Mixed Cryoglobulinaemia Vasculitis Treated with Obinutuzumab in a Patient Allergic to Rituximab

Cryoglobulinaemia is defined as the presence of cryoglobulins in the serum, which are immunoglobulins that reversibly precipitate and form a gel when the temperature is <37ºC. Autoimmune diseases such as Sjogren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis could be associated with mixed cryoglobulinaemia vasculitis (MCV). The treatment of MCV generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab. Here, we present a case of a 60-year-old woman who developed type II MCV in the context of overlap autoimmune disease and who has been treated with a new anti-CD20 agent, obinutuzumab.

Mixed Cryoglobulinaemia Vasculitis after Persistent Hepatitis C Virus Eradication

Mixed cryoglobulinaemia vasculitis (MCV) is a systemic vasculitis of the small and medium-size vessels caused by active hepatitis C (HCV) infection in >80% of cases. Beuthien et al. presented the first case of MCV with undetectable HCV after 10 months of therapy. In the last few years, more authors have described other cases of symptomatic MCV after 1 year of persistent HCV eradication. Here, we present a case report of a 57-year-old man who developed MCV with renal involvement after 3 years of HCV eradication with interferon therapy.

Noninfectious mixed cryoglobulinaemic glomerulonephritis associated with monoclonal gammopathy of undetermined significance

Background Cryoglobulins are cold-precipitable immunoglobulins that may be found in association with systemic vasculitis including cryoglobulinaemic glomerulonephritis (CGN). Type 1 cryoglobulins consist of isolated monoclonal immunoglobulin (mIg), whereas mixed cryoglobulins are typically immune complexes comprising either monoclonal (type 2) or polyclonal (type 3) Ig with rheumatoid activity against polyclonal IgG. Only CGN related to type 1 cryoglobulins has been clearly associated with monoclonal gammopathy of undetermined significance (MGUS) using the conventional serum-, urine- or tissue-based methods of paraprotein detection. Methods We retrospectively assessed our patient cohort of CGN related to mixed (type 2 or 3) cryoglobulins for those with a monoclonal band on serum protein electrophoresis (SPEP), with exclusion of infectious cases and those involving malignant clonal plasma cell or B cell disorders. Results We identified four patients with a median age of 54 years, including three women. Two patients had type 2 cryoglobulinaemia, one had type 3 cryoglobulinaemia, and one lacked definitive typing of the serum cryoprecipitate. The serum monoclonal band identified on SPEP was IgM-κ in all four cases. Treatments included corticosteroids, cyclophosphamide, plasma exchange, and rituximab. At median 3.5 years’ follow-up, no patient had developed a haematological malignancy or advanced chronic kidney disease. Other potential causes of mixed cryoglobulinaemia were also present in our cohort, notably primary Sjögren’s syndrome in three cases. Conclusions Our study raises questions regarding the attribution of causation to MGUS, and the role of clonally directed therapies outside the setting of haematological malignancy.

Direct-acting antiviral therapy improves kidney survival in hepatitis C virus–associated cryoglobulinaemia: the RENALCRYOGLOBULINEMIC study

Background Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. Methods The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. Results Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70–251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04–0.40]; P &lt; 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04–0.33); P &lt; 0.001]. Conclusions Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

Parvoviral infection with systemic impact and renal consequences

Parvovirus infection is usually asymptomatic especially in immunocompetent adults. When symptomatic it can range from mild to life threatening depending on the patient’s age and comorbidities. We report a case of a 40-year-old male patient with parvovirus infection who presented a purpuric rash in distal extremities, acute kidney injury, type II mixed cryoglobulinaemia and hypocomplementaemia. His renal biopsy showed a mesangioproliferative glomerulonephritis with positive immunoreactivity to C3, IgM and C1q. Parvovirus B19 was detected in the biopsy tissue by PCR. He was treated with prednisolone with total remission after 1 month. We discuss the diagnosis of kidney lesion due to parvovirus in an immunocompetent person, which is a very rare condition and its association with the cryoglobulinaemia diagnosis.