Chronic Cough

Teaching Topic

CLINICAL PROBLEM-SOLVING

A Surprising Cause of Chronic Cough

D. Damaraju and Others

       

Whipple's disease may be difficult to recognize; its rarity and nonspecific clinical features (overlapping with those of many chronic inflammatory diseases) often result in delayed diagnosis (up to 2 to 6 years after the onset of symptoms, according to some case series).

Clinical Pearls

  What causes Whipple's disease?

Whipple's disease is a chronic infectious disease that affects multiple organ systems; it is a rare disease, with a reported annual incidence of less than 1 case per 1,000,000 people. It is caused byTropheryma whipplei, a ubiquitous environmental organism. T. whipplei is thought to be acquired by fecal–oral transmission and is found in sewage-plant effluxes.

  What is the most common profile of a patient diagnosed with Whipple's disease?

The disease appears to occur more frequently in persons of European ancestry than in persons of other ancestries and more frequently in men than in women (male:female ratio, 4:1). It most often manifests in middle age, although cases occur across the age spectrum.

Morning Report Questions

Q. What are some of the typical manifestations of Whipple's disease?

A. Whipple's disease has a broad spectrum of symptoms and signs; typical manifestations (and their frequency in case series) include weight loss (in 92% of patients), diarrhea (in 76%), arthralgia (in 67%), abdominal pain (in 55%), fever (in 38%), supranuclear ophthalmoplegia (in 32%), headache (in 10%), anemia (in 85%), lymphadenopathy (in 60%), endocarditis (in 30%, and usually culture-negative), and pulmonary involvement (in 30 to 40%, approximately half of whom have cough). The typical presentation is a prodrome of arthritis, followed by persistent diarrhea and weight loss; arthritis can precede the gastrointestinal symptoms by many years. Although Whipple's disease is uncommon, chronic infection with T. whipplei should be considered in any patient with persistent unexplained arthralgias or gastrointestinal or systemic symptoms.

Q. What is the diagnostic test of choice for Whipple's disease and how is it treated?

A. The diagnostic test of choice is upper gastrointestinal endoscopy with biopsies (although other tissue sites may be sampled). Identification of the 16S ribosomal RNA gene with the use of a polymerase-chain-reaction assay (e.g., from feces or saliva) has high sensitivity and specificity for the organism but should not be used in isolation for diagnosis. Culture is not useful in diagnosis, because it may take months for the organism to grow and requires special techniques; serologic testing is nonspecific. In the absence of randomized trials, treatment recommendations are guided largely by case series. First-line treatment typically involves 2 weeks of ceftriaxone, followed by at least 1 year of trimethoprim–sulfamethoxazole. For patients who have a sulfa allergy or desire only oral therapy, doxycycline plus hydroxychloroquine may be substituted for either or both ceftriaxone and trimethoprim–sulfamethoxazole (with response rates in case series similar to those reported with standard therapy).

Figure 2. Pathological Findings.