Background
Whipple disease is a systemic bacterial disease caused by Tropheryma whippelii. Described by Whipple in 1907, it is a chronic disease involving mainly the intestine, causing diarrhea, malabsorption, and weight loss. There are a number of extraintestinal symptoms and occasional patients may not have malabsorption. Cases include lymphadenopathies and polyarthritis, cardiovascular manifestations such as endocarditis, and neurologic or ophthalmologic manifestations such as uveitis.
OUTLINE
CHARACTERIZATION Radiographs CT scan and MRI Laboratory Markers CultureN Engl J Med. 2000;342:620-625.
Human fibroblast cell line (HEL), in cultivating T. whippelii. They completed seven passages of an isolate obtained from the aortic valve of a patient with endocarditis due to Whipple's disease
Confirmation that the passaged isolates were T. whippelii was provided by the following findings:
PAS-positive bacilli (not acid-fast but gram-positive) were identified in an intracellular location in the cell-culture monolayer
Amplified sequences of the 16S rRNA gene of the isolate were identical to those of T. whippelii
Transmission electron microscopy of the isolate revealed the distinctive trilamellar appearance of Whipple's bacillus
Indirect immunofluorescence staining of the isolate in infected HEL cells with use of the patient's serum as the primary antibody were strongly positive
Polyclonal antibodies were produced in high titers in mice and used to detect the bacterium in the patient's excised heart valve PCRJ Clin Microbiol. 2000;38:595-599.
Ann Intern Med. 1997;126:520-527.Standard for diagnosing Whipple disease
PCR with 16S rDNA primers of T. whippelii has proved useful for monitoring the response to therapy. PCR results were positive in 36 of 38 specimens from patients with histologically confirmed or clinically suspected Whipple's disease
Good sensitivity despite false-negative results probably due to PCR inhibitors in the samplesSpecificity of intestinal PCR for Whipple disease has been shown to vary with different investigators and PCR procedures
4.8% of patients without Whipple disease have a PCR-positive duodenal biopsy sample, 11.4% have PCR-positive gastric fluid,17 and 35% have PCR-positive saliva
Discrepancy between the high prevalence of the bacterial genes in the population and the low prevalence of the disease could also be explained by pathogenic variations among strains SerologyN Engl J Med 2000;342:620-5.
Immunofluorescence serologic test with which they examined serum from 9 patients with Whipple's disease and 40 control subjectsWhen a cutoff value of 1:100 was selected, IgG antibodies against the bacillus were detected in serum samples from all nine patients with Whipple's disease as well as in almost 75 percent of samples from the control subjects
The specificity of the presence of IgM antibodies was greater; using a cutoff value of 1:50
Results were positive for 7 of 9 patients with Whipple's disease as compared with 3 of 40 control subjects. Also, higher titers of IgM antibodies (greater than or equal to 1:400) were present in three of seven patients with classic Whipple's disease and in both patients with Whipple's disease endocarditis but in none of the control subjects
CLINICAL VARIANTS CHARACTERIZATION GENERAL
- Whipple disease: a case report and review of the literature.
Muir-Padilla J, Myers JB.
Department of Pathology, Madigan Army Medical Center, Tacoma, Wash 98431, USA.
Arch Pathol Lab Med. 2005 Jul;129(7):933-6. Abstract quote
Whipple disease is a chronic, relapsing, and multisystem disease. It presents a diagnostic challenge for both clinicians and pathologists. Recent advances in isolation and culture have identified the organism responsible for the disease to be a member of the order Actinomycetes designated Tropheryma whipplei.
Several immune system changes have been noted in patients with Whipple disease, but whether these are primary or secondary is as yet undetermined.
Long-term antibiotic therapy is required, and relapses are common, especially with central nervous system involvement.VARIANTS BONE MARROW
Primary diagnosis of Whipple's disease in bone marrow.
Krober SM, Kaiserling E, Horny HP, Weber A.
Institute of Pathology, University of Tubingen, Tubingen, Germany.
Hum Pathol. 2004 Apr;35(4):522-5. Abstract quote
Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable.
Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level.
This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.SKIN
Erythema nodosum-like lesions in treated Whipple's disease: signs of immune reconstitution inflammatory syndrome.
Department of Dermatohistology, Catholic Clinics, Duisburg, Germany.
J Am Acad Dermatol. 2009 Feb;60(2):277-88. Abstract quote
Treatment of systemic infections due to mycobacteria and HIV infection can lead to paradoxical worsening, the immune reconstitution inflammatory syndrome, in a minority of patients.
Herein we describe a patient with Whipple's disease, a chronic systemic inflammatory disease caused by Tropheryma whipplei, who developed cutaneous and later ocular disease after initiation of antibiotic therapy. A 42-year-old man with a 12-year history of arthralgias presented with deteriorating health, including weight loss, diarrhea, fever, and acral hyperkeratosis. Whipple's disease was suspected and subsequently confirmed by finding periodic acid-Schiff (PAS)-positive foamy macrophages and T whipplei DNA by polymerase chain reaction (PCR) assays in duodenal biopsy specimens. After 5 weeks of antibiotic treatment with ceftriaxone, erythema nodosum (EN)-like lesions developed on the legs and trunk. Notably, lesional and nonlesional skin harbored intracellular and extracellular degenerated bacteria that were associated with a neutrophilic and granulomatous inflammatory response in lesional skin. Continued antibiotic therapy was associated with recurring EN-like skin nodules, orbital swelling, and facial herpes simplex virus 1 infection. Corticosteroid therapy controlled the duration and severity of the EN-like nodules and orbital swelling.
Apart from cutaneous hyperpigmentation, skin disease in Whipple's disease is infrequent and can be categorized as disorders due to malnutrition from malabsorption or so-called reversal reactions consisting of reactive erythemas, and neutrophilic and granulomatous responses to T whipplei, the latter of which can represent an immune reconstitution inflammatory reaction after initiation of antibiotic therapy. Finally, based on the presence of T whipplei in normal skin, skin biopsy may serve as another site for diagnostic testing in patients suspected of having Whipple's disease.
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Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
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Last Updated February 11, 2009
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