History and exam

Key diagnostic factors

common

presence of risk factors

Include male sex and age >50 years.

diarrhoea

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

weight loss

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

arthralgia

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

uncommon

supranuclear ophthalmoplegia

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

Other diagnostic factors

common

abdominal pain

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

lymphadenopathy

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

fever

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

steatorrhoea

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

anaemia

Present in up to 85% of patients with classic Whipple's disease, but anaemia is a non-specific diagnostic sign.[11][49]​​​

skin darkening

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

uncommon

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

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

apathy

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

anxiety, depression, hypomania, psychosis, change in personality

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

myoclonic signs

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

seizures

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

nystagmus

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

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

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

amenorrhoea, polydipsia, hyperphagia, decreased libido

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

ataxia

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

headaches

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

oculomasticatory and oculofacioskeletal myorhythmias

Present in 8% of patients with neurological 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 non-facial skeletal muscles.[50][52]

hemiparesis

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

cranial nerve involvement

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

extrapyramidal movement disorder

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

peripheral neuropathies

Present in 6% of patients with neurological 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 probably enabled by genetic risk factors, which are not confirmed. The only risk factor determined so far is a HLA antigen predisposition in patients with Whipple's disease.[26]

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