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QJM. 1995 Feb;88(2):115-26.

Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease. GISC. Italian Group for the Study of Cryoglobulinaemias.

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  • 1I Divisione di Medicina Generale, Saronno Hospital, Milan, Italy.


In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients with cryoglobulinaemias, divided as: (i) essential cryoglobulinaemias; (ii) cryoglobulinaemias secondary to connective tissue diseases (CTD), lymphoproliferative or other haematological diseases (LPD), chronic liver diseases (CLD), and 'other diseases'. Purpura was the commonest presenting feature in all groups and was more common in essential cryoglobulinaemias (p < 0.0001). Meltzer's triad (purpura, arthralgia, weakness) was less frequent, but similarly distributed. Renal involvement was randomly distributed. Neurological impairment was less frequent in cryoglobulinaemias secondary to CLD (p < 0.002). Raynaud's phenomenon, arthritis and sicca syndrome were more frequent in cryoglobulinaemias secondary to CTD. Essential cryoglobulinaemias had a significantly higher percentage of serum complement C4 < 8 mg/dl (p < 0.004), of detectable rheumatoid factor activity (p < 0.0002), and of type II cryoglobulins (p < 0.0001). Liver involvement was evident at presentation in 32.6% of essential cryoglobulinaemias, 27.1% of cryoglobulinaemias secondary to LPD and 12.2% of cryoglobulinaemias secondary to CTD. Antibodies to hepatitis B surface (HBsAg) and core (HBc) antigens were more frequent in cryoglobulinaemias secondary to CLD; anti-HBs antibodies were randomly distributed. Antibodies to hepatitis C (HCV) were tested for in 224 patients, and prevalence was high in all the groups, but lower in cryoglobulinaemias secondary to CTD (p < 0.0001). Type II and type III essential cryoglobulinaemias differed significantly in renal involvement (p < 0.0001), cryocrit > 3% (p < 0.0001), C4 < 15 mg/dl (p < 0.001), HBsAg prevalence (p < 0.01) and purpura (p < 0.05). Despite the high prevalence of HCV markers in all groups, the role of HCV in essential cryoglobulinaemia is not well defined; HBV seems to play only a marginal role.

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