INTRODUCTION: We present a case of a 48 year old Egyptian-born woman with initial presentation of persistent malaise, fever and an intermittent non-productive cough of 2 years duration.
CASE PRESENTATION: The patient's past medical history is significant only for a cholecystectomy with no chronic use of medications or allergies. She is a lifelong non-smoker and alcohol drinker. She emigrated from Egypt to Ohio, where she worked as an epidemiologist but no known infectious or environmental exposures. Due to the persistence of her symptoms, a chest x-ray and subsequent CAT Scan (CT) was obtained which revealed diffuse cervical, hilar and abdominal adenopathy and no pulmonary parenchymal disease. A fine needle aspiration (FNA) of the cervical lymph node revealed granulomatous adenitis with evidence of necrosis. She was eventually started on corticosteroid therapy for presumptive diagnosis of sarcoidosis (prednisone 30mg daily for two months) but therapy was halted as she had interval increase in the size of her cervical nodes. She was referred to our center where she had a biopsy of the left axillary lymph node (which was positron emission tomography (PET) positive) revealing non-caseating granulomas. The pathology obtained from a subsequent mediastinoscopy revealed granulomas with focal caseating necrosis, with negative work up for infectious etiology, including acid fast bacteria (AFB). Nearly one year after her initial symptoms, she continued to have diffuse increase in her lymphadenopathy and symptomatic hepatosplenomegaly. After a negative bone marrow biopsy, she later underwent splenectomy for a rapidly enlarging spleen for suspicion of occult lymphoma. The spleen pathology revealed focally necrotizing granulomatous splenitis, with negative stains for AFB and fungus. These results were confirmed with negative polymerase chain reaction (PCR) for mycobacterial DNA as well as negative flow cytometry. She subsequently underwent an extensive infectious disease evaluation which was negative for brucellosis, histoplasmosis, schistosomiasis, bartonella and Q fever. Her rheumatologic evaluation was also non-diagnostic which included normal values for anti-nuclear antibody (ANA), double stranded DNA (dsDNA), and rheumatoid factor. Other laboratory values revealed a normal serum angiotensin converting enzyme (ACE), albumin, and gamma globulin levels but mildly elevated alkaline phosphatase.
DISCUSSIONS: After her extensive workup, the patient was given a presumptive diagnosis of sarcoidosis with features of necrotizing sarcoid granulomatosis (NSG) predominantly involving the lymphatic system. NSG was first described by Liebow in 1973, and currently defined as involvement of the bronchovascular bundle with vasculitis and parenchymal necrosis (usually of the ischemic type) 1. It is generally considered a variant of nodular sarcoid and thus a diagnosis of exclusion. Clinically patients present with fevers, malaise, dyspnea with multiple pulmonary nodules2. However, unlike the classic presentation of NSG, our patient did not have pulmonary infiltrates and was essentially asymptomatic from a pulmonary standpoint with the exception of an intermittent cough. Furthermore, her imaging was free of any pulmonary nodules, thus her pathology lacked the classic vasculitis-induced ischemic necrosis. Kikuchi-Fujimoto disease as well as Katayama fever were considered in our differential diagnosis, but were ruled out, respectively, due to evidence of granulomatous necrosis and negative serology for schistosomiasis.
CONCLUSION: This patient's case is unusual as the majority of her disease remains extra-pulmonary leading to diffuse lymphadenopathy, hepatosplenomegaly, with disabling fever and malaise. Our working and unifying diagnosis remains sarcoidosis with atypical features of NSG. As a result of her unrelenting clinical course, the patient was eventually started on prednisone, hydroxychloroquine and methotrexate, with repeat PET scan revealing decreased uptake in the mediastinum, with stabilization of her symptoms.
DISCLOSURE: Ali Massoumi, No Financial Disclosure Information; No Product/Research Disclosure Information