Treated Whipple disease with erythema nodosum leprosum-like lesions: cutaneous PAS-positive macrophages slowly...

Area of Science:

• Infectious diseases
• Immunology
• Dermatology

Background:

• Whipple disease (WD) is pathologically defined by macrophages laden with Tropheryma whipplei (TW) bacilli, typically observed in the duodenum.
• Previous findings indicated the presence of these bacteria and macrophages in skin lesions during immune reconstitution inflammatory syndrome (IRIS) in a WD patient.

Observation:

• This study followed a patient with WD and IRIS for 5 years, observing the gradual abatement of IRIS over 18 months.
• No recurrence of WD was detected, with all biopsies testing negative for TW DNA.
• Periodic acid-Schiff (PAS)-positive macrophages, indicative of TW presence, were found in 96% of skin biopsies and decreased over time.
• ENL-like lesions exhibited significantly higher PAS+ macrophage counts compared to normal skin, and abdominal skin near lesions had more PAS+ macrophages than arm skin.
• Lymphangiectases, a sign of lymphostasis, were present in all skin biopsies.

Findings:

• The bacillary burden appears to influence immune tolerance to live TW in active WD and triggers ENL-like nodules against dead TW in treated WD.
• Poor lymphatic drainage may contribute to the slow clearance of TW from the skin.
• Impaired delayed-type hypersensitivity reactions in WD, potentially due to reduced immune cell trafficking, hinder adaptive immunity induction.

Implications:

• Understanding the role of bacillary burden and lymphatic drainage in WD pathogenesis can inform treatment strategies.
• These findings highlight the dynamic interplay between Tropheryma whipplei, host immunity, and clinical manifestations in Whipple disease.
• Further research into immune cell trafficking and lymphatic function could reveal new therapeutic targets for WD and related inflammatory conditions.