記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2340/00015555-3916

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1684/ejd.2021.4089

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. Cytotoxic T cells and associated effector molecules are known to drive SJS/TEN pathophysiology, but the contribution of innate immune responses is not well understood. We describe a mechanism by which neutrophils triggered inflammation during early phases of SJS/TEN. Skin-infiltrating CD8+ T cells produced lipocalin-2 in a drug-specific manner, which triggered the formation of neutrophil extracellular traps (NETs) in early lesional skin. Neutrophils undergoing NETosis released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1 expression caused keratinocytes to be vulnerable to necroptosis that caused further release of LL-37 by necroptotic keratinocytes and induced FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. The NETs-necroptosis axis was not observed in less severe cutaneous adverse drug reactions, autoimmune diseases, or neutrophil-associated disorders, suggesting that this was a process specific to SJS/TEN. Initiation and progression of SJS/TEN keratinocyte necroptosis appear to involve a cascade of events mediated by innate and adaptive immune responses, and understanding these responses may contribute to the identification of diagnostic markers or therapeutic targets for these adverse drug reactions.

DOI： 10.1126/scitranslmed.aax2398

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記述言語：英語  

DOI： 10.1111/jdv.17179

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記述言語：英語  

DOI： 10.1111/ajd.13597

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/jdv.17020

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdv.17020

記述言語：英語  

DOI： 10.1111/jdv.16872

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Punctate palmoplantar keratoderma type 1 (PPPK1) is a rare autosomal dominant disorder characterized by hyperkeratotic papules on the palms and soles. In 2012, heterozygous loss-of-function mutations in the AAGAB gene were identified as the cause of this disorder. To date, 51 AAGAB mutations have been reported in families with PPPK1, but clear genotype-phenotype correlations have not been established yet. In this report, we identified four Japanese patients with PPPK1 from two families with an identical novel heterozygous AAGAB mutation. All patients showed hyperkeratotic papules only on the soles. Direct sequencing analysis of the AAGAB gene using peripheral blood-derived genomic DNA samples revealed that all of the patients carried a heterozygous 1-bp substitution (c.844G>A, p.Glu282Lys) in exon 9, leading to a missense change. Since all patients with the same missense mutation showed a mild phenotype limited to the soles, there is thought to be a genotype-phenotype correlation regarding this mutation. The c.844G>A mutation is a known single-nucleotide polymorphism with a minor allele frequency of 0.000012. Because of its mild symptoms, individuals with this mutation can be misdiagnosed with clavus or verruca vulgaris; this suggests that there may be a high incidence of mild symptoms of skin lesions found only on the soles in patients with PPPK1. Therefore, it is necessary to consider this disease when keratotic papules are found on the soles.

DOI： 10.1111/1346-8138.16162

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.15036/arerugi.70.282

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane. SJS/TEN are considered to be on the same spectrum of diseases with different severities. They are classified by the percentage of skin detachment area. SJS/TEN can also cause several complications in the liver, kidneys, and respiratory tract. The pathogenesis of SJS/TEN is still unclear. Although it is difficult to diagnose early stage SJS/TEN, biomarkers for diagnosis or severity prediction have not been well established. Furthermore, optimal therapeutic options for SJS/TEN are still controversial. Several drugs, such as carbamazepine and allopurinol, are reported to have a strong relationship with a specific human leukocyte antigen (HLA) type. This relationship differs between different ethnicities. Recently, the usefulness of HLA screening before administering specific drugs to decrease the incidence of SJS/TEN has been investigated. Skin detachment in SJS/TEN skin lesions is caused by extensive epidermal cell death, which has been considered to be apoptosis via the Fas-FasL pathway or perforin/granzyme pathway. We reported that necroptosis, i.e. programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, and its interaction with the formyl peptide receptor 1 induce necroptosis. Several diagnostic or prognostic biomarkers for SJS/TEN have been reported, such as CCL-27, IL-15, galectin-7, and RIP3. Supportive care is recommended for the treatment of SJS/TEN. However, optimal therapeutic options such as systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-α antagonists are still controversial. Recently, the beneficial effects of cyclosporine and TNF-α antagonists have been explored. In this review, we discuss recent advances in the pathophysiology and management of SJS/TEN.

DOI： 10.12688/f1000research.24748.1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND:Localized bullous pemphigoid is a relatively rare variant of bullous pemphigoid. Lesions develop only in localized sites including the legs or palms and soles and occasionally appear in trauma-affected body parts. In some cases, the skin lesions spread to the entire body, while in others, they remain localized and improve spontaneously or with treatment using topical corticosteroids. Rarely, the lesions recur at sites different from those of the original lesions, after the initial lesions have completely healed. OBJECTIVES:To investigate the clinical course of patients with localized bullous pemphigoid. MATERIALS AND METHODS:Two cases of localized bullous pemphigoid that recurred at sites distant from those of the initial lesions were reported. RESULTS:Case 1 involved a 62-year-old woman with mucous membrane pemphigoid. One year after the improvement of mucosal symptoms, new lesions appeared in the periumbilical area. The lesions resolved after topical corticosteroid treatment. This case is the first report of localized bullous pemphigoid occurring after an improvement of mucous membrane pemphigoid. Case 2 involved an 81-year-old man who bruised his right lower leg and developed erythematous plaques and tense bullae. The patient was diagnosed with localized bullous pemphigoid and was treated with topical corticosteroid. However, six months later, new lesions appeared on the palms and soles. The patient responded well to oral prednisolone. CONCLUSIONS:Since localized bullous pemphigoid may have a variable clinical course, clinicians should observe affected patients carefully over a long period of time.

DOI： 10.1684/ejd.2019.3672

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jaip.2020.01.006

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jaci.2019.02.012

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A delicate balance between cell death and keratinocyte proliferation is crucial for normal skin development. Previous studies have reported that cellular FLICE (FADD-like ICE)-inhibitory protein plays a crucial role in prevention of keratinocytes from TNF-α-dependent apoptosis and blocking of dermatitis. However, a role for cellular FLICE-inhibitory protein in TNF-α-independent cell death remains unclear. OBJECTIVE: We investigated contribution of TNF-α-dependent and TNF-α-independent signals to the development of dermatitis in epidermis-specific Cflar-deficient (CflarE-KO) mice. METHODS: We examined the histology and expression of epidermal differentiation markers and inflammatory cytokines in the skin of CflarE-KO;Tnfrsf1a+/- and CflarE-KO;Tnfrsf1a-/- mice. Mice were treated with neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand to block TNF-α-independent cell death of CflarE-KO;Tnfrsf1a-/- mice. RESULTS: CflarE-KO;Tnfrsf1a-/- mice were born but experienced severe dermatitis and succumbed soon after birth. CflarE-KO;Tnfrsf1a+/- mice exhibited embryonic lethality caused by massive keratinocyte apoptosis. Although keratinocytes from CflarE-KO;Tnfrsf1a-/- mice still died of apoptosis, neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand substantially prolonged survival of CflarE-KO;Tnfrsf1a-/- mice. Expression of inflammatory cytokines, such as Il6 and Il17a was increased; conversely, expression of epidermal differentiation markers was severely downregulated in the skin of CflarE-KO;Tnfrsf1a-/- mice. Treatment of primary keratinocytes with IL-6 and, to a lesser extent, IL-17A suppressed expression of epidermal differentiation markers. CONCLUSION: TNF receptor superfamily 1 (TNFR1)-dependent or TNFR1-independent apoptosis of keratinocytes promotes inflammatory cytokine production, which subsequently blocks epidermal differentiation. Thus blockade of both TNFR1-dependent and TNFR1-independent cell death might be an alternative strategy to treat skin diseases when treatment with anti-TNF-α antibody alone is not sufficient.

DOI： 10.1016/j.jaci.2018.02.043

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier  

DOI： 10.1016/j.jaip.2019.05.002

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DOI： 10.1016/j.dsi.2018.02.001

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1684/ejd.2018.3314

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記述言語：英語  

DOI： 10.1016/j.jaci.2018.02.046

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/ced.13128

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語  

DOI： 10.1111/1346-8138.13560

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(一社)日本皮膚免疫アレルギー学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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