Xibao Zhang

Severe ichthyosis-related disorders in children: Response to acitretin

One case of keratitis ichthyosis deafness (KID) syndrome and two cases of bullous ichthyosiform erythroderma (BIE) were treated with systemic acitretin. The severe hyperkeratotic lesions improved dramatically with acitretin therapy in the KID case. Substantial improvement of the palmoplantar keratoderma was also observed. During follow‐up, laboratory results remained within normal limits and no skeletal abnormalities were detected. The two cases with BIE also showed good responses to acitretin. Long‐term follow‐up of these cases showed that signs and symptoms were well under control and no adverse effects were noted.

Clinical investigation of acitretin in children with severe inherited keratinization disorders in China

Objective: Investigation into the clinical efficacy, side effects and safety of oral acitretin on severe inherited disorders of keratinization in children. Methods: Acitretin was given as a treatment dose of 0.77–1.07 mg/kg·per day (mean 0.86±0.11) and maintenance dose of 0–0.94 mg/kg·per day (mean 0.33±0.26) to 28 children with severe inherited disorders of keratinization. Body height and weight were chosen as the monitoring indexes to evaluate the growth and development and other common side effects as the safety evaluation of the children for a follow‐up of 2–36 months. Results: After 2–4 months of treatment, the clinical cure rate was 82.1% and the effective rate was 17.9%. Most cases, such as bullous ichthyosiform erythroderma, lamellar ichthyosis, pityriasis rubra pilaris, and inflammatory linear verrucous epidermal nevus showed remarkable therapeutic response; non‐bullous ichthyosiform erythroderma was also effective. Two cases with Dariers disease were previously shown to be resistant to acitretin therapy, but improved after 6 months of treatment. No previous investigation had been made on a negative effect on the growth and development of such children. Conclusion: Acitretin showed a satisfactory therapeutic effect on severe inherited disorders of keratinization in children.

Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated from Guangzhou, China, 2000 to 2005 and 2008 to 2013.

A total of 1224 Neisseria gonorrhoeae isolates from Guangzhou in 2 periods (2000-2005 and 2008-2013) were subjected to antimicrobial susceptibility testing. The percentage of penicillin- and ciprofloxacin-resistant isolates increased from 71.1% (473/665) to 90.9% (508/559) and 88.9% (591/665) to 98.0% (548/559), respectively. All isolates remain susceptible to spectinomycin and ceftriaxone, with increasing minimum inhibitory concentrations.

Evidence for the absence of mutations at GJB3, GJB4 and LOR in progressive symmetrical erythrokeratodermia

Background.  Progressive symmetrical erythrokeratodermia (PSEK) is a rare inherited cornification disorder characterized by symmetrical erythematous hyperkeratotic plaques. The genetic basis for PSEK is not clear. PSEK shares many clinical features with erythrokeratodermia variabilis (EKV), which is associated with mutations in genes coding for gap junction beta (GJB) 3 and 4. A mutation in the loricrin gene (LOR) was found in patients with PSEK, who were members of a family with Vohwinkel syndrome. It would therefore be of interest to determine if PSEK is also caused by mutations in these genes.

Mutation of GJB2 in a Chinese patient with keratitis–ichthyosis–deafness syndrome and brain malformation

Objective.  Keratitis–ichthyosis–deafness syndrome (KID) is a rare congenital disorder. Mutations in the GJB2 gene have recently been identified as the causative mutations of KID.

Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway.

Dysregulation of miRNAs is a common feature in human cancers, but there are lack of studies on roles of miRNAs in cutaneous squamous cell carcinoma (CSCC). miR-148a, a member of the miR-148/152 family, has been found to be downregulated in different types of cancer and its role in CSCC remains unknown. The study was aimed to investigate the expression and cellular function of miR-148a in CSCC. We found that miR-148a was underexpressed in CSCC tissues and cell lines. MAP3K2, MAP3K4 and MAP3K9 were predicted as the target genes of miR-148a and the latter two genes were verified as the target genes of miR-148a in CSCC cells. Importantly, we demonstrated that the overexpression of miR-148a significantly inhibited CSCC cell proliferation and metastasis via down-regulation of MAP3K9 and MAP3K4 expression. MAP3K4 and MAP3K9 were negatively associated with the expression of miR-148a in CSCC tissues. Our results suggested indicated that miR-148a acts as a tumor suppressor of CSCC via inhibiting MAPK pathway. These results may provide a promising alterative strategy for CSCC therapy.

Ultrastructural Study of Symmetrical Acral Keratoderma

Abstract Background: Symmetrical acral keratoderma is characterized by symmetrical brown hyperkeratotic patches on the acral extremities. However, no studies about its electron microscopic examination have been documented. Objective: Our study was performed to further characterize the histopathology of symmetrical acral keratoderma. Methods: A biopsy was taken from brown hyperkeratotic patches on the wrists. Investigative studies included light and electron microscopy. Results: Light microscopy showed epidermal basket-weave hyperkeratosis and acanthosis. Ultrastructurally, the epidermis was thickened by acanthosis and compact stratum corneum. The horny cell layers were remarkably thicker in clinical affected skin than in adjacent clinically unaffected and healthy skin. The keratin filaments were remarkably clumped or aggregated and irregularly distributed in the horny, spinous, granular and basal cell layers. The tonofilaments formed tight clumps or aggregated at the perinuclear cytoplasm. Conclusion: The main ultrastructural features of symmetrical acral keratoderma were epidermal hyperkeratosis and abnormalities of the keratin filaments and tonofilaments.

Fine mapping of the disseminated superficial porokeratosis locus to a 2.7 Mb region at 18p11.3.

Disseminated superficial porokeratosis (DSP) is an autosomal dominant epidermal keratinization disorder. The genetic basis for DSP has not been clearly elucidated. We previously mapped the locus for DSP to a large region (5.7 Mb) at 18p11.3 in a four‐generation Chinese family with DSP, but no gene responsible for porokeratosis has been identified to date. To narrow the critical region for DSP, thereby facilitating the identification of this disease gene and possibly leading to an understanding of the pathogenesis of porokeratosis, genotyping was performed on the same Chinese family with DSP using nine heterozygous single‐nucleotide polymorphism markers at 18p11.3. We found the locus of DSP to be located within a 2.7 Mb region between markers rs58085394 and rs238533. Our study provides a map location for isolation of a gene causing DSP.

S159P mutation of keratin 10 gene causes severe form of epidermolytic hyperkeratosis

highlights MEC as a common finding in DA. Although mechanisms underlying formation of MEC in non-viral conditions are poorly understood, cell-cell fusion and disruption of cytokinesis are possible explanations. While viral infections must be excluded, our experience suggests the presence of MEC with greater than five nuclei, when accompanied by epidermal necrosis and in the appropriate clinical setting, may provide a clue to the diagnosis of DA in the paediatric population. J. Guitart had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: J. Guitart. Acquisition of data: S. Amin, O. Y elamos, M. Martinez-Escala, L. Shen., J. Guitart, M. Rosenbaum, B. Kenner-Bell, A. Mancini, A. Paller. Drafting of the manuscript: S. Amin, O. Y elamos, M. Martinez-Escala, J. Guitart. Critical revision of the manuscript for importance intellectual content: J. Guitart, B. Kenner-Bell, A. Mancini, A. Paller, M. Rosenbaum, P. Gerami. Administrative, technical or material support: J. Guitart, S. Amin, O. Y elamos, M. Martinez-Escala. Study supervision: J. Guitart.

Lack of association between cytotoxic T-lymphocyte antigen-4 + 49A/G polymorphism and psoriasis and vitiligo: A meta-analysis of case–control studies

BACKGROUND Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of T-cell activation and proliferation. Several studies have assessed the association between CTLA-4+49A/G polymorphism and psoriasis and vitiligo, but the results are inconsistent. AIMS This study was conducted to examine the association between CTLA-4+49A/G polymorphism and psoriasis and vitiligo susceptibility. METHODS The PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched according to predefined criteria for all relevant studies published prior to July 3, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs), and heterogeneity and publication bias tests were performed to estimate the strength of the association. RESULTS Fourteen studies comprising six on psoriasis (700 cases, 781 controls) and eight on vitiligo (1514 cases, 2049 controls) were included. Overall, no significant association was detected between CTLA-4+49A/G polymorphism and psoriasis. There was still no significant relationship when the studies were limited to ethnicity (Asian and Caucasian), HWE or heterogeneity, except the limitation to heterogeneity in the dominant (OR=0.69, 95% CI=0.51-0.93, I(2)=0.0%) and additive (OR=0.69, 95% CI=0.48-0.98, I(2)=0.0%) models, and the limitation to both heterogeneity and HWE in the dominant model (OR=0.68, 95% CI=0.48-0.98, I(2)=0.0%). Both overall and subgroup analyses based on ethnicity, genotype frequencies, and heterogeneity also failed to demonstrate an association between CTLA-4+49A/G polymorphism and vitiligo. CONCLUSION CTLA-4+49A/G polymorphism may not contribute to psoriasis and vitiligo susceptibility, but further well-designed studies with large sample size are warranted to confirm this conclusion.