Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease

Feurle, Gerhard E.; Junga, Natascha S.; Marth, Thomas

doi:10.1053/j.gastro.2009.10.041

Cited by 167 publications

(100 citation statements)

References 33 publications

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“…whipplei can also cause localized infections which do not develop into the classic form of Whipple's disease. In these cases, there is no systemic involvement of T. whipplei, and the stool and saliva samples tested by PCR and/or PAS-stained duodenal biopsy specimens may often be negative (18,73,147,148).…”

Section: Localized Chronic Infectionsmentioning

confidence: 99%

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

et al. 2017

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SUMMARY Whipple's disease is a rare infectious disease that can be fatal if left untreated. The disease is caused by infection with Tropheryma whipplei, a bacterium that may be more common than was initially assumed. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. On the other hand, due to the generic symptoms, infection with this bacterium is actually quite often in the differential diagnosis. The gold standard for diagnosis used to be periodic acid-Schiff (PAS) staining of duodenal biopsy specimens, but PAS staining has a poor specificity and sensitivity. The development of molecular techniques has resulted in more convenient methods for detecting T. whipplei infections, and this has greatly improved the diagnosis of this often missed infection. In addition, the molecular detection of T. whipplei has resulted in an increase in knowledge about its pathogenicity, and this review gives an overview of the new insights in epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Tropheryma whipplei infections.

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Section: Localized Chronic Infectionsmentioning

confidence: 99%

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

et al. 2017

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“…Massive infiltration of the duodenal mucosa by macrophages that are filled with huge amounts of T. whipplei is the pathognomonic hallmark of CWD. The disease is fatal if not treated with appropriate antimicrobials (6). The low incidence of CWD despite the ubiquitous presence of T. whipplei in the environment and in control persons (7,8) as well as effective humoral and cellular immunological responses against the agent in healthy adults (9,10) indicate predisposing immunological defects in patients with CWD.…”

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confidence: 99%

Regulatory T Cells in Patients with Whipple’s Disease

Schinnerling

Moos

Geelhaar

et al. 2011

The Journal of Immunology

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Classical Whipple’s disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflammatory reaction and the absence of T. whipplei-specific Th1 reactivity support persistence and systemic spread of the pathogen. In this article, we hypothesized that regulatory T cells (Treg) are involved in immunomodulation in CWD, and we asked for the distribution, activation, and regulatory capacity of Treg in CWD patients. Whereas in the lamina propria of CWD patients before treatment numbers of Treg were increased, percentages in the peripheral blood were similar in CWD patients and healthy controls. However, peripheral Treg of CWD patients were more activated than those of controls. Elevated secretion of IL-10 and TGF-β in the duodenal mucosa of CWD patients indicated locally enhanced Treg activity. Enhanced CD95 expression on peripheral memory CD4+ T cells combined with reduced expression of IFN-γ and IL-17A upon polyclonal stimulation by CD4+ cells from untreated CWD patients further hinted to Treg activity-related exhaustion of effector CD4+ T cells. In conclusion, increased numbers of Treg can be detected within the duodenal mucosa in untreated CWD, where huge numbers of T. whipplei-infected macrophages are present. Thus, Treg might contribute to the chronic infection and systemic spread of T. whipplei in CWD but in contrast prevent mucosal barrier defect by reducing local inflammation.

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“…Current treatment recommendations are not based on randomised controlled clinical trials but evidence from case series and retrospective analysis suggest the use of 2g intravenous ceftriaxone daily for two weeks followed by 960mg of oral co-trimoxazole for one to two years [3]. This has been suggested to cure all patients [11] but the susceptibility of T. whippelii to such antibiotics varies. The presence of mutations in the folP gene that encodes dihydropteroate synthase, the target of sulfamethoxazole, also contributes to clinical failure [12].…”

Section: Discussionmentioning

confidence: 99%

Palindromic Rheumatoid Arthritis-An Unorthodox Presentation of Whipple’s Disease

Santucci¹

2016

SJCM

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Whipple's disease is a rare infection of the gastrointestinal tract caused by the actinomycete Tropheryma whippelii.It most commonly presents with arthralgia, abdominal pain, diarrhoea and weight loss. Invasion of the bacterium through the gastrointestinal mucosa leads to small intestinal villus blunting and malabsorption. Diagnosis is made by histological examination of small bowel biopsies. We report the case of a 78 year old gentleman who had a two year history of fleeting joint pain and multiple hospital admissions for varying symptoms. He was treated with antibiotics for a chest infection with improvement only to present again after 1 year with anorexia, fatigue, blackish loose stools and epigastric pain. Microscopic examination of duodenal biopsies showed a stunted villous architecture and expansion of the lamina propria by foamy macrophages. These expressed CD68 and cytoplasmic contents were strongly PAS positive, consistent with a diagnosis of Whipple's disease. He was started on intravenous ceftriaxone and a prolonged course of oral co-trimoxazole (at least 1 year) with marked clinical improvement. In retrospect, the previous year's admissions might have also been due to Whipple's disease but since he did not have the full course of the appropriate treatment he relapsed. Whipple's disease is a difficult diagnosis to make because of the variety of clinical symptoms and the long time span between the initial unspecific symptoms (the prodromal stage) and the full-blown clinical picture of the illness (the steady-state stage). It may be misdiagnosed with a non-infectious rheumatic illness and may be fatal if untreated.

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Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease

Cited by 167 publications

References 33 publications

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Regulatory T Cells in Patients with Whipple’s Disease

Palindromic Rheumatoid Arthritis-An Unorthodox Presentation of Whipple’s Disease

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