Effects of metformin on clinical, hormonal and relevant gene expression parameters in patients with acne: an observational study.

BACKGROUND: Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established. AIM: To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS. METHOD: In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed. RESULTS: Metformin monotherapy significantly (P < 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P < 0.001) decrease in free androgen index resulting from a significant (P < 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated. CONCLUSION: Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.

Juvenile localized scleroderma: A single-centre experience from India.

BACKGROUND: Juvenile localized scleroderma (JLS) or morphoea, a rare chronic autoimmune disease predominantly affects skin, subcutaneous tissue and occasionally the adjacent muscle, fascia and bone. We report the largest single-centre cohort of patients with JLS from India. METHODS: Patients who were diagnosed to have JLS were enrolled from the Paediatric Dermatology Clinic and the Paediatric Rheumatology Clinic of a tertiary care referral hospital in India. Collected data included details of the clinical profile, laboratory investigations and management. RESULTS: We analysed 84 patients with Juvenile localized scleroderma. Median age of disease onset was 5 years, and median age at diagnosis was 8 years. Commonest subtype was linear scleroderma (57 patients, 67.7%) followed by plaque morphoea and generalized morphoea. Fourteen patients (16.6%) were noted to have extracutaneous manifestations (ECMs). These included arthritis in eight (33.3%), brain parenchymal abnormalities in four (4.7%) and pulmonary involvement in two (8.3%) patients. Antinuclear antibody (ANA) was positive in eight/25 patients (32%; diffuse and speckled pattern in four patients each). One amongst these also had elevated anti-dsDNA titres. Positive ANA was found to have no association with ECMs (p 1.000). Patients were treated using methotrexate (61 patients; 72.6%), dexamethasone oral mini-pulse (OMP; 35 patients; 41.6%), calcipotriol (39 patients; 46.4%), topical corticosteroids (32 patients; 38%) and topical tacrolimus (three patients; 3.7%). Using linear regression analysis, administration of dexamethasone OMP and calcipotriol was found to be a predictor of good treatment response (p 0.034 and 0.019, respectively). CONCLUSION: Early use of systemic corticosteroids along with methotrexate may be more beneficial than methotrexate therapy alone.

Clinico-epidemiological profile and long term follow up in melasma.

Melasma is a disorder of hyperpigmentation that is frustratingly resistant to therapy with a high recurrence rate on treatment discontinuation. With the scarcity of melasma epidemiological studies from India, we conducted this study to see clinico-epidemiological trends and therapeutic response. Totally 957 melasma patients were studied during the 5-year period between October 2014 and September 2019. A female preponderance was seen. Patients were classified as early, moderate, and late responders if they had more than 80% clinical improvement within 8, 8-12, and 12-16 weeks rest classified as nonresponders. Six hundred and forty-eight patients with mMASI of ≤5 had been prescribed non-hydroquinone-based therapies who had overall response rate of 40.9% by end of 16 weeks, 309 with mMASI >5 received hydroquinone based triple combination with a response rate of 33.6% at end of 16 weeks. A total of 33.65% responded to triple combination compared to 40.1% in the non-hydroquinone group. All nonresponders received oral tranexamic acid 250 mg twice daily. Most patients on oral tranexamic acid group developed recurrence by 6 weeks post discontinuation, compared with triple combination therapy group who had relapsed by 2 months post discontinuation and 4 months to relapse with non-hydroquinone-based therapies. Side effects experienced were 0.83% in hydroquinone group reporting erythema and burning. 0.57% in non-hydroquinone group perceived stinging sensation and none from tranexamic acid group. The longest follow up available in our study was for 18 months. The emergent need of the hour is a long, safe, and effective therapy for melasma.

Clinical and metabolic characteristics of males with early-onset androgenetic alopecia.

Background Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ≥3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA.

Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic.

Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy.

Hairless Hyperhidrotic Plaque in a Young Male.

An 18-year-old male presented with an erythematous plaque on the left side of face and neck since 4 years. The lesion was devoid of hair, had follicular prominences, and showed increased localized sweating. Histopathology revealed an increased number of eccrine glands in the myxoid stroma with multiple vascular elements in the dermis, favoring the diagnosis of eccrine angiomatous hamartoma. This case illustrates a relatively uncommon clinical presentation of eccrine angiomatous hamartoma as a hairless, hyperhidrotic plaque in the head and neck region.

Platelet-Rich Plasma: The Journey so Far !

Platelet-rich plasma (PRP) is an autologous blood product, obtained after blood centrifugation. PRP is rich in growth factors which promote tissue-healing, alter angiogenesis, and possess versatile immunomodulatory effects, in the relative absence of any significant demonstrable adverse effects. Consequently, PRP has found application in multiple specialities in recent years, including dermatology. A literature search was performed on PubMed, Medline database, and Google Scholar, using keywords like platelet-rich plasma (PRP), platelet-concentrated plasma, platelet-rich growth factors, autologous platelet concentrate. Relevant studies were selected, and data was analyzed following extraction. Studies show that PRP has not only been used as an adjunctive modality but has been employed as a stand-alone therapy as well. Multiple authors have reported PRP to be efficacious in disparate dermatological conditions, like alopecia, skin rejuvenation, healing of refractory cutaneous ulcers, and even acne scar management. The strongest evidence so far has been demonstrated in androgenetic alopecia and facial skin rejuvenation. However, routine use in dermatological conditions is hampered by the relative paucity of high-quality evidence and large randomized studies. Furthermore, PRP composition and preparation methods are not yet standardized and even the treatment regimens proposed too vary widely. The present review provides a bird's eye view of the evidence available so far regarding the use of PRP in dermatology. The review focusses more on recent prospective studies, including randomized trials and tries to summarize the evidence in a brief, but comprehensive manner.

To determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol in a North Indian location.

BACKGROUND: Psoralen with ultraviolet A is an effective photochemotherapeutic modality. A subtype of this, PUVAsol, uses sunlight as the natural source of ultraviolet A. The amount of sunlight received and the consequent ultraviolet A exposure vary according to the month in the year, time of the day and geographical location of a place. AIM: The aim of this study is to determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol. MATERIALS AND METHODS: This was an observational study carried out at Postgraduate Institute of Medical Education and Research, Chandigarh (30.7333°N, 76.7794°E), India using a photometer. Ultraviolet A irradiance was recorded at a fixed place at 10 AM, once weekly for a period of 12 months. RESULTS: The irradiance of peak ultraviolet A was found to be 3.1 mW/cm2 in June 2016 while irradiance of 0.64 mW/cm2 was recorded in January 2017. The exposure time needed for therapeutic dose of 2 J/cm2 was 11 min 6 s in June 2016 while exposure time for achieving therapeutic dose of 2 J/cm2 was 52 min 5 s in January 2017. The duration of exposure was found to be significantly longer in the winter months. LIMITATION: The limitation of the study is not determining ultraviolet B radiation and infrared exposure. Other limitation of this study is that the irradiance was measured only at 10 am. This data cannot be used to determine irradiance at different time points in the day as the patient may expose himself/herself to sunlight anytime depending on his/her convenience. CONCLUSIONS: The study demonstrates the mean exposure time required for a given therapeutic dose of ultraviolet A in different months. The wide variation in ultraviolet A irradiance in natural sunlight over the year in different months also suggests that exposure times for PUVAsol should be based on the season and geographical location at the site of therapy and not based on uniform guidelines.

The acute transcriptome response of the midbrain/diencephalon to injury in the adult mummichog (Fundulus heteroclitus).

Adult fish produce new cells throughout their central nervous system during the course of their lives and maintain a tremendous capacity to repair damaged neural tissue. Much of the focus on understanding brain repair and regeneration in adult fish has been directed at regions of the brainstem and forebrain; however, the mesencephalon (midbrain) and diencephalon have received little attention. We sought to examine differential gene expression in the midbrain/diencephalon in response to injury in the adult fish using RNA-seq. Using the mummichog (Fundulus heteroclitus), we administered a mechanical lesion to the midbrain/diencephalon and examined differentially expressed genes (DEGs) at an acute recovery time of 1 h post-injury. Comparisons of whole transcriptomes derived from isolated RNA of intact and injured midbrain/diencephalic tissue identified 404 DEGs with the vast majority being upregulated. Using qPCR, we validated the upregulation of DEGs pim-2-like, syndecan-4-like, and cd83. Based on genes both familiar and novel regarding the adult brain response to injury, these data provide an extensive molecular profile giving insight into a range of cellular processes involved in the injury response of a brain regenerative-capable vertebrate.