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The mechanisms underlying itch are not fully understood. Physicians usually encounter difficulty controlling itch in generalized pruritus. Since only a small percentage of patients with generalized pruritus respond to antihistamines (H 1 receptor antagonists), a variety of itch mediators and mechanisms other than histaminergic signals are considered to be involved in itch for these non-responsive patients. In 2012, we created guidelines for generalized pruritus. Those guidelines have been updated and revised to make some of the definitions, diagnostic terms, and classifications more applicable to daily clinical practice. Cutaneous pruritus as designated in these guidelines is a disease characterized by itch without an observable rash. Generalized pruritus (without skin inflammation) is defined as the presence of itch over a wide area, and not localized to a specific part of the body. This entity includes idiopathic pruritus, pruritus in the elderly, symptomatic pruritus, pregnancy-associated pruritus, drug-induced pruritus, and psychogenic pruritus. Localized pruritus (without skin inflammation) represents fixed itch localized to a specific part of the body, and includes anogenital pruritus, scalp pruritus, notalgia paresthetica, and brachioradial pruritus. These guidelines outline the current concepts and specify the diagnostic methods/treatments for cutaneous pruritus., (© 2021 Japanese Dermatological Association.)

Milia en plaque (MEP) is an uncommon disorder characterized by an erythematous plaque containing numerous milia. The pathogenesis of MEP is not clear. The authors report a man with an erythematous plaque on the right retroauricular area, containing numerous white-yellow cysts varying in size. Histological examination showed that multiple cystic structures at various levels of the dermis that were lined by stratified squamous epithelium and contained keratinous material-these findings were consistent with the diagnosis of multiple milia. In addition to epidermal cysts, however, the lesion consisted of a branched proliferation of pale-staining keratinocytes lined with basal keratinocytes budding from the overlying epidermis. Moreover, some cysts were formed within the branched epithelial proliferation, had thicker cyst walls than the ordinary milium, or had irregular or branched projections toward the surrounding dermis. From these findings, the authors conclude that MEP is a distinct follicular hamartoma with cystic trichoepitheliomatous features.

Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), beta-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a(+) dendritic cells (DCs), factor XIIIa(+) dermal DCs, and CD68(+) macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a(+) cells. Interestingly, factor XIIIa(+) cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a(+) cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.

p53 suppresses the genomic instability provoked by genotoxic agents. Ultraviolet (UV) B induces skin cancers by producing DNA damage and mutations in the skin genome, whereas the skin tissue responds to the UVB insult with cell cycle arrest and apoptosis as well as damage exclusion by DNA repair. To address the p53 contribution to these skin responses in vivo, we analyzed the time course of DNA damage removal, apoptosis induction and hyperplasia in the skin after UVB irradiation in p53-knockout mice. We also examined UVB-induced mutations in the skin. We found that p53 deficiency does not abolish the UVB-induced apoptotic response in the epidermis but delays the process and the following hyperplasia 12–24 h. Regardless of the p53 genotype, 1 kJ/m2 UVB induced a total replacement of the epidermal layer by destroying the damaged epidermis by apoptosis and rebuilding a new one through hyperplasia. We failed to detect a clear defect in removal of UVB-induced DNA photolesions from the genome of the p53-deficient skin except for a delay in the epidermis, which seemed to result from the delay in the apoptotic response. However, we found that p53 deficiency enhanced UVB-induced mutagenesis. Furthermore, in a genetic study using Xpa-knockout mice, we showed that the enhanced mutagenic response depends on the activity of nucleotide excision repair (NER), which was also supported by the mutation spectrum observed in the UVB-exposed p53-knockout mice. These results indicate that p53 protects the skin genome from the UVB genotoxicity by facilitating NER, whereas its contribution to the UVB-induced apoptosis is limited. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a 65-year-old Japanese woman with multiple red nodules on the lower leg's erythematous patch lesion. Physical examination showed a big scaly erythematous patch lesion on the lower leg, in which there were grouped, multiple and coalesced red nodules. A microscopic examination of a biopsy specimen from the nodules showed dense and spread lymphocytic infiltration comprising big pleomorphic cells fuse with a few eosinophils and neutrophils.

Mycosis fungoides (MF), a cutaneous T-cell lymphoma, is usually characterized by cell features of T-helper-2 (Th2) lymphocytes. MF has recently been reported to show increased CCR4 expression, a chemokine receptor specifically expressed in Th2. Previously, we have reported the effectiveness of interferon-γ (IFN-γ) for the treatment of CCR4+ MF. In this report, we describe two cases of CD4+, CCR4– MF successfully treated with IFN-α, but not IFN-γ. Although MF usually displays a Th2 profile, the tumor cells in our two cases did not express CCR4. Our cases suggest the effectiveness of IFN-α, but not IFN-γ, for CCR4– MF. [ABSTRACT FROM AUTHOR]

We describe an 81-year-old Japanese patient with erythroderma overlapping with widespread and symmetrical deposits of mucin in the upper dermis. Clinically, the mucinous lesions on the nape and upper trunk were localized papular mucinosis. Histologically, there was a perivascular infiltrate of lymphohistiocytic cells mingled with plasma cells in the upper dermis but no sclerosis. Immunohistochemical staining revealed that more than 90% of these infiltrating plasma cells produced immunoglobulin λ-chain. Both the erythroderma and generalized mucinosis responded to topical steroid and PUVA therapy. To the best of our knowledge, this is the first case of erythroderma accompanied by generalized mucinosis. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hiromi Kobayashi, MD, Setsuya Aiba, Yumiko Yoshino and Hachiro Tagami. Acute cutaneous barrier disruption activates epidermal p44/42 and p38 mitogen-activated protein kinases in human and hairless guinea pig skin Acute cutaneous barrier disruption of the skin elicits various homeostatic repair responses in the epidermis. Although several candidates for the signaling mechanisms that induce these responses have been reported, e.g. the calcium and ion concentration, peroxisome proliferator-activated receptor-α, and TNF-α signaling mediated by sphingomyelinases, the exact nature of the signals remains undetermined. Therefore, assuming that an important group of serine/threonine-signaling kinases, mitogen-activated protein kinases (MAPKs), such as p44/42 MAPK, p38 MAPK, and SAPK/JNK, might link the barrier disruption to the subsequent homeostatic responses, the activation of three MAPKs in hairless guinea pig or in human skin after barrier disruption was investigated. The epidermal barrier was insulted with tape stripping or organic solvents, and the activation of these MAPKs was examined with immunohistochemistry, Western blotting, and immune complex kinase assay. In the skin of hairless guinea pigs, p44/42 MAPK and p38 MAPK, but not SAPK/JNK, were activated in epidermal keratinocytes immediately after tape stripping, and continued to be activated for at least 180 min. The activation of p44/42 MAPK was well correlated with an increase in transepidermal water loss, which was positively correlated with the number of tape strippings, whereas the covering of the stripped skin with occlusive dressing or with Ca2++ K++sucrose solution suppressed its activation. The activation of p44/42 MAPK was also induced by treatment of the skin with organic solvents. In a similar fashion, p44/42 and p38 MAPKs were found to be activated in human skin after tape stripping. These results strongly suggest that the activation of p44/42 and p38 MAPKs links the stimuli of barrier disruption to the subsequent homeostatic responses to repair the barrier defect. [ABSTRACT FROM AUTHOR]

An unusual case of a non-pigmenting fixed drug eruption caused by allylisopropylacetylurea is reported. Several hours after taking an analgesic (New Kaiteki A®), a 30-year-old Japanese woman, who had experienced similar eruptions several times after taking other analgesics, developed numerous variously sized, itchy, round-to-oval erythematous eruptions on the trunk and extremities. After she discontinued taking this drug, all such eruptions resolved within 2 weeks, without leaving postinflammatory pigmentation. Patch testing with New Kaiteki A® itself and one of its active ingredients, allylisopropylacetylurea, on lesional skin, but not on uninvolved skin, showed positive erythematous reactions after 2 days. [ABSTRACT FROM AUTHOR]

The surface contours of lesional skin of certain skin diseases, such as parapsoriasis en plaque (PEP) and extramammary Paget''s disease (EMPD), in which there is a massive infiltration by non-epidermal cells, looks somewhat different from that of the adjacent normal skin, needless to state that they are apparently different from that of ordinary chronic inflammatory dermatoses where we found acanthotic epidermis accompanied by hyperkeratosis. We attempted to objectively characterize these unique skin surface changes qualitatively and quantitatively using non-invasive methods. Negative impression replicas were taken from the lesional skin of patients with EMPD or PEP as well as from the adjacent uninvolved skin. The findings were confirmed histologically. The replicas were examined by using computerized image analysis. Several parameters were analyzed that correlate with the changes in the anisotropy of the skin furrows (VC1), average skin roughness (KSD), average length of skin furrows (LEN), and number of skin furrows (NUM). There were significant decreases in KSD and NUM in EMPD, indicating a smoother skin surface in the lesional skin than in the adjacent normal skin. In contrast, the PEP lesion had an increase in VC1 and LEN and a decrease in NUM, which suggests larger skin ridges in the lesional skin than in the uninvolved skin. Thus the unique skin surface of the cutaneous disorders accompanied by epidermal invasion by non-epidermal cells, such as EMPD and PEP, was characterized both qualitatively and quantitatively using computerized image analysis of negative impression replicas. [Copyright &y& Elsevier]

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a+ dendritic cells (DCs), factor XIIIa+ dermal DCs, and CD68+ macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a+ cells and factor XIIIa+ cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa+ cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a+ cells. Interestingly, factor XIIIa+ cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a+ cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

To elucidate the pathogenesis of T cell-mediated inflammatory skin diseases, we examined the exact sites where CD8(+) T cells proliferate, correlating them with the localization of antigen-presenting dendritic cells. We performed CD8/Ki-67 double immunohistochemical staining and single staining for CD1a, CD68, and factor XIIIa on sections of paraffin-embedded tissue samples of inflammatory dermatoses in which T lymphocytes are thought to play a crucial role. The dermatoses were lichen planus (12 samples), acute graft-versus host disease (GVHD) (12 samples), chronic GVHD (10 samples), spongiotic dermatitis (8 samples) and psoriasis (7 samples). Labelling for Ki-67 among CD8(+) T cells was predominantly observed in the subepidermal lymphoid infiltrate, and was scanty in the epidermis. This suggested that proliferation of CD8(+) T cells occurred preferentially in the dermis. The labelling index for Ki-67 among dermal and epidermal CD8(+) cells was quite different among the different diseases studied (P < 0.05). They were rich in the subepidermal portion of the dermis of spongiotic dermatitis, acute GVHD and chronic GVHD, but rare in the dermis of psoriasis and lichen planus. A moderate infiltrate was also observed in lesional epidermis of spongiotic dermatitis, acute GVHD and chronic GVHD, whereas they was almost none in the epidermis of psoriasis and lichen planus. CD1a(+) dermal dendritic cells were densely distributed within the lymphoid infiltrate in the affected dermis of spongiotic dermatitis, psoriasis and lichen planus, whereas they were minimal in GVHD. These dermal dendritic cells are candidates as stimulators on T cells in the dermis. In conclusion, the proliferative status of T cells could be an important clue in the elucidation of the pathophysiology of T cell-mediated inflammatory dermatoses. [ABSTRACT FROM AUTHOR]

The occurrence of opportunistic infections is not rare during the treatment of connective tissue diseases, including dermatomyositis because of the patient's immuno-suppression. We describe here cytomegalovirus (CMV) infection that affected two of our patients with dermatomyositis. CMV infection has not been considered to be a frequent event in dermatomyositis, and its significance for disease progression has not been sufficiently recognized. Our case reports demonstrate the importance of close monitoring of such patients and prompt initiation of appropriate therapy to manage a suspected CMV infection. [ABSTRACT FROM AUTHOR]

The article presents a case report of a 38-year-old man who visited the hospital after suffering from a 6-month history of pruritic eruptions in his body and was treated for hypohidrosis. The patient underwent a skin biopsy from the abdomen and axilla which revealed a dense infiltration of mononuclear cells of eccrine glands due to anti-dermicidin antibodies. The article also discusses the use of Th17 cells as immune effectors in autoimmunity in various autoimmune disease.

A letter to the editor is presented about the case of a 2-year-old girl diagnosed with unilateral focal dermal hypoplasia resulting from a novel mutation in the PORCN gene.

The article presents a case study of a 62-year-old Japanese man with a three-year history scalp bleeding nodule. Biopsy showed that tumour cells proliferated primarily in the dermis, which forms solid pattern nests and pagetoid epidermal up migration, particularly at the hair follicle. The tumour comprised primarily of neoplastic cells having abundant eosinophilic cytoplasm, large nuclei with cytological pleomorphism and macronucleoli.

The article presents a case study of an old Japanese man with a band-like pigmented area on only the right side of his chest. The patient underwent an examination and found out that the pigmented plaque appeared more wrinkled than the surrounding normal skin, presenting a reticular pattern dotted with hypopigmented spotty areas. Despite that, the patient were not required any treatment for his skin lesions.

A letter to the editor is presented in response to the article "Intramuscular Triamcinolone Acetonide for Lupus Millaris Disseminatus Faciei," that was published in the March 8, 2007 issue.

The article reports on the use of aluminum chloride and salicylic acid ointments in treating plantar discomfort caused by Pachyonychia congenita. Pachyonychia congenita is an autosomal dominantly inherited disorder characterized by hypertrophic nail dystrophy. The authors presented a case demonstrating the effectiveness of the ointments in treating the condition.

We previously reported a dataset of the IL-8 Luc assay covering reference chemicals published by ECVAM, in which the effects of chemicals on IL-8 promoter activity were evaluated by an IL-8 reporter cell line, THP-G8 cells. To clarify its performance, we created another dataset of 88 sensitizers and 34 non-sensitizers. Simultaneously, to improve its performance, we changed the incubation time from 5 h to 16 h, deleted the criterion regarding the effects of N-acetylcysteine, and set an exclusion criterion for detergents. These modifications significantly improved its performance. In addition, we examined the following three criteria to judge chemicals as sensitizers: Criterion 1: Fold induction of SLO luciferase activity (FlnSLO-LA) ⩾ 1.4, Criterion 2: the lower limit of the 95% confidence interval of FInSLO-LA ⩾ 1.0, Criterion 3: the intersection of criteria 1 and 2. Among them, Criterion 1 produced the best performance, demonstrating that the accuracy, sensitivity and specificity were 81%, 79%, and 90%, respectively. In addition, we found that the IL-8 Luc assay solubilizing chemicals with X-VIVO substantially improved its performance. Finally, the IL-8 Luc assay combined with DPRA and DEREK could improve substantially its performance. These data suggest that the IL-8 Luc assay is a promising test method to screen skin sensitizers. [ABSTRACT FROM AUTHOR]

Abstract: In order to find a novel biomarker for a simple assay to predict skin sensitization, we evaluated cell-surface thiols as a biomarker reflecting intracellular signaling in THP-1 cells (human monocytic cell line). First, we found that a decrease of cell-surface thiols on hapten-treated THP-1 cells was induced in parallel with phosphorylation of p38 MAPK. Next, we confirmed that 2-mercaptoethanol in the culture medium and the differentiation state of THP-1 cells did not affect the changes of cell-surface thiols by hapten. Changes of cell-surface thiols on THP-1 cells were detected after 2h treatment with most allergens (e.g., DNCB, NiSO4), as well as some non-allergens (e.g., Tween80, benzalkonium chloride), though other non-allergens (e.g., SDS, glycerol) had no effect. When either a significant decrease or increase of cell-surface thiols (more than 15% in each case) was used as a criterion, the results using 36 allergens and 16 non-allergens were in good accordance with those of in vivo assays. Finally, we confirmed that ATP, which is released as a consequence of cytotoxicity, did not affect the changes of cell-surface thiols. Our results suggest that changes of cell-surface thiols may be useful for an in vitro sensitization assay, which we designate as the SH test. [Copyright &y& Elsevier]