Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients\' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

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UNASSIGNED: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives.
UNASSIGNED: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed.
UNASSIGNED: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16].
UNASSIGNED: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

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Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.

BACKGROUND: Vitamin K3 (VK3), a fat-soluble synthetic analog of the vitamin K family, has coagulant, anti-inflammatory, antibacterial, and anticancer properties. Pseudo allergy is a IgE-independent immune response associated with mast cells. This study investigated the role of VK3 in IgE-independent mast cell activation.
METHODS: Substance P (SP) was used to induce LAD2-cell activation in order to analyze the effects of VK3 in vitro. Cutaneous allergy and systemic allergy mouse models were used to analyze the anti-pseudo-allergic effects of VK3. Proteome microarray assays were used to analyze VK3-binding protein. Biolayer interferometry and immunoprecipitation were used to verify interaction between VK3 and its key targets. RNA interference was used to determine the role of GAB1 in LAD2cell activation.
RESULTS: VK3 inhibited SP-induced LAD2-cell activation, and resulted in the release of β-hexosaminidase, histamine and cytokines; VK3 inhibited SP-induced pseudo allergic reactions in mice, and serum histamine and TNF-α levels decreased. Degranulation of skin mast cells was reduced; GAB1 in mast cells was stably bound to VK3. GAB1 participated in SP-induced LAD2-cell activation. GAB1 knockdown in LAD2 cells prevented SP-induced β-hexosaminidase release, calcium mobilization and cell skeletal remodeling. VK3 directly binds to GAB1 and reduces its expression to inhibited SP-induced LAD2 cell activation.
CONCLUSIONS: The anti-pseudo-allergic activity of VK3 was confirmed in vitro and in vivo. VK3 can inhibit SP-induced mast cell activation by directly targeting GAB1. This study provides new insights on the activity of VK3 and the mechanism of pseudoallergic reaction.

This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced β-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced β-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.

BACKGROUND: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD).
OBJECTIVE: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA).
METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured.
RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside.
CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

OBJECTIVE: To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the combination of them in managing patients with IgE-mediated food allergies.
RESULTS: Recent studies suggest that OIT and biologics, alone or together, can have a role as disease-modifying treatments for food allergies. The FDA has recently approved omalizumab as a treatment for food allergy. Other biologics are currently under evaluation and further studies are needed to assess the efficacy and safety of these therapies.
CONCLUSIONS: The allergology scenario is rapidly evolving, the recent introduction and approval of new therapeutic strategies such as biotechnological drugs and allergen immunotherapy is changing the therapeutic paradigm: we are witnessing a shift from a strategy based on avoiding the trigger and reversing an allergic reaction already in progress, to one that aims to modify the natural history of the disease by acting on the immunological mechanisms that determine it. This approach is consistent with the modern perspective of a personalized patient-tailored medicine. In this opinion review, we will provide a brief analysis of current and future therapeutic options for IgE-mediated food allergy, focusing on OIT, biologics and their combination.

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