# Trust Your Gut: Recognizing Whipple’s Disease Beyond the Intestine

**Authors:** Rosélia Lima, Maria Soares, Mariana Baptista, Andreia Seixas, Margarida Mota

PMC · DOI: 10.7759/cureus.102877 · 2026-02-03

## TL;DR

This paper presents two cases of Whipple’s disease showing how it can affect organs beyond the gut, emphasizing the need for early diagnosis to avoid delays.

## Contribution

The novelty lies in highlighting the extraintestinal manifestations and diagnostic challenges of Whipple’s disease through real-world clinical cases.

## Key findings

- Whipple’s disease can present with inflammatory polyarthralgia and pericarditis before gastrointestinal symptoms.
- Diagnosis was confirmed using PAS staining and PCR in both cases.
- Treatment with ceftriaxone and trimethoprim-sulfamethoxazole led to favorable outcomes.

## Abstract

Whipple’s disease is a rare, chronic, multisystemic infection caused by Tropheryma whipplei (T. whipplei), classically presenting with gastrointestinal manifestations but frequently involving extraintestinal organs that may delay diagnosis. We report two cases illustrating the clinical spectrum of Whipple’s disease: a 59-year-old man with malabsorption, chronic diarrhea, and weight loss, and a 44-year-old man with inflammatory polyarthralgia and constrictive pericarditis who developed gastrointestinal symptoms eight years later. In both cases, diagnosis was established by duodenal biopsy demonstrating periodic acid-Schiff (PAS)-positive macrophages and polymerase chain reaction confirmation of T. whipplei. Both patients were treated with intravenous ceftriaxone followed by long-term trimethoprim-sulfamethoxazole, with favorable clinical outcomes. These cases highlight the diagnostic challenges posed by atypical Whipple’s disease and underscore the importance of considering this diagnosis in patients with unexplained multisystem inflammatory syndromes.

## Linked entities

- **Chemicals:** ceftriaxone (PubChem CID 5479530), trimethoprim-sulfamethoxazole (PubChem CID 358641)
- **Diseases:** Whipple’s disease (MONDO:0005116), constrictive pericarditis (MONDO:0006711)
- **Species:** Tropheryma whipplei (taxon 2039)

## Full-text entities

- **Genes:** PRTN3 (proteinase 3) [NCBI Gene 5657] {aka ACPA, AGP7, C-ANCA, CANCA, MBN, MBT}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MPO (myeloperoxidase) [NCBI Gene 4353]
- **Diseases:** Helicobacter pylori (MESH:D016481), extraintestinal disease (MESH:D004194), vasculitis (MESH:D014657), Inflammatory (MESH:D007249), gastrointestinal symptoms (MESH:D012817), steatorrhea (MESH:D045602), IRIS (MESH:D054019), Abdominal pain (MESH:D015746), anorexia (MESH:D000855), peripheral edema (MESH:D004487), hyponatremia (MESH:D007010), pleural thickening (MESH:D010995), multisystemic illness (MESH:D056587), inflammatory syndromes (MESH:D018746), Whipple's Disease (MESH:D008061), ANCA (MESH:D056648), calcification (MESH:D002114), cancer (MESH:D009369), fatigue (MESH:D005221), hypoalbuminemia (MESH:D034141), chronic diarrhea (MESH:D003967), hyperemia (MESH:D006940), lymphadenopathy (MESH:D008206), weight gain (MESH:D015430), nausea (MESH:D009325), neurological disease (MESH:D020271), Cytomegalovirus infection (MESH:D003586), vomiting (MESH:D014839), systemic vasculitic disease (MESH:D034721), fever (MESH:D005334), duodenal lymphangiectasias (MESH:D004382), malabsorption (MESH:D008286), constrictive pericarditis (MESH:D010494), viral hepatitis (MESH:D014777), anemia (MESH:D000740), pericarditis (MESH:D010493), lymphangiectasias (MESH:D008201), diarrheal (MESH:D004403), inflammatory arthralgia (MESH:D018771), dehydrated (MESH:D003681), arthropathy (MESH:D007592), weight loss (MESH:D015431), rheumatologic (MESH:D012216), pericardial calcification (MESH:D008476), emaciated (MESH:D004614), T. whipplei infection (MESH:D007239), synovitis (MESH:D013585), hypokalemia (MESH:D007008), Gastrointestinal malignancy (MESH:D005770), Cardiac involvement (MESH:D006331), intestinal tuberculosis (MESH:D014376), organ damage (MESH:D000092124), endocarditis (MESH:D004696), abdominal tenderness (MESH:D000007), hematochezia (MESH:D006471), fungal infection (MESH:D009181)
- **Chemicals:** potassium (MESH:D011188), sodium (MESH:D012964), iron- and folate-deficiency anemia (-), ceftriaxone (MESH:D002443), trimethoprim-sulfamethoxazole (MESH:D015662), alcohol (MESH:D000438)
- **Species:** Human immunodeficiency virus (species) [taxon 12721], Tropheryma whipplei (species) [taxon 2039], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961629/full.md

---
Source: https://tomesphere.com/paper/PMC12961629