Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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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.
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.
Genetic testing (prior to initiation of therapy)
Skin biopsy
Vital signs
Hematologic profile
Liver enzymes
Urinalysis
Drug allergy testing (skin testing, patch testing) and drug challenge in carefully selected cases
Chung W, Hung S, Chen Y. Expert Opin Drug Saf 2010; 9: 15–21.
A strong association of HLA-B*1502 with carbamazepine-induced SJS/TEN has been reported in southeast Asian patients. Although the evidence is limited, it is recommended that clinicians avoid phenytoin and fosphenytoin as alternatives to carbamazepine in patients who test positive for the HLA-B*1502 allele.
The FDA in the US, as well as several other regulatory agencies, have included information in the product monograph that states that patients should be screened for HLA-B*1502 allele as well as the HLA-A*3101 allele prior to starting treatment with carbamazepine.
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.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
