In Japan, the Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with psoriasis since 1982. The aim of this study was to conduct a recent ...epidemiological analysis of the psoriasis patients who were enrolled in the JSPR from 2013 to 2018. A total of 15 287 cases were enrolled from 132 medical institutions, out of which 65.3% (9989 cases) were male and 34.7% (5298 cases) were female. Approximately 50.0% of the cases had past history and comorbidities, such as hypertension (42.0%), dyslipidemia (30.0%), diabetes mellitus (23.7%), hyperuricemia (15.1%), cardiovascular disease (6.0%), and cerebral vascular disorders (6.0%). There was a yearly increase in the use of corticosteroid/vitamin D3 combinations and apremilast for treating psoriasis. In contrast, the use of phototherapy gradually decreased. From 2013 to 2018, approximately 18.6% of the cases were treated with biologics, such as infliximab (17.6%), adalimumab (23.3%), ustekinumab (21.4%), secukinumab (11.6%), ixekizumab (7.6%), brodalumab (6.3%), and guselkumab (4.3%). In the past decade, the biologics have changed the treatment and management of psoriasis. This survey includes significant information regarding the recent perspective of psoriasis in the Japanese Society, especially focusing on the treatment trends after the introduction of biologics.
To determine the characteristics and current status of Japanese patients with psoriatic arthritis, the Japanese Society for Psoriasis Research have started to conduct retrospective questionnaire ...surveys. The results collected from over a thousand patients with psoriatic arthritis have revealed several characteristics. The newly visited psoriatic arthritis patients accounted for approximately 10% of all new psoriatic patients who visited the dermatology department in many referral centers. The prevalence was nearly 15% of psoriatic patients, which was similar to a recent rheumatology and dermatology study in Japan with a large cohort. There was a male predominance. The mean age of onset for cutaneous psoriasis was in the late 30s, while that of arthritis was in the late 40s. If we compare the precedence of cutaneous psoriasis versus arthritis, the psoriasis precedent group accounted for nearly 75%, while arthritis accounted for 5% of cases. The mean duration in patients who developed psoriasis prior to arthritis was over 10 years, while that in patients preceded by arthritis was less than 5 years. According to the Moll and Wright criteria, polyarthritis type was most common, followed by distal interphalangeal type and oligoarthritis type. Biologics were used in over 50% of psoriatic arthritis patients, and TNF inhibitors were currently used in approximately 70% among biologics. Switching to other biologics or discontinuance was seen in 15%. This review shows the current status of psoriatic arthritis in Japan, as well as a comparison of the prevalence among East Asian countries.
Since 1982, the Japanese Society for Psoriasis Research has conducted annual epidemiological surveys of patients with psoriasis. Kawada et al. have reported data for 1982–2001 and Takahashi et al. ...have reported data for 2002–2008. The present study evaluated 9290 psoriatic cases according to age and sex (2009–2012). The male : female ratio was 2.08:1 (6281 male patients 67.6% to 3009 female patients 32.4%). The most prevalent type was psoriasis vulgaris (85.6% of all cases), which was followed by psoriasis arthropathica (6.0%), psoriasis guttate acuta (3.2%), Zumbusch‐type generalized pustular psoriasis (1.8%) and psoriasis erythroderma (1.5%). Psoriasis vulgaris was the most prevalent type for all ages, while psoriasis arthropathica and psoriasis guttate acuta were most prevalent among patients aged less than 65 years. The present survey detected an increased number of cases with comorbid diabetes and/or arthritis symptoms compared with the previous surveys. We found that treatments frequently involved topical corticosteroids (89.7% of cases) and vitamin D3 ointments (78.0% of cases), with a notable increase in the use of vitamin D3 ointments. Systemic treatments were used in 33.3% of cases, including cyclosporin (33.6%), etretinate (19.5%), methotrexate (8.6%), infliximab (11.4%), adalimumab (10.9%) and ustekinumab (6.2%). Phototherapy was used in 30.9% of cases. Although psoralen plus ultraviolet A therapy was the predominant phototherapy during previous studies, the present survey revealed that narrowband ultraviolet B therapy was used in 84.5% of phototherapy‐treated cases. Thus, the present survey revealed major changes in treatment trends.
T helper 17 (Th17) cells express CC chemokine receptor 4 (CCR4) and secrete cytokines such as interleukin-17A (IL-17A) and granulocyte macrophage colony-stimulating factor (GM-CSF), while dendritic ...cells (DCs) produce CC chemokine ligand 22 (CCL22), a CCR4 ligand, upon stimulation with GM-CSF. Th17 cells are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). CCL22 has also been shown to be up-regulated in the synovial tissues of RA patients. Here, we investigated the role of CCR4 in collagen-induced arthritis (CIA), a mouse model of RA. DBA/1J mice efficiently developed CIA as shown by erythema, paw swelling, joint rigidity, and joint destruction. Th17 cells were increased in the arthritic joints and regional lymph nodes (LNs) of CIA mice. A fraction of Th17 cells were also shown to produce GM-CSF. On the other hand, we observed no significant increases of Th2 cells or Treg cells, the T cell subsets also known to express CCR4, in these tissues. We further observed clusters of CCR4-expressing memory Th17 cells and CCL22-producing DCs in the regional LNs of CIA mice, supporting the role of the CCR4-CCL22 axis in the expansion of Th17 cells in the regional LNs. Compound 22, a CCR4 inhibitor, ameliorated the disease severity with reduction of Th17 cells in the arthritic joints and regional LNs and Th17-DC clusters in the regional LNs. We further confirmed that CCR4-deficient mice in the C57BL/6J background were highly resistant to CIA induction compared with wild-type mice. Collectively, CCR4 contributes to the pathogenesis of CIA and may thus represent a new therapeutic target for RA.
Piebaldism is an uncommon autosomal dominantly inherited pigment anomaly characterized by a congenital white forelock and leukoderma on the frontal scalp, forehead, ventral trunk and extremities. It ...is caused by a loss‐of‐function mutation in the KIT gene. Genetic analyses reveal a consistent genotype–phenotype relationship in piebaldism. However, recently reported cases of piebaldism that are milder or severer than genetically expected indicate that other factors, such as a modifier gene of MC1R, influence skin and hair color. The KIT ligand/KIT that triggers the Ras/mitogen‐activated protein kinase signaling pathway play essential functions in the migration, proliferation, survival, melanogenesis and melanosome transfer of the melanocytes. We summarize current research progress in piebaldism and related disorders.
Abstract
Extracellular ATP is known to promote Th17 cell differentiation in the intestinal lamina propria by stimulating CD70+CD11clow dendritic cells (DCs) via P2X receptors (P2XRs). Recent studies ...have also shown that Th17 cells enhance antitumor immunity by directly promoting proliferation of cytotoxic T lymphocytes (CTLs). These finding led us to test a P2XR agonist, αβ-methylene ATP (αβ-ATP), as a mucosal vaccine adjuvant to promote CTL responses through Th17 induction. We demonstrated that (i) CD70+CD11clow DCs were present in the nasal lamina propria and expressed P2X1R, P2X2R and P2X4R; (ii) CD70+CD11clow DCs isolated from the nasal lamina propria enhanced Th17 cell differentiation of cocultured splenic CD4+ T cells upon stimulation with αβ-ATP; (iii) mice intranasally immunized with ovalbumin (OVA) and αβ-ATP had increased OVA-specific Th17 cells and CTLs in the nasal lamina propria and regional lymph nodes; (iv) mice intranasally immunized with OVA and αβ-ATP also had elevated resistance to E.G7-OVA tumor growth compared with those intranasally immunized with OVA alone; (v) suramin, a broad-range inhibitor of P2 receptors, suppressed the increases of OVA-specific Th17 cells and CTLs in mice intranasally immunized with OVA and αβ-ATP; and (vi) suramin also abrogated the enhanced antitumor immunity of mice intranasally immunized with OVA and αβ-ATP against E.G7-OVA. Collectively, αβ-ATP may be a promising mucosal adjuvant that promotes antigen-specific CTL responses via CD70+CD11clow DC-mediated Th17 induction.
Intranasal P2XR agonist enhances anti-tumor immunization
Liver damage affects the prognosis of patients with erythropoietic protoporphyria (EPP). However, there is no radical cure for EPP patients with severe liver damage. This study aims to investigate ...the effectiveness of phlebotomy in patients with severe liver damage. We examined seven patients diagnosed with EPP and liver damage between 2010 and 2020. Of the 7 cases, phlebotomy was performed in 3 cases with severe hepatic disorder, and the improvement effect of hepatic disorder was observed in all cases. In addition, as an additional study, we also investigated the mechanism by which liver damage becomes more severe. Liver biopsy samples were stained with hematoxylin and eosin and immunohistochemistry was used to examine the expression of adenosine triphosphate-binding transporter G2 (ABCG2). Liver biopsies were performed in 3 of 7 patients with EPP. Of these three patients, ABCG2 expression was low in two patients, especially in the protoporphyrin (PP) deposition area. Two patients with reduced ABCG2 expression subsequently developed severe liver damage. However, the causal relationship between the decreased expression of ABCG2 and the exacerbation of liver damage has not been directly proved, and further investigation is required in the future. This study demonstrated the effectiveness of phlebotomy in EPP patients with severe liver damage.
To determine the characteristics of the early phase of psoriatic arthritis (PsA), we conducted a subanalysis of a retrospective survey of Japanese patients. In this study, we enrolled patients with ...early onset within either 2 years or 1 year from onset among the 1282 patients with PsA that had previously been reported. Among the total reported PsA patients, 304 (23.7%) were diagnosed with less than 2 years of onset of joint manifestation. The male : female ratio was 1.9:1, mean age at onset of cutaneous psoriasis 40.2 years, and that of joint manifestation 50.3 years. Age of less than 20 years at cutaneous psoriasis onset was observed in 22 cases, while that at joint manifestation was observed in two cases. Plaque‐type psoriasis accounted for 90.1%, followed by psoriasis erythroderma (3.9%), pustular psoriasis (3.9%), and nail psoriasis (1.3%). Polyarthritis was the most common joint manifestation (32.9%), followed by distal interphalangeal (DIP) type (29.6%), oligoarthritis type (27.3%), and ankylosing spondylitis type (4.9%). Enthesitis was observed in 27.3% and dactylitis in 61.8%. Biologics were used in 168 cases (55.3%). By contrast, 199 patients (15.5%) were diagnosed within 1 year of onset of joint manifestation, among whom polyarthritis was the most common (30.7%). Biologics were used in 50.8%. In conclusion, the present study showed that the frequency of early PsA within 2 years of onset accounted for 23.7%, and those within 1 year of onset was 15.5% among the Japanese patients with PsA. Polyarthritis was the most common in early PsA patients.
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