A previously healthy 43–year–old white man was hospitalized because of recurrent episodes of fever, hepatosplenomegaly, abdominal pain and pancytopenia over the past 6 months. Previous extensive workup was unrevealing in causation. The patient presented at the initial onset of fever for this admission and remained persistently febrile. He had continued abdominal pain and quickly developed pancytopenia (white blood cell 610/mL, hemoglobin 9.4 g/dL, platelets 26,000/mL) and transaminitis with aspartate aminotransferase 171 U/L and alanine aminotransferase 509 U/L. Extensive blood tests were normal, including serology for a systemic autoimmune disease, human immunodeficiency virus, hepatitis panel, quaniferon, Ebstein–Barr virus and cytomegalovirus, and parasites. Antibodies to Toxoplasma, Ehrlichia, Anaplasma, Coxiella, Rickettsia, Bartonella, were also negative. Computerized tomography (CT) scan showed upper lung patchy ground glass opacities, mildly enlarged mediastinal and hilar lymph nodes, hepatosplenomegaly, and periportal lymphadenopathy. Subsequent liver and bone marrow biopsies showed non–caseating granulomas, with negative cultures for microorganisms. The patient was started on doxycycline 100 mg BID to treat a presumed infectious process, with some improvement in fever, cell counts and liver enzymes. He was discharged home to complete a 21 day course of doxycycline and did well for 7 months when he again presented with fevers and abdominal pain. Doxycycline was tried again but without efficacy and the fever continued along with development of severe pancytopenia. CT scan showed resolution of the chest findings, but hepatosplenomegaly continued. This prompted us to consider sarcoidosis versus granulomatous lesions of unknown significance syndrome(GLUS). High dose prednisone (60 mg daily) was initiated and within 24 hours the patient defervesced. After 1 week his pancytopenia and transaminitis resolved. After discharge he was maintained on steroids and off all antibiotics and had no recurrence of symptoms. Steroids were then slowly tapered and methotrexate is being initiated for long term therapy.
GLUS syndrome is a clinical entity characterized by unexplained granulomatous disease in spite of extensive serologic, microbiologic and histologic examination. Patients have prolonged fevers in addition to multi–organ granulomatous lesions that have a tendency to recur. It is of utmost importance to properly investigate the etiology of the lesions, which is usually guided by the organs involved. For instance, in this case exploring standard autoimmune diseases, primary bone marrow processes and infectious etiologies were of paramount importance.
We describe here a unique case of GLUS syndrome which may mimic an infectious process. Physicians should be aware of this entity in patients with recurrent fever of unknown origin in the presence of other systemic manifestations.