Case Presentation: We present the case of a 59 year-old male with a history of Castleman’s Disease, anemia, hypothyroidism, hypertension, CKD3 and neurogenic bladder who presented to the Emergency Department (ED) from the Hematology clinic for abnormal labs, thrombocytopenia and acute kidney injury. In the ED patient was febrile and hypotensive. He received empiric antimicrobials and a 500cc 0.9% saline bolus. Following the bolus, the blood pressure improved, however he became hypoxic to 88% on room air and was accepted to the Medical Intensive Care Unit for concern for potential urgent dialysis and possible plasma exchange. Initial laboratory data revealed a WBC 8.32 K/uL, Hgb 9.6 g/dL, HCT 28.6%, plt 11 K/uL, Na 135 mmol/L, K 6.0 mmol/L, Cl 103 mmol/L, HCO3- 16 mmol/L, BUN 100 mg/dL, Cr 6.52 mg/dL and glucose 94 mg/dL. Peripheral blood smear showed schistocytes suggesting mircoangiopathic hemolysis. ADAMTS13 assay resulted as 44% (slightly below normal value of 50%), IL-6 level was 169 pg/mL, C3 Complement was 118mg/dL, and C4 Complement was 16 mg/dL. The patient completed meningococcal vaccination and received the terminal complement inhibitor, eculizumab, on 9/15. Bone marrow biopsy was performed and showed myelofibrosis (grade 2 fibrosis) with triple negative staining (JAK2, CALR and MPL) suggesting cytokine induced Castleman’s, or a rare subtype of Castleman’s syndrome termed TAFRO. TAFRO syndrome is a rare subtype of Castleman’s disease, characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly. Eculizumab provided minimal benefit in patient’s renal recovery and thrombocytopenia and he was started on situximab 10/3, with initial marginal improvement. He received a second dose on 10/24 without further significant benefit. On repeat imaging his spleen had increased in size and his retroperitoneal lymphadenopathy had slightly worsened. It was discussed with the patient that switching to another IL6 antibody, tocilizumab, may provide added benefit. The patient was amenable and received his first dose on 11/3. His renal function recovered, and his platelets increased to 70 K/uL. He was discharged to acute rehab for strengthening with outpatient Hematology follow-up.
Discussion: TAFRO syndrome is a recently recognized variation of idiopathic multicentric Castleman disease (iMCD). It is an acronym for a constellation of syndromes seen in the clinical presentation [T] thrombocytopenia, [A] anasarca, [F] fever, [R] reticulin fibrosis, and [O] organomegaly [1]. Recognized for the first time less than 15 years ago, TAFRO syndrome typically affects women more commonly than men and is usually seen in patients 30-40 years old [2]. Given the clinical and pathological similarities between iMCD and TAFRO syndrome, diagnostic distinction between the two can present challenges and lead to delay in care. Considering the novelty of the condition, treatment regimens are not well studied but include corticosteroids along with targeted therapies such as anti-IL-6 and anti-CD-20 therapy and cytotoxic chemotherapy [3-4]. Nearly half of the patients with TAFRO syndrome will fail the first line of therapy, but if treated promptly 2-year survival rates are still around 80-85% [3-4].
Conclusions: TAFRO syndrome is exceedingly rare and difficult to diagnose. Prompt diagnosis and appropriate treatment is crucial to ensure the best survival rates.