Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

Objective@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*Data sources@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*Study selection@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*Results@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*Conclusions@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Clinical and laboratory features of 58 patients with positive cryoglobulin / 中华全科医师杂志

Objective To study the disease spectrum,clinical and lab characteristic of cryoglobulinaemia.Methods The clinical and laboratory data of 58 patients with positive cryoglobulin admitted in Peking University People's Hospital from April 2010 to May 2014 were retrospectively analyzed.Results Among 58 patients,34 were diagnosed as autoimmune disease,8 as infectious disease,4 as hematological disease and 12 as primary cryoglobulinemia.Renal involvement was the most frequent clinical presentation among all cryoglobulin positive patients.Patients with autoimmune disease presented all clinical manifestations related to cryoglobulinaemia.Renal involvement (7/8) was prominent in patients with HBV/HCV infection,while other clinical presentations were rare.Among 4 patients with hematological disease,purpura was presented in 3 cases,renal involvement in 2,arthralgia in 2,fatigue,thrombosis or hyperviscosity was presented in 1 case,respectively;however,none of these patients had elevated rheumatoid factor (RF) level.Renal lesions were the most common reason for patients with primary cryoglobulinaemia to consult doctors,and 5 of them had positive antinuclear antibodies (ANA).Conclusions There is a broad spectrum of disease in cryoglobulinaemia.Multi-system involvement was most common in patients with autoimmune disease.For patients with HBV/HCV infection,extra-hepatic presentations were rare except renal involvement.Hyperviscosity syndrome tended to occur in patients with hematological disease.Since patients with primary cryoglobulinaemia had a relatively high rate of positive antinuclear antibodies,we should keep vigilance at the occurrence of autoimmune disease.

Influence of experimental conditions on the test results of cryoglobulin / 中华检验医学杂志

Objective This study was to observe the effects of different test conditions on the qualitative and quantitative detection of cryoglobulin .Methods We prepared 5 blood samples of different types of cryoglobulinemia . We detect the cryoglobulin qualitatively and quantitatively at different temperatures (37 ℃and room temperature of 20-25 ℃), and with different observation time (3 days and 7 days) and with different amount of blood (5 ml and 20 ml) .Further we will categorize the type of cryoglobulin and detect the components of cryoglobulin by immunofixation electrophoresis ( IFE) and other laboratory tests.Results (1) Blood samples from two groups were clotting and the serums were separated at 37 ℃ and room temperature respectively , and cryoglobulins of two groups were all qualitatively positive . Quantitative detection of cryoglobulins showed that the concentrations of cryoglobulins of room temperature group are lower than that of 37℃group;(2) Compared with 7 days, observing for only 3 days may lead to false-negative results in qualitative detection of cryoglobulin , and concentrations of cryoglobulin are also decreased;(3) Compared with 20 ml blood sample,5 ml blood sample is not enough for qualitative and quantitative detection of cryoglobulins .It may lead to false-negative results;(4) After purification, IFE and other laboratory tests can be used to categorize the types and find the components of cryoglobulins .Such examinations are helpful for finding the potential causes of cryoglobulinemia .Conclusions The positive of serum cryoglobulin is a key indicator of cryoglobulinemia .Detection of cryoglobulin can be affected by temperature, observed time and the blood volume for measurement .In addition, IFE and other laboratory tests are helpful for finding the type and the components of cryoglobulin .

Crioglobulina con propiedad crioaglutinina en un paciente con linfoma esplénico de zona marginal / Cryoglobulin with cold agglutinin properties in a patient with splenic marginal zone lymphoma / Crioglobulina com propriedade crioaglutinina em um paciente com linfoma esplênico de zona marginal

El objetivo del trabajo fue describir un caso de linfoma esplénico de zona marginal (LEZM) con un componente monoclonal que posee propiedades de crioglobulina y crioaglutinina, un hallazgo de muy baja frecuencia. Una paciente con LEZM padeció una anemia hemolítica autoinmune 5 años después del diagnóstico, con hematocrito de 0,15 L/L, hemoglobina 49 g/L, lactato deshidrogenasa 16,82 μkat/L, prueba de Coombs directa positiva con anti- IgG/C3d, bilirrubina total 90,6 μmol/L e indirecta de 58,1 μmol/L. No presentó evidencia clínica ni serológica de infección por VIH, hepatitis B ni C. El proteinograma sérico presentó un pico monoclonal de 14 g/L, con crioglobulinemia positiva a las 24 h, y un criocrito de 30%. La crioglobulina purificada fue de tipo I con un componente monoclonal IgM-lambda, coincidente al observado en suero. El suero, el eluato a 37 °C y la crioglobulina purificada de la paciente presentaron actividad de crioaglutinina con especificidad anti-I, fenómeno producido por la misma inmunoglobulina. El hallazgo de una crioglobulina con propiedades de crioaglutinina en pacientes con LEZM no ha sido descrito previamente en la bibliografía.

The aim of this paper is to describe a case of splenic marginal zone lymphoma (SMZL) with monoclonal component having properties of cryoglobulin and cold agglutinin, a finding of very low frequency. A patient with SMZL suffered autoimmune hemolytic anemia five years after diagnosis, with hematocrit 0.15 L/L, hemoglobin 49 g/L, lactate dehydrogenase 16.82 μkat/L, direct Coombs test with anti-IgG/C3d positive, total bilirubin 90.6 μmol/L and indirect 58.1 μmol/L. She presented no clinical or serological evidence of HIV, hepatitis B or C infection. Serum protein electrophoresis showed a monoclonal peak of 14 g/L, with positive cryoglobulinemia at 24 hours, and 30% cryocrit. Purified cryoglobulin was type I with a monoclonal IgM-lambda component coincident with that observed in serum. The patient serum, eluate at 37 °C and purified cryoglobulin showed cold agglutinin activity with anti-I specificity, phenomenon produced by the same immunoglobulin. The finding of a cryoglobulin with cold agglutinin properties in patients with SMZL has not been previously described in the literature.

O objetivo do trabalho foi descrever um caso de linfoma esplênico de zona marginal (LEZM) com um componente monoclonal com propriedades do crioglobulina e crioaglutinina, um achado de muito baixa frequência. Um doente com LEZM sofreu uma anemia hemolítica autoimune cinco anos após o diagnóstico, com hematócrito de 0,15 L/L, hemoglobina 49 g/L, lactato desidrogenase de 16,82 μkat/L, teste de Coombs direto positivo com anti-IgG/C3d, bilirrubina total 90,6 μmol/L e indireta 58,1 μmol/L. Não apresentou evidência clínica ou sorológica de infecção por HIV, hepatite B ou C. O proteinograma sérico mostrou um pico monoclonal de 14 g/L, com crioglobulinemia positiva 24 horas, e um criocrito de 30%. Crioglobulina purificada foi tipo I com o componente monoclonal IgM-lambda, coincidente com a observada no soro. O soro, o eluato a 37 ° C e a crioglobulina purificada do paciente mostraram atividade de crioaglutinina com especificidade anti-I, fenômeno produzido pela mesma imunoglobulina. O achado de uma crioglobulina com propriedades de crioaglutinina em pacientes com LEZM não foi previamente descrito na literatura.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

Crioglobulinemia mista em pacientes com infecção pelo vírus da hepatite C (VHC) / Mixed cryoglobulinaemia in patients with hepatitis C virus infection

Introdução: A infecção pelo vírus da hepatite C (VHC) está associada com várias manifestações extra-hepáticas, sendo a patogenia da maior parte baseada em mecanismos autoimunes ou linfoproliferativos. Objetivo: Identificar a prevalência de crioglobulinemia entre os pacientes com infecção pelo VHC. Pacientes e métodos: Foram estudados de forma prospectiva e consecutiva 67 pacientes com hepatite crônica pelo VHC, e avaliados quanto a presença de crioglobulinas, autoanticorpos e quanto a sintomas relacionados a crioglobulinemia. Resultados: Foi detectada a presença de crioglobulinas em 18 pacientes (27%). Quando comparados os pacientes com crioglobulinas com os demais, foi observado sexo feminino: 72% × 51%; média de idade: 49,8± 9,3 × 46,3± 13; nível de ALT: 114,05 × 119,18; genótipo: 1: 67% × 37%; cirrose: 22% × 14%; Artralgia em 39% × 28%; FAN em 11% × 6%; FR em 53% × 29%; anticorpo anti-tireoglobulina em 5% × 8% e anticorpo antimicrossoma em 5% × 2%. A síndrome clínica de crioglobulinemia mista foi diagnosticada em 2 pacientes (11%) e um deles apresentava glomerulonefrite crioglobulinêmica. Conclusão: A prevalência de crioglobulinemia mista em pacientes com infecção pelo VHC é elevada, porém a síndrome clínica é infreqüentemente detectada (AU)

Introduction: The hepatitis C vírus (HCV) infection is associated with many extrahepatic manifestations. The mechanisms are autoimmunes or limphoproliferatives. Objective: To identify the prevalence of cryoglobulinemia in the patients with HCV infection. Pacients and methods: Sixty seven patients with HCV chronic hepatitis were prospectively and consecutively studied. They were evaluated for the presence of cryoglobulins, autoantibodies and symptoms related to cryoglobulins. Results: The presence of cryoglobulins was detected in 18 patients (27%). When this group with cryoglobulins was compared to the others it was observed: women were more prevalent in the cryoglobulin group (72% × 51%); the mean age was 49,8± 9,3 × 46,3± 13; mean ALT was 114,05 × 119,18; genotype ? 1: 67% × 37%; cirrhosis: 22% × 14%; artralgia: 39% × 28%; FAN: 11% × 6%; reumathoid factor: 53% × 29%; anti-thyreoglobulin antibody: 5% × 8%; and anti-microssomal antibody: 5% × 2%. Clinical cryoglobulinemic syndrome was diagnosed in 2 patients (11%) and one of them presented cryoglobulinemic glomerulonephritis. Conclusion: The prevalence of mixed cryoglobulinemia in patients with HCV infection is high, however the clinical syndrome is not frequently detected (AU)

Evaluation of Early Screening Method Using Turbidity Measurement for Detection of Cryoglobulin / 대한류마티스학회지

OBJECTIVE: Cryoglobulins are immunoglobulins that tend to form reversible precipitations below 37degrees C, well known to be associated with various diseases such as autoimmune diseases, hematologic malignancies, chronic infections and renal diseases. In many cases, low amounts of cryoglobulins take a few days to be precipitated. In this study, we compared cryoglobulin early screening test with conventional method to evaluate its clinical efficacy. MEHTODS: 28 patients who showed cryoglobulinemia were selected and the time it took for visibly detecting the existence of cryoglobulin were recorded. Sera of cryoglobulinemiemic patients (n=19) and of control group (n=14) kept in two conditions of 37 degrees C and 4 degrees C for 1 hour and were then measured for delta optical density (DOD). RESULTS: In the cryoglobulin early screening test using the test tube, the median and range of the DOD for cryoglobulinemic patient group was 0.50 (0.17~0.99) while it was 0.18 (0.02~0.50) for the control group. The results showed statistically significant difference (p=0.001). In another method of using the microplate, there was no statistical significance between disease and control group. The area under the curve for test tube method was 0.857. The sensitivity and specificity were 89.5% and 71.4% respectively (cut-off value=0.23). CONCLUSION: Cryoglobulin early screening test provides the results within 2 hours and we thought this feature could give clinicians some helpful informations. More studies are needed in the future for increasing the sensitivity and specificity of this test.