Cryofibrinogenemia - an often-neglected rare disease: a case series

Cryofibrinogenemia (CF) is a rare systemic condition characterized by reversible precipitation of circulating plasma components such as fibrinogen, fibrin, or fibronectin at cold temperatures that resuspend upon rewarming to body temperature. It is crucial to consider the possibility of CF in the differential diagnosis of patients with purpura or ischemic skin lesions. PLEX may serve as an effective salvage treatment for severe CF manifestations, such as refractory skin ulcers or limb digital ischemia that do not respond to conventional immunosuppressive treatment. Unfortunately, randomized controlled trials are lacking, and no guidelines exist. Our current knowledge is based on case reports and case series.

We report a case series of three patients treated at IRCCS Policlinico San Matteo, Pavia, Italy, who presented with different clinical manifestations of CF refractory to conventional immunosuppressive therapies and were successfully treated with plasmapheresis (PLEX).

Management of CF includes glucocorticoids, whereas azathioprine, rituximab, cyclophosphamide, anticoagulants, and intravenous fibrinolysis have been reported to be effective in more severe cases. The proposed maintenance therapy for moderate disease is corticosteroids and low-dose aspirin or stanozolol. Treatment of refractory symptomatic CF remains challenging. Plasmapheresis (PLEX) has been reported in a few cases in the literature as a useful treatment for CF. The contribution of our cases highlights the importance of considering CF in the differential diagnosis among patients with purpura or ischemic skin lesions and PLEX as an effective salvage treatment for severe CF manifestations, such as refractory skin ulcers or limb/digital ischemia that do not respond to conventional immunosuppressive treatment.