Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Evaluation and comparison of the efficacy and safety of cross-linked and non-cross-linked hyaluronic acid in combination with botulinum toxin type A in the treatment of atrophic acne scars: A double-blind randomized clinical trial.

INTRODUCTION: Acne vulgaris is a common skin condition that affects a significant percentage of adolescents, with scarring being one of its permanent complications. This study aims to compare the efficacy and safety of using botulinum toxin type A (BTA) in combination with cross-linked and non-cross-linked hyaluronic acid (HA) for the treatment of atrophic acne scars. METHOD: Our study is a randomized, double-blind clinical trial conducted on 16 patients with atrophic acne scars. The patients were randomly assigned to one of two groups: one group received a single session of BTA and crossed link HA combination, while the other group received two sessions of BTA and non-crossed link HA, 1 month apart. The patients were followed up at 3 and 6 months after baseline to evaluate the number and area of fine and large pores and spots, scar grading, patient satisfaction, and complications. RESULTS: The mean age of individuals in both the cross-linked HA and non-cross-linked HA groups was 32.75 ± 4.26 and 31.50 ± 8.48 years, respectively (p = 0.71). In terms of gender, three (37.5%) and seven (87.5%) individuals in the cross-linked and non-cross-linked HA groups were female, respectively (p = 0.11). There were no significant differences in the count and area of fine and large pores and spots between the two groups at baseline and the first follow-up session. However, in the second follow-up session, the non-cross-linked HA group had significantly better results than the cross-linked HA group in terms of large pores count and area (p = 0.01). In terms of changes over time, the non-cross-linked HA group showed significantly better improvements in the count and area of large pores compared to the cross-linked HA group (p = 0.03). Additionally, both groups experienced a significant decrease in the count and area of fine pores over time (p = 0.001), but the amount of changes was not statistically significant between the two groups (p = 0.06). Concerning acne grade, initially, 62.5% and 12.5% of cases in the cross-linked HA and non-cross-linked HA groups, respectively, had severe grades. However, in the last session, these percentages significantly decreased to 0% for both groups (p = 0.002 and 0.005, respectively). In terms of treatment complications, none of the patients experienced any adverse effects. CONCLUSION: The study demonstrated that both cross-linked HA and non-cross-linked HA were effective in reducing acne severity and improving the appearance of pores and spots. The treatments had similar effects on fine pores, spots, and overall acne severity. However, non-cross-linked HA appeared to have a better result on large pores compared to cross-linked HA.

The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.

Evaluation of the effects of adding an adipose tissue-derived stromal vascular fraction to platelet-rich plasma injection in the treatment of androgenetic alopecia: A randomized clinical trial.

BACKGROUND: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet-rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. METHODS: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1-month intervals, while the SVF-PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. RESULTS: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF-PRP group, and the SVF-PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. CONCLUSION: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA.

Effectiveness, safety, and patient satisfaction of carboxytherapy as an adjunctive treatment for periorbital hyperpigmentation.

INTRODUCTION: Dark under-eye circles or periorbital hyperpigmentation constitute a prevalent and challenging cosmetic problem with diverse etiologies and types. While modifying exacerbating habits can provide partial relief for the pigmentary and vascular factors associated with this condition, and despite the abundance of available treatment options, there is currently a lack of gold-standard evidence-based treatments proposed for curing this disorder. OBJECTIVES: This study aimed to assess the safety and effectiveness of carboxytherapy in treating periorbital hyperpigmentation. MATERIAL AND METHODS: In this 4-week single-arm clinical trial, 20 eligible Iranian patients with symmetric periorbital hyperpigmentation received weekly intradermal carboxytherapy. The treatment involved administering 10-20 mL of CO2 at a rate of 20 mL/min and a temperature of 15°C for a duration ranging from a few seconds to 1 min. Follow-up assessments were conducted 1 month after the final session. The primary outcome was defined as the changes in ΔE or the variations in pigmentation observed between the orbital and extra-orbital skin before and after the trial. RESULTS: The patients reported satisfaction with the statistically significant reduction in hyperpigmentation achieved through carboxytherapy in the lateral (p = 0.002), middle (p = 0.001), and medial (p = 0.001) regions of the periorbital area. The total response rate of the patients was estimated at 20%. Patient satisfaction exceeded ΔE changes, with no significant linear relationship (p = 0.084). CONCLUSION: Carboxytherapy can be proposed as an effective and safe treatment for periorbital hyperpigmentation.

The burden of dermatitis from 1990-2019 in the Middle East and North Africa region.

BACKGROUND: There are several types of dermatitis, each capable of causing enduring changes that extend beyond physical discomfort. In severe cases, dermatitis can significantly affect mental health, social interactions, and the overall quality of life. This study reports the burden of dermatitis in the Middle East and North Africa (MENA) region from 1990 to 2019, according to sex, age category, and socio-demographic index (SDI). METHODS: Publicly available data regarding the point prevalence, incidence, and years lived with disability (YLDs) were collected from the Global Burden of Disease 2019 study for both the MENA region and its constituent countries. The point prevalence, incidence, and YLDs of dermatitis were represented as counts and age-standardised rates with 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence of dermatitis was 2744.6 (2517.8-3003.1) per 100,000 population, which was 2.3% lower than in 1990. The YLD rate was 92.3 (55.6-143.4) per 100,000 population, which was 3.1% lower than in 1990. The largest point prevalence rates were observed among those aged 70-74, for both sexes. The 2019 MENA/Global DALY ratio was not above one in any age group for either sex. During the period 1990 to 2019, there was no clear correlation between the burden of dermatitis and the SDI level. CONCLUSION: The dermatitis burden in the MENA region remained relatively stable from 1990 to 2019. Future prevention efforts should focus on improving healthcare access, health education, and workplace safety regulations.

A patient with PLACK syndrome with a novel splicing mutation in CAST: the evidence for a loss-of-function mechanism through mis-splicing.

PLACK syndrome is a relatively recently defined generalized peeling skin syndrome that has been reported with major skin manifestations and sometimes atypical features. We report the case of a 5-year-old boy with PLACK manifestations. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209+2T>G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene, leading to the addition of one nucleotide to the correct open-reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for this patient's phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK syndrome.

The efficacy and safety of endo-radiofrequency for the treatment of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic and recurrent disease of the axilla and groin with inflammatory lesions. There is no definitive medication or intervention to cure the disease. Radiofrequency (RF) is a modality to destroy the lesions by transferring heat into the skin. To date, few studies have been conducted to evaluate the efficacy and safety of RF at HS. METHODS: This 9-month, prospective, nonrandomized, and single-blinded study is a clinical trial conducted in 10 patients with refractory HS. In all patients, the initial grade of HS was evaluated. The procedure involved treating HS of the axilla with a endo-RF wave device. Post-treatment evaluation included: determination of the severity of the disease by a blinded dermatologist, the degree of patient satisfaction, tolerability in each patient, and complications of the procedure. We also evaluate the recurrence of the disease during a 6-month follow-up. RESULTS: The satisfaction level after the intervention among under-studied cases was excellent and good in six of cases. There was a significant difference in comparing the grading score of patients before and 3 months after receiving RF (P-value: 0.01). Regarding tolerability, eight of the patients could tolerate it. We had no complication after the intervention and four cases had not recurrence during a 6-month follow-up. CONCLUSION: Endo-RF is an effective and safe modality for treating HS however to prevent the recurrence, periodic therapy sessions are needed.

Efficacy, safety, tolerability, and satisfaction of N-acetylcysteine and pentoxifylline in lichen planopilaris patients under treatment with topical clobetasol: A triple arm blinded randomized controlled trial.

Lichen planoplaris (LPP) is one of the most common causes of inflammatory cicatricial alopecias. There is no definitive cure for the disease and most of the available therapeutic options can potentially lead to serious complications following their use for extended durations. In this study, we aimed to evaluate the efficacy, safety and tolerability of N-acetylcysteine (NAC) and pentoxyfillin (PTX), as adjunctive therapies, in the management of LPP. In a randomized, assessor- and analyst-blinded controlled trial, patients with proven LPP were randomly assigned to three groups of 10. Group I (the control group) received clobetasol 0.05%lotion; Group II, a combination of clobetasol 0.05% lotion and oral PTX; Group III, a combination of clobetasol lotion 0.05% and oral NAC. Lichen planopilaris activity index (LPPAI), the possible side effects, tolerability and patients satisfaction were assessed before and two and four months after the initiation of the treatments. Thirty patients, 96.7% women, with a mean age of 46.8 ± 13.3 years old, were included in the study. Four months into the treatments, the overall LPPAI and the severity and/or frequency of most of its determinants significantly decreased in all groups. In a comparison among the groups, patients who received either of the combination therapies showed more decline in their LPPAI than those receiving only clobetasol. The decline was more noticeable and statistically significant only in the NAC group. Three patients in the PTX group developed complications that were not statistically significant when compared with the other groups. There were no substantial differences in the tolerability of the treatments among the study arms. The use of oral NAC and PTX added to the therapeutic efficacy of topical clobetasol in the treatment of LPP, suggesting that they might be beneficial and safe adjuvant therapies and add to the efficacy of topical treatment without any noticeable impact on the adverse effects experienced by patients.

Efficacy and safety of topical timolol 0.5% plus saline 0.9% versus each one alone in acne scar trichloroacetic acid-CROSS therapy: A blinded randomized controlled trial.

Trichloroacetic acid-CROSS (TCA-CROSS) or chemical reconstruction of scars is an approved method in the treatment of ICE-PICK scars. Timolol is a blocker of beta-adrenergic receptors that speeds up the healing of skin wounds. In this study, for the first time, the TCA-CROSS technique was combined with the use of saline injection and topical timolol to increase the effectiveness of treatment, and reduce the number of treatment sessions and complications, and thus improve the aesthetic result. In this parallel-group split-face randomized controlled assessor and analyst-blinded study, 45 patients with atrophic acne scars were randomly divided into 3 equal groups. TCA-CROSS treatment was performed on all facial scars of patients. In group 1, before TCA-CROSS, saline was injected under the scars on one side of the face, in group 2, after TCA-CROSS, 0.5% timolol eye drops were applied on the scars on one side, and in group 3, saline was injected before TCA-CROSS. After that, timolol eye drops were applied on the scars of the same side. In all groups, the choice of control side was random. The number of scars and patient and physician satisfaction were the main variables evaluating the effectiveness of the treatment. TCA-CROSS improved scars in both control and treatment sides of all 3 groups. Although the number of scars decreased on the treatment side of groups 2 and 3, the decrease was not statistically significant. In the saline + TCA group, the number of scars on the treatment side was slightly more than on the control side. In the group of patients who used timolol, the severity and duration of scar hyperpigmentation were significantly lower (group 2 p = 0.016, group 3 p = 0.002). No permanent complication was observed in the patients. Patients' satisfaction in groups 2 and 3 was higher in the treatment side than the control side. The combination of saline injection followed by TCA-CROSS is not recommended. Application of 0.5% timolol after TCA-CROSS caused a slight decrease in scar severity and a significant reduction of post-inflammatory hyperpigmentation (PIH) duration. So, the topical timolol makes a better result of TCA-CROSS for acne scar treatment.

Comparison of efficacy, safety and satisfaction of latanoprost versus minoxidil, betamethasone and in combination in patients with alopecia areata: A blinded multiple group randomized controlled trial.

Alopecia areata (AA), a polygenic and chronic autoimmune disease and there is no definitive cure. We aimed to evaluate latanoprost effects in patients with AA. In this controlled randomized double-blind clinical trial, we enrolled patients with AA randomly assigned to six groups of 18; Group 1 received latanoprost eye drops; group 2 minoxidil 5% solution; group 3 latanoprost eye drops and minoxidil 5% solution; group 4 betamethasone and minoxidil 5% solution; group 5 betamethasone solution and latanoprost eye drops; group 6 (the control group) betamethasone solution. The alopecia severity in patients before and after treatment was assessed by severity of alopecia tool (SALT). One hundred and eight patients, 50% male (mean age: 32.6 ± 10.4) were studied. The overall SALT score decreased in all. After 2 weeks, patients receiving betamethason-minoxidil and betamethason-latanoprost showed more decline in their SALT than other groups. In final, there was statistically significant difference among betamethasone-latanoprost group with minoxidil, betamethasone-minoxidil and betamethasone groups. Regrowth was higher in latanoprost and betamethasone-latanoprost groups than minoxidil. Topical latanoprost added to therapeutic efficacy of topical betamethason and minoxidil in treating patchy AA, suggesting it being beneficial and safe adjuvant therapy and add to efficacy of topical treatments without any adverse effects.

Endolift laser an effective method for the lower eye bag treatment: a case series study.

Numerous individuals suffer from the lower eye bag. Lower eye bag treatment is a challenge that might require new methods. Depending on the cause, there are different treatment approaches to reduce puffiness under the eyes. In this pilot study, 9 patients with lower eye bags received Endolift therapy (200-300-nm fiber) and were followed up for 6 months. The patients were evaluated according to biometric characteristics. Additionally, outcomes were evaluated by three blinded dermatologists, and patients' satisfaction was assessed. The obtained biometric results showed that Endolift laser treatment could increase both the dermis and epidermis of the skin and skin elasticity in this area. Furthermore, the results indicated that Endolift therapy showed good and very good improvement in about 90% of patients. Photographic data evaluation indicated a 90% improvement in the appearance of eye bags (P < 0.05). Endolift laser seems to be a safe and effective method for lower eye bag treatment. It is a noninvasive treatment with satisfactory results with minimal downtime and side effects. Endolift therapy significantly reduces the appearance of eye bags and wrinkles and increases skin elasticity under the eyes; therefore, it is an effective method for lower eye bag treatment. The method is pain-free, bloodless, and without the need for stitches. Endolift therapy allows the patient to avoid surgery.

A systematic review of the histopathologic survey on skin biopsies in patients with Corona Virus Disease 2019 (COVID-19) who developed virus or drug-related mucocutaneous manifestations.

The mucocutaneous manifestations of Corona Virus Disease 2019 (COVID-19) logically may reflect systemic visceral involvements. These findings are visible and easy to approach like biopsies for exact histopathologic evaluations. This systematic review was conducted to collect the mucocutaneous histopathologic data of COVID-19 patients for future investigations and interpretations. The COVID-19 dermatology resource of the Centre of Evidence-Based Dermatology (CEBD) at the University of Nottingham, PubMed, Scopus, Google Scholar and Medscape was searched for relevant English articles published by June 3, 2020. This review included 31 articles, involving 459 patients. The common primary virus-related mucocutaneous manifestations are easy to approach in the course of COVID-19. The authors of this study supposed dermatopathological findings as the predictors of the nature of potential systemic involvements and outcomes of COVID-19. Scrutinizing these findings can help with adopting more effective therapeutic and management strategies; nevertheless, this review found the severity and time of onset of symptoms not to be associated with the laboratory and histopathological findings. Deterioration of clinical conditions and laboratory tests was also not related to the histopathological findings. It is recommended that meta-analyses be conducted in the future to detail on these data for having more comprehensive and better conclusion.

Systematic review of platelet-rich plasma in treating alopecia: Focusing on efficacy, safety, and therapeutic durability.

Considering the different forms, alopecia could be a very common condition with particular therapeutic concerns; thus, recent therapies still require further assessments. Aim of this systematic review was to evaluate efficacy, safety, and therapeutic durability of platelet rich plasma (PRP) in treating various forms of alopecia. A total of 64 articles were found through a systematic search, and eight original articles were included in the study, based on inclusion/exclusion criteria. In most studies (62.5%) patients' conditions had improved by receiving PRP therapy; these cases experienced an increase in growth and thickness of hair. Simultaneous use of PRP and Minoxidil demonstrated the highest rate of improvement and satisfaction. The highest efficacy in patients with alopecia areata was 76% and the lowest efficacy was 31.7% and in patients with androgenetic alopecia the highest efficacy was 42.75% and the lowest reported efficacy was 25.55%. The main side effect was pain due to PRP injection, which disappeared after ending the treatment and only one article reported more serious side effects. Recurrence after treatment was also reported in only one article. PRP is a safe and easy method for treating hair loss and has limited adverse effects. Optimization of this method depends on dosage, number of sessions and their intervals, and injection techniques. According to the results, the use of PRP due to its relatively high efficiency, low and tolerable side effects, and low recurrence rate can be a good method for the treatment of alopecia and hair loss.

Systematic review of low-dose isotretinoin for treatment of acne vulgaris: Focus on indication, dosage, regimen, efficacy, safety, satisfaction, and follow up, based on clinical studies.

Oral isotretinoin is the most effective treatment for moderate to severe acne and its side effects are mostly dose-dependent. Low dose isotretinoin (0.5 mg/kg/day for 1 week every 4 weeks for 6-months) could be effective and even in its end result, comparable with high or optimal doses. In this systematic review, we aimed to sum up the results of clinical trials regarding indications, dosage, prescription protocol, effectiveness, side effects, patient satisfaction, recurrence rate, and follow-up period of low dose isotretinoin in treatment of acne. Cochrane, Google Scholar, Science Direct, PubMed, and Medline were searched. A total of 460 articles were searched electronically and 382 articles were excluded. About 4 were non-English and 2, before 1980. The full text of 72 articles was reviewed. Finally 15 documents met the inclusion criteria for entering this systematic review. The standard dose of isotretinoin is 0.5-1 mg/kg/day for 4 months with a total dose of 120-140 mg/kg/day. Daily doses between 0.1 and 0.3 mg/kg can be recommended for more than 6 months due to the occurrence of fewer side effects and more economical concerns. For greater effectiveness, it could be combined with other medications.

A systematic review of the effect of platelet-rich plasma on androgenetic alopecia of women.

Androgenetic alopecia (AGA) is the most common disease associated with hair loss in both females and males. Given the high prevalence of AGA and limited therapeutic methods and the high cost of hair transplantation and ease of use or platelet-rich plasma (PRP) therapies, this systematic review study was conducted to evaluate the effect of PRP on AGA of women. In this systematic review study, English-language articles were searched on PubMed, ISI web of knowledge, and Google Scholar by the end of 2019 with a combination of keywords. Finally, six articles were evaluated. The total number of subjects in this systematic review study was 92 people in six studies. All studies were clinical trials. Most of the studied had been conducted as a pilot study. Follow-up period for patients varied from 6 to 12 months. Except for one study, other studies have reported a positive therapeutic effect for PRP. The major limitation of the studies was the pilot nature and small sample size of these studies. According to the limited studies included in this systematic review, PRP treatment had a positive effect on the improvement of AGA, increasing hair density, and improving hair diameter in affected women.

Mycophenolate mofetil treatment of an H syndrome patient with a SLC29A3 mutation.

H syndrome is a complex multi-organ disorder with autosomal recessive inheritance. The skin manifestations include early onset hyperpigmentation and hypertrichosis, followed by skin induration often diagnosed as scleromyxedema and morphea. There is no effective treatment. Our objective was to study the efficacy of mycophenolate mofetil in a patient with genetically confirmed H syndrome. We sought the genetic cause of H syndrome with whole-exome sequencing (WES) of the proband. Genome-wide homozygosity mapping (HM) provided additional evidence for causality of the variant suggested by WES. Here, we report a patient with characteristic clinical features of H syndrome, and the diagnosis was confirmed by identification of a homozygous SLC29A3 mutation (p.Gly437Arg). The patient was initially treated with prednisolone and cyclosporine, but after development of side-effects she was placed on mycophenolate mofetil. After the treatment with mycophenolate mofetil was initiated, resolution of hyperpigmentation was noted, and no new lesions developed during an 18-month follow-up period. Thus, mycophenolate mofetil could be considered as a safe and partially effective treatment of H syndrome.

N-acetylcysteine and coronavirus disease 2019: May it work as a beneficial preventive and adjuvant therapy? A comprehensive review study.

BACKGROUND: Coronaviruses are major pathogens of respiratory system causing different disorders, including the common cold, Middle East respiratory syndrome, and severe acute respiratory syndrome. Today's global pandemic coronavirus disease 2019 (COVID-19) has high mortality rate, with an approximate of 20% in some studies, and is 30-60 times more fatal than the common annual influenza, However, there is still no gold standard treatment for it. N-acetylcysteine (NAC) is a well-known multi-potential drug with hypothetically probable acceptable effect on COVID-related consequences, which we completely focused in this comprehensive review. MATERIALS AND METHODS: PubMed, Scopus, Science Direct, and Google Scholar have been searched. Study eligibility criteria: efficacy of NAC in various subclasses of pathogenic events which may occur during COVID-19 infection. Efficacy of NAC for managing inflammatory or any symptoms similar to symptoms of COVID-19 was reviewed and symptom improvements were assessed. RESULTS: Randomized clinical trials introduced NAC as an antioxidant glutathione analog and detoxifying agent promoted for different medical conditions and pulmonary disorders to alleviate influenza and reduce mortality by 50% in influenza-infected animals. The beneficial effects of NAC on viral disorders, including Epstein-Barr virus, HIV and hepatitis, and well-known vital organ damages were also exist and reported. CONCLUSION: We classified the probable effects of NAC as oxidative-regulatory and apoptotic-regulatory roles, antiviral activities, anti-inflammatory roles, preventive and therapeutic roles in lung disorders and better oxygenation functions, supportive roles in intensive care unit admitted patients and in sepsis, positive role in other comorbidities and nonpulmonary end-organ damages or failures and even in primary COVID-associated cutaneous manifestations. Based on different beneficial effects of NAC, it could be administered as a potential adjuvant therapy for COVID-19 considering patient status, contraindications, and possible drug-related adverse events.

Comparing the effectiveness of fractional CO2 laser and the combination therapy with micro-needling and topical 10% trichloroacetic acid to remove infra-orbital dark circles in Tehran women.

BACKGROUND: Infra orbital dark circles are now recognized as being a cosmetic problem that should be considered in treatment issue. The present study aimed to assess and compare the clinical efficiency of the combination of micro-needling and 10% trichloroacetic acid (TCA) cream as well as carbon dioxide laser in the management of infra-orbital dark circles. METHODS: This randomized clinical trial was performed on women aged 28-62 years who complained of infra-orbital dark circles. The patients were randomly assigned to be treated with micro-needling combined with 10% TCA cream topically or CO2 laser. The treatment period in each group included three sessions with an interval of one month between sessions. The assessment was based on both subjective and objective methods. RESULTS: the mean of ΔE (the difference in the intensity of darkening at infra-orbital points and other points of the face) was significantly higher in the laser group than in the other group in all sessions. The patients who were treated with laser were found to have a higher level of satisfaction in the fifth visit when compared to those who received the other treatment method. CONCLUSION: Regarding clinical effectiveness and the patients' compliance, fractional CO2 laser was more preferred in the combination therapy with micro-needling and topical TCA for removing infra-orbital dark circles.

Keratins and epidermolysis bullosa simplex.

Keratin intermediate filaments play an important role in maintaining the integrity of the skin structure. Understanding the importance of this subject is possible with the investigation of keratin defects in epidermolysis bullosa simplex (EBS). Nowadays, in addition to clinical criteria, new molecular diagnostic methods, such as next generation sequencing, can help to distinguish the subgroups of EBS more precisely. Because the most important and most commonly occurring molecular defects in these patients are the defects of keratins 5 and14 (KRT5 and KRT14), comprehending the nature structure of these proteins and their involved processes can be very effective in understanding the pathophysiology of this disease and providing new and effective therapeutic platforms to treat it. Here, we summarized the various aspects of the presence of KRT5 and KRT14 in the epidermis, their relation to the incidence and severity of EBS phenotypes, and the processes with which these proteins can affect them.