Classification of drug reactions.

10.1 Classification of drug reactions.

Clinical features

A thorough physical examination is essential in the evaluation of cutaneous drug eruptions (10.2). Cutaneous drug reactions may be associated with systemic anaphylaxis, or with extensive muco-cutaneous exfoliation and multisystem involvement. Signs warranting discontinuation of the drugs are: mucous membrane erosions, blisters, confluent erythema, angioedema and tongue swelling, palpable purpura, skin necrosis, lymphadenopathy, and fever.

The skin lesions should be described based on their distribution and morphology (Table 10.3) . The morphology of the lesions could provide a clue regarding the most likely culprit. Morbilliform or maculopapular exanthems are the most common patterns,

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to confluence of lesions and generalized erythroderma, or exfoliative dermatitis. A morbilliform eruption is often the initial presentation of a more severe reaction, such as toxic epidermal necrolysis (TEN), hypersensitivity syndrome, and serum sickness. Urticaria is the mildest form of cutaneous skin reactions and, although quite a few drugs are implicated, it is important to note that certain drugs, such as salicylates, opiates, and radio contrast agents, can cause urticaria by non-immune mechanisms (10.3). Re- administration of the offending drug may lead to anaphylaxis due to IgE-mediated mechanisms. Drugs also

Table 10.2 Gell and Coombs classification of

drug-induced hypersensitivity

Hypersensitivity Synonym Immunological Mediators of Examples

reactions mechanism tissue injury and inflammation

Type 1 Immediate

Anaphylaxis, urticaria, hypersensitivity drug-specific IgE products of

Mediated by

mast cells/basophils

Type 2 Antibody-

Complement Vasculitis mediated

Mediated by

drug-specific IgM

cytotoxic

and IgG

hypersensitivity antibodies Type 3

Immune

Complement Serum sickness complex-

Mediated by

vasculitis mediated

drug-specific IgG

and IgM

hypersensitivity antibodies Type 4

Cell-mediated

Contact sensitivity, hypersensitivity lymphocyte

Drug-specific T- Lymphokines

and monokine maculopapular rash,

mediated reaction

morbilliform eruption, fixed drug eruption, photodrug reaction, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

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10.2 Assessment of adverse reactions to drugs (ADRs). (ELISA, enzyme- linked immunosorbent assay; RAST, radio allergen sorbent test; SPT, skin prick test.)

Table 10.3 Cutaneous manifestation of drug

reactions

Cutaneous Drugs implicated manifestation

Urticaria Aspirin, NSAIDs, angiotensin-converting enzyme inhibitors, penicillin, cephalosporins, opiates, peptide hormones, radiocontrast dyes, vaccines

Maculopapular Aspirin, NSAIDs, ampicillin, anticonvulsants, barbiturates, isoniazid, eruptions

phenothiazines, quinalones, sulphonamides, thiazides, co-trimoxazole Pemphigus

Penicillamine, gold, levodopa, heroin, penicillin, rifampin, phenylbutazone

Photosensitivity Amiodarone, chlorpromazine, frusemide, quinalones, sulphonamides, tetracycline, thiazides

Fixed drug eruptions Acetaminophen, penicillin, anticonvulsants, barbiturates, metronidazole, OCPs

Steven-Johnson Sulphonamides, co-trimoxazole, tetracyclines, barbiturates, thiazetazone, syndrome, TEN

phenytoin, carbamazepine, phenylbutazone Vascullitis

Allopurinol, cimetidine, gold, phenytoin, quinalones, propyl-thio-uracil, thiazides, NSAIDs

Vesiculo-bullous Aspirin, NSAIDs, barbiturates, frusemide, griseofulvin, penicillamine,

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cause chronic urticaria and aspirin frequently exacerbates this problem. Erythema multiforme is an acute self-limiting inflammatory disorder of the skin and mucous membrane associated with sore throat and malaise. Typically, there are target, iris, or bull’s eye lesions, with a time course of <4 weeks.

Extensive lesions with mucous membrane involvement are called Steven-Johnson syndrome (SJS). The mortality rates have been reported to be as high as 5–15% for SJS. The more severe form of SJS is termed TEN. The discrimination between SJS and TEN is based on the extent of skin involvement. In SJS, there is detachment of <10% of epidermis, while TEN is associated with >30% involvement of the skin. The condition is characterized by confluent erythema followed by extensive areas of epidermal detachment, and there may be raised flaccid blisters, which spread with pressure. In cases of detachment of epidermis between 10–30%, it is considered as overlap between SJS and TEN. The epithelium of the airways and GI tract can also be involved. The presence of purpura and petichiae are often cutaneous stigmata of vasculitis.