Whipple disease is a rare systemic chronic infectious disease. It is caused by the bacterium Tropheryma whipplei, which is ubiquitous in the environment and is transmitted through contact with contaminated soil or sewage or through the fecal-oral route. The most common symptoms are gastrointestinal, but the disease can affect multiple body systems. There is a higher prevalence of Whipple disease in middle-aged white males of European ancestry, and so a genetic predisposition has been postulated. However, no definitive association has been demonstrated, and the mechanism of infection is unknown.

Signs / Symptoms:
Physical examination findings for Whipple disease are generally nonspecific, and diagnosis is thus often delayed. Many of these features develop over a period of 6-8 years before diagnosis.

Gastrointestinal – Gastrointestinal symptoms are most common and include weight loss, diarrhea, and abdominal pain and often lead to hypoalbuminemia and anemia. Malabsorption can progress to a wasting syndrome, and abdominal lymphadenopathy may occur.

Joints – Joint involvement occurs in 60%-90% of cases, typically with intermittent migratory polyarthritis, predominately of the large joints. Rarely, a chronic destructive seronegative polyarthritis can occur that may be mistaken for rheumatoid arthritis.

Central nervous system – Central nervous system (CNS) symptoms are seen in approximately one-half of cases. Headache is a common symptom. Other manifestations include cognitive impairment, altered level of consciousness, encephalopathy, depression, and personality changes. Disturbances of ocular movement with progressive supranuclear ophthalmoplegia with oculomasticatory myorhythmia or oculofacial-skeletal myorhythmia are pathognomonic. Prognosis is particularly poor for those with CNS involvement. Isolated neurological manifestations may occur without histologic evidence of intestinal involvement.

Ocular – Anterior or posterior uveitis is the most common ocular manifestation; optic neuritis and retinitis may also occur.

Cardiac – Pericarditis occurs in up to 40% of cases, and blood-culture negative endocarditis may be seen; the latter may occur in isolation without other manifestations.

Pulmonary – Pulmonary symptoms are rare, but a chronic cough can be a central feature of the disease. If there is pulmonary involvement, symptoms may include dry, chronic cough, dyspnea, pleural effusions, and other findings on chest imaging such as interstitial patterns and/or mediastinal lymphadenophy.

Microbiology:
Tropheryma whipplei is a rod-shaped gram-positive bacteria with a trilamellar plasma membrane typically found within macrophages of the lamina propria of the small intestine of patients with Whipple disease. The bacterium's cell wall contains an unusual inner layer comprised mainly of polysaccharides. On periodic acid-Schiff (PAS) stain, macrophages have characteristic foamy intracellular inclusions representing components of the degraded bacterial cell wall.

PAS-positive macrophages can also be detected from other involved sites including the cerebrospinal fluid (CSF), brain tissue, lymph nodes, synovium, heart valves, and bone marrow. The organism is one of the slowest growing human pathogenic bacteria, with an estimated generation time of 18 days, slower than some mycobacteria.