Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: A retrospective case series.

Rosacea is a chronic inflammatory skin disease characterized by facial erythema, papules, pustules, telangiectasia, and flushing. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway appears to play a role in the pathogenesis of rosacea. Our study preliminarily explored the efficacy of JAK inhibitor tofacitinib in the treatment of rosacea. We retrospectively reviewed the cases of 21 patients with rosacea who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg as either monotherapy or adjunctive therapy. We have observed that 15 out of 21 patients (71.4%) patients experienced significant regression of erythema on the face (IGA ≤ 1), and a mean change of -2.24 in the Investigator's Global Assessment (IGA) score was significant improvement from baseline. Treatment with oral tofacitinib might be a potentially effective treatment to ameliorate the symptoms of rosacea.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

Association of rs10954213 polymorphisms and haplotype diversity in interferon regulatory factor 5 with systemic lupus erythematosus: a meta-analysis.

The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.

Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels.

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.

Pathogen Analysis of Superficial Mucocutaneous Mycosis in a Tertiary A-level Hospital from 2007 to 2018.

OBJECTIVE: This study aimed to analyze the fungal species of pathogens isolated from patients with superficial mucocutaneous mycosis from May 2007 to December 2018. METHODS: A retrospective analysis was carried out to determine the pathogenic fungi isolated from patients with superficial fungal infections in the Medical Mycology Clinical Laboratory, Department of Dermatology and Venereology, Union Hospital, from May 2007 to December 2018. RESULTS: A total of 7639 strains were obtained, belonging to 21 genera and 36 species. They mainly consisted of Candida (3707/7639, 48.53%) and dermatophytes (3594/7639, 47.05%). The specimens were skin scales, nail shavings, secretions on the nail grooves, broken or diseased hair and dandruff, secretions or pseudomembrane of the external genitalia, and the oral mucosa. A total of 7300 patients were enrolled in this study, including 3301 males and 3999 females aged 2 months to 92 years old with a median age of 46.04 years old except for 633 patients whose ages were unknown. Two strains of different species were isolated from each of 339 patients at different body sites. The most frequent species were Trichophyton rubrum complex (2906/7639, 38.04%), Candida albicans (2619/7639, 34.28%), and unclassified Candida spp. Dermatophytes were mostly isolated from glabrous skin (2138/3594, 59.49%), with T. rubrum complex being the predominant species. Candida strains were most commonly isolated from mucosal sites (1979/3707, 53.39%), and C. albicans was the most prevalent causative agent. CONCLUSION: The main distribution of pathogenic fungal species isolated from patients with superficial mycosis from 2007 to 2018 in Wuhan, Hubei province and the surrounding areas was that Candida slightly outnumbered dermatophytes. Among all of the isolated strains, T. rubrum complex was the most abundant.

Identification and Interaction Analysis of Key Genes and MicroRNAs in Systemic Sclerosis by Bioinformatics Approaches.

Systemic sclerosis (SSc) is a highly heterogeneous autoimmune disease with a high mortality rate. However, the cellular and molecular mechanisms of SSc remain unclear. Here, we identified the key hub genes and microRNAs (miRNAs) that modulate the occurrence and development of SSc. We downloaded the microarray dataset GSE95065 from the Gene Expression Omnibus (GEO) database and then analyzed the data by using GEO2R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for functional pathway enrichment analyses of differentially expressed genes (DEGs), and Cytoscape software was used to generate the protein-protein interaction (PPI) network. In addition, OmicsNet was used to predict the miRNAs for the hub genes of SSc. As a result, 783 DEGs were identified, of which 770 genes (142 up-regulated genes and 628 down-regulated genes) were matched to the genes in SSc skin samples. Gene Ontology (GO) analyses by DAVID indicated that the up-regulated genes were mainly involved in immune response, and the down-regulated genes were greatly enriched in glycinergic synaptic transmission. In the PPI network, 22 nodes were selected as key genes, including several members of the chemokine family. Furthermore, after uploading these key genes to the OmicsNet tool, we found that hsa-miR-26b-5p might target CXCL9 and CXCL13. Moreover, we demonstrated that the hsa-miR-26b-5p inhibitor might inhibit fibrosis in TGF-ß-activated fibroblasts, which would be a promising target for SSc therapy.

Aneurysmal Fibrous Histiocytoma: Clinicopathology Analysis of 30 Cases of a Rare Variant of Cutaneous Fibrohistiocytoma.

Aneurysmal fibrous histiocytoma is often clinically misdiagnosed. In this study, we put forward an insight on how to help diagnose this disease clinically. A retrospective chart review was performed on all patients diagnosed with aneurysmal fibrous histiocytoma from 2007 to 2017 in the Department of Dermatology, Union Hospital, China, and all clinical data were collected from the hospital archives. From a total of 418 patients diagnosed with cutaneous fibrous histiocytoma, only 30 patients were confirmed to have aneurysmal fibrous histiocytoma out of which only 2 patients were clinically diagnosed with aneurysmal fibrous histiocytoma. The remaining 28 patients were diagnosed with various types of vascular tumors although pathology classified them as having aneurysmal fibrous histiocytoma. Among the 30 patients, 9 were male and 21 were female. There were following age groups: 13-19 (mean 16, n=4), 20-29 (mean 26.25, n=8), 30-39 (mean 33, n=7), 40-49 (mean 44, n=4), 50-59 (mean 56.75, n=4), 60 and above (mean 61, n=3). Tumors were present on the head, neck, back, waist, hips and upper and lower extremities. After complete excision, there was no recurrence and no complications. Histologically, lesions showed the typical pseudoangiomatoid spaces without endothelial lining and infiltration of fibrohistiocytes in hemosiderotic pigmentation. It was suggested that although the prognosis of aneurysmal fibrous histiocytoma is good, accurate diagnosis is paramount to avoid clinical misdiagnosis and subsequent complications.

[Clinicopathologic study of 8 cases of poorly differentiated cutaneous angiosarcoma of scalp].

OBJECTIVE: To study the clinical and pathologic characteristics of poorly differentiated cutaneous angiosarcoma of scalp. METHODS: Eight cases of poorly differentiated cutaneous angiosarcoma of scalp were enrolled into this study. The clinical manifestations and histopathologic features were analyzed. Immunohistochemical study for CD31, CD34, factor VIII-related antigen, vimentin, AE1/AE3, CAM5. 2, epithelial membrane antigen and carcinoembryonic antigen was performed. RESULTS: The mean age of the patients was 69 years. The male-to-female ratio was 5 : 3. The tumor manifested clinically as bruise-like lesion in early phase, indurated erythematous plaque accompanied by nodules, ulcerations and bleeding in advanced phase. Histologically, the tumor was composed of solid sheets of undifferentiated spindle cells which were not easily recognizable as vascular in origin. Nuclear atypia was always present. The tumor cells in all of the 8 cases strongly expressed CD31, factor VIII-related antigen and vimentin. Weak expression of CD34, AE1/AE3 and CAMS. 2 was noted in 2, 4 and 4 cases, respectively. The staining for epithelial membrane antigen, carcinoembryonic antigen and S-100 was negative. Conclusions Angiosarcoma needs to be excluded by histologic examination whenever bruise-like and erythematous lesions occurring on scalp skin of elderly patients. The endothelial origin of the tumor cells can be confirmed with immunostaining for CD31, CD34 and factor VIII-related antigen.

Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-ß/Smad Signal Pathway and Modulating YAP Subcellular Location.

Keloid may induce severe impairment of life quality for the patients, although keloid is a cutaneous benign tumor. Collagen triple helix repeat containing protein 1 (Cthrc1) was identified as a novel gene that was originally found in adventitial fibroblasts after arterial injury. To address the role of Cthrc1 in keloid, the expression level of Cthrc1 was assessed in normal skin and keloid tissue, as well as in normal fibroblasts (NFs) and keloid fibroblasts (KFs) by using quantitative PCR, Western blotting and immunohistochemical analysis. The results showed that Cthrc1 was increased in keloid tissue and KFs as compared with normal skin and NFs. Meanwhile, CCK8 and Transwell assays found the cellular proliferation and migration of KFs were increased as compared with NFs. Further, to verify the function of Cthrc1 in NFs and KFs, we increased Cthrc1 expression by transfecting lentivirus (LV) vectors LV-Cthrc1. The cellular proliferation and migration, collagen synthesis and the influence on TGF-ß and YAP signaling were tested. The cellular proliferation and migration were increased in NFs-Cthrc1 as compared with NFs-control. Meanwhile, YAP expression and nuclear-location was increased in NFs-Cthrc1. On the contrary, when Cthrc1 was overexpressed in KFs, the cellular migration was suppressed and YAP expression was reduced and transferred to cytoplasm in KFs-Cthrc1 as compared with KFs-control. But the expression level of collagen I was decreased and pSmad2/3 nucleus transfer was suppressed in both NFs-Cthrc1 and KFs-Cthrc1 by using Western blotting and immunofluorescence. Increased Cthrc1 activated NFs by promoting YAP nucleus translocation, whereas suppressed KFs by inhibiting YAP nucleus translocation. Enhanced Cthrc1 decreased collagen I in both NFs and KFs by inhibiting TGF-ß/Smad pathway. In conclusion, Cthrc1 may play a role in the pathogenesis of keloid by inhibiting collagen synthesis and fibroblasts migration via suppressing TGF-ß/Smad pathway and YAP nucleus translocation.

Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy - 1st case report and review of the literature.

INTRODUCTION: Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Narrowband ultraviolet B light (NBUVB) is used increasingly in treating MF because of its good toleration and well-established management. CONCERNS: To discuss the risk factors and underlying pathogenic factors in the patients with secondary skin diseases after NBUVB therapy. METHODS: We report in details the first case of a patient with MF accompanied with actinic keratosis (AK), AK with squamous cell carcinoma (SCC) transformation and porokeratosis after NBUVB therapy. Meanwhile, Sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. A literature search of the key word "narrowband ultraviolet B light "and "side effects" was performed on PubMed, 14 cases of this entity were found. A total of 15 patients including our case were reviewed in this study and meaningful conclusion could be drawn. OUTCOMES: The mean age at diagnosis of secondary skin dermatoses after NBUVB therapy was 62.08 years with a male to female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NBUVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only our patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C-G mutation of exon 4 of p53 was found in AK and MF specimens in our patient. CONCLUSION: To our knowledge, our case is the first MF patient accompanied with AK, AK with SCC transformation and Porokeratosis after NBUVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases after NBUVB treatment.

[Application of menisci reformation and repair in the treatment of the discoid meniscus injuries].

OBJECTIVE: To study the clinical effects of menisci reformation and repair for the treatment of discoid meniscus injuries and to explore the operation methods. METHODS: From Jun. 2005 to Dem. 2009, 28 patients underwent arthroscopic menisci reformation and repair for discoid meniscus, including 23 males and 5 females, ranging in age from 6 to 42 years, with an average of 32 years. The nature of meniscus and the type and range of tear were judged under arthroscope. The menisci reformation and repair were used to treat discoid meniscus tear at the edge. After the operation, the brace was used for 8 weeks, and heavy exercise should be avoided for 6 months. The Lysholm score was adopted to evaluate therapeutic effects. RESULTS: All the patients were followed up ranging from 3 to 36 months, averaged 8 months. The preoperative Lysholm scores ranged from 62 to 74, with a mean of (67.23 +/- 5.24), and the postoperative Lysholm scores ranged from 80 to 96, with a mean of (87.24 +/- 5.26). There was no occurrence of re-tear or re-operation due to symptom recurrence. CONCLUSION: The menisci reformation and repair has better clinical effects on the treatment of discoid meniscus tear and can be regarded as one of the operational options.

Childhood psoriasis: a study of 137 cases from central China.

BACKGROUND: Childhood psoriasis is common, but it has not been adequately reported in China. This study was undertaken to evaluate the epidemiological and clinical findings in children with psoriasis treated in a 9-year period and to compare the data with those from other studies. METHODS: The data were from 137 children (< or =14 years old) with psoriasis registered in two tertiary hospitals in Wuhan, China between January 2000 and December 2008. They were retrospectively studied. RESULTS: Of the 137 patients, aged between 3 and 14 years, 64 were males (46.7%) and 73 females (53.3%). Eleven patients (8%) had a family history of psoriasis. Infection was the most common precipitating factor (39, 28.5%). Seasonal influence was found in 57 patients (41.6%). Exacerbations in winter and spring were noted in 29 and 16 patients respectively. Plaque psoriasis was the most common type (72 patients, 52.6%), followed by guttate psoriasis (35, 25.5%), psoriasis pustulosa (15, 10.9%), and psoriasis erythroderma (7, 5.1%). The scalp was the most common initial site affected (69, 50.3%). Nail changes were found in 35 patients (25.5%), but no mucosal involvements were observed. Five patients had arthralgia and two showed abnormal X-ray appearance. Most of the affected children had pruritus. The co-morbidities of childhood psoriasis included allergic contact dermatitis (31, 22.6%), eczema (6, 4.3%), vitiligo (5, 3.6%), and alopecia areata (3, 2.2%). Psoriasis was sometimes misdiagnosed as dermatitis seborrheica (11, 8.0%), neurodermatitis (9, 6.6%) and balanitis (7, 5.1%). Some patients were treated with steroids, but there were obvious side-effects after longterm administration. Thiamphenicol was effective in the treatment of refractory psoriasis pustulosa in children. CONCLUSIONS: Our findings differ from those of previous studies, showing a lower rate of family history and a higher incidence of severe psoriasis. Differential diagnosis should be made especially when lesions occur at the scalp, elbow or balanus. Allergic contact dermatitis takes place more frequently in children with psoriasis than in normal children. Systemic corticosteroids should not be routinely used and other safer and more effective treatments are needed for severe cases.

Olmsted syndrome: a case report and review of literature.

We report a case of an 18-month-old boy with slightly whitened fingernails and toenails since birth. At the age of 100 days, he progressively developed bilateral palmoplantar keratoderma which resulted in painful walking and disabled grasping. Perianal keratotic plaques and perioral hyperkeratotic erythema could also be observed. Both fingernails and toenails were dystrophic. Scalp hairs were sparse, but total alopecia was no present. The histopathologic changes of the biopsy from the inner side of the right foot showed nonspecific changes, which mainly showed highly hyperkeratosis and acanthosis with slight superficial perivascular inflammatory infiltration. A clinical diagnosis of Olmsted syndrome was established according to the typical feature of the lesions, which is the presence of symmetrical palmoplantar keratoderma with periorificial keratotic plaques. We review the literature and present a summary of all reported cases to date.