Case Presentation: A 53 year-old man with a history of Hodgkin’s lymphoma status post splenectomy, mantle radiation, and ABVD chemotherapy, severe aortic stenosis, and moderate mitral stenosis attributed to chemoradiation presented with recurrent fevers and lower abdominal pain. He also reported six years of migratory polyarthritis formerly on prednisone and methotrexate, 45kg unintentional weight loss, and declining short term memory. He initially presented one month prior with fevers during work up for planned aortic valve replacement. Transthoracic echocardiogram revealed an aortic valve vegetation. Blood cultures (obtained prior to antibiotics) and serologies for Coxiella, Brucella, and Bartonella species were negative, as were the HIV antibody, Treponemal IgG, and Whipple’s DNA whole blood PCR tests. He was discharged on ceftriaxone and vancomycin for culture-negative endocarditis and had completed four weeks of a planned six week course.
At presentation, he was afebrile with an examination notable for left conjunctival injection, decreased vision, systolic and diastolic murmurs, bibasilar crackles, lower abdominal tenderness, and bilateral scrotal swelling. Labs were notable for leukocytosis and elevated inflammatory markers. Lumbar spine MRI was negative for osteomyelitis or abscess but showed paraspinal and psoas muscle inflammation. Scrotal ultrasound demonstrated bilateral epididymitis. Transthoracic echo demonstrated progression of his aortic valve vegetation from 1.2×0.8cm to 1.8×0.8cm and new mitral valve involvement.
He had bilateral vitreous fluid aspiration with intravitreal antimicrobial injection, followed by bilateral vitrectomy for endogenous endophthalmitis. He then underwent aortic and mitral valve replacement with aortic root and tricuspid valve repair and CABG. Vitreal and aortic valve samples were submitted for 16S rRNA gene sequencing and returned positive for Trophyerma whipplei. In the setting of four weeks of ceftriaxone therapy, his presentation was attributed to immune reconstitution inflammatory syndrome (IRIS). His inflammatory symptoms improved with fourteen additional days of ceftriaxone, followed by trimethoprim-sulfamethoxazole with a planned treatment course of one to two years.
Discussion: Whipple’s disease is a chronic infectious relapsing condition with protean manifestations and is one of the most common causes of culture-negative endocarditis. Favorable outcomes depend on appropriate and timely antimicrobial therapy. Our patient’s diagnosis was further confounded by Whipple’s-associated IRIS following discontinuation of immunosuppression. Tissue sampling with 16S RNA sequencing proved critical to diagnosis.
Conclusions: Whipple’s disease is often a diagnostic dilemma and remains one of the most common causes of culture-negative endocarditis. Although not yet widely available, PCR testing should be performed on all suspected endocarditis tissue samples, particularly when a diagnosis remains uncertain.