Case Presentation: A 60-year-old man presented with progressive fatigue, 30-pound weight loss, and arthralgias over six months. He also noted more recent onset of left upper quadrant abdominal discomfort and nonproductive cough. Past medical history was notable for idiopathic thrombocytopenic purpura (ITP) and nephrolithiasis requiring lithotripsy. He had never smoked cigarettes. Examination revealed tender splenomegaly and no peripheral lymphadenopathy. Laboratory results included hemoglobin 9.7 g/dL with MCV 93 fL and RDW 16%, total protein 7.8 g/dL, albumin 3.2 g/dL, BUN 21 mg/dL, creatinine 3.0 mg/dL, and calcium 13.8 mg/dL. Serum protein electrophoresis showed a polyclonal increase in gamma globulins. Intact parathyroid hormone (PTH) was 9 pg/mL (normal, 12-68 pg/mL). 1,25-dihydroxyvitamin D level was 121 pg/mL (normal, 18-64 pg/mL). CT of the chest, abdomen, and pelvis revealed tree-in-bud nodularity in bilateral upper lung fields, splenomegaly (21 cm), and mild diffuse lymphadenopathy. The differential diagnosis included lymphoma, endemic fungi, mycobacteria, sarcoidosis, and vasculitis. IV fluids were given, broad infectious and autoimmune workup sent, and PET scan obtained. The latter disclosed minimal increased tracer within the bilateral hila, diffuse tracer uptake within the enlarged spleen, and uptake in the sternum, right ilium, and left iliac wing. The patient subsequently underwent IR-guided biopsy of the iliac wing and bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Both biopsies were non-diagnostic. Angiotensin converting enzyme (ACE) level was 150 U/L (normal, 23-57 U/L). ANCA, blood cultures, TB quantiferon, urine Histoplasma and Blastomyces antigens, fungal serologies, EBV, and HIV were all negative. A splenic biopsy was performed. Bronchoscopy cytopathology returned with an elevated CD4 to CD8 ratio at 4.8. Splenic tissue displayed non-caseating granulomas with negative fungal stains. He was diagnosed with sarcoidosis and received systemic corticosteroids with rapid improvement in calcium and symptoms.

Discussion: Sarcoidosis is a systemic disorder of aberrant granuloma formation in various organs and tissues. The diagnosis is made with tissue biopsy showing non-caseating granulomas and supportive clinical and radiologic findings such as systemic symptoms and abnormal chest imaging. Granulomas produce 1-alpha-hydroxylase enzyme which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. The elevated active metabolite can lead to hypercalciuria but only leads to hypercalcemia in only 1 out of 10 patients. Splenomegaly is also possible but rarely seen. Spleen biopsy has been shown to be effective and with minimal risk. The mainstay of therapy is systemic corticosteroids, but other therapies such as methotrexate and TNF-alpha inhibitors can be utilized for refractory disease or intolerance to steroids.

Conclusions: Hospitalists should consider sarcoidosis in the differential diagnosis of multi-system abnormalities and elevated 1,25-dihydroxyvitamin D level. This case highlights an unusually explosive onset of common (constitutional and pulmonary symptoms) and less common (significant hypercalcemia and splenomegaly) manifestations of sarcoidosis. It also highlights the pattern recognition skills and the need for appropriate tissue biopsy to confirm the diagnosis.