State of the art: the treatment of systemic lupus erythematosus.

PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with dysregulated cells in the immune system. The disease affects organs like kidneys, nervous system, joints, and skin. To manage SLE effectively, novel treatments targeting immune system components have been developed. This review investigates the therapeutic potential of existing targeted therapies and explores future innovative approaches for well tolerated, personalized treatment. RECENT FINDINGS: SLE treatment involves cytokine targets and specific immunologic pathways, with even small molecules involved. SUMMARY: The advanced therapeutic options in SLE management give clinicians more tools to control disease activity according to personalized medicine.

COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation.

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

Eosinophil Cationic Protein Variation in Patients with Asthma and CRSwNP Treated with Dupilumab.

BACKGROUND: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a "type 2" (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. METHODS: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. RESULTS: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. CONCLUSIONS: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Giant cell arteritis and innovative treatments.

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is an idiopathic and persistent condition characterized by granulomatous vasculitis of the medium and large vessels with overlapping phenotypes, including conventional cranial arteritis and extra-cranial GCA, also known as large-vessel GCA. Vascular problems linked with large vessel involvement may partly be caused by delayed diagnosis, emphasizing the necessity of early detection and the fast beginning of appropriate therapy. Glucocorticoids are the cornerstone of treatment for GCA, but using them for an extended period has numerous, often severe, side effects. RECENT FINDINGS: clinical practice and novel discoveries on the pathogenic pathways suggest that steroid-free biologic treatments may be efficient and safe for GCA patients. SUMMARY: since now, only Tocilizumab is approved for GCA treatment, but several drugs are currently used, and ongoing trials could give both researchers and patients novel therapeutic strategies for induction, maintenance, and prevention of relapse of GCA. The aims of this work is to synthesize evidence from current studies present in scientific literature about innovative treatment of Giant cell artheritis.

Pancytopenia Secondary to Vitamin B12 Deficiency in Older Subjects.

BACKGROUND: Vitamin B12 (cobalamin CBL) is a water-soluble vitamin required to form hematopoietic cells (red blood cells, white blood cells, and platelets). It is involved in the process of synthesizing DNA and myelin sheath. Deficiencies of vitamin B12 and/or folate can cause megaloblastic anemia (macrocytic anemia with other features due to impaired cell division). Pancytopenia is a less frequent exordium of severe vitamin B12 deficiency. Vitamin B12 deficiency can also cause neuropsychiatric findings. In addition to correcting the deficiency, an essential aspect of management is determining the underlying cause because the need for additional testing, the duration of therapy, and the route of administration may differ depending on the underlying cause. METHODS: Here, we present a series of four patients hospitalized for megaloblastic anemia (MA) in pancytopenia. All patients diagnosed with MA were studied for a clinic-hematological and etiological profile. RESULTS: All the patients presented with pancytopenia and megaloblastic anemia. Vitamin B12 deficiency was documented in 100% of cases. There was no correlation between the severity of anemia and deficiency of the vitamin. Overt clinical neuropathy was present in none of the cases of MA, while subclinical neuropathy was seen in one case. The etiology of vitamin B12 deficiency was pernicious anemia in two cases and low food intake in the remaining cases. CONCLUSION: This case study emphasizes the role of vitamin B12 deficiency as a leading cause of pancytopenia among adults.

COVID-19 Vaccine Hesitancy among Italian Healthcare Workers: Latent Profiles and Their Relationships to Predictors and Outcome.

Vaccine hesitancy and conspiracy beliefs among healthcare workers (HCWs) represent operational priorities that require urgent attention. Identifying and classifying specific subpopulation of hesitancy is crucial to customize educational and intervention strategies to enhance the acceptance and uptake rate of vaccination. Thus, the main purpose of our study was to empirically identify latent profiles of vaccine hesitancy among Italian HCWs adopting a person-centered approach and investigating their relationships with antecedents and intention to get a fourth dose of COVID-19 vaccine. We conducted latent profile analyses (LPA) to identify different configurations of vaccine hesitancy based on five antecedents of vaccination: confidence, complacency, constraints, calculation, and collective responsibility among a sample of Italian HCWs (n = 573). LPA revealed four distinct profiles: believer (61.5%), middler (24.7%), hesitant (9.00%), and rejecter (4.7%). Having conspiracy beliefs was associated with a greater likelihood of membership in all but believer. Finally, the likelihood of intention to get a fourth dose of COVID-19 vaccine was lowest in the rejector and hesitant profiles. Theoretical contributions and implications for practice are discussed.