Transglutaminase 3 Attenuates Skin Inflammation in Psoriasis by Inhibiting NF-κB Activation through Phosphorylated STAT3-TET3 Signaling.

Transglutaminase 3 (TGM3) protects against skin inflammation in psoriasis, but the precise role and mechanism of action of TGM3 in the pathogenesis of psoriasis remain unclear. In this study, we show that TGM3 expression was increased in the skin lesions of patients with psoriasis and a mouse model of imiquimod-induced psoriatic dermatitis. TGM3 overexpression decreased the production of proinflammatory factors in cultured primary keratinocytes stimulated with psoriasis-related cytokines. TGM3 inhibited the phosphorylation of signal transducer and activator of transcription 3 and the recruitment of ten-eleven translocation 3 to the p65 gene promoter, resulting in decreased promoter demethylation and subsequent suppression of proinflammatory cytokine/chemokine production. TGM3-induced inhibition of phosphorylated p65 might also decrease ten-eleven translocation 3 expression. Moreover, topical application of Tgm3-specific small interfering RNA or the pan-transglutaminase inhibitor cysteamine exacerbated skin inflammation in mice with imiquimod-induced psoriatic dermatitis. Our study revealed an epigenetic pathway mediated by the interaction between TGM3 and ten-eleven translocation 3 in keratinocytes for regulation of skin inflammation in psoriasis, providing a potential target for psoriasis treatment.

Single dose pharmacokinetics of topical iodiconazole creams in healthy Chinese volunteers.

1.In this study, the pharmacokinetics of new triazole antifungal iodiconzole creams at target sites after single-dose topical application was investigated.2.30 healthy Chinese volunteers were randomly divided into three groups after being stratified by sex, each group was given a single topical dose of 1%, 2%, 4% iodiconazole cream (0.4 g). Stratum corneum (SC) samples of treated sites were collected by tape-stripping method after the chosen contact times, and were extracted and analysed by a validated LC-MS method.3.After single-dose topical application of 1%, 2%, 4% iodiconazole creams, the Cmax of iodiconazole in SC was 1.2 ± 0.7, 2.2 ± 1.0, 2.4 ± 1.0 mg/g; Tmax was 3.3 ± 1.1, 2.9 ± 1.1, 3.8 ± 0.4 h; t1/2 was 6.6 ± 3.4 h, 7.2 ± 4.1 h, 5.9 ± 2.9 h; AUC0-t was 10.9 ± 3.0, 20.8 ± 10.4, 20.9 ± 7.9 mg·h/g; AUC0-∞ was 11.6 ± 2.9, 23.5 ± 14.4, 22.2 ± 8.9 mg·h/g, respectively. The results showed that Cmax, AUC0-t and AUC0-∞ did not increase proportionately with dose, which could also be due to the drug being saturated in the formulation at ∼2%.4.The results of this study could provide reference for the clinical medication and further study of the formulations.

Primary Cutaneous Sarcomatoid Anaplastic Lymphoma Kinase-Positive Anaplastic Large-Cell Lymphoma With Linear Distributional Lesions.

We report a case of cutaneous anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALCL) with linear distributional lesions and sarcomatoid histologic features. A sarcomatoid variant is the rarest morphological pattern of ALCL. Interestingly, the morphology of tumor cells in the present case transitioned from a sarcomatoid variant of ALCL at first diagnosis to a classic variant at relapse. The case is a diagnostic challenge considering both the clinical and histologic aspects. Awareness of the sarcomatoid variant of ALCL and its morphological changes can lead to a correct diagnosis.

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis.

Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age≤18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis.

Prevalence of Atopic Dermatitis in Chinese Children aged 1-7 ys.

Prevalence of atopic dermatitis (AD) is increasing worldwide. Up to date, there has been no face-to-face nation-wide study in China. We aim to explore the prevalence of clinical diagnosed AD in children aged 1-7 ys in China. Twelve metropolises were chosen from different areas of China. In each region, we selected 4-10 kindergartens and 2-5 vaccination clinics randomly. A complete history-taking and skin examination were performed by dermatologists. The definite diagnosis of AD and the severity were determined by two or three dermatologists. All criteria concerned in UK diagnosis criteria, characteristic presentation of AD and atypical manifestations were recorded in detail. A total of 13998 children from 84 kindergartens and 40 vaccination clinics were included. The prevalence of AD was 12.94% by clinical diagnosis of dermatologists overall, with 74.6% of mild AD. Comparatively, prevalence of AD based on UK diagnostic criteria was 4.76%. This is the first face-to-face nation-wide study in Chinese children aged 1-7 ys, revealing that the prevalence of AD in children is closer to that of wealthier nations.

Cutaneous infections caused by rapidly growing mycobacteria: case reports and review of clinical and laboratory aspects.

Skin and soft tissue infections caused by rapidly growing non-tuberculous mycobacteria (RG-NTM) have become a growing clinical concern over the past decades. These RG-NTM are ubiquitous environmental organisms and most are resistant to traditional antituberculous agents. In this report, we describe 3 cutaneous infections caused by RG-NTM, namely, Mycobacterium abscessus, M. chelonae, and M. conceptionense, and present the clinical and laboratory characteristics of these infections.

A retrospective study on laser treatment of nevus of Ota in Chinese children--a seven-year follow-up.

OBJECTIVE: To retrospectively study laser treatment of nevus of Ota in children. METHODS: Clinically analyzing characteristics, effects, side effects, and recurrence of a 104 cases of nevus of Ota in children under 12 years, including 32 boys and 72 girls. RESULTS: After seven treatments, cure rate of lesion color fading and area reducing were 79.81% and 75.96%, respectively. After 10 treatments, both of the two cure rates were 96.15%. Later the cure rate was constant with even more treatments. The younger the first treating age, the lesser the treatments are. The younger the age of onset, the higher the relapse after clearance. CONCLUSION: Nevus of Ota should be treated as early as possible to reach better efficacy with less treatments. The younger the onset age, the easier it recurs.

The first case of cutaneous infection with Mycobacterium parascrofulaceum.

The authors present the first, to the best of their knowledge, reported case of cutaneous infection caused by Mycobacterium parascrofulaceum. A 42-year-old woman presented with asymptomatic reddish papules, nodules, plaques, and patches on the right side of her face and on her forehead that had persisted for 5 years, with the lesions gradually increasing in size over that time. No previous intervening medical treatment had been applied. No history or evidence of immunosuppression was found. A skin biopsy was performed for routine histological examination. Samples of lesioned skin were inoculated on Löwenstein-Jensen medium to determine the presence of acid-fast bacilli. Ziehl-Neelsen staining was used to confirm the presence of the organism. In vitro drug susceptibility testing was conducted using the microtiter plate method. Mycobacterium was identified by polymerase chain reaction-restriction fragment length polymorphism analysis and sequencing of the hsp65 and 16S rDNA genes. Cultures for aerobic and anaerobic bacteria, as well as fungus, were also conducted. Routine histopathology revealed granulomatous changes without caseation. Ziehl-Neelsen staining showed that the organisms in both the lesions and the cultures were acid-fast bacilli. The cultured colonies were grown in Löwenstein-Jensen medium and incubated at two different temperatures (32°C and 37°C) for 2-3 weeks, developing pigmentation both in the dark and in the light. In vitro drug susceptibility tests showed that the organism was sensitive to clarithromycin and moxifloxacin. Polymerase chain reaction-restriction fragment length polymorphism analysis and sequencing of the hsp65 and 16S rDNA genes confirmed that the isolated organisms were M. parascrofulaceum. Fungal and other standard bacterial cultures were negative. In conclusion, identification and diagnosis of nontuberculous mycobacteria should be performed promptly to obtain better prognoses. Empirical treatments may be feasible, and drug susceptibility tests are important.

Outbreak of a cutaneous Mycobacterium marinum infection in Jiangsu Haian, China.

Mycobacterium marinum is a slow-growing mycobacterium. In November 2008, we diagnosed a patient with M. marinum infection who worked at a fish farm in Jiangsu Haian, China. We conducted an investigation and found 18 patients with the same infection. In suspected cases, complete data were collected including medical history, clinical manifestations, laboratory features, and responses to treatment. Therapeutic regimens, including clarithromycin monotherapy or combined treatment with clarithromycin, rifampicin, and ethambutol, were prescribed. A total of 18 patients with M. marinum infection were found. All patients showed only skin lesions. Biopsies were performed and 16 patients showed infective granulomas. Acid-fast bacilli stain (Ziehl-Neelson stain) for cutaneous samples were positive in 7 patients. Ten patients were positive in purified protein derivative tests (tubercles were ≥10 mm in diameter). In 16 patients, colonies grew after tissue samples were incubated on Löwenstein-Jensen medium at 32 °C. All the isolates were identified as M. marinum by polymerase chain reaction-restriction fragment length polymorphism analysis, by direct gene sequencing, and by genotyping using mycobacterial interspersed repetitive units. Fifteen of the 18 patients were cured using clarithromycin-containing antibiotic regimens. The history of contact with fish and aquaria plays an important role in diagnosis. Clarithromycin-containing regimens were successful in most patients with M. marinum infections limited to the skin.

Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. Genetic studies have identified mutations in ADAR1 gene to be responsible for this disorder. We detected two mutations in two families with DSH, which include a heterozygous g-->a transversion at the first base of the 3'-acceptor splice site of intron 5 (c. 2080-1g>a, IVS5-1g>a) and a transition c.3076C>T. IVS5-1g>a should prevent proper splicing of the transcript while c.3076C>T leading to a missense mutation p.R1026W of the ADAR1 gene. Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH.