Case report: Scleromyxedema associated with a monoclonal gammapathy: Successful treatment with intravenous immunoglobulins.

Scleromyxedema is a rare idiopathic fibromucinous disorder characterized by a generalized papular and sclerodermoid cutaneous eruption. Patients often have praraproteinemia and extracutaneous, even lethal, manifestations. Yet the prognostic and therapeutic features of scleromyxedema are poorly documented. High-dose intravenous immunoglobulin (IVIG), used either alone or in conjunction with systemic steroids and/or thalidomide, has been suggested as a first-line treatment. We report the case of a 45-year-old woman diagnosed with scleromyxedema with paraproteinemia that initially did not respond to systemic steroids, retinoids, and thalidomide but greatly improvement in terms of systemic and cutaneous symptoms after treatment with IVIG.

Development and validation of the Vitiligo Extent Score for a Target Area (VESTA) to assess the treatment response of a target lesion.

Since localized treatment for vitiligo is as essential as systemic treatment, a reliable instrument for target evaluation is needed besides those for whole body evaluation. We developed the Vitiligo Extent Score for a Target Area (VESTA) using reference images of both marginal and perifollicular repigmentation to measure the repigmentation rate (%) in a target lesion. In the validation study, a total of 65 dermatologists in 10 institutes evaluated 17 pairs of vitiligo images (pre- and post-treatment) using both a rough estimate and the VESTA. The VESTA (concordance correlation coefficient: 0.949, 95% confidence interval [CI] 0.942-0.955) was significantly more accurate than the rough estimate (0.896, 95% CI: 0.883-0.908). It was also associated with better inter-rater reliability over the rough estimate, albeit not significant. The VESTA can afford intuitive, convenient, and reliable assessment of the treatment response in a target area, and would be useful in clinical practice as well as retrospective studies.

Clinical analysis and etiology of porokeratosis.

The present study was performed in order to define the clinical manifestations of porokeratosis, with particular emphasis on genital porokeratosis. A total of 55 cases of porokeratosis were retrospectively reviewed between 2000 and 2007 from Huashan Hospital (Shanghai, China). Out of 55 cases, there were 22 cases of porokeratosis of Mibelli, 17 cases of disseminated superficial actinic porokeratosis (DSAP), 15 cases of disseminated superficial porokeratosis and one case of linear porokeratosis. The ratio of males to females was 39:16. Among them, 12 cases had a family history of porokeratosis. During the five-year follow-up period, no malignant transformation was observed and no further aggravation of lesions was detected. The results indicated that the initial region of DSAP in the Chinese population may differ from Caucasians. In combination with other studies, the present study found that genital porokeratosis in the Chinese population is often associated with pruritus. Since no recurrence was observed in cases treated with surgical excision, it was suggested that surgical excision is a viable treatment strategy and should be used for porokeratotic lesions if possible. In addition, regular follow-ups are required, since the aggravation of porokeratosis may cause the development of malignancy transformation.

No association between Y chromosomal haplogroups and severe acne in the Han Chinese population.

Severe acne presents sexual dimorphism in its incidence in Chinese population. It is more prevalent in males. To assess the possible Y chromosomal contribution to severe acne risk in Han Chinese males, we analyzed 2041 Y chromosomal SNPs (Y-SNPs) in 725 severe acne cases and 651 controls retrieved from our recent genome-wide association study data. After data filtering, we assigned 585 cases and 494 controls into 12 Y chromosomal haplogroups based on 307 high-confidence Y-SNPs. No statistically significant difference in the distribution of Y chromosomal haplogroup frequencies was observed between the case and control groups. Our results showed a lack of association between the incidence of severe acne and the different Y chromosomal haplogroup in the Han Chinese population.

Successful treatment of recalcitrant dissecting cellulitis of the scalp with ALA-PDT: case report and literature review.

A case of refractory dissecting cellulitis of the scalp (DCS) in a forty-one-year-old Chinese female patient was treated with a total of 6 sessions of topical ALA-PDT at one week intervals. The patient tolerated and responded well to this new approach without any adverse events. This suggested that topical ALA-PDT could be an effective and safe alternative for DCS patients who were refractory to other conventional therapies. We also reviewed etiology, pathophysiology, natural history and treatment options for DCS.

Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris.

OBJECTIVES: To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different severity of acne vulgaris and optimize the treatment regimen. METHODS: A self-controlled multicenter clinical trial was carried out in 15 centers throughout China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation. The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120 J/cm(2). Clinical assessment was conducted before and after every treatment up to 8 weeks. RESULTS: The effective rate overall and of grade II, III and IV are 82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises significantly proportionally to the severity of acne (P<0.01). No significant differences are found in the efficacy between patients received 3-session and 4-session PDT treatments (P>0.05). The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment (P<0.01) and during the 8-week follow up (P<0.01 or P<0.05). Maximum efficacy is obtained at 8 weeks after the treatment completion. CONCLUSIONS: A low-dose topical ALA-PDT regimen using 5% ALA, 1h incubation and red light source of 3 treatment sessions is suggested as optimal scheme for the treatment of different severity of acne vulgaris in Chinese patients. Superior efficacy is found in severe cystic acne of grade IV with mild side effects.

Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.

To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, P(combined)=8.07 × 10(-12), odds ratio (OR)=1.18), 11q23.3 (rs638893, P(combined)=2.47 × 10(-9), OR=1.22), and 10q22.1 (rs1417210, P(combined)=1.83 × 10(-8), OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, P(combined)=8.57 × 10(-8), OR=0.88), 10p15.1 (rs3134883, P(combined)=1.01 × 10(-5), OR=1.11), and 22q12.3 (rs2051582, P(combined)=2.12 × 10(-5), OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations.

In vivo reflectance confocal microscopy for the differential diagnosis between vitiligo and nevus depigmentosus.

BACKGROUND: Nevus depigmentosus (ND) is frequently confused with vitiligo. Differential diagnosis can be difficult. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique for real-time en face imaging of the superficial layers of the skin down to the superficial dermis with cellular level resolution close to conventional histopathology. In this study, we tried to use this new technology to study the features of the distribution of pigment cells of these two hypopigmentation disorders and then concluded the differential features. METHODS: Sixty vitiligo patients and 62 ND patients were enrolled in the study. Three points in each patient (lesional, margin of the lesions and adjacent non- lesional points) were examined with RCM. The gray value of image was quantified using software, and we calculated the relative gray value. RESULTS: The RCM image feature was different between vitiligo and ND patients. The differential diagnosis was made based on the following four RCM features: complete absence of pigment cells; the distribution of pigment cells; the margins; and the relative gray value. CONCLUSION: RCM can be used as an auxiliary diagnostic tool for the differential diagnosis between vitiligo and ND.

Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.

We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined=1.48x10(-48), OR=1.90; rs9468925, Pcombined=2.21x10(-33), OR=0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined=9.72x10(-17), OR=1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.

Cutaneous infectious granuloma caused by Phenylobacterium in an adult with myelodysplastic syndrome: a first case report.

Painful granulomatous lesions appeared on the face of a 36-year-old man with myelodysplastic syndrome. Skin biopsy revealed chronic inflammatory granuloma. Bacterial cultures of the lesions and blood indicated the same unknown Gram-negative rod bacterium. The 16S ribosomal RNA sequence of the unknown bacterium yielded Phenylobacterium. Thus, we diagnosed cutaneous infectious granuloma caused by Phenylobacterium and myelodysplastic syndrome/refractory cytopenia with multi-lineage dysplasia. After treatment with combined antibacterials that were selected based on the tests for drug sensitivity, the lesions disappeared with only scars remaining and without any signs of relapse after 1 year. This is the first case report of cutaneous infectious granuloma caused by Phenylobacterium.

Reassessment of microarray expression data of porokeratosis by quantitative real-time polymerase chain reaction.

BACKGROUND: Porokeratosis (PK) is a heterogeneous group of keratinization disorders that exhibit similarities with psoriasis at both the clinical and molecular levels. METHODS: The transcript levels of keratin (KRT) 6A, 16, 17, S100A7, A8, A9, p53 and three candidate genes (i.e. SART3, SSH1 and ARPC3) were reassessed in pairwise lesional and uninvolved skin from nine patients with PK by real-time quantitative polymerase chain reaction (RTQ-PCR). RESULTS: The results of RTQ-PCR confirmed that KRT6A, 16, S100A7, A8 and A9 (p = 0.008) were mostly up-regulated in the lesional skin when compared with uninvolved skin. Different from the microarray data, there was no significant difference observed in KRT17 expression patterns between lesional and normal-appearing skin (p = 0.066). No statistical difference was observed in p53 and three candidate genes' expression patterns between lesional and uninvolved skin. CONCLUSIONS: In the present study, 9 of the 10 gene expression measured by RTQ-PCR in PK were statistically comparable to microarray data. KRT6A was identified as specific biomarker for porokeratotic keratinocytes, as it was the most significantly up-regulated gene in the nine patient samples.

Expression of pigment epithelium-derived factor in human melanocytes and malignant melanoma cells and tissues: Is loss of pigment epithelium-derived factor associated with melanoma?

BACKGROUND: Pigment epithelium-derived factor (PEDF) was first isolated from the medium conditioned by human fetal retinal pigment epithelial cells and has been detected in a broad range of human fetal and adult tissues. Recent studies have indicated that PEDF activity is inhibitory to angiogenesis. OBJECTIVE: To study the expression and distribution of pigment epithelium-derived factor (PEDF) in human melanocytes, malignant melanoma cells and tissues. RESULTS: PEDF was expressed in human melanocytes. The expression of PEDF protein diminished in the following orders healthy skin, pigmented nevus and human malignant melanoma (p < 0.001). Both the expression of PEDF mRNA and protein was much lower or almost absent in the malignant melanoma cell line A375 than that in human melanocytes (p < 0.001). METHODS: The expression and distribution of PEDF in human healthy skin, pigmented nevus and malignant melanoma were studied. The expression of PEDF mRNA in human melanocytes and malignant melanoma cell line A375 was measured by reverse transcription polymerase chain reaction (RT-PCR) and PEDF protein was detected by immunohistochemical method and Western blotting analysis. CONCLUSION: The lack of PEDF expression may contribute to the pathogenesis of malignant melanoma.

Topical 5-aminolevulinic acid photodynamic therapy for recalcitrant facial flat wart in Chinese subjects.

The facial flat wart (verruca plana) is not only a contagious viral disease, but also causes a disturbing cosmetic problem. Because 5-aminolevulinic acid photodynamic therapy has successfully treated human papilloma virus-related diseases, we employed 20% 5-aminolevulinic acid and a light emitting diode on three recalcitrant facial flat wart patients. Most lesions achieved complete remission after three or four sessions. However, a few non-elevated lesions did not respond to this method. An ablative therapeutic mode is required in addition to 5-aminolevulinic acid photodynamic therapy in such lesions. Therefore, we utilized an Er:YAG laser and 20% 5-aminolevulinic acid photodynamic therapy for one session and achieved an excellent result. Patients should be informed of the possible side-effects of this treatment, such as erythema, exfoliation and post-inflammatory hyperpigmentation, and the requirement for sun protection.

Evaluation of 308-nm monochromatic excimer light in the treatment of psoriasis vulgaris and palmoplantar psoriasis.

BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of 308-nm monochromatic excimer light (MEL) in the treatment of psoriasis vulgaris and palmoplantar psoriasis. METHODS: Thirty-five patients with psoriasis vulgaris and 15 patients with palmoplantar psoriasis were recruited for this study. Thirty patients with psoriasis vulgaris completed a total of 16 treatments with 308-nm MEL twice a week, and 15 patients palmoplantar psoriasis completed 25 treatments administered once weekly. The clinical response to therapy and adverse effects were recorded. RESULTS: Patients with psoriasis vulgaris (n=30) showed a 74.6% improvement in the mean psoriasis area and severity index score after a total of 16 MEL treatments (2 x /week) with 36.7% of the patients (n=11) achieving clearance. Patients with palmoplantar psoriasis (n=15) showed a 52.5% improvement in the mean severity index score after a total of 25 MEL treatments (1 x /week) with only one patient (6.7%) achieving clearance. The MEL therapy was well tolerated with a low incidence of side effects, which included pruritus, erythema and blister formation. CONCLUSION: The 308-nm MEL can be utilized as an effective and safe treatment modality for patients with mild-to-moderate psoriasis vulgaris and palmoplantar psoriasis.

Gene expression profiling of porokeratosis.

BACKGROUND: Porokeratosis (PK) represents a heterogeneous group of disorders of keratinization and has a wide variety of clinical manifestations. PK may exhibit similarities with psoriasis at both clinical and molecular levels. The genetic basis and pathogenesis for PK remain elusive. METHODS: We studied the transcriptional profiles of three pairwise lesional and uninvolved skin biopsies from patients with different subtypes of PK using the Illumina BeadArray platform. RESULTS: A total of 37 upregulated genes were identified in our study, including wound-induced keratins, S100 calcium-binding protein genes involved in epidermal differentiation, as well as genes involved in mediating intercellular communication and the immune response. To our knowledge, this is the first study that characterizes the immune profile of PK lesions. CONCLUSIONS: Here, we report that keratinocytes (KCs)-harboring lesions have activated and overexpressed wound-induced keratin genes, which appear to be coregulated with other genes involved in mediating epidermal differentiation, intercellular communication and immunity. This study, from the perspective of gene profiling, supports that gene misregulation in PK mimics that of psoriasis. Our data indicate that the genes implicated in the T-cell-mediated immune response pathway and activation of KCs play a key role in the pathogenesis of PK.

[Refinement of DSAP1 locus and mutation detection for candidate genes].

Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder,characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. In previous studies,the disease gene was mapped to 12q23. 2-24.1 (DSAP1), and 15q25. 1-26.1 (DSAP2). In this study,genome-wide scan was performed in two unrelated six-generation DSAP pedigrees to localize and identify the candidate gene(s) of disease. Linkage analysis showed that the cumulative maximum two-point lod score of 8.28 was obtained with the marker D12S84 at a recombination fraction theta of 0.00. Haplotype analysis defined an 8.0 cM critical region for DSAP gene(s) between markers D12S330 and D12S354 on 12q24. 1-q24. 2, which partially overlapped with the region identified for DSAP1. DNA sequencing of the coding exons of six candidate genes (CRY1, PWP1, ASCL4, PRDM4, KIAA0789 and CMKLR1) on the basis of their location in the critical overlap interval, failed to detect any mutation in DSAP patients. Thus, it is likely that these genes are not involved in DSAP.

Two closely linked variations in actin cytoskeleton pathway in a Chinese pedigree with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Recently, SSH1 was identified as the DSAP candidate gene. OBJECTIVE: Our purpose was to determine the locus of DSAP and identify the candidate gene(s) of the disease. METHODS: Genome-wide scanning and linkage analysis were performed in a 6-generation Chinese family with DSAP. The coding exons and promoter region of the candidate genes were screened for the nucleotide variations. RESULTS: A missense mutation (p.Ser63Asn) in SSH1 and a variation (dbSNP3759383: G>A) in the promoter region of ARPC3 were closely linked with DSAP in the pedigree. CONCLUSION: Both SSH1 and ARPC3 are involved in the actin cytoskeleton pathway and interacted with adherent junctions in the epidermal cells. We suggested that cytoskeleton disorganization in epidermal cells was likely associated with the pathogenesis of DSAP.