Whipple disease

Whipple disease is a rare multisystemic infection caused by the bacterium Tropheryma whipplei that can produce gastrointestinal, neurological, musculoskeletal, cardiovascular, and other systemic manifestations. A distinctive presentation may include the combination of unexplained cognitive or psychiatric deterioration with characteristic neurological findings—particularly vertical supranuclear gaze palsy, myoclonus, ataxia, or oculomasticatory myorhythmia—especially when accompanied by a history of diarrhoea, weight loss, abdominal pain, and migratory arthralgia. Importantly, the gastrointestinal symptoms and arthralgia may precede the neurological syndrome by years, but CNS disease can also occur with little or no systemic disease.

Exposure clues include occupational or environmental exposure to T. whipplei, although the epidemiological risk factors for acquiring Whipple disease are not well defined. The disease predominantly affects middle-aged men, and prior gastrointestinal, joint, or other systemic symptoms may provide important clues. Because CNS Whipple disease can occur in isolation, the absence of a known history of systemic Whipple disease does not exclude it.

It can present with psychiatric features such as depression, apathy, irritability, behavioural or personality change, sleep disturbance, impaired concentration, cognitive impairment, and progressive dementia. Psychotic symptoms and manic features have also been reported.

Other characteristic features include encephalopathy, myoclonus, ataxia, dysarthria, seizures, upper motor neuron signs, hypothalamic dysfunction, and sleep disturbance. Oculomasticatory myorhythmia and oculofacioskeletal myorhythmia are particularly distinctive and highly suggestive of CNS Whipple disease, although they are present in only a minority of patients. Ocular abnormalities may include supranuclear vertical gaze palsy, nystagmus, ophthalmoplegia, and other disorders of eye movement.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

• Cardiovascular: Culture-negative endocarditis and other cardiac involvement may occur and can occasionally be the predominant or presenting manifestation of T. whipplei infection.

• Hematologic: Anaemia and lymphadenopathy may occur, particularly in systemic disease.

• Musculoskeletal: Migratory arthralgia or arthritis is a classic early manifestation and may precede gastrointestinal or neurological disease by months or years.

• Dermatologic: Hyperpigmentation and, less commonly, other cutaneous manifestations may occur.

• Gastrointestinal: Chronic diarrhoea, abdominal pain, weight loss, malabsorption, steatorrhoea, and other manifestations of small-bowel involvement are characteristic of classical Whipple disease.

Early diagnosis is important because untreated CNS Whipple disease can cause progressive and potentially irreversible neurological and psychiatric injury, whereas appropriate antimicrobial therapy can produce substantial clinical improvement.