Insulin, insulin-like growth factor-1 (IGF-1) and essential amino acids activate the mechanistic target of rapamycin complex 1 (mTORC1), the main nutrient-sensitive kinase. Metformin, through inhibition of mTORC1 may improve acne. A 12-week, randomized, open-labeled study evaluated the efficacy and safety of metformin as an adjunct for moderate to severe facial acne. In total, 84 patients received either oral tetracycline 250 mg bd and topical benzoyl peroxide 2.5% with or without metformin 850 mg daily. Evaluations constituted lesion counts, the Cardiff Acne Disability Index (CADI), metabolic parameters and treatment success rate (Investigators Global Assessment score of 0 or 1 or improvement of two grades). Treatment success rates were higher in the metformin group (66.7% vs. 43.2%; p = .04). The mean percentage reduction from baseline in total lesion counts at Week 12 was greater in the metformin group (71.4% vs. 65.3%; p = .278). The CADI scores showed a greater mean reduction in the metformin group (4.82 vs. 4.22; p = .451). Metformin was equally efficacious in improving acne in lean and overweight subjects. Gastrointestinal symptoms were noted in 31.7% of subjects on metformin. This study presents favorable data for metformin as an adjunct for acne treatment. Further randomized placebo-controlled studies are required.
The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
The tenth edition of this extraordinary dermatologic congress was held in the Crowne Plaza Hotel in the magnificent Kuwait City on April 23-25, 2019, thanks to the patronage of His Excellency, the Honorable Dr. Basel H Al-Sabah, Minister of Health, Kuwait. It was organized and shepherded by the renowned Chairman of the Dermatology Council in Kuwait, Professor Nawaf Al-Mutairi, FRCP Edin This article is protected by copyright. All rights reserved.
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease. Biological therapy has revolutionized it's the treatment. Paradoxical HS occur with various biological and targeted agents. We report a patient with juvenile rheumatoid arthritis who developed HS after 6 months of tofacitinib therapy. A comprehensive literature review identified 43 cases of paradoxical HS among patients on biological and targeted agents. Pooled analysis of the cases showed Crohn's disease 18(41.8%) and RA 9(20.9%) as commonest indications for biological therapy. Adalimumab 20(46.5%) followed by infliximab 9(20.9%) were the commonest offending agents. Duration of biological treatment prior to HS manifestation was 12(1-120) months. Smoking 21(48.8%) and overweight or obese 20(46.5%) were most frequent HS risk factors. Fourteen (32.6%) patients had a second paradoxical event, 11(25.6%) developed psoriasis and 4(9.3%) Crohn's disease. Presence of ≥1 risk factor for HS, continuation of the implicated biological agent and occurrence of more than one paradoxical event were factors associated with poor paradoxical HS outcome.
Cryotherapy is a standard treatment for warts. Tuberculin immunotherapy is a novel therapeutic option. We compared the efficacy and safety of cryotherapy versus tuberculin immunotherapy in a randomized, assessor-blinded study. 15 patients were treated with intralesional tuberculin and 15 patients received cryotherapy every 2 weeks until complete wart resolution or a maximum of six sessions. Wart diameter, total number of warts and adverse effects were documented. Complete clearance of treated warts was achieved in 13(86.7%) and 11(73.3%) of patients with immunotherapy and cryotherapy respectively. Immunotherapy showed greater wart size reduction (51.88 ± 89.36 mm) than cryotherapy (32.99 ± 36.19 mm), (p = 0.46). Immunotherapy resulted in 64% reduction in total number of warts compared to 23.2% with cryotherapy, p
Methotrexate (MTX) is a first-line systemic psoriasis therapy with risk of liver fibrosis. Noninvasive tools for liver fibrosis screening are Fibroscan®, Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio (APRI) index. To compare Fibroscan®, FIB-4, and APRI in detecting fibrosis, determine association of fibrosis with MTX cumulative dose, and explore risk factors for fibrosis. A case-control study involving psoriasis patients aged ≥18 years with MTX cumulative dose ≥1 g, with age and sex-matched MTX naïve psoriasis patients was performed. Noninvasive tools were used to assess liver fibrosis. Sixty-one patients on MTX and 54 controls participated. Fibroscan® detected fibrosis in 22 (36.1%) patients on MTX compared to 11 (19.6%) controls (p = 0.05). FIB-4 predicted fibrosis in 13 (21.3%) patients on MTX and in 10 (17.9%) controls (p = 0.64) while APRI diagnosed 7 (11.5%) versus 7 (12.5%), p = 0.65. No significant correlation between Fibroscan® assessed liver stiffness and MTX cumulative dose (p = 0.47). Independent risk factors for liver fibrosis were MTX use with raised alanine aminotransferase (OR = 68.56, 95% CI 8.26; 568.86, p
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.
Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.