Whipple's Disease: Our Own Experience and Review of the Literature

Whipple's disease is a chronic infectious systemic disease caused by the bacterium Tropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.

[1]  M. Altwegg,et al.  Prevalence of Tropheryma whipplei DNA in Patients with Various Gastrointestinal Diseases and in Healthy Controls , 2003, Infection.

[2]  D. Raoult,et al.  Intrafamilial Circulation of Tropheryma whipplei, France , 2012, Emerging infectious diseases.

[3]  Annette Moter,et al.  Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipple's disease. , 2013, The Journal of infection.

[4]  M. Marcial,et al.  Whipple's disease with esophageal and colonic involvement: endoscopic and histopathologic findings. , 1997, Gastrointestinal endoscopy.

[5]  D. Raoult,et al.  Immunodetection of Tropheryma whipplei in intestinal tissues from Dr. Whipple's 1907 patient. , 2003, The New England journal of medicine.

[6]  D. Raoult,et al.  Whipple disease revealed by lung involvement: a case report and literature review. , 2012, Chest.

[7]  Feurle Ge.  La revue neurologique a reçu la correspondance suivante , 2004 .

[8]  V. Moos,et al.  Changing paradigms in Whipple’s disease and infection with Tropheryma whipplei , 2011, European Journal of Clinical Microbiology & Infectious Diseases.

[9]  A. Gunz,et al.  Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii. , 1997, The Journal of infectious diseases.

[10]  M. Muñoz-Navas,et al.  Refractory Whipple's disease. , 2007, Gastrointestinal endoscopy.

[11]  W. Strober,et al.  Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease. , 1997, Gastroenterology.

[12]  O. Burghuber,et al.  Severe pulmonary hypertension reversed by antibiotics in a patient with Whipple's disease. , 1997, Thorax.

[13]  I. Arruabarrena,et al.  Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001. , 2010, Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva.

[14]  A. Gérard,et al.  L'atteinte neurologique dans la maladie de Whipple , 2008 .

[15]  D. Raoult,et al.  Prevalence of asymptomatic Tropheryma whipplei carriage among humans and nonhuman primates. , 2008, The Journal of infectious diseases.

[16]  T. Marrie,et al.  Cultivation of the bacillus of Whipple's disease. , 2000, The New England journal of medicine.

[17]  D. Raoult,et al.  Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple's disease bacillus. , 2001, International journal of systematic and evolutionary microbiology.

[18]  H. Rousset,et al.  Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne. , 1997, Medicine.

[19]  M. Zeitz,et al.  Treatment of Refractory Whipple Disease with Interferon- , 1998, Annals of Internal Medicine.

[20]  P. Rutgeerts,et al.  Whipple's disease: A histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium , 1994, The Journal of pathology.

[21]  C. Loddenkemper,et al.  Whipple's disease: new aspects of pathogenesis and treatment. , 2008, The Lancet. Infectious diseases.

[22]  T. Hendrix,et al.  Combined electron and light microscopy in Whipple's disease. Demonstration of "bacillary bodies" in the intestine. , 1961, Bulletin of the Johns Hopkins Hospital.

[23]  S. Love,et al.  Tropheryma whipplei endocarditis without gastrointestinal involvement. , 2012, Interactive cardiovascular and thoracic surgery.

[24]  S. James,et al.  Chronic Infections of the Small Intestine , 2009 .

[25]  M. Zeitz,et al.  Reduced Peripheral and Mucosal Tropheryma whipplei-Specific Th1 Response in Patients with Whipple’s Disease1 , 2006, The Journal of Immunology.

[26]  A. Kukita,et al.  Generalized Hyperpigmentation of the Skin due to Vitamin B12 Deficiency , 2001, The Journal of dermatology.

[27]  K. Mönkemüller,et al.  Whipple's disease. , 2004, Gastrointestinal endoscopy.

[28]  G. Gay,et al.  Double balloon enteroscopy in Crohn's disease and related disorders: our experience. , 2007, Gastrointestinal endoscopy.

[29]  Emily S. Charlson,et al.  Widespread colonization of the lung by Tropheryma whipplei in HIV infection. , 2013, American journal of respiratory and critical care medicine.

[30]  G. Gay,et al.  Capsule endoscopy in non-steroidal anti-inflammatory drugs-enteropathy and miscellaneous, rare intestinal diseases. , 2008, World journal of gastroenterology.

[31]  P. Bianchi.  [Whipple's disease]. , 1962, Minerva medica.

[32]  H. Freeman.  Tropheryma whipplei infection. , 2009, World journal of gastroenterology.

[33]  W. Schlippert,et al.  Duodenoscopic findings in Whipple's disease. , 1978, Gastrointestinal endoscopy.

[34]  E. Montgomery,et al.  Whipple Disease a Century After the Initial Description: Increased Recognition of Unusual Presentations, Autoimmune Comorbidities, and Therapy Effects , 2012, The American journal of surgical pathology.

[35]  Yardley Jh,et al.  Combined electron and light microscopy in Whipple's disease. Demonstration of "bacillary bodies" in the intestine. , 1961 .

[36]  K. Wilson,et al.  Phylogeny of the Whipple's-disease-associated bacterium , 1991, The Lancet.

[37]  R. Katon,et al.  Small bowel involvement by Mycobacterium avium complex in a patient with AIDS: endoscopic, histologic, and radiographic similarities to Whipple's disease. , 1994, Gastrointestinal endoscopy.

[38]  D. Raoult,et al.  Molecular evaluation of antibiotic susceptibility of Tropheryma whipplei in axenic medium. , 2005, The Journal of antimicrobial chemotherapy.

[39]  M. Zeitz,et al.  Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease. , 2002, Gastroenterology.

[40]  Frank Schuhmacher,et al.  Environmental Occurrence of the Whipple’s Disease Bacterium (Tropheryma whippelii) , 1998, Applied and Environmental Microbiology.

[41]  G. Feurle,et al.  Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease. , 2010, Gastroenterology.

[42]  M. Cappell,et al.  Intestinal Mycobacterium avium complex infection initially misdiagnosed and mistreated as Whipple disease. , 2010, Gastrointestinal endoscopy.

[43]  S. Meuer,et al.  Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease. , 1994, Clinical immunology and immunopathology.

[44]  S. Fahn,et al.  Diagnostic guidelines in central nervous system Whipple's disease , 1996, Annals of neurology.

[45]  D. Raoult,et al.  Whipple's Disease , 2001, Clinical Diagnostic Laboratory Immunology.

[46]  M. Altwegg,et al.  Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method , 2002, Journal of Clinical Microbiology.

[47]  Jean-Marc Rolain,et al.  Antibiotic Susceptibility of Tropheryma whipplei in MRC5 Cells , 2004, Antimicrobial Agents and Chemotherapy.

[48]  X. Sagaert,et al.  Macrophage-related diseases of the gut: a pathologist's perspective , 2012, Virchows Archiv.

[49]  H. Rousset,et al.  Whipple Disease: Clinical Review of 52 Cases , 1997, Medicine.

[50]  A. Alzahrani,et al.  Severe primary hyperparathyroidism masked by asymptomatic celiac disease. , 2008, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[51]  Tadataka Yamada,et al.  Textbook of Gastroenterology , 1995 .

[52]  P. Rutgeerts,et al.  Whipple's disease: endoscopic aspects before and after therapy. , 1990, Gastrointestinal endoscopy.

[53]  J. Paulley.  A case of Whipple's disease (intestinal lipodystrophy). , 1952, Gastroenterology.

[54]  C. Müller,et al.  Tropheryma whipplei in the Environment: Survey of Sewage Plant Influxes and Sewage Plant Workers , 2007, Applied and Environmental Microbiology.