Different vitiligo characteristics as predictors of increased risk of metabolic syndrome and insulin resistance: A case-control study.

BACKGROUND: Autoimmune and metabolic disturbances have been reported in association with vitiligo, highlighting possible systemic associations that should be considered. AIMS: To assess the possible association of metabolic syndrome (MetS) as well as insulin resistance (IR) with vitiligo in different age groups. METHODS: This case-control study included 142 patients with vitiligo aging ≥ 6 years and 142 age- and sex-matched controls. Participants were assessed for MetS using the International Diabetes Federation (IDF) criteria in addition to IR via homeostasis model assessment of IR (HOMA-IR). The study was registered at Clinical Trials.gov, Identifier: NCT03622320, on August 9, 2018. RESULTS: As per the IDF criteria, patients with vitiligo showed significantly more frequent association with high fasting plasma glucose levels, high blood pressure readings, central obesity, dyslipidemia, and MetS than controls (p = 0.020, p = 0.034, p = 0.014, p < 0.001, and p = 0.002, respectively). Moreover, patients with vitiligo have significantly higher levels of fasting insulin and HOMA-IR (p ≤ 0.001). Results obtained from patients with vitiligo and controls with coexistent MetS/IR demonstrated vitiligo as a risk factor for both MetS and IR. Univariate and multivariate logistic regression highlighted that older age was the significant independent predictor for MetS and IR. CONCLUSION: Patients with vitiligo showed a significantly higher incidence of MetS than controls. Vitiligo per se can be considered a risk factor for MetS and IR. Therefore, regular follow-up and early metabolic derangement diagnoses are mandatory.

Possible enigmatic link between serum leptin and vitiligo with its metabolic derangements: A comparative controlled study.

OBJECTIVE: Serum leptin, an adipocytokine of interleukin-6 family, has been linked to vitiligo-associated metabolic derangements. Additionally, it has been proposed as an inflammatory mediator with possible influence on vitiligo pathogenesis. This study aimed at assessing serum leptin in vitiligo patients compared to controls and whether different vitiligo characteristics have an influence on serum leptin levels. METHODS: In this hospital-based, cross-sectional case-control study, 70 vitiligo (35 segmental vitiligo (SV) and 35 Non-segmental vitiligo (NSV)) and 70 age- and sex-matched controls were assessed for different anthropometric measurements including waist circumference (WC), index of central obesity (ICO), and body mass index (BMI) as well as serum leptin levels. RESULTS: Central obesity as per ICO showed no significant difference between patients and controls. Additionally, patients of SV and NSV collectively showed significant higher incidence of +ve serum leptin than their controls (41.4% vs. 22.9%%, P: 0.019). Mere presence of vitiligo and ICO >0.5 were highlighted as independent predictors of +ve serum leptin (P: 0.009 and <0.001, respectively). LIMITATION: Inability to determine a cause/effect relationship based on a cross-sectional study. Larger scale studies are needed to affirm our findings. CONCLUSION: Mere presence of vitiligo being an independent predictor for high serum leptin could be either a contributor to pathogenesis of vitiligo or a sequel to accumulating evidence of metabolic nature of vitiligo. This is likely to influence the investigative panel and treatment protocol for vitiligo patients.

Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study.

BACKGROUND: NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking. PURPOSE: To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V). METHODS: This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6 months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity. RESULTS: In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control. CONCLUSION: NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance.

Flavonoids of Salvadora persica L. (meswak) and its liposomal formulation as a potential inhibitor of SARS-CoV-2.

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.

Fractional Carbon Dioxide Laser is Effective in Amelioration of Pruritus in Primary Cutaneous Amyloidosis: A Clinical and Biochemical Study.

BACKGROUND AND OBJECTIVES: Primary cutaneous amyloidosis (PCA) is a pruritic disease characterized by amyloid deposition in the skin. Interleukin-31 (IL-31) is a pruritus-mediating cytokine. Fractional carbon dioxide (CO2 ) laser has shown efficacy in the treatment of PCA regarding the clinical appearance, histological pattern, and pruritus. The aim of this study is to assess the effect of fractional CO2 laser on pruritus associated with PCA, and analyze whether this effect is related to IL-31 and IL-31 receptor (R) expression. STUDY DESIGN/MATERIALS AND METHODS: The study included 24 patients with PCA and 24 healthy controls. Each patient received four fractional CO2 laser sessions, 4 weeks apart, using the superficial ablative mode. Skin biopsies were taken from patients before and after treatment, as well as controls, for assessment of IL-31 and IL-31R by real-time polymerase chain reaction. RESULTS: Treatment resulted in significant improvement of all clinical parameters, including pruritus (P < 0.001). Patients before treatment had significantly higher IL-31 and IL-31R than controls (P = 0.000 for both). In addition, there was a statistically significant decrease in IL-31 and IL-31R after treatment than their values before treatment (P = 0.000 for both). CONCLUSION: This study confirms the therapeutic efficacy of fractional CO2 laser in treatment of PCA. Reduction of IL-31 and its receptor seems to be one of the involved mechanisms; however, its relation to improvement of pruritus is still not clear. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Recipient site preparation by cryoblebbing in melanocyte keratinocyte transplantation procedure over the fingers in vitiligo: A pilot study.

Surgical treatment of vitiligo lesions over the fingers has poor outcome. In this intra-patient comparative study, 12 patients with stable non-segmental vitiligo (NSV) affecting the middle three fingers of one hand were included. Three variations were used in treatment of finger vitiligo lesions: minipuch grafting, melanocytes keratinocyte transplantation procedure (MKTP) preceded by cryoblebbing or full CO2 laser resurfacing of the recipient site. Liquid nitrogen was used to create blebs in one finger 24 hours before therapy. On the following day, the second finger was treated by minipunch grafting and the third finger was resurfaced by CO2 laser. A suspension was prepared and 0.1 mL was injected into each cryobleb. It was also applied to the resurfaced skin. All patients underwent topical PUVA therapy and were followed-up for 12 months. Ten cases with 52 lesions completed the follow-up period. About 4/18 lesions treated by cryoblebbing followed by MKTP showed ≥75% repigmentation while only 1/17 lesions treated by laser resurfacing + MKTP and 1/17 lesions treated by minipunch grafting showed 30% and 10% repigmentation, respectively. No complications occurred in MKTP treated lesions. Cryoblebbing of the recipient site seems to improve the outcome of MKTP in lesions over the fingers in stable NSV.

Upregulation of the miRNA-155, miRNA-210, and miRNA-20b in psoriasis patients and their relation to IL-17.

Psoriasis is an immune-mediated disease, with genetic background and triggering environmental factors; however, several gaps are still present in understanding the intertwined relationship between these elements. Epigenetic mechanisms, including microRNAs (miRNAs), play an important role in the pathogenesis of psoriasis. The relationship between interleukin (IL)-17, a key cytokine in psoriasis, and these epigenetic mechanisms still needs to be elucidated. This study aimed at assessing the expression of miRNA-155, miRNA-210, and miRNA-20b in skin and sera of psoriasis patients in relation to IL-17 levels. For 20 psoriasis patients and 20 matching controls, the expression of miRNA-155, miRNA-210, and miRNA-20b was assessed using real-time polymerase chain reaction (RT-PCR), whereas IL-17/IL-17A levels were measured using quantitative enzyme-linked immunosorbent assay (ELISA) technique. MiRNA-155 expression was significantly higher in lesional skin compared to controls (P = 0.001). MiRNA-210 expression was significantly higher in both, lesional skin (P = 0.010) and sera of patients (P = 0.001) in comparison with controls. A statistically significant positive correlation was found between serum miRNA-210 expression and serum levels of IL-17/IL-17A (P = 0.010, rs = 0.562). MiRNA-20b lesional and non-lesional expression was significantly higher than controls (P < 0.001; P = 0.018). In conclusion, the expression of miRNA-155, miRNA-210, and miRNA-20b is exaggerated in psoriasis and they may be involved in disease pathogenesis. A possible relationship between miRNA-210 and IL-17 may be suggested; however, further studies are still needed to verify this relation.

Molecular docking reveals the potential of Salvadora persica flavonoids to inhibit COVID-19 virus main protease.

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks. It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death. One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects. COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. Metabolic profiling of the aqueous extract of Salvadora persica L. (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS. All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-ß-d-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir. Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease. The results indicate that the basic flavonol nucleus possesses activity itself. Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability. This study provides a scientific basis for the health benefits of the regular use of S. persica as it leaches bioactive flavonoids in the aqueous saliva.

Treatment of atrophic acne scars using autologous platelet-rich plasma vs combined subcision and autologous platelet-rich plasma: A split-face comparative study.

BACKGROUND: Multiple therapeutic approaches are usually required when treating atrophic acne scars. Subcision was reported to be of value in improving rolling scars. Autologous platelet-rich plasma (PRP) has recently been proposed as an adjuvant treatment option for atrophic acne scars with few reports evaluating its efficacy. OBJECTIVE: Our objective was to compare the effect of intradermal injection of PRP vs combined PRP and subcision in the treatment of atrophic acne scars. METHODS: Thirty patients with bilateral atrophic acne scars were enrolled. Each patient received three monthly sessions. Each side of the face was randomly treated either with intradermal PRP alone or with combined treatment with subcision followed by PRP injection. Patients were assessed at 3 and 6 months following the last treatment session. Evaluation of serial photographs was performed by two blinded investigators. RESULTS: Platelet-rich plasma alone showed a better response, fewer side effects, and shorter downtime compared to combined subcision and PRP. CONCLUSION: Autologous PRP injection can be a therapeutic option in the treatment of atrophic acne scars, with fewer complications and better tolerability than combined subcision and autologous PRP.

Hypopigmented Interface T-Cell Dyscrasia and Hypopigmented Mycosis Fungoides: A Comparative Study.

Hypopigmented interface T-cell dyscrasia (HITCD) is a distinct form of lymphoid dyscrasia that may progress to hypopigmented mycosis fungoides (HMF). We compared both diseases as regards their CD4/CD8 phenotype and expression of granzyme B and tumor necrosis factor-alpha (TNF-α) and how these are affected by narrow-band UVB (nb-UVB). The study included 11 patients with HITCD and 9 patients with HMF. They received nb-UVB thrice weekly until complete repigmentation or a maximum of 48 sessions. Pretreatment and posttreatment biopsies were stained using anti CD4, CD8, TNF-α, and granzyme B monoclonal antibodies. Epidermal lymphocytes were CD8 predominant in 54.5% and 66.7% of HITCD and HMF cases, respectively, whereas dermal lymphocytes were CD4 predominant in 63.6% and 66.7%, respectively. Significantly, more dermal infiltrate was encountered in HMF (P = 0.041). In both diseases, granzyme B was only expressed in the dermis, whereas TNF-α was expressed both in the epidermis and dermis. No difference existed as regards the number of sessions needed to achieve repigmentation or cumulative nb-UVB dose reached at end of study. (P > 0.05). Narrow-band UVB significantly reduced only the epidermal lymphocytes in both diseases (P ≤ 0.05) with their complete disappearance in 8 (72.7%) HITCD and 6 (66.7%) HMF cases. In both diseases, nb-UVB did not affect granzyme B or TNF-α expression (P > 0.05). In conclusion, both diseases share the same phenotype, with HITCD being a milder form of T-cell dysfunction. In both diseases, epidermal lymphocytes are mainly CD8-exhausted cells lacking cytotoxicity, whereas dermal cells are mostly reactive cells exerting antitumor cytotoxicity. Tumor necrosis factor-alpha mediates hypopigmentation in both diseases and prevents disease progression. Repigmentation after nb-UVB in both diseases occurs before and independently from disappearance of the dermal infiltrate.

Effect of Procedural-Related Variables on Melanocyte-Keratinocyte Suspension Transplantation in Nonsegmental Stable Vitiligo: A Clinical and Immunocytochemical Study.

BACKGROUND: Melanocyte-keratinocyte suspension (M-K susp) is gaining popularity for vitiligo treatment. Few studies have addressed procedure-related variables. OBJECTIVE: To assess the effect of different M-K susp procedure-related variables on the clinical outcome in stable vitiligo. METHODS: This prospective multicenter comparative study included 40 cases with nonsegmental stable vitiligo. Donor site was either a skin graft in noncultured epidermal cell suspension (NCECS) or hair follicle units in outer root sheath hair follicle suspension (ORSHFS). Recipient site was prepared by either cryoblebbing or CO2 laser resurfacing. Cell counts and viability were recorded in the cell suspensions. Tissue melanocytes and keratinocytes were examined by melan-A and cytokeratin, respectively. Assessment of repigmentation was performed 18 months after the procedure. RESULTS: Thirty-seven subjects completed the study. Cell count was significantly lower in the ORSHFS compared with NCECS with no significant difference in the repigmentation outcome. On comparing techniques of recipient site preparation, homogenicity was better in the CO2 group. Elbows and knees responded better to CO2 resurfacing, whereas distal fingers responded better to combination of cryoblebbing with NCECS. CONCLUSION: Using different techniques in M-K susp produces comparable results. However, the distal fingers showed better results using combination of donor NCECS and recipient cryoblebs.

Combination of radiofrequency and intralesional steroids in the treatment of keloids: a pilot study.

BACKGROUND: None of therapeutic options for the treatment of keloids has been found completely effective and satisfactory. A combination approach is the best modality. OBJECTIVE: To assess the clinical safety and efficacy of radiofrequency (RF) followed by intralesional (IL) steroid injection in keloids. MATERIALS AND METHODS: This pilot study included 18 patients who were suffering from keloids. All patients were subjected to 3 to 4 sessions of RF followed by IL steroid injection. Assessment of the scar volume and both objective and subjective parameters has been performed before and after completion of the sessions. RESULTS: There was a significant reduction of volume of all lesions in all patients after a total of 3 to 4 sessions (p = .001), with a mean volume reduction of 95.4%. There was a significant reduction of keloid pliability, height, and erythema compared with baseline (p < .001). Patients reported a significant reduction of their subjective symptoms compared with baseline (p < .001). No pain, infection, nor bleeding were reported after the RF procedure. CONCLUSION: Radiofrequency tissue volume reduction combined with IL steroid is an effective treatment modality for keloids. It is an easy procedure with acceptable cosmetic outcome and less rate of recurrence.

Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.

Study of T helper 1 and T helper 2 responses in pemphigus vulgaris patients receiving interferon alpha 2a injections in addition to a standard protocol therapy: a randomized controlled trial.

T helper (Th)1 insufficiency was recently found to be related to the pathogenesis of pemphigus vulgaris (PV). Decreased Th1 response was particularly noticed in the early stages of PV. Therefore, administration of interferon alpha in the early stages of aggressive PV may lead to rapid control of the acute stage of the disease. Our aim was to evaluate the role of interferon alpha in the treatment of PV. 30 patients with acute severe PV (>60 % affection) and 30 age and sex-matched healthy subjects were included in this RCT. Patients were randomly divided into two groups (A and B). Group B patients received interferon retard (one subcutaneous injection/week for 4 weeks) in addition to our protocol for the treatment of PV (systemic pulse corticosteroids/cyclophosphamide in combination with sulphasalazine and pentoxifylline) that was administered to all the included patients. IFN-γ and IL-4 were estimated by ELISA before treatment, after 4 weeks and at the end of the study duration (12 weeks). Clinical assessment was done by PAAS on a biweekly basis. All PV patients showed significantly (P < 0.001) elevated levels of IL-4 and significantly (P < 0.001) depressed mean concentration of IFN-γ as compared with healthy controls. Twelve weeks after therapy both groups showed significant improvement in their mean PAAS being more evident and more rapid in group B. IFN-γ was elevated significantly and IL-4 was dropped significantly in group B patients in comparison to group A (P < 0.001). As a conclusion, interferon therapy in severe PV could achieve a more prompt and better clinical response.

Broadband ultraviolet A in the treatment of psoriasis vulgaris: a randomized controlled trial.

BACKGROUND: Broadband ultraviolet A (BB-UVA) has been successfully used in the treatment of scleroderma, a UVA1-responsive dermatosis. OBJECTIVE: To compare the efficacy of BB-UVA versus psoralen + UVA (PUVA) in psoriasis treatment and assess apoptosis as an effector mechanism. PATIENTS AND METHODS: This randomized controlled trial included 61 patients with chronic plaque psoriasis randomly divided into group I or II. Group I were further randomized to either IA or IB who received UVA 10 or 15 J/cm(2) per session, respectively, while group II received PUVA. Therapy was delivered thrice weekly until clearance or 48 treatments at most. The primary outcome measured was clearance of psoriasis. Dermal lymphocytic counts and bcl-2 expression were measured in 20 patients from each group. RESULTS: Final Psoriasis Area Severity Index scores were reduced within each group. The UVA group achieved results comparable to PUVA until session 24 but failed to match it at final evaluation, with significantly better clinical, immunohistochemical, and histopathological results achieved by PUVA (P ≤ 0.05). Both modalities caused a reduction in dermal lymphocytic counts and epidermal bcl-2 expression. CONCLUSION: BB-UVA appears to be safe and acceptable for the treatment of chronic plaque psoriasis possibly through bcl-2-mediated apoptosis of keratinocytes and epidermal lymphocytes.

BB-UVA vs. NB-UVB in the treatment of vitiligo: a randomized controlled clinical study (single blinded).

BACKGROUND: Vitiligo is an acquired pigmentary disorder that affects between 1% and 2% of the general population. Phototherapy remains the cornerstone of treatment, with NB-UVB being the most frequently used. BB-UVA can be a plausible alternative for darker population; skin photo type III and IV. PATIENTS AND METHODS: The study was a prospective, randomized, controlled, and single-blinded clinical trial, conducted on 40 patients with bilateral symmetrical vitiligo. The patients were randomly divided into two equal groups; group (A) received a fixed dose of 15 J/cm(2) BB-UVA, while group (B) received NB-UVB. The study was conducted for a period of 16 weeks (48 sessions). RESULTS: The final percentage of clinical improvement was significantly higher (P = 0.047) within the BB-UVA group (63.82% ± 27.42), than within the NB-UVB group (44.32% ± 29.78). CONCLUSION: BB-UVA can be considered as an alternative treatment line for vitiligo.

A comparative study of different treatment frequencies of psoralen and ultraviolet A in psoriatic patients with darker skin types (randomized-controlled study).

BACKGROUND: Photochemotherapy psoralen and ultraviolet A (PUVA) is a viable option for treatment of psoriasis. However, concerns about its side effects have raised the need to change current PUVA protocols. The aim of this study is to determine whether reducing the treatment frequency of PUVA to twice/week instead of three times/week would affect the efficacy of PUVA therapy. PATIENTS AND METHODS: The study included 20 psoriatic patients, randomized into two groups, 10 patients in each group. The first group received two weekly sessions, the second group received three. The study lasted until complete clearance or for 12 weeks (endpoint). Psoriasis area and severity index (PASI) score was done prior to therapy, at mid therapy and at end of therapy (PASI final). RESULTS: No significant different in PASI final and in the percentage of reduction of PASI score between both groups (P value >0.05) was found. However, a significant difference in the total number of sessions and the total cumulative UVA doses between both groups was found (P value <0.001). CONCLUSION: Our study suggests reducing PUVA frequency and the cumulative UVA dose does not compromise the efficacy of PUVA, but it may improve its benefit/risk ratio. RESTRICTIONS: Few number of cases.