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Adv Clin Chem ; 104: 299-340, 2021.
Article in English | MEDLINE | ID: covidwho-893387


Cryoglobulins consist of serum immunoglobulins that precipitate below 37°C and resolubilize upon warming. The clinical triad of cryoglobulinemia usually includes purpura, weakness, and arthralgia. Cryoglobulinemic syndrome, clinically defined as a systemic vasculitis, is associated with chronic infection with hepatitis C virus (HCV) and autoimmune disorders and can evolve into B-cell malignancies. While the current literature about HCV-associated cryoglobulinemia is not very limited, little is known about the immunologic and serologic profiles of affected patients. Therefore, comprehension of the pathogenetic mechanisms underlying cryoprecipitation could be very helpful. Due to the persistence of viral antigenic stimulation, biomarkers to use after the worsening progression of HCV infection to lymphoproliferative and/or autoimmune diseases are widely needed. Laboratory methods used to detect and characterize low concentrations of cryoprecipitates and immunotyping patterns could improve patient management. The most critical factor affecting cryoglobulin testing is that the pre-analytical phase is not fully completed at 37°C.

Biomarkers/blood , COVID-19/complications , Cryoglobulinemia/blood , Cryoglobulins/analysis , Hepatitis C/physiopathology , Animals , Autoantibodies/blood , Chemical Precipitation , Cryoglobulinemia/therapy , Cryoglobulins/chemistry , Hepatitis C/blood , Humans , Vasculitis/virology
Int J Dermatol ; 59(12): 1475-1484, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-868170


BACKGROUND: Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. METHODS: We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. RESULTS: Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. CONCLUSIONS: This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.

Betacoronavirus/isolation & purification , Chilblains/blood , Coronavirus Infections/complications , Cryoglobulinemia/epidemiology , Pneumonia, Viral/complications , Adolescent , Adult , Aged , Biopsy , COVID-19 , Chilblains/diagnosis , Chilblains/epidemiology , Chilblains/etiology , Child , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cryoglobulinemia/blood , Cryoglobulinemia/diagnosis , Cryoglobulinemia/etiology , Cryoglobulins/analysis , Female , Fibrinogens, Abnormal/analysis , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Prevalence , Prospective Studies , SARS-CoV-2 , Skin/pathology , Spain/epidemiology , Young Adult