Whipple's Disease

Authored by Dr Colin Tidy, 24 Jul 2015

Reviewed by:
Dr Adrian Bonsall, 24 Jul 2015

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A chronic, relapsing multisystem disease first described in 1907 by George Hoyt Whipple, an American pathologist.[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] 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]

Traditionally, Whipple's disease has presented a diagnostic challenge, both to clinicians and to pathologists.[5, 6]

Whipple's disease is an extremely rare condition. Incidence is estimated as less than 1 per 1,000,000 per annum.[2]

Risk factors[7, 8]

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.

Not everyone with infection develops symptoms, supporting the thought that a defect in cellular immune response may predispose certain individuals.[3] 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 and erythema nodosum.[10]

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.[13]
  • Antibiotics are the main treatment.[14] 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%.[7]

Further reading and references

  1. Fenollar F, Puechal X, Raoult D; Whipple's disease. N Engl J Med. 2007 Jan 4356(1):55-66.

  2. Desnues B, Ihrig M, Raoult D, et al; Whipple's disease: a macrophage disease. Clin Vaccine Immunol. 2006 Feb

  3. Deriban G, Marth T; Current concepts of immunopathogenesis, diagnosis and therapy in Whipple's Curr Med Chem. 200613(24):2921-6.

  4. 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.

  5. Rakshit RC, Mackay JD; A diagnostic conundrum. Postgrad Med J. 2003 Sep

  6. Mahnel R, Marth T; Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease. Clin Exp Med. 2004 Sep

  7. 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.

  8. Fenollar F, Celard M, Lagier JC, et al; Tropheryma whipplei endocarditis. Emerg Infect Dis. 2013 Nov19(11):1721-30. doi: 10.3201/eid1911.121356.

  9. 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.

  10. 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.

  11. 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.

  12. Marth T, Raoult D; Whipple's disease. Lancet. 2003 Jan 18

  13. 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.

  14. Basagiannis CS, Panagoulias GS, Tentolouris N, et al; Whipple disease. South Med J. 2010 Apr103(4):353-6.

Hi All,  I dont know if anyone has come across this.  I have a worm infestation in my face.  They travel around under the skin leaving tracks and bursting holes into my skin.  they create glass like...

nicolamc
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