Whipple's disease
Whipple's disease is a rare and chronic systemic infection caused by the gram-positive actinomycete bacterium Tropheryma whipplei. While it can affect individuals of any age, it predominantly occurs in middle-aged Caucasian men, with a notable male-to-female ratio of approximately 8:1 to 9:1. The disease presents a variety of symptoms, including significant weight loss, joint pain, diarrhea, and abdominal discomfort, often accompanied by complications such as cardiac issues and neurological symptoms. Diagnosis typically involves a combination of medical history, physical exams, and laboratory tests, including biopsies that reveal characteristic inclusions in tissue samples.
Treatment primarily consists of intravenous antibiotics followed by long-term oral antibiotics to eliminate the infection and manage symptoms. Despite treatment, relapses can occur in up to 40% of cases, particularly in individuals with severe neurological involvement. While the exact transmission routes for T. whipplei remain unclear, it is known that humans are the only hosts for this bacterium. Understanding Whipple's disease is crucial for early diagnosis and effective management, as untreated cases can lead to severe outcomes, including fatality.
Whipple's disease
- ANATOMY OR SYSTEM AFFECTED: All
Definition
Whipple’s disease is a rare, chronic, systemic infection caused by a gram-positive actinomycete, Tropheryma whipplei .
Causes
The bacterium T. whipplei is found ubiquitously in the general environment. However, its source and transmission is not well established.
Risk Factors
Whipple’s disease may occur in all age groups but mainly affects middle-aged Caucasian men. (The male-to-female ratio is estimated at 8:1 to 9:1.) Several hundred clinical cases have been reported, mostly from North America and Western Europe. Persons with Whipple’s disease have characteristic immunological defects associated with reduced Th1 and Th2 response (which are promoted by T lymphocytes).
Symptoms
The prodromal stage of the disease is characterized by nonspecific symptoms that last an average of six years. The progressive stage manifests by a broad spectrum of symptoms. The main clinical features include weight loss, arthralgia, diarrhea, abdominal pain, and, in some cases, fever, anemia, skin pigmentation, and lymphadenopathy. Cardiac involvement (such as chest pain, endocarditis, pericarditis, valve insufficiency, and heart failure) has been reported in 20 to 40 percent of cases. Pulmonary involvement (with a chronic cough, pleural effusion, pulmonary infiltration, or granulomatous mediastinal adenopathy) has been reported in 30 to 40 percent of cases. Neurological symptoms (such as memory impairment, confusion, depression, sleep disturbances, nystagmus, ataxia, seizures, and symptoms of cerebral compression) are found in up to 40 percent of affected persons. Ocular movement disturbances (such as progressive supranuclear ophthalmoplegia with oculomasticatory myorhythmia or oculofacioskeletal myorhythmia) are pathognomonic. Uveitis, retinitis, vitritis, keratitis, optic neuritis, and papilloedema may be present. Hearing loss and blurred vision has occasionally been reported. Rarely, hepatosplenomegaly and hepatitis may occur. If left untreated, the disease may be fatal, usually within one year.
Screening and Diagnosis
Diagnosis is based on medical history, physical examination, and laboratory evaluations. The initial diagnostic procedure requires an upper endoscopy with a small bowel mucosal biopsy, which shows periodic acid-Schiff-positive inclusions in the macrophages of lamina propria, representing the causative bacteria. T. whipplei can also be detected through specific polymerase chain reaction, immunohistochemistry, and electron microscopy. Whipple’s disease should be distinguished from malabsorptive and rare disorders such as celiac disease, Crohn’s disease, lymphoma, acquired immunodeficiency syndrome enteropathy, parasitic disorders, amyloidosis, hypogammaglobulinemia, and abetaproteinemia.
Treatment and Therapy
The management of Whipple’s disease is focused on reducing morbidity, preventing complications, and eradicating the infection. Treatment usually starts with intravenous antibiotics, such as ceftriaxone at 2 grams daily for two weeks, that achieve high levels in the central nervous system. Penicillin, other cephalosporins, carbapenems, or chloramphenicol may be used in cases of allergy or insufficient response to ceftriaxone. The induction therapy is followed by continuous treatment for one to two years with oral cotrimoxazole, twice daily. Doxycycline in combination with hydroxychloroquine, or cefixime alone, may be considered as possible alternatives to long-term cotrimoxazole.
In a majority of treated persons, diarrhea and fever resolve within one week, while other symptoms resolve within a few weeks. The disease relapses in up to 40 percent of treated cases. Patients with severe neurological manifestations may respond poorly to treatment. In these cases, additional treatment with corticosteroids or interferon gamma may be suggested.
Prevention and Outcomes
Humans are the only known host. The reservoir of T. whipplei, the transmission mechanisms, and the significance of asymptomatic carriers remain to be established. Fecal-oral transmission has been suggested, and there has been no evidence of person-to-person transmission or of epidemic outbreaks.
Bibliography
Fenollar, Florence, Xavier Puéchal, and Didier Raoult. “Whipple’s Disease.” New England Journal of Medicine 356 (2007): 55-66.
Marth, Thomas, and Thomas Schneider. “Whipple Disease.” Current Opinion in Gastroenterology 24 (2008): 141-148.
Schneider, Thomas, et al. “Whipple’s Disease: New Aspects of Pathogenesis and Treatment.” Lancet Infectious Diseases 8 (2008): 179-190.
"Whipple Disease." Medline Plus, 14 May 2024, medlineplus.gov/ency/article/000209.htm. Accessed 4 Feb. 2025.