Two days after undergoing uncomplicated bilateral total knee arthroplasties, a 72-year-old man had a temperature of 101°F and a pruritic, erythematous rash that originated on his trunk and spread peripherally to his arms and upper thighs over the course of 24 hours.
Although rare, cutaneous drug reactions such as acute generalized exanthematous pustulosis, the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, the Stevens–Johnson syndrome, and toxic epidermal necrolysis can cause dramatic presentations and critical illness. These syndromes have certain features in common, and there is some evidence that patients can have overlap syndromes. A new Clinical Problem-Solving article explains.
• How often is acute generalized exanthematous pustulosis caused by medications?
At least 90% of cases of acute generalized exanthematous pustulosis are attributed to medication exposure, with antibiotics, antiepileptic agents, and antihypertensive agents commonly cited as culprits. Other reported triggers include viral infection, mercury, and spider bites.
• What is known about the pathophysiology of acute generalized exanthematous pustulosis?
The pathophysiological basis of acute generalized exanthematous pustulosis remains unclear; however, researchers evaluating cells isolated from skin lesions have found that the initial cellular infiltrate consists primarily of CD4+ and CD8+ T cells. In cases of acute generalized exanthematous pustulosis that are precipitated by medications, these T cells are drug-specific. Data also suggest that the initial T-cell infiltrates release inflammatory mediators, such as interleukin-8.
Morning Report Questions
Q: Describe some of the clinical and histologic features of acute generalized exanthematous pustulosis.
A: Skin findings in this disorder typically consist of diffuse erythema and edema with pinpoint nonfollicular, sterile pustules that can develop hours or days after exposure to the offending agent. The pustules often develop initially in intertriginous areas but can spread diffusely and rapidly. After removal of the trigger, the intensity of the rash typically peaks within 2 weeks and is followed by superficial desquamation. A pathologically similar but more localized form, known as acute localized exanthematous pustulosis, can also occur. Other common clinical features in acute generalized exanthematous pustulosis include fever, leukocytosis, lymphadenopathy, transaminitis, hypocalcemia, and mild renal insufficiency. Patients may also report burning or itching. The diagnosis is confirmed on biopsy; common histologic features include subcorneal or intraepidermal spongiform pustules, edema, and neutrophilic or eosinophilic infiltrates.
Q: How is acute generalized exanthematous pustulosis managed?
A: The mainstay of treatment is removal of the offending agent, which typically leads to full resolution of the skin lesions. General skin care is important for the prevention of superinfection and to promote healing, and some centers have reported rapid improvement with topical glucocorticoid use. There are no clinical trial data to support systemic glucocorticoid administration, and many clinicians reserve glucocorticoid therapy for severely ill patients.