GastroenterologyTier 2Disease (DEADMAN)

Whipple disease

Description

Whipple disease - a rare, chronic systemic infection caused by the bacterium *Tropheryma whipplei*, classically causing malabsorption alongside arthralgia and, in later or disseminated disease, neurological and cardiac involvement

Very rare; predominantly affects middle-aged men, with a notable occupational association (farmers/agricultural workers, thought to reflect environmental exposure to the organism)

T. whipplei infects macrophages in the small bowel lamina propria (and can disseminate to other organs), which fail to adequately clear the organism - infected, distended macrophages (PAS-positive) accumulate in the lamina propria, distorting villous architecture and causing lymphatic obstruction, driving malabsorption

Classic evolution: migratory arthralgia often precedes GI symptoms by years, followed by chronic diarrhoea, weight loss, and malabsorption; CNS involvement (cognitive change, oculomasticatory myorhythmia - a rare but highly specific sign) and cardiac involvement (endocarditis) can occur, particularly in advanced/disseminated disease
Duodenal/jejunal biopsy showing PAS-positive macrophages in the lamina propria is classically diagnostic; *PCR for T. whipplei*** (on blood, biopsy tissue, or CSF if neurological involvement is suspected) supports and can confirm the diagnosis, particularly useful when histology is equivocal or to assess treatment response

Prolonged antibiotic therapy - typically an initial period of an agent with good CNS penetration (e.g. IV ceftriaxone) followed by a prolonged course of an oral agent (e.g. trimethoprim-sulfamethoxazole) for a year or more, given the risk of relapse (including CNS relapse) with shorter courses
Nutritional support/correction of deficiencies as for any malabsorptive disorder
CNS involvement must specifically be assessed and treated (with an antibiotic regimen achieving adequate CNS penetration) given the risk of neurological relapse if inadequately covered, even when GI symptoms have resolved

Culture-negative endocarditis (Whipple disease is a recognised cause), migratory arthralgia, PAS-positive macrophage disorders (differential includes Mycobacterium avium complex infection, which can mimic Whipple disease histologically but is distinguished by acid-fast staining)

Untreated Whipple disease is fatal; with appropriate prolonged antibiotic therapy, most patients recover well, though relapse (including CNS relapse presenting sometimes years after apparently successful initial treatment) is a recognised risk, underscoring the need for adequate treatment duration and CNS-penetrating antibiotic choice

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