Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism.

Hypoxia-inducible factor-1α (HIF-1α) is the master transcription factor of glycolysis, Th17 cell differentiation and suppression of regulatory T cells. In the skin and serum of patients with psoriasis vulgaris, increased expression of HIF-1α has been reported, whereas HIF-1α expression in the skin and serum of patients with hidradenitis suppurativa (HS) has not yet been studied. The objective of the study is to demonstrate is there a role for HIF-1α in the pathogenesis of hidradenitis suppurativa, and its relation to HS severity. Twenty patients suffering from hidradenitis suppurativa were included in the study. Punch biopsies were taken from lesional skin for the determination of HIF-1α expression by immunohistochemical staining, and HIF-1α gene expression by quantitative reverse transcription real time PCR. Quantification of HIF-1α protein concentration was done by enzyme-linked immunosorbent assay. Twenty socio-demographically cross-matched healthy volunteers served as controls. We found increased serum levels of HIF-1α. Literature-derived evidence indicates that the major clinical triggering factors of HS, obesity, and smoking are associated with hypoxia and enhanced HIF-1α expression. Pro-inflammatory cytokines such as tumor necrosis factor-[Formula: see text] via upregulation of nuclear factor [Formula: see text]B enhance HIF-1α expression. HIF-1α plays an important role for keratinocyte proliferation, especially for keratinocytes of the anagen hair follicle, which requires abundant glycolysis providing sufficient precursors molecules for biosynthetic pathways. Metformin via inhibition of mTORC1 as well as adalimumab attenuate HIF-1α expression, the key mediator between Th17-driven deviated immunity and keratinocyte hyperproliferation. In accordance with psoriasis, our study identifies HS as an HIF-1α-driven inflammatory skin disease and offers a new rationale for the prevention and treatment of HS by targeting HIF-1[Formula: see text] overexpression.

Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris.

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.

A split face comparative study using a novel triple combination therapy for the treatment of persistent post acne erythema.

Persistent post acne erythema (PAE) is common cosmetically unacceptable and challenging sequelae of acne lesions. Tranexamic acid (TXA) is an antifibrinolytic agent that shows a positive effect on wound healing in several studies, and it showed benefits in treating skin diseases like melasma, rosacea erythema and ultraviolet induced pigmentations. Oxymetazoline (OXZ) is a synthetic, highly selective agonist for alpha 1A-adrenoceptor. It is a potent vasoconstrictor. OXZ hydrochloride 1% cream was approved by the FDA in January 2017 as a topical treatment for persistent facial erythema in rosacea patients. Brimonidine tartrate (BMT) is highly selective α2 adrenergic receptor agonist, results in direct, potent vasoconstriction of small arterioles and veins. In 2013, brimonidine 0.33% gel was the first topical therapy to be FDA approved for the treatment of persistent facial erythema from rosacea. To evaluate the efficacy and safety of topical triple combination (TXA 5% + OXZ 1.5% + BMT 0.33%) in the treatment of PAE planned as split face comparative study. This study was conducted on 40 patients diagnosed with persistent PAE for at least 3 months, the right side of the face was treated with topical triple combination in liposomal base and was compared to the left side to which topical lipocream (placebo) was applied as a control. Our treatment plan lasted for 3 months. According to the investigator's global assessment of photographs and computerized analysis of erythema using image analysis software, topical triple combination applied on the right side of face was significantly effective in diminishing PAE when compared to topical placebo left side. Topical triple combination is a safe and cost-effective treatment for PAE.

A split face comparative study between intradermal tranexamic acid and Erbium-YAG laser in treatment of melasma.

BACKGROUND: Although there are different treatment modalities of melasma, it remains a challenging problem. Erbium-YAG laser proved its efficacy in melasma improvement with minimal downtime. Tranexamic acid (TA) is a new promising treatment of melasma. OBJECTIVE: The first objective is to compare between the efficacy of intradermal injection of TA and Erbium-YAG laser in the treatment of melasma. The second objective is to use the dermoscope as an objective evaluation method. PATIENTS AND METHODS: A split face study was conducted on 28 patients. One side of the face received intradermal TA injection. The other side was treated with laser. Melasma Area and Severity Index (MASI) and the dermoscope were used for evaluation of treatment. RESULTS: The MASI scores showed a significant decrease in TA treated side. The dermoscope assessment showed no significant difference in both treatment modalities. CONCLUSION: A promising results were obtained by both intradermal TA and Erbium:YAG laser; however, the TA yields a higher patient satisfaction because of its high efficiency and low cost.

Successful treatment of the face post acne erythema using a topically applied selective alpha 1-Adrenergic receptor agonist, oxymetazoline 1.5%, a controlled left to right face comparative trial.

BACKGROUND: Post-inflammatory erythema (PIE) is a common sequalae of acne inflammation, persistent post acne erythema (PAE) is cosmetically unacceptable and sometimes its complete clearance could not be achieved. Oxymetazoline (OXZ) is a synthetic, direct-acting, sympathomimetic agonist that is highly selective for the 1α-adrenoceptor. It is a potent vasoconstrictor and well known for its ability to clinically 'get the red out'. AIM: The aim of this study was to evaluate the efficacy and safety of topical oxymetazoline (OXZ) 1.5% in treatment of post acne erythema (PAE) in a left to right face comparative study. METHODS: This study was conducted on 40 patients diagnosed with post acne erythema for at least 3 months, the left side of the face was treated with topical OXZ 1.5% in liposomal base and was compared to the right side to which topical lipogel was applied as a control. RESULTS: According to the investigator's global assessment of photographs and the analysis of erythema with image analysis software, topical OXZ was significantly effective in diminishing PAE when compared to topical placebo lipogel. CONCLUSION: Topical OXZ is a safe and effective treatment for post-acne erythema.

The impact of isotretinoin on the pituitary-ovarian axis: An interpretative review of the literature.

Isotretinoin (13-cis-retinoic acid), a derivative of vitamin A, is used in the treatment of severe acne resulting in sebum suppression induced by sebocyte apoptosis. Isotretinoin treatment is associated with several adverse effects including teratogenicity, hepatotoxicity, and dyslipidemia. Isotretinoin's effects on endocrine systems and its potential role as an endocrine disruptor are not yet adequately investigated. This review presents clinical, endocrine, and molecular evidence showing that isotretinoin treatment adversely affects the pituitary-ovarian axis and enhances the risk of granulosa cell apoptosis reducing follicular reserve. Isotretinoin is associated with pro-apoptotic signaling in sebaceous glands through upregulated expression of p53, forkhead box O transcription factors (FOXO1, FOXO3), and tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Two literature searches including clinical and experimental studies respectively support the hypothesis that isotretinoin's toxicological mode of action on the pituitary-ovarian axis might be caused by over-expressed p53/FOXO1 signaling resulting in gonadotropin suppression and granulosa cell apoptosis. The reduction of follicular reserve by isotretinoin treatment should be especially considered when this drug will be administered for the treatment of acne in post-adolescent women, in whom fertility may be adversely affected. In contrast, isotretinoin treatment may exert beneficial effects in states of hyperandrogenism, especially in patients with polycystic ovary syndrome.

Fractional CO2 Laser for Transcutaneous Drug Delivery of Onabotulinum Toxin in Palmar Hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis is a common disorder of excessive sweating due to over-stimulation of cholinergic receptors on eccrine glands. OBJECTIVE: To compare the efficacy of laser-assisted drug delivery of onabotulinum toxin A (BoNTA) and intradermal BoNTA injections in the management of palmar hyperhidrosis. PATIENTS AND METHODS: This intrapatient comparative study was conducted on 30 adult patients with idiopathic palmar hyperhidrosis. The palms of the patients were divided into 2 groups. Group 1 was treated with intradermal injections of 50 units of BoNTA, whereas Group 2 was subjected to laser-assisted transcutaneous BoNTA delivery using fractional CO2 laser at different doses (25, 50, and 75 units). Each treatment modality was evaluated using the iodine starch test, hyperhidrosis disease severity scale, and gravimetric scoring. RESULTS: Delivery of 75 units of BoNTA to the dermis on the right-sided palms assisted by fractional CO2 laser was clinically equivalent to 50 units of injection on the left side. Pain intensity was significantly higher on the injected side than on the other side. CONCLUSION: Laser-assisted drug delivery of botulinum toxin can be considered an effective and safe alternative for treatment of palmar hyperhidrosis with minimal side effects and complications.

A comparative study between oral tranexamic acid versus oral tranexamic acid and Q-switched Nd-YAG laser in melasma treatment: a clinical and dermoscopic evaluation.

BACKGROUND: Melasma is a common acquired disorder of pigmentation. OBJECTIVE: To compare the efficacy of oral tranexamic acid (TA) versus oral TA and Q-switched Nd: YAG laser (1064-nm wavelength) in the treatment of melasma. MATERIALS AND METHODS: Sixty patients were divided into two groups. Group A: oral TA only and group B: oral TA plus Qs-Nd: YAG laser (1064 nm) sessions. Evaluations were performed on the clinical basis including the use of Modified Melasma Area and Severity Index (m MASI) and dermoscopy. Dermoscopic examinations were performed before and after the treatment sessions as well as at the 3-month follow up visit. RESULTS: There were statistically significant differences between the two studied groups regarding the change of m MASI after treatment and at the end of follow-up (p = .036) by using dermoscopy. Epidermal type of melasma showed the best response (0.048) and telangiectasias significantly improved in both groups of patients. CONCLUSIONS: Low-fluence 1064-nm Qs-Nd:Yag laser is effective and safe line of melasma treatment. Adding oral TA may enhance its clinical efficacy and decrease its side effects or complications. Dermoscopy is an important tool in pigment detection and vascular components in melasma, as well as their response to treatment.

Acne vulgaris: prevalence, severity, and impact on quality of life and self-esteem among Egyptian adolescents.

BACKGROUND: Acne vulgaris is the most common dermatoses affecting adolescents with significant impact on their quality of life (QoL). The current study aimed to estimate the prevalence of acne, severity, and its impact on QoL and self-esteem among Egyptian adolescents. METHODS: A cross-sectional study was conducted. A total of 787 students were selected using multistage stratified random sampling from 12 secondary schools in Alexandria, Egypt. Data was collected using a self-reported questionnaire, and clinical examination was performed. Severity of acne and its impact on QoL and self-esteem were assessed using the Global Acne Grading System (GAGS), Cardiff Acne Disability Index (CADI), and Coopersmith self-esteem scale, respectively. RESULTS: Prevalence of self-reported acne was 34.7%. Females significantly reported acne more frequently than males (39.1% vs. 30.3%, p = 0.009). Prevalence of clinically confirmed acne was 24.4%, with higher rates among females (28.6%) than males (20.2%, p = 0.006). The majority of students had mild acne (75.5%). CADI showed that 11.4% had severe disability. A significant medium positive correlation between GAGS and CADI was found (r = 0.338, p < 0.01). Among acne group, low self-esteem was more prevalent among females (67.0%) than males (45.0%, p = 0.004). CONCLUSIONS: Acne is a common problem among Egyptian school-aged adolescents with higher prevalence and impact in females. Our findings should alert health professionals and school authorities to timely identify, manage, and educate adolescents with acne.

Interferon-gamma serum level and immunohistochemical expression of CD8 cells in tissue biopsies in patients with alopecia areata in correlation with trichoscopic findings.

Alopecia areata (AA) is an autoimmune form of nonscarring hair loss. The aim of the study was to assess the serum concentration of interferon gamma (IFN-γ) and CD8 cell expression in lesional skin biopsies in correlation with the disease severity, activity, duration, and trichoscopic findings in patients with AA. The study included 30 patients with AA and 15 age- and sex-matched healthy controls. Trichoscopy was performed and photographs were captured for the alopecic areas, and the enzyme-linked immunosorbent assay technique was used for serum level of IFN-γ assessment and immunohistochemistry for CD8 cells. The results obtained indicate that IFN-γ serum level in patients was significantly higher than that of control subjects, and significantly correlated with the activity status and the duration of the disease. CD8+ T cells infiltrate intensity significantly correlated with severity. Yellow dots (YDs), vellus hair, black dot, and exclamation marks were the most common trichoscopic findings. The presence of black dots significantly correlated to the disease activity, duration, serum IFN-γ, and CD8+ infiltrate intensity. The presence of YDs significantly correlated with the mean serum IFN-γ level. Exclamation marks significantly correlated with the disease activity and the degree of CD8+ infiltrate. In conclusion, trichoscopy could be a reliable indicator of the IFN-γ serum level and CD8+ T cell infiltrate intensity in AA patient.

Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients.

Mycosis Fungoides (MF) is the most common type of cutaneous T-cell lymphomas. Early stage patients are treated with topical therapies and have normal life expectancy whereas patients with advanced disease encounter frequent relapses and have a five-year survival rate that does not exceed 15%. The aim of the present study was to characterize the expression of microRNA-16 (miR-16) and microRNA-93 (miR-93) in early and advanced cases of MF in relation to the clinicopathological parameters. Ten skin biopsies of early and advanced MF were investigated for the expression of miR-16 and miR-93 using RT-PCR. Immunohistochemical expression of apoptosis markers (BCL-2 and Survivin) were also investigated in the studied cases compared to normal skin and eczema biopsies. In the present study, BCL-2 and Survivin showed strong positive expression on neoplastic lymphocytes in all cases of MF regardless of their stage. We have also shown that miR-16 was significantly upregulated in advanced cases of MF compared to cases with early disease (p-value was less than 0.05). However, expression of miR-16 did not show any statistically significant correlation with age, gender, or expression of apoptotic markers. On the other hand, the expression of miR-93 showed significant downregulation in all lymphoma cases irrespective of their stage, compared to normal and eczema cases. Our results suggest that upregulation of miR-16 could be used to predict an aggressive course of the disease. We also suggest that miR-93 downregulation could serve as possible tool for establishing early diagnosis in early challenging cases. Our findings also provide consistent evidence that the anti-apoptotic molecules may play an important role in the pathogenesis of this type of cutaneous lymphomas and promote the idea that their inhibition could be an interesting novel therapeutic strategy in the treatment of MF.

Effect of oral isotretinoin on the nucleo-cytoplasmic distribution of FoxO1 and FoxO3 proteins in sebaceous glands of patients with acne vulgaris.

Oral isotretinoin is the most effective anti-acne drug with the strongest sebum-suppressive effect caused by sebocyte apoptosis. It has been hypothesized that upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin-induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the distribution of the pro-apoptotic transcription factors FoxO1 and FoxO3 in the nuclear and cytoplasmic compartments of human sebocytes in vivo before and during isotretinoin treatment of acne patients. Immunohistochemical analysis of skin biopsies with antibodies distinguishing phosphorylated and non-phosphorylated human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six weeks after initiation of isotretinoin therapy, and in acne-free control patients not treated with isotretinoin. Our in vivo study demonstrates a significant increase in the nucleo-cytoplasmic ratio of non-phosphorylated FoxO1 and FoxO3 during isotretinoin treatment of acne patients. Translational and presented experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3 proteins is involved in isotretinoin-induced pro-apoptotic signalling in sebocytes confirming the scientific hypothesis of isotretinoin-mediated upregulation of FoxO expression.

Benign prostatic hyperplasia, metabolic syndrome and androgenic alopecia: Is there a possible relationship?

OBJECTIVE: To evaluate the incidence of benign prostatic hyperplasia (BPH) and metabolic syndrome in patients with androgenetic alopecia (AGA) in comparison with those with no AGA, as several previous studies have reported inconsistent results of an association between metabolic syndrome and BPH with AGA. PATIENTS SUBJECTS AND METHODS: This cross-sectional study included 400 participants, divided into 300 patients diagnosed with AGA, with different grades according to Norwood-Hamilton classification, and 100 control subjects with no AGA. Criteria for diagnosis of metabolic syndrome according to Adult Treatment Panel-III criteria (waist circumference, blood pressure, fasting blood sugar, high-density lipoprotein and triglycerides), as well as criteria for diagnosis of BPH (prostatic volume, urine flow, and prostate-specific antigen) were assessed in all patients and compared with the control subjects. RESULTS: There were significant differences between the AGA and no-AGA groups for the following variables: waist circumference, body mass index, fibrinogen level, fasting blood sugar, cholesterol, C-reactive protein, erythrocyte sedimentation rate, and glycosylated haemoglobin. There was a significant difference in number of patients with AGA manifesting criteria of metabolic syndrome (51% vs 28%), as well as BPH diagnostic criteria (36% vs 6.8%) compared with the control subjects. Both BPH and metabolic syndrome were shown to be significant independent variables associated with AGA. CONCLUSIONS: Dermatologists, urologists, and primary care physicians should monitor patients with early onset AGA for the development of urinary symptoms, to permit an earlier diagnosis of BPH; and for metabolic syndrome symptoms, to permit early diagnosis of cardiovascular risk factors.

Serum level of macrophage migration inhibitory factor (MIF) in Egyptians with alopecia areata and its relation to the clinical severity of the disease.

BACKGROUND: Alopecia areata (AA) is a common dermatological problem that manifests as sudden loss of hair without any inflammation or scarring. Various cytokines are implicated in the pathogenesis of this disease. Macrophage migration inhibitory factor (MIF) is located at an upstream position in the events leading to the possible dysregulated immuno-inflammatory responses, and the high level of this cytokine in AA may suggest a role of MIF in the pathogenesis of AA. METHODS: This case-control study was carried out on 31 AA patients with different grades of severity and 15 apparently healthy subjects. Serum MIF level was measured by ELISA, and was correlated with the clinical severity of the disease using SALT (severity of alopecia tool) scoring system. RESULTS: In this study, there was a significant elevation in serum MIF levels in AA patients in comparison with controls. There was also a positive correlation between MIF levels and clinical severity and disease duration. CONCLUSION: MIF seems to have an essential role in the etiopathogenesis of AA. So, it is considered to be a promising target in the therapy of autoimmune diseases and as a future predictor of alopecia activity. Anti-MIF therapy might be added as one of the new biological treatments for AA.