Raynaud Phenomenon as a Manifestation of Sorafenib-Induced Thrombotic Microangiopathy: A Case Report

Introduction: Thrombotic microangiopathy (TMA) is a rare complication of stem cell transplantation, often linked to TKIs like Sorafenib. While typically renal-limited, systemic signs may be underrecognized. We report a case of Sorafenib-associated TMA with refractory Raynaud phenomenon that improved with Eculizumab, suggesting Raynaud may represent a systemic TMA manifestation and highlighting complement inhibition as a potential therapy. Case Description: A 42-year-old man with diabetes and hypertension underwent allogeneic PBSCT for FLT3-positive AML in January 2023, receiving TBI, chemotherapy, and Sorafenib (200 mg BID from March 2023). In July, he developed erythematous follicular papules; biopsy confirmed chronic GVHD, which responded to steroids, Ruxolitinib, and phototherapy. By August 2024, he presented with 2 months of leg edema and subnephrotic proteinuria. BP was 160/70. Labs: Hb 109, Plt 128, Cr 111, Alb 33, urine PCR 273 mg/mmol. Workup: normal complement, HbA1c 5.3, negative ANCA, anti-PLA2R, and APS; kappa/lambda ratio normal. Renal biopsy showed chronic TMA with glomerular double contours, arteriolar hyalinosis, and severe IFTA; no immune deposits. ADAMTS13 was preserved; no schistocytes or hemolysis. Managed conservatively with RAAS blockade and SGLT2i, with improving proteinuria (PCR 131, then 57 mg/mmol). In October, he developed cold-induced fingertip pain, bluish discoloration, and ulcers—diagnosed as Raynaud phenomenon, without scleroderma features. ANA nucleolar 1:1280, dsDNA 254, normal complements. CBC: macrocytic anemia, Plt 115, stable Cr. Adalat was started. Creatinine rose to 160 with flank pain; Doppler negative. Anticardiolipin IgG transiently elevated; APS unlikely. Sorafenib was stopped in November due to worsening renal function (Cr 170) and Raynaud symptoms. Eculizumab was initiated in December (900 mg weekly ×4, then 1200 mg biweekly). Raynaud resolved within weeks. By January 2025, renal function stabilized, proteinuria improved, and vasospastic symptoms resolved. Discussion: The findings supported that Raynaud phenomenon in this patient likely represented a systemic manifestation of sorafinib-induced TMA. The resolution of symptoms with Eculizumab highlights the potential role of complement inhibition in such cases and underscores the importance of recognizing Raynaud as a possible complication of TKI.