Tropheryma whipplei

Background

Ubiquitous environmental organism, but rarely causes disease with only about 12 new cases diagnosed annually worldwide
- Can be found in saliva of one third of healthy people
Disease is more common in white European (98%) males (85%)
Farming or occupational soil/animal exposures are commone

Cardinal features include: arthralgias, followed by weight loss, diarrhea, and abdominal pain
Arthralgias are typically migratory in the larger peripheral joints, including knees, ankles, and wrists, but can have essentially any presentation
- May be present for years before development of other symptoms
The diarrhea is intermittent, with colicky abdominal pain
- Diarrhea can be watery or have steatorrhea
- Occasional GI bleeding

Fever in 25 to 40%
Lymphadenopathy, mostly of mesenteric and mediastinal nodes
CNS disease
- Dementia, supranuclear ophthalmoplegia, nystagmus, and myoclonus
- Oculomasticatory myorhythmia and oculo-facial-skeletal myorhythmia with a supranuclear vertical gaze palsy
- Cerebellar ataxia
- Symptoms can occur with disease or as a post-treatment relapse
Cardiac disease
- Culture-negative endocarditis, pericarditis, and myocarditis
- Endocarditis may occur on its own without other features of disease
Skin hyperpigmentation in 40%
Pleural effusion, chronic cough, interstitial lung disease, pulmonary hypertension
Anemia in 80%, leukocytosis in 50%, thrombocytosis in 50%
Elevated C-reactive protein in 70%

Samples should be taken from involved sites, with a strong preference for small bowel biopsy if there are GI symptoms, but also synovial or cerebrospinal fluid or heart valve
- Up to 7 to 10 biopsies from small bowel, ideally
Diagnosis is based on:
- Periodic acid-Schiff-positive bacilli in macrophages
- PCR
- Immunohistochemistry

Generally treat with parenteral ceftriaxone 2 g IV daily or penicillin 2 MU IV q4h for 2 weeks followed by TMP-SMX DS PO bid for 1 year
- Treatment can precipitate a Jarisch-Herxheimer reaction
- May also see immune reconstitution inflammatory syndrome in early treatment
Other options include meropenem, doxycycline, macrolides, ketolides, aminoglycosides, rifampin, teicoplanin, and chloramphenicol
Consider repeating small bowel biopsies annually for a few years

Clinical improvement takes 1 to 3 weeks of treatment
Neurologic sequelae may be permanent
Relapses after treatment, including of CNS disease, can happen in up to a third of patients