A 49-year-old male presented for evaluation of recurrent vitritis, floaters, and decreased vision of the right eye over the preceding year. Past ocular history was significant for laser assisted in situ keratomileusis (LASIK) of both eyes (OU) 7 years before. Past medical history was notable for carpal tunnel surgery 20 years ago, a right ankle fracture decades ago, and an episode of abdominal shingles several years ago. He had a questionable diagnosis of rheumatoid arthritis due to right knee swelling and distal phalangeal joint disease. He had a history of right ankle swelling and scarring and had undergone two arthroscopies of his right ankle 4-6 years prior to presentation. There was no family history of ocular or autoimmune disease. He did not smoke, drank alcohol occasionally, and did not use illicit drugs. He had extensive travel history outside the US including to the Middle East, Europe, and Asia when he was in the military.
Examination demonstrated best corrected visual acuity of 20/50 OD and 20/20 OS. Pupillary exam and intraocular pressures were normal. Slit-lamp examination OD showed 1+ conjunctival injection, stromal scarring at the LASIK flap interface, 2+ cells in the anterior chamber, and pigment along with some white deposits on the anterior lens surface (Figure 1). His left eye exam was normal. Dilated fundus examination OD revealed vitreous debris but no retinal vasculitis or other chorioretinal lesions (Figure 1). Fluorescein angiography was unremarkable. He was diagnosed with anterior and intermediate uveitis OD and a systemic workup was initiated. Rapid plasma regain (RPR), angiotensin-converting enzyme (ACE), and HLA-B27 were negative, erythrocyte sedimentation rate (ESR) was elevated at 46, and a chest X-ray showed sequela of old granulomatous disease. Polymerase chain reaction (PCR) testing on aqueous fluid for herpes simplex virus (HSV) and varicella zoster virus (VZV) was negative. 
Despite treatment with topical, oral, and periocular corticosteroids OD, inflammation persisted and whitish, fluffy endothelial deposits near the limbus in both eyes and an infiltrating "snowflake-like" crystalline keratopathy at the level of the endothelium OD were observed (Figure 2). Injection of intravitreal vancomycin and ceftazidime was performed given the suspicion of infection and aqueous fluid was cultured for bacteria, fungus, acid fast bacilli and PCR testing was performed for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and VZV. In vitro response of aqueous fluid to mycobacterium tuberculosis was indeterminate and all remaining tests were negative. Further serological testing revealed negative antibodies for Toxoplasma, Leptospira, Hepatitis A, B, and C. EBV serology demonstrated evidence of past infection. Serum protein electrophoresis was unremarkable. A QuantiFERON gold test for mycobacterium tuberculosis was negative. A diagnostic and therapeutic vitrectomy was performed and testing of vitreous for Borrelia burgdorferi PCR and cytology was unrevealing. After cessation of corticosteroid treatment, the crystalline keratopathy (Figure 3) faded and intraocular inflammation resolved. Subsequent cataract surgery OD was performed without complication. 
Concurrent with his ocular inflammation, he was evaluated for decreased appetite, intermittent abdominal pain, and a 20-pound weight loss. Computed tomography (CT) of the abdomen and pelvis showed diffuse mild fatty infiltrates of the liver and borderline cardiomegaly. Lab work showed leukocytosis, which was felt to be reactive, iron deficiency anemia, and low folate levels. C-reactive protein (6.25) and ESR (34) were both elevated. He underwent genetic testing for hematological disorders and flow cytometry which were both unremarkable. He was started on iron and folate supplementation. He underwent upper GI endoscopy which showed a small sliding hiatal hernia and a colonoscopy which showed internal hemorrhoids. He underwent an upper GI biopsy demonstrated Barrett's esophagus. Thyroid testing and a cosyntropin stimulation test for adrenal insufficiency were normal.
Excisional biopsy was performed for an enlarged nontender right inguinal lymph node. Flow cytometry of the lymph node demonstrated a monoclonal population of lambda-restricted B cells with an immunophenotype consistent with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma. However, hematoxylin and eosin (H&E) sections of the lymph node did not show effacement of architecture and immunohistochemical stains did not detect sheets of B cells, characteristics usually present in CLL. These findings were suspicious but not diagnostic for CLL/small lymphocytic lymphoma. Histopathology also demonstrated scattered and grouped macrophages with periodic acid-Schiff- (PAS-) positive inclusions suggestive of Tropheryma whipplei infection.
He developed worsening dyspnea due to decompensated valvular heart disease with biventricular heart failure. Echocardiography confirmed severe aortic regurgitation with mild left ventricular enlargement and an ejection fraction of 50%. Left heart catheterization showed no obstructive coronary disease. He underwent aortic valve replacement with a bi-leaflet mechanical valve. Intraoperatively, diffuse pericarditis was noted. 
He was started on high-dose trimethoprim-sulfamethoxazole for presumed Whipple's disease. A CT of the abdomen and pelvis was obtained which showed retroperitoneal pelvic inguinal adenopathy. The lymph node and aortic valve pathology blocks were sent to the Centers for Disease Control (CDC, Atlanta, Georgia) for review, and the presence of T. whipplei was confirmed by PCR, immunohistochemistry (immunoalkaline phosphatase technique), and PAS staining that showed PAS-positive diastase-resistant organisms within macrophages (Figure 2).
Despite initial improvement in appetite and weight gain, he gradually developed an aortic perivalvular leak and severe aortic insufficiency thought to be secondary to possible re-infection of the mechanical valve. He underwent another aortic valve replacement, ascending aortic replacement, and a 2-vessel coronary artery bypass. The prosthetic valve was sent to the CDC and also showed evidence of T. whipplei infection by PCR, PAS, and immunohistochemistry stains. He developed complete heart block and ultimately expired due to cardiogenic shock and cardiac arrest 2 years after his initial presentation for decreased vision.