Treatment of Refractory Whipple Disease with Interferon-γ
Authors: Thomas Schneider
Journal: Annals of Internal Medicine (1998)

Brief Communications1 December 1998Treatment of Refractory Whipple Disease with Interferon-γThomas Schneider, MD, PhD, Andreas Stallmach, MD, Axel von Herbay, MD, Thomas Marth, MD, Warren Strober, MD, and Martin Zeitz, MDThomas Schneider, MD, PhDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892., Andreas Stallmach, MDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892., Axel von Herbay, MDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892., Thomas Marth, MDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892., Warren Strober, MDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892., and Martin Zeitz, MDFrom University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-11_Part_1-199812010-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Whipple disease is an infectious, chronic multisystem disorder characterized by diarrhea, malabsorption, arthralgias, and (in later stages) involvement of the central nervous system [1]. The infection is caused by an intracellular bacterium for which the name Tropheryma whippelii has been proposed [2]. The pathogen has only recently been successfully isolated and propagated by using interleukin-4-deactivated macrophages [3]. Before the use of antibiotics, Whipple disease was fatal [4]; even with antimicrobial therapy, some patients have severe relapse [5-7].The pathogenesis of T. whippelii infection is poorly understood; immune defects involving T cells and macrophages have been described [8-12]. Recently, reduced interleukin-12 ...References1. 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; 63:539-51. Google Scholar2. Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992; 327:293-301. Google Scholar3. Schoedon G, Goldenberger D, Forrer R, Gunz A, Dutly F, Hochli M, et al. Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii. J Infect Dis. 1997; 176:672-7. Google Scholar4. Paulley JW. A case of Whipple's disease (intestinal lipodystrophy). Gastroenterology. 1952; 22:128-33. Google Scholar5. Feurle GE, Volk B, Waldherr R. Cerebral Whipple's disease with negative jejunal histology. N Engl J Med. 1979; 300:907-8. Google Scholar6. Feldman M, Hendler RS, Morrison EB. Acute meningoencephalitis after withdrawal of antibiotics in Whipple's disease. Ann Intern Med. 1980; 93:709-11. Google Scholar7. Keinath RD, Merrell DE, Vlietstra R, Dobbins WO 3d. Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients. Gastroenterology. 1985; 88:1867-73. Google Scholar8. Maizel H, Ruffin JM, Dobbins WO 3d. Whipple's disease: a review of 19 patients from one hospital and a review of the literature since 1950. Medicine (Baltimore). 1970; 49:175-205. Google Scholar9. Martin FF, Vilseck J, Dobbins WO 3d, Buckley CE 3d, Tyor MP. Immunological alterations in patients with treated Whipple's disease. Gastroenterology. 1972; 63:6-18. Google Scholar10. Bjerknes R, Odegaard S, Bjerkvig R, Borkje B, Laerum OD. Whipple's disease. Demonstration of a persisting monocyte and macrophage dysfunction. Scand J Gastroenterol. 1988; 23:611-9. Google Scholar11. Ectoers N, Geboes K, Rutgeerts P, Delabie J, Desmet V, Janssens J. RFD7-RFD9 coexpression by macrophages points to T cell macrophage interaction deficiency in Whipple's disease [Abstract]. Gastroenterology. 1992; 106:A676. Google Scholar12. Marth T, Roux M, von Herbay A, Meuer SC, Feurle GE. Persistent reduction of complement receptor 3 α-chain expressing mononuclear blood cells and transient inhibitory serum factors in Whipple's disease. Clin Immunol Immunopathol. 1994; 72:217-26. Google Scholar13. Marth T, Neurath M, Cuccherini BA, Strober W. Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease. Gastroenterology. 1997; 113:442-8. Google Scholar14. Holland SM, Eisenstein EM, Kuhns DB, Turner ML, Fleisher TA, Strober W, et al. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon γ. A preliminary report. N Engl J Med. 1994; 330:1348-55. Google Scholar15. Gallin JI, Farber JM, Holland SM, Nutman TB. Interferon-γ in the management of infectious diseases. Ann Intern Med. 1995; 123:216-24. Google Scholar16. von Herbay A, Ditton HJ, Maiwald M. Diagnostic application of a polymerase chain reaction assay for the Whipple's disease bacterium to intestinal biopsies. Gastroenterology. 1996; 110:1735-43. Google Scholar17. 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; 113:434-41. Google Scholar Author, Article, and Disclosure InformationAuthors: Thomas Schneider, MD, PhD; Andreas Stallmach, MD; Axel von Herbay, MD; Thomas Marth, MD; Warren Strober, MD; Martin Zeitz, MDAffiliations: From University of the Saarland, Homburg/Saar, Germany; University of Heidelberg, Heidelberg, Germany; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.Dr. von Herbay: Institute for Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.Dr. Strober: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10/11N238, Bethesda, MD 20892.Acknowledgments: The authors thank Dr. S. Kewenig for flow-cytometric analysis, Drs. M. Maiwald and H.-J. Ditton (Heidelberg) for help with polymerase chain reaction examination, and Mr. P. Rieger (Heidelberg) for help with electron microscopy.Grant Support: By grant 01 KI 9468 from the Bundesminister fur Bildung und Forschung and grant Ze 188/7-1 from the Deutsche Forschungsgemeinschaft.Corresponding Author: Martin Zeitz, MD, Internal Medicine II, University of the Saarland, D-66421 Homburg/Saar, Germany.Current Author Addresses: Drs. Schneider, Stallmach, Marth, and Zeitz: Internal Medicine II, University of the Saarland, D-66421 Homburg/Saar, Germany PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCentral Nervous System Whipple Disease Presenting as HypersomnolenceIsolated central nervous system Whipple diseaseTreatment of disseminated nocardiosis: a host–pathogen approach with adjuvant interferon gammaCNS Whipple's DiseaseLong-term morbidity and mortality in Whipple's disease: a single-center experience over 20 yearsBacterial and Fungal DiseasesEpidemiology of Whipple's Disease in the USA Between 2012 and 2017: A Population-Based National StudyTropheryma Whipplei Agent of Self-Limiting Infections and Whipple's DiseaseClinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei InfectionsTropheryma whipplei infection and Whipple's diseaseChronic Infections of the Small IntestineWhipple´s Disease: A Case ReportTropheryma whippleiSystematic review: Whipple's disease ( Tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitorsWhipple's DiseaseMorbus Whipple, genuine intestinale Lymphangiektasie, exsudative EnteropathieMedikamentöse Therapie der infektiösen DiarrhöRepublished: Whipple's diseaseRapid bacterial genome sequencing: methods and applications in clinical microbiologyWhipple's diseaseChanging paradigms in Whipple's disease and infection with Tropheryma whippleiInfektionen mit Tropheryma whippleiNew insights into Whipple's disease and Tropheryma whipplei infectionsNeue therapeutische Ansätze bei speziellen Erkrankungen des DünndarmsWhipple DiseaseWhipple DiseaseWhipple's DiseaseWhipple's DiseaseBacterial and Fungal DiseasesMaladie de WhippleActinomycosis and Whipple DiseaseTropheryma whipplei infectionWhipple's Disease—Generalized StageNeurological presentation of Whipple's disease after long-term antibiotic treatment: a case reportWhipple's disease: new aspects of pathogenesis and treatmentWhipple diseasePossible Case of CNS Whipple's Disease in an Adolescent With AIDSLa maladie de WhippleWhipple's disease: current problemsWhipple's DiseaseLa maladie de Whipple de 1907 à 2003Enfermedad de Whipple y sistema nervioso centralReduced Peripheral and Mucosal Tropheryma whipplei -Specific Th1 Response in Patients with Whipple's DiseaseWhipple's diseaseWhipple's Disease: a Macrophage DiseaseManifestations neurologiques de la maladie de WhippleIL-16 Is Critical for Tropheryma whipplei Replication in Whipple's DiseaseManifestaciones infrecuentes de la enfermedad de Whipple. 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