Atopy Does Not Influence the Clinical Outcome of Acute Urticaria: A Retrospective Study.

BACKGROUND: Acute urticaria (AU) may be associated with atopy, but the relationship between atopic status and the clinical features of the disease has not been fully described. OBJECTIVES: The aim of the study was to determine the proportion of atopy in AU patients and to see whether atopy is related to the clinical characteristics of AU and whether it has an impact on the outcome of the disease. MATERIALS AND METHOD: A retrospective analysis of patients with AU was performed. Demographic data, clinical features, and laboratory results were compared and analyzed between the atopic and non-atopic AU (napAU). RESULTS: In total, 139 participants were included. 54 (38.8%) patients were atopic AU (apAU) and 85 (61.2%) were napAU. Compared with napAU patients, apAU patients were more likely to have anaphylaxis, higher levels of C4, and lower levels of antistreptolysin. There were no significant differences between the two groups in terms of other clinical features, laboratory tests, the natural course of the disease, or disease outcomes. CONCLUSION: Atopy does exist in some patients with AU, and AU patients with an atopic background are at higher risk for anaphylaxis. Atopy does not influence the clinical outcome of AU and is not correlated with other clinical features and laboratory results of AU.

Higher House Dust Mite-Specific IgE Levels among Chronic Spontaneous Urticaria Patients May Implicate Higher Basophil Reactivity.

INTRODUCTION: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. METHODS: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. RESULTS: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. CONCLUSION: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.

Single-cell RNA-seq reveals abnormal differentiation of keratinocytes and increased inflammatory differentiated keratinocytes in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease characterized by severe pruritus and eczematous lesions. Heterogeneity of AD has been reported among different racial groups according to clinical, molecular and genetic differences. OBJECTIVE: This study aimed to conduct an in-depth transcriptome analysis of AD in Chinese population. METHODS: We performed single-cell RNA sequencing (scRNA-seq) analysis of skin biopsies from five Chinese adult patients with chronic AD and from four healthy controls, combined with multiplexed immunohistochemical analysis in whole-tissue skin biopsies. We explored the functions of IL19 in vitro. RESULTS: ScRNA-seq analysis was able to profile a total of 87,853 cells, with keratinocytes (KCs) in AD manifesting highly expressed keratinocyte activation and pro-inflammatory genes. KCs demonstrated a novel IL19+ IGFL1+ subpopulation that increased in AD lesions. Inflammatory cytokines IFNG, IL13, IL26 and IL22 were highly expressed in AD lesions. In vitro, IL19 directly downregulated KRT10 and LOR in HaCaT cells and activated HaCaT cells to produce TSLP. CONCLUSION: Abnormal proliferation and differentiation of keratinocytes contribute immensely to the pathogenesis of AD, whereas AD chronic lesions have witnessed significant presence of IL19+ IGFL1+ KCs, which may be involved in the disruption of the skin barrier, the connection and magnification of Th2 and Th17 inflammatory responses, and mediation of skin pruritus. Furthermore, progressive activation of multiple immune axes dominated by Type 2 inflammatory reaction occur in AD chronic lesions.

Does microneedle fractional radiofrequency system inactivate botulinum toxin type A?

BACKGROUND: The combination of botulinum toxin type A (BoNT/A) and energy equipment have been widely used in the clinic. AIMS: To determine whether the energy of microneedle fractional radiofrequency (MFR) affects the efficacy of BoNT/A and to provide an optimal strategy for the energy device in combination with BoNT/A in the clinic. METHODS: First, a total of 45 females with moderate-to-severe periorbital crow's feet wrinkles were enrolled and divided into three groups according to different treatment methods and intervals, including BoNT/A injection alone, BoNT/A injected immediately after MFR treatment and BoNT/A injected 7 days after MFR treatment. The photographs were compared before treatment and 4 weeks after treatment. Then, the mouse models were established by combining MFR with BoNT/A at different intervals, to evaluate muscle strength, muscle mass, muscle nutritional markers, and important cytokines levels. RESULTS: All patients in each group had high satisfaction. The MFR + BoNT/A (immediately) group could improve dynamic wrinkles, but the others had more significant efficacy (p < 0.05). The results of mouse models showed that all BoNT/A groups induced different degrees of muscle paralysis in vivo, but the paralytic effect induced by the BoNT/A group, MFR + BoNT/A (interval of 3-day) group, and MFR + BoNT/A (interval of 7-day) group were higher than others and the expression levels of muscle nutritional markers in NMJ tissues were significantly upregulated. CONCLUSION: MFR has a certain reduction effect on the activity of BoNT/A, and this reduction effect would last for 3 days after MFR treatment.

Allergen-specific immunotherapy induces monocyte-derived dendritic cells but attenuates their maturation and cytokine production in the lesional skin of an atopic dermatitis mouse model.

Atopic dermatitis (AD) is a common inflammatory skin disease, but current treatments for AD are mostly limited to the alleviation of symptoms and inhibition of inflammation. Allergen-specific immunotherapy (ASIT) is the only curative approach for allergic diseases and could be a promising way to cure AD. Although ASIT has been gradually applied to patients with AD, there are still few studies on its efficacy evaluation and mechanisms. Based on our previous established AD mouse model by dinitrofluorobenzene and an extract of Dermatophagoides farina, we performed ASIT on this AD model through subcutaneous injection of Dermatophagoides farina extracts to evaluate the efficacy of ASIT and study its underlying mechanisms. Our results showed that ASIT could not only alleviate skin lesions and scratching behaviors of AD mice but also inhibit their Th2-type immune responses. Furthermore, ASIT could increase the infiltration of monocyte-derived dendritic cells in skin lesions but attenuated their maturation and production of interleukin 1α and interleukin 12/23 p40. As immature and semi-mature dendritic cells preferentially induce tolerance, accumulation but inhibition of maturation of monocyte-derived dendritic cells after ASIT may indicate a novel mechanism of ASIT and a potential therapeutic target for AD.