A chronic, relapsing multisystem disease first described by George Hoyt Whipple, an American pathologist, in 1907. 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. 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.
Traditionally, Whipple's disease has presented a diagnostic challenge to both clinicians and pathologists.
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.
- Sewage plant workers, farmers and agricultural workers.
Not everyone with infection develops symptoms, supporting the thought that a defect in cellular immune response may predispose certain individuals. There may be many different forms of presentation with the common ones being:
- Polyarthralgia - transient and episodic (often a prodromal symptom).
- Gastrointestinal symptoms:
- 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.
- AIDS with Mycobacterium avium complex infection of the small intestine.
- Coeliac disease.
- Reiter's syndrome.
- Familial Mediterranean fever.
- Behçet's disease.
- Intestinal lymphoma.
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.
- Antibiotics are the main treatment. Expert microbiological advice will be needed. Prolonged treatment for up to one year is usually advised.
- Repeat PCR at the end of treatment.
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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