Introduction

Whipple’s disease, caused by Tropheryma whipplei, is a rare multisystem infection. Although classically presenting with malabsorption or arthralgia, atypical manifestations may mimic hematologic disorders, leading to diagnostic delay. Accurate diagnosis relies on integrating clinical, biochemical, imaging, histologic, and molecular findings (1). We report a case of Whipple’s disease in which diffuse lymphadenopathies and marked inflammation initially raised concern for a lymphoproliferative disorder.

Case Description

A 39-year-old woman with perinatal hypoxic brain injury was referred for persistent systemic inflammation associated with chronic peri-umbilical pain, vomiting and a 20 kg weight loss over two years. Laboratory investigations demonstrated CRP up to 120 mg/L, ESR 115 mm/h, polyclonal hypergammaglobulinemia, elevated vitamin B12. Autoimmune work-up showed an elevated rheumatoid factor, while anti-CCP was negative and C3/C4 levels were within normal range. Infectious work-up including blood cultures and Quantiferon was negative.

CT and PET-CT revealed multiple supraclavicular, mediastinal, mesenteric, and retroperitoneal lymphadenopathies with hypermetabolic activity suggesting lymphoma. Peripheral blood immunophenotyping identified a monoclonal B-cell population compatible with marginal zone lymphoma.  Supraclavicular lymph node biopsy was unremarkable.

EUS showed a cluster of hyperechoic retroperitoneal mesenteric lymph nodes, the largest 2 cm near the SMV, sampled using FNB. Endoscopy revealed a brownish, atrophic duodenal mucosa with suspected lymphoid infiltration. Duodenal biopsies and lymph node FNB demonstrated numerous PAS- and PAS-diastase–positive macrophages. Molecular analysis and PCR on paraffin-embedded material confirmed Tropheryma whipplei, establishing disseminated Whipple’s disease.

The patient was initiated on intravenous ceftriaxone for 14 days, followed by long-term oral doxycycline for 12 to 24 months. 

Conclusion

This case illustrates an uncommon presentation of Whipple’s disease mimicking lymphoma and underlines the important role of endoscopy providing histology and PCR testing for Tropheryma whipplei in unexplained systemic inflammation and atypical lymphadenopathy.