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ADVERSE CUTANEOUSDRUG REACTIONS

Muh. Eko IrawantoBag/SMF Ilmu Kesehatan Kulit dan Kelamin FK UNS/ RS dr Moewardi Surakarta

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Urtikaria

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Acute generalized exanthematous pustulosis (AGEP)

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Drug Reaction with Eosinophilia and SystemicSymptoms (Drug-Induced Hypersensitivity Syndrome) / DRESS / DIHS

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Angioedema

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Vasculitis

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EXANTHEMATOUS DRUG REACTIONS

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EXANTHEMATOUS DRUG REACTIONS

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EPIDEMIOLOGY Age of Onset

Less common in the very young. Incidence

Most common type of cutaneous drug reaction

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ETIOLOGY Drugs with a high probability of reaction (3 –

5%): penicillin and related antibiotics, carbamazepine, allopurinol, gold salts (10–20%).

Medium probability : sulfonamides (bacteriostatic, antidiabetic, diuretic), nonsteroidal anti-inflammatory drugs (NSAIDs), hydantoin derivatives, isoniazid, chloramphenicol, erythromycin, streptomycin.

Low probability (<1%): barbiturates, benzodiazepines, phenothiazines, tetracyclines

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PATHOGENESIS Exact mechanism unknown. Probably delayed hypersensitivity.

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CLINICAL MANIFESTATIONS

Onset Early Reaction In previously sensitized

patient, eruption starts within 2 or 3 days after readministration of drug.

Late Reaction Sensitization occurs during administration or after completing course of drug; peak incidence at ninth day after administration.

However, ACDR may occur at any time between the first day and 3 weeks after the beginning of treatment.

Reaction to penicillin can begin ≥2 weeks after drug is discontinued.

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Skin Symptoms Usually quite pruritic, disturbs sleep. Painful skin lesions suggest development

of a more serious ACDR, such as TEN. Systems Review

Fever, chills.

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Skin Lesions Macules and/or papules, a few millimeters to

1 cm in size (Figs. 22-1 and 22-2). Bright or “drug” red. Resolving lesions have hues of tan and purple. In time, lesions become confluent forming

large macules, polycyclic/ gyrate erythema, reticular eruptions, sheetlike erythema (Fig. 22-1), erythroderma; alsoerythema multiforme–like.

Scaling and/or desquamation may occur with healing.

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Distribution Symmetric (Fig. 22-1). Almost always on trunk and extremities. Confluent lesions in intertriginous areas,

i.e., axilla, groin, inframammary area. Palms and soles variably involved. In children, may be limited to face and

extremities.

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

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Mucous Membranes Enanthem on buccal mucosa.

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LABORATORY EXAMINATIONS Hemogram

Peripheral eosinophilia. Dermatopathology

Perivascular lymphocytes and eosinophils.

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MANAGEMENT The definitive step in management is to

identify the offending drug and discontinue it. Symptomatic Treatment

Oral antihistamine to alleviate pruritus. Glucocorticoids

Potent Topical Preparation May help speed resolution of eruption.

Oral or IV Provides symptomatic relief. If offending drug cannot be substituted or omitted,

systemic glucocorticoids can be administered to treat the ACDR; also, to induce more rapid remission.

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FIXED DRUG ERUPTION

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FIXED DRUG ERUPTION

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PATHOGENESIS Unknown.

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CLINICAL MANIFESTATION Drug History Patients frequently give a

history of identical lesion(s) occurring at the identical location.

Skin symptoms : Usually asymptomatic. May be pruritic, painful, or burning. Painful when eroded.

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Time to onset of lesion(s) : Occur from 30 min to 8 h 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.

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Skin Lesions The characteristic early lesion is a

sharply demarcated macule, round or oval in shape, occurring within hours after ingestion of the offending drug.

Initially erythema, then dusky red to violaceous.

Most commonly, lesions are solitary and can spread to become quite large (Fig. 22-9A), but they may be multiple (Fig. 22-9B) with random distribution;

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Lesions become edematous, thus forming a plaque, which may evolve to become a bulla (Fig. 22-8B) and then an erosion.

Eroded lesions, especially on genitals or oral mucosa, are quite painful.

After healing, dark brown with violet hue postinflammatory hyperpigmentation.

Genital skin (Fig. 35-19) is frequently involved site, but any site may be involved; perioral, periorbital (Fig. 22-8A).

Occur in conjunctivae, oropharynx.

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LABORATORY EXAMINATIONS Dermatopathology

Similar to findings in erythema multiforme and/or TEN.

Patch Test Suspected drug can be placed as a patch

test at a previously involved site

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MANAGEMENT Identify and withhold the offending drug. Non-eroded lesions can be treated with a

potent topical glucocorticoid ointment. Eroded cutaneous lesions can be treated

with an antimicrobial ointment and a dressing until the site is reepithelialized.

For widespread, generalized, and highly painful mucosal lesions, oral prednisone 1 mg/kg body weight tapered over a course of 2 weeks.

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THANK YOU

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