Further Outpatient Care

Regular visits in various specialty clinics targeting monitoring clinical response to treatment of significant symptoms and laboratory tests should be pursued.

Significant symptom inventory should be reviewed with the patient at each clinic visit.

Treatment adherence should be emphasized continuously.

Guidelines for response assessment should be reviewed consistently with other specialty teams involved in the care of the patient.

CSF PCR analysis should be used as the ultimate tool in monitoring response and treatment decision making.

Further Inpatient Care

Diagnosis and treatment of patients with Whipple disease should be based on a multiteam approach, targeting early involvement of gastroenterology, neurology, ophthalmology, cardiology, and rheumatology specialists.

No patients in whom multiple target-organ routine inventory status has been pursued, unless indicated by symptomatology or clinical examination (except for CNS), have been reported.

Some have speculated that by the time the CNS involvement becomes clinically relevant in patients with Whipple disease, they also might have disseminated pulmonary, cardiovascular, hepatic, and/or ocular disease. Furthermore, the choice and duration of antibiotic treatment might be influenced by the presence of disease in these organs.

The role of routine echocardiogram and chest and abdomen imaging (CT scan or MRI) remains to be established; these should be pursued on an individual case basis and on the clinician's need to know for significant management decisions and prognostic evaluation.

Inpatient and Outpatient Medications

A long course of antibiotics (more than 1 y) that has good BBB penetrance represents the key in successful treatment of patients with Whipple disease.

Deterrence/Prevention

Limited information suggests that the WD bacillus is a saprobe.

A limited number of cases have been reported of patients diagnosed with WD several months after spending vacation time in lake regions.

In patients who might have a specific IL-12–gamma-interferon axis defect, swimming in lakes may be hazardous, especially in those where accidental drainage of sewage water took place.

El-Abassi R, Soliman MY, Williams F, England JD. Whipple's disease. J Neurol Sci. 2017 Jun 15. 377:197-206. [QxMD MEDLINE Link].
Compain C, Sacre K, Puéchal X, Klein I, Vital-Durand D, Houeto JL, 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. [QxMD MEDLINE Link].
Balasa M, Gelpi E, Rey MJ, Vila J, Ramió-Torrentà L, Quiles Granado AM, et al. Clinical and neuropathological variability in clinically isolated central nervous system Whipple's disease. Brain Pathol. 2014 Apr. 24(3):230-8. [QxMD MEDLINE Link].
Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Johns Hopkins Hosp Bull. 1907. 18:382-391.
Black-Schaffer B. The tinctorial demonstration of a glycoprotein in Whipple's disease. Proc Soc Exp Biol Med. 1949. 72:225.
Paulley JW. A case of Whipple's disease (intestinal lipodystrophy). Gastroenterology. 1952. 22:128-33.
Keinath RD, Merrell DE, Vlietstra R, Dobbins WO 3rd. Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology. 1985 Jun. 88(6):1867-73. [QxMD MEDLINE Link].
Wilson KH, Blitchington R, Frothingham R, Wilson JA. Phylogeny of the Whipple's-disease-associated bacterium. Lancet. 1991 Aug 24. 338(8765):474-5. [QxMD MEDLINE Link].
Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992 Jul 30. 327(5):293-301. [QxMD MEDLINE Link].
Ramzan NN, Loftus E, Burgart LJ, et al. Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med. 1997 Apr 1. 126(7):520-7. [QxMD MEDLINE Link].
Raoult D, Birg ML, La Scola B, Fournier PE, Enea M, Lepidi H, et al. Cultivation of the bacillus of Whipple's disease. N Engl J Med. 2000 Mar 2. 342(9):620-5. [QxMD MEDLINE Link].
Raoult D, Ogata H, Audic S. Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome. Genome Res. 2003 Aug. 13(8):1800-9. [QxMD MEDLINE Link].
Raoult D, Ogata H, Audic S, et al. Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome. Genome Res. 2003 Aug. 13(8):1800-9. [QxMD MEDLINE Link].
Bentley SD, Maiwald M, Murphy LD, Pallen MJ, Yeats CA, Dover LG, et al. Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei. Lancet. 2003 Feb 22. 361(9358):637-44. [QxMD MEDLINE Link].
Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000 Dec. 11(4):321-33. [QxMD MEDLINE Link].
Fenollar F, Laouira S, Lepidi H, Rolain JM, Raoult D. Value of Tropheryma whipplei quantitative polymerase chain reaction assay for the diagnosis of Whipple disease: usefulness of saliva and stool specimens for first-line screening. Clin Infect Dis. 2008 Sep 1. 47(5):659-67. [QxMD MEDLINE Link].
Bonhomme CJ, Renesto P, Nandi S, Lynn AM, Raoult D. Serological microarray for a paradoxical diagnostic of Whipple's disease. Eur J Clin Microbiol Infect Dis. 2008 Oct. 27(10):959-68. [QxMD MEDLINE Link].
Panegyres PK, Foster JK, Fallon M, Connor C. The amnesic syndrome of primary Whipple disease of the brain. Cogn Behav Neurol. 2010 Mar. 23(1):49-51. [QxMD MEDLINE Link].
Schwartz MA, Selhorst JB, Ochs AL, Beck RW, Campbell WW, Harris JK, et al. Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple's disease. Ann Neurol. 1986 Dec. 20(6):677-83. [QxMD MEDLINE Link].
Brandle M, Ammann P, Spinas GA, Dutly F, Galeazzi RL, Schmid C, et al. Relapsing Whipple's disease presenting with hypopituitarism. Clin Endocrinol (Oxf). 1999 Mar. 50(3):399-403. [QxMD MEDLINE Link].
von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M. Whipple's disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology. 1997 Aug. 113(2):434-41. [QxMD MEDLINE Link].
De Coene B, Gilliard C, Indekeu P, Duprez T, Trigaux JP. Whipple's disease confined to the central nervous system. Neuroradiology. 1996 May. 38(4):325-7. [QxMD MEDLINE Link].
Le Scanff J, Gaultier JB, Durand DV, Durieu I, Celard M, Benito Y, et al. [Tropheryma whipplei and Whipple disease: false positive PCR detections of Tropheryma whipplei in diagnostic samples are rare]. Rev Med Interne. 2008 Nov. 29(11):861-7. [QxMD MEDLINE Link].
Seneca V, Imperato A, Colella G, Cioffi V, Mariniello G, Gangemi M. Recurrent acute obstructive hydrocephalus as clinical onset of cerebral Whipple's disease. Clin Neurol Neurosurg. 2010 Oct. 112(8):717-21. [QxMD MEDLINE Link].
Adams M, Rhyner PA, Day J, DeArmond S, Smuckler EA. Whipple's disease confined to the central nervous system. Ann Neurol. 1987 Jan. 21(1):104-8. [QxMD MEDLINE Link].
Benito-León J, Sedano LF, Louis ED. Isolated central nervous system Whipple's disease causing reversible frontotemporal-like dementia. Clin Neurol Neurosurg. 2008 Jul. 110(7):747-9. [QxMD MEDLINE Link].
Clarke CE, Falope ZF, Abdelhadi HA, Franks AJ. Cervical myelopathy caused by Whipple's disease. Neurology. 1998 May. 50(5):1505-6. [QxMD MEDLINE Link].
Comer GM, Brandt LJ, Abissi CJ. Whipple's disease: a review. Am J Gastroenterol. 1983 Feb. 78(2):107-14. [QxMD MEDLINE Link].
Cooper GS, Blades EW, Remler BF, Salata RA, Bennert KW, Jacobs GH. Central nervous system Whipple's disease: relapse during therapy with trimethoprim-sulfamethoxazole and remission with cefixime. Gastroenterology. 1994 Mar. 106(3):782-6. [QxMD MEDLINE Link].
Dobbins WO 3rd. The diagnosis of Whipple's disease. N Engl J Med. 1995 Feb 9. 332(6):390-2. [QxMD MEDLINE Link].
Fenollar F, Birg ML, Gauduchon V. Culture of Tropheryma whipplei from human samples: a 3-year experience (1999 to 2002). J Clin Microbiol. 2003 Aug. 41(8):3816-22. [QxMD MEDLINE Link].
Fenollar F, Fournier PE, Robert C. Use of genome selected repeated sequences increases the sensitivity of PCR detection of Tropheryma whipplei. J Clin Microbiol. 2004 Jan. 42(1):401-3. [QxMD MEDLINE Link].
Knox DL, Green WR, Troncoso JC, Yardley JH, Hsu J, Zee DS. Cerebral ocular Whipple's disease: a 62-year odyssey from death to diagnosis. Neurology. 1995 Apr. 45(4):617-25. [QxMD MEDLINE Link].
Kowalczewska M, Villard C, Lafitte D, Fenollar F, Raoult D. Global proteomic pattern of Tropheryma whipplei: a Whipple's disease bacterium. Proteomics. 2009 Mar. 9(6):1593-616. [QxMD MEDLINE Link].
Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J. Diagnostic guidelines in central nervous system Whipple's disease. Ann Neurol. 1996 Oct. 40(4):561-8. [QxMD MEDLINE Link].
Lynch T, Odel J, Fredericks DN, Louis ED, Forman S, Rotterdam H, et al. Polymerase chain reaction-based detection of Tropheryma whippelii in central nervous system Whipple's disease. Ann Neurol. 1997 Jul. 42(1):120-4. [QxMD MEDLINE Link].
Marth T, Neurath M, Cuccherini BA, Strober W. Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease. Gastroenterology. 1997 Aug. 113(2):442-8. [QxMD MEDLINE Link].
Marth T, Roux M, von Herbay A, Meuer SC, Feurle GE. Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease. Clin Immunol Immunopathol. 1994 Aug. 72(2):217-26. [QxMD MEDLINE Link].
Masselot F, Boulos A, Maurin M. Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Antimicrob Agents Chemother. 2003 May. 47(5):1658-64. [QxMD MEDLINE Link].
Moos V, Kunkel D, Marth T, Feurle GE, LaScola B, Ignatius R, et al. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple's disease. J Immunol. 2006 Aug 1. 177(3):2015-22. [QxMD MEDLINE Link].
Pollock S, Lewis PD, Kendall B. Whipple's disease confined to the nervous system. J Neurol Neurosurg Psychiatry. 1981 Dec. 44(12):1104-9. [QxMD MEDLINE Link].
Richardson DC, Burrows LL, Korithoski B, Salit IE, Butany J, David TE, et al. Tropheryma whippelii as a cause of afebrile culture-negative endocarditis: the evolving spectrum of Whipple's disease. J Infect. 2003 Aug. 47(2):170-3. [QxMD MEDLINE Link].
Ryser RJ, Locksley RM, Eng SC, Dobbins WO 3rd, Schoenknecht FD, Rubin CE. Reversal of dementia associated with Whipple's disease by trimethoprim-sulfamethoxazole, drugs that penetrate the blood-brain barrier. Gastroenterology. 1984 Apr. 86(4):745-52. [QxMD MEDLINE Link].
Sanavro SM, Voerman HJ. Whipple's disease: easily diagnosed, if considered. Neth J Med. 2009 Mar. 67(3):108. [QxMD MEDLINE Link].
Schneider T, Stallmach A, von Herbay A. Treatment of refractory Whipple disease with interferon-gamma. Ann Intern Med. 1998 Dec 1. 129(11):875-7. [QxMD MEDLINE Link].
Schnider P, Trattnig S, Kollegger H, et al. MR of cerebral Whipple disease. AJNR Am J Neuroradiol. 1995 Jun-Jul. 16(6):1328-9. [QxMD MEDLINE Link].
Sloan LM, Rosenblatt JE, Cockerill FR. Detection of Tropheryma whipplei DNA in clinical specimens by LightCycler real-time PCR. J Clin Microbiol. 2005 Jul. 43(7):3516-8. [QxMD MEDLINE Link].
Swartz MN. Whipple's disease--past, present, and future. N Engl J Med. 2000 Mar 2. 342(9):648-50. [QxMD MEDLINE Link].
Wilson KH. New vistas for bacteriologists: analysis based on 16S rRNA sequences provides a rapid and reliable approach to the identity of human pathogens. ASM News. 1992. 58:318-21.

Media Gallery

of 0

Author

George C Bobustuc, MD Consulting Staff, Department of Neuro-oncology, MD Anderson Cancer Center of Orlando

George C Bobustuc, MD is a member of the following medical societies: American Academy of Neurology, Texas Medical Association, Society for Neuro-Oncology, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Florian P Thomas, MD, PhD, MA, MS Chair, Neuroscience Institute and Department of Neurology, Director, Hereditary Neuropathy Center, Co-Director, Center for Memory Loss and Brain Health, Co-Director, ALS Center, Hackensack University Medical Center; Associate Dean of Faculty, Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine

Florian P Thomas, MD, PhD, MA, MS is a member of the following medical societies: Academy of Spinal Cord Injury Professionals, American Academy of Neurology, American Neurological Association, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary's Stroke Program, SSM Neurosciences Institute, SSM Health

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Additional Contributors

Norman C Reynolds, Jr, MD Neurologist, Veterans Affairs Medical Center of Milwaukee; Clinical Professor, Medical College of Wisconsin

Norman C Reynolds, Jr, MD is a member of the following medical societies: American Academy of Neurology, The Society of Federal Health Professionals (AMSUS), International Parkinson and Movement Disorder Society, Sigma Xi, The Scientific Research Honor Society, Society for Neuroscience

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Mark Gilbert, MD to the development and writing of this article.

Sections CNS Whipple Disease
Overview
Presentation
- History
- Physical
- Causes
- Complications
- Show All
DDx
Workup
Treatment
Medication
Follow-up
References

CNS Whipple Disease Follow-up

Further Outpatient Care

Further Inpatient Care

Inpatient and Outpatient Medications

Deterrence/Prevention

References

Tables

Contributor Information and Disclosures

What would you like to print?