Defined as a drug reaction that affects the structure or function of the skin, its appendages, or mucous membranes.
Common adverse skin reactions to systemic drugs include: maculopapular skin reactions; urticaria and angio-oedema; and the spectrum of skin lesions including fixed drug eruptions, erythema multiforme, DRESS (drug reaction with eosinophilia and systemic symptoms; also called drug hypersensitivity syndrome), Stevens-Johnson syndrome, and toxic epidermal necrolysis. Together these account for the majority of all drug-induced skin manifestations.
Any drug can cause a predictable or unpredictable reaction; those commonly implicated include beta-lactam antibiotics, muscle relaxants used in anaesthesia, sulfonamides and structurally related drugs, contrast media, and gelatins.
A history of previous reactions to drugs should always be taken before prescribing.
Skin tests (prick tests, intradermal tests, patch tests) can occasionally be useful in diagnosing allergic reactions retrospectively, especially contact dermatitis.
After anaphylactic reactions, serum tryptase activity can help in diagnosis.
Cutaneous drug reactions are common. They are adverse drug reactions (ADRs) producing a wide range of skin manifestations. An ADR may be defined as an undesirable clinical manifestation resulting from administration of a particular drug. Another definition is that of an appreciably harmful or unpleasant reaction resulting from an intervention related to using a medicinal product. An ADR may be either immunological (i.e., drug allergy) or non-immunological (i.e., drug intolerance). Drug allergies are estimated to account for <10% of all adverse drug reactions, with drug intolerance accounting for the other 90%.
Adverse reactions usually predict hazard from receiving the drug in the future and warrant prevention, specific treatment, alteration of the dose regimen, or withdrawal of the product. They range from common irritant eruptions to rare, life-threatening drug-induced diseases.
A serious adverse reaction is any untoward medical occurrence that at any dose: results in death; is life threatening; requires or prolongs hospital admission; requires medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure; is a congenital anomaly; or is any medical event that would be regarded as serious if it had not responded to immediate treatment.
The most common skin drug eruptions typically present as pruritus, maculopapular eruptions, urticaria, angio-oedema, phototoxic and photoallergic reactions, fixed drug reactions, vesiculobullous reactions, and exfoliative lesions. These manifestations clinically resemble an allergic response and are considered drug hypersensitivity reactions.
Drug reactions can be solely limited to the skin, or they may be part of a systemic reaction.
History and exam
Key diagnostic factors
- presence of risk factors
- history of drug exposure
- skin lesions
- variable skin reactions within 5 to 15 minutes of drug exposure
- variable skin reactions within a few hours of drug exposure
- variable skin reactions within 2 weeks of drug exposure
- variable skin reactions within months to years of drug exposure
- previous exposure and reaction to drug
Other diagnostic factors
- associated non-cutaneous features
- virus infections
- HIV infection
- HLA-B*5701 polymorphism
- HLA-B*1502 polymorphism
- HLA-B*5801 polymorphism
- female sex
Investigations to consider
- blood (whole blood, plasma, serum) drug concentration
- serum tryptase concentration (anaphylaxis)
- complement pathway assay
- histology of lesion biopsy
- FBC and differential
- anti-histone antibodies to single-stranded DNA (lupus-like syndrome)
- skin tests (prick tests, intradermal tests, patch tests)
- drug-specific IgE
- basophil activation test
- lymphocyte proliferation assay (LPA/LTT)
- enzyme-linked immunospot assay (ELISPOT test)
serious cutaneous adverse reactions
non-serious cutaneous adverse reactions
following acute episode
- Systemic lupus erythematosus
- Auto-immune blistering disorders
- Staphylococcal scalded skin syndrome
- Web-based integrated guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care
- British Association of Dermatologists’ guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in children and young people, 2018
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