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A diagnostic conundrum

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Q1: What is the diagnosis in this case?

The diagnosis is Whipple’s disease. This is a rare multisystem disorder characterised by weight loss, diarrhoea, abdominal pain, arthralgia and lymphadenopathy, though presentation may be very variable. It is caused by a Gram positive, PAS positive bacillus called Tropheryma whippelii which was identified in 1992.1

It has been reported in all age groups, though it is commonest in middle aged white males. Whipple’s disease commonly involves the gastrointestinal tract causing a dilated thickened intestine with villous atrophy and malabsorption, resulting in anorexia, weight loss, abdominal pain, anaemia, hypoalbuminaemia and rarely, clotting disorders.

The heart and all its layers can be affected. Polyarthralgia is common though transient and episodic. Generalised hyperpigmentation can be found in up to 50% of patients. One of the striking features is mesenteric, abdominal, retroperitoneal, mediastinal, and peripheral lymphadenopathy which can often be mistaken for lymphoma, sarcoidosis, or other granulomatous disorders. Ten percent of patients have neurological involvement at some stage of their illness. Dementia, ophthalmoplegia, and facial myoclonus are the commonest features.2

Q2: What is the pathognomonic central nervous system manifestation?

The answer is facial and ocular myoclonus. This includes oculomasticatory myorhythmia and oculofacial-skeletal myorhythmia.3 The former is characterised by a slow, smooth convergent-divergent pendular nystagmus associated with synchronous contractions of the jaw and the latter is associated with contractions of other body parts.

These are rare findings present in 20% of patients with central nervous system disease and are as diagnostic as a positive biopsy or a positive polymerase chain reaction assay of the bacterial RNA.

Q3: What is the diagnostic test?

The diagnosis of Whipple’s disease requires a high index of clinical suspicion. Routine blood tests are non-specific as are tests of malabsorption. Histopathological examination of biopsies of the organs involved reveal PAS positive macrophages containing clumps of T whippelii. In about 30% of cases this is negative. The current diagnostic test is polymerase chain reaction of bacterial 16S ribosomal RNA from tissue biopsies, cerebrospinal fluid, blood, etc.4

Q4: How does one treat this condition?

Current treatment is long term co-trimoxazole (trimethoprim-sulphamethoxazole).5 Initial treatment in those with neurological involvement is an intravenous combination of cephalosporins and aminoglycosides, followed by oral co-trimoxazole. Locomotor and gastrointestinal symptoms may show improvement in days while histological remission may take 1–2 years. Relapse rates can be up to 35%.

Final diagnosis

Whipple’s disease.

References

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