DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

Subcision in acne scarring: A review of clinical trials.

Post-acne scarring is the most common permanent consequence of acne vulgaris. Subcision is an intervention in which a needle or blunt cannula is inserted under the scar and moved back and forth to cut fibrotic strands and form new connective tissue, thereby elevating the atrophic scars. In this study, we reviewed the efficacy and adverse effects of different subcision techniques alone or in combination with other modalities to manage acne scars. The terms (subcision), (subcision AND acne scar), and (subcision AND scar) were searched in PubMed and Google Scholar. We included all available reports on clinical trials written in English and published before June 2022. A total of 16 relevant articles were identified after reviewing the abstracts and full texts. Four articles compared blunt cannula-based subcision as a modified technique with needle-based subcision as a conventional method, while the others investigated the combination of subcision with other modalities. According to our findings, subcision is a safe and effective method for treating atrophic acne scars. Needle-based subcision and cannula-based subcision offer comparable efficacy, with the latter causing fewer side effects and inducing greater patient satisfaction. Combining subcision with the application of autologous tissues (platelet gel) or artificial materials (hyaluronic acid gels and threads) as fillers can improve outcomes and prevent the re-depressing of scars, as can its combination with frequent suctioning. Combinations with microneedling or fractionated microneedle radiofrequency have also been safe and effective. We conclude that modifications of the subcision procedure lessen its side effects, and combination therapies improve its efficacy.

"The efficacy and adverse effects of treatment options for facial pores: A review article".

INTRODUCTION: Skin pores are enlarged openings of the pilosebaceous follicles that can be affected by age, gender, genetics, exposure to UV light, ethnicity, and sebum secretion. Many treatment modalities reduce facial pores' count and area, including oral and topical medications as well as different wavelengths of lasers. Finding a safe and cost-effective treatment protocol is necessary since facial pores are one of the main reasons for cosmetic complaints. AIM: This review compares available treatment options for reducing facial pores' number and area according to the published clinical trials. METHODS: A search on PubMed and Google Scholar was performed. Nineteen published clinical trials regarding treatment options for facial pores were included and reviewed based on the authors' clinical experience. RESULTS: A total number of 591 cases (83.7% female) aged 18-80 years were included. Three assessment methods including digital imaging, physician assessment, and patient' satisfaction were used in the studies to evaluate the therapeutic efficacy of each modality. Furthermore, combining different modalities increased the efficacy of reducing pores' size and number. Mild, reversible burning and erythema were common side effects. CONCLUSION: Multiple sessions and combination therapies improve facial pores' area and number. In young patients, the focus should be on controlling sebum production, while in older patients, the focus should be on rejuvenation in addition to the control of sebum production.

Laser treatment of benign melanocytic lesion: a review.

Treatment of pigmented lesions is one of the major challenges of laser and cosmetic practitioners. The most common pigmented lesions that are treated by lasers are melanocytic nevi, ephelides, solar lentigines, and café au lait macules. Melanin absorbs different wavelengths (500-1100 nm); thereby, treatment of various pigmented lesions requires the application of lasers with different wavelengths. Choosing the most appropriate type of laser depends on various factors such as the chromophore and the location of a specific lesion in the skin. In this paper, we aim to review the most efficient laser treatment protocols for each pigmented skin lesion and compare their efficacy in each part based on the previous studies.

Efficacy and safety of topical brimonidine in dermatology: A review article.

Brimonidine is a vasoconstrictive agent used to treat several dermatologic disorders. Here, we review the uses of brimonidine in different aspects of dermatology. We searched keywords including rosacea, erythema, topical brimonidine, dermatology, and skin disease in PubMed, Cochrane, and Google Scholar to collect the related published articles. In a review of 15 articles, we found topical brimonidine improved the facial erythema of rosacea. In addition, it reduced the erythema associated with alcohol flushing syndrome, intense pulsed light therapy, and photodynamic therapy. Furthermore, topical brimonidine was used as a hemostatic agent in dermatosurgery procedures such as Mohs surgery and nail surgery to reduce intra-operative and postoperative bleeding. Some side effects such as erythema, flushing, and burning were reported in a few patients. Based on our findings, brimonidine is a beneficial drug that can be used in various dermatologic disorders with negligible side effects.

JAK inhibitors in lichen planus: a review of pathogenesis and treatments.

Lichen planus (LP) is an auto-inflammatory skin disorder identified by a presence of T-cell lymphocytes at the dermal-epidermal junction. It is hypothesized that the INF-γ/CXCL10 axis fulfills a major role in the onset and persistence of chronic inflammation in LP. Since Janus kinases (JAKs) are involved in the transduction of INF-γ signals, they may be good targets for LP treatment. Several case reports and case series described the safety and efficacy of upadacitinib (2 articles), tofacitinib (6 articles), baricitinib (4 articles), and Ruxolitinib (1 Article) in the treatment of LP variants. The predominant variants that JAK inhibitors improved were lichen planopilaris, nail LP, and erosive LP. Considering the role of the JAK pathway in LP pathogenesis and the evidence provided by these reports, it seems JAK inhibitors would be effective therapeutic agents for LP treatment. Hence, these agents should be trialed and evaluated further.

Whole-transcriptome sequencing-based concomitant detection of viral and human genetic determinants of cutaneous lesions.

Severe viral infections of the skin can occur in patients with inborn errors of immunity (IEI). We report an all-in-one whole-transcriptome sequencing-based method by RNA-Seq on a single skin biopsy for concomitantly identifying the cutaneous virome and the underlying IEI. Skin biopsies were obtained from healthy and lesional skin from patients with cutaneous infections suspected to be of viral origin. RNA-Seq was utilized as the first-tier strategy for unbiased human genome-wide rare variant detection. Reads unaligned to the human genome were utilized for the exploration of 926 viruses in a viral genome catalog. In 9 families studied, the patients carried pathogenic variants in 6 human IEI genes, including IL2RG, WAS, CIB1, STK4, GATA2, and DOCK8. Gene expression profiling also confirmed pathogenicity of the human variants and permitted genome-wide homozygosity mapping, which assisted in identification of candidate genes in consanguineous families. This automated, online, all-in-one computational pipeline, called VirPy, enables simultaneous detection of the viral triggers and the human genetic variants underlying skin lesions in patients with suspected IEI and viral dermatosis.

Increased risk of subclinical atherosclerosis and metabolic syndrome in patients with vitiligo: a real association or a coincidence?

Inflammatory and autoimmune skin diseases such as vitiligo may be associated with systemic disorders, including endocrine and cardiovascular diseases, due to some similarities in the pathogenesis. It was aimed to evaluate metabolic syndrome and subclinical atherosclerosis in patients with vitiligo. Seventy patients with nonsegmental vitiligo and 70 age-matched and gender-matched healthy controls participated in the study. These participants were investigated for metabolic syndrome criteria. The mean intima-media thickness of the common carotid artery (MIMT-CCA) of the subjects was measured for assessment of subclinical atherosclerosis. Metabolic syndrome and subclinical atherosclerosis were significantly more frequent in vitiligo patients compared with the controls (P = .006 and P = .002, respectively). In addition, metabolic syndrome and subclinical atherosclerosis had positive, significant correlations with the severity and duration of vitiligo (P = .031 and r = .482; P < .01, respectively). Our study suggested that patients with vitiligo, especially those with more chronic and severe disease or concomitant metabolic syndrome, are at a higher risk of developing cardiovascular diseases. Therefore, early diagnosis and treatment of metabolic syndrome in patients with vitiligo to prevent cardiovascular complications were recommended.

Different distribution patterns of plasmacytoid dendritic cells in discoid lupus erythematosus and lichen planopilaris demonstrated by CD123 immunostaining

Abstract Background: Clinical and histological features may overlap between lichen planopilaris-associated and discoid lupus erythematosus-associated scarring alopecia. Objectives: The aim of this study was to demonstrate the cutaneous infiltration of plasmacytoid dendritic cells and to compare their distribution pattern in discoid lupus erythematosus and lichen planopilaris. Methods: Twenty-four cases of discoid lupus erythematosus and 30 cases of lichen planopilaris were examined for immunostaining of the CD123 marker. The percentage and distribution pattern of plasmacytoid dendritic cells and the presence of the plasmacytoid dendritic cells clusters were evaluted in the samples. Results: The number of plasmacytoid dendritic cells was higher in the discoid lupus erythematosus specimens. Aggregations of 10 cells or more (large cluster) were observed in half of the discoid lupus erythematosus specimens and only 2 lichen planopilaris, with 50% sensitivity and 93% specificity for differentiating discoid lupus erythematosus from lichen planopilaris. Study limitations: Incidence and prevalence of discoid lupus erythematosus-associated scarring alopecia in the scalp are low, so the samples size of our study was small. Conclusions: We suggest that a plasmacytoid dendritic cells cluster of 10 cells or more is highly specific for distinguishing discoid lupus erythematosus from lichen planopilaris. It also appears that CD123 immunolabeling is valuable in both active and late stages of the disease.

Different distribution patterns of plasmacytoid dendritic cells in discoid lupus erythematosus and lichen planopilaris demonstrated by CD123 immunostaining.

BACKGROUND: Clinical and histological features may overlap between lichen planopilaris-associated and discoid lupus erythematosus-associated scarring alopecia. OBJECTIVES: The aim of this study was to demonstrate the cutaneous infiltration of plasmacytoid dendritic cells and to compare their distribution pattern in discoid lupus erythematosus and lichen planopilaris. METHODS: Twenty-four cases of discoid lupus erythematosus and 30 cases of lichen planopilaris were examined for immunostaining of the CD123 marker. The percentage and distribution pattern of plasmacytoid dendritic cells and the presence of the plasmacytoid dendritic cells clusters were evaluted in the samples. RESULTS: The number of plasmacytoid dendritic cells was higher in the discoid lupus erythematosus specimens. Aggregations of 10 cells or more (large cluster) were observed in half of the discoid lupus erythematosus specimens and only 2 lichen planopilaris, with 50% sensitivity and 93% specificity for differentiating discoid lupus erythematosus from lichen planopilaris. STUDY LIMITATIONS: Incidence and prevalence of discoid lupus erythematosus-associated scarring alopecia in the scalp are low, so the samples size of our study was small. CONCLUSIONS: We suggest that a plasmacytoid dendritic cells cluster of 10 cells or more is highly specific for distinguishing discoid lupus erythematosus from lichen planopilaris. It also appears that CD123 immunolabeling is valuable in both active and late stages of the disease.

Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo.

Increasing evidence on the association of MTHFR gene polymorphism and serum homocysteine levels with autoimmune diseases such as vitiligo has made the MTHFR gene a very interesting candidate to be evaluated in different ethnicities and populations. We aimed to evaluate the levels of serum homocysteine and vitamin B12 and their associations with MTHFR C677T polymorphism in the Iranian population. This case-control study included 104 patients with vitiligo and 100 age- and sex-matched healthy control subjects. Serum vitamin B12 and homocysteine levels were measured by a chemiluminescence assay. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping the polymorphism. The mean serum homocysteine levels were significantly higher in cases than controls and associated with disease activity (p < .001). Furthermore, the homozygous MTHFR C677T variant genotype was associated with vitiligo development (adjusted OR: 3.52, 95% CI: 1.09-11.32, p = .02) and elevated homocysteine level (p < .001). There was no association between serum vitamin B12 levels and the MTHFR C677T genotype. The homozygous variant MTHFR C677T may be considered as a risk factor for both elevated homocysteine levels and the development of vitiligo in the Iranian population. Although these results are not conclusive, they could elucidate the contribution of genetic and immune-mediated inflammatory factors to the pathogenesis of vitiligo.

Genital Lesions Masquerading as Condyloma Acuminata: A Case Series Report.

Herein we report three married women referred to Dermatology Clinic of Loghman Hakim Hospital, Tehran, Iran in 2017 for evaluation and treatment of genital warts. Two patients were complaining of flat-topped papules on their labia major and the third one was presented with asymptomatic papillary projections on her vestibule and inner aspect of both labia minora. Histological examination revealed the diagnosis of syringoma, lymphangioma circumscriptum (LC) and vestibular papillomatosis respectively. Familiarity with these uncommon conditions which clinically mimic genital warts helps to prevent labeling a patient with sexually transmitted disease before histological confirmation and prevent unnecessary treatment.

Atypical Cutaneous Mucinosis Treated with Intravenous Immunoglobulin and Corticosteroid.

FA 25-year-old man presented with a 12-month history of progressive skin lesions involving the face, upper areas of the trunk, arms, and natal cleft. There was moderate pruritus, disfiguring lesions of the face, and mild arthralgia. No therapy had been applied before the referral to our clinic. On physical examination, there were skin-colored nodules on the face (Figure 1A), along with multiple firm subcutaneous nodules and tumors with a fairly symmetrical distribution on the extensor surface of the hands and forearms (Figure 2A). Dense papular lesions were found on the upper part of the back (Figure 3A). There was also a waxy infiltrated plaque in the natal cleft area (Figure 4A).