Investigating melanogenesis-related microRNAs as disease biomarkers in vitiligo.

Vitiligo is considered a disabling disease that affects physical, social, psychological, and occupational aspects of an individual's quality of life. The search for non-invasive and reliable biomarkers for vitiligo's early diagnosis, prognosis, and treatment prediction is under intensive investigation. There is currently an emerging interest in employing miRNAs as biomarkers to predict vitiligo diagnosis and prognosis, inspired by the well-preserved nature of miRNAs in serum or plasma. In the current study, we assessed a panel of 20 melanogenesis pathway-related microRNAs (miRNAs) using quantitative real-time PCR technique in 85 non-segmental vitiligo (NSV) patients compared to 85 normal controls followed by function and pathway enrichment analysis for the miRNAs with significant results. Twelve out of the 20 circulating miRNAs showed significantly higher expression levels in vitiligo patients relative to controls where miR-423 show the highest expression level followed by miR-182, miR-106a, miR-23b, miR-9, miR-124, miR-130a, miR-203a, miR-181, miR-152, and miR-320a. While six miRNAs (miR-224, miR-148a, miR-137, and miR-7, miR-148b, miR-145, miR-374b, and miR-196b) didn't show significant expression level. The analysis of the receiver operating curve indicated that miR-423, miR-106a, and miR-182 were outstanding biomarkers with the highest areas under the curve in vitiligo. This study is the first Egyptian study to investigate a panel of miRNAs expression profile in the plasma of patients with NSV. Our results suggest that specific circulating miRNAs signature might be implicated in vitiligo pathogenesis and could potentially be used as biomarkers in vitiligo.

Hair Follicle-Related MicroRNA-34a Serum Expression and rs2666433A/G Variant in Patients with Alopecia: A Cross-Sectional Analysis.

Alopecia areata (AA) is a type of immune-mediated alopecia. Recent studies have suggested microRNAs' (miRNAs) implication in several cellular processes, including epidermal and hair follicle biology. Single nucleotide polymorphisms (SNPs) can modify gene expression levels, which may induce an autoimmune response. This case−control study included 480 participants (240 for each case/control group). MicroRNA-34a gene (MIR-34A) rs2666433A/G variant was genotyped using real-time allelic discrimination polymerase chain reaction (PCR). Additionally, circulatory miR-34a levels were quantified by quantitative reverse transcription PCR (qRT-PCR). On comparing between alopecia and non-alopecia cohorts, a higher frequency of A variant was noted among patients when compared to controls­A allele: 28 versus 18% (p < 0.001); A/A genotype: 9 versus 2%; A/G genotype: 39 versus 32% (p < 0.001). A/A and A/G carriers were more likely to develop alopecia under heterozygote comparison (OR = 1.83, 95% CI = 1.14−2.93), homozygote comparison (OR = 4.19, 95% CI = 1.33−13.1), dominant (OR = 2.0, 95% CI = 1.27−3.15), recessive (OR = 3.36, 95% CI = 1.08−10.48), over-dominant (OR = 1.65, 95% CI = 1.04−32.63), and log additive (OR = 1.91, 95% CI = 1.3−2.82) models. Serum miR-34a expression levels were upregulated in alopecia patients with a median and quartile fold change of 27.3 (1.42−2430). Significantly higher levels were more pronounced in A/A genotype patients (p < 0.01). Patients carrying the heterozygote genotype (rs2666433 * A/G) were two times more likely to develop more severe disease grades. Stratified analysis by sex revealed the same results. A high expression level was associated with concomitant autoimmune comorbidities (p = 0.001), in particular SLE (p = 0.007) and vitiligo (p = 0.049). In conclusion, the MIR34A rs2666433 (A/G) variant is associated with AA risk and severity in the studied population. Furthermore, high miR-34a circulatory levels could play a role in disease pathogenesis.

Serum level of interleukin-22 in patients with cutaneous warts: A case-control study.

BACKGROUND: Warts are viral cutaneous infections caused by human papilloma virus (HPV), presented by verrucous growth over the skin surface. The immune response is considered to play a crucial role in HPV clearance. It depends on intact cellular immunity including natural killer (NK) cell and cytotoxic T cells. It has been clarified that T-helper (Th) 1 cytokines (interleukin (IL)-2, interferon-γ, and tumor necrosis factor-a) and IL-17 are involved in HPV clearance. IL-22 is one of IL-10 family of cytokines produced by NK cells, Th1, Th17, and Th22 cells. In the skin, IL-22 reduces keratinocyte cornification and enhances keratinocyte production of antimicrobial peptides. IL-22 overexpression has been demonstrated in various viral infections and skin inflammatory disorders. AIM: The aim of this study was to assess serum levels of IL-22 in patients with warts and its association with their different clinical characteristics. METHODS: The study included 20 patients with warts and 20 control subjects. Serum concentration of IL-22 was measured by enzyme-linked immune sorbent assay. RESULTS: Serum levels of IL-22 were significantly higher in patients with warts than in control subjects (P < .001). The levels were significantly higher in patients with recurrent warts after prior treatment than in patients with first-time warts (P = .007). Moreover, a significant positive correlation was detected between serum levels of IL-22 and the number of warts (P = .017). CONCLUSION: Serum level of IL-22 was elevated in patients with warts. Thus, IL-22 may have a crucial role in the antiviral immune response against this infection.

Effect of Cluster Allergen-Specific Immunotherapy in Patients with Atopic Dermatitis Sensitive to House Dust Mite.

Atopic dermatitis (AD) is a chronic IgE-mediated skin disorder. Clinical usefulness of allergen-specific immunotherapy in the treatment of AD is still controversial. We assessed the effect of cluster allergen-specific subcutaneous immunotherapy (SCIT) in patients with AD sensitive to house dust mite. The study included 43 patients (32 with mild to moderate AD and 11 with severe AD). Disease severity was assessed by SCORAD index. Patients were treated by cluster SCIT for 8 weeks. SCORAD index, total IgE serum level and blood eosinophilic count (BEC) were assessed at the baseline visit and after the end of immunotherapy. Thirty-one patients (72.1%) responded to SCIT. Responders showed significant decrease in SCORAD index (P < 0.001) and BEC (P < 0.05) compared to non-responders. SCORAD index, total IgE and BEC were significantly decreased in responded patients after SCIT compared to the baseline. The reduction in SCORAD index was 49%. Patients with mild to moderate AD showed no difference in the serum IgE level after SCIT compared to the baseline, but a significant difference was reported in the SCORAD index and BEC. Patients with severe AD showed significant difference in SCORAD index, total IgE, and BEC between baseline and post-SCIT values. Patients with mild to moderate AD showed more reduction in SCORAD index than patients with severe AD (53.8% vs. 43.6%). No adverse reactions were reported during immunotherapy. We concluded that cluster allergen-specific immunotherapy is an effective and well-tolerated therapeutic modality for both mild to moderate and severe AD.

Female Genital Dialogues: Female Genital Self-Image, Sexual Dysfunction, and Quality of Life in Patients With Vitiligo With and Without Genital Affection.

Vitiligo has a major effect on sexual health because of the disfiguring skin lesions affecting self-image and self-esteem. However, this topic has not explored. This article aimed to assess the effect of vitiligo on genital self-image, sexual function, and quality of life in female patients. This cross-sectional study included 50 sexually active women with vitiligo and 25 women without vitiligo. All participants subjected to full history taking and examination. Extent of vitiligo was assessed with the Vitiligo Area Scoring Index score, sexual function with the Female Sexual Function Index, genital self-image with Female Genital Self-Image Score and quality of life with the Dermatology Life Quality Index questionnaires. The main outcome measures were correlation between Vitiligo Area Scoring Index, Female Genital Self-Image Score, Female Sexual Function Index, and Dermatology Life Quality Index domains was determined using t test and Pearson correlation. This study revealed a negative correlation between the Vitiligo Area Scoring Index score and sexual satisfaction. Vitiligo Area Scoring Index and Dermatology Life Quality Index score was significantly correlated with Arabic Version of the Female Genital Self-Image Score alone and with Arabic Version of the Female Sexual Functioning Index alone and with both the Arabic Version of the Female Genital Self-Image Score and the Arabic Version of the Female Sexual Functioning Index (p <.05). Sexual and psychological assessment of patients with vitiligo is imperative to improve outcomes and increase patients' compliance with treatment.

Carbon dioxide laser plus topical 5-fluorouracil: a new combination therapeutic modality for acral vitiligo.

BACKGROUND: Acral vitiligo (AV) is resistant to treatment. AIM: To evaluate efficacy and safety of combining carbon dioxide (CO2) laser and 5-fluorouracil (5FU) in treating AV. METHODS: This study included 68 adult patients with AV. After randomly assigning patients into 3 groups, patients in group I were treated using 5FU, group II were treated using CO2 laser, and group III were treated using CO2 laser followed by 5FU for a maximum period of 5 months. The lesions were then evaluated both qualitatively and quantitatively. RESULTS: Almost half (49.8%) of the lesions in group III achieved G4, and 6.1% of lesions achieved G3 re-pigmentation. This response was statistically significantly higher than that in the other two groups. This was not achieved in periungual areas in the hands and feet. The pain was tolerable during sessions or at sites of 5FU application. Transient hyperpigmentation, brownish spot on nail plates, itching, and infection were temporary side effects; however, Koebnerization was not detected. CONCLUSION: We concluded that prior use of CO2 laser skin ablation, followed by 5FU application for AV is a safe and tolerable technique that improves the outcome and increases patient compliance.

Assessment of female sexual function in patients with psoriasis.

INTRODUCTION: Psoriasis has a major impact on sexual health due to the disfiguring skin lesions affecting self-image and self-esteem. However, this topic has not been fully explored. AIM: The study aims to assess sexual function in female patients with psoriasis. METHODS: This cross-sectional study included 52 sexually active female patients with psoriasis regardless of their age (group I) and 30 normal volunteers (who were age matched with the patients) who served as a control group (group II). Full history taking, general and systemic examination, including sexual history, together with clinical examination to evaluate the extent of skin disease using Psoriasis Assessment Severity Index (PASI) score and evaluation of sexual function using the Female Sexual Function Index (FSFI) Questionnaire, were done for all the subjects enrolled in the study. MAIN OUTCOME MEASURES: Correlation between PASI and FSFI domain scores was determined in matched groups using Pearson correlation. RESULTS: This study revealed a negative correlation between the PASI score and the overall sexual satisfaction in the studied group. Also, psoriatic female patients with genital psoriasis have more significantly impaired sexual function compared with either those without genital lesions or those with lesions elsewhere in the body. CONCLUSIONS: It is imperative to do full sexual and psychological assessment of psoriatic patients to improve outcomes and increase patients' compliance with treatment.

Interleukin-18 gene polymorphisms in Egyptian patients with allergic diseases.

BACKGROUND: Allergic diseases, such as allergic rhinitis (AR) and atopic dermatitis (AD), affect a large proportion of people worldwide. Both have environmental and genetic predisposing factors. Single nucleotide polymorphisms (SNPs) in interleukin (IL)-18, may play a direct role in the disease pathogenesis. This study was designed to investigate the association of the IL-18 gene SNPs (-137 G/C [rs187238], and -140 C/G [rs360721]) with AR and AD, as well as their relations to the diseases' severity. METHODS: Seventy-five individuals were enrolled in the study including, 25 AD children, 25 AR patients, and 25 unrelated healthy adult volunteers who served as controls. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: AR and AD patients showed no significant differences in the genotype distribution and allele frequencies of -137 G/C and -140 C/G SNPs when compared independently with the control group. However, the -140 GG genotype and the -140 G allele were more often associated with severe AD compared with mild and moderate phenotypes (p = 0.01 and 0.001, respectively; odds ratios [ORs], 14.25 [95% CI, 1.48-143.2] and 16 [95% CI, 2.8-90.46], respectively). Moreover, the -137 G allele was associated with moderate/severe AR (p = 0.019; OR, 6.1 [95% CI, 1.34-28.1]). CONCLUSION: This preliminary study indicates that the studied polymorphisms do not confer susceptibility to allergy in Egyptian patients but may be related to the disease phenotype. However, the role of IL-18 in allergy may be too complex to be reflected in a simple association study.

Lymphangiogenesis and angiogenesis in non-phymatous rosacea.

BACKGROUND: Our study evaluated the expression of vascular endothelial growth factor (VEGF), CD31 and D2-40 in involved and uninvolved skin of 18 patients with rosacea. METHODS: Immunostaining of facial skin specimens with VEGF, CD31 and D2-40 was compared between the lesional and the non-lesional skin of patients with erythemotelangiectatic and papulopustular rosacea. RESULTS: Significantly increased dermal expression of VEGF in lesional vs. non-lesional skin (88.9% and 55.6%) was observed. Dermal expression of CD31 and D2-40 was also increased in lesional vs. non-lesional skin. There was no statistically significant difference in cutaneous expression of VEGF, CD31 and D2-40 between patients with papulopustular and erythemotelangiectatic rosacea, and no correlation was found between disease duration and immunoreactivity of VEGF, CD31or D2-40. CONCLUSIONS: Our study showed marked immunostaining of lesional skin with VEGF, CD31 and D2-40 compared with non-lesional skin. Increased immunoreactivity of D2-40 in lesional skin is interesting, given that none of the patients had facial edema. There are no published data regarding the role of lymphangiogenesis in patients with non-phymatous rosacea; thus, our study represents a new understanding of its pathogenesis. Lack of correlation between D2-40 expression and disease duration suggests that lymphatics are involved early in the pathogenesis of rosacea and do not constitute a late event.

Cutaneous immunoreactivity of D2-40 antibody beyond the lymphatics.

Recent research suggests that the D2-40 monoclonal antibody recognizes the 40,000 Da O-linked sialoglycoprotein podoplanin. Podoplanin not only is highly expressed in lymphatic endothelium but also in other cell types, including sebaceous carcinoma cells. Using the D2-40 antibody, our purpose was to evaluate expression of podoplanin in sebaceous glands of normal skin. Twenty-four formalin-fixed, paraffin-embedded normal skin specimens (10 from scalp and 14 from cheeks) were immunostained using the D2-40 mouse monoclonal antibody. Strong immunostaining with D2-40 antibody was observed at the periphery of sebaceous glands and in skin lymphatic endothelium of all specimens, demonstrating that podoplanin is expressed in sebaceous glands of normal skin.