7

Erupsi obat
alergi dan
peny kulit
berlepuh

Dr. Encep Kusnandar Sp.KK (K)

1

Adverse Cutaneous Drug Reactions

Introduction
- ACDR are common, occurring in 2 % to 3 % of
hospitalized patients.
- ACDR in an ambulatory practice occurs frequently.
- The majority of reactions are mild, accom-panied by
pruritus,resolving promptly after the offending drug is
discontinued.
- However, severe, life-threatening ACDRs do occur
and are unpredictable.
- Drug eruptions are caused by immunologic or
nonimmunologic mecha-nisms & are provoked by
systemic or topical administration of a drug.
- The majority are based on a hypersensitivity
mechanism and may be of types I, II, III, or
IV.
2

Classification
Type I: Immediate-Type Immunologic Reactions
IgE-mediated.
Drug (penicillin).
Manifested: urticaria & angioedema of skin/mucosa
& edema of other organs & fall in blood pressure
(anaphylactic shock).
Occur more commonly if drug (antigen) is
administered intravenously than by mouth.

Type II: Cytotoxic Reactions

Drug (penicillin, cephalosporins, sulfonamides, rifampin)
plus cytotoxic antibodies causes lysis of cells such as
platelets or leuko-cytes.
Alternatively, drug (quinine, quinidine, salicylamide,
isoniazid, chlorprom-azine, sulfonamides, sulfonyl-ureas)
plus antibodies (immune complexes form) causes lysis
or phagocytosis.

Type III: Serum Sickness, Drug-Induced Vasculitis

IgG or, less commonly, IgM antibodies formed against
drug.
Mediated by deposition of immune complexes in
small vessels, activated by complement and recruitment
of granulocytes.
Onset of reaction: 5 to 7 days between introduction of
drug and appearance of reaction.
Manifested by vasculitis, urticaria-like lesions, arthritis,
nephritis, alveolitis, hemolytic anemia,
thrombocytopenia, agranulocytosis.

Type IV: Morbilliform (Exanthematous)

Reactions
Cell-mediated immune reaction.
Sensitized lymphocytes react with drug,
liberating cytokines, which trigger cutaneous
inflammatory response.

Immunologic hypersensitivity reactions are manifested

by a variety of distinct clinical patterns:
Exanthematous reactions
Type Ill, IV(?)
Urticaria, angioedema
Type I, III
Fixed drug eruption
Type III, IV(?)
Bullous eruptions
Type IV(?)
Stevens-Johnson syndrome/
toxic epidermal necrolysis
Type III, IV(?)
Vasculitis
Type III
Lichenoid eruptions
Type IV(?)
Photoallergic reactions
Type IV

The nonimmunologic drug eruptions are caused by

(1) idiosyncrasy sensu strictiorireactions due to
hereditary enzyme deficiencies;
(2) cumulation, such as melanosis due to gold or
amiodarone;
(3) irritancy of a topically applied drug;
(4) an individual idiosyncrasy to a topical or systemic drug
(5) mechanisms not yet known
(6) reactions due to the combination of a drug with
ultraviolet irradia-tion (photosensitivity). These may
have a toxic (T) or immunologic (allergic) (A) pathology.

Guidelines for Assessment of Possible Adverse Drug

Reactions
Alternative causes should be excluded, especially
infections, in that many infections (especially viral) are
difficult to distinguish clinically from the adverse effects of
drugs used to treat infections.
The interval between introduction of a drug and onset of
the reaction should be examined.
Any improvement after drug withdrawal should be noted.
The caregiver should determine whether similar reactions
have been associated with the same compound.
Any reaction on readministration of the drug should be
noted.
9

Findings Indicating Possible Life-Threatening

ACDR* Clinical Findings
CUTANEOUS
Confluent erythema
Facial edema or central facial involvement
Skin pain
Palpable purpura
Skin necrosis
Blisters of epidermal detachment
Positive Nikolskys sign (epidermis separates
readily from dermis with lateral pressure)
Mucous membrane erosions
Urticaria
Swelling of the tongue
10

GENERAL
High fever (temperature >40C)
Enlarged lymph nodes
Arthralgias or arthritis
Shortness of breath, wheezing, hypotension

11

Exanthematous Drug Eruption

An exanthematous drug eruption is
an adverse hypersensitivity reaction to an
ingested or parenterally administered drug
characterized by a cutaneous eruption that
mimics a measles-like viral exanthem; systemic
involvement is minimal.
Synonyms: Morbilliform drug eruption,
maculopapular drug eruption.

12

Epidemiology and Etiology

Incidence Most common type of cutaneous drug

reaction
Age Less common in the very young
Etiology
Drugs with a high probability of reaction (3 % to
5 %): penicillin and related antibiotics,
carbamazepine, allopurinol, gold salts (10 % to 20
%).
Medium probability: sulfonamides (bacteriostatic,
antidiabetic, diuretic), NSAIDs, hydantoin
derivatives, isoniazid, chloramphenicol,
erythromycin, streptomycin.
Low probabil-ity(1 % or less): barbiturates,
benzodiazepines, phenothiazines, tetracyclines.
13

Physical Examination
Vital Signs Elevated temperature (drug fever)
Skin Lesions
Macules and/or papules, a few millimeters to
1 cm in size.
Purpura may be seen in lesions of lower legs.
May progress to generalized exfoliative
dermatitis, especially if drug not discontinued.
Scaling and/or desquamation may occur with healing

14

 Arrangement of multiple lesions macules and

papules frequently become confluent.
Distribution symmetric. Almost always on trunk and
extremities.
Palms and soles variably involved. In children,
may be limited to face and extremities.
Eruption may be accentuated in striae. Reactions
to ampicillin usually appear initially on the elbows,
knees, and trunk, extending symmetrically to most
areas of body.
Mucous membranes exanthem on buccal mucosa

15

Differential diagnosis
- Exanthematous eruption viral exanthem
- Secondary syphilis
- Atypical pityriasis rosea
- Early widespread allergic contact dermatitis
Diagnosis
Clinical diagnosis, at times confirmed by histologic
findings
Pathophysiology
Exact mechanism unknown. Probably delayed
hypersensitivity.
16

Course and Prognosis

After discontinuation of drug, rash usually fades; In
some cases of exanthematous penicillin reactions,
readministration of the drug does not cause the
eruption. Duration of ampicillin eruption following
discontinuation of drug: 3 to 5 days.
Of more concern, a morbilliform eruption may be the
initial presentation of a more serious eruption
toxic epidermal necrolysis
Stevens-Johnson syndrome
hyper-sensitivity syndrome, or serum sickness.
17

Management
- The definitive step in management is to identify the
offending drug and discontinue it.
- Indications for Discontinuation of Drug Urticaria
(concern for anaphylaxis), facial edema, blisters,
mucosal involvement, ulcers, palpable or extensive
purpura, fever, lymphadenopathy
- Symptomatic Treatment Oral antihistamine to alleviate
pruritus
- Corticosteroids
Potent topical corticosteroid preparation
May help speed resolution of erup-tion, especially if
secondary changes of eczematous dermatitis have
occurred due to scratching
18

Oral or iv corticosteroids
- Usually not indicated or helpful if the offending drug
has been discontinued
- If the drug cannot be substituted or omitted,
systemic corti-costeroids can be administered to treat the
ACDR; also, to induce more rapid remission.
- Prevention The patient must be aware of his or her
specific drug hypersensitivity and that other drugs of the
same class can crossreact. Although an exanthematous
drug eruption may not recur if the drug is given again,
readministration is best avoided by using a different
agent. Wearing a medical alert bracelet is advised.
19

Exanthematous drug
eruption:
ampicillin
Symmetrically
arranged
brightly erythematous
macules&papules,
discrete in some
areas and confluent
in others on the back
and extremities.

B
C

20

Exanthematous drug
eruptions.
(A) Numerous pink
papules on the trunk due
to a cephalosporin
(B) Confluence of lesions
on the trunk
(C) annular plaques on the
forehead secondary to
phenobarbital.

21

Drug-Induced Acute Urticaria,

Angioedema,Edema,and Anaphylaxis
Drug-induced urticaria and angioedema occur due to a
variety of mechanisms and are characterized clinically
by transient wheals and larger edematous areas that
involve the dermis and subcutaneous tissue
(angioedema).
In some cases, cutane-ous urticaria/angioedema is
associated with systemic anaphylaxis, which is
manifested by respiratory distress, vascular collapse,
and/or shock.
Synonym: Angioneurotic edema.
22

Epidemiology and Etiology

Classification
Immune-mediated (allergic) urticaria/angioedema
IgE-Mediated Antibiotics (especially penicillins),
radiographic contrast agents.
Complement-Mediated
By way of immune complexes activating
complement and releasing anaphylatoxins
that induce mast cell degranulation.
Serum sick-ness, administration of whole blood,
immunoglobulins.
Immune Complex-Mediated Reactions resemble
serum sickness, penicillin.
23

Nonallergic urticaria (anaphylactoid reactions)

Analgesics/Anti-inflammatory
Drugs (NSAIDs) Drugs inhibit or block
cyclooxygenase enzyme in prostaglandin synthesis. Also
associated with rhinosinusitis and asthma.
Radiographic Contrast Media Most reactions are
nonallergic; rarely, allergic.
Angiotensin-Converting Enzyme (ACE) Inhibitors In
0.1 % to 0.2 % of patients,

24

Drugs causing urticaria/angioedema/anaphylaxis

1. Antibiotics and chemotherapeutic agents
- Penicillins: ampicillin, amoxicillin,dicloxacillin,
mezlocillin, penicillin G, penicillin V, ticarcillin.
- Cephalosporins,including third generation.
- Sulfonamides and derivatives.
2. Immunotherapeutics, vaccines
antilymphocyte serum, levamisole, horse serum
3. Cytostatic agents
l-asparaginase, bleomycin, cisplatin, daunorubicin, 5fluoro-uracil, procarbazine, thiotepa
4. ACE Inhibitors captopril, enalopril, lininopril
5. Calcium-channel blockers
nifedipine, diltiazem, verapramil

25

Drugs releasing histamine

Centrally acting drugs (morphine, meperidine, atropine,
codeine, papaverine
Incidence
- Angioedema occurs in 1 per 10,000 courses of
penicillin and leads to death in 1 to 5 per 100,000
courses.
- Angioedema associated with angiotensinconverting enzyme (ACE) inhibitors occurs in 2 to 10
per 10,000 new users.

26

History
Time from Initial Drug Exposure to Appearance of Urticaria
IGE-MEDIATED Initial sensitization,
usually 7 to 14 days
urticaria may occur In previously sensitized
individuals, usually within minutes or hours.
IMMUNE COMPLEX-MEDIATED Initial sensitization,
usually 7 to 10 days, but as long as 28 days;
in previously sensitized individuals, symptoms
appear 12 to 36 hours after drug readministered.

27

 ANALGESICS/ANTI-INFLAMMATORY DRUGS
Occurs following administration of drug by
20 to 30 minutes (up to 4 hours).
Prior Drug Exposure
RADIOGRAPHIC CONTRAST MEDIA
25 % to 35 % probability of repeat reaction in individuals with history of prior reaction to contrast
media
Duration of Lesions Hours
28

Symptoms
- Pruritus, burning of palms/soles, auditory canal.
- With airway edema, difficulty breathing.
Constitutional Symptoms IgE-mediated:
flushing, sudden fatigue, yawning, headache,
weakness, dizziness
numbness of tongue, sneezing, bronchospasm,
substernal pressure, palpitations
nausea, vomiting, crampy abdominal pain,Diarrhea

29

Differential Diagnosis
Acute Edematous Red Pruritic Plaque(s)
Allergic contact dermatitis (poison ivy, poison oak
dermatitis)
Cellulitis
insect bite(s)

Diagnosis
Clinical diagnosis, at times confirmed by histologic findings
Course and Prognosis
Drug-induced urticaria/angioedema usually resolves within
hours to days to weeks
after the causative drug is withdrawn.
30

Management
The offending drug should be identified and withdrawn as
soon as possible.
Prevention
Previously sensitized individuals
The patient should carry information listing drug
sensitivities (wallet card, bracelet).
Radiographic contrast media
Avoid use of contrast media known to have caused prior
reaction. If not possible, pretreat patient with antihistamine
and prednisone (1 mg/kg) 30 to 60 minutes prior to contrast
media exposure.
31

Treatment of Acute Severe Urticaria/Anaphylaxis

Epinephrine (0.3 to 0.5 mg of a 1 : 1000 dilution)
subcutaneously, repeating in 15 to 20 minutes. Maintain
airway. Intravenous access.
Antihistamines H 1 blockers or H 2 blockers or
combination
Systemic Corticosteroids
Intravenous Hydrocortisone or methylprednisolone for
severe symptoms
Oral Prednisone 70 mg, tapering by 10 or 5 mg daily
over 1 to 2 weeks, is usually adequate.

32

Angioedema swellings are

deeper than wheals and may
affect mucosal sites. They
are often pale and poorly
defined.

Urticaria secondary to
penicillin. Several of the
lesions have a figurate
appearance.
33

Fixed Drug Eruption

A fixed drug eruption (FDE) is an adverse
cutaneous reaction to an ingested drug
characterized by the formation of a solitary, but at
times multiple, plaque, bulla, or erosion
if the patient is rechallenged with the offending
drug, the FDE occurs repeatedly at the identical
skin site (i.e., fixed) within hours of ingestion.
Epidemiology
Age Rare in children
34

Etiology
Drugs most commonly implicated:
Phenolphthalein
Antimicrobial agents
Tetracyclines (tetracycline, minocycline)
Sulfonamides, including nonabsorbable drugs;
crossreactions with anti-diabetic & diuretic sulfa drug
may occur.
Metronidazole
Nystatin
Anti-inflammatory agents
Salicylates
NSAIDs
Food: peas, beans, lentils have been implicated.
Food coloring: in food or medications
35

History
Drug History Patients frequently give a history of
identical lesion(s) occurring at the identical location.
Skin Symptoms Usually asymptomatic.
May be pruritic or burning.
Painful when eroded.
Patients note a residual area of postinflammatory
hyperpigmentation between attacks.
Time to Onset of Lesion(s)
Occur from 30 minutes to 8 hours after ingestion of
drug in previously sensitized individual.
Duration of Lesion(s)
Lesions persist if drug is continued. Resolve days to
few weeks after drug is discontinued.
36

Physical Examination Skin Lesions

1. TYPE
The characteristic early lesion is a sharply
demarcated macule.
Within a few hours the lesion becomes edematous,
thus forming a plaque, which may evolve to become
a bulla and then an erosion.
2. COLOR
Initially, erythema, then dusky red to violaceous.
After healing,dark brown with violet hue
postinflammatory hyperpigmentation.
3. PALPATION
Eroded lesions, especially on genital or oral mucosa,
are quite painful(Figures 22-5 & 22-6).
37

4. ARRANGEMENT
Single lesions most common. When multiple,
random. A greatnumber of lesions may simulate
toxic epidermal necrolysis (Figure 22-7).
5. DISTRIBUTION
The genital skin is the most commonly involved
site, but any site may be involved.
Face: perioral, periorbital.
Mucous Membranes FDEs may occur within the
mouth or on the conjunctivae.
May simulate herpes simplex, conjunctivitis, or
urethritis.
38

Differential Diagnosis
Solitary Genital Erosion Recurrent herpetic lesion
Multiple Erosions Stevens-Johnson syndrome,
toxic epidermal necrolysis
Oral Erosion(s) Aphthous stomatitis, primary
herpetic gingivostomatitis,
Erythema multiforme
Laboratory and Special Examinations
Patch Test The suspected drug can be placed as
a patch test at a previously in-volved site;
an inflammatory response occurs in 30 % of cases.
39

Diagnosis
Made on clinical grounds. Readministration of the drug
confirms diagnosis but should be avoided.
Pathogenesis
Unknown
Course and Prognosis
FDE resolves within a few weeks of withdrawing the
drug.
Recurs within hours following ingestion of a single dose
of the drug.
40

Management
Treatment of Lesion(s) Identify and withhold the
offending drug.
Potent topical corticosteroid ointment.
Bacitracin or Silvadene ointment
Postinflammatory hyperpigmentation (dermal
melanin) may persist at the site of an FDE for months
or years and does not respond to hydroquinone
therapy.
Prevention Identify and withhold the offending drug.
Various types of sulfa drugs may crossreact.

41

Fixed drug eruption:

phenolphthalein A violet plaque on the
wrist, eroded plaques on the glans
penis and scrotum, associated with
extensive intraoral erosions.
This was the fourth such episode and
followed ingestion of a phenolphthaleincontaining laxative.

Fixed drug eruption:

phenylbutazone A large, oval,
red-violet plaque with central
bulla formation on the lower
abdomen and inguinal region.
42

Generalized fixed drug eruption:

tetracycline Multiple, confluent,
violaceous-red, oval erythematous areas,
some of which later became bullous.
The eruption may be difficult to distinguish
from toxic epidermal necrolysis.

43

Penyakit kulit berlepuh

Sinonim
Peny.vesiko bulosa.
Definisi
Yaitu peny2 kulit yg effl terutama vesikel dan bula.
Banyak yang termasuk, diantaranya:
1.Pemfigus.
2.Dermatitis herpetiformis.
3.Pemfigoid bulosa.
4.Epidermolisis bulosa hereditaria
44

 Pemfigus
Merupakan segol. penyakit yg terdiri dr bbrp type:
1. Pemfigus vulgaris.
2. Pemfigus vegetans.
3. Pemfigus foliaceus.
4. Pemfigus eritematosus.

Penyebab:
Termasuk penyakit auto-imum, terdapat auto-antibodi
terhadap jaringan interseluler epidermis.
45

Perjalanan penyakit dan gejala klinis.

- kronik residif.
- Efloresensi yg terpenting : bula seluruh tubuh.
- Bula bersifat lembek, berisi cairan jernih kmd jadi
seropurulen bahkan hemoragik
- Bula tersebut terdpt pd kulit yg tdk eritema
- Bula mudah pecah meninggalkan hiperpigmentasi
tanpa sikatriks.
- Tanda Nikolsky positif yg menandakan hilangnya
ikatan antara lapisan2 kulit, yg dpt diperiksa dg
terkelupasnya kulit yg tampaknya sehat setelah ditekan
dan digesek.
46

Diagnosa dan Diagnosa banding:

D/ berdasarkan gejala klinis khas yaitu
sifat bula yg lembek dan tanda Nikolsky positif.
Pemeriksaan pembantu:
- Histopatologi/Tzank test
- Imunofluoresenditemukan IgG pd
interseluler epidermis

47

Tanda diagnostik.
a.Bula lembek.
b.Tanda Nikolsky positif.
c.Tzank test.positif.
d.Kronik residif.

Diagnosa banding.
a.Dermatitis herpetiformis Duhring.
b.Pemfigoid bulosa.
c.Sindroma Steven Johnson
d.Impetigo vesiko bulosa.
e.T.E.N.
48

Pengobatan.
- Kortikosteroid tinggi jangka panjang,kmd di
tapering off sesuai dg keadaan klinisnya,
diberikan prednison 80-120 mg.
- Antibiotika utk infeksi sekunder.
- Anabolik.
- Diet TKTP.
- Pengobatan topikal. Kompres mis dg sol PK
1/10.000, ssd kering beri krem kortikos-teroid.

49

50

51

Dermatitis herpetiformis duhring

Bersifat kronik residif dg efloresensi polimorf tesusun
berkelompok disertai rasa gatal dan biasanya simetris.

Gejala klinis
- Anak dan dewasa.
- Predileksi: punggung, lengan, ketiak bg belakang
dan bokong.
- Efloresensi : papula, pustula dan bula, yg menonjol
adalah vesikula berkelompok disertai eritem dan
berdinding tegang.
- Pemeriksaan darah tepi ada eosinofilia.
- Pada vesikel ada sel2 eosinofil.
52

Diagnosa banding :
* Pemfigus.
* Pemfigoid.
* Eritema multiforme.

Pengobatan :
* DDS 3x100 mg/hari.
* Corticosteroid.
* Topical steroid.

53

Pemfigoid bulosa
- Jarang ditemui dengan penyebab belum diketahui.
- Simptomatologi.
- Keadan umum penderita baik.
- Efl berupa: bula yg bedinding tegang.
- Predileksi: ketiak,lengan bg flexor dan lipat paha.
- Pada cairan bula banyak sel eosinofil.
- Percobaan Tzank negatif.
54

Histopatologi.

Bula di subepidermis,akantolisis (-)

Diagnosa banding.
Pemfigus.
Dermatitis herpetiformis.

Pengobatan.
Kortikosoeroid.
Antibiotika pd inf sekunder.
Dapson juga efektif.

55

Epidermolisis bulosa hereditaria.

Sinonim
- Akantolisis bulosa.
- Congenital traumatic pemphigus.
Timbul pada waktu lahir atau segera sesudah lahir,
Bersifat herediter
Disebabkan kekurangan jaringan elastin dari kulit.

Simtomatologi
- bayi dan anak-anak.
- Tempat predileksi: tempat yang mudah kena trauma
punggung dan extensor extremitas
- Timbul bula berisi cairan serosa, purulen/hemoragik.
56

Klasifikasi.

- Congenital timbul sejak lahir.

- Aquiredyang didapat atau timbul kemudian

Bentuk klinik
- Benigna atau simpleks
apabila bula memecah tdk meninggalkan sikatriks
hanya bercak hiperpigmentasi.
Bentuk ini diturunkan secara dominan.
- Distrofik
jika bula memecah meningalkan sikatriks yg atrofi
Kalau lebih dalam menyebabkan kontraktur.
Pada tangan dapat terjadi claw hand.
Kuku dpt tkena jd atrofi,kdg2 rusak sama sekali.
Selain itu dapat juga mengenai selaput lendir.
Bntk ini diturunkan secara dominan dan
resesif.
57

Pengobatan.
- Kortikosteorid sistemik dan topikal.
- Antibiotika utk inf sekunder.

Diagnosa banding.
- Impetigo bulosa pada bayi baru lahir.
- Porphyria cutanea tarda.
- TEN.

Tanda diagnostik.
Suspek pada bayi atau anak yg mudah tbl bula oleh
gesekan atau trauma ringan.
58

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