Whipple Disease

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

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)

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

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

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