History and exam

Key diagnostic factors

common

diarrhea

Present in up to 85% of patients with classic Whipple disease.​[50]​​[52][53][71]​​

weight loss

Present in nearly all patients with classic Whipple disease.[49]​​[50]​​[52][53]​​[72]

arthralgia

Present in up to 90% of patients with classic Whipple disease.[49]​​[50][51][52][53][71][72]​​​​​[73]​​

uncommon

supranuclear ophthalmoplegia

Present in 32% of Whipple disease patients with neurologic signs.​[50][51][52][53]

Other diagnostic factors

common

abdominal pain

Present in up to 72% of patients with classic Whipple disease.​[50]​​[52][53][73]

lymphadenopathy

Present in up to 66% of patients with classic Whipple disease.​[50]​​[52][53]

fever

Present in up to 55% of patients with classic Whipple disease.[49]​​[50]​​[52][53][71]​​[73]​​​​​

steatorrhea

Present in up to 93% of patients with classic Whipple disease.​​​​[53][73]

anemia

Present in up to 85% of patients with classic Whipple disease, but anemia is a nonspecific diagnostic sign.[11][49]​​

skin darkening

Present in up to 54% of patients with classic Whipple disease.[49][50][52]​​​​[74]​​​

uncommon

confusion, memory impairment, altered level of consciousness, or dementia

Present in about 25% of Whipple disease patients with neurologic signs.​[50][51][52][53]

apathy

Present in 21% of patients with neurologic signs.[53]​​

anxiety, depression, hypomania, psychosis, change in personality

Psychiatric signs are present in 19% of patients with neurologic signs.[53]​​

myoclonic signs

Present in 16% of patients with neurologic signs.[53]​​

seizures

Present in 14% of patients with neurologic signs.[53]​​

nystagmus

Present in 14% of patients with neurologic signs.[53]​​

brisk reflexes, extensor plantar responses, weakness predominating in arm extensors and leg flexors, hypertonia

Upper motor neuron dysfunction is present in 14% of patients with neurologic signs.[53]​​

amenorrhea, polydipsia, hyperphagia, decreased libido

Hypothalamic symptoms are present in 11% of patients with neurologic signs.[53]​​

ataxia

Cerebellar pathology is present in 10% of patients with neurologic signs.[53]​​

headaches

Present in 10% of patients with neurologic signs.[53]​​

oculomasticatory and oculofacioskeletal myorhythmias

Present in 8% of patients with neurologic signs.[53][54]

Oculomasticatory and oculofacioskeletal myorhythmias are defined as pendular vergence oscillations (PVOs) of the eyes (rhythmic, smooth, convergent eye movements) synchronous with myorhythmias (regular repetitive contractions) of the masticatory, facial, and pharyngeal muscles. Oculomasticatory myorhythmia is defined as PVOs with masticatory, facial, and pharyngeal myorhythmia. Oculofacioskeletal myorhythmia is defined as PVOs with myorhythmia of nonfacial skeletal muscles.[50][52]

hemiparesis

Present in 8% of patients with neurologic signs.[53]​​

cranial nerve involvement

Present in 7% of patients with neurologic signs.[53]​​

extrapyramidal movement disorder

Present in 7% of patients with neurologic signs.[53]​​

peripheral neuropathies

Present in 6% of patients with neurologic signs.[53]​​

Risk factors

strong

age >50 years

Infection tends to affect mainly older patients.[19]

male sex

Historically, more common in males: up to 86% of patients have been reported to be male.[14]

Data from 2012 to 2017 suggest no difference in disease prevalence with respect to sex, while hospital admission data from 2016 to 2018 showed 67% male prevalence.[19][20]​​

genetic factors

Pathogenesis is most likely enabled by genetic risk factors, which are not confirmed. The only risk factor determined so far is an HLA antigen predisposition in patients with Whipple disease.[26]

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