Whipple's Disease: A Challenging Diagnosis

Abstract

Whipple's disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei. It is a rare condition with a wide spectrum of clinical presentations, necessitating a high clinical suspicion to arrive at the diagnosis. We present the case of a 65-year-old woman who experienced chronic, intermittent, and migratory polyarthralgia, weight loss, anorexia, and pyrosis. She was admitted due to bilateral deep vein thrombosis (DVT). She exhibited lymphadenopathy without hepatosplenomegaly, and lymph node biopsy revealed reactive lymphadenitis with intrahistiocytic bacilli that reacted positively to periodic acid-Schiff staining. This led to the suspicion of WD, which was subsequently confirmed through small bowel biopsies. She initiated treatment with ceftriaxone and experienced rapid clinical improvement. WD poses a diagnostic challenge. The signs and symptoms are often nonspecific and can result in misdiagnosis as a rheumatic or neoplastic disease. The presentation with DVT, while unusual, has been reported as a manifestation of WD.

Keywords: deep vein thrombosis (dvt); polyarthralgia; reactive lymphadenitis; tropheryma whipplei; whipple's disease.

Figure 1. Echo-Doppler ultrasound of the lower limbs

Heterogeneous luminal filling and lack of compressibility on the left (L) and right (R) popliteal veins, aspects compatible with bilateral deep vein thrombosis

Figure 2. Anatomopathological study of lymph node

(A) Lymph node exhibiting distorted architecture characterized by a significant number of histiocytes, at times aggregated and forming non-necrotizing granulomas (black arrows). (B) Histochemical examination revealed threadlike structures, resembling bacilli, located intrahistiocytically, and these structures tested positive for PAS (Periodic Acid-Schiff) and PAS-diastase. No morphological or immunohistochemical evidence of neoplastic tissue was identified. Images kindly provided by Dr. Joaquim Tinoco (Anatomical Pathology Service of Hospital Prof. Doutor Fernando Fonseca)

Figure 3. Histopathological study of small intestine biopsies

(A) Proximal intestine with relatively preserved crypt architecture, alongside mucosal expansion in certain villi due to the presence of xanthochromic macrophages (black arrows), H&E 4x. (B) In the histochemical analysis, intracytoplasmic bacilli that tested positive for PAS (Periodic Acid-Schiff) and PAS-D (Diastase) were identified. The Ziehl-Neelsen staining showed negative results, PAS-D 10x Images kindly provided by Dr. Joaquim Tinoco (Anatomical Pathology Service of Hospital Prof. Doutor Fernando Fonseca)