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The Cochrane Database of Systematic... Oct 2023Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy.
OBJECTIVES
To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults.
SEARCH METHODS
The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA.
DATA COLLECTION AND ANALYSIS
We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings.
MAIN RESULTS
We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up.
AUTHORS' CONCLUSIONS
We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Alopecia Areata; Minoxidil; Network Meta-Analysis; Immunosuppressive Agents; Prednisolone; Betamethasone; Cyclosporins; Biological Products
PubMed: 37870096
DOI: 10.1002/14651858.CD013719.pub2 -
Toxicology and Applied Pharmacology Nov 2023Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The...
Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.
Topics: Adult; Male; Humans; Animals; Mice; Minoxidil; Finasteride; Alopecia; Administration, Oral; Prostatic Hyperplasia; Treatment Outcome
PubMed: 37805090
DOI: 10.1016/j.taap.2023.116710 -
International Journal of Dermatology Aug 2020Topical minoxidil has been used for almost 40 years to treat alopecia. There is growing evidence supporting off-label use of low-dose oral minoxidil.
BACKGROUND
Topical minoxidil has been used for almost 40 years to treat alopecia. There is growing evidence supporting off-label use of low-dose oral minoxidil.
OBJECTIVE
To conduct a systematic review evaluating the use of oral minoxidil for all types of alopecia.
METHODS
A primary literature search was conducted using PubMed in May 2019, utilizing the search term "oral minoxidil AND (hair loss OR alopecia OR baldness)". Reviews, non-English studies, and articles concerning only topical minoxidil were excluded.
RESULTS
Ten articles were included for review comprising a total 19,218 patients (215 women and 19,003 men). Oral minoxidil dose ranged from 0.25 to 5 mg daily to twice daily. The strongest evidence existed for androgenetic alopecia and alopecia areata (AA), with 61-100% and 18-82.4% of patients demonstrating objective clinical improvement. Successful treatment of female pattern hair loss, chronic telogen effluvium, monilethrix, and permanent chemotherapy-induced alopecia was also reported. The most common adverse effects with oral minoxidil included hypertrichosis and postural hypotension.
CONCLUSION
Oral minoxidil is a safe and successful treatment of androgenic alopecia and AA. In addition to its therapeutic benefits, practical advantages over topical minoxidil stem from improved patient compliance.
Topics: Administration, Topical; Alopecia; Alopecia Areata; Female; Humans; Hypertrichosis; Male; Minoxidil; Treatment Outcome
PubMed: 32516434
DOI: 10.1111/ijd.14933 -
Journal of the European Academy of... Apr 2023Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer... (Review)
Review
Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side-effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase-4 (PDE-4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE-4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long-term studies could shed light on the utility of the newer agents in altering the progression of AA.
Topics: Adult; Humans; Alopecia Areata; Janus Kinase Inhibitors; Phosphodiesterase 4 Inhibitors; Cyclic Nucleotide Phosphodiesterases, Type 4; Biological Products; Alopecia; Protein Kinase Inhibitors
PubMed: 36478475
DOI: 10.1111/jdv.18810 -
Aesthetic Plastic Surgery Jun 2020The combination of finasteride and topical minoxidil has been used for treating patients with androgenetic alopecia (AGA). However, whether combining these two... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The combination of finasteride and topical minoxidil has been used for treating patients with androgenetic alopecia (AGA). However, whether combining these two medications results in greater efficacy than monotherapy is a question worth exploring.
OBJECTIVE
This meta-analysis aims to determine the efficacy and safety of combined treatment of finasteride and topical minoxidil.
METHODS
A comprehensive search of the Embase, PubMed, and the Cochrane Library databases was performed. Data were extracted and analyzed according to predefined clinical endpoints.
RESULTS
Five randomized controlled trials (RCTs) were included in our meta-analysis. All studies compared combined therapy with minoxidil, but only 2 RCTs compared combined therapy with finasteride. Compared with minoxidil or finasteride alone, the combined group had a significantly higher global photographic evaluation score (P < 0.00001), more patients with marked improvement (P < 0.001), and fewer patients with deterioration or no change (P < 0.001). There was no significant difference between the combined group and minoxidil- or finasteride-only groups in the number of patients with moderate and mild improvements, hair density change, or adverse events.
CONCLUSIONS
In patients with AGA, the combination treatment of finasteride and topical minoxidil has better therapeutic efficacy than and similar safety as monotherapy. However, the best concentration of combination treatment requires further studies with sound methodological quality.
LEVEL OF EVIDENCE III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Topics: Alopecia; Finasteride; Hair; Humans; Minoxidil; Photography; Treatment Outcome
PubMed: 32166351
DOI: 10.1007/s00266-020-01621-5 -
Frontiers in Immunology 2023Alopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the widespread application of JAK inhibitors in immune-related diseases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the widespread application of JAK inhibitors in immune-related diseases, attention is being given to their role in the treatment of AA. However, it is unclear which JAK inhibitors have a satisfactory or positive effect on AA. This network meta-analysis aimed to compare the efficacy and safety of different JAK inhibitors in the treatment of AA.
METHODS
The network meta-analysis was performed according to the PRISMA guidelines. We included randomized controlled trials as well as a small number of cohort studies. The differences in efficacy and safety between the treatment and control groups were compared.
RESULTS
Five randomized controlled trials, two retrospective studies, and two prospective studies involving 1689 patients were included in this network meta-analysis. In terms of efficacy, oral baricitinib and ruxolitinib significantly improved the response rate of patients compared to placebo [MD = 8.44, 95% CI (3.63, 19.63)] and [MD = 6.94, 95% CI, (1.72, 28.05)],respectively. Oral baricitinib treatment significantly improved the response rate compared to non-oral JAK inhibitor treatment [MD=7.56, 95% CI (1.32,43.36)]. Oral baricitinib, tofacitinib, and ruxolitinib treatments significantly improved the complete response rate compared to placebo [MD = 12.21, 95% CI (3.41, 43.79)], [MD = 10.16, 95% CI (1.02, 101.54)], and [MD = 9.79, 95% CI, (1.29, 74.27)], respectively. In terms of safety, oral baricitinib, tofacitinib, and ruxolitinib treatments significantly reduced treatment-emergent adverse event rates compared with conventional steroid treatment [MD = 0.08, 95% CI (0.02, 0.42)], [MD = 0.14, 95% CI (0.04, 0.55)], and [MD = 0.35, 95% CI, (0.14, 0.88)], respectively.
CONCLUSION
Oral baricitinib and ruxolitinib are excellent options for the treatment of AA owing to their good efficacy and safety profiles. In contrast, non-oral JAK inhibitors do not appear to have satisfactory efficacy in treating AA. However, further studies are required to verify the optimal dose of JAK inhibitors for AA therapy.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Network Meta-Analysis; Prospective Studies; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 37138884
DOI: 10.3389/fimmu.2023.1152513 -
American Journal of Therapeutics Feb 2021Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic...
BACKGROUND
Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic transaminases, dizziness, neutropenia, and alopecia.
AREAS OF UNCERTAINTY
The main question of the systematic review is if albendazole administration can cause liver injury or liver failure.
DATA SOURCES
Two researchers conducted the search on PubMed and the key words used were: "albendazole," "anthelmintic," "drug-induced liver injury," and "acute hepatitis." Two new case reports were included in the systematic review.
RESULTS
Literature search concluded in 10 cases listed on PubMed. Another 2 new case reports from our experience are included in the systematic review. Most common symptoms presented are jaundice, anorexia, and vomiting after the single-use of albendazole or long-term usage. All cases presented high levels of transaminases, with remission after stopping the administration of albendazole. The treatment with albendazole was mostly given for liver hydatid cysts or empirically.
CONCLUSIONS
Albendazole is a prescription-based drug used by most patients without medical advice, without knowing the risk of side effects. The anthelmintic drug may induce liver injury, even in small doses; in result, practitioners and patients should take this information in consideration.
Topics: Albendazole; Anthelmintics; Chemical and Drug Induced Liver Injury, Chronic; Echinococcosis, Hepatic; Humans
PubMed: 33590990
DOI: 10.1097/MJT.0000000000001341 -
Archives of Dermatological Research Aug 2021While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable...
While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable and versatile therapy for a wide variety of dermatologic conditions yet to be explored. This systematic review comprehensively recounts the success of oral isotretinoin in non-acne cutaneous diseases and provide insight into future directions of isotretinoin utility. A systematic literature review was performed using PubMed. Search terms included "isotretinoin" OR "accutane" AND "skin" OR "dermatology" OR "hair" OR "nails" OR "rosacea" OR "psoriasis" OR "pityriasis rubra pilaris" OR "condyloma acuminata" OR "granuloma annulare" OR "darier's disease" OR "non-melanoma skin cancer" OR "frontal fibrosing alopecia" OR "cutaneous lupus erythematosus" OR "hidradenitis suppurativa" OR "photodamaged skin" OR "skin aging" OR "wart" OR "flat warts" OR "plane warts" OR "lichen planus" OR "dissecting cellulitis" OR "folliculitis decalvans" OR "sebaceous hyperplasia" OR "cutaneous t-cell lymphoma" OR "mycosis fungoides." A total of 169 studies discuss the use of oral isotretinoin for 16 non-acne dermatologic conditions, the most common being non-melanoma skin cancers (0.2-8.2 mg/kg/day), cutaneous T-cell lymphomas (0.5-2 mg/kg/day), and rosacea (0.22-1 mg/kg/day). Inflammatory conditions such as rosacea, granuloma annulare, and hidradenitis suppurativa benefit from lower oral isotretinoin dosage of 0.3-1 mg/kg/day, whereas, hyperkeratotic diseases such as psoriasis and pityriasis rubra pilaris, consistently respond better to higher dosages of up to 2-4 mg/kg/day for lesion clearance. Recurrence of disease following discontinuation of isotretinoin have been reported for rosacea, psoriasis, granuloma annulare, Darier's disease, dissecting cellulitis, and non-melanoma skin cancers. Disease exacerbation was reported in some patients with hidradenitis suppurativa. Off-label isotretinoin is an effective treatment choice for dermatological conditions beyond acne. Further prospective, randomized human trials are needed to clarify when and how to prescribe off-label isotretinoin for maximum efficacy and safety.
Topics: Administration, Oral; Dermatologic Agents; Dose-Response Relationship, Drug; Humans; Isotretinoin; Off-Label Use; Skin Diseases; Treatment Outcome
PubMed: 33151346
DOI: 10.1007/s00403-020-02152-4 -
Association between alopecia areata, anxiety, and depression: A systematic review and meta-analysis.Journal of the American Academy of... May 2023To date, there is no comprehensive meta-analysis analyzing the association between alopecia areata, anxiety, and depression. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, there is no comprehensive meta-analysis analyzing the association between alopecia areata, anxiety, and depression.
OBJECTIVE
We sought to analyze the existing literature to examine the association between alopecia areata, anxiety, and depression.
METHODS
We extracted literature from 4 databases including MEDLINE, Embase, PsychINFO, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (ie, PRISMA) reporting guidelines to finalize a list of relevant articles to be included in our systematic review and meta-analysis. There were no restrictions placed on publication year or age of participants.
RESULTS
Eight studies that included 6010 patients with AA and 20 961 control individuals were included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-control studies. Analysis of these studies showed a positive association with anxiety (pooled odds ratio, 2.50; 95% confidence interval, 1.54-4.06) and depression (pooled odds ratio, 2.71; 95% confidence interval, 1.52-4.82).
LIMITATIONS
Publication bias may be a limitation of the study.
CONCLUSION
This study suggests that patients with AA are at higher risk of both anxiety and depression. Health care professionals must be cognizant of this higher risk and consider routine assessment of these conditions and referral to appropriate providers when indicated.
Topics: Humans; Alopecia Areata; Depression; Cross-Sectional Studies; Anxiety
PubMed: 31163237
DOI: 10.1016/j.jaad.2019.05.086 -
Allergy, Asthma, and Clinical... Sep 2021Atopic dermatitis is the most common chronic inflammatory skin disease and presents a major public health burden worldwide. Recent observational studies revealed the... (Review)
Review
BACKGROUND
Atopic dermatitis is the most common chronic inflammatory skin disease and presents a major public health burden worldwide. Recent observational studies revealed the potential association between atopic dermatitis with autoimmune disorders. However, there is no meta-analysis of the prevalence or incidence of autoimmune diseases in atopic dermatitis. Therefore, considering the potential clinical implications of these associations, we aimed to assess the risk of autoimmune diseases in patients with atopic dermatitis using this method.
METHODS
PubMed, Embase, and Web of Science were searched from inception to October, 2020. Observational studies which provided estimate effects with 95% CI or raw data were included. The quality of selected studies was evaluated using the Newcastle-Ottawa Scale. Odds ratio and relative risks were pooled using a random effects model and expressed with 95% confidence intervals.
RESULTS
Fourteen observational studies were included in this systematic review and meta-analysis. The random-effects meta-analysis of case-control and cross-sectional studies showed a significant association of atopic dermatitis with mutiple autoimmune diseases, including alopecia areata, celiac disease, Crohn's disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. Furthermore, pooling of the results of cohort studies showed that patients with atopic dermatitis were more likely to develop these autoimmune diseases.
CONCLUSION
Our meta-analysis showed that patients with atopic dermatitis were at higher risk of multiple autoimmune diseases including alopecia areata, celiac disease, Crohn's disease, rheumatoid arthritis, systematic lupus erythematosus, ulcerative colitis and vitiligo. It is important for early detection of the affected group so that timely management can be initiated. Dermatologists and allergists should be aware of the autoimmune diseases in patients with atopic dermatitis and develop interventions if necessary. Also, limited by the present research, we still require more large-scale studies to further establish the association between atopic dermatitis and autoimmune diseases.
PubMed: 34563251
DOI: 10.1186/s13223-021-00597-4