Tranilast Inhibits TRPV2 and Suppresses Fibrosis Progression and Weight Gain in a NASH Model Mouse.

BACKGROUND/AIM: This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. MATERIALS AND METHODS: C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines. RESULTS: Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels. CONCLUSION: In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.

Disease Control and Treatment Satisfaction in Patients with Chronic Spontaneous Urticaria in Japan.

Background: Chronic spontaneous urticaria (CSU), characterized by the recurrence of pruritic hives and/or angioedema for >6 weeks with no identifiable trigger, has a negative impact on health-related quality of life (HRQoL). Methods: The objective of this web-based cross-sectional study was to evaluate disease control, disease burden, and treatment satisfaction in Japanese adults with CSU using the Urticaria Control Test (UCT), HRQoL outcomes, and the Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9). Results: In total, 529 adults were included in the analysis (59.9% female), with a mean ± standard deviation (SD) in CSU duration of 13.2 ± 13.0 years. Based on UCT scores, two-thirds of patients had poor (score of 0-7; 23.6%) or insufficient (score of 8-11; 43.3%) symptom control, and one-third had good control (score of 12-16; 33.1%). Overall treatment satisfaction was not high, with mean ± SD TSQM-9 scores of 55.5 ± 17.6% for effectiveness, 68.2 ± 18.8% for convenience, and 59.2 ± 18.4% for global satisfaction. No apparent differences in TSQM-9 scores were observed between patients receiving different medications. HRQoL outcomes were worse among patients with poor/insufficient symptom control. Conclusions: Japanese adults with CSU have a high disease burden, and better treatment options are needed to increase treatment satisfaction.

Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Solar urticaria: clinical characteristics, treatment effectiveness, long-term prognosis, and QOL status in 29 patients.

Introduction: Solar urticaria (SU), a relatively rare skin inflammatory and photosensitivity disease, is often resistant to standard urticaria treatment. Quality of life (QOL) among SU patients has not been extensively explored. This study was performed to clarify the clinical features and effectiveness of therapies (e.g., hardening therapy) for SU and to determine QOL among SU patients. Methods: The authors examined the characteristics, treatments, and QOL statuses of 29 Japanese SU patients using medical records and a questionnaire approach. Results: Among 29 patients, H1 antihistamine therapy (H1) was effective in 22 (75.8%) patients. H2 antihistamine therapy (H2) was effective in three of seven (42.9%) patients. Ultraviolet radiation A (UVA) hardening therapy was effective in eight of nine (88.9%) patients. Visible light (VL) hardening therapy was ineffective in three of three patients. In one patient who underwent both UVA and VL hardening therapy, only UVA hardening therapy was effective. In the questionnaire, 18 patients (90%) reported some improvement compared with disease onset (four had complete remission, six had completed treatment although mild symptoms persisted, and eight were receiving treatment with moderate symptoms), whereas two patients reported exacerbation. Patients in complete remission had a mean disease duration of 4 years, whereas patients not in remission had a mean disease duration of 8.8 years. The mean Dermatology Life Quality Index (DLQI) score for the current status was 7.4. There was a correlation between DLQI and symptom/treatment status. However, neither DLQI and action spectra nor DLQI and treatments exhibited significant differences. Discussion: The questionnaire revealed current QOL status and long-term prognosis in SU patients. Compared with disease onset, most patients showed improvement when assessed for this study. Both H1 and H2 should be attempted for all SU patients. UVA hardening therapy may be an option for SU patients with an action spectrum that includes UVA.

Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.

Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment.

Dietary Intervention for Control of Clinical Symptom in Patients with Systemic Metal Allergy: A Single Center Randomized Controlled Clinical Study.

Patients with eczema with a systemic metal allergy, such as nickel (Ni), cobalt (Co), chromium (Cr), and tin (Sn), should pay attention to symptomatic exacerbation by excessive metal intake in food. However, dietary intervention for systemic metal allergy can be difficult. In this study, we evaluated the effect of dietary intervention by a registered dietitian on clinical symptoms in patients with a systemic metal allergy. Forty-four patients with cutaneous symptoms who were diagnosed with a metal allergy were randomly assigned to the dietary intervention group (DI group, n = 29) by a registered dietitian or the control group (C group, n = 15). The DI group was individually instructed by a registered dietitian how to implement a metal-restricted diet and then evaluated 1 month later. Dermatologists treated skin lesions of patients in both groups. Skin symptoms assessed by the Severity Scoring of Atopic Dermatitis (SCORAD) index, blood tests, and urinary metal excretion were evaluated. The DI group showed decreased Ni, Co, Cr, and Sn intake (all P ≤ 0.05), and an improved total SCORAD score, eczema area, erythema, edema/papulation, oozing/crust, excoriation, lichenization and dryness after 1 month of intervention compared with before the intervention (all P ≤ 0.05). However, the C group showed decreased Ni and Sn intake and an improved oozing/crust score (all P < 0.05). It showed the effective reduction of dietary metal intake controls dermatitis due to a metal allergy. In conclusion, dietary intervention by a registered dietitian is effective in improving skin symptoms with a reduction in metal intake.

Novel UV-B Phototherapy With a Light-Emitting Diode Device Prevents Atherosclerosis by Augmenting Regulatory T-Cell Responses in Mice.

BACKGROUND: Ultraviolet B (UV-B) irradiation is an effective treatment for human cutaneous disorders and was shown to reduce experimental atherosclerosis by attenuating immunoinflammatory responses. The aim of this study was to clarify the effect of specific wavelengths of UV-B on atherosclerosis and the underlying mechanisms focusing on immunoinflammatory responses. METHODS AND RESULTS: Based on light-emitting diode technology, we developed novel devices that can emit 282 nm UV-B, which we do not receive from natural sunlight, 301 nm UV-B, and clinically available 312 nm UV-B. We irradiated 6-week-old male atherosclerosis-prone Apoe-/- (apolipoprotein E-deficient) mice with specific wavelengths of UV-B and evaluated atherosclerosis and immunoinflammatory responses by performing histological analysis, flow cytometry, biochemical assays, and liquid chromatography/mass spectrometry-based lipidomics. Irradiation of 282 nm UV-B but not 301 or 312 nm UV-B significantly reduced the development of aortic root atherosclerotic plaques and plaque inflammation. This atheroprotection was associated with specifically augmented immune responses of anti-inflammatory CD4+ Foxp3 (forkhead box P3)+ regulatory T cells in lymphoid tissues, whereas responses of other immune cells were not substantially affected. Analysis of various lipid mediators revealed that 282 nm UV-B markedly increased the ratio of proresolving to proinflammatory lipid mediators in the skin. CONCLUSIONS: We demonstrated that 282 nm UV-B irradiation effectively reduces aortic inflammation and the development of atherosclerosis by systemically augmenting regulatory T-cell responses and modulating the balance between proresolving and proinflammatory lipid mediators in the skin. Our findings indicate that a novel 282 nm UV-B phototherapy could be an attractive approach to treat atherosclerosis.

Effect of lanadelumab on attack frequency and QoL in Japanese patients with hereditary angioedema: Report of five cases.

Lanadelumab, a recombinant human anti-kallikrein monoclonal antibody, is recommended as the first-line option for long-term prophylaxis (LTP) in hereditary angioedema (HAE). However, the efficacy of lanadelumab and its effects on the quality of life (QoL) in Japanese HAE patients using real-world data have not been reported. Herein, we report the outcomes of five HAE patients who were treated with lanadelumab at two Japanese institutions. We retrospectively collected data on attack frequency and on-demand treatment frequency using an angioedema quality of life (AE-QoL) questionnaire. Our data corresponded to five Japanese HAE patients who started lanadelumab treatment: four with HAE due to C1-inhibitor deficiency (HAE-1) and one with HAE with a normal C1-inhibitor (HAE-nC1-INH). Two HAE-1 patients showed a reduction in both attacks and number of on-demand treatments. The other HAE-1 patients had an increase in the number of on-demand treatments, although there was no apparent reduction in attacks. The HAE-nC1-INH patient showed a slight increase in both attacks and number of on-demand treatments. Only one HAE-1 patient discontinued treatment after 1 month owing to side effects, including dizziness and headache. All four who continued treatment showed improved AE-QoL total and domain scores. Therefore, in this study, using real-world data, we demonstrated that lanadelumab reduced attack frequency and improved QoL in Japanese HAE patients.