Cryoglobulinemic vasculitis: a 2023 update.

PURPOSE OF REVIEW: Cryoglobulinemic vasculitis (CV) is an immune complex mediated small vessel vasculitis characterized by the presence of cryoglobulins in serum, often associated with hepatitis C infection, systemic autoimmune diseases or hematological conditions. The focus of this review is to provide an update on new insights into pathogenesis, epidemiology and therapies of infectious and noninfectious type II and type III CV. RECENT FINDINGS: The introduction of new antiviral drugs for treatment of hepatitis C infection implied major changes in HCV-related CV, allowing to shed new lights on CV pathogenesis and mechanisms of relapse and, therefore, to increase the relevance of autoimmune diseases in CV epidemiology. Specific B-cell clones are involved in the production of pathogenic immune complexes that leads to small-vessel vasculitis. Therefore, both antiviral treatments [direct-acting antivirals (DAAs) and oral nucleot(s)ide analogues] and targeted anti-CD20 therapies (rituximab) prove to be safe and effective options, leading to a better prognosis. Association of Sjögren syndrome and CV defines a specific phenotype of patients, characterized by severe manifestations and poor outcome. SUMMARY: Removing viral stimulation on B-cells through direct-acting antivirals and blocking B-cells proliferation and differentiation with rituximab are the goals of treatment of CV. However, further research is needed to identify prognostic factors of refractory and relapsing disease.

Exploring relief for Behçet's disease refractory oral ulcers: a comparison of TNF inhibitors versus apremilast.

OBJECTIVES: Oral and genital ulcers are the hallmark manifestation of Behçet's disease (BD), significantly impacting patients' quality of life. Our study focuses on comparing the effectiveness and safety of TNF inhibitors (TNFis) and apremilast in controlling oral ulcers of BD, aiming to provide evidence-based guidance for physicians in selecting appropriate treatment modalities. METHODS: A retrospective analysis was performed on BD patients treated between December 2016 and December 2021 with TNFis or apremilast for refractory oral ulcers. The study assessed treatment response by the absence of oral ulcers at 3 and 6 months, with additional evaluations for genital ulcers and articular involvement. RESULTS: The study included 78 patients, equally allocated between TNFis and apremilast treatments. Both groups showed significant oral ulcer reduction at 3 (p< 0.001) and 6 months (p= 0.01) with no significant difference between the treatments. Apremilast had a notable corticosteroid-sparing effect by the 3-month follow-up, persisting through 6 months. Both treatments were equally effective in reducing genital ulcers, with TNFis showing greater effectiveness in addressing articular involvement. Apremilast had a higher discontinuation rate due to gastrointestinal side effects. CONCLUSION: TNFis and apremilast are both effective for treating BD refractory oral ulcers. While TNFis may offer broader benefits for other disease manifestations, apremilast is distinguished by its corticosteroid-sparing effect, especially for patients with a milder disease phenotype. Treatment selection should consider individual disease severity and clinical features to ensure a personalized and effective management strategy.

The impact of environmental factors on aetiopathogenesis and clinical manifestations of Behçet's syndrome.

Behçet's syndrome (BS) is a rare multisystem vasculitis involving blood vessels of any size. BS aetiology is still unclear to date, and the heterogeneity of clinical expression among ethnics and genders make early diagnosis challenging. However, so far, considerable efforts have been made toward the understanding of BS, leading researchers to agree that the coexistence of some environmental triggers and a genetical susceptibility both underlie BS aetiopathogenesis. In particular, viral agents, oral microbial flora, and mucosal microbiota have been widely explored in this regard, but still no specific microorganism has been definitely linked to the disease aetiology. Likewise, the concept that some environmental factors may play a role in BS clinical presentation has emerged based on the growing evidence that disease severity is usually higher in male patients, and that diet and fatigue may be involved in disease recurrence, especially in mucocutaneous manifestations. Moreover, smoke cessation is acknowledged as a risk factor for oral ulcerations, although the underlying mechanism is still not clear. All those environmental factors play their effects through epigenetic mechanisms. The aim of this review is to discuss the evidence on the role of environmental factors in BS aetiopathogenesis and clinical course.

The role of tobacco smoking in anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Baricitinib and Pulse Steroids Combination Treatment in Hyperinflammatory COVID-19: A Rheumatological Approach in the Intensive Care Unit.

Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.

Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study.

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.