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# Whipple disease: foamy PAS-positive macrophages in the villi

- Lesion

A rare bacterial infection fills the small-bowel lining with swollen macrophages that block fat transport and cause diarrhoea and joint pain.

Updated Nov 12, 2026

## Key points

- Classic triad: diarrhoea (malabsorption), weight loss and arthralgia; joint symptoms may come years first.
- Histology: sheets of foamy macrophages distending villi; PAS-positive, diastase-resistant granules.
- Acid-fast stain negative, which separates it from Mycobacterium avium complex (also PAS-positive foamy macrophages).
- Electron microscopy shows rod-shaped bacilli; PCR confirms.
- Other sites: lymph nodes, synovium, heart valves, brain.
- Most common in middle-aged white men, often with soil or animal exposure.

## What it is

Whipple disease is a rare chronic multisystem infection by the actinomycete Tropheryma whipplei. Macrophages stuffed with partly digested bacteria accumulate in the lamina propria of the small intestine and in mesenteric lymph nodes, obstructing lymphatic drainage. The malabsorption is therefore lymphatic, not epithelial. Infection is rare despite many healthy carriers, suggesting host susceptibility.

## Structure

- Gross and endoscopy: shaggy mucosa with white-yellow plaques from dilated lymphatics and lipid.
- Micro: lamina propria effaced by distended foamy macrophages; dilated lacteals and fat deposits.
- Similar macrophages in nodes, synovium, valves and the CNS.

## Step by step

- T. whipplei is acquired from the environment.
- Macrophages ingest the bacteria but fail to kill them.
- Laden macrophages pack the villi and mesenteric nodes.
- Lymph drainage is obstructed, so absorbed fat cannot leave.
- Malabsorptive diarrhoea follows, with systemic spread to joints, heart and brain.

## Markers

- PAS-positive, diastase-resistant
- Acid-fast negative
- PCR for T. whipplei

## Clinical notes

- Untreated it is fatal; long antibiotic courses cure most patients, though relapse can occur.
- In a patient with HIV, foamy macrophages are more likely Mycobacterium avium complex: the acid-fast stain decides.

## Memory aid

Whipple: Weight loss, Wobbly joints, Watery stools, With PAS-pink foamy macrophages.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does Whipple disease cause malabsorption?

Bacteria-laden macrophages in the lamina propria and mesenteric nodes obstruct lymphatic drainage.

## Which stain separates Whipple disease from Mycobacterium avium complex infection?

The acid-fast stain: mycobacteria are positive, T. whipplei is negative; both are PAS-positive.

## What is the classic clinical triad of Whipple disease?

Diarrhoea, weight loss and arthralgia.

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## Connections

## Related 3

- [Malabsorption and diarrhoea](https://durgical.com/en/general-pathology/malabsorption-and-diarrhoea/)
- [Coeliac disease](https://durgical.com/en/general-pathology/coeliac-disease/)
- [Special stains in diagnosis: Congo red, Prussian blue, PAS, Ziehl–Neelsen, Gram](https://durgical.com/en/general-pathology/special-stains-in-diagnosis-congo-red-prussian-blue-pas-ziehl-neelsen-gram/)

## Related conditions 2

- [Whipple disease](https://durgical.com/en/conditions/whipple-disease/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)

## Microorganisms 1

- [Tropheryma whipplei](https://durgical.com/en/microbiology/tropheryma-whipplei/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Whipple disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000209.htm) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/whipple-disease-foamy-pas-positive-macrophages-in-the-villi/