Late manifestations of Whipples disease
• CNS manifestations: CNS manifestations are the third most frequent manifestation (following arthralgia/arthritis and gastrointestinal) and affect 6% to 63% of individuals with Whipple’s disease. Symptoms can be central or peripheral, isolated or multifocal. Even in Whipple’s patients without neurologic symptoms, 50% can have PCR-positive cerebrospinal fluid (CSF); therefore, all patients should have CSF tested before therapy, regardless of symptoms. Postmortem examination of Whipple’s disease patients and T. whipplei carriers found that 90% of these individuals had brain and spinal cord lesions. The CNS lesions typically consist of necrosis with inflammatory cells and astrogliosis. The lesions have perivascular macrophages containing PAS-positive rod-shaped structures intracellularly. In patients who develop neurologic symptoms, dementia is the most frequent symptom (70%). Psychiatric symptoms (50%), supranuclear vertical gaze palsy (50%), hypothalamic involvement (33%), and myoclonus (25%) are also common. Both oculofacial-skeletal myorhythmia (OFSM) and oculomasticatory myorhythmia (OMM) are virtually pathognomonic of CNS Whipple’s disease. OMM is characterized by slow convergent-divergent pendular nystagmus of the eyes at 1 Hz, associated with synchronous contractions of the masticatory muscles and of the proximal and distal skeletal muscles at 1–2 Hz. OFSM is characterized by slow, smooth, convergent-divergent pendular nystagmus associated with synchronous contractions of other body parts. Other associated neurological signs include supranuclear ophthalmoplegia (usually vertical), facial weakness, and bilateral ptosis. The classic CNS Whipple’s disease triad of dementia, supranuclear ophthalmoplegia, and myoclonus is very specific and should warrant further investigation. Brain biopsy and positive PCR of CSF are diagnostic in 90% of cases. The prognosis for patients with symptomatic CNS involvement is poor as the 4-year survival rate is <75% and major sequelae are seen in 25%.
• Cardiovascular involvement: T. whipplei has been a rare cause of culture-negative endocarditis. Cardiac involvement of the pericardium, myocardium, and endocardium including valves is found at autopsy in almost all patients with classic Whipple’s disease. However, only 17% to 55% of cases are symptomatic.
• Ophthalmologic manifestations: Panuveitis is the most common ocular manifestation and diagnosis is made by PAS stain for macrophages and PCR testing of the vitreous humor. Other manifestations include keratitis, retinitis, choroiditis, optic neuritis, and orbital inflammatory disease including orbital pseudotumor. Crystalline keratopathy has been reported as a characteristic of ocular Whipple’s disease.
• Other manifestations may accompany a classic Whipple’s presentation. These include pulmonary involvement (30%), mesenteric more than peripheral adenopathy with noncaseating granulomas (9%), and rarely genitourinary involvement.
