There are four key findings in patients with suspected severe drug reactions: a high risk medication, mucosal involvement, presence of pustules, and laboratory abnormalities, especially a CBC with differential and liver function tests, James R. Treat, MD, said at a pediatric dermatology meeting sponsored by Rady Children’s Hospital–San Diego and UC San Diego School of Medicine.
Several cutaneous drug reactions that were discussed during the conference included acute generalized exanthematous pustulosis (AGEP), a drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN).
Dr. James Treat
AGEP is characterized by fever and generalized pustular eruption arising swiftly after administration of the causative drug. Such drugs include antibiotics, contrast agents, antifungals, and calcium channel blockers. Withdrawal of the offending drug and optimization of fluid and electrolyte balance are warranted in the management of AGEP. Topical steroids may decrease hospital length-of-stay and help with symptomatic treatment of AGEP, said Dr. Treat, a pediatric dermatologist at Children’s Hospital of Philadelphia and an assistant professor of pediatrics and dermatology at the Perelman School of Medicine at the University of Pennsylvania.
A DRESS, also known as drug hypersensitivity syndrome, or drug-induced hypersensitivity syndrome, is a skin eruption that generally occurs 2-6 weeks after the patient starts the offending medication. Clinical signs of this condition include ill-appearance, fever (greater than 100.4° F), facial and hand edema, lymphadenopathy, and lab abnormalities, including hypereosinophilia, atypical lymphocytosis, transaminitis, and human herpesvirus 6 reactivation. DRESS may be misdiagnosed as viral infection, Kawasaki’s disease, or SJS.
Commonly implicated drugs include antiepileptic drugs, antibiotics, HIV medications, and sulfa-containing medications.
“While withdrawal of the offending drug is promptly warranted, this condition may require other therapeutics, particularly if there is significant systemic involvement,” Dr. Treat emphasized. There is evidence that systemic steroids (1-2 mg/kg/day) and cyclosporine can help improve the disease course, although their use is off-label.
SJS and TEN are other severe cutaneous adverse reactions caused by Mycoplasma infection or medications, such as anticonvulsants, antibiotics, HIV medications, and sulfa-containing drugs. “These entities are characterized by an ill-appearing, febrile patient with painful skin and mucosal membrane involvement,” Dr. Treat described.
Mucosal predominance may be seen in cases associated with Mycoplasma and have been termed “Mycoplasma-induced rash and mucositis,” although the terminology is controversial. In a case series by Darren G. Gregory, MD, treatment with amniotic membrane transplantation applied to the eyelid margins, palpebral conjunctiva, and ocular surface during the acute phases of SJS and TEN has been shown to be effective, decreasing the risk of significant oculovisual sequelae (Ophthalmol. 2011 May;118[5]:908-14).
Diagnostic criteria have been detailed to classify each of these adverse reactions. Dr. Treat concluded his lecture with a discussion of a retrospective study by Bouvresse et al. that projected AGEP, DRESS, and SJS-TEN as distinct entities (Orphanet J Rare Dis. 2012. doi: 10.1186/1750-1172-7-72).
Dr. Treat reported having no relevant financial disclosures.