Severe Cutaneous Adverse Reactions (SCAR)

Concerning features that should prompt further investigation and consideration of a more serious drug eruption include fevers, swelling of the face and/or lymph glands, involvement of mucous membranes (such as the eyes, mouth and urogenital tract), blistering and skin pain (as opposed to itch).

Stevens-Johnson syndrome/toxic epidermal necrolysis is an uncommon but severe drug reaction with blistering. It often begins with “target” lesions similar to erythema multiforme, which then blisters as the epidemis detaches from the dermis. When this epidermal detachment affects more than 30% of the body surface area the condition is referred to as toxic epidermal necrolysis. Fever and flu-like symptoms may precede the eruption, which begins anywhere from 4-21 days after starting the drug. Mucosa (mouth, eyes, urethra, and/or vulva) are almost always involved.  Sulfa drugs and aniepileptics are the most common culprits. Other causes include anticonvulsants, NSAIDs, and allopurinol. Management is as with burns: supportive care, nutritional/fluid support, and protection from infections due to loss of the skin barrier. Prompt discontinuation of the culprit medication is required.  Treatments TNF alfa inhibitors seem most beneficial, but cyclosporin, IVIG and corticosteroids have also been used.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), presents with fever and a rash. It also generally has a delayed onset – at least two weeks after initiating the medication. Laboratory abnormalities may include elevation of eosinophils, presence of atypical lymphocytes, elevated creatinine, and transaminitis. The rash itself looks similar to a morbilliform drug eruption but may be accompanied by facial edema, lymphadenopathy and lip cracking. Medications that commonly cause DRESS include antibiotics (trimethoprim-sulfamethoaxole, vancomycin, etc.), anticonvulsants (carbamazepine, lamotrigine, phenytoin, etc.) and allopurinol. In addition to discontinuing the responsible medication, patients should be seen by any relevant specialists if there is evidence of organ involvement, as they may require treatment with systemic corticosteroids.

Acute Generalized Exanthematous Pustulosis (AGEP) has a relatively rapid onset within 5 days after the culprit medication is started. The rash is distinct and consists of numerous small pustules on a background of erythema. Fever and elevated neutrophils and/or eosinophils are common. Beta-lactam and macrolide antibiotics are the most common cause. Management is similar to a morbilliform drug eruption: withdrawal of the medication and symptomatic treatment of itch. Most patients with AGEP improve quickly once the culprit medication is discontinued.

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