Case Presentation: A previously healthy 32yo male presented to the hospital with bilateral lower extremity swelling and abdominal distention. Three months prior he had sought care for abdominal pain and fatigue. There was interval improvement for approximately one month without intervention, however, he subsequently developed night sweats, fatigue, and malaise for which he was treated for pericarditis with colchicine and steroids. After 3 days of receiving treatment for pericarditis, his edema and ascites worsened and he returned to the hospital. The exam was notable for ill-appearing male, temporal wasting, tense abdominal distention with a positive fluid wave and shifting dullness, pitting edema bilaterally, and axillary lymphadenopathy (LAN). Laboratory workup was remarkable for anemia, thrombocytopenia, acute kidney injury, and high inflammatory markers. A broad infectious and rheumatologic workup was unrevealing. A CT chest, abdomen, and pelvis demonstrated bilateral pleural effusions, axillary and retroperitoneal LAN with hepatosplenomegaly. An abdominal ultrasound showed large volume ascites with subsequent diagnostic paracentesis revealing exudative ascites, negative for infection. Tissue workup was pursued. Bone marrow biopsy exhibited increased reticulin staining consistent with fibrosis. Kidney biopsy showed renal-limited thrombotic microangiopathy without signs of peripheral hemolysis. Initial lymph node (LN) biopsy showed reactive lymphoid hyperplasia, without signs of malignancy. Therefore, a PET scan was obtained to guide the next LN biopsy; an excisional cervical LN biopsy showed a thickened mantle zone, consistent with onion-skinning, and atretic germinal centers with increased vascularization (“lollipop” follicles). HHV-8 testing was negative. Collectively, this was consistent with the idiopathic TAFRO (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) variant of idiopathic (HHV-8 negative) multicentric Castleman’s disease (iMCD).
Discussion: iMCD-TAFRO is a rare condition with a poorly understood etiology and pathogenesis. However, it is understood that there is significant cytokine dysregulation and IL-6 elevation is a necessary part of the iMCD symptomatology (1). Renal-limited TMAs have been reported in this disorder due to pro-thrombotic effects of IL-6 (2). This cytokine is involved in many functions within the immune system and is the main therapeutic target for the treatment of iMCD with monoclonal antibodies such as tocilizumab (IL-6 receptor inhibitor) or siltuximab (IL-6 inhibitor).In this case, despite having an initial tissue biopsy, a repeat biopsy was required for a unifying diagnosis, iMCD-TAFRO. The patient’s IL6 was elevated to 6.7 pg/mL (normal < 2). He was started on pulse-dose steroids and tocilizumab with subsequent improvement in his inflammatory markers, cytopenias, and creatinine.
Conclusions: iMCD-TAFRO should be considered in the differential for patients with peripheral lymphadenopathy, constitutional “B” symptoms, and elevated inflammatory markers especially once ruling out common mimics such as Hodgkin lymphoma, rheumatoid arthritis, and other rheumatological connective tissue disorders.