An Unsuspected Case of Idiopathic Multicentric Castleman Disease (iMCD) Presenting with Renal Microangiopathy

Introduction: iMCD remains an elusive diagnosis because of the non specific clinical manifestations that are common in other systemic diseases. Renal manifestations are rare, but can provide insight in the diagnosis of this elusive disease. Case Description: A 20-year-old caucasian male presented with fevers, anemia, thrombocytopenia, hepatosplenomegaly, anasarca and unclear etiology of multiorgan failure that required vasopressors, ventilator support and dialysis. He was treated initially empirically for sepsis with antibiotics and then with steroids for autoimmune disease of unknown etiology. After improvement in his respiratory and hemodynamic status he had a renal biopsy with evidence of widespread glomerular endotheliosis with rare RBC fragments and no evidence of immunecomplexes by IF and EM. TTP was ruled out and no other common causes of microangiopathy was found. Bone marrow biopsy had no evidence of malignancy, but excisional axillary lymph node biopsy was consistent with mixed hyaline vascular and plasma cell Castleman disease, HHV8 negative. Discussion: HHV8 negative iMCD is an uncommon lymphoproliferative disorder characterized by inflammatory systemic manifestations mediated by increased IL-6 and VEGF. Renal manifestations are rare and usually associated with severe disease manifestations as TAFRO syndrome. It can present as a microangiopathy with severe diffuse glomerular capillary endoteliosis and reduction in glomerular filtration rate to require dialysis. Fibrin thrombi or fibrinoid necrosis may not be present as seen in other causes of thrombotic microangiopathy. Some patients have a paradoxical downregulation in renal VEGF expression with similar histologic features as seen with VEGF antagonists. Delayed diagnosis and severity of the disease is associated with worst outcomes. iMCD is difficult to diagnose since the systemic manifestations are non specificic and should be suspected in renal microangiopathies of unclear etiololgy so early therapy can be prescribed.