Erythema nodosum-like lesions in treated Whipple's disease: signs of immune reconstitution inflammatory syndrome.

Treatment of systemic infections due to mycobacteria and HIV infection can lead to paradoxical worsening, the immune reconstitution inflammatory syndrome, in a minority of patients. Herein we describe a patient with Whipple's disease, a chronic systemic inflammatory disease caused by Tropheryma whipplei, who developed cutaneous and later ocular disease after initiation of antibiotic therapy. A 42-year-old man with a 12-year history of arthralgias presented with deteriorating health, including weight loss, diarrhea, fever, and acral hyperkeratosis. Whipple's disease was suspected and subsequently confirmed by finding periodic acid-Schiff (PAS)-positive foamy macrophages and T whipplei DNA by polymerase chain reaction (PCR) assays in duodenal biopsy specimens. After 5 weeks of antibiotic treatment with ceftriaxone, erythema nodosum (EN)-like lesions developed on the legs and trunk. Notably, lesional and nonlesional skin harbored intracellular and extracellular degenerated bacteria that were associated with a neutrophilic and granulomatous inflammatory response in lesional skin. Continued antibiotic therapy was associated with recurring EN-like skin nodules, orbital swelling, and facial herpes simplex virus 1 infection. Corticosteroid therapy controlled the duration and severity of the EN-like nodules and orbital swelling. Apart from cutaneous hyperpigmentation, skin disease in Whipple's disease is infrequent and can be categorized as disorders due to malnutrition from malabsorption or so-called reversal reactions consisting of reactive erythemas, and neutrophilic and granulomatous responses to T whipplei, the latter of which can represent an immune reconstitution inflammatory reaction after initiation of antibiotic therapy. Finally, based on the presence of T whipplei in normal skin, skin biopsy may serve as another site for diagnostic testing in patients suspected of having Whipple's disease.