Whipples Disease

Whipple's disease is caused by the rod-shaped bacillus Tropheryma whippelii and presents with arthralgias, abdominal pain, fever, diarrhea, malabsorption, and weight loss.y , y Whipple's disease occurs predominantly in middle- aged men and most often in farmers. Approximately 6 to 7 percent of patients with Whipple's disease have neurological manifestations, but many cases of CNS involvement in Whipple's disease go unrecognized. y The characteristic triad of Whipple's disease is dementia, ophthalmoplegia, and myoclonus.y Nearly all cases of ophthalmoplegia involve a conjugate vertical gaze palsy. A peculiar mixture of

smooth convergent-divergent pendular oscillations of the eyes with synchronous rhythmical contractions of the jaw, oculomasticatory myorhythmia, is thought to be unique to Whipple's disease. The diagnosis of CNS Whipple's disease is difficult. Examination of the CSF may be normal or may demonstrate a mild pleocytosis. Para-aminosalicylic acid-positive cells are rarely identified in CSF, but if they are, CNS Whipple's disease is a strong possibility. Para- aminosalicylic acid staining of a CSF cytocentrifuged pellet should therefore be performed in all patients in whom CNS Whipple's disease is suspected. y The para-aminosalicylic acid reagents will also stain Mycobacterium avium complex, Histoplasma capsulatum, and nonmicrobial glycoprotein. The PCR technique has allowed for the identification of T. whippelii from small intestinal biopsy tissue, lymph node tissue, and CSF. y Brain biopsy is not routinely recommended for CNS Whipple's disease. T. whippelii infection of the duodenal mucosa can be detected by PCR in patients in whom an isolated extraintestinal disease exists and in patients with isolated CNS disease. It has been suggested, therefore, that a patient with suspected CNS Whipple's disease should undergo a duodenal tissue biopsy by endoscopy, and the material obtained should be examined by PCR for T. whippelii. PCR-based Whipple's disease diagnostic tests, however, are not yet standardized. y Trimethoprim-sulfamethoxazole appears to be the most effective therapy for the treatment and prevention of CNS Whipple's disease. Treatment should be initiated with trimethoprim-sulfamethoxazole 160 mg/800 mg by mouth 2 to 3 times daily, procaine penicillin G 1.2 million units intramuscular injection daily, and streptomycin 1 g by intramuscular injection daily. Penicillin and streptomycin are continued for a total of 14 days. Trimethoprim-sulfamethoxazole should be continued for at least 1 year. Some clinicians continue antibiotic therapy for CNS Whipple's disease for at least 2 years, and some indefinitely. y


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