Abstract: PUB309
Castleman Disease of Renal Significance: Recognizing TAFRO Syndrome
Session Information
Category: Onconephrology
- 1700 Onconephrology
Authors
- Ramanand, Akanksh, Northwestern Memorial HealthCare, Chicago, Illinois, United States
- Thach, Lonnie, MedStar Washington Hospital Center, Washington, District of Columbia, United States
- Kisley, Zach, Northwestern Memorial HealthCare, Chicago, Illinois, United States
- Kanwar, Yashpal S., Northwestern Memorial HealthCare, Chicago, Illinois, United States
- Aggarwal, Vikram, Northwestern Memorial HealthCare, Chicago, Illinois, United States
Introduction
Castleman disease is characterized by nonneoplastic lympadenopathy (LAD) with increased lymphoid follicles, germinal center involution, and capillary proliferation. The most acute form, iMCD-TAFRO, is marked by Thrombocytopenia, Ascites, Fever, Organomegaly, and Renal failure. This case series shows the importance of recognizing renal manifestations of TAFRO syndrome.
Case Description
Case 1: Presented with fever, anasarca, and AKI. She was admitted to the ICU, required vasopressors, intubation, and CRRT. Workup showed thrombocytopenia, hepatosplenomegaly, and LAD. Bone marrow biopsy (BM Bx) revealed mild to mod fibrosis. She received IVIG and high dose steroids, with partial improvement in cytopenias and full renal recovery. Due to refractory AKI and TAFRO features, she was treated with tocilizumab for 2 months and then siltuximab. Symptoms resolved within 4 weeks.
Case 2: Presented with fever and weakness with labs showing thrombocytopenia and oliguric AKI requiring CRRT. PET-CT revealed LAD, splenomegaly, and anasarca. BM Bx confirmed HLH with histiocytosis and polyclonal plasma cells. Treatment with steroids and anakinra improved cytopenias and AKI. One month later, she presented with TAFRO features. LN biopsy confirmed iMCD, and kidney biopsy showed glomerular capillary endotheliosis. She was treated with siltuximab, leading to resolution of AKI. However, thrombocytopenia worsened after 2 doses, thus was switched to rituximab, resulting in recovery.
Case 3: Presented with swelling, rash, and cyclical fevers. A LN biopsy suggested Castleman-like features, but patient left AMA. Later, he returned with TAFRO features. A biopsy showed MPGN without immune complex deposition, raising suspicion for Castleman’s despite normal IL-6 levels. He was admitted to ICU and required HD. BM Bx revealed eosinophilia and mild dysplasia, linked to DRESS syndrome. Tocilizumab treatment led to dramatic improvement, followed by high-dose steroids with further recovery.
Discussion
iMCD-TAFRO is a diagnostic dilemma. TAFRO syndrome develops sub-acutely, progresses rapidly, and can often prove fatal. Thus, prompt diagnosis and treatment is critical.
TAFRO defining features and clinical characteristics of the three patients
| Clinical characteristics | Age/Gender/Race | Past medical history | TAFRO Features | Thrombocytopenia (< 100 K) | Ascites | Fever | Renal dysfunction (< 60ml/min) | Organomegaly | Proinflammatory cytokines | Interleukin 6 (IL-6) | Vascular endothelial growth factor (VEGF) | Renal involvement | Serum Creatinine (mg/dL) | Proteinuria (UPCR mg/mg) | Hematuria (RBC cells /hpf) | Hypertension | Dialysis requirements | Lactate dehydrogenase | C3 Complement/ C4 Complement | Peripheral blood smear. | Kidney biopsy findings |
| Patient 1 | 34 yrs/F/Hispanic | None | Present | Present | Present | Present | Present | 52 pg/mL | 190 pg /ml | 1.49 | 0.39 | 11-50 | No | Yes | 165 | 104/18 | Normocytic anemia and thrombocytopenia. No schistocytes. | Glomerular endotheliosis | |||
| Patient 2 | 22 yrs/F/African American | Adult onset Still disease | Present | Present | Present | Present | Present | 41.5 pg/mL | 126 pg/mL | 1.25 | 1.13 | 11-50 | Yes | Yes | 288 | 53/20 | Normocytic anemia and thrombocytopenia. No schistocytes. | Glomerular endotheliosis | |||
| Patient 3 | 38 yrs/M/Caucasian | Guillan-Barre syndrome and HTN | Present | Present | Present | Present | Present | 21.6 pg/mL | 266 pg/mL | 3.73 | 0.2 | None | Yes | Yes | 203 | 78/15 | Normocytic anemia and thrombocytopenia. Rare schistocytes | MPGN pattern with IC deposits |