A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak. OBJECTIVES: The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA). METHODS: A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted. RESULTS: A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI. CONCLUSION: This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.

Assessing the 5-year persistence in positive clinical response with innovative psoriasis treatments: a network meta-analysis of pasi score.

BACKGROUND: Psoriasis is a chronic skin condition, for which the approval of several biologics has made a dramatic impact. Despite their initial treatment effectiveness, the challenge lies in understanding the long-term responses, as they may diminish over time. Limitations of the drug survival analysis warrant the application of additional outcomes to fully capture the performance of a biologic. We aimed to provide a broader perspective on the global landscape of biologic agents' persistence in positive clinical response by comparing innovative therapies over a 5-year period through a systematic review and network meta-analysis (NMA). METHODS: We comprehensively identified studies in Pubmed, EMBASE, Scopus and clinicaltrial.gov. We defined two outcomes: 1) "persistence at optimal response" (POR) or "clinical remission", and 2) "persistence at suboptimal response" (PSR) or "low disease activity" as the proportion of patients with continuous exposition to a biologic who achieved a PASI 100 or PASI 90 responses, respectively, at the end of the predefined 5-year follow-up period. RESULTS: Eleven publications, comprising 18 RCTs and 11,202 patients met inclusion criteria and were included in the NMA. In the ranking analysis, guselkumab exhibited the highest cumulative (0.8397250), followed by ixekizumab (0.8185545), and risankizumab (0.7643864). Conversely, etanercept (0.4152295), brodalumab (0.3633977), apremilast (0.2452136), and placebo (0.0263) showed the lowest cumulative probability of POR. For PSR, guselkumab (0.86083636), ixekizumab (0.74931136), and risankizumab (0.71293182) also held the top ranks, while brodalumab (0.41740227), secukinumab (0.231575), etanercept (0.192775), and placebo (0.01934545) presented the lowest PSR probabilities. CONCLUSION: The highest rates of persistence with clear or almost clear skin can be expected with guselkumab, ixekizumab and risankizumab compared to other biologics. The proposed proxy definitions of long-term persistence (POR and PSR) are reliable measures of patients being successfully treated that warrant further exploration and validation.

Comparative efficacy of oral Janus kinase inhibitors and biologics in adult alopecia areata: A systematic review and Bayesian network meta-analysis.

Alopecia areata (AA) is an autoimmune disorder that affects the hair follicles, resulting in patchy recurrent hair loss. A large body of evidence has demonstrated the favourable clinical response of the Janus kinase (JAK) inhibitors and biologics, but a lack of comprehensive comparison among these therapies exists in the current literature. This study aimed to compare their efficacy. A systematic review and meta-analysis were performed including randomized trials that report the outcomes of the Severity of Alopecia Tool (SALT)50 and/or the mean change in SALT. These articles were pooled and a network meta-analysis (NAM) was conducted. Based on the surface under the cumulative ranking curve estimates obtained for the mean change in SALT score, baricitinib_4 mg (0.7949656) had the best probability of being the most effective therapy, followed by ritlecitinib_200_50 mg (0.7391906) and ivarmacitinib_4 mg (0.7292594). In contrast, dupilumab, secukinumab, tralokinumab and apremilast were less likely to be effective. Targeting the JAK signalling pathway holds great potential for restoring hair regrowth, albeit the contribution of JAK1, JAK2, JAK3 and TYK2 inhibition to the therapeutic effect on AA is apparently different. Baricitinib_4 mg and ritlecitinib 200_50 mg demonstrated notable efficacy, and both molecules displayed a dose-dependent effect, which is not observed with ivarmacitinib. Further investigations into the specific mechanisms of action of these JAK inhibitors are warranted to elucidate the reasons behind these differences.

Effects of probiotic supplementation in adult with atopic dermatitis: a systematic review with meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The effect of probiotic administration on the severity of AD in adults has shown inconsistent results. OBJECTIVES: To determine the effectiveness of probiotic supplementation as a therapeutic tool for adult AD. METHODS: PubMed, Scopus and Embase were systematically searched to collect data from studies in which probiotics were administered to treat adult AD. RESULTS: Out of 413 publications, 9 papers were included in the meta-analysis. Significant differences in the ScORing Atopic Dermatitis tool favouring probiotics were observed [relative risk (RR) -5.93, 95% confidence interval (CI) -8.43 to -3.43]. Lactobacillus salivarius presented with largest effect size (RR -9.79, 95% CI -13.04 to -6.54), followed by L. acidophilus (RR -5.77, 95% CI -10.82 to -0.72) and L. plantarum (RR -3.76, 95% CI -6.36 to -1.16). No benefit was observed with L. fermentum. Based on the severity of AD, probiotics showed better results in people with moderate-to-severe AD (RR -9.12, 95% CI -12.17 to -6.08) than in individuals with mild disease (RR -2.67, 95% CI -4.67 to -0.66). Serum levels of IgE and eosinophil count remained significantly unchanged after the probiotic intervention (RR 0.25, 95% CI -0.10 to 0.60; RR -0.27, 95% CI -0.68 to 0.13, respectively). CONCLUSIONS: Current evidence supports a role for some probiotics as a therapeutic tool for the treatment of adult AD, particularly in patients with severe AD. The efficacy of probiotics is strain specific, with L. salivarius and L. acidophilus having the largest clinical benefit. Such benefit is apparently independent of IgE levels and eosinophil count. Despite these encouraging results, the decrease in AD severity did not translate into a clinically meaningful better quality of life as assessed by the Dermatology Life Quality Index. There currently is not enough reliable data to reach conclusions about the optimal dose and duration for probiotic treatment.

Bayesian network meta-analysis of head-to-head trials for complete resolution of nail psoriasis.

BACKGROUND: Almost 50% of patients with skin psoriasis have concomitant nail involvement. The comparative effectiveness of the available biologics for nail psoriasis (NP) is still an area of contention because of limited data on nails. OBJECTIVES: We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics in achieving complete resolution of NP. METHODS: We identified studies in PubMed, EMBASE and Scopus. The eligibility criteria included randomized controlled trial (RCTs) or cohort studies for psoriasis or psoriatic arthritis with at least two arms of active comparator of biologic reporting at least one efficacy outcome of interest: that is the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI or the Physician's Global Assessment of Fingernail Psoriasis with a score of 0. RESULTS: Fourteen studies comprising seven treatments met the inclusion criteria, and were included in the NMA. The NMA showed the odds of complete NP resolution were superior with ixekizumab [risk ratio (RR) 1.4, 95% confidence interval (CI) 0.73-3.10] compared with the treatment of reference (adalimumab). Brodalumab (RR 0.92, 95% CI 0.14-7.40), guselkumab (RR 0.81, 95% CI 0.40-1.80), infliximab (RR 0.90, 95% CI 0.19-4.60) and ustekinumab (RR 0.33, 95% CI 0.08-1.60) demonstrated worse therapeutic effect compared with adalimumab. According to the surface under the cumulative ranking curve, ixekizumab 80 mg every 4 weeks had the highest probability of being the best treatment. CONCLUSIONS: The interleukin-17A inhibitor ixekizumab has the highest rate of complete nail clearance and it can be considered the best-ranked therapy from the present evidence. This study is relevant to daily practice as it facilitates the decision when choosing between the wide variety of available biologics in patients for whom clearance of nail symptoms is the first concern.

Meta-analysis on preventive and therapeutic effects of probiotic supplementation in infant atopic dermatitis.

Despite a large body of research, the effect of probiotic administration on the incidence and severity of atopic dermatitis (AD) shows conflicting results. We aimed to investigate whether probiotic supplementation reduces the incidence and severity of AD. Three databases were systematically searched. A 22% lower incidence of AD was found in the probiotic group. The reduction in incidence was 49% when probiotics were given to pregnant and lactating mothers, and 27% when they were given to pregnant mothers and infants. A 39% reduction of AD incidence was achieved when administered to pregnant-breastfeeding mothers and infants. Significant differences in SCORAD (SCORing Atopic Dermatitis) favoring probiotics were observed, but the IDLQI remained unchanged. Lactobacillus (L.) rhamnosus was the most documented strain, but it turned out to be ineffective in reducing SCORAD. Conversely, L. paracasei and L. sakei showed a significant decrease in SCORAD. Probiotics are effective in the prevention of AD, but the effect is less conclusive for the treatment of AD, especially in infants <1 year. The intake of probiotics by breastfeeding mothers is an important measure and may become a novel preventive strategy. The preventive effect of probiotics against AD is not associated with family background or AD risk. L. paracasei and L. sakei show the greatest reduction in SCORAD.

Real-world experience and long-term evaluation of tofacitinib in refractory alopecia areata: A prospective, open-label, single-center study in Asian Arab population.

Tofacitinib is a pan-janus kinase inhibitor (JAK) which has been tested off-label in alopecia areata (AA) with promising results. However, evidence of tofacitinib in real-life setting is still poor. We evaluated long-term efficacy and safety of tofacitinib for refractory AA. This is a prospective, open-label, observational, single-center cohort study conducted between January 2018 and December 2020. Primary end-point was the percent change in Severity of Alopecia Tool (SALT) at the basal visit and at the most recent follow-up visit. Three categories of treatment response were analyzed. Data on 47 participants of Arab-Asian heritage were analyzed. A complete and partial regrowth was observed in 18 patients (41.86%) and 11 patients (25.58%), respectively. In 12 patients (27.9%), no response was obtained. Most of the non-responders belonged to the alopecia universalis group (66.67%). No statistical differences were observed in rates of regrowth between pediatric and adult individuals (p = 0.52), nor between women and men. Significant differences in the average duration of tofacitinib treatment were obtained among the three categories of regrowth (p < 0.003), notably duration of AA did not impact the clinical regrowth (p = 0.62). To the best of our knowledge, this is the first prospective, observational, long-term study using tofacitinib in refractory AA. Rates of regrowth and side effects are analogous to previous works. Length of tofacinitib therapy should last for 12 months before considering any discontinuation or change, since early cessation can lead to treatment failures or incomplete regrowth. Maintenance therapy after complete regrowth has demonstrated to be safe and effective to prevent recurrences of hair loss.

Laser and light-based therapies in the management of rosacea: an updated systematic review.

Unlike other rosacea therapies which need daily takings or applications over long periods, the edge of lasers and light-based therapies (LLBT) is the limited number of sessions to achieve improvement. The proper selection of the adequate physical device in accordance with the patients' skin features and rosacea-related signs and symptoms should be considered and the management with physical sources should be updated as new data become available. This article reviews and discusses the current use of lasers and light-based therapies in rosacea with reference to all the available literature.This systematic review demonstrates the quality of evidence to support any recommendation on LLBT in rosacea is low-to-moderate. Among all the available devices, PDL holds the most robust evidence. Treatments options should be tailored for each specific clinical scenario as it is unlike that single modality results in complete resolution. Platforms that include two or more devices and combined therapies with topical agents are suitable and they warrant further investigations.

Comparative appraisal with meta-analysis of erbium vs. CO2 lasers for atrophic acne scars.

Recent advances in laser technology allowed the development of systems that improve texture, appearance and pliability of skin in acne scars (AS). Currently, comprehensive comparative studies on the efficacy of the most commonly used fractional systems in AS are lacking. Thus, the aim of this work was to appraise and compare the clinical response to erbium versus CO2 lasers in AS in the form of a meta-analysis. The databases MEDLINE, EMBASE, Cochrane library were searched. Main clinical outcomes were investigator-reported scar improvement and participant-reported scar improvement. Five studies were included in this meta-analysis. Scar improvement was similar for both types of laser in terms of investigator-reported scar improvement (RR: 0.60 95 % CI: 0.35-1.02) and participant-reported scar improvement (RR: 0.99 95 % CI: 0.79-1.25). A sensitivity analysis that excluded studies with high risk of bias found the CO2 lasers to be superior to the erbium lasers (RR: 0.47 95 % CI: 0.24-0.93): However, the subgroup analysis showed the CO2 laser not to be significantly different from either the non-ablative erbium (RR: 0.65 95 % CI: 0.34-1.24) or the ablative erbium laser (RR: 0.60 95 % CI: 0.35-1.02). The CO2 laser produced a slightly greater clinical response compared to the erbium lasers based on the physician's assessment. Overall, the two devices do not differ largely in terms of efficacy but may be complementary, with each resurfacing laser better suited for different clinical tasks.

Evaluation of the efficacy of subantimicrobial dose doxycycline in rosacea: a systematic review of clinical trials and meta-analysis.

BACKGROUND: Low-dose doxycycline (SDD) is an antimicrobial agent that appears to improve common inflammatory skin diseases. Few data are available regarding the overall effectiveness, appropriate length of treatment and optimal patient selection for rosacea. We therefore reviewed the efficacy of sub-antimicrobial doses of SDD in papulopustular rosacea (PPR) and aimed to determine the most suitable patients for this approach. METHODS: From July to September 2019, we carried out a comprehensive search of literature from five databases, using a combination of "rosacea" AND "doxycycline". RESULTS: Our search yielded 532 potentially relevant studies. Our meta-analysis showed no significant difference between SDD and a comparator (RR: 1.12, 95 % CI: 0.78-1.62, I2 =  86 %). Subgroup analysis of studies comparing doxycycline with placebo yielded a clear difference in favor of doxycycline (RR: 1.45, 95 % CI: 1.22-1.72, I2 =  31 %), while subgroup analysis of studies comparing active drugs revealed no difference between interventions (RR: 0.52, 95 % CI: 0.17-1.63, I2 =  90 %). CONCLUSIONS: There is strong evidence that SDD is more effective than placebo. However, other drugs such as minocycline or isotretinoin have shown outcomes at least similar to that of SDD. We suggest that the anti-inflammatory properties of SDD may be of more value for mild cases of rosacea than for moderate to severe cases, for which higher (antimicrobial) doses of doxycycline may be a more suitable choice.

Efficacy of topical ivermectin and impact on quality of life in patients with papulopustular rosacea: A systematic review and meta-analysis.

Rosacea is a chronic dermatosis which affects negatively patients' quality of life (QoL). There is shortage of high-quality evidence comparing the efficacy of ivermectin cream (IVM) 1% with other available topical choices. Besides, the well-documented impaired of self-esteem and stigmatization of rosacea patients make essential to address which treatment provides the greatest psychological and social benefit. Our objective is to critically review and appraise the efficacy of IVM 1% in PPR and the impact in patients' QoL against other options. We carried out a literature search from PubMed, MEDLINE, EMBASE, Cochrane, and clinicaltrials.gov using the following descriptors: "rosacea" AND "ivermectin." Efficacy was assessed with the Investigator Global Assessment (IGA), and the impact on QoL was based on the DLQI score. Six studies from four published articles were included. The meta-analysis estimated that more participants achieved "success" (IGA ≤ 1) and "complete clearance" (IGA = 0) with IVM1%. The overall effect estimate for IGA ≤ 1 was: 1.56 [1.23-1.97], whereas for IGA = 0, it was: 1.72 [1.40-2.11]. The rate of participants achieving lower DLQI score, and thus, better QoL was with IVM 1%. The overall effect estimate was: 1.71 [1.34-2.18] at week 16# and 1.64 [1.38-1.94] at week 52#. This meta-analysis confirms IVM 1% cream as the most effective topical treatment and it satisfies the impairment of social life with sustained better QoL. Further studies extending this period of remission are warranted, as well as researches about the potential application of this agent combined with other agents. KEY POINTS: Question: What is the current efficacy of ivermectin versus other choices in papulopustular rosacea and its impact on patients' quality of life? Findings: In this meta-analysis, ivermectin showed higher efficacy than metronidazol, azelaic acid, and placebo measured by Investigator Global Assessment. Parallely, the DLQI score highlighted that this agent was more beneficious in both short and long-term. Meaning: This meta-analysis gives strong evidence that ivermectin is the most effective topical treatment. Besides, this agent provides the greatest psychological benefit as it satisfies the stigmatization of rosacea patients as well as the impairment of social and working life with a sustained better QoL above other alternatives.

Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy from neuroendocrine cells in the skin. Despite being one of the most life-threatening of skin cancers, little is known about the potential signaling mechanism that drives carcinogenesis in MCC. The purpose of this study is to assess the impact of Merkel cell polyomavirus (MCPyV), p53, and c-kit on the histological features and clinical prognosis of MCC treated in our regional hospitals. METHOD: The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software. RESULTS: Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001). CONCLUSION: We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.

Molluscum Contagiosum Infection Involving a Benign Epidermoid Cyst in an Immunocompetent Patient.

A 78-year-old man presented with a round- to oval-shaped nodule on his right eyebrow. The lesion first developed 5 years ago as a small solitary white nodule and subsequently enlarged over the past 2 years. His medical history was unremarkable. Clinical examination revealed a 2-cm round to oval dome-shaped yellowish nodule with a dimple on the top center (Figure 1). No similar lesions were found elsewhere. With a clinical suspicion of sebaceous carcinoma, an excision of the lesion was performed under local anesthesia. The histopathologic analysis showed an epidermal cyst containing molluscum bodies along the keratin inside the cyst (Figure 2). With these findings, the diagnosis of molluscum contagiosum (MC) infection into an epidermoid cyst was made. Neither recurrence nor new similar lesions were observed at follow-up.

Management of acne vulgaris with hormonal therapies in adult female patients.

Acne vulgaris is a very common condition affecting up of 93% of adolescents. Although rare, this disease may persist in adulthood. In adult women with acne (those older than 25 years old), this condition is particularly relevant because of the refractory to conventional therapies, which makes acne a challenge for dermatologists in this group of patients. In order to its potential risk for chronicity and the involvement of visible anatomical sites such as face and upper torso, acne has been associated with a wide spectrum of psychological and social dysfunction such as depression, anxiety, suicidal ideation, somatization, and social inhibition. In particular, adult women with acne have been shown to be adversely impacted by the effect of acne on their quality of life. For the last four decades, dermatologists have used hormonal therapies for the management of acne vulgaris in adult women, which are considered a rational choice given the severity and chronicity of this condition in this group of patients. The aim of this work is to review the hormonal drugs for management of acne.

Safety and effectiveness of ustekinumab for treatment of moderate to severe psoriasis: a prospective study in a clinical setting.

BACKGROUND: There are few studies analyzing the behavior of ustekinumab in the complex management of psoriasis within diary clinical practice setting. OBJECTIVE: To assess the utility of ustekinumab in a psoriasis unit. METHODS: Analysis of the prospective data gathered during the follow-up of 30 consecutive psoriasis patients treated with ustekinumab at a single referral centre. Three effectiveness endpoints were defined 12 weeks, 28 and "long-term treatment". The main outcome measure was improvement from baseline PASI at week 28 and at a point of adjustment of prolonged treatment signed as "long-term treatment". RESULTS: Overall 82.1% and 42.8% patients achieved respectively PASI75 and PASI90 response rates at week 28. Long-term treatment maintained efficacy outcomes 81.5% and 40.7% PASI75 and PASI90, respectively were observed. At week 28, patients naïve to TNFα- blockers agents and patients with a baseline PASI >10 had better PASI75 and PASI90 response rates than previously treated patients. CONCLUSIONS: In clinical practice, the efficacy and patient adherence to ustekinumab are excellent and even better to the data obtained in clinical trials. Clinical indicators of psoriasis severity: previous treatments with tumor necrosis factor α blockers agents and active treatment beside small increases in PASI determine a delayed maximal response.

Comparative efficacy and therapeutic positioning of biologics in hidradenitis suppurativa: A systematic review with network meta-analysis of randomised trials.

Background Hidradenitis suppurativa (HS) is a challenging inflammatory skin condition. Recently, many different biologics have been tested for HS, but the paucity of head-to-head comparative trials makes it difficult to determine the real value of each biological intervention. We aimed to determine the relative efficacy among biologics in treating moderate-to-severe HS throughout a network meta-analysis (NMA) and, to identify which pathogenetic pathways may be the most appropriate to target. Methods We comprehensively identified studies in 3 databases and clinicaltrials.gov. The eligibility criteria included randomised controlled trials (RCTs) reporting data on the efficacy of moderate-to-severe HS. Results The NMA comprised 13 studies comprising 14 interventions on 2,748 participants in the network. The NMA showed the odds of achieving the clinical response were significantly superior with adalimumab (RR: 0.37, 95% CI = 0.06-0.63), adalimumab QW (RR: 0.63, 95% CI = 0.43-0.87), MAB1p (RR: 1.33, 95% CI = 0.03-3.12), secukinumab (RR: 0.25, 95% CI = 0.11-0.47) and secukinumabQ2W (RR: 0.24, 95% CI = 0.1-0.46) compared to placebo. Conclusion Based on the NMA, inhibiting tumour necrosis factor (TNF)-a with adalimumab appears to be the best strategy, followed by the blockade of IL--17 with secukinumab. Data for bimekizumab and CJM112 are promising. Infliximab has inconsistent clinical response, and more data are necessary to confirm this molecule as a potential third-line therapy in HS. The blockade of IL-23 and CD5a pathways is not relevant, or at least the current evidence is insufficient to recommend further investigation of guselkumab, risankizumab, and vilobelimab in phase III trials.