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Journal of the European Academy of... Jun 2021Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic... (Review)
Review
Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic review of the literature about the treatment of alopecia areata in children (≤18 years old) was performed on 11 May 2020 by searching the PubMed, Scopus and EBSCO databases. The terms used for the search were: 'alopecia areata', 'alopecia totalis' or 'alopecia universalis' combined with 'paediatric', 'children' or 'childhood'. A total of 89 articles were included in final evaluation. The most commonly assessed treatment options in paediatric alopecia areata were topical immunotherapy (response rate in monotherapy: 54%; 187/345) intralesional glucocorticosteroids (75%; 211/280), systemic glucocorticosteroids (73%; 102/140), and anthralin (42%; 31/74). Topical glucocorticosteroids (81%; 35/43), systemic Janus kinase (JAK) inhibitors (90%; 27/30), topical calcineurin inhibitors (42%; 8/19), topical JAK inhibitors (65%; 11/17), PUVA therapy (56%; 9/16) and 308-nm excimer laser (77%; 10/13) were also evaluated. Additionally, evaluation in smaller numbers of paediatric patients included methotrexate (100%; 10/10), topical minoxidil (44%; 4/9) and cyclosporine (83%; 5/6). There were limited data considering children with alopecia areata treated with azathioprine, hydroxychloroquine, topical sildenafil, topical prostaglandin analogues, fractional carbon dioxide laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab, botulinum toxin, and compound glycyrrhizin. On the basis of the limited data available glucocorticosteroids (systemic, intralesional or topical) and JAK inhibitors (systemic or topical) may be considered the best documented and most effective treatment options in alopecia areata in children. There are no sufficient paediatric data to compare treatment safety and relapse rates in these therapeutic modalities.
Topics: Adolescent; Alopecia; Alopecia Areata; Child; Humans; Janus Kinase Inhibitors; Leflunomide; Minoxidil; Treatment Outcome
PubMed: 33630354
DOI: 10.1111/jdv.17187 -
Journal of the American Academy of... Mar 2020Alopecia areata (AA) is a common autoimmune alopecia with heterogeneous severity and distribution. Previous studies found conflicting results about AA epidemiology. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alopecia areata (AA) is a common autoimmune alopecia with heterogeneous severity and distribution. Previous studies found conflicting results about AA epidemiology.
OBJECTIVE
To determine the prevalence, incidence, and predictors of AA, alopecia totalis, alopecia ophiasis, and alopecia universalis.
METHODS
A systematic review of all published cohort and cross-sectional studies that analyzed AA and its subtypes. MEDLINE, Embase, LILACS, Scopus, Cochrane Library, and GREAT were searched. At least 2 reviewers performed study title/abstract review and data extraction. Random-effects meta-analysis was used because of significant heterogeneity (I = 99.97%).
RESULTS
Ninety-four studies met the inclusion criteria. The pooled prevalence (95% confidence interval, N) of AA overall was 2.11% (1.82-2.42, N = 302,157,365), with differences of population-based (0.75% [0.49-1.06%], N = 301,173,403) and clinic-based (3.47% [3.01-3.96], N = 983,962) studies. The prevalences of alopecia totalis, ophiasis, and universalis were 0.08% (0.04-0.13, N = 1,088,149), 0.02% (0.00-0.06, N = 1,075,203), and 0.03% (0.01-0.06, N = 1,085,444), respectively. AA prevalence (95% confidence interval) increased over time (<2000: 1.02% [0.85-1.22]; 2000-2009: 1.76% [1.51-2.03]; >2009: 3.22% [2.59-3.92]; P < .0001) and differed by region. AA prevalence was significantly lower in adults (1.47% [1.18-1.80]) than children (1.92% [1.31-2.65]; P < .0001).
CONCLUSIONS
AA affects 2% of the global population. AA prevalence is lower in adults than children, is increasing over time, and significantly differs by region.
Topics: Alopecia; Alopecia Areata; Humans; Incidence; Prevalence
PubMed: 31437543
DOI: 10.1016/j.jaad.2019.08.032 -
Journal of the American Academy of... Jan 2018Many therapies are available for the treatment of alopecia areata, including topical, systemic, and injectable modalities. However, these treatment methods produce... (Review)
Review
Many therapies are available for the treatment of alopecia areata, including topical, systemic, and injectable modalities. However, these treatment methods produce variable clinical outcomes and there are no currently available treatments that induce and sustain remission. When making management decisions, clinicians must first stratify patients into pediatric versus adult populations. Disease severity should then be determined (limited vs extensive) before deciding the final course of therapy. The second article in this continuing medical education series describes the evidence supporting new treatment methods, among them Janus kinase inhibitors. We evaluate the evidence concerning the efficacy, side effects, and durability of these medications. An overview of conventional therapy is also provided with new insights gleaned from recent studies. Finally, future promising therapeutic options that have not yet been fully evaluated will also be presented.
Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Alopecia Areata; Dermatologic Agents; Education, Medical, Continuing; Female; Humans; Immunotherapy; Injections, Intralesional; Male; Methotrexate; Minoxidil; Quality of Life; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 29241773
DOI: 10.1016/j.jaad.2017.04.1142 -
JAMA Network Open Oct 2023Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.
IMPORTANCE
Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified.
OBJECTIVE
To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023.
EXPOSURES
Receipt of diagnosis of COVID-19.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses.
RESULTS
A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19.
CONCLUSIONS AND RELEVANCE
In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.
Topics: Adult; Humans; Female; Middle Aged; Retrospective Studies; Crohn Disease; COVID-19; Connective Tissue; Sarcoidosis; Alopecia; Vasculitis
PubMed: 37801317
DOI: 10.1001/jamanetworkopen.2023.36120 -
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 -
Expert Opinion on Investigational Drugs Dec 2021Alopecia areata (AA) is an inflammatory and autoimmune form of hair loss, which can present with one patch of hair loss, but in more extreme cases can lead to total body... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Alopecia areata (AA) is an inflammatory and autoimmune form of hair loss, which can present with one patch of hair loss, but in more extreme cases can lead to total body hair loss. There are limited therapeutic options and no cure, but medication can sometimes induce sustained remission. Disease control cannot be guaranteed; even those who regrow all hair on treatment can experience relapse. There are no FDA approved systemic treatments; therefore, an unmet need for safe, and effective treatments exists. Few treatments have been evaluated by randomized controlled trials. Case reports and series indicate oral Janus Kinase (JAK) inhibitors as a potential therapy. Ritlecitinib is a novel oral JAK3-selective inhibitor being investigated as an AA treatment.
AREAS COVERED
This article introduces ritlecitinib as treatment for AA and considers the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety [reporting data from a 24-week, phase 2a double-blinded placebo-controlled trial of ritlecitinib in patients with AA who have more than 50% scalp hair loss].
EXPERT OPINION
Ritlecitinib offers a novel mode of action, rapid onset, and the capacity for a superior safety profile over other JAK inhibitors. If approved, ritlecitinib will be widely prescribed by physicians overseeing the more severe AA patients for the foreseeable future. As JAK inhibitors regulate the hair growth cycle and have anti-inflammatory effects, the implementation of ritlecitinib in hair loss disorders other than AA, may prove beneficial.
Topics: Alopecia; Alopecia Areata; Drugs, Investigational; Humans; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Pyrimidines
PubMed: 34826225
DOI: 10.1080/13543784.2021.2012149 -
Journal of the American Academy of... May 2023
Topics: Humans; Adolescent; Alopecia Areata; Retrospective Studies; Alopecia; Pyrazoles
PubMed: 36623557
DOI: 10.1016/j.jaad.2022.12.033 -
JAMA Dermatology Apr 2023Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Methotrexate Alone vs Methotrexate Plus Low-Dose Prednisone in Patients With Alopecia Areata Totalis or Universalis: A 2-Step Double-Blind Randomized Clinical Trial.
IMPORTANCE
Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata (AA). Methotrexate, an inexpensive treatment, might be effective in AU and AT.
OBJECTIVE
To evaluate the efficacy and tolerance of methotrexate alone or combined with low-dose prednisone in patients with chronic and recalcitrant AT and AU.
DESIGN, SETTING, AND PARTICIPANTS
This academic, multicenter, double-blind, randomized clinical trial was conducted at 8 dermatology departments at university hospitals between March 2014 and December 2016 and included adult patients with AT or AU evolving for more than 6 months despite previous topical and systemic treatments. Data analysis was performed from October 2018 to June 2019.
INTERVENTIONS
Patients were randomized to receive methotrexate (25 mg/wk) or placebo for 6 months. Patients with greater than 25% hair regrowth (HR) at month 6 continued their treatment until month 12. Patients with less than 25% HR were rerandomized: methotrexate plus prednisone (20 mg/d for 3 months and 15 mg/d for 3 months) or methotrexate plus placebo of prednisone.
MAIN OUTCOME AND MEASURES
The primary end point assessed on photos by 4 international experts was complete or almost complete HR (Severity of Alopecia Tool [SALT] score <10) at month 12, while receiving methotrexate alone from the start of the study. Main secondary end points were the rate of major (greater than 50%) HR, quality of life, and treatment tolerance.
RESULTS
A total of 89 patients (50 female, 39 male; mean [SD] age, 38.6 [14.3] years) with AT (n = 1) or AU (n = 88) were randomized: methotrexate (n = 45) or placebo (n = 44). At month 12, complete or almost complete HR (SALT score <10) was observed in 1 patient and no patient who received methotrexate alone or placebo, respectively, in 7 of 35 (20.0%; 95% CI, 8.4%-37.0%) patients who received methotrexate (for 6 or 12 months) plus prednisone, including 5 of 16 (31.2%; 95% CI, 11.0%-58.7%) who received methotrexate for 12 months and prednisone for 6 months. A greater improvement in quality of life was observed in patients who achieved a complete response compared with nonresponder patients. Two patients in the methotrexate group discontinued the study because of fatigue and nausea, which were observed in 7 (6.9%) and 14 (13.7%) patients receiving methotrexate, respectively. No severe treatment adverse effect was observed.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, while methotrexate alone mainly allowed partial HR in patients with chronic AT or AU, its combination with low-dose prednisone allowed complete HR in up to 31% of patients. These results seem to be of the same order of magnitude as those recently reported with JAK inhibitors, with a much lower cost.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02037191.
Topics: Adult; Humans; Male; Female; Methotrexate; Prednisone; Alopecia Areata; Quality of Life; Neoplasm Recurrence, Local; Double-Blind Method; Treatment Outcome
PubMed: 36884234
DOI: 10.1001/jamadermatol.2022.6687