A chronic, relapsing multisystem disease first described in 1907 by George Hoyt Whipple, an American pathologist. 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.[3, 4]
Whipple's disease is an extremely rare condition. Incidence is estimated as less than 1 per 1,000,000 per annum.
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:
- Abdominal pain.
- Anorexia and weight loss.
- 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 and erythema nodosum.
- AIDS with Mycobacterium avium complex infection of the small intestine.
- Coeliac disease.
- Reactive arthritis.
- 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 1-2 years is usually advised.
- Repeat PCR at the end of treatment.
- Insidious progression and fatal if untreated.
- Locomotor and gastrointestinal symptoms may improve very rapidly with treatment but histological remission can take several years.
- Follow up closely for signs of recurrence - there is relapse in about 40%.
Further reading and references
Fenollar F, Puechal X, Raoult D; Whipple's disease. N Engl J Med. 2007 Jan 4356(1):55-66.
Desnues B, Ihrig M, Raoult D, et al; Whipple's disease: a macrophage disease. Clin Vaccine Immunol. 2006 Feb
Deriban G, Marth T; Current concepts of immunopathogenesis, diagnosis and therapy in Whipple's Curr Med Chem. 200613(24):2921-6.
Schneider T, Moos V, Loddenkemper C, et al; Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar8(3):179-90.
Rakshit RC, Mackay JD; A diagnostic conundrum. Postgrad Med J. 2003 Sep
Mahnel R, Marth T; Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease. Clin Exp Med. 2004 Sep
Amendolara M, Barbarino C, Bucca D, et al; Whipple's disease infection surgical treatment: presentation of a rare case and literature review. G Chir. 2013 Apr34(4):117-21.
Fenollar F, Celard M, Lagier JC, et al; Tropheryma whipplei endocarditis. Emerg Infect Dis. 2013 Nov19(11):1721-30. doi: 10.3201/eid1911.121356.
Martinetti M, Biagi F, Badulli C, et al; The HLA alleles DRB1*13 and DQB1*06 are associated to Whipple's disease. Gastroenterology. 2009 Jun136(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 Feb60(2):277-88.
Murray JA, Rubio-Tapia A; Diarrhoea due to small bowel diseases. Best Pract Res Clin Gastroenterol. 2012 Oct26(5):581-600. doi: 10.1016/j.bpg.2012.11.013.
Marth T, Raoult D; Whipple's disease. Lancet. 2003 Jan 18
Yajima N, Wada R, Kimura S, et al; Whipple disease diagnosed with PCR using formalin-fixed paraffin-embedded specimens of the intestinal mucosa. Intern Med. 201352(2):219-22. Epub 2013 Jan 15.
Basagiannis CS, Panagoulias GS, Tentolouris N, et al; Whipple disease. South Med J. 2010 Apr103(4):353-6.