Pathogenesis of Chronic Spontaneous Urticaria With or Without Angioedema.

Chronic spontaneous urticaria (CSU) is a complex, immune-mediated skin disorder characterized by the appearance of wheals and/or angioedema. Histopathologic analysis reveals skin mast cell degranulation and a perivascular infiltrate composed of lymphocytes, eosinophils, neutrophils, and basophils. Mast cells and basophils are key effector cells in the pathogenesis and severity of CSU, and both cells can be activated by IgE-dependent and independent mechanisms.

Efficacy of complement inhibition with pegcetacoplan in children with C3 glomerulopathy.

Background: C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G.

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments.

Chronic spontaneous urticaria (CSU) is a complex dermatological condition characterized by recurrent wheals and/or angioedema lasting for more than six weeks, significantly impairing patients' quality of life. According to European guidelines, the first step in treatment involves second-generation H1-antihistamines (sgAHs), which block peripheral H1 receptors to alleviate symptoms. In cases with inadequate responses, the dose of antihistamines can be increased by up to fourfold.

Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition.

Background: Atypical-hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy often due to uncontrolled complement activation, characterized by high risk of end-stage kidney disease (ESKD). Eculizumab has improved the outcome, however, its efficacy varies among patients and its discontinuation is debated.

Methods: To identify characteristics associated with treatment response, we analyzed 244 aHUS patients referred to our center.

Nailfold Videocapillaroscopic Alterations as Markers of Microangiopathy in COVID-19 Patients.

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.

IgG and IgE Autoantibodies to IgE Receptors in Chronic Spontaneous Urticaria and Their Role in the Response to Omalizumab.

Chronic spontaneous urticaria (CSU) is defined as the recurrence of unprovoked transient wheals and itch for more than 6 weeks. Currently, there is an unmet need concerning response prediction in CSU. The present study investigated biomarkers of type I and type IIb autoimmunity as potential predictors of response to omalizumab in CSU.

Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients.

Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome.

Disease-modifying anti-rheumatic drugs improve the cardiovascular profile in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting about 0. 5-1% of the adult population and manifesting as persistent synovitis, systemic inflammation and production of autoantibodies. Patients affected by RA not only experience chronic disease progression, but are also burdened by a 1.

Biologics for chronic spontaneous urticaria: toward a personalized treatment.

Introduction: Chronic spontaneous urticaria (CSU) is characterized by the recurrent occurrence of short-lived wheals with or without angioedema for more than 6 weeks. Although its pathogenesis is not completely defined, several mechanisms seem involved, including autoimmunity and autoallergy with complement and coagulation activation. Various biologics are currently available or under investigation to counteract different CSU pathomechanisms.

Effects of Antibody Responses to Pre-Existing Coronaviruses on Disease Severity and Complement Activation in COVID-19 Patients.

The severity of coronavirus disease 2019 (COVID-19) may be influenced by pre-existing immune responses against endemic coronaviruses, but conflicting data have been reported. We studied 148 patients who were hospitalised because of a confirmed diagnosis of COVID-19, classified mild in 58, moderate in 44, and severe in 46. The controls were 27 healthy subjects.

Urticarial vasculitis: Clinical and laboratory findings with a particular emphasis on differential diagnosis.

Urticarial vasculitis (UV) is a rare cutaneous vasculitis of small vessels characterized by recurrent episodes of wheal-like lesions that tend to last more than 24 hours, healing with a residual ecchymotic postinflammatory hyperpigmentation. The histopathologic pattern of UV is that of leukocytoclastic vasculitis, consisting of fibrinoid necrosis of dermal vessels' walls and neutrophil-rich perivascular inflammatory infiltrates. Although its etiopahogenesis remains still undefined, UV is now regarded as an immune complex-driven disease with activation of the complement cascade, leading to exaggerated production of anaphylatoxins that are responsible for neutrophil recruitment and activation.

Eculizumab treatment in atypical hemolytic uremic syndrome: correlation between functional complement tests and drug levels.

Background: Atypical hemolytic uremic syndrome (aHUS) is characterized by platelet consumption, hemolysis, and renal injury. Eculizumab, a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule has not yet been clearly defined.

Methods: Herein we report our experience with eculizumab maintenance treatment, in which the interval between subsequent doses was adjusted based on classical complement pathway (CCP) activity, targeted to < 30% for the prevention of relapses.

Side effects among healthcare workers from a large Milan university hospital after second dose of BNT162b2 mRNA COVID-19 vaccine.

Background: In Italy, healthcare workers (HCWs) were among the first to receive COVID-19 vaccination. Aim of the present study is to evaluate frequency and severity of adverse events (AEs) following the second dose of BNT162b2 vaccine among HCWs of a large university hospital in Milan, Italy.

Methods: One month after having received the second dose of vaccine, HCWs filled-in a form about type, severity, and duration of post-vaccination local and systemic symptoms.

Consumption of complement in a 26-year-old woman with severe thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination.

Extremely rare reactions characterized by thrombosis and thrombocytopenia have been described in subjects that received ChAdOx1 nCoV-19 vaccination 5-16 days earlier. Although patients with vaccine-induced thrombotic thrombocytopenia (VITT) have high levels of antibodies to platelet factor 4 (PF4)-polyanion complexes, the exact mechanism of the development of thrombosis is still unknown. Here we reported serum studies as well as proteomics and genomics analyses demonstrating a massive complement activation potentially linked to the presence of anti-PF4 antibodies in a patient with severe VITT.

Increased Risk of Urticaria/Angioedema after BNT162b2 mRNA COVID-19 Vaccine in Health Care Workers Taking ACE Inhibitors.

Urticarial eruptions and angioedema are the most common cutaneous reactions in patients undergoing mRNA COVID-19 vaccinations. The vasoactive peptide bradykinin has long been known to be involved in angioedema and recently also in urticaria. Bradykinin is mainly catabolized by angiotensin-converting enzyme (ACE), which is inhibited by ACE inhibitors, a commonly employed class of antihypertensive drugs.