grown in a chick embryo fibroblast culture. antigen specific IL 2 responsiveness (non immediate reactions to gelatin). angioedema.

1996. mumps. Clin. REFERENCES • • Bruno G. measles immunization may be routinely administered nner without prior skin testing. Umetsu A. Chiba S. Allergy. Yamanaka T. Kurimoto F. Kimura K. 3/ Measles vaccine or MMR is contraindicated in individuals with a previous anaphylactic reaction to vaccine containing measles . Immunol. “Measles vaccine in egg-allergic children: poor immunogenicity of the Edmoston-Zagreb strain”. Allergy. Novello F. administer the total dose of vaccine. Pediatr.256 - . Inouye S. some doctors perform skin prick-tests with vaccine (1/10).. Kanamura N. J. Ridolfi B.5 ml subcutaneously under medical supervision (30 minutes). Can. 1997. Dis. Saito S. Wataya Y. Commun. 0. Businco L. — if positive administer subcutaneously 0. and varicella vaccines” . Immunization should be performed where adequate facilities are available to manage anaphylaxis. rubella.5 ml (at 15 minute intervals) — if negative perform an intradermal tests with measles vaccine 1/100 if positive. Resp. Furukawa H.05 ml at 1/100. Lucenti P.e. 100: 130-4 National advisory committee on immunization (NACI). 4/ Observation for post measles-vaccine anaphylaxis should be improved. 8: 17-20 Kumagai T. “Gelatin specific humoral and cellular immune responses in children with immediate and non immediate-type reactions to live measles. pure up to a total dose of 0. 1/ 10. Sugawara N. and prospective studies should be initiated to better define the risk in individuals with egg allergy. 2/ egg allergy is not a contraindication to immunization with MMR. At-risk patients should be observed for 30 minutes. proceed in the same way as for a positive prick-test if negative. This protocol is contested by many authors who prefer the following recommendations: 1/ all immunizations should be performed by those capable of managing vaccine-associated anaphylaxis. Immunol. 22 (14): 113-5 • .SERA AND VACCINES In egg-allergic patients. Grandolfo M. 1997. In individuals with a history of anaphylaxis to eggs. i. Ikeda K. Supplementary statement MMR vaccine and anaphylactic hypersensitivity to egg or egg related antigens. Sakaguchi M.

Roberson P. N. mumps. generalized pruritic rash.1992. nausea. DIAGNOSTIC METHODS Cutaneous testing: positive tests to vaccine and mock vaccine. laryngeal edema. “Safe administration of the measles vaccine to children allergic to eggs”. J. fever and malaise. and rubella vaccine”. Eng. type III reactions occurred in 6% of immunized individuals boosted with the current HDC rabies vaccine. J.SERA AND VACCINES • • James J.A. Wood R. 332: 1262-6 Fasano M. Sampson H. arthritis. CLINICAL MANIFESTATIONS Type I: within minutes or hours after a dose of HDCV: bronchospasm.K. Burks A. Specific IgE (immunofluorescence): the specificity of this method has been confirmed by solid phase binding of the vaccine to antigens (19 out of 21 cases of urticaria).A.. Med. “Egg hypersensitivity and adverse reactions to measles.A. .K. urticaria or angioedema. 1995. Cooke S. angioedema. Type III: occurring 2 to 21 days after a dose or doses of HDCV: generalized pruritic rash or urticaria. INCIDENCE 108/100000-87/100000 type III reactions 9/100000 type I reactions In some reports.W. arthralgias. vomiting. Pediatr.B.M.257 - . 120: 878-81 RABIES VACCINE Human diploid cell rabies vaccine is an inactivated vaccine prepared from the rabies virus grown in human diploid cell cultures then dissolved in tributyl phosphate and inactivated a second time with b-propiolactone. RISK FACTORS Booster doses for type III reactions. Sampson H.

5. “Immunologic studies in subjects with a serum sickness-like illness after immunization with human diploid cell rabies vaccine”.11 (14): 1390-4 Swanson MC. 1993. Chin JE. Lyssavac-HDC Berna is safer (no type III hypersensitivity reactions). “Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: a nationwide prospective study”. REFERENCES • • Briggs DJ. J. Rubin M. Boosters should only be administered to risk-group patients The use of the intradermal route for both primary and booster injections may result in lower rates of reactions. Rosanoff E.. The vaccine should be prepared without b-propiolactone (inactivation with formalin or tributylphosphate only). Aoki FY. The principal antigen implicated in the IgE-mediated response is a modified protein component of the vaccine: a b-propiolactone human serum albumin (BPL-HSA) complex formed during preparation of the vaccine. 909–913.258 - . Allergy. Martens CJ. Dreesen DW. Glück R. Wkly. Schnurrenberger P. Briggs DJ. Reed CE. Warrington RJ. Clin.14 (14): 1361-5 Fishbein DB. 1984. 1987. Mehta N. 1987. 1996. “Safety and immunogenicity of Lyssavac Berna human diploid cell rabies vaccine in healthy adults”. Cryz SJ. “IgE and IgG antibodies to beta propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine”. Seedle CD. Type III hypersensitivity. Dis. Dreesen DW. Morgan P. Rep. MANAGEMENT The new HDC rabies vaccine. Deitch M. Immunol. Teplis CF. Gurwith M. 155. Yenne KN. Rutherford WJ.33 (14): 185-7 • • • . Vaccine. Cryz L. J. Vaccine.79: 605-10 Anonymous “Systemic allergic reactions following immunization with human diploid cell rabies vaccine” MMWR Morb. Infect. Some individuals produce a dual reaction (IgG and IgE) against BPL-HSA and fetal calf serum. Mortal.SERA AND VACCINES MECHANISMS Type I hypersensitivity.

Bronchospasm. Specific IgE (controversial) Positive in patients with anaphylaxis but: 50% of infants develop specific IgE antibodies after vaccination. Nasal and ophthalmic pruritus.259 - . Vasculitis. CLINICAL MANIFESTATIONS Anaphylactic shock. . angioedema. INCIDENCE Local reactions after booster injections: pain . False positive and negative are frequent. Glomerulonephritis. Intradermal skin tests positive at 1/10000. Anaphylaxis: 1/million. RISK FACTORS Previous history of reaction to tetanus toxoid. Skin prick tests positive at 1/1000. rashes. However. a few immediate and delayed reactions have been observed. Urticaria. Positive in a few patients with anaphylaxis. DIAGNOSTIC METHODS Cutaneous testing (controversial).SERA AND VACCINES TETANUS TOXOID Tetanus toxoid has been in use for several decades and has proven its effectiveness and safety. 25% of subjects receiving tetanus booster injections have substantial IgE antibodies.30% marked swelling: 2% abscess: 6 to 10/million doses.tenderness: 50 -85% erythema-edema: 20 .

1 2 3 4 5 6 7 8 • • • 0.20 cc 1/1 000 1/100 1/10 1/10 Full strength Full strength Full strength Full strength ID ID SC SC SC SC SC SC At 30 min intervals REFERENCES Piletta PA. Venereol.02 cc 0.260 - . Schmutz JL.02 cc 0. Infect.10 cc 0. 52 (6): 676-7 Barbaud A. Use a tetanus toxoid formulation with a different preservative. 30 (1): 83-4 . Detection of circulating immune complexes in patients with vasculitis MECHANISMS IgE-mediated hypersensitivity: exceedingly rare. “Immediate local reaction to tetanus toxoid booster”.SERA AND VACCINES IgE response to tetanus toxoid is higher in atopic children. Do not overlook the role played by thimerosal and aluminum hydroxide in some reactions. Ann. Dermatol.02 cc 0. “Immunization against tetanus in a hypersensitive individual using a graded dosing regimen (letter)”. Mougeolle JM.15 cc 0. Boyter AC. Saurat JH.05 cc 0. Mac Connachie AM.10 cc 0. MANAGEMENT Obtain an antitetanus IgG titer to verify the need for a booster. Use an isolated tetanus toxoid which has less reactogen than associations (diphtheria/ tetanus) Desensitization has been reported to be effective. “Reactions immunoallergiques cutanées dues aux vaccins”. Hauser C. Allergy. 1995. 1995. 122: 129-38 Uriel AJ. J. Type III reaction (hyperimmunization): there is correlation between circulating tetanus toxoid IgG levels and the degree of local reaction. Nathwani D. Pasche-Koo F. 1997.

“Diagnosis and “desensitization” in tetanus vaccine hypersensitivity”. Ann. “Adverse reactions to tetanus toxoid”. 1994. Meltzer EO. JAMA. 1992.SERA AND VACCINES • • Sutter RW. 271 (20): 1629 Carey AB. 69 (4): 336-8 . Allergy.261 - .

262 - .SERA AND VACCINES .

VITAMINS XII VITAMINS .263 - .

Laplanche G. DIAGNOSTIC METHODS Patch-tests with the cream (ointment is irritant) or better with calcipotriol 10 µg/ml in isopropanol. 123: 196-7 de Groot A.VITAMINS CALCIPOTRIOL Calcipotriol is a vitamin D3 derivative widely used in the treatment of psoriasis. Avoidance in cases of contact allergy. 1-alphahydroxyvitamin D3 and 25-hydroxyvitamin D3. Sometimes delayed contact hypersensitivity. “Eczéma de contact au calcipotriol”. 1994. MECHANISMS Irritation. Dermatol. Cross-reactivity may exist between calcipotriol. MANAGEMENT Cream and solution are less irritant than ointment. Contact allergy (underestimated). “Contact allergy to calcipotriol”. Dermatitis. INCIDENCE High: 20% of patients. Bazex J. 30: 242-3 . Patch-tests with propylene-glycol. 1996. REFERENCES • • Giordano-Labadie F. Ann.264 - . Venereol.. Contact. CLINICAL MANIFESTATIONS Lesional and perilesional irritation.

. RISK FACTORS Intravenous administration. pruritus. Recurrence of allergic reactions to vitamin B12 may occur after ingestion of Marmite (yeast derived extract containing at least 15 µg of cyanocobalamin/100 g). DIAGNOSTIC METHODS Cutaneous testing: usually negative but: — skin-prick tests: positive with pure hydroxocobalamin — intradermal skin-tests: positive at 1/100 to 1/10 dilution in one patient. eczematous rash. CLINICAL MANIFESTATIONS (occurring within weeks or months. INCIDENCE Rare. Deaths reported. No specific IgE found Specific histamine-release: positive in one patient. angioedema. but sometimes after several years of treatment) General: anaphylactic shock Cutaneous: generalized urticaria. Respiratory: bronchospasm.VITAMINS CYANOCOBALAMIN/ HYDROXOCOBALAMIN Vitamin B12 is widely-used as a supplement for patients with ileal malabsorption and those with pernicious anemia.265 - .

. 1997. Genereau T. MANAGEMENT Cross-sensitivity between hydroxocobalamin and cyanocobalamin has been described but is not always found. “IgE-mediated reaction to hydroxocobalamin injection in a patient with pernicious anaemia”. Lancet..T.5 ml pure (500 µg) Oral route may be an alternative. Weyer A. Haematol.F. 1998.. if cutaneous testing shows negative results. Guinnepain M. Lortholary O. Desensitization in patients allergic to both hydroxocobalamin and cyanocobalamin may be performed. cyanocobalamin can be used in increasing intramuscular doses (0.A. REFERENCES • • • • Tordjman R. 339: 1535-6 .H. Lab.1 ml (1/100 = 10 µg/ ml) to 0. Clode M. Contact dermatitis has been reported.VITAMINS MECHANISMS The vitamin itself. 60 (4): 269-70 Branco-Ferreira M. 1 mg). For example with cyanocobalamin: 0. “Anaphylactic reaction to hydroxycobalamin”. Royer I.G. Baumann R. Possible IgE-mediated hypersensitivity (positive cutaneous tests. Allergy. Sager M. Haematol.5mg. 1996. but reactions have been reported and therapeutic efficacy is lower. 1992. Amin S. the preservatives (benzyl alcohol) or some contaminants may be involved. “Reintroduction of vitamin B12 in 2 patients with prior B12-induced anaphylaxis”. 0. Adjunction of corticosteroids or antihistamines may be useful. In patients with hydroxocobalamin allergy. 52 (1): 118-9 Denis R. Casassus P. Palma-Carlos A. Pauli G. due to the cobalt ring contained in this vitamin. Chamouard P. Clin. J.1mg.266 - . Alt M. Guillevin L. Pereira-Barbosa M. “Sensitivity reaction to parenteral vitamin B12: recurrence of symptoms after Marmite ingestion”. Cummins D. specific histamine release). 18 (2): 129-31 de Blay F. Eur. Hirth C.

INCIDENCE 9 deaths reported between 1965 and 1985. urticaria. CLINICAL MANIFESTATIONS General: anaphylactic shock Respiratory: bronchospasm. Digestive: nausea. but only 0. SC). .267 - . itching of palms. MANAGEMENT Administration of parenteral thiamine only when required (thiamine defiency). Thiamine is the most allergenic vitamin. DIAGNOSTIC METHODS Cutaneous testing. abdominal cramps. MECHANISMS Thiamine may act as a hapten (transformation to an azoprotein). RISK FACTORS Multiple large doses. Cutaneous: erythema. Allergic symptoms upon prior administration. IM. A few cases of positive skin prick-tests or intradermal tests (0.1% major reactions and 1% minor local reactions in a large study (1070 consecutive parenteral administrations of thiamine hydrochloride).5 to 5 mg/ ml) Specific IgE and IgG (ELISA). Specific histamine release.VITAMINS THIAMINE (VITAMIN B1) Vitamin B1 or thiamine hydrochloride is used in thiamine deficiency syndromes (cardiovascular beriberi syndrome and central Wernicke-Korsakoff syndrome). Parenteral administration (IV.

K. Barcelo M. INCIDENCE Contact dermatitis is infrequent. J. CLINICAL MANIFESTATIONS Contact dermatitis. DIAGNOSTIC METHODS Cutaneous testing Patch -tests and photopatch-tests: pyridoxine hydrochloride (1% pet). 1992. 1995. photosensitive dermatitis.D.M. “Anaphylaxis to thiamine (vitamin B1)”. Photoallergy is exceptional.268 - . Immunol. Merk H. Allergy. 18: 867-70 VITAMIN B6 Pyridoxine. Ann. Med.. Photoallergy. Emerg. 1997.. 10 (1): 61-3 Wrenn K. “Anaphylaxis from administration of intravenous thiamine”. Clin. Munoz C.M.S. Torrecillas M. 95: 1059-60 Stephen J. Slovis C. “Specific IgE and IgG serum antibodies to thiamine associated with anaphylactic reaction”.. MECHANISMS Delayed hypersensitivity. pyridoxal and pyridoxamine are 3 biologically similar interchangeable compounds referred to as vitamin B6. Yeh C. Blanca M. MANAGEMENT Avoidance.M. Am. Jugert F. Murphy F. Pyridoxine is widely used in the preparation of medications and cosmetics (hair lotion). 1989. . Allergy.F. 52: 958-60 Proebstle T. Emerg. “A toxicity study of parenteral thiamine hydrochloride”. Gall H.. Med.VITAMINS REFERENCES • • • • Fernandez M. Grant R. Sterry W. J.

loss of consciousness. at the injection site (IM or SC) with oil soluble vitamin K1 (phytomenadione) — pseudo-sclerodermatous lesion: from 2 months to 1. Lluch M. Cutaneous: — erythematous plaque like dermatitis: after 4 to 21 days.269 - . J. abdominal pain. 94 cases of cutaneous hypersensitivity reactions to vitamin K up to 1988 (Japan). 1996.02 ml phytomenadione 0. pharmaceutical or veterinary laboratory) — urticaria: one patient after IM injection of vitamin K1. 23 (2): 115 VITAMIN K Vitamin K is mainly used in patients with hypoprothrombinemia. 23 (10): 708-9 Camarasa J. “Contact allergy to vitamin B6”.. pharmaceutical factory. Intradermal skin-tests: 0. Dermatol.05% in NaCl 0.VITAMINS REFERENCES • • Tanaka M. DIAGNOSTIC METHODS Cutaneous testing. .9%. Dermatitis . Niizeki H. “Photoallergic drug eruption due to pyridoxine hydrochloride”. Miyakawa S. 1990. CLINICAL MANIFESTATIONS General (intravenous vitamin K1): anaphylactic shock. Serra-Baldrich E. facial flush. Contact.5 years following administration of vitamin K1 around the injection site — contact dermatitis: occupational handling of vitamin K3 (pig feed. INCIDENCE 52 cases of cutaneous hypersensitivity reactions to vitamin K from 1964 to 1995 (Europe and North America). Shimizu S.G.

Dermatol. Cross-reactivity between vitamin K3 and K4 has been described. vitamins K1. intradermal skin-tests are usually positive in erythematous plaque-like dermatitis and pseudo-sclerodermatosis lesions.1% in pet. “Hypersensibilité cutanée au point d’injection de vitamine K1". could be the antigenic site.. 1996.VITAMINS Patch-tests: phytomenadione 0. When administered orally. Prefer oral and water-soluble formulations of vitamin K Slow infusion of vitamin K1 diluted in a physiological solution may decrease the rate of anaphylactic reactions. K3.270 - . MANAGEMENT Vitamin K exists in 4 different pharmacological forms: — vitamin K1 (phytomenadione): naturally occurring form (oil soluble) — vitamin K2 (menaquinone): synthesized by bacteria in intestine — vitamin K3 (menadione): synthetic analogue (oil soluble) — vitamin K4 (menadiol): synthetic analogue (water soluble). Ann. Giordano-Labadie F. Bazex J. REFERENCES • Moreau-Cabarrot A. Type IV hypersensitivity (positive patch-tests). but not between vitamin K1 and other vitamin K derivatives. spongiosis. The phytyl moiety contained in phytomenadione. Patch-tests are positive in contact dermatitis. Venereol. and K4 do not result in skin disease. intraepidermal vesiculation. 123 (3): 177-9 . MECHANISMS Cremophor EL used in some countries as a solvent for intravenous formulation of vitamin K1 is thought to be the culprit in anaphylactoid reactions. but not in other forms of vitamin K.03% and 0. Skin-biopsy: erythematous plaque like lesions: parakeratosis.

L. Contact. Folkers E.J. Morales-Olivas F. Dermatitis. 32 (2): 78-82 Lemlich G. “Cutaneous reactions to vitamin K1 injections”. Am. Green M. Don P..271 - . Lebwohl M. Gordon M. Hebeda C. J. DICP. Dermatol. 25 (7-8): 871-2 . 28 (2. Phelps R.2): 345-7 Martinez-Abad M. Bruynzeel D. 1991. “Vitamin K1 and anaphylactic shock”. Palop V.P. Acad.VITAMINS • • • Bruynzeel I. “Cutaneous hypersensitivity reactions to vitamin K: 2 case reports and a review of the literature”. 1995. Delgado F. 1993.

272 - .VITAMINS .

MISCELLANEOUS XIII MISCELLANEOUS .273 - .

MANAGEMENT Non life-threatening anaphylactoid reactions to intravenous Nacetylcysteine are easily treated: flushing requires no treatment. Intravenous use (no report following oral administration). Respiratory: bronchospasm (sometimes in asthmatic patients by intravenous or inhalation route). fever (inhalation therapy). INCIDENCE 0. urticaria should be treated with antihistamines. Direct non immunological histamine release.MISCELLANEOUS ACETYLCYSTEINE Intravenous acetylcysteine is the treatment of choice for acetaminophen poisoning and more recently for anticonvulsantinduced hypersensitivity syndrome. DIAGNOSTIC METHODS None. urticaria. pruritus. MECHANISMS Hypotension seems to result from a vasodilator action on resistance vasculature (dose-dependent). Cutaneous: rash.274 - . angioedema and . angioedema. N-acetylcysteine is a known precursor of glutathione involved in detoxification from several drugs. Deaths reported (overdose is likely). CLINICAL MANIFESTATIONS (occurring 20 minutes after starting of treatment) General: anaphylactic shock. RISK FACTORS Overdose.2 to 3% of courses of intravenous acetylcysteine.

Dermatol. Ann.N. INCIDENCE 2% of users develop a mild cutaneous rash.F. Tempowski J. Med.275 - .. Sever P.C. Volans G. 1998. “Hazards of therapy with high doses of N-acetylcysteine for anticonvulsant-induced hypersensitivity syndrome”. 1998. Mc Guigan M. Med.A. “Anaphylactoid response to intravenous acetylcysteine”. Br. Allopurinol hypersensitivity syndrome: 100 cases described in the literature (1993) Mortality: 27% (allopurinol hypersensitivity syndrome). 1992. “Anaphylactoid reaction to intravenous acetylcysteine associated with electrocardiographic abnormalities”. Hulisz D. Oral methionine and mercaptamine may be used as alternative antidotes. Talbot J. 138 (3): 553 Sunman W. Vereecken P. N-acetylcysteine should be stopped but can be started again one hour after administration of antihistamines. Ann. Emerg. In cases of angioedema and respiratory symptoms. Severe reaction: 1/260. 26 (1): 22-5 Mant T. Traeger S. J.G. 31 (6): 710-5 Simonart T. RISK FACTORS Impaired renal excretion. 1984.. “Adverse reactions to acetylcysteine and effects of overdose”. 1992. J. Martin B. 339 (8803): 1231-2 Bonfiglio M.H.4-d) pyramidine) is the drug most commonly prescribed for the treatment of hyperuricemia.R. 289 (6439): 217-9 ALLOPURINOL Allopurinol (4 hydroxypyrazolol (3. Tugendhaft P..D.M. REFERENCES • • • • • Bailey B. Thiazide diuretics (co-administration). Hughes A. Lancet. .T.. Pharmacother.S. de Dobbeleer G. Br. “Management of anaphylactoid reactions to intravenous N-acetylcysteine”. Heenen M.MISCELLANEOUS respiratory symptoms require antihistamines and symptomatic therapy.

2— Clinical picture including: a) at least 2 of the major criteria — worsening renal function (84%) — acute hepatocellular injury (88%) — rash (93.7%) erythema multiforme (8. exfoliative dermatitis (20.276 - . focal necrosis of hepatocytes.9%). DIAGNOSTIC METHODS Skin-biopsy: granular deposits of IgM at the dermal-epidermal junction.8%) OR b) one of the major criteria + at least one of the minor criteria — fever (95%) — eosinophilia (60%) — leukocytosis (40%) AND 3— Lack of exposure to another drug which may have caused similar clinical manifestations.1%): toxic epidermal necrolysis (25.5%). Renal-biopsy: linear deposits of IgG and complement along the glomerule basement membrane.MISCELLANEOUS CLINICAL MANIFESTATIONS (developing days or weeks after initiation of treatment) Criteria for diagnosis: 1— Clear exposure to allopurinol. Liver-biopsy: T lymphocyte infiltration. Lymphocyte stimulation test: positive with oxypurinol but not allopurinol in 3 patients with allopurinol hypersensitivity syndrome. diffuse maculopapular rash (53. C3 deposits along tubular basal membrane. mesangium and arterioles. . granulomas.

277 - . Allopurinol should only be prescribed in good indications: — primary gout with tophi or uric acid stones (over production) — uric acid stones or calcium oxalate stones without gout combined with increased urinary excretion of urate — secondary renal gout with tophi — myeloproliferative diseases or other malignancies — high frequency of attacks despite colchicine prophylaxis — intolerance to uricosuric agents — Lesch-Nyhan syndrome — Von Gierke disease . Allopurinol dose must be adjusted to renal function. T cell-mediated immune reaction could be involved in the pathogenesis of allopurinol hypersensitivity syndrome. Generalized vasculitis (formation of immune complexes that precipitate in the vascular endothelium and lead to complement activation and development of inflammatory reactions in and around arteriolar walls). 3— Type III hypersensitivity reactions. MANAGEMENT Asymptomatic hyperuricemia is not an indication of allopurinol prescription. Consumption of complement.MISCELLANEOUS MECHANISMS 1— Allopurinol accumulation. 2— Type IV hypersensitivity reactions. The risk of development of allopurinol hypersensitivity syndrome is related to the level of oxypurinol (metabolite of allopurinol). circulating immune complexes and deposition of antibodies in different organs. The accumulation of oxypurinol leads to tissue damage with development of antibodies against tissue components and formation of immune complexes.

100 mg at 30 minute intervals Desensitization can give life-threatening reactions. 25 mg.F. 1mg Day 6: 2 mg. Mizutani H.1): 286-7 Hamanaka H. J. Sastre J.Intravenous desensitization (when oral desensitization fails. 400 µg Day 5: 600 µg.MISCELLANEOUS Desensitization 1. chronic tophaceous gouty arthritis) Day 1 to 3: 50 µg Day 4 to 6: 100 µg Day 7 to 9: 200 µg Day 10 to 12: 500 µg Day 13 to 15: 1 mg Day 16 to 18: 5 mg Day 19 to 21: 10 mg Day 22 to 24: 25mg Day 25 to 27: 50 mg Day 28 and nexts: 100 mg 3. Clin. 60 µg Day 3: 70 µg. Exp. 20 µg. 800 µg. 52 (3): 107-10 Umpierrez A.278 - . Dermatol. 200 µg. Med. Lluch-Bernal M. 2 mg. “The allopurinol hypersensitivity syndrome”... 5 mg.Fixed drug eruption (50 mg of allopurinol powder dissolved in 500 ml of distilled water with 14/1000 sodium bicarbonate) Day 1: 10 µg.J. 23 (1): 32-4 . Cuesta-Herranz J. 90 µg Day 4: 100 µg. in less than 12 hours) — 0. 1998. 1 µg. 35 mg Day 8: 50 mg Day 9: 75 mg Day 10: 100 mg Day 11: 125 mg Day 12: 150 mg Day 13: 175 mg Day 14: 200 mg Day 15: 250 mg Day 16: 300 mg 2. Shimizu Y. 50 µg. Van Deuren M. 80 µg. 50 mg. Wetzels J. 100 µg.1 µg. Shimizu M. REFERENCES • • • Pluim H. 101 (2. 1998. 1998. 10 µg. de las Heras M. Clin. J. Neth. 50 µg. “Successful desensitization of a fixed drug eruption caused by allopurinol”. 4 mg. “Allopurinol hypersensitivity syndrome: hypersensitivity to oxypurinol but not allopurinol”. 500 µg at 15 minute intervals — 1 mg. 8 mg Day 7: 16 mg. 20 mg. Allergy. Figueredo E. Immunol. 10 mg. 30 µg Day 2: 40 µg.Oral desensitization in minor rashes (renal insufficiency.. Nouchi N.

CLINICAL MANIFESTATIONS (occurring one week to 3 months (average 4 weeks) after starting therapy) Carbamazepine hypersensitivity syndrome: fever + lymphadenopathy (pseudolymphoma syndrome) + generalized rash.L. INCIDENCE Cutaneous reactions: 3 to 16%. Ann. Beswick T. eosinophilia. trigeminal neuralgia and affective disorders. exfoliative dermatitis. 1994.MISCELLANEOUS • • • Braden G. Immunol.A. Respiratory: cough. purpura. dyspnea. 1987. Ophthalmic: conjunctivitis. agranulocytosis. lymphopenia. erythema multiforme.T: pharyngitis. edema of the face. “Desensitisation to allopurinol”. . Blake D. Struthers G. hepatitis Renal: acute tubulointerstitial nephritis.N. Stevens-Johnson’s syndrome: 1/5000 to 1/10000. 27 (3): 337-43 Kelsey S.. Ballow M. Cutaneous: macular or maculopapular rash. erythroderma. Sacristan J. 46 (1): 84 CARBAMAZEPINE Carbamazepine is a drug widely used in the treatment of epilepsy. glandular fever-like syndrome.R.. E. Ann. “Cell-mediated immunity in allopurinol-induced hypersensitivity”.R. toxic epidermal necrolysis. hypersensitivity vasculitis. Rheum. Hematological: leukocytosis. 70 (2): 145-51 Arellano F. leukopenia. hands and feet. Clin. Other: serum sickness. Immunopathol. systemic lupus erythematosus-like syndrome. Golightly M. 1993. Warzynski M. hypersensitivity vasculitis. Pharmacother. eczematoid dermatitis.. thrombocytopenia. aplastic anemia.279 - . Kawasakilike syndrome.M.J. “Allopurinol hypersensitivity syndrome: a review” . pneumonitis. Dis. urticaria. necrotizing granulomatous vasculitis. Digestive: hepatosplenomegaly.

MANAGEMENT Systemic corticosteroids are recommended in the management of carbamazepine hypersensitivity syndrome. REFERENCES • • Morkunas A. 13 (4): 727-39 de Vriese A.1% in pet.R. Miller M. de Cuyper C. Cross-reactivity between carbamazepine. Louagie A.MISCELLANEOUS DIAGNOSTIC METHODS Cutaneous testing.280 - . Haye’s patch-tests chambers: carbamazepine 100%.M. “Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature”. The results of the patch-tests and lymphocyte transformation tests indicate the presence of a specific T-cell reactivity. Care. Van Renterghem D. Crit. Clin. MECHANISMS Highly reactive arene oxide or epoxide metabolites formed by cytochrome P 450. Medicine (Baltimore). 1997. Patch-tests. Hindryckx P.S. phenytoin. 10%. production of numerous auto-antibodies. Presence of immunosuppressive cytokines. 1995. “Anticonvulsivant hypersensitivity syndrome”. Matthys E.A. deposits of immune complexes in the skin..H. jelly and in acetone: positive in patients with carbamazepine hypersensitivity syndrome. 1% and 0. Desensitization is possible (isolated skin rash).B.G. Lymphocyte transformation test : positive in patient with carbamazepine hypersensitivity syndrome. and phenobarbital is common. or other metabolites formed by myeloperoxidase bind to tissue macromolecules causing cell damage or act as haptens and elicit an immune response. Philippe J. Anticarbamazepine antibodies have been detected. 74 (3): 144-51 .

Cross-reactivity with chlorpromazine may occur. Guze B.M. Park B. Shah B. Roberts P. Graham A. erythematous and confluent) involving face. 1996.. DIAGNOSTIC METHODS Lymphocyte transformation test: one positive case in a patient with parotitis.281 - . Smith D.MISCELLANEOUS • Pirmohamed M. Biol. J. MECHANISMS Unknown. 1991. 40 (11): 1185-6 . Clin.. Chadwick D. trunk Photosensitivity. MANAGEMENT Avoidance. Parotitis. CLINICAL MANIFESTATIONS Urticarial rash (maculopapular. Br.05%. Psychiatry. “Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine”. Myocarditis. Breckenridge A. REFERENCES • Kuintana J. neck. INCIDENCE 0. Pharmacol.K. Agranulocytosis. “Clozapine-chlorpromazine allergic crossreactivity in a psychotic patient with asymptomatic AIDS”. 32 (6): 741-9 CLOZAPINE Dibenzodiazepine used as an alternative treatment for refractory psychotic patients.

“Photosensitivity to clozapine”. pharyngeal irritation. dry mouth. CLINICAL MANIFESTATIONS Anaphylactic shock: 3 cases published. 56 (12): 589 Goumemiouk A. Psychiatry. “A case of drug interaction involving clozapine”. Schreiber W. Am. INCIDENCE About 20 cases reported in the literature. Skin prick-tests (10 mg/ ml): positive in a few patients. Mac Ewan G. Losonczy M. Becker E. J. One death (bronchospasm). myositis. 1995. Psychiatry. J. . 153 (6): 840 Howanitz E. 36: 234 CROMOLYN/SODIUM CROMOGLYCATE/DSCG Disodium cromoglycate or cromolyn. Rhinitis. Specific IgE (RAST) by spontaneous binding of DSCG to human serum albumin (one case). Differentiate from dermatitis.W..D. gastroenteritis (2% of patients) and cough. Stein G. urticaria. “Clozapineinduced parotitis: an immunological cause ?”. Intradermal skin tests (10 mg/ ml): positive with syndromic reaction in one case. Psychiatry. 1996. Ancill R. mild transient bronchospasm (attributed to local irritant effects of the powder on hyperreactive airways). Clin.W. Can. Pollmacher T. conjunctivitis. 1991. DIAGNOSTIC METHODS Cutaneous testing.J.282 - .. available since 1973 is an antiasthmatic/ antiallergic drug acting as a mast cell stabilizer. J. Pardo M. Bronchospasm: one death reported.MISCELLANEOUS • • • Hinze-Selch D.

MISCELLANEOUS

Conjunctival challenge test (20 mg/ ml). Bronchial challenge (20 mg/capsule).

MECHANISMS
IgE-mediated hypersensitivity (positive skin tests, passive transfer, specific IgE). DSCG is a weak hapten (only hydrogen bonds can be found between drug and host cells or tissue).

MANAGEMENT
Avoidance.

Allergic sensitization may disappear with the time. REFERENCES
• • • • Ibanez M.D, Laso M.T, Martinez-San Irineo M, Alonso E, “Anaphylaxis to disodium cromoglycate (see comments)”, Ann. Allergy. Asthma. Immunol., 1996; 77 (3): 185-6 Shearer W.T, “Anaphylaxis to disodium cromoglycate (editorial)”, Ann. Allergy. Asthma. Immunol., 1996; 77 (3): 165 Mansfield L.E, “Disappearance of allergic reaction to cromolyn (cromoglycate) by avoidance and then reintroduction”, J. Asthma., 1991; 28 (6): 447-50 Wass U, Plaschke P, Bjorkander J, Belin L, “Assay of specific IgE antibodies to disodium cromoglycate in serum from a patient with an immediate hypersensitivity reaction”, J. Allergy. Clin. Immunol, 1988; 81 (4): 750-7

DEFEROXAMINE
Specific iron chelating agent used in the treatment of hemochromatosis and acute iron poisoning.

INCIDENCE
High.

- 283 -

MISCELLANEOUS

CLINICAL MANIFESTATIONS
General: anaphylactic shock Respiratory: bronchospasm, hypersensitivity pneumonitis, laryngospasm. Cutaneous: pruritus, urticaria.

DIAGNOSTIC METHODS
Cutaneous testing: false positive. No IgE antibodies excepted in lung biopsies.

MECHANISMS
Direct non-immunological activation of the dermal mast cells (subcutaneous route).

MANAGEMENT
Numerous desensitization protocols have been published in adults and children; by intravenous or subcutaneous route. For example in adults: Starting with a dose of 0.015 mg in 50 cc for 30 minutes, gradually increase (6 hours) to 1 500 mg in 50 cc for 30 minutes. Then administer 1 500 mg per day by continuous infusion for 4 days. Then 1 500 mg per 12 hours for 2 weeks. Finally, 1 500 mg every 2 days. High dose intravenous deferoxamine delivery is highly effective, but can lead to severe hypersensitivity pneumonitis. Other iron chelators (oral deferiprone) are under clinical evaluation.

REFERENCES
• • La Rosa M, Romeo M.A, Di Gregorio F, Russo G, “Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia”, J. Allergy. Clin. Immunol, 1996; 97: 127-8 Lombardo T, Ferro G, Frontini V, Percolla S, “High dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration”, Am. J. Hematol., 1996; 51 (1): 90-2

- 284 -

MISCELLANEOUS

• • •

Shalit M, Tedeschi A, Miadonna A, Levy-Shaffer A, “Desferal (desferrioxamine)-a novel activator of connective tissue-type mast cells”, J. Allergy. Clin. Immunol, 1991; 87: 854-60 Bousquet J, Navarro M, Robert G, Aye P, Michel F.B, “Rapid desensitization for desferrioxamine anaphylactic reaction”, Lancet., 1983; ii: 859-60 Miller K.B, Rosenwasser L.J, Bessette J.M, “Rapid desensitization for desferrioxamine anaphylactic reaction”, Lancet., 1981; i: 1059

D. PENICILLAMINE
D. Penicillamine is the product of acid hydrolysis of penicillin. It is used in the treatment of rheumatoid polyarthritis, Wilson’s disease, scleroderma, cystinuria, and heavy metal poisoning.

INCIDENCE
High. 50 % of patients will have an adverse drug reaction during the first 6 months of therapy (600 mg/day) and about 1/4 to 1/3 will discontinue therapy.

CLINICAL MANIFESTATIONS
Cutaneous: maculopapular and pruriginous eruptions, urticaria (early), autoimmune bullous syndrome almost of pemphigus type and rare but severe cicatricial pemphigoides (late), contact allergy (eye drops). Renal: glomerulonephritis with membrane proliferation. Hematological: neutropenia, thrombocytopenia, aplastic anemia. Autoimmune: myasthenia, polymyositis, dermatomyositis, lupus, Goodpasture’s syndrome. Respiratory: obstructive bronchiolitis, pneumonitis, asthma.

DIAGNOSTIC METHODS
No in vivo or in vitro diagnostic methods are currently available, other than the lymphocyte stimulation test which may be positive in some cases of glomerulonephritis and polymyositis.

- 285 -

MISCELLANEOUS

Patch-tests (penicillamine 0.15 M aq.): positive in contact allergy. D. penicillamine-induced pemphigus generally has a lower prevalence of tissue-fixed or circulating antibodies than spontaneous pemphigus.

MECHANISMS
Unknown.

MANAGEMENT
If severe glomerulonephritis occurs, do not attempt to re-administer unless no other therapeutic option is available. If use is absolutely necessary, first perform the following desensitization to avoid risk of severe delayed reactions: — first week: 1/ 100th of the total dose — second week: 1/ 10th of the total dose — third week: 1/3 rd of the total dose — fourth week: total dose. Should kidney dysfunction or other severe manifestations develop, discontinueD.penicillamine and give 40 to 80 mg of prednisone/ day. In Wilson’s disease, alternative treatments are trientine and zinc; desensitization can be performed as follows: — day 1: prednisone 30 mg — day 3-4-5: D. penicillamine 125 mg — day 6-7-8: D.penicillamine 250 mg — day 9-10-11: D. penicillamine 375 mg — day 12-13-14: D.penicillamine 500 mg — day 15-16-17: D.penicillamine 750 mg — day 18 and subsequently: D.penicillamine 1 g. If a patient allergic to penicillin requires treatment with D.penicillamine, start with 1/ 1000th of the total dose then 3 to 10 times more every 30 minutes (although no cross-reactivity has been clinically demonstrated between penicillin and D. penicillamine).

- 286 -

MISCELLANEOUS

REFERENCES
• • • • Bialy-Golan S, Brenner S, “Penicillamine-induced bullous dermatoses”, J. Am. Acad. Dermatol., 1996; 35:732-42 Chan C.Y, Baker A.L, “Penicillamine hypersensitivity: successful desensitization of a patient with severe hepatic Wilson’s disease (see comments)”, Am. J. Gastroenterol., 1994; 89 (3): 442-3 de Moor A, Van Hecke E, Kestelyn P, “Contact allergy to penicillamine in eye drops”, Contact Dermatitis, 1993; 29 (3): 155-6 Matsumura T, Yuhara T, Yamane K, Kono I, Kabashima T, Kashiwagi H, “D. penicillamine-induced polymyositis occurring in patients with rheumatoid arthritis: a report of 2 cases and demonstration of positive lymphocyte stimulation test to D penicillamine”, Henry Ford Hosp. Med. J, 1986; 34: 123-6 Jaffe I.A, “Adverse effects profile of sulfhydryl compounds in man”, Am. J. Med, 1986; 80: 471-6

FACTOR VIII
Recombinant factor VIII products are used in the treatment of hemophilia.

INCIDENCE
0.1 to 0.75% (rashes).

CLINICAL MANIFESTATIONS
General: anaphylactic shock. Cutaneous: erythematous or urticarial rashes.

DIAGNOSTIC METHODS
Specific IgE (Intermediate purity factor VIII concentrates).

MECHANISMS
IgG 4 antibodies to bovine factor VIII? IgE-mediated hypersensitivity? Antibodies against human serum albumin? Ethyleneoxide allergy?

- 287 -

MISCELLANEOUS

MANAGEMENT
Premedication with antihistamines and corticosteroids. Desensitization.

REFERENCES
• • • • Shopnick R.I, Kazemi M, Brettler D.B, Buckwalter C, Yang L, Bray G, Gomperts E.D, “Anaphylaxis after treatment with recombinant factor VIII” , Transfusion., 1996; 36: 358-61 Bove J.R, “Anaphylactic reaction to purified anti-hemophilic factor concentrate (letter)”, Transfusion, 1988; 28: 603 Jamieson D.M, Stafford C.T, Maloney M.J, Lutcher C.L, “Desensitization to factor VIII in a patient with classic hemophilia and C2 deficiency”, Ann. Allergy., 1987; 58: 215-20 Shakib F, Stanworth D.R, “IgG 4: a possible mediator of anaphylaxis in a haemophiliac patient”, Clin. Allergy., 1979; 9: 597-603

HYDROXYZINE
Hydroxyzine hydrochloride is a piperazine derivative, structurally based on a dimer of ethylenediamine and possessing antihistaminic and anticholinergic activity.

INCIDENCE
Rare.

RISK FACTORS
Positive patch-tests to ethylenediamine.

CLINICAL MANIFESTATIONS
Cutaneous: urticaria, eczema, fixed drug eruption (oral or genital mucous membrane, after 6 hours or more), systemic contact dermatitis (baboon syndrome, vesicular hand eczema, toxico derma-like rash).

- 288 -

REFERENCES • • • • Stingeni L. Contact. Patch-tests with hydroxyzine 2%. Drug re-challenge. Ricci F..289 - . MECHANISMS The drug may act as a hapten and bind to protein components or receptor cells of the lower dermis. 10% aq. MANAGEMENT Cross-reactions among ethylenediamine. hydroxyzine. Harel L. Matalon A. “Systemic contact dermatitis to hydroxyzine”. This complex is similarly presented to the Langherans cells as in contact dermatitis (fixed drug eruption).J. patients sensitive to hydroxyzine are also sensitive to ethylenediamine. 37 (5): 24950 Michel M. 1997. 1997. 5%.F (macrophage migration inhibitory factor): positive in some cases of fixed drug eruption. Agostinelli D. “Skin reactions to hydroxyzine”. 1997. M. “Maculopapular and urticarial eruption from cetirizine”.. Leroy D. Dermatitis.I. 31 (3): 327-9 LATEX Natural latex is extracted from the Hevea brasiliensis tree and is used to produce rubber (latex + low molecular weight chemical . Dermatitis.. Louvet S. Contact. Castel B. Szczurko C. Pharmacother. Generally. 36 (3): 147-9 Ash S. Scheman A. Barzilai A. “Fixed drug eruption of the penis due to hydroxyzine hydrochloride”.MISCELLANEOUS DIAGNOSTIC METHODS Cutaneous testing. and cetirizine are influenced by sensitivity to diethylenediamine (common piperazinic ring). Ann. 1997. Contact. Dermat. 8 (1): 2-5 Cohen H. Am. Lisi P. J.A. Dompmartin A. Caraffini S. Gross S.

290 - . Ophthalmologic: conjunctivitis. Anaphylactic shock has been reported during gynecological examinations or after dental work (latex cofferdams). . angioedema. Anaphylactic shock may occur while putting latex gloves on. CLINICAL MANIFESTATIONS General: perioperative anaphylactic shock usually occurs more than 15 minutes after induction of anesthesia. contact dermatitis or urticaria.The first manifestation described in 1927 was the case of a chronic urticaria due to a dental prosthesis made with latex. balloons. Contact dermatitis or urticaria due to glove wearing is observed in 6% of the medical and paramedical operating room staff. In children: spina-bifida and multiple surgical procedures. The first symptom is rash or urticaria followed 2 or 3 minutes later by severe collapse with or without bronchospasm requiring blood volume expansion and adrenaline. Occupational contact. Fruit allergy.N. Cases of anaphylactic shock due to glove wearing were reported from 1987. cofferdams used in dentistry. Cutaneous: flush. INCIDENCE 20% of the anaphylactic shocks occurring during general anesthesia. caps. condoms. RISK FACTORS Atopy (70% of cases).MISCELLANEOUS additives). face masks. Latex sensitization (majority without clinical manifestations) is found in 1-6 % of the general population. Main products: household and surgical cloves.T: rhinitis. E. Respiratory: asthma.

Often detected in patients with anaphylactic shock Nasal or bronchial provocation tests. specific histamine release). carba mix. latex or extracts from Hevea brasiliensis leaves. At present.MISCELLANEOUS DIAGNOSTIC METHODS Cutaneous testing. metal salts). MANAGEMENT — Avoiding thr use of powdered latex gloves reduces the risk of latex sensitization and clinical symptoms. Prick. . rule out sensitivity to rubber additives (patch-tests with rubber mix. intradermal. PPD mix. kiwi. Prick and intradermal skin-tests are positive in case of anaphylactic shock due to surgical gloves. specific IgE. MECHANISMS IgE-mediated hypersensitivity (immediate positive skin-tests. — Avoid any systematic preoperative testing in a non at-risk po pulation. — Use of non latex gloves and “latex-free” operating room for allergic patients under surgery. naphtyl mix. Specific latex IgE antibodies (UniCAP®/Pharmacia CAP System™ and other methods). avocado.291 - . tomato). — Avoid mentioning “hypoallergenic gloves”. In patients who develop contact dermatitis after wearing gloves. — Careful medical questionnaire before any surgical procedure. chestnut. The role of several identified proteins (Hev1-7) was shown and may explain some cross-reactivity with fruits (banana. and scratch skin tests with the supernatant of the preparation used to make latex gloves. Delayed-type allergy in contact dermatitis. prick-tests can be performed with commercial standardized natural latex extract. patch.

Charpin D. 1998... 1997. Temporary hypotension: 1%. INCIDENCE Uncommon. Mäkinen-Kiljunen S. Cutaneous: flushing. 51: 593-602 Laxenaire M. Clin. Charpin D.C et le groupe d’étude des réactions anaphylactoïdes peranesthesiques. Camboulives J. “Latex and food allergy”. “Prevalence of latex sensitization in subjects attending health screening: implications for a perioperative screening”. 27: 413-17 Turjanmaa K. Allergy. “Natural rubber latex allergy”. Didelot R. Lemiere C. Anesthesiology. Birnbaum J.A. “Latex allergens: a review” . Reunala T. facial edema. 1996. Palomo T.A. Birnbaum J. “Association between latex sensitization and repeated latex exposure in children”. Lantaume A. Clin. Exp. Charpin D. Guilloux L. Allergy. Lanteaume A. Alenius H. Vervloet D. 47: 579-87 • • • LDL APHERESIS Low density lipoprotein apheresis is used in the treatment of severe familial hypercholesterolemia and advanced coronary heart disease. Exp. Anesth. Baur X. Lemiere C. Allergol. bradycardia. Vervloet D. “Substances responsables des chocs anaphylactiques peranesthesiques. 37: 1188-94 Porri F. RISK FACTORS Concomitant use of ACE inhibitors. Troisième enquête multicentrique française (1992-1994)”. 28: 134-40 Levy D. CLINICAL MANIFESTATIONS General: hypotension.292 - . Reanim. Allergy. Allergy.. 1997. Vervloet D. Pradal M. Fr. Chen Z. Raulf-Heimsoth M. Rev. 1996.L. 1992. Leynadier F. Mege J. Leynadier F. Ann. 86 (3): 597-602 Porri F. 15: 1211-8 Levy D. 1997. fr.MISCELLANEOUS REFERENCES • • • • Posch A. “Allergy to latex”. Pecquet C. .

“Anaphylactoid reactions.F. dextran sulphate is a potent activator of the contact activation system (Hageman factor. Nagano T. 340 (8824): 908-9 • • • • .A.A. coagulation factor XI). 1993. Lancet. “Anaphylactoid reactions and bradykinin generation in patients treated with LDL-apheresis and an ACE inhibitor”.293 - . Transplant. Bradykinin is a potent vasodilator and smooth muscle constrictor in bronchi and intestine.. Kagasawa K. Bradykinin catabolism is decreased by ACE inhibitors. 1997. MANAGEMENT Withdraw captopril 24 hours before treatment. LDL apheresis with dextran sulphate is associated with increased bradykinin generation. high molecular weight kininogen. Lancet. Digestive: nausea. Riester U. Lancet. 12 (5): 1083-4 Koga N. 1992. MECHANISMS Because of its strong negative charges. “ACE inhibitors and LDL-apheresis with dextran sulphate adsorption”. Kiral A. Kroon A. Sato T. 340 (8833): 1476 Olbricht C. REFERENCES • Schwarzbeck A. “Anaphylacotid reactions during dextran apheresis may occur even in the absence of ACE-inhibitor administration”. 1993. Mol M. Kiral A. abdominal pain..J. Nephrol. Rambausek M. Bahr F.MISCELLANEOUS Respiratory: dyspnea. Kallikrein generates bradykinin from high molecular weight kininogen. ASAIO J. Grutzmacher P. 39 (3): M288-91 Keller C. Schwarzbeck A. Dial. No reaction is observed when futhan is used instead of heparin (protease inhibitory activity of futhan). Hilgenfeldt U.J. 341 (8836): 60-1 Kroon A. Schaumann D. “LDLapheresis with dextran sulphate and anaphylactoid reactions to ACE inhibitors”. Fischer D. and ACE inhibitors”. prekallikrein. 1992. Stalenhoef A. LDL apheresis with dextran sulphate.

M. REFERENCES • Mira-Perceval J.6 . laryngeal stridor. gastroesophageal reflux and hypersecretory states. 97: 855 .A. Sarrio F. belonging to the group of imidazole derivatives. MECHANISMS IgE-mediated hypersensitivity (positive skin tests. Ortiz J.D. Allergy. Clin. Immunol. Lopez-Sanchez J. 1996. Pagan J. INCIDENCE One case reported.J.L. Hernandez J.294 - . NegroAlvarez J.C. Used in the treatment of gastric and duodenal ulcers. Cutaneous: urticaria. Intradermal skin tests: positive at 1/10000 to 1/1000. positive oral challenge). CLINICAL MANIFESTATIONS General: anaphylactic shock Respiratory: dyspnea.. Garcia-Selles F. Skin prick-tests: 10 mg/ ml: negative.L.MISCELLANEOUS NIZATIDINE Specific H2 receptor antagonist. Miralles J. Oral challenge test. DIAGNOSTIC METHODS Cutaneous testing. angioedema of lips and tongue. MANAGEMENT No cross-reactivity found with other anti H2 drugs (oral challenge). “Nizatidine anaphylaxis”. J.

Phaff R.5% of patients). Drug re-challenge MECHANISMS Unknown. 15: 36 .. J.5 .A.R.H. REFERENCES • • • • Ottervanger J.M. “Anaphylaxis to omeprazole”.295 - .. Contact Dermatitis. urticaria. INCIDENCE Uncommon (skin inflammation. angioedema (2 cases).adenosine triphosphatase. Allergy. Vermeulen E. 1994.R. B. Clin. “Contact allergy to omeprazole”. Cutaneous: rashes.A.1. Hematological: thrombocytopenia. urticaria. 1986. DIAGNOSTIC METHODS Cutaneous testing.P.MISCELLANEOUS OMEPRAZOLE Omeprazole reduces acid gastric secretion by specific binding to the parietal cell proton pump H+/ K+. Dickens G. 14 (1): 119-22 Haeney M.. Prick-tests (4 mg/ ml) positive in one patient who experienced anaphylactic shock. epidermal necrolysis. CLINICAL MANIFESTATIONS General: anaphylactic shock (one case). alopecia and dry skin have been reported in 0. Stricker B.. pruritus. 1992.G. contact dermatitis. 1996. Pharmacotherapy. “Angioedema and urticaria associated with omeprazole” . Immunol. “Angioedema and urticaria associated with omeprazole confirmed by drug re-challenge”.J. 97: 1413-4 Bowlby H. 305: 870 Meding B. MANAGEMENT Eviction.

1 to 4 weeks after starting the therapy (when re-challenge within hours). myalgias. INCIDENCE 22 patients with local cutaneous reactions to intravenous phenytoin (1991). leukopenia.296 - . rhabdomyolysis Mortality 18 to 40% when liver is involved. Autosomal pattern of inheritance. Cutaneous reactions to phenytoin up to 19% (maculopapular rash). anemia. 1/1000 to 1/10000 exposures (phenytoin hypersensitivity syndrome). extremities. — fever (90 to 100%) — rash (90%): exanthema +/.pruritus involving upper trunk. Patients who experienced prior reactions to phenytoin. face — lymphadenopathy — liver abnormalities (30 to 60%): hepatosplenomegaly. thrombocytopenia.MISCELLANEOUS PHENYTOIN Widely used antiepileptic drug. severe hepatitis — hematological abnormalities: lymphocytosis (65%). Siblings of patients with an history of anticonvulsant hypersensitivity syndrome. pneumonitis (9 to 12%) — arthralgias. RISK FACTORS Elderly black men (more severe reactions). phenobarbital. . leukocyt osis. eosinophilia (30%). More than 100 cases of the complete syndrome have been reported. aplastic anemia. CLINICAL MANIFESTATIONS Phenytoin hypersensitivity syndrome. carbamazepine. — renal dysfunction (11%).

Patch-tests: phenytoin 1. positive in some cases of phenytoin hypersensitivity syndrome. toxic epidermal necrolysis. The lymphocyte toxicity studies suggest a genetic basis (autosomal co-dominant pattern). DIAGNOSTIC METHODS Cutaneous testing. Stevens Johnson’s syndrome. Immune mechanisms. mild edema. exfoliative dermatitis. occasional dyskeratosis. Lymphocyte toxicity testing. The arene oxide metabolites derived from the 3 anticonvulsants are highly electrophilic compounds that covalently bind to macromolecules and disrupt cellular function (cytotoxicity) or to form neoantigens that trigger an immunological response. frequent multinucleated keratinocytes.297 - . and aq. erythema multiforme. vasculitis. . periarteris nodosa. Positive patch-tests. Morbilliform eruption. superficial perivascular chronic inflammation. angioedema. Skin-biopsies. 5. lupus erythematosus. Epidermal necrosis. scarlatiniform dermatitis. MECHANISMS The 3 major anticonvulsants have a common aromatic benzene ring that is metabolized via cytochrome P450 to an arene oxide. 20% in pet. positive lymphocyte stimulation tests. This metabolites are highly unstable an can be detoxified by — conversion to a dihydrodiol by epoxide hydrolase — reduction by binding to glutathione — spontaneous rearrangement to form a phenol. cutaneous pseudolymphoma.MISCELLANEOUS Isolated cutaneous manifestations. Deficient enzymatic reduction by epoxide hydrolase leads to toxic intermediate metabolite with resultant cytotoxicity (hepatitis) and hypersensitivity reactions. circulating antibody drug complexes.

“Cross-sensitivity of skin rashes with antiepileptic drugs”..A. Whittaker S. Miller M. Feo Brito F. Clin.J.. Substitute for benzodiazepines. “Phenytoin hypersensitivity syndrome”. Miss. Muglia J. 1996. Med. Intern.Y. Romero Aguilera G. 13 (4): 727-39 Hyson C.C. Care. State Med. 8 (3): 18690 Morkunas A. “Anticonvulsant hypersensitivity syndrome”. 155 (21): 2285-90 • • • • • • RANITIDINE Histamine H2 receptor antagonist used in the treatment of gastric and duodenal ulcers. 1997. “Phenytoin-induced toxic epidermal necrolysis: a case report”. 24 (3): 245-9 Conger L. “Dilantin* hypersensitivity reaction”.P. gastroesophageal reflux and hypersecretory states. 1998. Grabski W. Neurol. Allergol. Clin. Arch. Encinas Barrios C. Cortina de la Calle P. Dermatol. J.. Carlton F.. 1996. “Phenytoin hypersensitivity syndrome with positive patch-tests.B. Immunol. J.. 75% of a series of patients with anticonvulsant hypersensitivity syndrome to one of the oxide metabolites producing anticonvulsants showed in vitro cross-sensitivity to the other two. Garcia Rodriguez R.R.A Jr.. valproic acid. “Anticonvulsant hypersensitivity syndrome”. A possible cross-reactivity with amitriptyline”. J.MISCELLANEOUS MANAGEMENT Phenytoin should not be administered intravenously into dorsal hand veins. Crit.J. Exp.R. .D.B. 1995. Assoc. Smith N.298 - . 1997. lamotrigine Cross-reactivity with amitriptyline may occur. 37 (2): 471-5 Creamer J. Sadler M. Can.J. Phenytoin given intravenously must be administered only in larger veins at a rate < 50 mg/ min. 57 (4): 223-6 Sanders D. 1996. Thompson J. 21 (2): 116-20 Vittorio C. Sci. Kerr-Muir M. Clin. Cutis. Gomez Torrijos E. Investig. REFERENCES • Galindo Bonilla P.

. mild gastrointestinal disturbance. 3 cases described in obstetric patients. tiredness. MECHANISMS IgE-mediated hypersensitivity (positive skin tests. cutaneous delayed reactions (papular eruptions). Direct histamine release. Skin prick-tests: 10 mg/ ml positive with ranitidine. positive oral challenge). maculopapular rash. MANAGEMENT Cross-reactivity with other H2 receptor antagonists is exceptional (one case published) Omeprazole can be used in obstetric patients to reduce gastric acid production. laryngeal edema. dizziness. edema of the face. toxic epidermal necrolysis. DIAGNOSTIC METHODS Cutaneous testing. negative with famotidine. Digestive: acute cholestatic hepatitis with rash and hypereosinophilia (one case).299 - . CLINICAL MANIFESTATIONS Differentiate from other side-effects: headaches. tongue. Oral challenge. nizatidine. nitrofurantoin. Intradermal skin tests: one case positive 1/1000.MISCELLANEOUS INCIDENCE Uncommon. Cutaneous: pruritus. arms. No specific IgE found. urticaria. General: anaphylactic shock Respiratory: dyspnea. bronchospasm.

Contact. Rovira-Farre I.05 ml 500 µg/ml (25 µg): negative 0. MANAGEMENT Avoidance. Intensive. Igea J. 1996. 51 (9): 659-60 Lazaro M. Revenga-Arranz F. INCIDENCE One report.300 - .. “Cutaneous delayed reaction to ranitidine”.M. Intradermal skin-tests: 0. “Anaphylactic reaction to ranitidine” .A. 21 (5): 702-3 Picardo M.. Marcos C.J. 9: 327 RECOMBINANT HUMAN TYPE I IL-1 RECEPTOR (rhu IL-1R) Recombinant human type I IL-1 receptor is used to suppress inflammatory disorders. Compaired J. Specific IgE (ELISA): positive in one patient. Anaesth. Santucci B. Davila I. . 48 (5): 385-7 Powell J. Care. Allergy. “Urticaria from ranitidine”. Skin prick-tests: negative.A. de la Hoz B. CLINICAL MANIFESTATIONS Cutaneous: erythema. “Anaphylactoid reaction to ranitidine in an obstetric patient”.MISCELLANEOUS REFERENCES • • • • Gonzalo-Garijo M. pruritus at the injection site within 15 minutes.A. 1983.. Dermatitis. The specificity of antibodies is confirmed by inhibition ELISA studies. DIAGNOSTIC METHODS Cutaneous testing.05 ml 2500 µg/ml (125 µg): positive. Allergy. Maycock E. Losada E. 1993. 1993.

erythrodermia. lupus — Cutaneous: rash (1% of treatments).MISCELLANEOUS REFERENCES • Grammer L. CLINICAL MANIFESTATIONS Manifestations may be divided in two categories: I/ Dose-dependent manifestations linked to the rate of acetylation of sulfapyridine are frequent (30%) under the following conditions: — doses > 4 g/ day — serum levels of sulfasalazine > 50µg/ ml — patients presenting slow acetylation rate. Allergy. vasculitis. Lyell’s syndrome. arthralgia. epigastralgia — Hematological: hemolytic anemia. independently of the dose or rate of acetylation.. J. Stevens-Johnson’s syndrome. INCIDENCE 5 to 55% of patients present side-effects.301 - . Hypersensitivity is involved only in 2% of these manifestations. 1997. — General: prolonged fever. hemolysis without anemia. erythema multiforme. Roberts M. Clin. methemoglobinemia — Cutaneous: bluish skin. It consists of a sulfonamide moiety linked by a nitrogen bond to aminosalicylate. “Cutaneous allergy to recombinant human type I IL-1 receptor (rhu IL-1R)”. discomfort — Digestive: nausea. These manifestations are: — General: headache. vomiting.C. anorexia. . 99 (5): 714-5 SULFASALAZINE Sulfasalazine is used chiefly in the treatment of hemorrhagic ulcerative colitis and Crohn’s disease. urticaria. are uncommon (2%). II/ Hypersensitivity manifestations occurring early. Immunol.

1000 mg. 2 deaths). 800 mg. MECHANISMS Unknown. DIAGNOSTIC METHODS No in vivo or in vitro method is currently available. Absolute contra-indications: toxic epidermal necrolysis. MANAGEMENT 91% of sulfasalazine intolerant patients are able to tolerate at least one of the three 5 ASA preparations (mesalazine. 4 mg. pancreatitis. 10 mg. bloody diarrhea. diffuse interstitial fibrosis. obliterans bronchiolitis.MISCELLANEOUS — Hematological: autoimmune anemia. balsalazide). 40 mg. 2000 mg. aplastic anemia — Respiratory: bronchospasm. diarrhea and sometimes hypersensitivity reactions. 400 mg. . thrombocytopenia. fibrosing pulmonary alveolitis. neurotoxicity. but the following hypotheses have been proposed: Cytotoxicity in hematological manifestations. but adverse effects may occur: colitis. eosinophilic pneumonia. pulmonary infiltrates and eosinophilia. other than stopping and then restarting sulfasalazine. If a reaction occurs. massive hemolytic anemia. 80 mg. subacute hypersensitivity pneumonitis — Digestive: hepatitis (12 cases. slow the progression. olsalazine. agranulocytosis. 2 mg. 8 mg.302 - . For example: starting with 1 mg and doubling the dose each week: 1 mg. leukopenia. 200 mg. Many protocols have been published. Desensitization is a safe approach in mild hypersensitivity reactions (rash. bone marrow aplasia. 100 mg. fever). Immune complexes in cutaneous vasculitis. agranulocytosis. 20 mg. granulomatous hepatitis. Delayed cell-mediated hypersensitivity in some cutaneous manifestations.

H. 11 (2): 169-70 Tolia V. Nawata H.J. general papular. Aliment. Kabemura T. Hermier M. . Gastroenterol. Rheumatol. Respiratory: tightness of the chest. Holdsworth C. 1992. Oral drug challenge.. Pediatr. erythema multiforme. 1993. hand and face contact dermatitis (handling of the drug). Interêt de la désensibilisation par voie orale”. “Clinical tolerance to three 5aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine”. Aboufadel A. 4 (2): 144-6 Akahoshi K.. 29 (6): 772-5 Koski J. urticaria. Ther. maculopapular or purpuric rash. Legall C. 1994. angioedema. Arch. Pharmacol. Gastroenterol.. 87 (8): 1029-32 Giaffer M. Exp.MISCELLANEOUS REFERENCES • • • • • Lachaux A. Akamine Y. INCIDENCE 2/4767 recipients of benzodiazepine drugs.. Loras-Duclaux I. Okabe H. “Sulfasalazine desensitization in children and adolescents with chronic inflammatory bowel disease”. J. Chijiiwa Y. Am. 1992.303 - . used as muscle relaxants (50 to 200 mg daily). 1997.. “Desensitization to sulphasalazine in patients with arthritis” . Clin. “Desensitization for sulfasalazine-induced skin-rash in a patient with ulcerative colitis”. J.: positive in all cases. DIAGNOSTIC METHODS Cutaneous testing.D. “Hypersensibilité à l’acide 5-aminosalicylique. O’Brien C. CLINICAL MANIFESTATIONS Cutaneous: pruritus. 6 (1): 51-9 TETRAZEPAM Tetrazepam is a benzodiazepine with the general properties of diazepam.M. Patch-tests with tetrazepam 1% aq or 1% and 5% pet.

Burger T. Contact. “Cross-reactive type IV hypersensitivity reactions to benzodiazepines revealed by patch testing”.R. Mora C. “Delayed cell-mediated hypersensitivity to tetrazepam”. MANAGEMENT Avoidance of all benzodiazepines is not mandatory. 1996.B. Contact. CLINICAL MANIFESTATIONS Urticaria. Barranco P. 1997. INCIDENCE 3/2664 (rashes). 34 (2): 139 Kämpgen E. Patch-tests (15% in vaseline): negative. Klein E. 33 (5): 356-7 Camarasa J. . Quirce S. since crossreactivity is not always found in oral challenge tests.L. Gala G. Dermatitis.MISCELLANEOUS MECHANISMS Type IV hypersensitivity. Dermatitis. Romualdo L. “Tetrazepam allergy detected by patch-test”. Skin prick-tests: ubiquinone (5 mg/ ml): negative. REFERENCES • • • • Blanco R. Allergy. “Delayed hypersensitivity to tetrazepam”. 1995. Dermatitis. 52 (11): 1146-7 Ortega N.304 - . 1990. 22 (4): 246 UBIQUINONE Ubiquinone (coenzyme Q): 2-3 dimethoxy 5 methyl-6-decaphenyl benzoquinone is used in the treatment of mitochondrial myopathies and encephalomyopathies. Contact. Brocker E. Serra-Baldrich E. Diez-Gomez M. DIAGNOSTIC METHODS Cutaneous testing.G. Lopez-Serrano C.

050 mg.5 mg. 10 mg. MANAGEMENT Desensitization (every 30 minutes).305 - . 3.5 mg. 15 mg. “Rush desensitization with ubiquinone”. 12. Misuraca C. 1 mg.5 mg. 17. 1997. Zoppi A. 7. 17. 20 mg: positive in one patient. MECHANISMS Unknown. 52 (7): 783-4 . 5 mg. 2 mg Day 2: 3. 15 mg. Allergy. Nucera E.5 mg.5 mg. 10 mg Day 3: 10 mg.MISCELLANEOUS Oral challenge tests: 5 mg. Patriarca G. Day 1: 0.5 mg. Day 4: 15 mg. REFERENCES: • Schiavino D.25 mg.

.......................................................................... 274 ACTH ............................................................................. 180. 6-mercaptopurine .......... 168 Alphazurin 2 G ........................ 218 Alkylating agents ............................................. 8 Alphaxalone........................................................................ 106 Allergoids ... 111 Aminoglycosides ...................................................................................................................................................... 93 Acetylcysteine ................................................................................................................................................................................................................. 170 Amitriptyline ..................................................................................................................................................................................................... 275 Allylamines...................................... 168 Aluminum hydroxide.............................. 249 Amidophenazone ..... 54 Adenocorticotrophic hormone ..................................................................................... 298 150 148 130 117 .................................... 292 Acetaminophen ................................................ 189 Allopurinol ......................................................306 - ... 48 Amikacin .................................................................. 55 Alminoprofen ......................................................................................................................................................... A ACE inhibitors ............................................ 218 Actinomycin ..... 50 Alphacaine ...................... 139 Acyclovir ....................... 136......................... 206 Althesin........................... 178 Aminophylline .......................................INDEX INDEX 2 -mercaptoethane sulphonate ........................ 5 hydroxytryptamine 3 receptors antagonists .. 46 Acetazolamide .................................................................................................................... 5-fluorouracil ............................ 193........................................... 55................................................................................ 56 Aminoglutethimide .......................................

.............................................. 40 Anti-inflammatory drugs ... 34 An 69 membrane ................................... 241 Antiviral ............................................. 37 Antibiotic additive ... 152 Aniline ........................ 206 Antazoline phosphate ......... 240 Antitoxin ....................................................................... 113 Anthralinic acid derivatives..................................................................................................... 53 Antrafenine ........ 189 Antibiotics ................................................................................................................................................................................................ 10................................... 236 Argatroban ......................INDEX Amphotericin b ............................... 236 Anesthetics ................................................................... 49 ............................. 148 Ancrod ........................... 244 Antituberculosis..................307 - ........................... 229 Articaine ............................................................................. 8 Arylpropionic derivatives ........................... 296 Antidepressants................ 172 Anthracycline antibiotics .......................................................................................................................................................................................................................................................................................................................................................................... 40 Aprotinin...................................................... 53..................................................... 180.............................................................................. 192 Antilymphocyte globulin ...................... 37 Ancillary drugs . 178 Antifungal drugs ................... 189 Antihistamines ...................................................... 9.................................................................................. 53 Antihepatitis B ..................................................... 210................................................................................................... 250 Antiseptics ................................ 59 Ampicillin ................................. 236 Antifungal creams ........................................................................................................................................................................................... 77 Amylopectin .............. 193 Analgesics................................................................................................ 229........ 8 Angiotensin Converting Enzyme Inhibitors (ACE) .................................................................................................. 180 Anticonvulsant................ 173 Antihepatitis B vaccine....... 180 Antifibrinolytics ...................................................................................................... 163 Antithymocyte globulins ... 173 Antivenoms..............................

.................................................................. 164 Barium sulfate ........................................................................................ 95 Atracurium ........ 156 Beta-lactams ...................................... 221 Atovaquone........... 8 Benzodiazepine....................... 42 Benzocaine .................................. 60 B B-propiolactone ................................................................................................... 76 Benzylpenilloate .. 76 Benzylpenicilloate salt................................................ 50 Benzothiazepines ........................................................... 11 Barium enema .......................................................... 303 Barbiturates................................................................................................................... 64 Balsalazide................... 177 Betamethasone......... 258 Bacitracin............... 223 Betaxolol...... 96 Bcg vaccine .............................................................. 304 Benzophenones .........................308 - ................................ 23 Atropine ......................... 76 Benzylpenicilloic acid ................ 41.................................. 158 .......................... 42 Azathioprine ................................................. 74 Betadine ............................................................................................................................................................................................. 117 Azithromycin ........................................................... 243 Benoxaprofen ...........................................INDEX Aspirin ............................................................................................................................................ 198 Basic tetracycline.......................................................................................................... 298......................................................... 76 Benzylpenicilloylamine ..................................................................................... 17. 223 Betamethasone-valerate............................................................................................................................................................................................. 95 Azole derivatives .................................................................................................................................................................................................................................................................. 76 Beta-blockers ............ 174 Benzocaine ....................................................................................................... 159 Benzylpenicillin. 223 Betamethasone-dipropionate ............................. 26........................................................................................................ 155 Azapropazone .......................................................

... 85 Chlorothiazide .............................................................................. 108 Chloramphenicol ............................................................ 223 Bumetanide ........................................................................................ 180 Budesonide ......................................... 281 Chlorpropanol ................. 65 Chlorhexidine .................................................................. 137 Carboxymethylcellulose ..................................... 212 Ciprofloxacin ................... 8 Buserelin ......................... 119..............INDEX Bleomycin......... 106................................................... 105 Chlorambucil ............................... 96 Choline salicylate ....................................................................................... 134.............................................. 293 Carbamazepine ....................................................................................................................309 - .............................................. 219 Calcium channel blockers.............. 296 Carbinoxamine ........................................................... 159 Captopril ........................................................................................... 139 ........... 279.................................................................................... 23 Cisplatin.............................. 164......... 93 Chlorprocaine ..................................... 244 Bronchodilators ............................................. 139 Botulinal antitoxin ................................................................................................................. 85 Cisatracurium ................... 120 Butylparaben...................................................... 280......................................... 74 Cetirizine ................................................................... 8 Chlorpromazine ........................................ 153................................................ 264 Calcitonin ................................. 165 Chloroquine ........................................................... 222 Cephalosporins .................................................................................... 171 Carboplatin ....................... 45 Chymopapain.................................................................................................................................................. 289 Chemotherapy drugs and immunosuppressors ................................................................ 161 Bupivacaine .............................................................. 222................................ 174 C Calcipotriol .......................................................................................................... 225 Busulfan........................................................................................................................... 93 Chlortetracycline .............

........................... 111....................................................... 223 Dexamethasone..... 44 Clozapine .................................................................................................................................................... 187 Cuprammonium cellulose hemodialyzers ........ 8 Codeine ...... 305 Collagen.................................................................................... 107............................................................................................ 164 Cotrimoxazole .....................................................................................................l............................ 192............................................. 139 Cyclosporine ......................................................................................... 221 Dextran ...............................INDEX Clarithromycin .......... 223 Desoxymethasone ...........310 - ............................ 31 Contrast agents ................................................................................................................ 191........ 125 Daktarin ........................ 199 Corticosteroids.................................................................................... 29............................................... 197............................................................ 113 Deferoxamine ................ 178... 282 Cuprammonium cellulose dialyzers .................. 69 Daunorubicin ............. 221 Corticotrophin.......................................................................................................................................... 281 Cocaine ........................................................................................................................................................................................................................................................ 95 Clemastine ... 180 Desonide .................................. 67....... 244 .. 171 Clindamycin ................................................................................. 164.......................... 168 Cytarabine....................................................... 285 Dacarbazine .............................................. 265 Cyclophosphamide ....................................... ........... Penicillamine ................................ 186 Cyanocobalamin/hydroxocobalamin ........................... 168 Dapsone ..................................... 18 Coenzyme Q ............ 95 Clonixin .................................. 283 Desipramine............................. 168 Cromolyn ..................... 91 Cremophor e........... 121................................................................................................................................................ 204 Contrast media .................................................................................... 218 Cortivazol .. 123 D D.....................................................................

...................... 28 Dyes ........................................ 8 Diclofenac.......................................................................................................................................................................................... 168 Equine rabies immunoglobulins ................................................... 26.................... 69 Diatrizoate ...................................... 289 Diethylglycine ........................... 44 Dihydropyridines ......... 126 Diazoxide.. 168 Disinfectant.............................................................................................................................. 195 Dialyzers ............................................................................................................................... 165 Disodium cromoglycate.......................................................... 93 Dibenzodiazepine ................................. 56 Diltiazem .......... 178 Droperidol.......... 200 Diazepam .......................................................................... 171 Diprivan ......................................................................................... 168 Diaziquone...................................................................... 42...................................................................................................... 238 Epontol ........................... 159 Dihydrostreptomycin ................... 10......... 9.......................................................................................... 142 Doxorubicin ............................... 238 Epidophyllotoxins.................................................................................................................................................................... 192........ 85 Enzymes ... 168 Diethylenediamine....................INDEX Dextran sulphate ..................... 46 Diflunisal ............................ 44... 127 Epinephrine............................ 186............................................................................................................................ 163 E Enoxacin ..................................................... 159 Diphenhydramine ................................. 114.............. 282 Docetaxel .................... 97........................................................................... 178..................................................................................................................................................... 281 Dibucaine......................................................... 189 Diaminodiphenylsulfone .......................................................... 187........................... 293 Diagnostic agents...................... 209 Ephedrine.......................................................... 45 Didemnin B ............................................................................... 247 .................. 134 Doxycycline........311 - ..........................................................

. 223 F Factor VIII .......... 249 Framycetin ................................................................................................................................................................................ 42 Fenofibrate ......................................................................................................................................... 160 Futhan ......................................... 40 Fluconazole.............................................................................. 299 Fenbrufen ..................... 8 Etofenamic..................................................... 287 Ethylenediamine .............................................................................. 50 Fenoprofen ..... 20 Floctafenine ... 14 Etoposide ............................................................................. 40 Etomidate........................................................... 127 Examethasone ..................................................................................................................................................................................................INDEX Erythromycin .................................................................................... 223 Fluorescein ..................................... 93................ 186................................................ 293 G Gadolinium chelates ............................................... 60 Flufenamic .................................................................................................................................. 50 Fentanyl .................... 204 ........................ 187...................................................................................................................... 182 Ethylparaben ............... 57 Furosemide ............................................................................. 44............................................................................... 70 Ethylene oxide ................ 50 Formaldehyde ........................................... 85 Flunitrazepam ............................................. 26 Fluocortolone ................................................................................................................................................. 287 Famotidine .... 73 Erythrosine ................................. 169 Ethambutol ............. 40 Flumequin .......................... 289 Ethylmercurychloride ............................ 196 Flurbiprofen ............... 170............................................................. 45.................................... 189 Formalin ................................................................................................................................................................................................................... 174 Etidocaine .........................................................312 - .........

................................................................ 204 Gastrografin ..................................................................................................................................... 250 Hexadimethrine ........................................................313 - ....................................................................................................... 236 Hirudin ........................................................ 131 Hydroxyzine ............................................. 228 GnRH analogues ...................................................... 225 Goserelin.................... 44................................... 172........................ 223 Hydroxyethylstarch (HES) .......................................... 248 Hetastarch .................................................................................................................................... 178 Glafenine .......... 42. 227......................................................................... 217 Human serum albumin .. 11 I Ibuprofen .................. 148 Guanosine ........................... 204 Gadoteridol ................ 204 Gadoterate meglumine................... 293 Hepatitis b vaccine ................................................................................. 85 Glucose polymers ........... 288 Hypnotics.................. 236 Hormones ....................... 186 Heparin ...................................................... 54 H Hemodialyzer ...... 56.......... 56 Hydroxyurea ..................................... 50 .................................................................. 197 Gelatin ........... 34 Heterologous sera . 29 Glycosaminoglycans...... 221..................................... 31.............................................................................................................................................INDEX Gadopentetate dimeglumine .................. 34 Hydroxystreptomycin ........................................................................................................................................................................................................... 223 Hydrocortisone-17-butyrate .................................................................................................................................................... 225 Granisetron .................................. 225 Gonadorelin ..................................................... 40................................................................................................................................................................. 229............................................. 251 Hydrocortisone ........................................ 198 Gastrointestinal contrast media ................... 255 Gentamicin ..........

.............................................................. 61 K Kanamycin................. 300 Imidazobenzodiazepine ........................................................................... 72 Isonixin .............................. 230 Interleukin 2...... 42..... 200 Ioxaglate ................................................... Ketoconazole ............................................................................................ 247.............................................................................................................................................................................................. 200 Iothalamate ..................... 200 Iotrolan ..................................................................................... 200 Ioxitol .............................................................................................................. 198 Indomethacin ..................................... 191 Isoniazid ........................................................ 200 Iopentol .................................................................................................................................................................................................. 199 Iodixanol ...................................................................... Ketalar ..........INDEX Ifosfamide .................... 44.......................................... 200 Iopromide ......... 180 Immunoglobulin ....................................................................................... 253 Iodamide ....................... 200 Iopamidol .......................................................................................... 200 Iohexol ......................... 56 15 15 62 49 ......................................................................................................................................................................... 45 Imipramine ............................................................................................. 44 Itraconazole .......................................................................... 108 IL-1 receptor ............................................................. 200 Iron dextran ............................ 253 Indocyanine green ........................................................ Ketamine..... 200 Ioversol ...................................................................................... 27 Imidazole salicylate .........................314 - ................. 200 Iomeprol ....................................................................................................................... 200 Iodinated contrast media............................................................ 44 Insulin ......................................... Ketoprofen .......................................... 201 Intravenous immunoglobulins ................. 200 Ioxythalamate ..................................................................................................................... 107......................................................................................................

..................................................................................... 178 Lincomycin .................................................................. 73 Mannitol ................................................................................................................................................... 303 .......................................................................... 8 Lomefloxacin............. 254 Mechlorethamine ........................................................................................ 172.................................................................................... 8 Mercurochrome ...................................................................................................................................... 289 Ldl apheresis ...... 172 Mercury chloride ................... 45 Konakion ..............................INDEX Ketorolac ............................................................................................................................................ 56 Marmite .................... 168 L L-asparaginase ................................................................. 258 M Macrolides ................................ 292 Leuprolide................. 40...................................................................................................................................... 109 Meclofenamic acids .......................... 21 Mepivacaine ....... 225 Leuprorelin ...................................... 40 Mefenamic acid ...................................... 35 Manosidostreptomycin ............................................ 154 Lyssavac-HDC Berna ................................. 181 Mesalazine ............ 225 Lidocaine ...315 - ..................................... 110 Meperidine........................................................................... 292 Lozartan .............................. 8............................. 108............. 249.................................................................................... 173 Merthiolate ........ 173 Mercury nitrate ............................................................................................................................................................................ 85 Low density lipoprotein apheresis .......... 115 Lamotrigine .......................... 298 Latex .................................................................................................................. 198...................... 44 Melphalan ................... 173 Mercury antiseptics ...... 67 Local anethetics .................................................................................................. 265 Measles vaccine ...........................................................................................................................................................................

.... 50 Neomycin .............. 97 Mitomycin ................................................................................................................................................... 56 Neuroleptics................................................................................................................ 159 Nimesulide....... 44...................... 238 Netilmicin .................. 23 N Nafarelin ... 27 Minocycline ...................................................................................... 299 ................................................................ 132 Methylmorphine .................................................................................. 45 Nitrofurantoin ........................................................................................................................................... 18 Muscle relaxants ........................................................................................................................................................................................316 - ................................................................................................................................................................ 255 Neoral .................................... 134................................................................................................................. 200 Metronidazole ................................................................................................................ 48 Methadone .................................................................. 135 Mivacurium ................................. 23 Morphine ............. 85 Naproxen ......................................... 63 Miconazole ..... 178 Metrizamide....................................................................................................................INDEX Mesna .... 122 Neosynephrine . 28 Nicotinamide ........................................................... 42............................................................................ 174 Methylprednisolone ............................ 18 Methylparaben ........................................................................................................................................................................................................................................................................ 221 Metoclopramide............................. 11 Methotrexate ..................................................................... 225 Nalidixic acid............................................. 19 Methohexital ..... 18 Morphinomimetics . 168 Midazolam .................................... 82 Nifedipine .................................................................................................................................... 56............................................... 22 Morphine monomethyl ether ......................................................................................................... 200 Metrizoate ..... 147 Mitoxantrone ...... 150 Metamizol ....

............................................. 154 P Paclitaxel .................................................................................................................................................................................................. 222 Paracetamol .................................................................................................................................................. 18 Oxolinic acid .......................................................... 44 Paramagnetic contrast agents .... 238 Norfloxacin .............................................................. 299 Non Steroid Anti-Inflammatory Drugs (NSAIDs) ............................................................................................ 41 Non-barbiturates ................................................................................................................................................................................. 204 Paramomycin .................................................. 294...................................................................... 79 Pentastarch....... 206 Pefloxacin ..................... 85 Oxyphenylbutazone ........................................................................................................ 85 Novocaine .. 295 Ondansetron............................... 9........................................................................... 39........................................................................................................................................... 85 Olsalazine ........................................................................................................... 303 Omeprazole............... 21 .................................................................... 148 Opiod ........................ 32 Oxytetracycline........... 14 Norephedrine ......................................... 85 Penicillin ....... 96 Ozagrel ...................................... 42 Oxypolygelatins............................... 173......................................... 23 Papain .............................................. 178 O Ofloxacin ....... 34 Pentostatin ................................................................................................... 168 Pancuronium ..................................... 144...................................... 56 Patent blue dye ....................................................................................................................................... 212 Para-phenylendiamine .................................................................................................................. 74 Pentamidine ................................. 136 Pethidine ....... 85 Nizatidine ........................................... 175 Paraben .....INDEX Nitroxolin ............................................................317 - ...................

......... 164 Prednisone ..... 8 Procaine ............... 8 Procarbazine ........... 176 Praziquantel ......................................... 223 Prednisolone acetate ............................................................... 280................................................ 168 Propoxycaine ................... 81 Prazosin .................................. 162 Prednisolone .................... 45 ........................................................ 296 Pipemidic acid ...................................................................... 221.......................... 141 Propacetamol ............................................................................................................................... 280................ 137 Polyacrylonitrile an 69 membrane........................ 19............................................................................................................................................................................................................................ 42........................................................................... 193 Polyvinyl pyrrolidone ................. 177 Povidone ........................ 48 Phenobarbital ................................................... 8 Piroxicam .............. 171 Piperocaine .............................................................................. 44 Plasma substitutes ........................................................................................................................ 175 Potassium metabisulfite ............................................................................. 168 Propranolol ........................... 221 Preservatives .............................................................. 163 Prilocaine ....................................................................................................... 46 Propacetamol hydrochloride ..................................... 44 Phenylephrine ..............................318 - ............................................................................................................................................................... 159 Phenylbutazone......... 85 Piperazine ........................ 42.. 16.................................................... 20 Phenytoin ....................................................................................................................... 156 Propofol .................................................. 175 Povidone iodine .......INDEX Phenazone .................................. 141.......................................................................................................... 296 Phenothiazine ........................................................................................................ 15........................... 172 Phenylpiperidine ........... 28 Phenylalkylamines.......................................................................... 8 Propoxyphene ................................... 29 Platinum compounds .............................. 238 Phenylmercuric acetate .............................................................................................................................. 39 Propanidid.......

82 Pyrazoline drugs ............................................................................. R Rabies immunoglobulin....................................................................................................................................................................... 298 Recombinant human type 1 il-1 receptor ..................... 86 Rifampicine ........................... 174 Propylphenazone .............. 56 24 84 83 85 ...319 - .......................................................................................... 44 Sandimmune ................ 168 Sera ........................................................................................................................ 88 Rocuronium .......................... 88 Rifamycin sv ................................................................................................ 300 Rifabutine ... 239 Sisomicin ...... 48 Protamine ............................................................ 48 Pyridoxal.................. 268 Pyridoxine................................................. Quinine ............................................................................... 237 Pyrazinamide ........................................................... 42........................................................... 48 Pyrazolones...................................................................... 45 Salsalate ....................................................................................................... 89 Rifampicin ............... 235 Pseudoephedrine ............ 232..........................................................................................................................INDEX Propylparaben ..................... 268 Pyrimethamine ............................................ 95 Q Quarternary ammonium..................... Quinidine .................................................................................................................................................................................................................................. 257 Ranitidine ...................................................... 89 Rifamycin B.......... 23 S Salicylate ............... 67.............................. Quinolones............................................ 268 Pyridoxamine .................................................................................................................................................................................................................................................................. 122.................................................................................... 247 Rabies vaccine ......................................................

... 218 Tetracycline group ........... 180 Stesolid mr ...................................... 70 Sulfasalazine ...................................... 101 Teniposide...................................................................................................................... 91 Sulfapyridine . 214 Streptomycin............................................................... 93 Sulfamethoxazole-Trimethoprim (SMX-TMP) . 45 Sodium sulfite ................................................................................... 85 Steroids ............... 177 Sodium cromoglycate ......................... 128...................................... 222 Sulfonamides ............................. 42 Sulphadiazine .............................. 259 Tetracaine ............................. 168 Streptokinase ...... 168 Terbinafine ........................................................................................................................................... 177 Sodium salicylate............................................................ 9............ 90 Sodium glutamate ...................INDEX Sodium bisulfite................. 57 Sulfadiazine ......................................................................................... 168 Teicoplanin ..... 177...... 55 Tetanus toxoid ..................... 8 Tetracosactrin ............................................................................................................. 23 T Tartrazine ......... 154.......................................................................................................... 161............................................................ 102................................................................................. 175 Sulfurous anhydride........................................................................................................................................... 142 Taxol ............................................................... 91......................................................................................................... 56..................................................................................................................................................................................................... 282 Sodium fusidate ........................................................................................ 177 Sulindac ............................................... 177 Sparfloxacin ............................ 244 Sodium metabisulfite .. 96 Tetrazepam .................................................................................... 45 Suxamethonium ...................... 180 Taxanes .................................................................................................................................................... 301 Sulfites .........................................320 - ............. 304 ............................................................................................................................... 95 Suprofen .............................

......................................... 223 Topical non-steroidal antiinflammatory drugs (NSAIDs) ..................................... 54 Valproic acid ............................ 172.................. 13 Thiosalicylic acid............................ 223 Triamcinolone acetonide ............. 173...... 64 Tixocortol pivalate ...INDEX Theophylline ........................................................... 267 Thiazide .................................................................................. 85 Timolol maleate ...................................................................................................................................................................................... 42.... 181 Thiomersal ............................................................................................................ 50 Tiliquinol ........................... 102 Tiaprofenic acid ......... 42 Topical corticosteroids........... 182 Thiotepa ................................................ 148 Tryphenylmethane dyes ................... 225 Tropisetron ............................ 223 Tobramycin ....................... 56 Tolbutanol ................................................................................................................................................................... 206 U Ubiquinone ....................................................................................................................................... 156 Tinidazole ...................... 286 Trimethoprim ......... 239 Valacyclovir ................................................................. 298 ............................................... 305 V Vaccines ................. 249 Thiopental ................................... 172 Tripterolin ................... 93 Tolmetine ......................................................................................................................................... 164 Trientine .............................................................................. 275 Thimerosal ....................................................................................... 146 Thymidine............................... 222........................................................................................................................ 98 Tripelennamine hydrochloride ...........................................................321 - ........................ 170 Thiamine (vitamin b1) ....................................................................................................................................... 49 Triamcinolone ......................... 12 Thiopentone ........................................................................................................... 181...................................................................................................................

................................................INDEX Vancomycin ......................................................................... 263 Vumon .......... 42.................. 100 Vecuronium .......................... 147 Vitamin B.............................................322 - ...................................................... 134.......... 168 Vitamins ................................................................................................................................................................................................................................ 178 Vitamin B1.................................................................................................................... 159 Vinblastine ............................................. 44 ............................................. 147 Vinca alkaloids ........................................................................................................................................................ 139................. 147 Vincristine ........................................................................... 264 Vitamin K ............................. 23 Verapamil ......... 268 Vitamin D3 ....................... 267 Vitamin B6.................. 168 Z Zidovudine......................................................................................................................................... 147 Vindesine ................... 269 Vitamin K1 ..................................................................................... 102 Zomepirac ......

INDEX .323 - .

.

.

.

.

.

.

diagnostics@eu.pnu.Pharmacia & Upjohn Diagnostics AB.com ISBN 91-973440-0-1 52-5103-59/02 . Sweden. SE-751 82 Uppsala. +46 18 16 30 00. e-mail: marketing.