SAT-366 Hypercalcemia Due to Castleman’s Disease

Abstract

Castleman’s disease is a group of poorly understood lymphoproliferative disorders in which pro-inflammatory cytokines are hyper-produced, causing a constellation of symptoms. This patient was diagnosed with a rare subtype of idiopathic multicentric Castleman’s called TAFRO, which is a subclass characterized by thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). This is a case of hypercalcemia likely secondary to Castleman’s disease. To our knowledge, only two such cases have been reported, and none with this rare subtype of the disease. The mechanism of hypercalcemia in Castleman’s disease is thought due to lymph node macrophages expressing vitamin D activating enzyme 25-hydroxyvitaminD 1-alpha-hydroxylase, and possibly due to increased bone-turnover from osteoclasts production by IL-6. The treatment is managing the primary cause of the disorder: high doses of systemic steroids, immunosuppressants and IL6-inhibitors. We present a case of a 53 year old Hispanic female with a PMH of type 2 diabetes mellitus. She had hypercalcemia with a corrected calcium 12 mg/dl and a normal PTH 16.2pg/ml, with low levels of 1,25-OH vitamin D 8.3pg/ml, and 25-OH vitamin D 16.6ng/ml. PTHrP was undetectable. Phosphorous was normal at 3.3 mg/dl. Given that the iPTH was low normal, and with low 25-OH and 1,25-OH vitamin D levels, primary hyperparathyroidism was thought unlikely. SPEP showed a chronic disease pattern. TSH was also noted to be normal. Quantiferon tuberculin test, HHV6, HHV8 and HIV were negative. IgG, IgA, IgM levels were normal. She also had elevated alkaline phosphatase at 108 U/L. No other bone markers were checked. After steroid therapy, her corrected calcium came down to 10.1. Her Castleman’s disease was diagnosed via histopathology of lymph node biopsy showing follicular hyperplasia with atretic germinal centers, penetrating blood vessels, expanded mantle zones, hypervascular interfollicular regions and intense interfollicular plasmacytosis consistent with Castleman’s disease. Initial CT Chest with contrast showed diffuse lymphadenopathy in the retropectoal, axillary, prevascular, pretracheal, paratracheal, and retroperitoneal regions. She had anasarca with ascites, requiring paracentesis with ascites fluid that was negative for malignancy. She was also diagnosed with acute thrombotic microangiopathy via kidney biopsy for workup of thrombocytopenia and acute renal injury. She was initially treated with PLEX and dexamethasone 40mg, then switched to methylprednisolone, was also tried on riuxamab and cylclosporine. She failed therapy with an IL-6 inhibitor, Siltuximab, due to pulmonary edema requiring hospitalization. Currently, she is on a drug holiday and will resume lower doses of cyclosporine. Clinicians should consider an underlying lymphoproliferative disorder in the differential for a patient with hypercalcemia.