Description
Whipple’s disease is a rare, chronic, multisystem infectious disorder caused by the gram-positive bacillus Tropheryma whipplei. It predominantly affects the gastrointestinal system, but it can involve any organ system, including the cardiovascular, nervous, and musculoskeletal systems. It is characteristically recognised by malabsorptive diarrhoea, weight loss, arthropathy, and neurological manifestations.
Pathogenesis
Tropheryma whipplei, the causative organism, is an intracellular bacterium which primarily affects the macrophages. The bacterium is believed to be ubiquitous in the environment but only causes disease in a small subset of individuals with a specific genetic predisposition that impairs their ability to generate an effective immune response against the bacterium. This results in a proliferation of the bacterium within macrophages in various tissues, leading to the varied clinical manifestations of the disease.
Subtypes
No known subtypes of Whipple’s disease are currently recognised.
Epidemiology, Risk Factors & Associations
- More prevalent in middle-aged males (60-70% of patients are males aged 40-60 years).
- Often associated with individuals who have regular contact with soil and animals, suggesting a potential environmental source of the bacterium.
Clinical Features
- Gastrointestinal symptoms: diarrhoea, abdominal pain, and malabsorption leading to weight loss.
- Arthropathy: transient, migratory and non-deforming, affecting large joints.
- Neurological symptoms: cognitive impairment, ophthalmoplegia, ataxia, myoclonus, seizures.
- Cardiac involvement: endocarditis and myocarditis.
Complications
- Chronic malabsorption can lead to malnutrition and vitamin deficiencies.
- Untreated, the disease can progress to severe weight loss, immunosuppression, and death.
Pathological Features
Histopathology
- Macroscopic: No specific macroscopic findings, apart from distension and thickening of the small bowel wall.
- Microscopic: The characteristic finding is foamy macrophages in the lamina propria filled with Periodic acid-Schiff (PAS)-positive granules.
Serology
- Tropheryma whipplei can be detected in the blood by PCR.
Biochemistry
- As a result of malabsorption, laboratory tests may show iron deficiency anaemia, low serum albumin, and fat in the stool.
Radiological Features
General Features
- Characteristically demonstrates dilatation and thickening of the small bowel loops, especially the jejunum.
- Associated mesenteric lymphadenopathy is often present.
CT
- Non-contrast: Thickenings and increased attenuation of the jejunal folds, distention of small bowel loops.
- Contrast-enhanced: Mucosal enhancement of the thickened folds, mesenteric lymphadenopathy, ascites.
MRI
- T1WI: Small bowel wall thickening with low signal intensity.
- T2WI: High signal intensity of the bowel wall.
- T1 C+: Enhancement of the bowel wall and lymph nodes.
- DWI/ADC: Restricted diffusion in the bowel wall suggestive of inflammation.
Grading and Staging
Not applicable as Whipple’s disease is an infectious condition.
Diagnosis
The definitive diagnosis is established by histopathologic examination of a small bowel biopsy showing PAS-positive foamy macrophages in the lamina propria. PCR for T. whipplei in the blood or CSF can also be diagnostic.
Differential Diagnosis
- Other causes of malabsorption, such as coeliac disease, tropical sprue, and intestinal lymphoma.
- Neurological diseases, such as multiple sclerosis and Creutzfeldt-Jakob disease, when neurological symptoms predominate.
Management
The treatment of choice is long-term antibiotic therapy, typically with ceftriaxone or penicillin G intravenously for two weeks, followed by trimethoprim-sulfamethoxazole orally for one to two years. The patient should be referred to a specialist in infectious diseases for management.