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Clinical Therapeutics

Conclusion:  Fenofibrate-photo-induced hypersensitivity is a known Allopurinol-induced hypersensitivity syndrome was suspected


adverse effect of the drug. Besides, clinicians should be aware of the and the drug was withdrawn. All symptoms were relieved after two
possibility of oral hyperpigmentation related to fenofibrate. weeks. Four months later, the patient exhibited an extensive pruritic
skin rash associated with fever and hypereosinophilia, 2 days after
amoxicillin intake for respiratory tract infection. Symptoms disap-
Generalized bullous fixed Drug peared few days after amoxicillin withdrawal. We noted that our
eruption: a case series patient was previously exposed to amoxicillin without any history of
hypersensitivity to the drug or to other beta-lactam drugs.
H. Ben Romdhane1; S. Larif1; R. Slim1; N. Fathallah1;
Discussion:  Allopurinol hypersensitivity syndrome is a severe adverse
C. Belajouza2; N. Ghariani2; and C. Ben Salem1
1 reaction characterized by rash, fever, internal organ involvement occur-
Faculty of Medicine of Sousse, Tunisia; and 2Farhat Hached
ring 2 to 6 weeks after drug initiation. It is more frequently associated
University Hospital of Sousse, Tunisia
with chronic renal insufficiency in relation to the accumulation of
Introduction:  Generalized bullous fixed drug eruption (GBFDE) is
allopurinol’s metabolite leading to tissue damage. Hypersensitivity to
a rare and severe form of fixed drug eruption (FDE) that may be
amoxicillin after allopurinol-related DRESS, two drugs without any
misdiagnosed with other forms of bullous drug eruptions (BDE).
chemical or antigenic similarity, are rare and are due at least in part, to
Herein, we report three cases of GBFDE.
the administration of amoxicillin during the period of immunological
Case Reports:  Case 1: An 89-year-old man developed an indurated
depression following the hypersensitivity to allopurinol.
edematous plaque on his arm 1 day after acetaminophen ingestion.
Conclusion:  Clinicians should be cautious when prescribing amoxi-
There was an extension of the lesion with occurrence of flaccid vesi-
cillin to a patient with a previous history of hypersensitivity syndrome
cles. There was a previous history of recurrent reaction in the same
to allopurinol.
sites. The rash resolved after acetaminophen withdrawal. Case 2:
A 48-year-old woman presented with well-defined bullous lesions
and ovular patches spread diffusely over her arms, trunk and face,
which appeared 1 day after the consumption of mefenamic acid. Hypersensitivity to penicillins diagnosed
The diagnosis of GBFDE was considered especially with a reported with delayed reading prick tests
history of a previous reaction occurring in the same site. A patch S. Larif; N. Fathallah; R. Slim; H. Zayani; and C. Ben Salem
test with mefenamic acid revealed a positive reaction. Case 3: A Faculty of Medicine of Sousse, Tunisia
51-year-old man developed well-limited bullous lesions located on Background:  Penicillins are widely prescribed class of antibiotics
the trunk, arms and scrotum, 24h after mefenamic acid intake. He because of their activity spectrum and cost effectiveness. Nevertheless
reported two other previous episodes occurring in the same site. The they can be prohibited because of allergic reactions. In these cases,
role of mefenamic acid was confirmed by a patch test on a residual skin tests can be useful and have to be applied according to the
pigmented lesion. pathomechanism of the allergy-induced by the drug. In immediate
Discussion:  Differential diagnosis to GBFDE is BDE such as Stevens- beta-lactam drug allergy, an Ig E-mediated reaction can be demon-
Johnson syndrome and toxic epidermal necrolysis. A history of strated by a positive skin prick test with a reading at 20 mn. Herein,
hyperpigmented and bullous lesions occurring at the same sites we report a case of hypersensitivity to penicillin diagnosed with a
related to drug consumption may be helpful in diagnosing GBEDE. delayed reading prick tests.
Positive rechallenge with the suspected drug is useful with FDE but Case Report:  A 27 year old female with an unconfirmed history of
it may be dangerous with GBFDE as lesions may be extensive and anaphylaxis reaction to beta-lactamins in the age of 3 years is presented
more severe. Patch tests on lesional skin may be a safe alternative to to our department in order to confirm this allergy. Clinical investiga-
identify the incriminated drug in GBFDE. tion included a skin Prick test to co-amoxicillin, oxacillin, ampicillin
Conclusion:  Clinicians should be aware of the risk of GBFDE. Patch and cefotaxim. The reading at 20 mn and 30 mn was negative. We have
test may be a useful tool in identifying GBFDE. proposed for our patient intradermal test (IDT) but she refused. Forty-
eight hours later, warm pruritic and erythematous nodules appeared in
the area of the co-amoxicillin and ampicillin prick tests.
Hypersensitivity to Amoxicillin after Conclusion: Skin prick tests are the safest and easiest tests for
allopurinol-induced hypersensitivity detecting immediate drug reactions. The result is evaluated after15-
syndrome: a co-sensitization to 20 mn. If negative, IDT can be performed. We present evidence
unrelated drugs that prick skin tests should be evaluated certainly after 20 mn but
even after 24 and 48 hours. Both patients and clinicians should be
N. Fathallah1; R. Slim1; S. Larif1; A. Aounallah2; N. Ghariani2;
aware of the risk of switching from negative to positive reactions
R. Nouira2; and C. Ben Salem1
1 after prick skin tests.
Faculty of Medicine of Sousse, Tunisia; and 2Farhat Hached
University Hospital of Sousse, Tunisia
Introduction:  Allopurinol hypersensitivity syndrome is a rare but
severe adverse drug reaction. Although cross-reactivity reactions are Nummular eczema secondary to
reported with chemically related drugs, drug hypersensitivity after a interferon BETA-1B therapy in a patient
history of DRESS syndrome induced by chemically unrelated drugs is with multiple Sclerosis
exceptional. Herein, we point out a possible co-sensitization to chem- S. Larif1; N. Fathallah1; R. Slim1; H. Zayani1; N. Ghariani2; and
ically and antigenically unrelated drugs: amoxicillin and allopurinol. C. Ben salem1
1
Case description:  A 76-year-old female with a 10-year history of Faculty of Medicine of Sousse, Tunisia; and 2Farhat Hached
hypertension and a six-year history of chronic renal failure was University Hospital of Sousse, Tunisia
initiated on allopurinol for the treatment of hyperuricemia. Three Introduction:  Interferon beta-1b is an immunomodulatory drug with
weeks later, the patient developed generalized exanthema with fever proven efficacy in the treatment of multiple sclerosis (MS). Herein,
and cervical lymphadenopathy. Biochemical investigation revealed we report an unusual case of nummular eczema following exposure
hypereosinophilia with cytolysis. to interferon beta-1b in a middle-aged woman with MS.

e52 Volume 37 Number 8S


Poster Presentations

Case Description:  A woman in her 40S was diagnosed with the Conclusion:  In children, increase in awareness enables early recog-
relapsing remitting form of MS. Four months after the first dose nition of anticonvulsant-induced DRESS syndrome so as to reduce
of interferon beta-1b (8 million units, one time weekly), the patient morbidity and mortality.
was seen in the dermatology clinic for evaluation of pruritus and
multiple eczema-like lesions on the legs and bottom. Physical exami-
nation findings revealed erythematous nummular patches on the legs
and bottom with linear excoriations (Figure 1). Involved skin biopsy Pharmacogenetic tests: new tools for
revealed a mild epidermal hyperplasia with spongiosis and lympho- old questions in adverse Drug reactions?
cyte exocytosis, overlying parakeratosis and a perivascular lympho- N. Fathallah; R. Slim; S. Larif; and C. Ben Salem
cytic dermal infiltrate including rare eosinophils. Interferon beta-1b Department of clinical Pharmacology, Matebolic biophysics,
was withdrawn, and the patient received 0.05% betamethasone professional toxicology and applied Environmental Laboratory
dipropionate ointment. There was an improvement of the lesions. LR12ES02, Faculty of Medicine of Sousse, Sousse University,
Two months later, interferon was readministrated and few days later Tunisia
the patient noted an aggravation of the previous lesions with develop- Background:  The interindividual variability to the standard dose of
ment of new lesions. Interferon was definitely stopped. certain drugs remains a major problem in clinical practice. It manifests
Discussion:  In our case, the pathogenic role of the interferon beta-1b either by a therapeutic insufficiency or the occurrence of side effects
seems likely, because the lesions occurred during the course of treat- that are a considerable cause of morbidity and mortality. The variability
ment, regressed after withdrawing the treatment, reappeared after the is related mainly to genetic factors. Pharmacogenetics is a recognized
reintroduction of interferon, and other evident etiologies of eczema discipline within pharmacology that involves testing relevant human
were absent. Skin manifestations resulting from treatment with inter- genes, whose products are involved with the inter-individual variability
feron beta-1b consist principally of injection-site reaction with lesions of a drug’s pharmacokinetics, pharmacodynamics and human leukocyte
varying from sclerotic dermal plaques to erythematous plaques to antigen profile. The promise of pharmacogenetics is to improve the
cutaneous ulcers. The etiology of nummular eczema is multifactorial, therapeutic efficacy of drugs while reducing the incidence and sever-
involving allergic, environmental, emotional, and nutritional factors. ity of adverse drug effects, and drive the optimum drug selection for
Drugs such as isotretinoin, interferon alfa-2b and ribavirin are rarely therapy. The aim of this overview is to provide the situation today of
reported to be a trigger factor. using pharmacogenetic testing in elucidating adverse drug reactions.
Conclusion:  Physicians should be aware of this side effect induced Methods:  Literature review using Pubmed system is conducted and
by interferon beta-1b. articles concerning pharmacogenetics and adverse drug reactions are
selected from 2000 to 2014.
Results:  Most adverse drug reactions are type A reactions and repre-
sent major causes of hospitalization, in some cases leading to death.
Anticonvulsivant-induced dress Pharmacogenetic tests seem to have an important role in minimizing
syndrome in Children: two cases adverse drug reactions. However, the use of these tests faces substantial
N. Fathallah1; A. Mlika2; R. Slim1; S. Larif1; H. Zayani1; challenges and it is not usually used. In our overview, we provide a list of
L. Boughammoura2; and C. Ben Salem1 the most implicated drugs in adverse drug reactions that are metabolized
1
Faculty of Medicine of Sousse, Tunisia; and 2Farhat Hached by enzymes with variant alleles associated with a poor metabolism pro-
University Hospital of Sousse, Tunisia file. Our findings reveal that pharmacogenetic test, for some polymor-
Introduction:  Drug Rash with Eosinophilia and Systemic Symptoms phisms, may be considerably efficacious in preventing adverse effects.
(DRESS) is a severe drug-induced hypersensitivity syndrome associ- Conclusion:  Most of side effects can be avoided if pharmacoge-
ated with multisystem involvement. It may occur in both adults and netic tests become routinely applicable. Although differences in
children. However, it is poorly known by pediatricians and rarely drug response are increasingly recognized, there is an urgent need to
reported in children. We report two cases of DRESS syndrome- translate the knowledge in this area into clinical recommendations.
induced by anticonvulsivants occurring in children. Pharmacogenetic tests may be a safe and reproducible tool in the
Case Reports:  Case 1: A 9-year-old boy with a medical history of prevention of adverse drug reaction.
partial seizures treated by carbamazepine presenting with three days
history of generalized erythema and facial edema associated with
fever, lymph node enlargements and hypereosinophilia, one week
after CBZ initiation. Case 2: A 7 year-old boy presented a generalized Hypolipidemia and Antidiabetic effect
exanthema with fever, hypereosinophilia and cytolysis three weeks of aqueous extract of Mesocarp
after lamotrigine initiation for the treatment of partial seizures. layer (spongy layer) of cocos
Discussion:  DRESS-syndrome is a rare drug-induced hypersensitiv- nucifera nut in white albino rats
ity reaction. Compared to adults, fewer cases involving children are and medicinal evaluation of the
reported in the literature. Nevertheless, it is considered to be a pedi- extract using Phytochemical analysis,
atric emergency owing to its potential life-threatening consequences. Gas Chromatography and Mass
In children, DRESS syndrome may mimic infectious, neoplastic and Sectrophotometer (GC-MS)
immunologic conditions. This may delay the diagnosis and the S.S. Onasanya1; R.O. Tijani1; and O.A. Jokotaga2
1
prompt management. DRESS syndrome is characterized by diffuse Moshood Abiola Polytechnic, Ojere, Abeokuta, Ogun State,
maculopapular rash, lymphadenopathy, multivisceral involvement, Nigeria; and 2Abraham Adesanya Polytechnic, Ijebu igbo, Nigeria
eosinophilia and/or atypical lymphocytes. The pathophysiology of Background:  This study investigated the effect of the aqueous extract
DRESS syndrome remains unclear. It has been recently classified of the mesocarp layer of Cocos Nucifera on blood sugar level and
under a delayed type IVb hypersensitivity reaction where T-helper lipid profile in normal and Streptozocin- induced diabetes rats and in
type 2 cells play a significant role. Early recognition of the syndrome rats fed on a high fat diets {HFD} after which Phytochemical analysis
and withdrawal of the culprit drug may be the key step to preventing and Gas chromatography-Mass Spectrophotometric evaluation of
mortality or substantial organ damage. the extract was done.

August 2015 e53


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