Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 15-27: Malabsorption + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Multisystem disease Fever, lymphadenopathy, arthralgias Weight loss, malabsorption, chronic diarrhea Duodenal biopsy with periodic acid-Schiff (PAS)–positive macrophages with characteristic bacillus +++ General Considerations ++ Rare multisystem illness caused by infection with the bacillus Tropheryma whipplei Source of infection is unknown; no cases of human-to-human spread have been documented +++ Demographics ++ Estimated prevalence is 1 per 100,000 May occur at any age but most commonly affects white men in the fourth to sixth decades + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Clinical manifestations are protean However, the most common are arthralgias, diarrhea, abdominal pain, and weight loss Arthralgias or a migratory, nondeforming arthritis in 80% Gastrointestinal symptoms in 75% include Abdominal pain Diarrhea Variable malabsorption with distention, flatulence, and steatorrhea Weight loss in almost all patients Protein-losing enteropathy with hypoalbuminemia and edema Intermittent low-grade fever in > 50% Generalized lymphadenopathy Myocardial involvement: heart failure or valvular regurgitation CNS involvement Dementia Lethargy Coma Seizures Myoclonus Hypothalamic dysfunction Cranial nerve findings: ophthalmoplegia or nystagmus Physical examination Low-grade fever Hypotension (late) Evidence of malabsorption Lymphadenopathy (in 50%) Heart murmurs Peripheral joint inflammation, swelling Neurologic findings Hyperpigmentation on sun-exposed areas (in up to 40%) +++ Differential Diagnosis ++ Malabsorption due to other cause, eg, celiac disease or tropical sprue Inflammatory bowel disease Sarcoidosis Reactive arthritis Systemic vasculitis Infective endocarditis Intestinal lymphoma Familial Mediterranean fever Behçet syndrome Intestinal Mycobacterium avium-intracellulare (in AIDS) + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Polymerase chain reaction (PCR) Asymptomatic central nervous system infection Occurs in 40% of patients Examination of the cerebrospinal fluid by PCR should be performed routinely PCR or immunohistochemistry of duodenal biopsies or extraintestinal fluids (cerebrospinal, synovial) or tissue (lymph nodes, synovium, endocardium) confirms cases not established by endoscopic biopsy of duodenum Sensitivity of 97% Specificity of 100% +++ Diagnostic Procedures ++ Endoscopic biopsy of the duodenum Establishes diagnosis in 90% of cases Demonstrates infiltration of the lamina propria with PAS-positive macrophages that contain gram-positive, non–acid-fast bacilli, and dilatation of the lacteals Biopsy of other involved organs or lymph nodes for histologic evaluation of the involved tissues may be necessary + Treatment Download Section PDF Listen +++ +++ Medications ++ Ceftriaxone, 1 g intravenously twice daily, or meropenem, 1 g intravenously three times daily for 2 weeks Then, trimethoprim-sulfamethoxazole 160/800 mg twice daily for 12 months For patients allergic to sulfonamides or resistant to therapy, consider long-term treatment with doxycycline or hydroxychloroquine + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ After treatment, repeat duodenal biopsies at 6 and 12 months for histologic evaluation; absence of PAS-positive material predicts a low likelihood of clinical relapse +++ Complications ++ Some neurologic signs may be permanent +++ Prognosis ++ Antibiotic therapy results in a dramatic clinical improvement within several weeks Complete response within 1–3 months Relapse may occur in up to one-third of patients after discontinuation of treatment If untreated, the disease is fatal + References Download Section PDF Listen +++ + +Biagi F et al. What is the best therapy for Whipple's disease? Our point of view. Scand J Gastroenterol. 2017 Apr;52(4):465–6. [PubMed: 27924649] + +Elchert JA et al. Epidemiology of Whipple's disease in the USA between 2012 and 2017: a population-based national study. Dig Dis Sci. 2019 May;64(5):1305–11. [PubMed: 30488239] + +Hujoel IA et al. Tropheryma whipplei infection (Whipple disease) in the USA. Dig Dis Sci. 2019 Jan;64(1):213–23. [PubMed: 29572616]