Does vitamin D deficiency predispose to keloids via dysregulation of koebnerisin (S100A15)? A case-control study.

Keloids result from uncontrolled inflammation and fibrosis during wound healing. Vitamin D can regulate skin proliferation and inflammation. Fibroblasts are vitamin D-responsive target cells and are source of koebnerisin (an antimicrobial peptide released during inflammation and wound healing). This study aimed to assess the levels and correlations between the serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin (S100A15) in patients with keloids. Nineteen patients with keloids and 20 matched controls were recruited. From each keloid patient, a serum sample and two biopsies were taken from the keloid (lesional) (Tissue A) and from normal skin (non-lesional) (Tissue B). From controls, a serum sample and a tissue biopsy from normal skin were taken. Serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin were measured in retrieved samples using ELISA. Results revealed a significantly lower serum 25-Hydroxyvitamin D, tissue vitamin D receptors, as well as, serum and tissue koebnerisin in keloid patients compared to controls. Tissue 25-Hydroxyvitamin D was significantly lower in keloidal skin biopsy (Tissue A) compared to non-lesional normal skin biopsy (Tissue B). Tissue koebnerisin showed a significant positive correlation with tissue vitamin D receptors, and a significant negative correlation with tissue 25-Hydroxyvitamin D. There was a significant negative correlation between serum 25-Hydroxyvitamin D and duration of keloid. Accordingly, low serum and tissue 25-Hydroxyvitamin D and deficient tissue vitamin D receptors contribute to the pathogenesis of keloids. This can be partly mediated by dysregulation of the antimicrobial peptide; koebnerisin. Artificial antimicrobial peptides and koebnerisin-modifying drugs, for example, vitamin D and TNF-α inhibitors can have a role in keloid prevention and treatment.

The efficacy of oral vs different dilutions of intradermal tranexamic acid microinjections in melasma-A randomized clinical trial.

Melasma is a common acquired disorder of pigmentation, remains challenging despite numerous treatment modalities. Tranexamic acid (TXA) has emerged as a potential treatment for melasma. Different forms of TXA (oral, topical, and intradermal microinjections) have shown promising results. To evaluate and compare the efficacy of oral vs different dilutions of intradermal TXA in melasma. A total of 45 female patients with melasma were randomly and equally assigned to three treatment groups. Group A (oral TXA 250 mg bid), Group B (100 mg/mL intradermal TXA) & Group C (4 mg/mL intradermal TXA) every 2 weeks, treatment period was 8 weeks. At 8 weeks, a significant reduction in the mMASIwas noted in groups A, B, and C (P value .002, .003, and .005). Melanin index (MI) was significantly reduced in groups A, B, and C (P value .016, .005, and .003). Erythema index (EI) showed significant improvement in group A (P value .028), however was statistically insignificant for groups B and C. No statistically significant difference was found between the three groups as regards changes in mMASI, MI, and EI at 8 weeks. Both oral and intradermal microinjections of TXA regardless dilution appear to be effective and safe in treatment of melasma with comparable results.

Estimation of Homocysteine Level and Methylenetetrahydrofolate Reductase (MTHFR) Gene and Cystathionine B Synthase (CBS) Gene Polymorphisms in Vitiligo Patients.

BACKGROUND: Vitiligo is an acquired, multifactorial disorder of the skin and mucous membranes. An elevated homocysteine level has been described in vitiligo. Methylenetetrahydrofolate reductase (MTHFR) and cystathionine B synthase (CBS) are major determinants of the homocysteine metabolism. OBJECTIVES: Determine serum homocysteine levels in vitiligo patients as well as the association between MTHFR (C677T, A1298C) and CBSgene polymorphisms and susceptibility to vitiligo in a sample of those populations. METHODS: Homocysteine levels were estimated by radioimmunoassay while MTHFR (C677T, A1298C) and CBSgene polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism technique in 100 vitiligo patients and 80 healthy controls. RESULTS: The homocysteine level was significantly higher in vitiligo patients than controls (p = 0.000). Significant differences in the genotype and allele distributions of single nucleotide polymorphisms of the MTHFR (C677T, A1298C) with the mutant genotypes are more common in the controls than patients (p = 0.001, 0.029, respectively). CBS gene mutant genotypes and alleles are more common in vitiligo patients than controls (p = 0.002). CONCLUSION: CBSand MTHFRgene polymorphisms may play a major role in the genetic susceptibility to vitiligo.

Transforming growth factor-ß1 gene polymorphism in psoriasis vulgaris.

BACKGROUND: Increased transforming growth factor beta 1 (TGF-ß1) in the epidermis and serum has been found in psoriatic patients. The mechanism for this increase remains unclear. OBJECTIVE: To study the TGF-ß1 gene polymorphism at codon 10 and its relation to psoriasis susceptibility in a sample of Egyptian patients. MATERIALS AND METHODS: This cross-sectional study involved 70 patients with psoriasis vulgaris and 100 age- and sex- comparable healthy volunteers as a control group. Genomic DNA was prepared from peripheral blood lymphocytes from all subjects using QIAamp DNA mini kit (QIAGEN Inc., Germany). The TGF-ß1 polymorphism was genotyped by PCR-based restricted fragment length polymorphism (PCR-RFLP) analysis. Amplification of codon 10, located in exon 1 of TGFß1 gene was done through PCR reaction using gene-specific primers. RESULTS: Statistically significant difference was found between psoriasis patient and controls as regards TGF-ß1 (T869C) polymorphism (P=0.045). The presence of TT genotype was associated with a 3-fold risk of psoriasis compared to CC genotype (P=0.016, OR: 3.13 95% CI: 1.24-7.88). T allele was significantly more frequent in psoriasis patients (P=0.017). TGF-ß1 gene mutation was significantly higher among psoriasis patients with positive family history (P=0.007). CONCLUSION: TGF-ß1 gene polymorphism at codon 10 (T869C) is significantly associated with susceptibility to psoriasis in Egyptian patients. This polymorphism is more common in patients with a positive family history of psoriasis.

Antiangiogenic effect of methotrexate and PUVA on psoriasis.

Vascular endothelial growth factor (VEGF) is important factor for angiogenesis in psoriasis. Methotrexate and psoralen and ultraviolet light A (PUVA) mainly target the T cell-mediated immunopathology of psoriasis. Our work aimed at estimating VEGF mRNA in psoriatic patients and investigating whether the standard therapeutic modalities (methotrexate and PUVA) exert their antiangiogenic activity through altering VEGF levels. Twenty-four chronic plaque psoriasis patients were enrolled. Patients were divided into two groups (12 patients each); group A received intramuscular methotrexate and group B was treated by PUVA three times/week in a PUVA 1000 cabin for 10 weeks each. Twelve healthy volunteers served as controls. A skin biopsy was taken from lesional skin before and after treatment for RT-PCR detection of VEGF mRNA. Capillary perfusion scanning using LASER Doppler perfusion imaging was performed on the same psoriatic plaque before and after treatment and was also done for the controls. Following both methotrexate and PUVA, a significant reduction in the amount of VEGF mRNA (P < 0.001 and P = 0.002, respectively) and capillary perfusion (P = 0.002) occurred. These reductions were significantly higher in the methotrexate group (P < 0.001 and  P = 0.001, respectively) than in the PUVA group. The percentage of clinical improvement in the examined psoriatic plaque was significantly positively correlated with the percentage of reduction in the amount of VEGF mRNA (r = 0.850, P < 0.001) and the percentage of reduction in the capillary perfusion (r = 0.684, P < 0.001). Both modalities may exert an antiangiogenic effect. Methotrexate appears to have possibly a more potent antiangiogenic effect than PUVA.

Sulfasalazine and pentoxifylline in psoriasis: a possible safe alternative.

BACKGROUND: Conventional therapy of extensive psoriasis is effective but has complications. Biologics are safer but expensive. OBJECTIVE: To assess the efficacy of sulfasalazine and pentoxifylline, which have TNF antagonizing and anti-proliferative action in the treatment of psoriasis. METHODS: In this randomized controlled trial, 32 patients with extensive psoriasis were divided into four groups: group A received sulfasalazine; group B received pentoxifylline; group C received both drugs; and group D received methotrexate. The Psoriasis Area and Severity Index (PASI) score was done at weeks 0, 2, 4, 6 and 8. RESULTS: A significant reduction in PASI score occurred in groups C and D (p = 0.043 and 0.018, respectively). A significantly higher percentage of PASI score reduction occurred in group D compared with groups A, B and C (p = 0.006, 0.003 and 0.030, respectively). An excellent response occurred in one patient (14.3%) in group D. A very good response occurred in two patients (22.2%) in group C, and in five patients (71.4%) in group D. A moderate response occurred in three patients (37.5%) in group A, one patient (12.5%) in group B, and one patient (14.3%) in group D. CONCLUSION: Although incomparable to methotrexate, combined sulfasalazine and pentoxifylline produced a good response in cases of extensive psoriasis. Multicentre studies are needed to validate these results.