History

Whipple disease was first described by Dr. George H. Whipple in 1907.^[24]The classic presentation of Whipple disease is that of a wasting illness characterized by arthralgias, arthritis, fever, and diarrhea; however, this form is rare.^{[15, 25]}Lymphadenopathy may be present.

If Whipple disease affects the small intestine, steatorrhea often is present.

Approximately 90% of patients with Whipple disease present with weight loss, and 70% of patients with Whipple disease complain of either diarrhea or arthralgias. In about three quarters of patients, the joint manifestations are followed by weight loss and diarrhea, with a mean time of 6 years from onset of the joint symptoms to diagnosis of Whipple disease.^[26]

Whipple disease may mimic chronic inflammatory rheumatic disorders and present with atypical manifestations.^{[27, 28, 29]}Case reports exist in which patients with Whipple disease were diagnosed in the context of an inflammatory disease that was refractory to treatment with anti-tumor necrosis factor alpha (anti-TNF-a).^{[27, 28]}The joint manifestations of Whipple disease are nondeforming.

Occult gastrointestinal (GI) bleeding can be found in 80% of patients of Whipple disease, but frank hematochezia is uncommon.

Cardiac involvement occurs in approximately 30% of cases.

Physical Examination

Swelling of the joints may occur, but frankly deforming arthritis is quite rare.^[30]Sacroiliitis, pancarpal narrowing, and cervical epiphyseal fusion have been described in selected patients.

Patients with Whipple disease may have any of the physical findings associated with malabsorption. These findings are nonspecific but include the following:

Cachexia
Distended abdomen
Glossitis
Perlèche (angular cheilitis)
Chvostek or Trousseau sign (secondary to hypocalcemia)
Gingivitis and parafollicular hemorrhages (secondary to vitamin C deficiency)
Night blindness (secondary to vitamin A deficiency)
Visible peristalsis with borborygmi
Hyperpigmentation around the orbital and malar areas of the face (occasionally)

When the CNS is involved, patients may demonstrate signs of frontal release (as seen with dementia), meningoencephalitis, or ataxia and clonus (if the cerebellum is affected).^{[31, 32, 33]}One review noted that supranuclear ophthalmoplegia and cerebellar ataxia were two of the most common neurologic findings.^[34]

In a retrospective study, neurologic symptoms in 18 patients with Whipple disease and CNS infection (median follow-up, 6 y) included the following: confusion or coma related to meningoencephalitis or status epilepticus (17%); delirium (17%); cognitive impairment (memory loss, attention defects, typical frontal lobe syndrome) (61%); hypersomnia (17%); abnormal movements (eg, myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron symptoms (44%); extrapyramidal symptoms (33%); and ophthalmoplegia, with/without progressive supranuclear palsy (17%).^[35]

Differential Diagnoses

Relman DA, Schmidt TM, MacDermott RP, et al. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30. 327(5):293-301. [Medline].
Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple's disease. N Engl J Med. 2000 Mar 2. 342(9):620-5. [Medline].
Herrmann MD, Neumayr A, Essig A, et al. Isolated Whipple's endocarditis: an underestimated diagnosis that requires molecular analysis of surgical material. Ann Thorac Surg. 2014 Jul. 98(1):e1-3. [Medline].
Arnold CA, Moreira RK, Lam-Himlin D, De Petris G, Montgomery E. Whipple disease a century after the initial description: increased recognition of unusual presentations, autoimmune comorbidities, and therapy effects. Am J Surg Pathol. 2012 Jul. 36(7):1066-73. [Medline].
Dray X, Vahedi K, Delcey V, et al. Mycobacterium avium duodenal infection mimicking Whipple's disease in a patient with AIDS. Endoscopy. 2007 Feb. 39 Suppl 1:E296-7. [Medline].
Patel SJ, Huard RC, Keller C, Foca M. Possible case of CNS Whipple's disease in an adolescent with AIDS. J Int Assoc Physicians AIDS Care (Chic). 2008 Mar-Apr. 7(2):69-73. [Medline].
Ramzan NN, Loftus E Jr, Burgart LJ, et al. Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med. 1997 Apr 1. 126(7):520-7. [Medline].
Marth T, Schneider T. Whipple disease. Curr Opin Gastroenterol. 2008 Mar. 24(2):141-8. [Medline].
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. [Medline].
O'Duffy JD, Griffing WL, Li CY, et al. Whipple's arthritis: direct detection of Tropheryma whippelii in synovial fluid and tissue. Arthritis Rheum. 1999 Apr. 42(4):812-7. [Medline].
Celard M, de Gevigney G, Mosnier S, et al. Polymerase chain reaction analysis for diagnosis of Tropheryma whippelii infective endocarditis in two patients with no previous evidence of Whipple's disease. Clin Infect Dis. 1999 Nov. 29(5):1348-9. [Medline].
Gubler JG, Kuster M, Dutly F, et al. Whipple endocarditis without overt gastrointestinal disease: report of four cases. Ann Intern Med. 1999 Jul 20. 131(2):112-6. [Medline].
Gerard A, Sarrot-Reynauld F, Liozon E, et al. Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore). 2002 Nov. 81(6):443-57. [Medline].
Kelly CA, Egan M, Rawlinson J. Whipple's disease presenting with lung involvement. Thorax. 1996 Mar. 51(3):343-4. [Medline].
Marth T. Tropheryma whipplei, immunosuppression and Whipple's disease: from a low-pathogenic, environmental infectious organism to a rare, multifaceted inflammatory complex. Dig Dis. 2015. 33(2):190-9. [Medline].
Ehrbar HU, Bauerfeind P, Dutly F, et al. PCR-positive tests for Tropheryma whippelii in patients without Whipple's disease. Lancet. 1999 Jun 26. 353(9171):2214. [Medline].
Dick J, Krauss P, Hillenkamp J, Kohlmorgen B, Schoen C. Postoperative Tropheryma whipple endophthalmitis - a case report highlighting the additive value of molecular testing. JMM Case Rep. 2017 Oct. 4(10):e005124. [Medline].
Street S, Donoghue HD, Neild GH. Tropheryma whippelii DNA in saliva of healthy people. Lancet. 1999 Oct 2. 354(9185):1178-9. [Medline].
Dobbins WO 3rd. HLA antigens in Whipple's disease. Arthritis Rheum. 1987 Jan. 30(1):102-5. [Medline].
Fenollar F, Puechal X, Raoult D. Whipple's disease. N Engl J Med. 2007 Jan 4. 356(1):55-66. [Medline].
Durand DV, Lecomte C, Cathebras P, et al. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore). 1997 May. 76(3):170-84. [Medline].
Keinath RD, Merrell DE, Vlietstra R, et al. Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology. 1985 Jun. 88(6):1867-73. [Medline].
Fleming JL, Wiesner RH, Shorter RG. Whipple's disease: clinical, biochemical, and histopathologic features and assessment of treatment in 29 patients. Mayo Clin Proc. 1988 Jun. 63(6):539-51. [Medline].
Antunes C, Singhal M. Whipple Disease. StatPearls [Internet]. 2019 Jan. [Medline]. [Full Text].
Cunningham S, Maulucci F, Zufferey P, Ribi C, Maillard MH. [Whipple's disease, when to think about it?] [French]. Rev Med Suisse. 2015 Sep 2. 11(484):1582, 1584-6. [Medline].
Puechal X. Whipple's arthritis. Joint Bone Spine. 2016 Dec. 83(6):631-5. [Medline].
Marth T. Systematic review: Whipple's disease (Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Aliment Pharmacol Ther. 2015 Apr. 41(8):709-24. [Medline].
Ramos JM, Pasquau F, Galipienso N, et al. Whipple's disease diagnosed during anti-tumor necrosis factor alpha treatment: two case reports and review of the literature. J Med Case Rep. 2015 Jul 28. 9:165. [Medline].
Gaude M, Tebib J, Puechal X. Atypical focal forms of Whipple's disease seen by rheumatologists. Joint Bone Spine. 2015 Jan. 82(1):56-9. [Medline].
Scheib JS. Whipple disease revisited: radiographic features of a patient with 35 years of undiagnosed arthritis. J Clin Rheumatol. 2004 Apr. 10(2):69-73. [Medline].
Matthews BR, Jones LK, Saad DA, et al. Cerebellar ataxia and central nervous system Whipple disease. Arch Neurol. 2005 Apr. 62(4):618-20. [Medline].
Fenollar F, Nicoli F, Paquet C, et al. Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis. BMC Infect Dis. 2011 Jun 15. 11:171. [Medline]. [Full Text].
Pessa ME, Baldi A, Gigli GL, Valente M. A case of rapidly progressive dementia: Whipple disease of CNS. Neurol Sci. 2018 Mar. 39(3):591-2. [Medline].
Suzer T, Demirkan N, Tahta K, Coskun E, Cetin B. Whipple's disease confined to the central nervous system: case report and review of the literature. Scand J Infect Dis. 1999. 31(4):411-4. [Medline].
Compain C, Sacre K, Puechal X, et al. Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. Medicine (Baltimore). 2013 Nov. 92(6):324-30. [Medline].
Glaser C, Rieg S, Wiech T, et al. Whipple's disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure. Orphanet J Rare Dis. 2017 May 25. 12(1):99. [Medline]. [Full Text].
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. 2013. 52(2):219-22. [Medline].
Moter A, Schmiedel D, Petrich A, et al. Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years' experience in a National Reference Laboratory. J Clin Microbiol. 2013 Nov. 51(11):3858-61. [Medline]. [Full Text].
Whistance RN, Elfarouki GW, Vohra HA, Livesey SA. A case of Tropheryma whipplei infective endocarditis of the aortic and mitral valves in association with psoriatic arthritis and lumbar discitis. J Heart Valve Dis. 2011 May. 20(3):353-6. [Medline].
Balducci C, Foresti S, Ciervo A, et al. Primary Whipple disease of the central nervous system presenting with rhombencephalitis. Int J Infect Dis. 2019 Aug 23. 88:149-51. [Medline]. [Full Text].
Saito H, Shiode J, Ohya S, et al. Whipple's disease with long-term endoscopic follow-up. Intern Med. 2018 Jun 15. 57(12):1707-13. [Medline]. [Full Text].
Gunther U, Moos V, Offenmuller G, et al. Gastrointestinal diagnosis of classical Whipple disease: clinical, endoscopic, and histopathologic features in 191 patients. Medicine (Baltimore). 2015 Apr. 94(15):e714. [Medline].
Fenollar F, Lagier JC, Raoult D. Tropheryma whipplei and Whipple's disease. J Infect. 2014 Aug. 69(2):103-12. [Medline].
Vayssade M, Tournadre A, D'Incan M, Soubrier M, Dubost JJ. Immune reconstitution inflammatory syndrome during treatment of Whipple's disease. Joint Bone Spine. 2015 Mar. 82(2):122-4. [Medline].
Vindigni SM, Taylor J, Quilter LA, et al. Tropheryma whipplei infection (Whipple's disease) in a patient after liver transplantation. Transpl Infect Dis. 2016 Aug. 18(4):617-24. [Medline].
Tabuas-Pereira M, Vicente M, Coelho F, Santana I. Prosopagnosia as the presenting symptom of Whipple disease. Cogn Behav Neurol. 2016 Jun. 29(2):100-6. [Medline].
Loiodice A, Losurdo G, Iannone A, Rossi R, Fiore MG, Piscitelli D. Transmission electron microscopy helpfulness in Whipple's disease masked by immunosuppressant therapy for arthritis. APMIS. 2018 Jan. 126(1):92-6. [Medline].

Media Gallery

of 0

Whipple Disease Clinical Presentation

History

Physical Examination

About

Membership

Apps

WebMD Network

Editions

Whipple Disease Clinical Presentation

History

Physical Examination

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions