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Background: Chronic urticaria (CU) appears to be of autoimmune origin in about half of all patients, since several autoreactive immunoglobulin Gs (IgGs), such as anti-FcεRIα and anti-IgE, are detected in the sera of such patients. However, whether autoreactive IgE is associated with CU remains unclear. In this study, we attempted to identify autoreactive IgE antibodies in sera from patients with CU. Methods: Sera were collected from 67 normal subjects, 85 patients with CU and 28 patients with atopic dermatitis (AD). An autologous serum skin test (ASST) was performed on 27 of the CU patients. Autoreactive IgE and IgG levels against self-antigens were measured using enzyme-linked immunosorbent assays. The basophils were activated with dsDNA, and the CD63 expression level was examined using a fluorescence-activated cell sorter. Results: The anti-dsDNA IgE levels were significantly higher in patients with CU and AD than in normal subjects, but no differences in the anti-dsDNA IgG levels were seen. The levels of thioredoxin-, peroxiredoxin- and thyroglobulin-reactive IgE and IgG were not significantly higher in the CU patients than in the other 2 groups. There was no significant difference in the levels of anti-dsDNA IgE between ASST-positive and ASST-negative patients. The basophils from 2 out of 9 CU patients exhibited degranulation in response to dsDNA. Conclusions: Our data suggest that anti-dsDNA IgE is involved in the pathogenesis of some cases of CU.

For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2 generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU. This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration. Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively. Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile. https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

We previously reported results of a web‐based questionnaire conducted to better understand real‐world clinical management of urticaria and angioedema. We here described a sub‐analysis of the data with stratification by the type of participants’ workplaces and the length of their clinical experience of dermatology. This study revealed that treatments and examinations for urticaria and angioedema are affected by length of experience and type of physicians’ workplaces to manage the diseases.

A 50-year-old Japanese woman presented with a 4-day history of multiple purpura on her extremities and myalgia. She had been receiving nivolumab therapy for stage IV renal cell carcinoma for 18 months. Nivolumab was temporarily discontinued due to liver dysfunction and resumed 3 months before. Biopsy specimen revealed leukocytoclastic vasculitis, and direct immunofluorescence showed deposition of IgA and C3 in the vessel walls of the upper dermis. Based on these findings, a diagnosis of IgA vasculitis was made. She was treated with  20 mg/day of  oral prednisolone, which resulted in the complete disappearance of purpura and myalgia. Although the patient needed temporary cessation of nivolumab therapy, she experienced no recurrence of purpura or myalgia, and the dose of prednisolone was gradually tapered to 5 mg/day. Although nivolumab can lead to various immune-related adverse events, vasculitis is rare. To the best of our knowledge, this is the second case of IgA vasculitis during nivolumab therapy.

Spitz nevus is an important differential diagnosis of malignant melanoma, especially in young adults. This case provides a significant information about unusual dermoscopic features of adult Spitz nevus, which may reflect changes over the years. Spitz nevus is an important differential diagnosis of malignant melanoma, especially in young adults. This case provides a significant information about unusual dermoscopic features of adult Spitz nevus, which may reflect changes over the years.

In the past few years, the advancement of 16S rRNA metagenomic analysis sequencing has enabled assessing the impact of gut microbiota on the development of skin disease. Alopecia areata (AA) is a nonscarring hair loss disorder with an unknown etiopathogenesis, however, it is hypothesised that a combination of genetic and environmental factors might be involved. Although numerous studies have shown that the microbiome plays a key role at the beginning of skin diseases, the link between AA and gut dysbiosis remains unclear. To analyse the intestinal microbiome in patients suffering from AA. The study describes the conceivable involvement of gut microbiota in the unclear pathogenesis of AA. We enrolled 25 patients, over 18 years of age with an active state of AA who donated their stool samples. The samples were examined at the human gut microbial community at the species level by metataxonomic analysis of the full-length 16S V3-V4 sequencing. The four major genera that constitute the microbiome's core are Lachnoclostridium, Bifidobacterium, Streptococcus, and Eubacterium, as well as three major phyla: Firmicutes, Proteobacteria, and Actinobacteria. Firmicutes and Proteobacteria are overrepresented in the microflora, which might suggest a disturbed microflora. Furthermore, the composition of bacterial communities suggests a loss of overall richness and a decrease in taxonomic diversity across all samples. This study describes, for the first time, the characteristics of the gut microbiome in AA patients and may provide new insight into the gut microbiome that may play a role in the development of AA.

A 57-year-old Japanese male visited our department with a 16-month history of chronic spontaneous urticaria (CSU) that had been turning for the worse in the last 6 weeks. He was taking oral epinastine, lafutidine, and montelukast. He had a history of renal cell carcinoma and diabetes mellitus. At presentation, urticaria control test (UCT) score was 7, and 7-day urticaria activity score (UAS7) was 28, indicating a severe condition. Serum IgE level was 246 IU/ml. Omalizumab (300 mg) therapy was initiated because his urticaria was intractable. However, he had a fever the day after the first omalizumab administration. Since the polymerase chain reaction (PCR) test was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the patient was hospitalized. On admission, the laboratory test showed normal white blood cell count (5300/µl) and elevated C-reactive protein (2.07 mg/dl) and IgE (507 IU/ml). Treatment with favipiravir (3600 mg on the first day and 1600 mg/day for following 4 days) and dexamethasone (6 mg/day) was started on the second day (Day 2) of admission. As the fever persisted, wheals with strong itch began to appear throughout the body (Figures 1 A, B) even with continuous epinastine, lafutidine, and montelukast. Because of persistent fever, exertional dyspnoea, and interstitial pneumonia identified by computed tomography (Figure 2), nafamostat and antibiotics were also administered. The plasma D-dimer concentration was 7.6 µg/ml at this time. His fever subsided on Day 9, and urticarial symptoms disappeared simultaneously. The D-dimer level was below the detection limit when the patient was discharged on Day 16. His urticaria was well controlled thereafter with epinastine, lafutidine, and montelukast. One month after the discharge, UCT score was 15. Since urticarial symptoms recurred 2 months after recovery from coronavirus disease 2019 (COVID-19) with UCT score 4, omalizumab was resumed, which rapidly improved the UCT score to 13 one month later.In general, CSU can be exacerbated by viral infections. In addition, COVID-19 has been reported to complicate the symptoms of CSU [1]. Urticarial lesions accounted for 8.1–26.6% of cutaneous manifestation of COVID-19 [2]. In particular, it is reported that 10% of COVID-19-associated urticarial eruptions developed before the onset of its classical signs including fever and respiratory symptoms [3]. Furthermore, Kocatürk et al. published data of the patients affected by COVID-19...View full text...