Drug eruptions

Drug eruptions

Neil H. Shear and Sandra R. Knowles

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


Drug eruptions are common drug-induced diseases, often with a known etiology but a poorly understood pathogenesis. Most cutaneous reactions are broadly classified as either allergic (immunologic) or idiosyncratic. Drug eruptions can range from a mild, simple exanthematous eruption to severe eruptions with systemic involvement, such as toxic epidermal necrolysis. The image above shows a widespread exanthematous eruption. This can be localized to skin or, in the presence of fever, may be part of a systemic reaction.

Management strategy

There are two steps in diagnosing drug eruptions. First, determine the morphology, e.g., exanthematous (‘maculopapular eruption’ – the most common), urticarial, blistering, or pustular. Second, look for signs of systemic involvement, such as fever, lymphadenopathy, or malaise. Examples of simple eruptions without systemic disease are maculopapular eruption, urticaria, fixed drug eruption, and drug-induced acne. Examples of complex eruptions with systemic disease are drug rash eosinophilia systemic syndrome (DRESS, also known as hypersensitivity drug reaction), serum sickness-like reaction, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).

After a diagnosis is considered, it is important to try and identify the relevant drug exposure, consider a differential diagnosis, and remember that each drug exposure has a possible etiologic role. In general, most drug eruptions occur within 3 months of starting therapy, although some eruptions can develop after 1 to 2 years (e.g., drug-induced lupus).

Treatment involves stopping drugs that have a high probability of being the cause, while providing supportive therapy for symptoms. Laboratory investigations may identify internal organ toxicity, and systemic therapy may be considered. The patient should be advised of the interpretation of the adverse event, what drugs were likely causes, whether tests will help confirm the cause, and what drugs should be avoided in the future. For severe reactions relatives may need to be informed, because some systemic reactions (e.g., DRESS, TEN) have a genetic susceptibility.

Specific investigations

Skin testing in delayed reactions to drugs.

Barbaud A. Immunol Allergy Clin North Am 2009; 29: 517–35.

Skin tests (prick, intradermal tests and patch tests) have been used in the investigation of cutaneous adverse drug reactions. In general, it is recommended that drug skin tests be done within 6 months following the cutaneous adverse drug reaction. Patch tests are of potential value in patients with a history of a maculopapular rash, symmetric drug-related intertriginous and flexural exanthema, AGEP, and fixed drug reaction.

Patch tests and prick tests can be done with any form of the commercialized product, whereas intradermal tests can be done only if an injectable form of the drug is available commercially. A table summarizing the concentrations used for patch testing for various drugs is also included in this article.

Drug provocation tests in hypersensitivity drug reactions.

Rerkpattanapipat T, Chiriac AM, Demoly P. Drug provocation tests in hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol 2011; 11: 299–304.

Drug provocation testing is used as a tool to evaluate causality in drug-induced eruptions; it is often considered the ‘gold standard’ in the diagnosis of drug hypersensitivity. However, because of the potential risks, it is usually reserved when the implicated drug is required for treatment, alternative test methods have failed and there are no contraindications. Drug provocation tests are used for beta-lactam antibiotics (often in conjunction with negative skin tests), ASA/NSAIDs, glucocorticoids and local anesthetics.

Drug provocation test with the implicated drug is often done, although it can not be recommended for patients with histories of a severe reaction. The clinical question should be ‘What drug can the patient use in the future?’ not ‘What drug caused the reaction?’.

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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Drug eruptions

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