Abstract
Whipples disease (WD) is a rare chronic infectious disorder caused by the rod- shaped bacterium Tropheryma whipplei. The disorder is characterized clinically by arthralgia, abdominal pain, diarrhea, malabsorbtion and progressive weight loss. Other important sites of infection include the heart (resulting in the clinical picture of endocarditis and heart failure) and the central nervous system (CNS) (manifestations include confusion, memory loss, focal cranial nerve signs, nystagmus and ophtalmoplegia). The bacterium is presumed to be ubiquitously present. A defect in cellular immune response may predispose patients for an infection with T. whipplei and this might explain the rarity of the disorder despite the ubiquitous bacterial presence. The presumed immunological defect is likely to be quite specific for T. whipplei, since patients are not generally affected by other infections. Decreased production of Interleukin(IL)-12, IL-2 and Interferon (IFN)-γ accompanied by an increased secretion of IL-4 are the main features of this defective immunological response. The finding of periodic acid-Schiff (PAS)-positive macrophages in the lamina propria of tissue samples obtained by duodenal biopsy usually establishes the diagnosis. The PAS-positive inclusions represent the remnants of the bacteria. Attempts to isolate the causative agent were unsuccessful for nearby 100 years after the first recognition of the disease. In the year 2000, the bacterium was finally successfully grown on a human fibroblast cell line. Untreated WD patients suffer from a chronic progressive disorder which possibly leads to death. Most patients show a fast clinical improvement to antibiotic therapy, but clinical relapses are described frequently. There is a number of patients, unable to eradicate the bacterium even after several antibiotic treatments and patients with CNS disease, in both of whom alternative therapy strategies are necessary.
Keywords: Whipple's disease, tropheryma whipplei, immunology, pathogenesis, clinical features, therapy
Current Medicinal Chemistry
Title: Current Concepts of Immunopathogenesis, Diagnosis and Therapy in Whipples Disease
Volume: 13 Issue: 24
Keywords: Whipple's disease, tropheryma whipplei, immunology, pathogenesis, clinical features, therapy
Abstract: Whipples disease (WD) is a rare chronic infectious disorder caused by the rod- shaped bacterium Tropheryma whipplei. The disorder is characterized clinically by arthralgia, abdominal pain, diarrhea, malabsorbtion and progressive weight loss. Other important sites of infection include the heart (resulting in the clinical picture of endocarditis and heart failure) and the central nervous system (CNS) (manifestations include confusion, memory loss, focal cranial nerve signs, nystagmus and ophtalmoplegia). The bacterium is presumed to be ubiquitously present. A defect in cellular immune response may predispose patients for an infection with T. whipplei and this might explain the rarity of the disorder despite the ubiquitous bacterial presence. The presumed immunological defect is likely to be quite specific for T. whipplei, since patients are not generally affected by other infections. Decreased production of Interleukin(IL)-12, IL-2 and Interferon (IFN)-γ accompanied by an increased secretion of IL-4 are the main features of this defective immunological response. The finding of periodic acid-Schiff (PAS)-positive macrophages in the lamina propria of tissue samples obtained by duodenal biopsy usually establishes the diagnosis. The PAS-positive inclusions represent the remnants of the bacteria. Attempts to isolate the causative agent were unsuccessful for nearby 100 years after the first recognition of the disease. In the year 2000, the bacterium was finally successfully grown on a human fibroblast cell line. Untreated WD patients suffer from a chronic progressive disorder which possibly leads to death. Most patients show a fast clinical improvement to antibiotic therapy, but clinical relapses are described frequently. There is a number of patients, unable to eradicate the bacterium even after several antibiotic treatments and patients with CNS disease, in both of whom alternative therapy strategies are necessary.
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Current Concepts of Immunopathogenesis, Diagnosis and Therapy in Whipples Disease, Current Medicinal Chemistry 2006; 13 (24) . https://dx.doi.org/10.2174/092986706778521913
DOI https://dx.doi.org/10.2174/092986706778521913 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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