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Real-life evidence on the quality of treatment with brodalumab in patients with plaque psoriasis based on patient-reported outcomes remains limited.To assess the effectiveness of brodalumab in achieving treatment satisfaction for real-life Japanese patients with psoriasis.As part of a single-arm, open-label, multicenter, prospective study (ProLOGUE), Psoriasis Area and Severity Index (PASI) scores, body surface area (BSA), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) domain scores were assessed at baseline and Weeks 12 and 48 of brodalumab treatment. Patient Global Assessment (PtGA) scores were captured at Weeks 12 and 48.Seventy-five patients were enrolled, of whom 73 received brodalumab. PASI scores and BSA significantly reduced from baseline at Weeks 12 and 48 (all P 0.0001). Most (90%) patients felt the treatment was effective on the PtGA scale at Weeks 12 and 48. TSQM-9 domain scores significantly improved at Weeks 12 and 48 (all P 0.0001). A PASI score of ≤ 2 was suggested as a treatment goal for biologic treatment of psoriasis from a receiver operating characteristic curve analysis, although some of the TSQM-9 domain scores did not improve in patients achieving this goal. No new safety signals were observed.Treatment with brodalumab was associated with improved objective symptoms and satisfaction in Japanese patients with psoriasis. A PASI score of ≤ 2 as a goal for biologic treatment of psoriasis may be feasible, although achieving this PASI goal alone may be insufficient to clearly improve long-term patient satisfaction (Japan Registry of Clinical Trials identifier: jRCTs031180037).

Zinc deficiency has long been known as acrodermatitis enteric dermatitis (congenital zinc deficiency). On the other hand, acquired zinc deficiency has attracted attention as a familiar disease in recent years. Epidemiological studies in Japan have shown that acquired zinc deficiency is more common than expected. It is also known that serum zinc levels fall markedly with age. In this report, several cases of acquired zinc deficiency that caused cheilitis are described. In all cases, the only symptom was cheilitis, the serum zinc level was low, and all cases were relieved by zinc supplementation. Zinc deficiency is associated with a range of pathological conditions, including mucocutaneous symptoms, delayed wound healing, dysgeusia, anemia, impaired immunity, and retarded growth development disorders. However, zinc deficiency may be overlooked even in cases of cheilitis alone. Especially in intractable cases, it is important to suspect zinc deficiency as one at the differential diagnoses.

Background Plaque psoriasis significantly affects patients’ health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important. Objective To assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis. Methods This was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results Of the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5. Conclusion DLQI may be useful for assessing patients’ concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.

Myiasis refers to the infestation of living humans and vertebrate animals by dipterous larvae. Many organs can be infested by fly larvae, but cutaneous and wound myiases are the most frequently encountered clinical forms. Persistent ulcer or non-healing wound is one of the symptoms of squamous cell carcinoma which is the second most common skin cancer in the world. Here we report a case of an elderly man with a severe wound myiasis in a squamous cell carcinoma lesion of the scalp. The maggots were confirmed to be

Psoriasis is an immune cell-mediated inflammatory skin disease. The interleukin (IL)23/IL17 axis plays an important role in the development of psoriasis. The effectiveness of biologic treatments such as tumor necrosis factor (TNF)α inhibitors (infliximab, adalimumab, certolizumab pegol), IL23 inhibitors (ustekinumab, guselkumab, tildrakizumab, risankizumab), and IL17 inhibitors (secukinumab, ixekizumab, brodalumab) have verified these findings. Immune-related cells such as dendritic cells (DCs) and macrophages, in addition to Toll-like receptors and cytokines such as interferon (IFN)α, TNFα, IFNɤ, IL12, IL22, IL23, and IL17, are related to the pathogenesis of psoriasis. Here, we first review new insights regarding the pathogenesis of psoriasis, as it relates to DCs, Langerhans cells, macrophages, the signal transducer and activator of transcription 3 pathway, and aryl hydrocarbon receptor in cutaneous vascular endothelial cells. Based on these findings, we summarize currently available oral treatments and biologics. Furthermore, we describe a new treatment option including Janus kinase inhibitor, tyrosine kinase 2 inhibitor, modulator of sphingosine 1-phosphate receptor 1, and Rho-associated kinase 2 inhibitor.

Ticks have a cosmopolitan distribution and, as such, are also found in Japan. Ticks are typically ectoparasites of wild animals, however, humans can also be bitten when visiting environments inhabited by ticks. Herein, we describe two cases with atypical tick bites. Case 1 was an elderly Japanese male patient who presented with a fully engorged tick measuring 20 × 17 × 8 mm; it is rare for ticks to attain a length of 20 mm. Case 2 was an elderly Japanese female with severe dementia who presented with multiple tick bites, which is rare, after going missing for 6 days before being found in a densely wooded area. Ticks are responsible for the transmission of many infectious agents, such as bacteria, viruses and parasites. The National Institute of Infectious Diseases and the Ministry of Health, Labour and Welfare regularly inform citizens of the risks posed by tick bites. However, the tick bites could not be prevented in our patients. Further edification about tick bites, tick-borne diseases, and their prevention are considered necessary in Japan.

Background Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. Funding This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).

In recent years, BCG vaccination is routinely performed worldwide. The Ministry of Health, Labor and Welfare of Japan reported that the vaccination rate was as high as 92.9% in 2011. Majority of the reported local adverse reactions to BCG vaccination included lymph node swelling, keloid formation, and abscesses. Subcutaneous tuberculous granuloma is a rare local adverse reaction to BCG vaccination. Herein, we report two cases of developing subcutaneous tuberculous granuloma associated with BCG vaccination. Both of them were treated with isoniazid. There is no standard management for BCG-induced subcutaneous tuberculous granuloma, however, treatment with anti-tuberculosis drugs should be considered for cases of BCGinduced subcutaneous tuberculous granuloma with abscesses or ulcerations.

To review patients who were treated at Tokai University Hospital with biologic agents for psoriasis vulgaris and psoriatic arthritis and analyze the biological retention rate, reasons for switching biologics, and investigate possible clinical prognostic factor which may affect whether a patient preferred one biologic to another.Clinical courses of 63 patients who received biologic agents between Sep of 2010 to June of 2019 were investigated. Biological retention rate of each biologic agents, reasons of switching to another biologic agent, and prognostic factors, if any, between switched and non-switched patients were examined.The biological retention rate of ustekinumab (UST) was significantly longer than that of infliximab (IFX) or adalimumab (ADA). The major reason of switching was due to secondary loss of efficacy. Patients being treated with UST were more likely to switch to another biologic when they exhibited nail lesions.These results suggested that biological retention rate of UST was superior than that of IFX or ADA. Furthermore, with patients administered UST, nail symptom suggested possible clinical prognostic factor for switching to other biologic agents.

Objective To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177). Methods Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks. Results Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients). Limitations Lack of comparison treatment group after week 12. Conclusion IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.

Here, we report the case of cutaneous metastases from testicular diffuse large B-cell malignant lymphoma (DLBCL) concurrent with Bowen disease evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). A 60-year-old male underwent orchiectomy to remove his left testicle because of DLBCL. Multiple skin lesions appeared 1 month postoperatively. Furthermore, an intractable erythematous plaque localized to the right lower leg was present from 2 years before the operation. 18F-FDG PET-CT images revealed multiple skin lesions with marked FDG uptakes in the face, neck, and thigh of this patient, as well as a lower leg lesion with minimal FDG uptake. Biopsy of both lesions revealed cutaneous metastases from DLBCL and Bowen disease (BD) of the lower leg lesion. 18F-FDG PET-CT images following chemotherapy and resection of BD demonstrated no FDG uptake.

Background Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. Objective To assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. Methods These subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest. Results Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. Conclusion These findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis., Linked article: This article is commented on G. Egawa et al., p. 259 in this issue. To view this article visit https://doi.org/10.1111/jdv.15416

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® . The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in seven of 10 (70%) and five of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.

A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL limited to the skin and reviews the medical published work.

Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. To elucidate major histocompatibility complex-linked systemic sclerosis genetics, we performed genotyping of major histocompatibility complex-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed two major histocompatibility complex haplotypes associated with systemic sclerosis. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in RXRB as a susceptibility variant ( P = 1.3 × 10 −15 ; odds ratio [OR] = 9.4) with amino acid substitution p.V95A on the risk haplotype harboring HLA-DPB1∗13:01 . No identical variant in the other haplotype including DPB1*09:01 was observed, though that haplotype also showed a significant association ( P = 8.5 × 10 −22 ; OR = 4.3) with systemic sclerosis. Furthermore, the number of risk factors was shown to be a predominant factor, as individuals with two factors had elevated risk ( P = 6.7 × 10 −13 ; OR = 30.2). We concluded that RXRB may be involved in antifibrotic activity in skin and chromatin remodeling.

Apocrine hidrocystomas are mostly found on the cheeks and eyelids but also on the scalp and neck. The age distribution is from 30 to 70 years old. We report a case of an apocrine hidrocystoma on the genitalia of a 9-year-old girl.

Background A quantitative understanding of the histological alteration of the skin is important for assessing the severity of photoaging. Methods We performed Elastica-van Gieson staining and immunohistochemistry for decorin on 34 facial skin sections. We evaluated the alteration of collagen fibers and decorin (a modulator for collagen fibrillogenesis), according to the 5 grades of morphological change in elastic fibers that was established by Kligman (1969). The objectivity of a stage (Stages I–VI), which was established in this study, was evaluated using weighted kappa statistical analysis based on the degree of agreement in stage determination by 11 observers using a blind procedure. Correlation between the crow's-feet-area wrinkles grades of another 26 women and stages was also analyzed. Results The initial alteration of elastic fibers was observed in the deep dermis. Decorin was not detected in very severely altered skin. Based on the combination of changes in the elastic fibers, collagenic fibers, and decorin, skin tissues were categorized into 6 stages according to severity. The statistical analysis showed almost perfect agreement between observers. Significant positive correlation between stages and wrinkle scores was found. Conclusions We propose a new objective histological scale that is useful for assessing the severity of photoaging.

Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease involving hair loss, but its pathogenesis remains poorly understood. Many autoimmune diseases are genetically associated with alleles of the human leukocyte antigen (HLA) genes within the major histocompatibility complex. Associations between AA and HLA genes were previously observed in some different ethnic groups. However, the results were inconsistent, and a primary susceptibility HLA gene and/or region has not yet been assigned for AA. The aim of this study was to evaluate whether an allele of the HLA-C locus, HLA-C*07:04, which was strongly associated with AA in Chinese Hans, could be replicated in the Japanese population. The HLA-C locus was genotyped by the SSO method using 156 AA patients and 560 healthy controls. As a consequence, among the 17 alleles detected, only two alleles, C*04:01 (OR = 2.25, CI 95 % = 1.35-3.75, P = 1.84E-03) and C*15:02 (OR = 2.52, CI 95 % = 1.37-4.64, P = 2.90E-03), were significantly associated with AA after Bonferroni correction. Further, the stratification analysis suggested that C*04:01, C*07:02, and C*15:02 represented different AA genetic risk factors in each sub-phenotype.

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage. Recent studies have described COMP as a pathogenic factor that promotes collagen deposition in fibrotic skin disorders such as scleroderma and keloid skin. Although collagen, a major dermis component, is thought to decrease in photoaged skin, recent reports have demonstrated the presence of tightly packed collagen fibrils with a structural resemblance to fibrosis in the papillary dermis of photoaged skin. Here we examined how photoaging damage relates to COMP expression and localization in photoaged skin. In situ hybridization revealed an increase in COMP-mRNA-positive cells with the progress of photoaging in preauricular skin (sun-exposed skin). The signal intensity of immunostaining for COMP increased with photoaging in not only the papillary dermis but also the reticular dermis affected by advancing solar elastosis. Immunoelectron microscopy detected the colocalization of COMP with both elastotic materials and collagen fibrils in photoaged skin. Ultraviolet light A irradiation of human dermal fibroblasts induced COMP expression at both the mRNA and protein levels. Ultraviolet light A-induced COMP expression was inhibited by an anti-transforming growth factor-β antibody or SB431542, an activin receptor-like kinase 5 inhibitor. These results suggest that the transforming growth factor-β-mediated upregulation of COMP expression may contribute to the modulation of dermal extracellular matrix in the photoaging process.

We have identified and characterized a new gene sequence, TXNRD3NT1, whose transcripts, corresponding to the EST AA430236, were found by Affymetrix DNA chip analysis to be significantly down regulated in affected psoriatic tissue. The full-length cDNA of TXNRD3NT1 was isolated and characterized by combining 5'- and 3'-RACE (rapid amplication of cDNA ends) with screening a keratinocyte cDNA library, designing appropriate PCR primers, cloning amplified products, sequencing, and sequence analysis. Because part of this gene overlaps the previously described thioredoxin reductase 3 (TXNRD3) gene, we have named it TXNRD3NT1 (TXNRD3 new transcript 1). The full-length TXNRD3NT1 cDNA has 1133 nucleotides with a 251-bp 3-UTRand 2 poly(A)signal variants and 2 poly (A) sites. The TXNRD3NT1 cDNA ORF encodes for 133 amino acids, with the first four residues coding for a tubulin-beta mRNA autoregulation signal. Mapping the cDNA nucleotide sequence to the human genome sequence revealed that the TXNRD3NT1 gene has 4 exons located on Chromosome 3, at position 3q21. Exons 1 and 2 of the TXNRD3NT1 gene overlap with exons 15 and 16 of the thioredoxin reductase 2 gene which has different ORFs to that of TXNRD3NT1. The translation initiation codon ATG was found in exon 3 of the TXNRD3NT1 gene. RT-PCR showed that the full-length variant of the TXNRD3NT1 gene was expressed in only four issues (pancreas, esophagus, bone marrow, and keratinocytes) of the 30 different tissues tested. In most other tissues, an aberrant and truncated form of the transcript (i.e., missing exon 3 and part of exon 4) was detected. The result of a preliminary association study between psoriasis and single microsatellite marker of the TXNRD3NT1 gene suggests that it may not be a significant genetic determinant of psoriasis. However, we cannot exclude the possibility that other sequence variants may still exist within the TXNRD3NT1 gene. Sequence analysis of the TXNRD3NT1 gene from 8 psoriasis patients and 8 healthy controls revealed a number of synonymous SNPs that may be useful markers for future disease association studies.

We describe the isolation and characterization of a full-length cDNA encoded by a gene that was significantly down-regulated in the affected skin of patients with psoriasis vulgaris. The cDNA was isolated from a keratinocyte cDNA library and its sequence was found to correspond to a hypothetical locus recorded in GenBank with the accession number LOC146206. The nucleotide sequence of the full-length cDNA was found to have an open reading frame of 1365 amino acids and to span approximately 12 kb of genomic DNA with 39 exons on chromosome 16q22. The deduced amino acid sequence contains four distinct structural regions, an RGD motif, a leucine-rich repeat (LRR) region, a tropomodulin domain, and a proline-rich domain. The gene was consequently designated as RLTPR (RGD, leucine-rich repeat, tropomodulin and proline-rich containing protein). The RLTPR hypothetical protein has a functional domain organization similar to Acan125, a myosin-binding protein expressed by Acanthamoeba castellanni. RT-PCR with RLTPR PCR primers amplified products from cDNAs prepared from all of the 30 different tissues that we examined including thymus, spleen, colon, skin, skin keratinocytes, skin fibroblasts and fetal skin. During the course of screening the human keratinocyte cDNA library, some alternative splicing was also detected in three regions of the RLTPR gene. In addition, sequence analysis of the RLTPR genes from eight psoriasis patients and eight healthy controls revealed a number of synonymous and nonsynonymous SNPs that may be useful markers for future disease association studies.

Secukinumab, a fully human anti-IL-17A monoclonal antibody, neutralizes IL-17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate-to-severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52-week, double-blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI-111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co-primary endpoints (Week 12) were ≥75% improvement in psoriasis area-and-severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5-point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA-C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA-Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA-Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA-C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex- and age-matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early-onset type of psoriasis with HLA-C*06:02 allele in Japanese. In addition, we detected the association between the late-onset type of psoriasis and the HLA-C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.

A 7-year-old boy, taking lessons at a yacht school at Enoshima in Kanagawa prefecture in Japan, recognized a linear eruption on his left lower leg during practice in August 2012. As it gradually enlarged, he visited a local medical clinic. The eruption initially improved with topical treatment but exacerbated in October of the same year. Although topical treatment was started again, there was minimal improvement, so the patient visited our hospital in December. At his first visit, he had a hard linear nodule on his left lower leg, and papules with excoriation were scattered over the lower limbs. Considering eczema, topical steroid treatment and occlusive dressing technique were started but the nodule remained. Based on the clinical course, clinical features, and laboratory findings, the lesion was considered to be delayed flare-up allergic dermatitis caused by a jellyfish sting [1].

We experienced a case of granuloma formation by subcutaneous injection of leuprorelin acetate for treatment of prostate cancer. This patient was an 80-year-old man visiting the clinic of gastroenterological surgery as an outpatient after gastric cancer surgery with a one-week's history of rash on the abdomen. Based on the history of gastric cancer and prostate cancer, though ultrasonography and CT were performed, the possibility of metastatic skin tumor could still not be ruled out. Finally, finding of a foreign-body granuloma in the subcutaneous adipose tissue was recognized histological. Then, an interview with the patient revealed that he had received subcutaneous injection of a 3-month depot formulation of leupurorelin acetate at the site of the lesion about two months earlier. Among urologists, as side effects for treatment, foreign body granuloma induced by subcutaneous injection of leuprorelin maybe well known. Therefore, it is tried to analyze as to clinical findings, especially granuloma formation for 335 cases that received leuprorelin acetate treatment at our hospital. In this report, we analyzed reported case and 335 cases that received leuprorelin acetate treatment at our hospital and summarized the cases that developed the granuloma formation by it.

Background Impaired wound healing in skin ulcer is one of the major medical issues in the aged society. Wound healing is a complex process orchestrated by a number of humoral factors and cellular components. TGF-β is known to stimulate collagen production in dermal fibroblasts while inhibiting proliferation of epidermal keratinocyte. A screening of small compounds that suppress type I collagen production in fibroblasts has identified HSc025 that antagonizes the TGF-β/Smad signal. Objective We examined the effects of HSc025 on dermal wound healing and elucidated the underlying mechanisms. Methods Effects of HSc025 on the wound closure process were evaluated in a murine full-thickness excisional wound healing model. Cell proliferation and migration were estimated using primary cultures of human keratinocytes and fibroblasts. Comprehensive analyses of gene expression profiles were performed using untreated and HSc025-treated fibroblasts. Results Oral HSc025 administration suppressed macrophage infiltration and accelerated wound closure as early as at day 2 after the dermal excision. Treatment of cultured keratinocytes with HSc025 counteracted the inhibitory effects of TGF-β on cell proliferation and migration. On the other hand, HSc025 stimulated migration, but not proliferation, of dermal fibroblasts independently of TGF-β. Experiments using an artificial dermis graft revealed that HSc025 stimulated migration of collagen-producing cells into the graft tissue. A cDNA microarray analysis of untreated and HSc025-treated fibroblasts identified pirin as a critical mediator accelerating fibroblast migration. Conclusion HSc025 accelerates wound healing by modifying infiltration, proliferation and migration of distinct cellular components, which provides a novel insight into the therapy for intractable skin ulcer.

Background Cyclosporine is usually administered after meals. Preprandial administration of cyclosporine has been shown to enhance drug absorption in patients with nephritic syndrome. Methods We compared the pharmacokinetics of cyclosporine after preprandial and postprandial administration in patients with psoriasis. The study group comprised 12 patients (10 men and two women) with psoriasis vulgaris with a mean age of 47.1 years (range, 27–58 years). The subjects received an oral dose of cyclosporine microemulsion (Neoral®) once daily in the morning, either before or after breakfast. The mean dose of cyclosporine was 1.8 mg/kg/day (range, 1.0–2.8 mg/kg/day). Blood samples were collected immediately before and 1, 2, 3, and 4 h after treatment. Results After the postprandial administration of cyclosporine, the mean area under the drug concentration–time curve from 0 to 4 h after treatment (AUC0−4) was 1393.5 ng h/mL and the mean maximum drug concentration (Cmax) was 604.1 ng/mL. After preprandial administration, the mean AUC0−4 was 2195.2 ng h/mL and the mean Cmax was 1054.9 ng/mL. AUC0−4 and Cmax were significantly greater after preprandial administration of oral cyclosporine than after postprandial administration. Conclusions Our results suggest that the preprandial administration of cyclosporine enhances drug absorption in patients with psoriasis, potentially allowing the daily dose of cyclosporine to be reduced when compared with postprandial administration.

A 73-year-old male with diabetes mellitus had been treated with insulin for six years. He developed a solid mass on his left lateral of the abdomen at the insulin injection site. A firm subcutaneous mass with dark-red erythema was overlaid by dark-brown keratinized plaques. On histological examination of the mass, keratin proliferation and epidermal papilloma were observed. There were four previously reported cases of acanthosis nigricans that were considered to be caused by continuous injections of insulin. Using immunohistochemistry, in our case the findings were positive in the basal epithelial and prickle cell layers when the patient's lesion was dyed with insulin-like growth factor (IGF)-1 antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found in our patient has not been reported previously, to our knowledge.

Disseminated herpes zoster is not rare in immunocompromised patient. It is defined as at least 20 lesions in multiple dermatomes that occur within a week of the onset of local eruption. Herein, we report that a case of disseminated vesicles of herpes zoster (HZ) that developed one day before the onset of local eruption in an immunocompromised patient. A 44 year-old Japanese male, who had been in the hospital with acute myelocytic leukemia, developed disseminated hemorrhagic vesicles of 5 to 10 mm in diameter. The next day, grouped vesicles, including hemorrhagic vesicles erupted on the right side of the second to third cervical (C2-C3) dermatomes. At this point, the diagnosis was made as disseminated herpes zoster. The activation of varicella-zoster virus (VZV) is believed to be due to waning of VZV-specific memory T cell responses. In our case, the memory immunity to VZV which had been increased by last episode of HZ might affect on the appearance of skin eruptions.

To evaluate the diagnostic usefulness of Doppler sonography for amelanotic melanoma (AM), the correspondence between the findings of dermoscopy and Doppler sonography was investigated in AM in comparison with other hypopigmented tumors. Seven cases with AM and 11 cases with squamous cell carcinoma (SCC), 10 cases with non- or hypopigmented basal cell carcinoma (NP-BCC) and six cases with eccrine poroma (EP) as hypopigmented tumors were investigated. EP is readily recognized by differences from AM and SCC based on a single vertical and non-torvtuous vessels. NP-BCC is distinguished from AM based on tortuosity running in a vertical direction. Though findings of tortuosity in vessels and heterogeneity of vessel size are recognized both in AM and SCC: (i) abundant blood flow was recognized more clearly in AM; (ii) total blood flow was more than 40% in most cases of AM (average, 60.9%); and (iii) more vessels which flow into a tumor are found in AM (85.7%). There is no relationship between dermoscopic findings of vessel types and Doppler sonography findings of vessels. In this study, the diagnostic usefulness of the above-mentioned specific findings in examination may suggest using Doppler sonography for AM as one non-invasive method.

A 72-year-old woman visited our clinic with fever of unknown origin above 38°C and arthralgia from 7 months before. Her symptoms recurred as oral steroid was reduced. Random skin biopsy was carried out from five points. One of the five specimens taken from abdomen revealed large atypical lymphoid cells in the vascular space of subcutaneous fat. Immunohistochemical analysis showed that these cells were positive for CD20, CD79a, bcl-2, bcl-6 and MUM-1. From these findings, a diagnosis of intravascular large B cell lymphoma was made.

The aim of this study was to assess the quality of life (QOL) of patients with psoriasis in Japan using Dermatology Life Quality Index (DLQI). Furthermore, we had evaluated the correlation between DLQI and clinical severity of psoriasis.The Japanese version of DLQI was used to assess the QOL of patients. Psoriasis area and severity index (PASI) and Itch visual analogue scale (VAS) were used to assess clinical severity of psoriasis.The subjects were 102 Japanese patients with mild to severe psoriasis (77 males, 25 females, mean age 55.2 ± 14.2). There were no statistically significant differences in age, PASI, and itch VAS between male and female. The mean DLQI scores in total were 3.6 ± 3.2 in male and 7.2 ± 1.2 in female. The mean total DLQI scores in female were higher than that in male (p = 0.0016). Significant correlation was observed between DLQI scores and PASI score (p0.001) or itch VAS score (p0.001).The mean total DLQI scores in female were significantly higher than that in male. Also, we confirmed the correlation between DLQI and clinical severity of psoriasis. These findings suggest that QOL assessment plays a greater role in females than in the males, when assessing the severity of psoriasis.

During the past 5 years, genome-wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. These studies appeared to provide strong evidence because the susceptibility genes are involved in the interleukin-23/T-helper 17 axis of psoriasis immunopathogenesis and/or skin barrier functions. However, the "identified" genes only explained a small proportion of psoriasis heritability, although it is known to be comparatively higher than that of other common diseases. GWAS are based on the hypothesis that disease-causing variants are high frequency variants within populations. However, this hypothesis is problematic because deleterious variants such as those predisposing to specific diseases will generally not be maintained by selection pressure throughout human evolution. This issue also affects psoriasis studies. Here, we review the current paradigm shift in human genetic analyses and its implications for detection of psoriasis-causing variants based on linkage analysis and GWAS, except the well-known psoriasis susceptibility locus HLA-C.

CADM2, a candidate gene for psoriasis, was identified by a genome-wide association study using microsatellites in the Japanese population (561 cases and 561 controls). Moreover, haplotype analysis included an additional 68 SNPs and indicated that a 110-kb haplotype block was detected for the protective risk haplotype of psoriasis. We also identified an initial exon of novel splicing variants in this haplotype block. A functional analysis by qRT-PCR using RNAs from the blood of 56 cases and 64 controls significantly demonstrated an inverse correlation between expression frequencies in a novel splicing variant and the number of alleles associated with psoriasis. To confirm these results, we must perform replication studies using other ethnic groups and more functional analysis particularly for skin tissues.

Nocardiosis is caused by gram-positive aerobic actinomycetes that live in soil and are known to be responsible for opportunistic infections. The condition mostly affects the lung, brain or skin. Here, we present a 24-year-old Japanese woman who had had systemic lupus erythematosus since the age of 20 years, and lupus nephritis since the age of 23 years. She developed cutaneous lymph duct-type nocardiosis due to Nocardia araoensis while on immunosuppressant therapy. The patient had cutaneous findings from the right inguinal region to the right lower thigh and did not have lesions on the rest of the body. Minocycline and co-trimoxazole were co-administrated, and her condition improved. To our knowledge, this is the first case in which N. araoensis was detected by analysis on rRNA base sequence in skin lesions.

Chromomycosis is a chronic fungal disease of the skin and subcutaneous tissues caused by a group of dematiaceous black fungi. Small lesions can be removed with excision, but other cases are difficult to treat. We report a case of chromomycosis caused by Fonsecaea pedrosoi (F. pedrosoi). The case involved a 74-year-old man, who had noted a lesion on the back of the right thigh, that was gradually enlarging and reaching up to 30 cm in diameter, in 20-years. From microscopic examination, sclerotic cells were seen. We diagnosed this case as chromomycosis caused by F. pedrosoi on mycological examination. The patient was initially treated with oral terbinafine (250 mg/day) as the lesion was very large. After the 18 months treatment, the size of the lesion reduced to 1 cm, then the remaining lesion was excised.

Contains fulltext : 96094.pdf (Publisher’s version ) (Closed access) A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OR(Overall) = 1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR = 1.27 (1.16-1.34)) and Mongolian (OR = 2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis.

Oxidative stress derived from ultraviolet (UV) light in sunlight induces different hazardous effects in the skin, including sunburn, photo-aging and DNA mutagenesis. In this study, the protein-bound lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8OHdG) were investigated in chronically sun-exposed and sun-protected human skins using immunohistochemistry. The levels of antioxidative enzymes, such as heme oxygenase 1 and 2, Cu/Zn-SOD, Mn-SOD and catalase, were also examined. Oxidative stress is also implicated in the activation of signal transduction pathways, such as mitogen-activated protein kinase (MAPK). Therefore, the expression and distribution of phosphorylated p38 MAPK, phosphorylated Jun N-terminal kinase (JNK) and phosphorylated extracellular signal-regulated kinase (ERK) were observed. Skin specimens were obtained from the surgical margins. Chronically sunlight-exposed skin samples were taken from the ante-auricular (n = 10) and sunlight-protected skin samples were taken from the post-auricular (n = 10). HNE was increased in the chronically sunlight-exposed skin but not in the sunlight-protected skin. The expression of heme oxygenase-2 was markedly increased in the sunlight-exposed skin compared with the sun-protected skin. In contrast, the intensity of immunostaining of Cu/Zn-SOD, Mn-SOD and catalase was not different between the two areas. Phosphorylated p38 MAPK and phosphorylated JNK accumulated in the ante-auricular dermis and epidermis, respectively. These data show that particular anti-oxidative enzymes function as protective factors in chronically sunlight-exposed human skin. Taken together, our results suggest (1) antioxidative effects of heme oxygenase-2 in chronically sunlight-exposed human skin, and that (2) activation of p38 MAPK may be responsible for oxidative stress.

In some herpes zoster (HZ) patients, one symptom is problematic; postherpetic neuralgia (PHN), a persistence of pain such as spontaneous pain and stimulus-evoked pain, allodynia or hyperpathia, for more than 6 months after healing of the vesicular eruptions. In our previous study, we reported the association between HLA alleles, HLA-A*33 and B*44, and PHN patients. In this study, we aim to refine the association of these alleles with PHN or HZ using higher-resolution HLA typing technique with an increased sample size.HLA allele frequencies were compared in 70 PHN patients, 80 HZ patients, 52 HZ(-) patients, and 140 Japanese controls using HLA typing kits of SSOP protocols.The allele frequencies of HLA-A*3303, B*4403, and DRB1*1302 in PHN(+) patients were significantly higher than those in Japanese controls (P=0.00007, P=0.000002, and P=0.0003, respectively). The frequencies of above alleles in PHN(+) patients were also significantly higher than those in PHN(-) patients (P=0.03, P=0.006 and P=0.03, respectively). However, no association was found in comparison of HZ(+) patients and HZ(-). And the frequency of HLA-B*5101 in HZ(-) patients was significantly higher than those in HZ(+) and PHN(+) patients (P=0.003 and P=0.009, respectively) indicating that HLA-B*5101 functions as a protective allele to HZ.

A 66-year-old Japanese man had skin lesions on the left side of his trunk and the left upper extremity for approximately 10 years. The skin lesions were asymptomatic but increased gradually, which brought the patient to our hospital. On the initial examination, we noticed 5 mm x 5 mm to 15 mm x 5 mm, round or oval, light to dark brown keratotic papules on the left side of chest and abdomen and the left upper extremity. The papules were aligned in an S-shaped line on the trunk and in a straight line on the upper extremity. Clinical and histopathological findings led to a diagnosis of seborrheic keratosis that followed Blaschko's lines. To our knowledge, no such a case has been reported previously. Our case supports the hypothesis that seborrheic keratosis can be associated with genetic mosaicism.

A 70-year-old Japanese woman visited our clinic with a pigmented patch on her face from her upper lip to under her nose following laser therapy 15 years ago. Physical examination revealed an asymmetrical dark brown macule with a clear border along with irregular black dots measuring 20 mm. A biopsy specimen showed some irregular-sized atypical melanocytes with deep-colored nuclei on staining. There were observed on the basal layer and a few of them in the prickle-cell layer only in the epidermis. We diagnosed this case as lentigo maligna (LM). Total resection and reconstruction with the Abbe flap were carried out. We searched previous literature for reports on laser therapies resulting in LM and determined the following: (1) there were no reports indicating that laser therapy is one of the causes of LM, (2) judging from invalidity of treatment or recurrence of the condition, laser therapies were considered ineffective for LM treatment, and (3) the numbers of patients undergoing laser therapies, who were not diagnosed with LM, were increasing.

The association between psoriasis and the HLA antigens encoded by the Major Histocompatibility Complex (MHC) genomic region is well known, but the role of the HLA class II region in susceptibility to psoriasis is unclear.The purpose of this study is to map the psoriasis-susceptibility locus within the HLA class II region.Three hundred seventy five unrelated Japanese patients with psoriasis vulgaris and 375 unrelated Japanese healthy controls were studied by an association analysis using 15 polymorphic microsatellite markers.Statistically significant differences were found at three microsatellite loci. The most significant association of psoriasis vulgaris with the microsatellite markers was found with DRA_CA (pc=0.0000135), the second with DQCARII (pc=0.0000840) and the third with G5_11525 (pc=0.0240). These significant microsatellite markers are in close vicinity to the DQA2, DQB1, DRB1, DRA and BTNL2 genes.The results suggest that there are psoriasis susceptibility genes located within the HLA class II region and therefore strongly support previous findings of a positive association between psoriasis and certain alleles of the DQB1 and DRB1 genes.

Autoimmune bullous diseases are classified into pemphigus and pemphigoid. Pemphigus is designated as incurable disease by the Ministry of Health, Labor and Welfare, and it is said that pemphigus is difficult to care and can be fatal. The clinical course of bullous pemphigoid (BP) is better than that of pemphigus. However, as to the incidence of internal malignancies, it is well known that there is a significant difference between the two diseases. As the incidence of internal malignancies is high in BP, it is described in textbooks that patients with BP should be followed by a detailed screening for internal malignancies. We investigated the incidence of internal malignancies in 204 Japanese patients with autoimmune bullous disease who visited Tokai University Hospital in Kanagawa, Japan. We found that the incidence of internal malignancies was 11.2% in patients with pemphigus and 10.4% in patients with BP. Among pemphigus variants, the incidence was as high as 20% for pemphigus erythematosus. No relationship was found between malignancies and the severity of the autoimmune bullous diseases. Therefore it is clinically important to carry out a detailed screening for internal malignancies in patients with pemphigus as well as in patients with BP.

Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. HUG95A Affymetrix DNA chips that contained oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student t-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signalling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases, including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T cells. Some of the up-regulated genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the up-regulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic interferon- and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.

hRDH-E2 is a member of the short-chain alcohol dehydrogenase/reductase (SDR) family that converts retinol to retinaldehyde as the first and rate-limiting step in the retinoic acid synthetic pathway. This pathway is critical for the maintenance of epidermal homeostasis in vivo. Previously, we reported that the mRNA levels of hRDH-E2 in psoriatic skin were elevated significantly compared with that in healthy individual skin and psoriatic unaffected skin. The gene encoding hRDH-E2 is located on Chromosome 8 close to a candidate region for psoriasis and therefore is a functional and positional candidate for this disorder. In the present study, the transcription start sites for hRDH-E2 gene transcription in the lung were found to be more upstream of those that were identified previously in keratinocytes. Consequently, differences in the nucleotide sequence were determined for all of the coding exons, untranslated regions, and at least 2850 bp of 5'-noncoding sequence of hRDH-E2 by direct sequencing of polymerase chain reaction (PCR)-amplified DNA samples obtained from 8 psoriatic patients and 8 healthy controls. One polymorphic microsatellite marker at the noncoding 3' end of the gene and six single nucleotide polymorphisms (SNPs) (three in the 5' flanking sequence, two in the coding sequence, and one in the intronic sequence) were identified. One of the SNPs was nonsynonymous in the second exon with an allelic variation between the amino acid sequences Arg and Trp. The microsatellite marker and the six SNPs were all genotyped in 100 Japanese psoriatic patients and 120 controls. However, there were no statistically significant differences in the genotype or allele frequency distributions between the cases and controls. On this basis, we conclude that the polymorphisms that we detected for the hRDH-E2 gene do not contribute to the etiology of psoriasis but may be important in diseases of other tissues.

Atopic dermatitis (AD) is presumed to be influenced by genetic and environmental factors. In this study, 54 patients with AD were examined for disease association by the use of 12 microsatellite markers. Several significant associations were recognized in the alleles on chromosome 5, 7 and 11. AD genes were mapped near the FC epsilon RI beta gene (around D11S1314 locus) on chromosome 11, the IL4 gene cluster on chromosome 5 and the TCR gamma gene on chromosome 7. This distribution in close proximity to candidate loci for AD is very similar to that of atopic genes, therefore implying that an atopic trait is genetically responsible for the development of AD.