Cryoglobulinemia Vasculitis

International audienceCryoglobulinemic vasculitis (CryoVas) is a small vessel vasculitis involving mainly the skin, the joints, the peripheral nerve system and the kidneys. Type I CryoVas are single monoclonal immunoglobulins related to an underlying B-cell lymphoproliferative disorder. Type II and III cryoglobulins, often referred to as mixed cryoglobulinemia, consist of polyclonal IgG with or without monoclonal IgM with rheumatoid factor activity. Hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas. The 10-year survival rates are 63%, 65% and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas and type I CryoVas patients, respectively. In HCV-positive patients, baseline poor prognostic factors include the presence of severe liver fibrosis, and central nervous system, kidney, and heart involvement. Treatment with antivirals is associated with a good prognosis whereas use of immunosuppressant (including corticosteroids) is associated with a poor outcome. In HCV-negative patients, pulmonary and gastrointestinal involvement, renal insufficiency and age>65 years are independently associated with death. Increased risk of lymphoma should also be underlined. Treatment of type I CryoVas is that of the hemopathy; specific treatment also include plasma exchange, corticosteroids, rituximab and ilomedine. In HCV-CryoVas with mild to moderate disease, an optimal antiviral treatment should be given. For HCV-CryoVas with severe vasculitis (i.e. worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia…) control of disease with rituximab, with or without plasmapheresis, is required before initiation of antiviral therapy. Other immunosuppressants should be given only in case of refractory forms of CryoVas, frequently associated with underlying B-cell lymphoma

Correspondence on “Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry” by Machado et al

We read with great interest the article by Machado et al who describe safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal disease. 1 The authors observed that vaccine against SARS-CoV-2 is well tolerated with rare report of I-RMD flare and very rare reports of serious adverse events. We observed that the authors included only 27 patients with autoinflammatory diseases. We thus propose to complete their observation with the result of our study about 190 patients with autoinflammatory disease (AID). A web survey assessing adverse effects after COVID-19 vaccination was sent on 7-30 June 2021 to patients with AID followed in the French national adult AID reference centre, and already included in the Juvenile Inflammatory Rheumatism (JIR) cohort. The patients were asked whether they had received a COVID-19 vaccination, the type of vaccine and number of injections. Severe adverse events were defined by the need for hospitalisation. Local reaction, fever, headache, arthralgia, myalgia, allergic reaction, fatigue, nausea, adenopathy, heart disorder, venous thromboembolism and stroke were monitored after the first and the second injection. The survey was sent by email to 445 patients with AID: 225 (50%) patients answered it, 168 aged between 18 and 55 years old and 57 aged above 55 years old. Among the 190 patients who received two doses of COVID-19 vaccines (online supplemental table), most patients had familial Mediterranean fever (FMF) (n=128, 67.4%); other AID were undefined systemic AID (n=20), TNF-α receptor-associated periodic syndrome (n=13), cryopyrin-associated periodic syndrome (n=9), adult-onset still disease (n=9), mevalonate kinase deficiency (n=7) and A20 haploinsufficiency (n=4). Eleven patients declared also having AA amyloidosis (5.7%). Colchicine was the most used treatment (n=138, 72.6%); 37 (19.5%) patients were on biotherapy, mostly interleukin-1 inhibitors (n=33) and 15 patients were not taking any treatment. Forty-six patients had already contracted SARS-CoV-2. Out of the 190 (84.4%) vaccinated patients with AID, BNT162b2 (Pfizer/ BioNTech) (n=157, 82.6%) and ChAdOx1 nCoV-19 (AstraZeneca) (n=22, 11.5%) were the most common vaccines; few patients received CX-024414 (Moderna) (n=11, 5.8%). Eighty-eight patients (46%) developed mild adverse events after the first injection and 70 patients (54%) after the second injection. Among the 153 patients who received BNT162b2, tenderness at the injection site was the most reported event (n=39, 25.5%); others were myalgia (n=28, 18.3%), fever (n=20, 13%) and headache (n=16, 10.5%). Concerning ChAdOx1 nCoV-19, reported events were fever (n=13, 59%), myalgia (n=11, 50%) and intense fatigue (n=2, 9%). Concerning CX-024414, four patients reported fever and myalgia (36%). No severe adverse event requiring hospitalisation has been reported. Twelve patients with FMF (9.3%) reported a mild flare after the first injection, which did not require hospitalisation. No vaccinated patient had developed COVID-19 after the second vaccine injection. Altogether, this study shows that adverse event of COVID-19 vaccination in patients with AID are similar to the expected adverse effects reported in the general population. 2 Especially among patients with FMF on colchicine treatment, the vaccine is very safe and should be highly recommended to patients with risk factors of severe COVID-19, since we previously reported death among such patients with FMF. 3 It also suggests that COVID-19 vaccination does not usually trigger an AID flare; these data were also reported in patients with autoimmune diseases 4 and AID. 5 To our knowledge, this is the largest study describing the effects of COVID-19 vaccination among patients with AID: the vaccine is well tolerated; these data combined with the results from Machado et al 1 could reassure patients displaying immune systemic disorders including AID patients who are still hesitant about COVID-19 vaccination, especially in the actual context of the resurgence of the epidemy

Extrahepatic manifestations of chronic hepatitis C virus infection

International audienceDuring hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined

Algorithmes diagnostiques et thérapeutiques des maladies auto-inflammatoires monogéniques présentant des fièvres récurrentes chez l'adulte

International audienceAutoinflammatory diseases (AID) are defined as disorders of innate immunity. They were initially defined in contrast to autoimmune diseases because of the lack of involvement of the adaptive immune system and circulating autoantibodies. The 4 monogenic AIDs first described are called the "historical" AIDs and include: Familial Mediterranean Fever (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), Tumor Necrosis Factor Receptor-associated Periodic Syndrome (associated with TNFRSF1A mutations) and Mevalonate Kinase Deficiency (associated with MVK mutations). In the last 10 years, more than 50 new monogenic AIDs have been discovered due to genetic advances. The most important discovery for adult patients is VEXAS syndrome associated with somatic UBA1 mutations leading to an autoinflammatory disease affecting mostly elderly men. Diagnosis of monogenic AIDs is based on personal and family history and detailed analysis of symptoms associated with febrile attacks, in the context of elevated peripheral inflammatory markers. This review proposes a practical approach of the diagnosis of the main monogenic AIDs among adult patients to guide the clinician

Autoinflammatory diseases: State of the art

International audienceAutoinflammatory diseases are characterized by innate immunity abnormalities. In autoinflammatory diseases (AID), inflammatory blood biomarkers are elevated during crisis without infection and usually without autoantibodies. The first 4 described AID were familial Mediterranean fever, cryopyrin-associated periodic fever syndrome (CAPS) or NLRP3-associated autoinflammatory disease (NRLP3-AID), mevalonate kinase deficiency (MKD) and TNFRSF1A-receptor associated periodic fever syndrome (TRAPS). Since their description 20 years ago, and with the progresses of genetic analysis, many new diseases have been discovered; some with recurrent fever, others with predominant cutaneous symptoms or even immune deficiency. After describing the 4 historical recurrent fevers, some polygenic inflammatory diseases will also be shortly described such as Still disease and periodic fever with adenitis, pharyngitis and aphtous (PFAPA) syndrome. To better explore AID, some key anamnesis features are crucial such as the family tree, the age at onset, crisis length and organs involved in the clinical symptoms. An acute phase response is mandatory in crisi

Systemic autoinflammatory diseases: Clinical state of the art

International audienceSystemic autoinflammatory diseases (SAIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases due to the lack of involvement of the adaptive immune system and circulating autoantibodies. The four historical monogenic diseases are familial Mediterranean fever (associated with MEFV mutations), cryopyrinopathies (NLRP3 mutations), tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A mutations), and mevalonate kinase deficiency (MVK mutations). In the last 10 years, more than 50 new monogenic SAIDs have been discovered thanks to advances in genetics. Diagnosis is largely based on personal and family history and detailed analysis of signs and symptoms associated with febrile attacks, in the setting of elevated inflammatory markers. Increasingly efficient techniques of genetic analysis can contribute to refining the diagnosis. This review is a guide for the clinician in suspecting and establishing a diagnosis of SAID.Systemic autoinflammatory diseases (SAIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases due to the lack of involvement of the adaptive immune system and circulating autoantibodies. The four historical monogenic diseases are familial Mediterranean fever (associated with MEFV mutations), cryopyrinopathies (NLRP3 mutations), tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A mutations), and mevalonate kinase deficiency (MVK mutations). In the last 10 years, more than 50 new monogenic SAIDs have been discovered thanks to advances in genetics. Diagnosis is largely based on personal and family history and detailed analysis of signs and symptoms associated with febrile attacks, in the setting of elevated inflammatory markers. Increasingly efficient techniques of genetic analysis can contribute to refining the diagnosis. This review is a guide for the clinician in suspecting and establishing a diagnosis of SAID