Background
Whipple disease is a systemic disease most likely caused by a gram-positive bacterium, Tropheryma whipplei (formerly T whippelii). [1, 2] Although the first descriptions of the disorder described a malabsorption syndrome with small intestine involvement, the disease also affects the joints, central nervous system, and cardiovascular system. T whipplei infection is recognized to be a major cause of culture-negative endocarditis. [3] Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. [4]
Pathophysiology
Whipple disease is a rare multisystem inflammatory disease. The clinical manifestations of the disease are believed to be caused by infiltration of the various body tissues by T whipplei. The patient's immune system reacts by incorporating the organisms into tissue macrophages.
These macrophages can be easily observed infiltrating the tissues using conventional light microscopy. The macrophages are easily observed when periodic acid-Schiff stain is used for the histologic sections. However, positive periodic acid-Schiff–stained macrophages infiltrating body tissues are not pathognomonic for Whipple disease. These microphages also can be detected in infection due to Mycobacterium avium intracellulare, cryptococcosis, or other parasitic organisms (usually observed in patients who are immunosuppressed with HIV disease). [5, 6] Stains for fungal organisms and acid-fast bacilli are helpful in ruling out Whipple disease.
Diagnostic electron microscopy reveals coccobacillary bodies that represent the T whipplei organism. This is diagnostic because a positive polymerase chain reaction (PCR) for T whipplei will be present in the affected tissue. [7, 8, 9]
The malabsorption observed in the small bowel that is associated with this condition is believed to be secondary to the disruption of normal villous function due to infiltration of the lamina propria of the small bowel. Patients with arthralgias have been found to have the organism in the synovial tissues. [10] The organisms have been detected in the heart valves of patients with cardiac Whipple disease [11, 12] and in the CNS of patients with neurologic disease. [13] Rarely, the organism can be detected in the lungs of affected patients. [14] In short, although Whipple disease represents a systemic condition, only a few organ systems of the body are affected overtly.
Etiology
Whipple disease is believed to be due to a disordered host response to the bacterium T whipplei. [15] Of note, patients with human immunodeficiency virus (HIV) infection do not acquire the disease.
Data that suggest that T whipplei DNA may be found in patients who are asymptomatic. [15, 16, 17] One study revealed its presence in saliva in 35% of a sample of 40 healthy patients. [18] This suggests that Whipple disease is a manifestation of an abnormal host response to a microorganism that may occur frequently in humans (perhaps in a similar manner to that observed with Helicobacter pylori).
To date, Koch's postulates have not been fulfilled completely (infection of an animal model and isolation of the organism from the animal). However, T whipplei bacteria have been grown successfully in HEL (a human fibroblast line) cells. [2] The production of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies has been shown. The organism has been cultured from affected cerebrospinal fluid (CSF) and vitreous humor of patients with Whipple disease.
Epidemiology
International statistics
Whipple disease is extremely rare worldwide; only several hundred clinical cases have been reported, mostly from North America and western Europe. The disease appears to be associated with the human leukocyte antigen B27 (HLA-B27) haplotype. [19] The incidence has been estimated to be less than 1 per 1,000,000. [20]
Race-, sex-, and age-related demographics
Whipple disease is most common in white males [15] and rarely is described in females (male-to-female ratio: approximately 8-9:1). The route of disease transmission is not known but may be associated with occupational exposure to animals and soil.
Whipple disease is usually observed in middle-aged [15] and elderly persons (older than 40 y).
Prognosis
If Whipple disease is untreated, the prognosis is poor, and mortality approaches 100% after 1 year in patients who do not receive the correct diagnosis and therapy. [21, 22, 23]
If this condition is treated for a full year, the prognosis usually is good. Clinical remission occurs in approximately 70% of patients.
Complications
Up to 30-40% of patients may relapse, and relapse appears to be more common in patients with central nervous system (CNS)–related Whipple disease.
A potential complication is a reaction or allergy to antibiotics that could require changing the antibiotic agent.
