Whipple's arthritis: Direct detection ofTropheryma whippelii in synovial fluid and tissue

O’Duffy, J. Desmond; Griffing, W. Leroy; Li, Chin Yang; Abdelmalek, Manal F.; Persing, David H.

doi:10.1002/1529-0131(199904)42:4<812::aid-anr27>3.0.co;2-s

Cited by 88 publications

(34 citation statements)

References 12 publications

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“…However, the clinical sensitivity, i.e., the sensitivity with regard to the detection of patients with Whipple's disease, is only 63% but still significantly higher than that of histopathology (4,17,19,23), with a clinical sensitivity of only 12.5% in our small series. This confirms that PCR from duodenal biopsies and stool specimens is significantly more sensitive than histopathology and that a number of patients with Whipple's disease show no gastrointestinal evidence (clinical or laboratory) whatsoever for the presence of this disease (9,11,20).…”

Section: Discussionsupporting

confidence: 69%

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

2002

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Whipple's disease is a rare multisystemic bacterial infection with variable clinical manifestations. For decades, the laboratory diagnosis was based on the demonstration of periodic acid Schiff-positive inclusions in macrophages of gastrointestinal biopsies. PCR has improved the diagnosis of Whipple's disease due to its increased sensitivity compared to histopathological analysis. To avoid invasive procedures for taking specimens, we have investigated the possibility of detecting Tropheryma whipplei DNA in feces rather than in biopsies or gastric aspirate of patients with and without Whipple's disease. Total bacterial DNA was isolated from stool specimens using Qiagen columns followed by a T. whipplei-specific hybridization step with a biotinylated capture probe and streptavidin-coated magnetic particles. The captured DNA was then amplified using the same seminested PCR targeting the 16S rRNA gene of the organism that had been applied to other specimens without capturing. For five of eight patients with Whipple's disease, duodenal biopsies and stool samples were PCR positive, whereas for the three other patients, both specimens were PCR negative. Of 84 patients without Whipple's disease, 75 tested negative in the duodenal biopsy and in the stool sample. For four, both specimens were positive. Five patients tested positive in the stool sample but not in the biopsy. However, for three of these five patients, the gastric aspirate had been PCR positive, indicating that the stool PCR result was true rather than false positive. Compared to PCR from duodenal biopsies, stool PCR has a sensitivity of 100% and a specificity of 97.3%. Additionally, 15 PCR-positive and 22 PCR-negative stool samples were extracted using the Invisorb Spin Stool DNA kit. The simplified stool extraction showed 93.3% sensitivity and 95.5% specificity compared to the target capture method. We conclude that PCR with stool specimens with either extraction method is a sensitive and specific diagnostic tool for the detection of T. whipplei DNA and one not requiring invasive sampling procedures.

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Section: Discussionsupporting

confidence: 69%

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

2002

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“…In order to minimize the chance of false-positive results caused by contamination or due to a nonspecific PCR, qPCR should preferably be performed on more than one sample and whenever possible also include invasive samples, for instance, blood or biopsy specimen (40). In cases of arthralgia and arthritis, qPCR on joint fluids has become the preferred method of diagnosis (190). In addition, it is good practice to test the cerebrospinal fluid by PCR, as even without clinical signs of neurological involvement in many patients, T. whipplei is present in the CNS (73,102,147,148).…”

Section: Histopathology (Pas and Hematoxylin-and-eosin Stain [Hande]mentioning

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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“…Extraintestinal disease most frequently involves the heart and CNS. Cases having neurological, cardiac or ocular involvement without overt gastrointestinal manifestations have been increasingly reported (20)(21)(22)(23)(24)(25)(26)(27). Cases having CNS involvement without systemic involvement are characterized primarily by dementia, headaches, meningitis, myoclonus, seizures and somnolence.…”

mentioning

confidence: 99%

Rare but Not so Rare? The Evolving Spectrum of Whipple′s Disease

Conly

2001

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Knowledge about Whipple's disease began to emerge in 1907, when George Hoyt Whipple recognized the first case of the disease that now bears his name. He reported the case of a 36-year-old physician with "a gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs, and a peculiar multiple arthritis" (1). Findings at autopsy consisted of poly-serositis, aortic valve vegetations and deposition of fat in the intestinal mucosa and regional lymph nodes with marked infiltration by foamy macrophages (1). It was originally thought to be a disorder of fat metabolism, and the term 'intestinal lipodystrophy' was proposed. Whipple's disease has since been recognized as a rare, multivisceral, chronic disease with a clinical presentation dominated by a symptom triad of diarrhea, weight loss and malabsorption. However, digestive symptoms are often preceded for months or years by other symptoms, the most common being arthralgia, although cardiovascular, neurological or pulmonary involvement may be more prominent at times. Once considered the ideal case report, recent characterization ofTropheryma whippeliiby means of broad range bacterial ribosomal DNA polymerase chain reaction (PCR) analysis (2,3) and its subsequent cultivation (4) has led to a veritable explosion of individual case reports, case series and hitherto unrecognized manifestations of the disease, such that it is now considered an underdiagnosed infectious disease (5). It is timely to provide an update on new developments in Whipple's disease.

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Whipple's arthritis: Direct detection ofTropheryma whippelii in synovial fluid and tissue

Cited by 88 publications

References 12 publications

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

Rare but Not so Rare? The Evolving Spectrum of Whipple′s Disease

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