title: Prevalence of mixed cryoglobulinaemia syndrome and circulating cryoglobulins in a population-based survey: the Origgio study.
abstract: Mixed cryoglobulinaemia syndrome (MCS) is associated with a number of infectious, autoimmune and lymphoproliferative disorders, particularly chronic hepatitis C infection. Although circulating mixed cryoglobulins (cMCGs) are a frequent finding in HCV-infected patients, only a minority of them develop a frank MCS. The only available data concerning the prevalence of MCS, which is generally considered a rare disease, come from hospital records. The aim of this investigation was to estimate the prevalence of cMCGs and MCS in a population-based study. All of the adult residents in Origgio, a town of about seven thousand inhabitants in northern Italy, were mailed a validated questionnaire, and a randomly selected sample of respondents was invited to undergo a clinical examination and laboratory tests including the determination of cMCGs. The 1594 respondents to the questionnaire (54.3% women, 64.5% aged >49years) accounted for 26.4% of the total adult population. Forty-nine (3.1%) positively responded to at least two questions, including a disproportionately high number of people aged >70years (p=0.001). Of the 266 randomly selected subjects invited to undergo a clinical examination and laboratory tests, 147 accepted, 30 (20.4%) of whom had asymptomatic type III cMCGs and four MCS. The risk of cMCG positivity was independently associated with C4 levels of <16mg/dL (adjusted odds ratio [AOR] 4.40, 95% confidence interval [CI] 1.07-18.08; p=0.040) and HCV positivity (AOR 6.87, 95% CI 1.16-40.79; p=0.034). No co-morbidities known to be related to cMCG production could be detected in more than 50% of the positive cases. After including the other positive respondents who agreed to undergo a clinical examination, the number of diagnosed MCS increased to seven: five HCV-related, one HBV-related, and one essential MCS. In conclusion, MCS seems to be more frequent than expected for a 'rare' disease, and the unexpectedly high prevalence of cMCGs raises questions about the frequency with which they are triggered, the spectrum of diseases involved in triggering them, and their real role as disease indicators.
authors.affiliation: Busto Arsizio, Ospedale di Saronno UO Medicina Interna, Pz.le Borella 1, 21047 Saronno, Italy. Electronic address: gmonti@aobusto.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Monti
authors.affiliation: Busto Arsizio, Ospedale di Saronno UO Medicina Interna, Pz.le Borella 1, 21047 Saronno, Italy. Electronic address: fsaccardo@aobusto.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccardo
authors.affiliation: Busto Arsizio, Ospedale di Saronno UO Medicina Interna, Pz.le Borella 1, 21047 Saronno, Italy. Electronic address: laura.castelnovo@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Castelnovo
authors.affiliation: Busto Arsizio, Ospedale di Saronno UO Medicina Interna, Pz.le Borella 1, 21047 Saronno, Italy. Electronic address: pnovati@aobusto.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Novati
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Milan, Luigi Sacco Hospital, via GB Grassi 74, 20157 Milan, Italy. Electronic address: salvatore.sollima@unimi.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sollima
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Milan, Luigi Sacco Hospital, via GB Grassi 74, 20157 Milan, Italy. Electronic address: agostino.riva@unimi.it.
authors.forename: Agostino
authors.initials: A
authors.lastname: Riva
authors.affiliation: Rheumatology Unit, University of Milan, Luigi Sacco Hospital, via GB Grassi 74, 20157 Milan, Italy. Electronic address: piercarlo.sarziputtini@unimi.it.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.affiliation: Clinic of Rheumatology, Department of Medical and Biological Sciences, University of Udine, P.za Misericordia, 33100 Udine, Italy. Electronic address: quartuccio.luca@aoud.sanita.fvg.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Quartuccio
authors.affiliation: Clinic of Rheumatology, Department of Medical and Biological Sciences, University of Udine, P.za Misericordia, 33100 Udine, Italy. Electronic address: salvatore.devita@med.uniud.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Milan, Luigi Sacco Hospital, via GB Grassi 74, 20157 Milan, Italy. Electronic address: massimo.galli@unimi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
mesh_terms: D003449:Cryoglobulinemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D003450:Cryoglobulins / Q000032:analysis*; D006801:Humans; D007558:Italy; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires
chemical_list: D003450:Cryoglobulins
keywords: Chronic hepatitis C infection; Cryoglobulins; Mixed cryoglobulinaemia syndrome