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Treatment of Refractory Whipple Disease with Interferon-γ
- Thomas Schneider, MD, PhD;
- Andreas Stallmach, MD;
- Axel von Herbay, MD;
- Thomas Marth, MD;
- Warren Strober, MD; and
- Martin Zeitz, MD
- 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. 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. Requests for Reprints: 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 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.
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 and interferon-γ production in patients with Whipple disease has been detected [13]. These cytokines may be important in this context because of their ability to contain and clear intracellular bacteria [14, 15]. Therefore, we tested the usefulness of antibiotic therapy supplemented by interferon-γ in treating a patient with a 10-year history of antibiotic-resistant Whipple disease.
Case Report
In 1985, Whipple disease was diagnosed by periodic acid-Schiff (PAS)-positive macrophages in the duodenal biopsy specimen of a 66-year-old patient. The patient had a 10-year history of diarrhea and weight loss and was continuously treated with antibiotics to eradicate the bacterium. However, the patient had …
