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Key Features

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

  • May occur at any age but most commonly affects white men in the fourth to sixth decades

Clinical Findings

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

  • Central nervous system 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

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

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

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

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