Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Award type：International academic award (Japan or overseas)  Country：Japan

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/bjd/ljad082

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Authorship：Corresponding author   Language：English  

DOI： 10.1111/1346-8138.16880

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DOI： 10.1111/1346-8138.16726

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DOI： 10.2302/kjm.2023-0008-IR)

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Our Research Group for Rare and Intractable Skin Diseases operates within the Project for Research on Intractable Diseases of the Ministry of Health, Labour, and Welfare of Japan and is conducting research on eight rare intractable skin diseases. Five of these are monogenic disorders (epidermolysis bullosa, congenital ichthyoses, oculocutaneous albinism, pseudoxanthoma elasticum, and hereditary angioedema), and for a sixth [generalized pustular psoriasis (GPP)], genetic predisposing factors are important. This review introduces our activities for raising public awareness of these six intractable hereditary skin diseases and summarizes our recent achievements in clarifying the situation of medical treatments for these diseases in Japan. We note our current progress in elucidating the pathogeneses of these diseases and in developing new treatment methods, and we discuss our progress in establishing clinical practice guidelines. A nationwide survey on epidermolysis bullosa and a clinical survey on congenital ichthyoses are progressing. The Angioedema Activity Score and the Angioedema Quality-of-Life Questionnaire, the latter of which is a quality-of-life evaluation tool, have been established for hereditary angioedema. Registries of patients with oculocutaneous albinism and pseudoxanthoma elasticum have been created, and the registry for the latter has achieved its target of 170 cases. For GPP, the results of our survey on clinical practice were published in 2021. Information regarding all six of these hereditary skin diseases has been disseminated to academic societies, medical professionals, patients, and the general public.

DOI： 10.2302/kjm.2023-0008-IR

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DOI： 10.1093/bjd/ljad207

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DOI： 10.1111/1346-8138.16857

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

DOI： 10.1111/exd.14846

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Darier's disease (DD) is a rare autosomal dominantly inherited disorder. DD patients usually present with widespread keratotic eruptions with itching in the seborrheic regions that are exacerbated by various factors, including heat, sweat, and physical trauma. The SARS-CoV-2 (COVID-19) pandemic has stirred confusion among the medical community, including dermatologists, as this infection has been implicated in various skin conditions. Only a handful of reports have documented DD associated with COVID-19. Here, we report a 30-year-old male with Darier's disease whose symptoms were exacerbated following both COVID-19 vaccination and COVID-19 infection. The patient had noticed slight eruptions 7 years prior, but was not particularly concerned. After COVID-19 vaccination and infection, he had erythematous maculopapular lesions in large areas of the trunk and extremities. The previously reported pathogenic variant c.2255_2257del (p.(Ile752_Tyr753delinsAsn)) in ATP2A2 was detected in the present patient. Oral etretinate greatly improved his DD manifestations. As far as we know, the present patient is the first genetically confirmed DD case who showed both COVID-19 infection- and vaccination-related DD exacerbations independently. We think that the further accumulation of DD cases exacerbated by COVID-19 infection/vaccination is needed to clarify the mechanisms of DD aggravation.

DOI： 10.1111/1346-8138.16725

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/1346-8138.16704

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.16704

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DOI： 10.1111/1346-8138.16707

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DOI： 10.1111/1346-8138.16798

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DOI： 10.1111/1756-185X.14654

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/bjd/ljac036

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Blockade of the secretion of immunoglobulins leads to their accumulation in plasma cells, resulting in condensed immunoglobulins in the rough endoplasmic reticulum of plasma cells, termed Russell bodies. They are sometimes found in lymphoplasmacellular inflammation of the intestinal mucosa and in lymphoid cell malignancies, but only very rarely in skin diseases. Here, we report an 86-year-old female who presented with a lesion with the prominent accumulation of Russell bodies underlying pseudocarcinomatous hyperplasia with fungal infection in the face. Immunohistochemical staining showed the cells containing Russell bodies to be positive for CD138 and the Russell bodies to be positive for immunoglobulin κ and λ light chains. The present case suggests that when inflammatory cell infiltration with abundant round intracellular eosinophilic materials is observed in the dermis, the dermal accumulation of Russell bodies should be considered in cases with reactive pseudocarcinomatous hyperplasia with fungal infection.

DOI： 10.18999/nagjms.85.1.123

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Authorship：Corresponding author   Language：English  

DOI： 10.1111/jdv.18894

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DOI： 10.55563/clinexprheumatol/fnrck0

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DOI： 10.1111/1346-8138.16587

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DOI： 10.1111/1346-8138.16601

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DOI： 10.1684/ejd.2023.4414

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DOI： 10.1016/j.jim.2022.113400

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DOI： 10.1111/cea.14267

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Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with inflammatory myopathies. Since the myositis of anti-ARS-positive patients is characterized by a unique set of non-myopathic manifestations, including interstitial lung disease, mechanic's hands, and arthralgia, the patients are classified as having anti-synthetase syndrome. Autoantibodies have been identified to eight kinds of ARSs. Of the other 12 ARSs, eight are components of the "OJ" multi-synthetase complex. Autoantibodies to the four remaining ARSs (CysARS, ValARS, SerARS, and TrpARS) have not been reported to be present in patients with inflammatory myopathies. In this study, we first screened samples from more than 300 Japanese patients majorly consisting of those with dermatomyositis (DM) by our established in-house ELISA to find autoantibodies against the four ARSs described above. Since sera from two DM patients specifically reacted to CysARS or ValARS, we determined their reactivities by immunoprecipitation (IP) with the corresponding recombinant proteins and IP-Western blotting with cellular extract. One patient had several features found in anti-synthetase syndrome, but the other did not. The clinical differences among the various anti-ARS antibodies should be explored in a future work.

DOI： 10.1016/j.autrev.2022.103204

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Self-healing collodion baby (SHCB), also called "self-improving collodion baby", is a rare mild variant of autosomal recessive congenital ichthyosis and is defined as a collodion baby who shows the nearly complete resolution of scaling within the first 3 months to 1 year of life. However, during the neonatal period, it is not easy to distinguish SHCB from other inflammatory forms of autosomal recessive congenital ichthyosis, such as congenital ichthyosiform erythroderma. Here, we report a case study of two Japanese SHCB patients with compound heterozygous mutations, c.235G>T (p.(Glu79*))/ c.1189C>T (p.(Arg397Cys)) and c.1295A>G (p.(Tyr432Cys))/ c.1138delG (p.(Asp380Thrfs*3)), in CYP4F22, which encodes cytochrome P450, family 4, subfamily F, polypeptide 22 (CYP4F22). Immunohistochemically, inflammation with the strong expression of IL-17C, IL-36γ, and TNF-α was seen in the skin at birth. CYP4F22 is an ultra-long-chain fatty acid (FA) ω-hydroxylase responsible for ω-O-acylceramide (acylceramide) production. Among the epidermal ceramides, acylceramide is a key lipid in maintaining the epidermal permeability barrier function. We found that the levels of ceramides with ω-hydroxy FAs including acylceramides and the levels of protein-bound ceramides were much lower in stratum corneum samples obtained by tape stripping from SHCB patients than in those from their unaffected parents and individuals without SHCB. Additionally, our cell-based enzyme assay revealed that two mutants, p.(Glu79*) and p.(Arg397Cys), had no enzyme activity. Our findings suggest that genetic testing coupled with non-invasive ceramide analyses using tape-stripped stratum corneum samples might be useful for the early and precise diagnosis of congenital ichthyoses, including SHCB.

DOI： 10.1016/j.jlr.2022.100308

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DOI： 10.1111/1346-8138.16618

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In dermatology, biologics that block signaling pathways of TNF-α, IL-4/IL13, IL-17s, and IL-23 are widely used for the treatment of several inflammatory skin diseases, such as atopic dermatitis and psoriasis. They have shown excellent efficacy with an acceptable safety profile. However, these biologics targeting pathogenic cytokines and their receptors could modulate immunological balance, leading to the development of other inflammatory or autoimmune skin diseases in some cases. In this study, we present a patient who suffered pemphigus vegetans and showed an exacerbation of pemphigus foliaceus after secukinumab loading for the treatment of complicated generalized pustular psoriasis and pyoderma gangrenosum.

DOI： 10.1111/1346-8138.16563

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BACKGROUND: Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder whose causative gene is the fatty aldehyde dehydrogenase ALDH3A2 and of which ichthyosis is the major skin symptom. The stratum corneum contains a variety of ceramides, among which ω-O-acylceramides (acylceramides) and protein-bound ceramides are essential for skin permeability barrier formation. OBJECTIVES: To determine the ceramide classes/species responsible for SLS pathogenesis and the enzymes that are impaired in SLS. METHODS: Genomic DNA was collected from peripheral blood samples from an SLS patient and her parents, and whole-genome sequencing and Sanger sequencing were performed. Lipids were extracted from stratum corneum samples from the SLS patient and healthy volunteers and subjected to ceramide profiling via liquid chromatography coupled with tandem mass spectrometry. RESULTS: A duplication (c.55_130dup) and a missense mutation (p.Lys447Glu) were found in the patient's ALDH3A2 gene. The patient had reduced levels of all acylceramide classes, with total acylceramide levels at 25 % of healthy controls. Reductions were also observed for several nonacylated ceramides: ceramides with phytosphingosine or 6-hydroxysphingosine in the long-chain base moiety were reduced to 24 % and 41 % of control levels, respectively, and ceramides with an α-hydroxy fatty acid as the fatty acid moiety were reduced to 29 %. The fatty acid moiety was shortened in many nonacylated ceramide classes. CONCLUSION: These results suggest that reduced acylceramide levels are a primary cause of the ichthyosis symptoms of SLS, but reductions in other ceramide classes may also be involved.

DOI： 10.1016/j.jdermsci.2022.08.003

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DOI： 10.1093/rheumatology/keac170

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Darier disease (DD), also called keratosis follicularis, is an autosomal dominant hereditary keratinization disorder that manifests as keratotic papules with plaques in seborrheic areas. There are no validated curative treatments for DD, with the majority of cases treated symptomatically. We report the efficacy of a topical over-the-counter agent which contains retinyl palmitate, vitamin E, and urea for a patient with DD. A 13-year-old girl had brown papules on her scalp, neck, shoulders, and axillae since entering elementary school. A skin biopsy revealed hyperkeratosis, suprabasal acantholysis, and dyskeratosis manifested as corps ronds and grains in the epidermis. Sanger sequencing found the previously reported heterozygous mutation c.1484C>T in ATP2A2. The application of an over-the-counter topical agent containing retinyl palmitate 2750 μg/g (5000 IU/g), tocopheryl acetate 20 mg/g, urea 200 mg/g, and monoammonium glycyrrhizinate 5 mg/g twice daily for 2 months improved the papules without serious adverse events. Oral or topical aromatic vitamin A analogs (retinoids) are often used to treat DD. However, several adverse events are associated with retinoid treatment, and many patients only undergo their intermittent use or discontinue the treatments. Retinyl palmitate is more stable and has a lower irritative profile than other retinoic acids. When applied topically, however, retinyl palmitate cannot penetrate the skin as well as retinol can. Some reports have noted that vitamin E increases the biological availability of vitamin A and that urea helps mechanical percutaneous drug delivery. Our case suggests that retinyl palmitate has a sufficient therapeutic effect when combined with vitamin E and urea. In conclusion, we propose that topical agents containing retinyl palmitate, vitamin E, and urea might have a satisfactory effect on the skin lesions of DD patients, without the serious risks of adverse events.

DOI： 10.1111/1346-8138.16395

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Language：Japanese   Publisher：WILEY  

DOI： 10.1111/1346-8138.16399

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DOI： 10.1111/1346-8138.16402

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DOI： 10.1111/1346-8138.16348

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient's age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.

DOI： 10.3390/ijms23147791

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NLRP1 (NACHT and leucine-rich repeat-containing protein family, pyrin domain-containing protein 1) is an innate immune sensor that is involved in the formation of inflammasome complexes. NLRP1 hyperactivity has been reported to cause inherited autoinflammatory diseases including familial keratosis lichenoides chronica and NLRP1-associated autoinflammation with arthritis and dyskeratosis. We generated Nlrp1b (the mouse homologue of human NLRP1) gain-of-function knock-in (Nlrp1b KI) mice with UVB irradiation-induced autoinflammatory skin lesions. We demonstrated that UVB irradiation induces IL-1β upregulation and IL-1β-dependent inflammation via caspase-1 activation in these Nlrp1b KI mice. RNA sequencing revealed the upregulation of inflammasome pathway-related genes, keratinocyte stress marker genes, and keratinocyte differentiation marker genes in the Nlrp1b KI mice after UVB irradiation. The skin inflammation and hyperkeratosis from UVB irradiation in the Nlrp1b KI mice were inhibited by both intraperitoneal and subcutaneous administration of anti-IL-1β antibodies before UVB irradiation. UVB irradiation and the IL-1β pathway are important in the pathogenesis of NLRP1-associated autoinflammatory skin lesions.

DOI： 10.3389/fimmu.2022.876390

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DOI： 10.1111/jdv.17890

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

OBJECTIVE: Anti-NOR90 antibodies are usually found in patients with systemic sclerosis (SSc); however, their clinical relevance remains obscure. We developed an enzyme-linked immunosorbent assay (ELISA) for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies. METHODS: Serum samples from 1,252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation. RESULTS: Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, 3 with limited cutaneous SSc, and 1 with Raynaud's disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs. 0/936, P<0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs. 0/528, P<0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the 4 anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and 2 of those 4 had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All 3 of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and 2 of those 3 had cancer or skin lesions observed in SSc. CONCLUSIONS: Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients.

DOI： 10.1093/rheumatology/keab575

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DOI： 10.1111/1346-8138.16277

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DOI： 10.1111/jdv.17752

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Dominant and recessive mutations in the desmosomal cadherin, desmoglein-1 (DSG1), cause the skin diseases palmoplantar keratoderma (PPK) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, respectively. Here, we compare two dominant missense mutations in the DSG1 transmembrane domain (TMD), G557R and G562R, causing PPK (DSG1PPK-TMD) and SAM syndrome (DSG1SAM-TMD), respectively, to determine the differing pathomechanisms of these mutants. Expressing the DSG1TMD mutants in a DSG-null background, we use cellular and biochemical assays to reveal differences in the mechanistic behavior of each mutant. Super resolution microscopy and functional assays showed a failure by both mutants to assemble desmosomes due to reduced membrane trafficking and lipid raft targeting. DSG1SAM-TMD maintained normal expression levels and turnover relative to DSG1WT, but DSG1PPK-TMD lacked stability, leading to increased turnover through lysosomal and proteasomal pathways and reduced expression levels. These results differentiate the underlying pathomechanisms of these disorders, suggesting that DSG1SAM-TMD acts dominant negatively while DSG1PPK-TMD is a loss-of-function mutation causing the milder PPK disease phenotype. These mutants portray the importance of the DSG TMD in desmosome function and suggest that a greater understanding of the desmosomal cadherin TMDs will further our understanding of the role that desmosomes play in epidermal pathophysiology.

DOI： 10.1016/j.jid.2021.07.154

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We read the report by Mecoli et al on the relationship between cancer and anti-Th/To antibodies (AThAs) in patients with systemic sclerosis (SSc) (1). It is interesting that the presence of AThAs was reported to confer a protective effect against cancer development in those patients. However, cancer development in AThA-positive patients was significantly suppressed only within the first 3 years after SSc onset, and there was no significant difference in the number of deceased between the AThA-positive and AThA-negative patients.

DOI： 10.1002/art.41945

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Heterozygous mutations in JAK1 which result in JAK-STAT hyperactivity have been implicated in an autosomal dominant disorder that features multi-organ immune dysregulation. This study identifies another previously unreported heterozygous missense JAK1 mutation, H596D, in an individual with a unique autoinflammatory keratinization disease associated with early-onset liver dysfunction and autism. Using CRISPR-Cas9 gene targeting, we generated mice with an identical Jak1 knock-in missense mutation (Jak1 H595D/+;I596I/+;Y597Y/+ mice) that recapitulated key aspects of the human phenotype. RNA sequencing of samples isolated from the Jak1 H595D/+;I596I/+;Y597Y/+ mice revealed the upregulation of genes associated with the hyperactivation of tyrosine kinases and NF-κB signaling. Interestingly, there was a strong correlation between genes downregulated in Jak1 H595D/+;I596I/+;Y597Y/+ mice and those downregulated in the brain of model mice with 22q11.2 deletion syndrome that showed cognitive and behavioral deficits, such as autism spectrum disorders. Our findings expand the phenotypic spectrum of JAK1-associated disease and underscore how JAK1 dysfunction contributes to this autoinflammatory disorder.

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Publisher：Nishinihon Journal of Dermatology  

DOI： 10.2336/nishinihonhifu.84.418

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Publisher：Nishinihon Journal of Dermatology  

DOI： 10.2336/nishinihonhifu.84.9

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DOI： 10.1016/j.imlet.2021.08.002

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A 55-year-old Japanese man was diagnosed with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which is a newly documented adult-onset autoinflammatory disease caused by somatic UBA1 mutations [1], after four years of symptoms. He had suffered from recurrent fever after the onset of systemic arthralgia, scleritis, periorbital/orbital inflammation, optic perineuritis (A, B, T1-weighted contrast-enhanced magnetic resonance imaging in C and D, arrow in D), and myelodysplastic syndrome.

DOI： 10.1002/art.41775

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DOI： 10.1684/ejd.2021.4138

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DOI： 10.1111/1346-8138.15976

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DOI： 10.1111/jdv.17201

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DOI： 10.1111/1346-8138.15951

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OBJECTIVE: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with idiopathic inflammatory myopathies (IIMs). Anti-OJ antibodies, which recognize multi-enzyme synthetase complexes including isoleucyl-tRNA synthetase (IARS) and lysyl-tRNA synthetase (KARS), are among the anti-ARS antibodies. Although testing antibodies to other ARSs have been used clinically, no validated immunoassays for detecting anti-OJ antibodies are available. We aimed to establish an anti-OJ ELISA. METHODS: Serum samples were collected from 279 patients with IIMs and 22 patients with idiopathic interstitial pneumonia. Sixty-four of the samples that had been confirmed to be negative for anti-OJ by standard immunoprecipitation were used as the negative control, and 12 anti-OJ-positive reference sera were used as the positive control. Antibodies to IARS and KARS were assayed by ELISA using biotinylated recombinant proteins generated by in vitro transcription/translation. RESULTS: The anti-OJ-positive sera strongly reacted with the KARS and IARS recombinant proteins in ELISA. Although all 12 reference sera were positive in the anti-KARS ELISA, 4 of the 64 anti-OJ-negative sera were also weakly positive. The sensitivity and the specificity were 100% and 93.8%, respectively. Since our anti-KARS ELISA performed well, showing a high agreement with the results for immunoprecipitation (Cohen's κ > 0.8), the remaining 237 samples were also tested. Thirteen anti-KARS-positive sera were newly found by ELISA, all of which were anti-OJ positive by immunoprecipitation. CONCLUSION: Immunoassays for detecting anti-OJ antibodies using KARS and IARS recombinant proteins were developed. Our ELISAs performed well, with very high agreement of the results by immunoprecipitation and can be applied to the first reliable, easy-to-use measurement assays for anti-OJ antibodies.

DOI： 10.1016/j.jaut.2021.102680

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DOI： 10.1016/j.jdermsci.2021.06.002

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2340/00015555-3844

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Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

DOI： 10.1038/s41598-021-91345-6

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Revertant mosaicism, or "natural gene therapy," refers to the spontaneous in vivo reversion of an inherited mutation in a somatic cell. Only approximately 50 human genetic disorders exhibit revertant mosaicism, implicating a distinctive role played by mutant proteins in somatic correction of a pathogenic germline mutation. However, the process by which mutant proteins induce somatic genetic reversion in these diseases remains unknown. Here we show that heterozygous pathogenic CARD14 mutations causing autoinflammatory skin diseases, including psoriasis and pityriasis rubra pilaris, are repaired mainly via homologous recombination. Rather than altering the DNA damage response to exogenous stimuli, such as X-irradiation or etoposide treatment, mutant CARD14 increased DNA double-strand breaks under conditions of replication stress. Furthermore, mutant CARD14 suppressed new origin firings without promoting crossover events in the replication stress state. Together, these results suggest that mutant CARD14 alters the replication stress response and preferentially drives break-induced replication (BIR), which is generally suppressed in eukaryotes. Our results highlight the involvement of BIR in reversion events, thus revealing a previously undescribed role of BIR that could potentially be exploited to develop therapeutics for currently intractable genetic diseases.

DOI： 10.1016/j.ajhg.2021.04.021

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DOI： 10.1016/j.jid.2020.09.035

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DOI： 10.1016/j.jaad.2020.07.131

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DOI： 10.1111/jdv.17098

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DOI： 10.1016/j.jdermsci.2021.03.003

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Basal cell nevus syndrome (BCNS) is an autosomal dominant skin disorder characterized by multiple basal cell nevi. Patients with BCNS tend to develop basal cell carcinoma (BCC) and frequently show skeletal abnormalities. Most cases of BCNS are caused by mutations in patched 1 (PTCH1). PTCH1 encodes a transmembrane receptor protein for the secreted molecule sonic hedgehog, which plays a key role in the development of animals ranging from insects to mammals. We analyzed two Japanese BCNS patients from two independent families. Both of our patients had multiple jaw keratocysts. In one patient, these were the key to noticing his BCNS, as he had no skin tumors. The early detection of PTCH1 mutations would enable BCNS patients to be carefully followed up for the occurrence of BCC. The diagnosis of BCC at the early stage leads to prompt surgical treatments, resulting in a good prognosis. The present cases suggest that keratocysts of the jaw might be an important clue for diagnosing BCNS.

DOI： 10.18999/nagjms.83.2.393

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DOI： 10.1111/1346-8138.15795

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DOI： 10.1111/1346-8138.15777

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Dermal extramedullary hematopoiesis (EMH) is seen as a normal process from the first to the fifth month of gestation, and it is a process in which undifferentiated dermal mesenchymal cells retain their hematopoietic potential.1 However, after sixth months of gestation, hematopoiesis does not occur in the dermis except in a few conditions, such as in myeloproliferative disorders.1-3.

DOI： 10.1111/jdv.16990

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Language：Japanese   Publisher：JOHN WILEY & SONS LTD  

Systemic sclerosis (SSc) is a multi-system autoimmune disease. Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against enzymes found within primary granules of neutrophils and lysosomes in monocytes. Although up to 12% of SSc patients have ANCA, only a minority of these patients develop an overlap syndrome with ANCA-associated vasculitis. We summarize previous reports on SSc patients with ANCA-associated neuropathy. In all the reported cases, the SSc diagnosis preceded the ANCA-associated neuropathy diagnosis. Seven of the eight patients with limited cutaneous SSc had interstitial lung disease (ILD). Thus, patients with ANCA-associated neuropathy in lSSc may be prone to complication with ILD.

DOI： 10.1002/cia2.12153

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.2340/00015555-3764

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：JOHN LIBBEY EUROTEXT LTD  

DOI： 10.1684/ejd.2021.4017

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

A 55-year-old man who had been diagnosed with autoimmune pancreatitis five years earlier was referred to our department because of finger swelling, finger stiffness and the presence of interstitial lung disease (ILD). The patient was diagnosed with Sjögren's syndrome according to the pathological findings of minor salivary glands and positive anti-SS-A antibodies. Later, at age 58, he was hospitalised due to the exacerbation of the ILD. Serum IgG4 level was checked and was found to be elevated (417 mg/dL). After the introduction of cyclosporine in addition to the prednisolone, at age 60, the ILD disease activity stabilised. However, at age 62, fever, myalgia and mechanic's hands appeared. His serum creatine kinase level was high, and magnetic resonance imaging showed inflammatory findings of muscle. In-house ELISA clarified that his serum carried anti-PL-7 antibody among anti-aminoacyl-tRNA synthetase antibodies. This is a unique case who had overlapping features of IgG4-related autoimmune pancreatitis, Sjögren's syndrome and anti-synthetase syndrome. Although the aetiology of the complications in this patient is obscure, autoimmunity might have played a significant role in the disease conditions and prognosis of the present case with IgG4-related disease.

DOI： 10.1080/24725625.2020.1816675

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Caspase recruitment domain family member 14 (CARD14) is an activator of nuclear factor kappa-light-chain-enhancer in activated B cells (NF-κB) and contributes to inflammatory responses within the epidermis. CARD14 mutations are associated with autoinflammatory keratinization diseases, such as psoriasis and familial pityriasis rubra pilaris (PRP). Recently, Craiglow et al. proposed CARD14-associated papulosquamous eruption (CAPE), a spectrum that includes clinical features of psoriasis and PRP. Characteristic features of patients with CAPE include early onset, prominent facial involvement, and favorable response to ustekinumab therapy. Here, we describe a unique CAPE patient with atopic dermatitis (AD)-like features and extend the spectrum of CAPE.

DOI： 10.1111/jdv.16799

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DOI： 10.1111/1346-8138.15645

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Language：Japanese   Publisher：WILEY  

DOI： 10.1111/1346-8138.15612

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1684/ejd.2020.3956

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Language：Japanese   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.jdermsci.2020.05.001

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OBJECTIVES: The myositis-specific autoantibodies that characterise certain forms of idiopathic inflammatory myopathy (IIM) are useful for diagnosing dermatomyositis (DM) / polymyositis (PM) and predicting its prognosis. The autoantibody to phenylalanyl-tRNA synthetase (anti-Zo) has been identified as a disease marker antibody for anti-synthetase syndrome only in a UK cohort. Here we aim to establish an ELISA for the measurement of anti-Zo and to characterise the clinical features of Japanese patients who have this autoantibody. METHODS: Anti-Zo was investigated by immunoprecipitation with recombinant phenylalanyl-tRNA synthetase α/β proteins. The results were confirmed by immunoprecipitation-Western blotting with cell extract. Sera from patients with DM/PM (n=224) were screened by an ELISA with the recombinant proteins. Medical records were retrospectively reviewed to obtain detailed information on the clinical phenotypes of the anti-Zo-positive patients. RESULTS: Only two male patients were confirmed to have anti-Zo. Both patients had fever, myopathy, interstitial lung disease, and mechanic's hands, and these clinical features are consistent with those of anti-synthetase syndrome. Another patient's serum showed a higher level than the cut-off value for anti-phenylalanyl-tRNA synthetase α by our in-house ELISA, but was judged to be negative for anti-Zo by immunoprecipitation-Western blotting. CONCLUSIONS: This is the first report of anti-Zo-positive IIM patients from Asia. Although Japanese patients with anti-Zo have a clinical phenotype similar to that of Caucasian patients, further large cohort studies are necessary to confirm the frequency of anti-Zo in Japanese IIM patients. Our newly developed ELISA should be validated for sensitivity and specificity in large cohorts.

DOI： 10.55563/clinexprheumatol/q70vmh

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DOI： 10.1111/1346-8138.15525

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER MEDICAL ASSOC  

This nonrandomized clinical trial evaluates the association of topical minoxidil with hypotrichosis in patients with autosomal recessive woolly hair/hypotrichosis carrying LIPH pathogenic variants.

DOI： 10.1001/jamadermatol.2020.2195

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Language：English   Publisher：JOHN WILEY & SONS LTD  

During the COVID-19 pandemic, clinicians are facing a difficult but important question: Should we try to reduce immunosuppressant use or postpone immunosuppressant therapies for newly diagnosed autoimmune disease patients with mild to moderate symptoms? We would like to alert your readership that although potential chronic inflammation itself is not always critical, it can trigger a hyper-inflammatory condition in patients who become infected with COVID-19. We should be careful when reducing immunosuppressant use.

DOI： 10.1002/cia2.12132

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DOI： 10.1016/j.jdermsci.2020.08.008

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DOI： 10.1111/1346-8138.15513

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BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

DOI： 10.1097/MD.0000000000022043

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DOI： 10.1111/1346-8138.15476

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Publisher：Journal of Cutaneous Immunology and Allergy  

DOI： 10.1002/cia2.12122

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：JOHN LIBBEY EUROTEXT LTD  

DOI： 10.1684/ejd.2020.3812

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACTA DERMATO-VENEREOLOGICA  

DOI： 10.2340/00015555-3570

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Language：Japanese   Publisher：ELSEVIER IRELAND LTD  

© 2020 Japanese Society for Investigative Dermatology Among the components of the barrier structure of the stratum corneum in human skin, the corneocyte lipid envelope (CLE) is extremely important for the skin barrier. The importance of the CLE and esterified ω-hydroxy sphingosine (CerEOS), its main precursor, has been suggested from the fact that mutations in a number of genes involved in CerEOS synthesis and CLE formation have been identified as genetic causes of congenital ichthyoses, which are severe genetic skin disorders. However, the molecule/mechanism involved in the covalent binding of CerEOS to proteins on the outer surface of the cornified cell envelope had been a missing part. Very recently, we proposed new potential modes of protein binding by covalent reactions of CerEOS-epoxy-enone. We revealed the biochemical function of short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), encoded by SDR9C7, as catalyzing the dehydrogenation of the lipoxygenase products that are esterified in CerEOS. Epoxy-enone produced by SDR9C7 covalently binds to proteins on the outer extracellular surface of the cornified cell envelope. Importantly, our recent striking findings were derived from the detailed lipid analysis of only one ARCI patient with SDR9C7 mutation. The combination of detailed analyses of precious samples from a rare patient and the establishment of corresponding animal models is an effective and powerful tool for analyzing rare inherited diseases. This review summarizes this newly revealed mechanism in skin barrier formation, describes the characteristic features of patients with SDR9C7 mutations, and introduces the clinical value of non-invasive analyses for patients with very rare intractable skin diseases.

DOI： 10.1016/j.jdermsci.2020.03.005

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：FRONTIERS MEDIA SA  

© Copyright © 2020 Takeichi and Akiyama. Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is a rare autosomal recessive skin disorder characterized by palmoplantar keratoderma, linear hyperkeratotic plaques, ichthyosiform scaling, circular constrictions around the fingers, and numerous papules distributed linearly in the arm folds and on the wrists. Histologically, the affected skin shows hypertrophy and hyperplasia of the spinous, granular, and horny epidermal layers with mild infiltration of inflammatory cells in the upper dermis. There are 14 patients with KLICK syndrome described in the literature, and they all carry the same nucleotide deletion. Proteasome maturation protein (POMP), encoded by POMP, is an ubiquitously expressed protein that functions as a chaperone for proteasome maturation. KLICK syndrome is caused by a reduction in POMP levels that leads to proteasome insufficiency in differentiating keratinocytes. It is noteworthy that POMP is also known to be the causative gene for proteasome-associated autoinflammatory syndrome-2 (PRAAS2). It is considered that the disrupted proteasome assembly caused by the POMP mutation might lead to both skin inflammation and then hyperkeratosis in KLICK syndrome. Inflammation caused by the hyperactivation of innate immunity occasionally leads to inflammatory diseases of the skin, recently denoted as autoinflammatory keratinization diseases (AiKDs). We propose that KLICK syndrome caused by the specific 1-bp nucleotide deletion mutation in the regulatory region of POMP might be in a spectrum of proteasome-associated phenotypes.

DOI： 10.3389/fimmu.2020.00641

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Extramammary Paget’s disease (EMPD) is a neoplastic skin disease of indeterminate origin with an unknown genetic cause. We performed a comprehensive genetic analysis or targeted gene sequencing in 48 patients with EMPD. We identified FOXA1 mutations, a GAS6–FOXA1 fusion gene, and somatic hotspot mutations in the FOXA1 promoter region in 11 of the 48 EMPD patients (11/48, 23%). Additional mutations were identified in PIK3CA (six patients) and in HIST1H2BB, HIST1H2BC, and SMARCB1 (one patient each), but none were found in other frequently mutated genes in cancer. A global gene expression analysis using EMPD clinical samples found the upregulation of PI3 kinase–AKT–mTOR signaling. ABCC11, which is specifically expressed in the apocrine secretory cells and is necessary for their sweat secretion, was upregulated in the EMPD samples. This upregulation suggests that Paget cells originate from apocrine secretory cells. Immunohistochemical staining revealed that FOXA1 expression was prevalent in all of the EMPD samples analyzed and was associated with estrogen receptor expression. Our genetic analysis indicates that EMPD frequently involves FOXA1 mutations. FOXA1 is a transcriptional pioneer factor for the estrogen receptor, and the present results suggest that certain treatments for hormone-dependent cancers could be effective for EMPD.

DOI： 10.3390/cancers12040820

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© 2019, Springer Nature Switzerland AG. Generalized pustular psoriasis (GPP) is a chronic, systemic inflammatory disease accompanied by high fever and general malaise. Diffuse erythema and swelling of the extremities occur, with multiple sterile pustules all over the body in GPP patients. GPP often relapses over the lifetime and can be life-threatening. Recent discoveries of the underlying molecular genetic basis of many cases of this disorder have provided major advances to clinicians and researchers towards an understanding of the pathomechanism of GPP. However, the therapeutic management of GPP still faces many challenges and much uncertainty, and an evidence-based review summarizing the available clinical data on the management of this heterogeneous disease is needed. The present review addresses challenges regarding the precise clinical diagnosis and evaluation of clinical symptoms in GPP. In addition, we update and briefly summarize the current understanding of molecular pathomechanisms behind GPP as an autoinflammatory keratinization disease. Recent publications have clarified the genetic backgrounds of patients with GPP and ethnic differences in predisposing factors. Although there are ethnic differences in the prevalences of these pathogenic alleles, from recent reports, at most 60.5% (IL36RN), 5.9% (CARD14), and 10.8% (AP1S3) of GPP patients have the mutations/variations of these genes. All the reported biologics studied seemed effective and relatively well tolerated. Although it is difficult to evaluate therapeutic efficacy from studies on just a few cases, recent findings suggest that biologics can be a useful, powerful tool for controlling skin and systemic inflammation in GPP and for improving the quality of life of GPP patients.

DOI： 10.1007/s40257-019-00492-0

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DOI： 10.1111/1346-8138.15210

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DOI： 10.1111/1346-8138.15228

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1684/ejd.2019.3681

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Language：Japanese   Publishing type：Research paper (scientific journal)  

© 2020, American Society for Clinical Investigation. The corneocyte lipid envelope, composed of covalently bound ceramides and fatty acids, is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7-/- epidermis, quantitative liquid chromatography-mass spectometry (LC-MS) assays revealed almost complete loss of a species of ω-Oacylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy- 11E-13-ketone, a reactive moiety known for its nonenzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis.

DOI： 10.1172/JCI130675

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DOI： 10.1111/bjd.18445

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Language：Japanese   Publishing type：Research paper (scientific journal)  

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin-and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.

DOI： 10.3390/ijms21030913

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DOI： 10.1111/ced.13938

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DOI： 10.1111/bjd.18343

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DOI： 10.1111/1346-8138.15110

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DOI： 10.1111/jdv.15892

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Language：Japanese   Publishing type：Research paper (scientific journal)  

© 2019 Japanese Society for Investigative Dermatology Background: NIPAL4, encoding the NIPA-like domain containing 4 protein (NIPAL4), is one of the causative genes of autosomal recessive congenital ichthyosis (ARCI). The physiological role of NIPAL4 and the pathogenetic mechanisms of ARCI caused by NIPAL4 mutations remain unclear. Objective: To clarify the changes of ceramide components in the lesional stratum corneum (SC) and the gene expression profile in the lesional skin of an ARCI patient with a novel frameshift mutation in NIPAL4. Methods: We performed ultrastructural and immunohistochemical analyses of the skin. We used RNA sequencing to determine the mRNA expression in the skin of the patient and healthy individuals. We investigated ceramide components using tape stripped SC samples from the patient. Results: mRNA expression profiling in the patient's skin showed significant upregulation of IL-17/TNFα-related genes (IL17C, IL36A, IL36G, S100A7A, S100A9) and psoriasis hallmark genes (VNN3, LCE3D, PLA2G4D), and significant downregulation of lipid-associated genes (GAL, HAO2, FABP7). Ceramide analysis in the patient's SC revealed amounts of CER[NS] with carbon chain-length (C) 32–52 were increased, while amounts of most acylceramide with C66:2 - C72:2 were reduced relatively to those in healthy individuals. After the retinoid treatment, CER[NS] with carbon chains C46–54, CER[EOH] and CER[EOP] increased. Conclusion: IL-17C and IL-36 family cytokines might be involved in the pathogenetic process of ARCI with NIPAL4 mutations. Reduced amounts of the acylceramides in the SC are associated with the skin phenotype due to NIPAL4 mutations. Efficacy of the oral retinoid treatment might be due to restored amounts of CER[EOH] and CER[EOP] in the SC.

DOI： 10.1016/j.jdermsci.2019.12.001

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1684/ejd.2020.3868

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：ACTA DERMATO-VENEREOLOGICA  

DOI： 10.2340/00015555-3277

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DOI： 10.1111/ced.13979

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DOI： 10.1111/1346-8138.14905

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DOI： 10.1111/1346-8138.14748

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DOI： 10.1111/1346-8138.14777

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DOI： 10.1111/bjd.17405

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DOI： 10.1016/j.jaci.2018.11.044

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DOI： 10.1111/1346-8138.14666

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DOI： 10.1111/1346-8138.14626

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Authorship：Lead author   Language：Japanese   Publisher：Journal of Cutaneous Immunology and Allergy  

Psoriasis is a common skin disorder that is characterized by hyperkeratosis, epidermal hyperplasia, T-cell and neutrophil recruitment, and changes in the vascular endothelial system. The several upregulated variable lipid mediators, including the eicosanoids, in psoriatic keratinocytes were described previously, although some results were contradictory. Since hepoxilin is less stable than other eicosanoids such as hydroxyeicosatetraenoic acid (HETE), the measurement of hepoxilin is difficult. In this study, to clarify the relationship between hepoxilin/hepoxilin-related fatty acid derivatives and psoriasis vulgaris, we evaluated the amount of production of lipid mediators including hepoxilins in skin tissues of patients with psoriasis vulgaris in comparison with normal controls by high-performance liquid chromatography/mass spectrometry. Most of the hepoxilins and related lipids evaluated in this study tended to be more abundant in the lesional skin from the psoriasis patient group (PPG) than in the skin from controls. Interestingly, 12R-HETE was markedly higher in the skin samples from the PPG. In addition, the lipids produced in the lipoxygenase pathway, including hepoxilin, were elevated in the skin lesions of the PPG compared with those of normal controls, whereas the lipids produced in the cyclooxygenase pathway were decreased in the skin lesions from the PPG. Our results suggest that an imbalance between the lipoxygenase and cyclooxygenase pathways may contribute to psoriatic pathomechanisms.

DOI： 10.1002/cia2.12039

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DOI： 10.2336/nishinihonhifu.81.382

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A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

DOI： 10.11406/rinketsu.60.1641

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.

DOI： 10.1194/jlr.P087536

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DOI： 10.1111/bjd.16823

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DOI： 10.1111/jdv.15004

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DOI： 10.1111/1346-8138.14350

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in patients. However, the effects of CIs on patient QOL have not been studied sufficiently. OBJECTIVE: To investigate the association between disease severity and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic forms (ISFs) METHODS: Clinical information of patients with HI and ISFs from 2010 to 2015 were obtained from 100 dermatology departments/divisions of principal institutes/hospitals throughout Japan. We examined the relationship between disease severity and QOL in patients with HI and ISFs. Patients who were aged 8 years or older and participated in a multicenter retrospective questionnaire survey in Japan were assessed by dermatology life quality index (DLQI, range of 0-30) and clinical ichthyosis score (range of 0-100). RESULTS: Netherton syndrome patients had a significantly higher risk of allergy to food or environmental allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness (KID) syndrome patients showed a significantly higher risk of skin infections than patients with other phenotypes. Complete data on DLQI were obtained from 13 patients, whose median age was 21 (8-71) years. Nine patients were male, and 4 were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The Spearman's correlation coefficient between the clinical ichthyosis score and DLQI was 0.611 (P < 0.05). CONCLUSION: We confirmed that Netherton syndrome and KID syndrome patients have a higher risk of allergy to food or environmental allergens and of skin infections, respectively. QOL impairment correlates with disease severity in HI and ISFs patients.

DOI： 10.1016/j.jdermsci.2018.08.008

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DOI： 10.1111/bjd.16895

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DOI： 10.1111/1346-8138.14330

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DOI： 10.1111/jdv.15076

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DOI： 10.1038/s41598-018-30757-3

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DOI： 10.1111/bjd.16610

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DOI： 10.1111/bjd.16712

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DOI： 10.1111/bjd.16375

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Dyschromatosis symmetrica hereditaria (DSH) is one of the genetic pigmentation disorders and shows characteristic mixture of hyper- and hypo-pigmented small macules on the extremities. Heterozygous mutations in the adenosine deaminase acting on RNA1 gene (ADAR1) cause DSH. In the present study, we report five cases of DSH and identify a distinct known mutation in each patient. Furthermore, we review previously described cases with the five ADAR1 mutations found in the present study. We reviewed clinical and molecular findings in the present and previously reported cases and found an identical mutation can result in various phenotypic severities, even in one family. We found novel phenotype-genotype correlations between the presence/absence of facial lesions and the ADAR1 mutation c.3286C>T. The absence of freckle-like macules in the face was found to be more commonly associated with the mutation c.3286C>T than with the other 4 ADAR1 mutations (odds ratio = 0.056 [95% CI: 0.007-0.47, p < 0.005]). We objectively evaluated the severity of skin manifestations in the extremities using our definition of severity levels for such manifestations. This is the first semi-quantitative evaluation of skin manifestations in DSH. Using our definition, we found that patients with facial lesions with or without hypopigmented macules tend to show more severe symptoms on the extremities than patients without facials lesions show. Furthermore, no significant difference in the severity of the skin lesions was observed between the upper and the lower extremities, suggesting that sun exposure does not affect significantly the pathogenesis of DSH skin lesions.

DOI： 10.18999/nagjms.80.2.267

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DOI： 10.1016/j.jid.2018.03.264

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DOI： 10.1111/1346-8138.14307

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DOI： 10.1016/j.jdermsci.2018.01.017

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DOI： 10.1016/j.jdermsci.2018.01.012

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DOI： 10.1111/bjd.15869

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DOI： 10.1111/1346-8138.13851

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

DOI： 10.1111/jdv.14531

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DOI： 10.1111/1346-8138.14241

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

DOI： 10.1111/jdv.14439

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DOI： 10.1684/ejd.2018.3259

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DOI： 10.1684/ejd.2018.3313

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DOI： 10.1684/ejd.2018.3415

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© 2017 British Association of Dermatologists Patients with deficiency of interleukin-36 receptor antagonist (DITRA), due to mutation of IL36RN, exhibit psoriatic phenotypes, typically generalized pustular psoriasis (GPP). We report a paediatric patient with DITRA, whose cutaneous lesions varied from psoriasis vulgaris in infancy to annular pustular psoriasis with acute exacerbation to GPP at 13 years of age. Conventional systemic treatments for GPP, which include oral retinoids, ciclosporin and methotrexate, are controversial in paediatric cases, because of their adverse effects and uncertain long-term consequences. Granulocyte monocyte apheresis, a process associated with few adverse events, promptly controlled the GPP of our paediatric patient, and has potential as a suitable alternative treatment for paediatric patients with DITRA.

DOI： 10.1111/bjd.15509

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Adult-onset Still's disease (AOSD) is characterized by multiple systemic inflammation of unknown etiology. Although the typical eruption of AOSD is salmon-pink rheumatoid rash on the trunk and extremities, persistent pruritic papules and plaques have also been reported. Correlations between serum cytokines, including interleukin-6 and -18, and disease activity in AOSD have been reported. Activated signal transducer and activator of transcription 3 (STAT3) is transported into the nucleus, where it functions as a transcription factor that regulates genes involved in cell survival and inflammation. To assess whether STAT3 was phosphorylated in skin samples from AOSD patients, we conducted immunohistochemical analysis of affected and unaffected lesions from four AOSD patients in comparison with 10 normal controls. Quantitative analysis was conducted by measuring the ratio of epidermal keratinocytes with phosphorylated STAT3 (p-STAT3)-positive nuclei to total epidermal keratinocytes. p-STAT3 was found to be more strongly expressed in the nuclei in the epidermis of AOSD than in normal controls. Quantification of the data revealed significant differences in staining for p-STAT3 between AOSD and normal skin. Our findings suggest that phosphorylation of STAT3 may be a potential therapeutic target for AOSD.

DOI： 10.1111/1346-8138.13888

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DOI： 10.1111/bjd.15442

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is missing (Short communication).

DOI： 10.2340/00015555-2729

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DOI： 10.1016/j.jdermsci.2017.05.012

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DOI： 10.1016/j.jid.2017.04.036

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DOI： 10.1111/bjd.15315

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DOI： 10.1111/bjd.15070

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DOI： 10.2340/00015555-2549

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DOI： 10.1111/jdv.13906

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DOI： 10.1684/ejd.2016.2920

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DOI： 10.2340/00015555-2553

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

DOI： 10.1111/bjd.14845

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/jdv.13877

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DOI： 10.2340/00015555-2501

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DOI： 10.1001/jamadermatol.2016.3601.

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DOI： 10.1684/ejd.2017.3049

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DOI： 10.1371/journal.pgen.1004276

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Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：加齢皮膚医学研究会  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：加齢皮膚医学研究会  

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Language：Japanese   Publisher：日本小児皮膚科学会  

7歳男児。1歳頃より嗄声に気づき、6歳時に近医耳鼻科受診。声帯の結節性病変を指摘され、その後病理所見から慢性喉頭炎および軽度〜中等度異形成と診断された。7歳頃より両上眼瞼に白色を帯びた、直径約1mmの平滑な丘疹が数珠状に多数並ぶようになり、当科紹介受診。初診時、舌にも白色斑がみられた。眼瞼皮疹の病理では真皮乳頭に好酸性無構造物質が沈着していた。歯牙の異常なし。両親、妹弟に同症状はない。Extracellular matrix protein 1(ECM1)をコードするECM1遺伝子にホモ接合性c.879G>A変異あり、lipoid proteinosis(LP:リポイドタンパク症)と診断した。父親にはヘテロ接合性に同遺伝子変異があり、母親は野生型であった。3年間経過観察したところ、両頬粘膜に萎縮性白色斑が新たに出現した。本症は稀な疾患で特に小児例の報告は少ないことからその皮膚粘膜症状について報告する。(著者抄録)

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(一社)日本小児神経学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント ・Conradi-Huenermann-Happle(CHH)症候群は遺伝学的検査だけでなく,ステロール解析を行うことで,より正確な診断につながる.・CHH症候群の遺伝カウンセリングでは,X連鎖優性(顕性)の遺伝形式をとることに注意し,個々の症例に合わせたフォローが必要である.

Language：Japanese   Publisher：(公社)日本整形外科学会  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

乳房外パジェット病(EMPD)患者を集積し、包括的な遺伝子解析を行ったところ、EMPD全症例においてパジェット細胞の核にFOXA1が強く発現していることが分かった。EMPD細胞におけるFOXA1の高発現はホルモン依存性の癌でみられるような細胞増殖や生存を引き起こす可能性がある。EMPDにおけるFOXA1変異の頻度は乳癌に比較して高いため、FOXA1の発現異常に対する分子標的治療法の開発が期待される。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20220311230005&doc_link_id=1390573242795193088&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390573242795193088&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

Language：Japanese   Publisher：加齢皮膚医学研究会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)学研メディカル秀潤社  

Language：Japanese   Publisher：加齢皮膚医学研究会  

Language：Japanese   Publisher：(株)学研メディカル秀潤社  

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Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント ・膿疱性乾癬の初期症状として掌蹠膿疱症の臨床所見を呈し,グセルクマブが奏効した.・掌蹠膿疱症と膿疱性乾癬は類縁疾患と示唆された.

Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント ・膿疱性乾癬の初期症状として掌蹠膿疱症の臨床所見を呈し,グセルクマブが奏効した.・掌蹠膿疱症と膿疱性乾癬は類縁疾患と示唆された.

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01268&link_issn=&doc_id=20210428580014&doc_link_id=20210727480027&url=http%3A%2F%2Fsearch.jamas.or.jp%2Flink%2Fbc%2F20210727480027&type=jamaslink&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F99999_1.gif

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞角質細胞脂質エンベロープ(corneocyte lipid envelope:CLE)がしっかりと機能することで,蛋白質と脂質という異質な成分をつなぎ,強固な皮膚バリアを維持することができる.CLE形成に関わる分子をコードする遺伝子の変異により,皮膚バリア機能異常の代表的な疾患である先天性魚鱗癬が引き起こされる.CLEは結合型セラミドを主成分とするが,そのセラミドがCLEを形成する際に周辺帯蛋白質と結合するメカニズムは,これまで不明であった.われわれは,先天性魚鱗癬の原因遺伝子の1つのSDR9C7にコードされるSDR9C7が産生する,ケトン体の脂肪酸を持つアシルセラミドが,特定の酵素反応を必要とせずに周辺帯蛋白質と結合することを明らかにした.魚鱗癬患者が有する変異型SDR9C7の機能障害がCLEの形成不全をきたし,魚鱗癬を発症すると考えられる.SDR9C7を標的とした新規治療法の開発が期待される.

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：日本皮膚科学会-大阪地方会・京滋地方会  

Language：Japanese   Publisher：日本皮膚科学会-大阪地方会・京滋地方会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publishing type：Meeting report   Publisher：(公社)日本皮膚科学会  

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Language：Japanese   Publisher：(株)北隆館  

遺伝性角化症の病因遺伝子変異の解明は、次世代シークエンシング技術の登場により新たな局面を迎えている。全エクソームシークエンシングによる網羅的遺伝子変異検索法は、遺伝子診断の効率を向上させ、同時に、各々の遺伝性角化症患者の病状に合わせた、いわゆるオーダーメイド治療に繋がる多くの発見をもたらした。本稿では、近年蓄積された遺伝性角化症に関する新しい知見やエビデンスを基に、個々の遺伝性角化症症例に最適な医療を届けるための道筋を、いくつかの疾患群に焦点を絞り、今後の方向性も含めて概説する。(著者抄録)

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公財)上原記念生命科学財団  

Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

骨髄移植後に再発した骨髄異形成関連変化を伴う急性骨髄性白血病患者(47歳,男性)に臍帯血移植を実施した。生着前に広域抗菌薬不応の発熱性好中球減少症および全身性の有痛性結節が出現した。皮膚生検と血液培養で糸状菌を認め真菌血症と診断,さらに培養コロニーの検鏡,質量分析,塩基配列決定からFusarium solaniによる播種性感染症と確定診断した。Liposomal amphotericin B(L-AMB)5mg/kg/日の投与により熱型と皮疹は改善し始めた。Day19に生着し,皮膚急性移植片対宿主病stage3は外用ステロイド剤で寛解した。Day38にvoriconazoleへ変更したところFusarium感染症は増悪した。その後はL-AMB計19週間の投与で治癒した。生着前の播種性Fusarium感染症は極めて予後不良である。本症例では,好中球の生着に加え,速やかな確定診断,適切な抗真菌薬の選択,その十分量かつ長期間の投与,ステロイド剤全身投与回避などが功を奏したと考えられた。(著者抄録)

Language：Japanese   Publisher：(一社)日本皮膚免疫アレルギー学会  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

症例1:43歳,男性。両親は血族婚。小児期より顔面を含む全身に角化性紅斑を生じた。近医で毛孔性紅色粃糠疹と診断され,ステロイド外用やエトレチナート内服等で加療された。成長と共に顔面,体幹の紅斑は自然に軽快したが,掌蹠の過角化は残存していた。当科初診時,下顎,両耳介,前胸部に境界明瞭な鱗屑性紅斑および掌蹠の著明な角化を認めた。病理組織では過角化と表皮肥厚を認め,顆粒層は一部で消失しており,毛孔一致性に角栓形成を認めた。全身narrow band ultraviolet B(NB-UVB),掌蹠に対してはターゲット型NB-UVBの照射療法,エトレチナート再投与により皮疹は軽快した。症例2:45歳,女性。症例1の姉。生下時より掌蹠に角質増殖がみられ,成長と共に全身に紅斑と落屑が拡大した。エトレチナート,シクロスポリン内服で加療したところ,皮疹は掌蹠にわずかな角質増殖と,膝蓋に角質増殖を残すのみとなった。2症例とも,毛孔性紅色粃糠疹と一旦診断したが,whole-exome-sequencing解析の結果,ABCA12遺伝子に新規のミスセンス変異(c.4601C>T,p.Thr1534Met)をホモ接合体で認め,先天性魚鱗癬様紅皮症と改めて診断した。毛孔性紅色粃糠疹と先天性魚鱗癬様紅皮症の鑑別診断には遺伝子検査が有用であると考えた。(著者抄録)

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)協和企画  

＜文献概要＞症例のポイント ・ロリクリン角皮症は山本らによって提唱された疾患概念で,角層細胞の周辺帯を形成するロリクリンという表皮のタンパク構造をコードするLOR(ロリクリン)遺伝子の変異によって生じる,非常にまれな常染色体優性遺伝性の角化異常症である.本症は,これまでに,世界でも18家系しか報告されていない.・自験例は先天性魚鱗癬様紅皮症との鑑別を要し,全エクソームシークエンスによってLOR遺伝子変異を同定したことでロリクリン角皮症と確定診断した.今回の変異はc.684dupGで,ロリクリン角皮症の原因遺伝子変異として8家系において報告されている.

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：日本臨床皮膚科医会  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞74歳,男性.初診1年前から頭部,顔面に紅斑が出現した.近医を受診し,尋常性乾癬の診断で治療されたが症状の拡がりを認めたため,当科を紹介受診した.初診時,鱗屑,水疱,紅斑,びらん等,全身に多彩な皮疹を認めた.皮膚生検にて,表皮内水疱を認め,水疱内に好中球,棘融解細胞がみられた.直接蛍光抗体法にて表皮細胞間のIgGの沈着と,基底膜部のC3の沈着を認めた.血清中自己抗体検査(CLEIA法)にて,抗デスモグレイン1抗体が3,180U/mlと高値であった.抗BP 180抗体も33.8U/mlと陽性であった.以上の所見より落葉状天疱瘡と診断した.ステロイド単独治療では症状の改善に乏しく,免疫グロブリン大量静注療法の併用により病勢は制御できた.多彩な皮疹を呈している症例は診断が難しく繰り返し精査を行い,診断を確定し適切な治療を開始することが重要である.

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(一社)日本皮膚免疫アレルギー学会  

Language：Japanese   Publisher：(一社)日本皮膚免疫アレルギー学会  

Language：Japanese   Publisher：日本皮膚科学会-大阪地方会・京滋地方会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞Ichthyosis with confetti(IWC,別名congenital reticular ichthyosiform erythroderma)とは,全身の皮膚にさまざまな程度の過角化,鱗屑を認める疾患である.&quot;confetti&quot;と呼ばれる白色皮膚部分が,加齢とともに全身に増えてくることがこの疾患の大きな特徴である.この白色皮膚部分では,体細胞組換えにより病因遺伝子変異が消失し,いわゆる「自然治癒」が起きていると考えられている.われわれは,この自然治癒を起こす病態を解明するために,IWC家系の組織を用いて,whole-exome sequenceなどの詳細な病態解析を行った.その結果,過去に報告のない,KRT1遺伝子のイントロン1からイントロン5までを含む2209塩基の欠失変異を同定した.本研究により,KRT1遺伝子の広範囲欠失変異により,IWCを引き起こすことが証明された.

DOI： 10.11477/mf.1412205379

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：日本小児皮膚科学会  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)医薬情報研究所  

Language：Japanese   Publisher：(株)協和企画  

＜症例のポイント＞常染色体劣性先天性魚鱗癬の4つ目の疾患概念としてpleomorphic ichthyosisという病型が提唱されている。pleomorphic ichthyosisの表現型の1つにself-improving collodion ichthyosisが含まれる。コロジオン児として発症、生活6ヵ月以降には皮膚症状がほぼ改善したSICIの症例を経験した。SICIの病因遺伝子としてはTGM1、ALOX12B、ALOXE3が今までのところ同定されている。(著者抄録)

Language：Japanese   Publisher：日本皮膚科学会-西部支部  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

Web of Science

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

DOI： 10.14924/dermatol.127.1222

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：角化症研究会事務局  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Language：Japanese   Publisher：(株)学研メディカル秀潤社  

Language：Japanese   Publisher：(公社)日本皮膚科学会  

Event date： 2021.12

Language：English   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.11

Language：English   Presentation type：Oral presentation (keynote)  

Event date： 2021.10

Language：English   Presentation type：Oral presentation (general)  

Event date： 2021.9

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2021.8

Language：Japanese   Presentation type：Oral presentation (general)