Whipple Disease

Whipple disease is a rare multisystem illness caused by infection with the bacillus Tropheryma whipplei. It may occur at any age but most commonly affects white men in the fourth to sixth decades. The source of infection is unknown, but no cases of human-to-human spread have been documented.

Whipple disease interferes with normal digestion by impairing the breakdown of foods, and hampering your body’s ability to absorb nutrients, such as fats and carbohydrates.

The disease usually occurs in the gastrointestinal system, but may affect any part of the body including the heart, lungs, brain, joints, and eyes. In the gastrointestinal system, it interferes with the body’s ability to absorb certain nutrients. This leads to a condition known as malabsorption. Whipple disease causes weight loss, incomplete breakdown of carbohydrates or fats, and problems with the immune system.

Symptoms

These symptoms may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom.

Digestive signs and symptoms are common in Whipple disease and may include:

• Diarrhea
• Stomach cramping and pain, which may worsen after meals
• Weight loss, associated with the malabsorption of nutrients

Other frequent signs and symptoms associated with Whipple disease include:

• Inflamed joints, particularly the ankles, knees and wrists
• Fatigue
• Weakness
• Anemia

Less common signs and symptoms

In some cases, signs and symptoms of Whipple disease may include:

• Fever
• Cough
• Enlarged lymph nodes
• Skin darkening in areas exposed to the sun and in scars
• Chest pain

Brain and nervous system (neurological) signs and symptoms may include:

• Difficulty walking
• Vision problems, including lack of control of eye movements
• Confusion
• Memory loss

Diagnosis

The diagnosis of Whipple disease is established in 90% of cases by endoscopic biopsy of the duodenum with histo­logic evaluation, which demonstrates infiltration of the lamina propria with PAS-positive macrophages that con­tain gram-positive bacilli (which are not acid-fast) and dilation of the lacteals. The remainder of cases are diag­nosed by T whipplei–specific polymerase chain reaction (PCR) or immunohistochemistry of duodenal biopsies or extraintestinal fluids (cerebrospinal, synovial) or tissue (lymph nodes, synovium, endocardium).

The sensitivity of PCR is 97% and the specificity 100%. Because asymptom­atic central nervous system infection occurs in 40% of patients, examination of the cerebrospinal fluid by PCR for T whipplei should be performed routinely.

Differential diagnosis

Whipple disease should be considered in patients who present with signs of malabsorption, fever of unknown origin, lymphadenopathy, seronegative arthritis, culture-negative endocarditis, or multisystem disease. Small bowel biopsy readily distinguishes Whipple disease from other mucosal malabsorptive disorders, such as celiac sprue.

Treatment

Antibiotic therapy results in a dramatic clinical improvement within several weeks, even in some patients with neurologic involvement. The optimal regimen is unknown. Complete clinical response usually is evident within 1–3 months; how­ever, relapse may occur in up to one-third of patients after discontinuation of treatment. Therefore, prolonged treat­ment for at least 1 year is required. Drugs that cross the blood-brain barrier are preferred.

A randomized controlled trial in 40 patients with 3–10 years’ follow-up demonstrated 100% remission with either ceftriaxone 1 g intravenously twice daily or meropenem 1 g intravenously three times daily for 2 weeks, followed by trimethoprim-sulfamethoxa­zole 160/800 mg twice daily for 12 months.

After treatment, repeat duodenal biopsies for histologic analysis and cere­brospinal fluid PCR should be obtained every 6 months for at least 1 year. The absence of PAS-positive material predicts a low likelihood of clinical relapse.