5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Comprehensive Review of the Literature

Hypertrophic (HTSs) and keloid scars are common dermatological complaints produced by disruption of the normal wound-healing process. Despite a wide array of therapeutic options available to treat these lesions, HTSs and keloids continue to pose a significant challenge to clinicians in everyday practice. The chemotherapeutic drug 5-fluorouracil (5-FU) is a well-known treatment option reserved for recalcitrant HTSs and keloid lesions. We present clinicians with a comprehensive review of the published data concerning the use of 5-FU in the treatment of HTSs and keloids. The current evidence suggests that 5-FU is a safe and practical alternative for the treatment of HTSs and keloids as it may substantially improve the appearance of proliferative scars and reduce the chance of recurrence. This therapeutic option is most effective in conjunction with adjuvant therapy such as corticosteroids. Additional randomized controlled clinical trials with large sample sizes should be conducted to corroborate the existing efficacy and safety data in patients with HTSs and keloids. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13555-016-0118-5) contains supplementary material, which is available to authorized users

Evaluation of the efficacy and treatment-emergent adverse events of deuruxolitinib for moderate to severe alopecia areata: a dose-ranging meta-analysis of 1,372 randomized patients

IntroductionAlopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the increasing use of Janus kinase (JAK) inhibitors in immune-related conditions, their potential role in AA treatment is gaining attention. Deuruxolitinib has emerged as a potential treatment for moderate to severe AA. This is the first systematic review and meta-analysis that aims to assess the efficacy of deuruxolitinib in moderate to severe AA.MethodsWe systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and ClinicalTrials.gov for relevant data. Deuruxolitinib vs. placebo was evaluated, and efficacy was measured using severity of alopecia tool (SALT) and Hair Satisfaction Participants Reported Outcome (SPRO), with the primary time point of assessment at week 24. Treatment-emergent adverse events (TEAEs) such as increased creatinine kinase (CPK), acne, and headache were specifically assessed at week 28. Effect sizes were presented using mean difference (MD) or risk ratio (RR). Statistical heterogeneity was measured by I2, with a 95% confidence interval (CI) and p-value less than 0.05 considered significant. Risk of bias was assessed using the Revised Cochrane risk of bias tool. Subgroup analysis was conducted for different regimens (8 mg and 12 mg) and TEAEs of interest. This research was registered in PROSPERO (CRD42023417104).ResultsThree randomized controlled trials involving 1,372 patients were included. Deuruxolitinib demonstrated a significant improvement in SALT score change from baseline [MD = −47.26, 95% CI = (−53.47, −41.05), p < 0.00001, I2 = 76%], with a significant number of patients achieving 75% [RR = 93.66, 95% CI = (23.42, 374.65), p < 0.00001, I2 = 0%] and 90% [RR = 65.26, 95% CI = (16.28, 261.58), p < 0.00001, I2 = 0%] improvement from baseline. Patients randomized to deuruxolitinib reported a significant improvement in SPRO [MD = −1.52, 95% CI = (−1.76, −1.27), p < 0.00001, I2 = 69%], with many experiencing more than two points of improvement [RR = 4.98, 95% CI = (3.79, 6.54), p < 0.00001, I2 = 0%]. TEAEs included elevated CPK levels [RR = 2.79, 95% CI = (1.5, 4.99), p = 0.0006, I2 = 0%], headaches [RR = 1.49, 95% CI = (0.98, 6.54), p = 0.06, I2 = 44%], and acne (significant in the 12 mg dose only) [RR = 1.80, 95% CI = (0.84, 3.88), p = 0.13, I2 = 64%].DiscussionIn conclusion, deuruxolitinib shows promising efficacy in treating moderate to severe AA, leading to significant improvements in hair regrowth and patient-reported satisfaction. While certain TEAEs such as increased CPK levels, headaches, and acne (especially at the 12 mg dose), they were generally manageable. Further research and vigilant monitoring for long term safety are necessary before widespread adoption of deuruxolitinib for AA treatment

The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis

BackgroundAtopic dermatitis (AD) is a chronically relapsing disease. Few biologics are approved for moderate-to-severe AD, and novel interventions are emerging. We aimed to evaluate the safety and efficacy of lebrikizumab, an IL-13 immunomodulator, as monotherapy vs. placebo in treating moderate-to-severe AD.MethodsCochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and ClinicalTrials.gov registry (CT.gov) databases were systematically searched. We evaluated lebrikizumab vs. placebo and measured efficacy using Eczema Area and Severity Index (EASI), Body Surface Area (BSA), and Investigator’s Global Assessment (IGA) change from baseline to week 16. Safety was evaluated by the incidence of serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality. The risk of bias was investigated using the Revised Cochrane risk of bias tool.ResultsThree RCTs (n = 1,149) included 543 (47.25%) men vs. 606 (52.75%) women. Meta-analysis showed statistically significant improvement in EASI, IGA, and BSA. EASI75 at week 16 for all regimens was (RR = 2.62, 95% CI [2.06, 3.34], p < 0.00001) with the first regimen (500 mg loading dose then 200 mg every 2 weeks) showing the most significant improvement (RR = 3.02, 95% CI [2.39, 3.82], p < 0.00001). The pooled analysis of safety outcomes concluded that lebrikizumab did not correlate significantly with the incidence of SAEs, NSAEs, and mortality.ConclusionOverall, lebrikizumab showed a significant improvement in all efficacy outcomes. Additionally, it did not contribute to any significant incidence of SAEs, NSAEs, or mortality. The risk of bias in included RCTs was minor except in the randomization domain. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of the outcomes ranged from low to high, but predominantly high certainty of evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022362438

The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis

BackgroundAtopic dermatitis (AD) is a chronically relapsing disease. Few biologics are approved for moderate-to-severe AD, and novel interventions are emerging. We aimed to evaluate the safety and efficacy of lebrikizumab, an IL-13 immunomodulator, as monotherapy vs. placebo in treating moderate-to-severe AD.MethodsCochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and ClinicalTrials.gov registry (CT.gov) databases were systematically searched. We evaluated lebrikizumab vs. placebo and measured efficacy using Eczema Area and Severity Index (EASI), Body Surface Area (BSA), and Investigator’s Global Assessment (IGA) change from baseline to week 16. Safety was evaluated by the incidence of serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality. The risk of bias was investigated using the Revised Cochrane risk of bias tool.ResultsThree RCTs (n = 1,149) included 543 (47.25%) men vs. 606 (52.75%) women. Meta-analysis showed statistically significant improvement in EASI, IGA, and BSA. EASI75 at week 16 for all regimens was (RR = 2.62, 95% CI [2.06, 3.34], p &amp;lt; 0.00001) with the first regimen (500 mg loading dose then 200 mg every 2 weeks) showing the most significant improvement (RR = 3.02, 95% CI [2.39, 3.82], p &amp;lt; 0.00001). The pooled analysis of safety outcomes concluded that lebrikizumab did not correlate significantly with the incidence of SAEs, NSAEs, and mortality.ConclusionOverall, lebrikizumab showed a significant improvement in all efficacy outcomes. Additionally, it did not contribute to any significant incidence of SAEs, NSAEs, or mortality. The risk of bias in included RCTs was minor except in the randomization domain. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of the outcomes ranged from low to high, but predominantly high certainty of evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022362438.</jats:sec

Hyperhidrosis and Stress

Hyperhidrosis is a psychological skin condition characterized by uncontrollable, excessive amounts of sweat in specific body locations. Although not a physically debilitating condition, those individuals affected with this condition commonly experience psychosocial stress during regular social encounters and exhibit low self-confidence, thus drastically decreasing the quality of life of these individuals (Coutinho dos Santos et al. Pediatr Dermatol 26(4):439–444, 2009; Glogau, Dermatol Surg 24(8):817–819, 1998; Kouris et al. Pediatr Dermatol 32(2):226–230, 2015). Hyperhidrosis is often diagnosed in patients suffering from psychosocial disorders such as social anxiety, suggesting a psychological factor may influence it’s onset. Various management options exist for the treatment of hyperhidrosis including fractionated microneedle radio (FMR) treatment, botulinum toxin type A (BTXA), surgery, oral administration of the anticholinergic drug glycopyrronium bromide (glycopyrrolate), aluminum chloride antiperspirants, iontophoresis, and endoscopic thoracic sympathectomy (Glogau, Dermatol Surg 24(8):817–819, 1998; Kouris et al. Pediatr Dermatol 32(2):226–230, 2015; Bajaj and Langtry, Br J Dermatol 157(1):118–121, 2007; Fatemi Naeini et al. Australas J Dermatol 56(4):279–284, 2015; Kobayashi et al. J Dermatol 21(8):575–581, 1994; Rompel and Scholz, J Eur Acad Dermatol Venereol 15(3):207–211, 2001). Currently, endoscopic thoracic sympathectomy is the only current, permanent treatment option. However, new therapeutic options on the horizon such as lasers and microwave thermolysis demonstrate promising results