Overview
- Definition
A chronic bacterial infection caused by Tropheryma whipplei
Primarily affects the gastrointestinal (GI) tract but may affect other organs, such as lungs, joints, heart, kidney, central nervous system (CNS), and eyes
Severe abdominal disease leads to malabsorption and is associated with CNS co-morbidities, and can be potentially fatal
Ocular involvement (mainly keratitis, uveitis, and neuro-ophthalmic): 6–8%
Well-known yet unexplained propensity in middle-aged, white males
- Symptoms
Blurry vision
Floaters
- Laterality
Unilateral or bilateral
- Course
Systemic disease is chronic and relapsing.
Ocular disease presents late.
- Age of onset
55 years
- Gender/race
M:F = 3:1
Caucasian
- Systemic association
- GI and joint symptoms are most common
Weight loss (80–90%)
Abdominal pain (50–95%)
Diarrhea/steatorrhea (70–85%)
- Migratory, non-deforming polyarthralgia (70–90%)
May precede GI symptoms by months to years
- Other findings
Intermittent, low-grade fever
Lymphadenopathy
Cardiac (endocarditis, pericarditis, Congestive heart failure (CHF))
Pulmonary (pleural effusion, pulmonary infiltrates)
CNS (dementia, supranuclear ophthalmoplegia, myoclonus, hypothalamic signs)
Possible association with HLA-B27, HLA-DRβ1*13, and DQβ1*06
Exam: Ocular
Anterior Segment
Keratitis
Mutton-fat keratic precipitates (KPs)
Iris nodules
Posterior Segment
Vitritis
Pars plana snowbanks and snowballs
Cotton-wool spots and retinal hemorrhages
Vitreous hemorrhage
Retinitis and choroiditis
Retrobulbar optic neuritis
Neuro-ophthalmic (Less Common than Ocular, about 10%)
Gaze palsy
Nystagmus
Myoclonus
- Oculomasticatory myorhythmia (OMM)
Pathognomonic.
Pendular vergent oscillations or smooth vergent nystagmus associated with tongue and mandibular myoclonus.
Patients often have gaze paralysis, hypersomnia, and arthralgia without magnetic resonance imaging (MRI) change or GI findings initially.
Exam: Systemic
Joint swelling and tenderness (more commonly large joints)
Distended abdomen
Skin hyperpigmentation and nodules
Murmurs (pericardial effusion)
Dullness to chest percussion, diminished breath sounds or pleural rub by stethoscope (pleural effusion)
Peripheral edema (protein-wasting enteropathy)
Altered mental status (confusion, memory loss)
Imaging
n/a
Laboratory and Radiographic Testing
- Gastroscopy with small bowel biopsy is the diagnostic procedure of choice.
Light microscopy (LM): clubbed villi and a lamina propria infiltrated with Pas-positive inclusions within and outside of foamy macrophages
Electron microscopy (EM): characteristic trilaminar outer cell wall structure (“bacillary bodies”)
polymerase chain reaction (PCR) (done also on vitreous sample): high sensitivity; based on the nucleotide sequence of T. whipplei 16S ribosomal RNA
Differential Diagnosis
Sarcoidosis
Behcet’s disease
Collagen vascular diseases
Amyloidosis
Lyme disease
Mycobacterium avium complex (MAC) infection
Tuberculosis
Histoplasmosis
Intraocular lymphoma
Treatment
- Initial treatment for CNS and ocular involvements
Intravenous (IV) ceftriaxone 2 g BID=twice daily plus streptomycin 1 g QD × 2 weeks, or
IV trimethoprim sulfamethoxazole (TMP-SMX) 960 mg BID × 1–2 weeks, or
IV penicillin, 1.2 million units QD=once daily plus streptomycin 1 g QD × 2 weeks
- Maintenance therapy for 1–2 years (<1 year is associated with high relapse rate)
PO=per os=orally TMP-SMX, 960 mg twice daily +/− rifampin 600 mg QD, or
PO doxycycline plus hydroxychloroquine
The most common and serious complication is neurologic relapse, even after apparently successful treatment and systemic improvement.
Therapeutic and diagnostic vitrectomy for marked vitreous opacities.
Referral/Comanagement
Infectious disease
Gastroenterology
Neurology