History

Whipple disease was first described by Dr. George H. Whipple in 1907.^[24]The classic presentation of Whipple disease is that of a wasting illness characterized by arthralgias, arthritis, fever, and diarrhea; however, this form is rare.^{[15, 25]}Lymphadenopathy may be present.

If Whipple disease affects the small intestine, steatorrhea often is present.

Approximately 90% of patients with Whipple disease present with weight loss, and 70% of patients with Whipple disease complain of either diarrhea or arthralgias. In about three quarters of patients, the joint manifestations are followed by weight loss and diarrhea, with a mean time of 6 years from onset of the joint symptoms to diagnosis of Whipple disease.^[26]

Whipple disease may mimic chronic inflammatory rheumatic disorders and present with atypical manifestations.^{[27, 28, 29]}Case reports exist in which patients with Whipple disease were diagnosed in the context of an inflammatory disease that was refractory to treatment with anti-tumor necrosis factor alpha (anti-TNF-a).^{[27, 28]}The joint manifestations of Whipple disease are nondeforming.

Occult gastrointestinal (GI) bleeding can be found in 80% of patients of Whipple disease, but frank hematochezia is uncommon.

Cardiac involvement occurs in approximately 30% of cases.

Physical Examination

Swelling of the joints may occur, but frankly deforming arthritis is quite rare.^[30]Sacroiliitis, pancarpal narrowing, and cervical epiphyseal fusion have been described in selected patients.

Patients with Whipple disease may have any of the physical findings associated with malabsorption. These findings are nonspecific but include the following:

Cachexia
Distended abdomen
Glossitis
Perlèche (angular cheilitis)
Chvostek or Trousseau sign (secondary to hypocalcemia)
Gingivitis and parafollicular hemorrhages (secondary to vitamin C deficiency)
Night blindness (secondary to vitamin A deficiency)
Visible peristalsis with borborygmi
Hyperpigmentation around the orbital and malar areas of the face (occasionally)

When the CNS is involved, patients may demonstrate signs of frontal release (as seen with dementia), meningoencephalitis, or ataxia and clonus (if the cerebellum is affected).^{[31, 32, 33]}One review noted that supranuclear ophthalmoplegia and cerebellar ataxia were two of the most common neurologic findings.^[34]

In a retrospective study, neurologic symptoms in 18 patients with Whipple disease and CNS infection (median follow-up, 6 y) included the following: confusion or coma related to meningoencephalitis or status epilepticus (17%); delirium (17%); cognitive impairment (memory loss, attention defects, typical frontal lobe syndrome) (61%); hypersomnia (17%); abnormal movements (eg, myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron symptoms (44%); extrapyramidal symptoms (33%); and ophthalmoplegia, with/without progressive supranuclear palsy (17%).^[35]

Differential Diagnoses

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