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An aid in diagnosis of Whipple disease, especially for identifying inconclusive or suspicious cases
Whipple disease is a chronic, systemic illness that in the majority of cases involves the small intestine and its lymphatic drainage. The disease primarily affects middle-aged individuals, with a peak incidence in the third and fourth decades. Clinical findings may include malabsorption, chronic diarrhea, abdominal pain, arthralgia, fever, and central nervous system symptoms.
Pathologic changes associated with Whipple disease are distinctive, with diagnosis dependent on histologic examination of biopsy specimens from involved tissues. Electron microscopic or special high-resolution light microscopic examination of the lamina propria of the small intestine of patients with untreated Whipple disease patients reveals many rod-shaped bacillary organisms. These tiny bacilli, referred to as Whipple bacilli, measure about 0.25 micrometer long and are seen as periodic acid-Schiff-positive granules within macrophages. These inclusions represent fragments of the cell walls from degenerating bacilli.
Culture of Whipple bacilli from biopsy material is laborious and the organism is very slow growing. Definitive identification of the Whipple-associated bacillus has been difficult because of these limitations. Recently, molecular techniques using PCR and nucleotide sequencing allowed classification of this bacillus as an actinomycete not closely related to any other known species, which has been named Tropheryma whipplei.
A positive result is considered diagnostic of Whipple disease.
A negative result does not negate the presence of the organism or active disease, as false negative results may occur due to inhibition of PCR, sequence variability underlying the primers and probes or the presence of Tropheryma whipplei in quantities less than the limit of detection of the assay.
Test results should be used as an aid in diagnosis and not be considered diagnostic in themselves. The single assay should not be used as the only criteria to form a clinical conclusion, but results should be correlated with patient symptoms and clinical presentation. A negative result does not negate the presence of the organism or active disease.
A total of 321 clinical specimens (including blood, tissue, cerebrospinal fluid, and synovial fluid) were evaluated for the presence of Tropheryma whipplei DNA by targeting the heat shock protein 65 gene using the LightCycler Whip assay and results were compared to those of a conventional PCR assay. The sensitivity and specificity of the LightCycler Whip assay compared to conventional PCR were 98% and 99%, respectively. The analytical sensitivity was less than 50 targets per reaction. The LightCycler Whip showed no cross reaction when tested on a panel of 28 organism genotypically closely related to Tropheryma whipplei by BLAST analysis.
1. Ramzan NN, Loftus E Jr, Burgart LJ, et al: Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med 1997;126:520-527
2. Morgenegg S, Dutly F, Altwegg M: Cloning and sequencing of a part of the heat shock protein 65 gene (hsp65) of “Tropheryma whippleii“ and its use for detection of “T. whipplei“ in clinical specimens by PCR. J Clin Microbiol 2000;38:2248-2253
3. von Herbay A, Ditton HJ, Schuhmacher F, et al: Whipple's disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology 1997;113(2):434-441