# Whipple’s Disease: A Diagnostic Challenge in Patients With Chronic Diarrhea

**Authors:** Elisa Veigas, João Lança Pereira, Marta Marques, Pedro Rodrigues, Jorge Correia

PMC · DOI: 10.7759/cureus.102988 · 2026-02-04

## TL;DR

Whipple’s disease is a rare, hard-to-diagnose condition that can cause chronic diarrhea and other symptoms, but early detection and treatment lead to good outcomes.

## Contribution

This case highlights the diagnostic challenges of Whipple’s disease and the importance of repeat endoscopy and timely antibiotic treatment.

## Key findings

- Whipple’s disease was confirmed through histology showing characteristic foamy macrophages in the duodenum.
- The patient achieved clinical remission with a prolonged course of antibiotics.
- Repeat endoscopy was crucial in diagnosing the condition after initial tests were normal.

## Abstract

Whipple’s disease, associated with chronic infection by Tropheryma whipplei, is an uncommon multisystem condition. It is frequently underdiagnosed because of its nonspecific and variable symptoms. Early recognition is important, as delays in diagnosis can result in multisystem involvement and potentially serious outcomes.

A 74-year-old man experienced chronic diarrhea, weight loss, and fatigue over three months. Initial investigations, including imaging and endoscopy, did not reveal any abnormalities. As symptoms persisted, a repeat endoscopy was performed after one month, showing multiple whitish elevated plaques in the duodenum. Histology identified periodic acid-Schiff and CD68-positive foamy macrophages with negative Ziehl-Neelsen staining, confirming Whipple’s disease. The patient was treated with ceftriaxone for two weeks, followed by a year of doxycycline and hydroxychloroquine, leading to rapid clinical remission. Due to ongoing histological changes, antibiotic therapy was continued for another year with trimethoprim-sulfamethoxazole and an additional six months of doxycycline. The patient remains asymptomatic on follow-up. Whipple’s disease has clinical features that overlap with other chronic gastrointestinal and rheumatologic disorders, often leading to diagnostic challenges. This case demonstrates the importance of maintaining a high index of suspicion and performing repeat endoscopic evaluation if symptoms continue despite unremarkable initial findings. Timely administration of suitable antibiotic therapy is associated with favorable clinical outcomes, even in cases with prolonged or atypical presentations.

## Linked entities

- **Chemicals:** ceftriaxone (PubChem CID 5479530), doxycycline (PubChem CID 54671203), hydroxychloroquine (PubChem CID 3652), trimethoprim-sulfamethoxazole (PubChem CID 358641)
- **Diseases:** Whipple’s disease (MONDO:0005116)

## Full-text entities

- **Genes:** CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}
- **Diseases:** gastrointestinal and rheumatologic disorders (MESH:D005767), weight loss (MESH:D015431), Chronic Diarrhea (MESH:D003967), Whipple's Disease (MESH:D008061), infection (MESH:D007239), fatigue (MESH:D005221)
- **Chemicals:** doxycycline (MESH:D004318), ceftriaxone (MESH:D002443), hydroxychloroquine (MESH:D006886), trimethoprim-sulfamethoxazole (MESH:D015662)
- **Species:** Homo sapiens (human, species) [taxon 9606], Tropheryma whipplei (species) [taxon 2039]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12872331/full.md

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Source: https://tomesphere.com/paper/PMC12872331