title: Treated Whipple disease with erythema nodosum leprosum-like lesions: cutaneous PAS-positive macrophages slowly decrease with time and are associated with lymphangiectases: a case report.
abstract: Pathologically, Whipple disease (WD) is characterized by the accumulation of myriad macrophages parasitized by Tropheryma whipplei (TW) bacilli denoted by periodic acid-Schiff (PAS) positivity. These PAS+ macrophages are typically found in the duodenum associated with lymphangiectasia. Recently, we reported the presence of PAS+ macrophages and free TW in erythema nodosum leprosum (ENL)-like lesions and normal skin in a patient with WD who suffered from the immune reconstitution inflammatory syndrome (IRIS). We extend that report by describing the clinical and pathologic findings over 5 years of follow-up. First, the IRIS gradually diminished and abated over 18-month time. Second, at no point did WD recur, and all duodenal and skin biopsies tested by polymerase chain reaction were negative for TW DNA. Third, PAS+ macrophages were identified in 26 of 27 skin biopsies (96%) and decreased along with free TW over time. Fourth, ENL-like lesions had significantly greater numbers of PAS+ macrophages than normal skin. Moreover, normal abdominal skin (region of ENL-like lesions) had greater PAS+ counts than arm skin (not a site of IRIS). Last, lymphangiectases, a histologic sign of lymphostasis, was found in all skin biopsies. Overall, these findings implicate bacillary burden as a factor in the immune tolerance to live TW in active WD and the initiation of ENL-like nodules against dead/nonreplicative TW in treated WD. In addition, poor lymphatic drainage is likely responsible for the gradual clearance of TW from the skin and the impaired delayed-type hypersensitivity reaction (absence of activated macrophages) against TW found in WD, presumptively due to reduced/absent immune cell trafficking necessary for lymphocyte-macrophage interactions and induction of adaptive immunity.
authors: Divisions of Dermatopathology and Dermatology, Department of Pathology, Albany Medical College, Albany, NY, USA.
authors: Joan
authors: J
authors: Paul
authors: Jörg
authors: J
authors: Schaller
authors: Angela
authors: A
authors: Rohwedder
authors: J Andrew
authors: JA
authors: Carlson
mesh_terms: D000328:Adult; D004893:Erythema Nodosum / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000382:microbiology / Q000473:pathology; D008200:Lymphangiectasis / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008061:Whipple Disease / Q000276:immunology / Q000382:microbiology / Q000473:pathology*