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A chronic, relapsing multisystem disease first described by George Hoyt Whipple, an American pathologist, in 1907.[1] He described the disease as an intestinal lipodystrophy characterised by:
- Weight loss.
- Chronic cough.
- Fat accumulation in the intestine, mesenteric lymph nodes and stool.
It is now thought to be due to infection with actinomycete Tropheryma whipplei combined with defective cell-mediated immunity.[2][3] It is probably acquired as an enteric infection as this organism is commonly found in sewage effluent. It has also been detected in soil and is presumed to be ubiquitous.[4][5]
Traditionally, Whipple's disease has presented a diagnostic challenge to both clinicians and pathologists.[6][7]
Epidemiology
Whipple's disease is an extremely rare condition.[3] Incidence is estimated as less than 1 per 1,000,000 per annum.[2][8]
Risk factors[3]
Incidence is increased in:
- Middle-age and older individuals.
- Males more than females.
- Caucasian patients.
- Family clusters (suggesting an immunogenetic component).
- HLA-B27 antigen; HLA-DRB1*13 and DQB1*06 alleles.[9]
- Sewage plant workers, farmers and agricultural workers.
Presentation[6][8]
Not everyone with infection develops symptoms, supporting the thought that a defect in cellular immune response may predispose certain individuals.[4] There may be many different forms of presentation with the common ones being:
- Polyarthralgia - transient and episodic (often a prodromal symptom).
- Gastrointestinal symptoms:
- Abdominal pain.
- Diarrhoea.
- Anorexia and weight loss.
- Distension.
- Flatulence.
- Steatorrhea (due to malabsorption).
- Gastrointestinal bleeding.
- Intermittent low-grade fever.
- Chronic cough.
- Hyperpigmentation (occurs in 50%).
There may also be:
- Generalised lymphadenopathy.
- Anaemia and, more rarely, clotting abnormalities.
- Cardiac involvement - pericarditis, myocarditis, valve lesions.
- Central nervous system (CNS) involvement in 10% - headache, confusion, dementia, ophthalmoplegia, myoclonus, oculomasticatory movements (convergent eye movements with simultaneous chewing movements), gait abnormalities, seizures, coma.
- Ocular involvement - uveitis, vitritis, keratitis, retinitis, retinal haemorrhages.
- Pulmonary involvement - pleural effusion, mediastinal widening (due to lymphadenopathy).
- Protein-losing enteropathy with hypoalbuminaemia and oedema (due to protein loss).
- Skin involvement - very rare; may be due to malnutrition or an immune reaction to T. whipplei leading to conditions including eczematous plaques, psoriasis, erythema nodosum.[10]
Differential diagnosis
- AIDS with Mycobacterium avium complex infection of the small intestine.
- Coeliac disease.
- Sarcoidosis.
- Reiter's syndrome.
- Familial Mediterranean fever.
- Behçet's disease.
- Intestinal lymphoma.
Investigations[11]
Diagnosis requires a high index of clinical suspicion:
- Routine blood and malabsorption tests are nonspecific.
- Imaging will confirm involvement of different organs but is not diagnostic.
- Biopsy of affected tissue, usually the duodenum, shows infiltration of the lamina propria with periodic acid-Schiff stain (PAS)-positive macrophages with intracellular clumps of T. whipplei.
- PCR of bacterial RNA (unique 16s rRNA sequence) is increasingly used in diagnosis and can be done from peripheral blood, CSF and other tissue samples.
Management
- Antibiotics are the main treatment.[12] Expert microbiological advice will be needed. Prolonged treatment for up to one year is usually advised.[3]
- Repeat PCR at the end of treatment.
Prognosis
Further reading & references
- Sackmann M, Vehling V, Schmidt KD, et al; Persistent diarrhea. J Gastrointestin Liver Dis. 2008 Sep;17(3):327-8.
- Fenollar F, Puechal X, Raoult D; Whipple's disease. N Engl J Med. 2007 Jan 4;356(1):55-66.
- Desnues B, Ihrig M, Raoult D, et al; Whipple's disease: a macrophage disease.; Clin Vaccine Immunol. 2006 Feb;13(2):170-8.
- Roberts IM; Whipple Disease, Medscape, Aug 2008
- Deriban G, Marth T; Current concepts of immunopathogenesis, diagnosis and therapy in Whipple's Curr Med Chem. 2006;13(24):2921-6.
- 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.
- Rakshit RC, Mackay JD; A diagnostic conundrum.; Postgrad Med J. 2003 Sep;79(935):540, 545-6.
- Mahnel R, Marth T; Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease.; Clin Exp Med. 2004 Sep;4(1):39-43.
- Oxford textbook of medicine, 4th edition. Ed. D. Warrel et al. OUP Feb 2004 ISBN 0198529988
- Martinetti M, Biagi F, Badulli C, et al; The HLA alleles DRB1*13 and DQB1*06 are associated to Whipple's disease. Gastroenterology. 2009 Jun;136(7):2289-94. Epub 2009 Jan 27.
- Schaller J, Carlson JA; Erythema nodosum-like lesions in treated Whipple's disease: signs of immune J Am Acad Dermatol. 2009 Feb;60(2):277-88.
- Marth T, Raoult D; Whipple's disease.; Lancet. 2003 Jan 18;361(9353):239-46.
- Basagiannis CS, Panagoulias GS, Tentolouris N, et al; Whipple disease. South Med J. 2010 Apr;103(4):353-6.
| Original Author: Dr Chloe Borton | Current Version: Dr Michelle Wright | |
| Last Checked: 23/05/2011 | Document ID: 846 Version: 22 | © EMIS |
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