PO:35:221 | Cryofibrinogen: a cold case. Characteristics and clinical outcomes from a cryofibrinogen positive cohort

Daniele Catameró¹, Andrea Cito¹, Cristiana Colaprico¹, Teresa Caferri¹, Teresa Troiano¹, Anna Marinaccio¹, Marco Fornaro¹, Giuseppe Lopalco¹, Florenzo Iannone¹. | ¹Unit of Rheumatology , Department of Precision and Regenerative Medicine, Area Jonica DiMePRe-J, University of Bari, Bari, Italy.

Background. Cryofibrinogen (CF) is a protein tangle mainly made of fibrinogen, fibrin and fibronectin that precipitates when exposed to cold temperatures. Unlike cryoglobulins (CG), CF significance is still poorly understood. Objective: to characterize patient with CF positivity and to define its clinical impact and therapeutic outcomes.

Materials and Methods. We retrospectively collected data focusing on 46 CF positive patients. Demographic, clinical and therapeutic features were assessed at baseline (To), after the first determination (T1) and at each CF finding. Standard descriptive statistics were employed for our analysis.

Results. 20 patients (43.5%) presented with CF alone, whilst 26 (56.5%) showed CF + CG. Female sex was prevalent (76.1%) with an average age of 54.1 (±14.6) years. 41.3% of patients were diagnosed with vasculitis, 14 of which cryoglobulinaemic, 13% arthritis, 23.9% connectivitis, 21.7% had no defined diagnosis. Clinical involvement ranged from neurological (58.2%), to cutaneous (purpuric rash 48.9%, skin ulcers 20%), inflammatory arthralgias (34.8%), cardiovascular (13%) and renal (6.5%). We then provided a statistical analysis dividing patients into two subgroups depending on CF positivity alone or CF + CG positivity. Groups were homogeneous for demographic, therapeutic, clinical features and outcomes (Figura 1.a). We then performed a comparison between patients who experienced a resolution of the symptomatology (responders) and those who haven’t (non-responders). Non-responders showed a significantly more frequent CG positivity (72.7% vs 41.7%, p=0.04) and a similar trend for ANA positivity (57.1 vs 29.2, p=0.07). On the other hand, a significant lower baseline employment rate of csDMARD was observed among responders 12.5% vs 36.4%, p=0.05), being hydroxychloroquine the most frequent among non-responders (55.1% vs 0%). More responders were administered corticosteroids at T1 (83.3% vs 59.1) even if statistical significance wasn’t achieved, whilst other medication didn’t differ between groups. Finally, skin affection was more frequent among responders, specifically purpuric lesions (73.9% vs 22.7%) and cutaneous ulcers (34.8% vs 4.5%) with a statistical significance of respectively p=0.001 and p=0.02 (Figura 1.b). When confronted, patients that didn’t experience cutaneous affection, showed higher rates of ANA (57.9% vs 30,8%, p=0.06) and anti-ENA (47.4% vs 11.5%, p=0.07) positivity, csDMARD intake at T0 (40% vs 11.5%, p=0.04) and fewer overall T1 corticosteroid employment (55% vs 84.6%, p=0.03). Moreover, a 76.9% rate of clinical improvement was observed among subjects with skin involvement (vs 20%, p=0.0001). CF serum levels were more frequently reducing (37.5% vs 10%, p=0.36) in skin affected patients, whilst only 8.3% (vs 35%, p=0.05) showed stability (Figura 1.c), not such differences were observed in responders vs non-responders.

Conclusions. CF positivity alone showed with important clinical implications. Our analysis suggests a more profound immunological disruption in those patients who experienced worse clinical outcomes. Skin affection and corticosteroid intake seemed positively predict for better outcomes.