(1) Background: The COVID-19 pandemic has resulted in the exacerbation of various chronic diseases. Due to the potential impact of SARS-CoV-2 on mast cells, we aimed to analyze the relevance of COVID-19 disease on chronic spontaneous urticaria (CSU) clinical presentation and biological profile. (2) Methods: This study is a retrospective case series of patients with CSU diagnosed and treated in the Allergy Department of the Professor Doctor Octavian Fodor RIGH, (Cluj-Napoca, Romania). Patients were assessed for disease activity and level of control with the weekly urticaria activity score and the visual analogue scale. Results were correlated with COVID-19 severity and with nonspecific markers of inflammation during and after the SARS-CoV-2 infection. (3) Results: SARS-CoV-2 impacted a significant proportion (33%) of the CSU patients, of which 71% developed a moderate-severe form of COVID-19. Most of the patients (68%) had moderate-severe forms of CSU and 65% took AH1 treatment (one dose, two-fold dose or four-fold dose). The rest of them (35%) received the second-line treatment (40.3% Omalizumab, 53% Prednisolone and 4.8% Cyclosporine). In Omalizumab treated group of UCS patients we observed that COVID-19 disease was not severe. We established a positive correlation between the severity of the infection and that of the CSU clinical presentation, with most bothersome symptoms of urticaria being experienced by moderate to severe COVID-19 CSU patients (47%). Inflammatory markers were positively correlated (p = 0.01) with a more severe clinical profile of CSU, in accordance with our hypothesis that the level of inflammation triggered by COVID-19 disease has a role in CSU exacerbation. The non-specific inflammatory markers, such as CRP, were positively associated with the UAS7 score (R2 = 0.363; p = 0.001). An increased rate of exacerbation of CSU was observed in moderate-severe COVID-19 infection. (4) Conclusions: COVID-19 disease can result in the exacerbation of chronic spontaneous urticaria, more likely in moderate to severe forms of infection.

Chronic urticaria (CU) is a condition characterized by intensely pruritic, edematous, erythematous papules lasting for more than 6 weeks. Over half of the cases have concomitant swelling of deeper tissues, known as angioedema. The socio‑economic burden of the disease is significant. Unfortunately, patients with severe CU, refractory to conventional treatment, have limited and expensive therapeutic options. The pathogenesis of CU is not yet completely understood. Therefore, elucidating the pathophysiological mechanisms involved would potentially identify new therapeutic targets. It has been accepted in recent years that mast cells and their activation, followed by excessive degranulation represent the key pathophysiological events in chronic spontaneous urticaria (CSU). The triggering events and the complexity of the effector mechanisms, however, remain intensely debated topics with conflicting studies. One pathogenetic mechanism incriminated in chronic spontaneous urticaria is the response mediated by the high‑affinity receptor for IgE (FcεRI) expressed on mast cells. Increasing recognition of chronic spontaneous urticaria as an autoimmune disease linked to the cytokine‑chemokine network imbalance resulting from alteration of innate immune response is another pathogenetic explanation. It is likely that these different pathological mechanisms are more interconnected, both acting synergistically, rather than separately, to produce the clinical expression of CU. The discovery and understanding of pathogenic mechanisms represent the premise for the development of safe and effective immunomodulators and targeted biological treatment for severe, refractory CU.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33’s correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms.

Aim: The present study analyzed clinical and biological factors that might predict achievement of tolerance in patients with IgE-mediated cow milk allergy (CMA). Method: Seventy patients with IgE-mediated CMA (44.24 ± 24.16 months) were included in the study. The patients were evaluated clinically through skin prick test and sIgE to whole milk, casein, beta-lactoglobulin and alpha-lactalbumin. An eviction diet of 6 months was established, followed by oral food challenge test (OFC) and oral immunotherapy (OIT) with baked milk for 6 months. The tolerance was assessed after 2 years follow up. Results: Thirty percent of patients presented anaphylaxis of different degrees of severity as first manifestation of CMA. Sixty-two patients followed OIT or an accelerated reintroduction of milk. Ten patients (14.28%) did not obtain tolerance to milk within 2 years. A larger wheal in SPT and higher sIgE to milk, casein and betalactoglobulin were noted in patients with positive OFC. A basal level of <2.5 kU/l for sIgE to milk and <11.73 kU/l for sIgE to caseins predicted the occurrence of tolerance in patients with all types of clinical manifestations, including anaphylaxis. Conclusion: Basal levels of sIgE to milk and casein may help to identify patients that could become tolerant to milk.

Benralizumab is a humanized recombinant mAb that binds to the interleukin 5 receptor (IL-5R) expressed on eosinophils and is approved for the treatment of severe eosinophilic asthma. There are a series of severe eosinophilic disorders that may benefit from this treatment, and it could be a life-saving therapy. In this paper, we present two severe patients with eosinophil-induced diseases that had a good resolution after one dose of Benralizumab 30 mg. The first case is a severe non-necrotizing eosinophilic vasculitis following critical COVID-19 disease and the second case is a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms Syndrome) due to allopurinol. Conclusions: The successful administration of Benralizumab in rare or severe eosinophilic disease could be an option for life-saving therapies when conventional treatments fail.