A 62–year–old man presented with a 3–day history of fever, chills, night sweats, fatigue, and arthralgias, associated with generalized non–pruritic painless skin rash. He has past medical history significant for hypertension, ulcerative colitis in remission and CAD status post bypass surgery. He was taking azathioprine, mesalamine, simvastatin and lisinopril. On presentation, temperature was 39.0°C, heart rate 90/min, respiratory rate 18/min, BP 125/70 and O2 Sat. 96% on room air. He had maculopapular and urticarial rash involving the chest, abdomen, and extremities. Heart auscultation revealed a 2/6 midsystolic murmur at the aortic area. The remaining of physical examination was unremarkable. Laboratory studies were significant for WBC 13.0 and hemoglobin 11.2. His CMP, chest radiography and urinalysis were normal. The patient was admitted for further work up of fever of undetermined etiology. Blood tests included multiple blood cultures, west Nile virus, hepatitis profile, HIV, parvovirus, Q fever, and rickettsia were all negative. The patient remained febrile with worsening rash and lethargy for which he was started on empiric antibiotics. His ESR was 85 and CRP 179. ANA and rheumatoid factor were negative. Echocardiogram showed no vegetations. Biopsy of the skin rash showed histopathologic changes consistent with leukocytoclastic vasculitis (LCV). Transesophageal echocardiogram showed a small, mobile echodensity on the aortic valve. The patient was continued on IV antibiotics for assumed infective endocarditis. Few days later, his fever improved and skin rash started to fade away. He was treated with intravenous antibiotics for an additional 6 weeks and has been well since.
Infective endocarditis (IE) has multifarious manifestations. IE can be challenging especially in patients with negative blood cultures. In this particular case, several findings like anemia, skin rash, persistent fever and elevated inflammatory markers are also seen in other systematic diseases. These includes; IE, vasculitis, connective tissue diseases and hidden malignancy. Furthermore, in patients presenting with vasculitic phenomena, infective endocarditis has to be included in the differential diagnosis, particularly if an audible murmur, fever and other generalized constitutional symptoms are present. Reports in the literature showed that leukocytoclastic vasculitis (LCV) which is a hypersensitivity vasculitis may constitute the presenting manifestation of endocarditis and has been observed in 3% of IE cases. Circulating immune complexes play a role in the pathogenesis of LCV and treatment has to be directed to the underlying disease.
Persistent fever and vasculitic skin eruption should raise attention to underlying serious medical disease and should not be overlooked by the hospitalist despite negative blood cultures. A thorough cardiac examination and evaluation with thoracic and esophageal echocardiogram is a crucial step before initiating empiric treatment.
Figure 1Panel A, B &C: A maculopapular and urticarial rash over the chest, upper and lower extremities. Panel D: Transesophageal echocardiogram showed a cross section of the aortic valve with a 0.6 × 0.8 cm mobile echodensity (vegetation) on aortic valve leaflet. (RA: right atrium, AoV: aortic valve)