Whipple's Disease

A chronic, relapsing multisystem disease first described by GH Whipple, an American pathologist, in 1907. He described the disease as an intestinal lipodystrophy characterised by weight loss, chronic cough, fat accumulation in the intestine, mesenteric lymph nodes and stool.

It is now thought to be due to infection with actinomycete Tropheryma whippelii combined with defective cell-mediated immunity.¹ It is probably acquired as an enteric infection as this organism is commonly found in sewage effluent.

Traditionally, Whipple's disease presents a diagnostic challenge for both clinicians and pathologists.^2,3

This is a rare condition.
Risk Factors are:

• Middle-aged and elderly white males
• Family clustering (suggesting an immunogenetic component)
• HLA-B27 association

Many different forms of presentation with the common ones being:

• Polyarthralgia - transient and episodic (often first symptom)
• GI symptoms - abdominal pain, diarrhoea, distension, flatulence and steatorrhea (due to malabsorption)
• [Anorexia and weight loss
• Intermittent low-grade fever
• Chronic cough
• Hyperpigmentation - occurs in 50%

May also be:

• Generalised lymphadenopathy
• Anaemia and more rarely clotting abnormalities
• Cardiac involvement - pericarditis, myocarditis, valve lesions
• CNS involvement in 10% - dementia, opthalmaplegia, myoclonus, occulomasticatory movements (convergent eye movements with simultaneous chewing movements), gait abnormalities, seizures, coma.
• Occular involvement - uveitis, vitreitis, keratitis, retinitis, retinal haemorrhages
• Pulmonary involvement - pleural effusion, mediastinal widening (due to lymphadenopathy)
• Protein-losing enteropathy with hypoalbuminaemia and oedema (due to protein loss)

• AIDS with M. avium complex infection of small intestine
• Coeliac disease
• Sarcoidosis
• Reiter's syndrome
• Familial Mediterranean fever
• Behcet's disease
• Intestinal lymphoma

• Diagnosis requires a high index of clinical suspicion
• Routine bloods and malabsorption tests are non-specific
• Imaging will confirm involvement of different organs but is not diagnostic
• Biopsy of affected tissue, usually the duodenum, shows infiltration of the laminae propria with PAS(periodic acid Schiff stain)-positive macrophages with intracellular clumps of T.Whippeli. This test is negative in about 30%, more commonly those without GI involvement and biopsy of other organs or lymph nodes may be indicated.
• PCR of bacterial RNA (unique 16s rRNA sequence) is increasingly used in diagnosis and can be done from peripheral blood, CSF and other tissue samples.

Oral Cotrimoxazole for at least one year. If allergic, ceftriaxone or chloramphenicol. Repeat PCR at the end of treatment. With neurological involvement, often commence with IV cephalosporin and aminoglycoside.

• Insidious progression and fatal if untreated
• Locomotor and GI symptoms may improve very rapidly with treatment but histological remission can take several years.
• Follow up closely for signs of recurrence - relapse in about 35%.