Identification of Key Predictors of Cryoglobulinemia Severity at Diagnosis: Threshold, Type, and Severity Score at Diagnosis

<b>Background</b>: Cryoglobulinemia (CG) syndrome is a heterogeneous condition characterized by the presence of cryoglobulins in serum, often leading to vasculitis with protean clinical manifestations. Understanding the presentation of cryoglobulinemia-related symptoms based on cryoprecipitate levels, GC type, and severity at diagnosis is essential for effective management. Hence, this study aimed to provide a comprehensive analysis of patients with positive cryoglobulin detection to investigate these aspects. <b>Methods</b>: We conducted a retrospective review of clinical charts from patients with positive cryoglobulin detection at Colmar Hospital between May 2015 and April 2019. <b>Results</b>: Among 166 patients with positive cryoglobulins, the median cryoprecipitate value was 37 mg/L [IQR: 25-70], with 62% of patients below the 50 mg/L threshold. High cryoprecipitate levels were associated with C-virus hepatitis (<i>p</i> = 0.0007), increased fatigue (<i>p</i> = 0.001), fever (<i>p</i> = 0.0013), weight loss (<i>p</i> = 0.028), and musculoskeletal symptoms (<i>p</i> = 0.002). These patients also exhibited decreases in complement fractions (<i>p</i>-values 0.017 to 0.006). At the end of the one-year follow-up, they required frequent renal replacement therapy (<i>p</i> < 0.0001) and had a higher mortality rate (<i>p</i> = 0.02). Based on the CG type, patients with type I GC had splenomegaly (<i>p</i> = 0.039) and hemopathy (<i>p</i> = 0.001). According to severity at initial presentation, the severe patients had more purpura (<i>p</i> < 0.001), Raynaud's phenomenon (<i>p</i> = 0.039), and leukocytoclastic vasculitis on skin biopsy (<i>p</i> < 0.001), along with higher cryoprecipitate levels (<i>p</i> = 0.011). Multivariate analysis identified purpura (OR: 10.25), hematological malignancy (OR: 7.06), Raynaud's phenomenon (OR: 6.41), and cryoprecipitate levels (OR: 1.02) as significant markers of disease severity serving for the development of a severity score for clinical practice. <b>Conclusions</b>: This study identifies severity markers in patients with positive cryoprecipitate and proposes a score related to severity at diagnosis.