Whipple disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 20 Apr 2025

Last updated: 20 Sep 2023

Whipple disease is a chronic multisystemic disease caused by the gram-positive bacterium Tropheryma whipplei, first described by G.H. Whipple in 1907.

Affected patients are typically middle-aged white men, who may present with weight loss, arthralgia, diarrhea, and fever.

The infection is very rare, even though T whipplei is ubiquitously present in the environment.

Diagnosis is mainly based on duodenal biopsies. Histologic findings are characterized by foamy macrophages in the lamina propria that contain large amounts of diastase-resistant periodic acid-Schiff (PAS)-positive particles in the cytoplasm. Polymerase chain reaction (PCR)-based diagnosis can be established from cerebrospinal fluid (CSF) or synovial fluid.

Recommended treatment is with intravenous ceftriaxone for 14 days, followed by oral trimethoprim/sulfamethoxazole for 1 year.

Definition

Whipple disease is a rare, multisystemic, chronic infective disease caused byTropheryma whipplei, a gram-positive bacterium from the Actinomycetes clade with a genome rich in guanine and cytosine (G-C) nucleotides.[1][2]T whipplei is found ubiquitously in the environment and in healthy carriers.[3][4][5][6][7][8][9][10] A genetic predisposition for Whipple disease seems to enable the establishment of an infection.[11][12] Patients are typically middle-aged white men, who present with arthralgia, weight loss, diarrhea, and fever.[11][12][13][14]

History and exam

Key diagnostic factors

diarrhea
weight loss
arthralgia
supranuclear ophthalmoplegia

Full details

Other diagnostic factors

abdominal pain
lymphadenopathy
fever
steatorrhea
anemia
skin darkening
confusion, memory impairment, altered level of consciousness, or dementia
apathy
anxiety, depression, hypomania, psychosis, change in personality
myoclonic signs
seizures
nystagmus
brisk reflexes, extensor plantar responses, weakness predominating in arm extensors and leg flexors, hypertonia
amenorrhea, polydipsia, hyperphagia, decreased libido
ataxia
headaches
oculomasticatory and oculofacioskeletal myorhythmias
hemiparesis
cranial nerve involvement
extrapyramidal movement disorder
peripheral neuropathies

Full details

Risk factors

age >50 years
male sex
genetic factors

Full details

Diagnostic tests

1st tests to order

CBC
serum albumin
serum CRP
serum ESR
upper GI endoscopy
Periodic acid-Schiff (PAS) staining of duodenal biopsies
PCR
Tropheryma whipplei-specific immunohistochemistry

Full details

Emerging tests

electron microscopy
culture
serology

Treatment algorithm

ACUTE

patients without CNS involvement

patients with CNS involvement

Contributors

Authors

Thomas Schneider, MD, PhD

Professor

Medical Department I

Charité - University Medicine Berlin

CBF

Berlin

Germany

Disclosures

TS is an author of a number of references cited in this topic.

Verena Moos, PhD

Scientist

Medical Department I

Charité - University Medicine Berlin

CBF

Berlin

Germany

Disclosures

VM is an author of a number of references cited in this topic.

Peer reviewers

Stephen G. Baum, MD

Professor of Medicine

Department of Microbiology and Immunology

Albert Einstein College of Medicine

Bronx

Disclosures

SGB declares that he has no competing interests.

Chris Huston, MD

Assistant Professor of Medicine

Division of Infectious Diseases

University of Vermont

Burlington

Disclosures

CH declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Schneider T, Moos V, Loddenkemper C, et al. Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar;8(3):179-90. Abstract

Fenollar F, Puechal X, Raoult D. Whipple's disease. N Engl J Med. 2007 Jan 4;356(1):55-66.

Dobbins WO. Whipple's disease. Springfield, IL: Thomas; 1987.

Louis ED, Lynch T, Kaufmann P, et al. Diagnostic guidelines in central nervous system Whipple's disease. Ann Neurol. 1996 Oct;40(4):561-8. Abstract

Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. Gastroenterology. 2010 Feb;138(2):478-86; quiz 11-2.Full text Abstract

Feurle GE, Moos V, Bläker H, et al. Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipple's disease. J Infect. 2013 Mar;66(3):263-70. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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Whipple disease

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Emerging tests

Treatment algorithm

patients without CNS involvement

patients with CNS involvement

Contributors

Authors

Thomas Schneider, MD, PhD

Disclosures

Verena Moos, PhD

Disclosures

Peer reviewers

Stephen G. Baum, MD

Disclosures

Chris Huston, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice