Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2023;13(4):e2023255 1 The Efficacy and Adverse Effects of Corticosteroid Pulse Therapy in Alopecia Areata: A Review Article Fatemeh Rastaghi¹, Roxana Kaveh², Nazafarin Yazdanpanah³, Akram Sadat Sahaf4, Najmeh Ahramyanpour1,5 1 Department of Dermatology, Afzalipour Hospital, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran 2 Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran 3 Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 4 Department of Dermatology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 5 Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran Key words: alopecia areata, corticosteroid, pulse therapy Citation: Rastaghi F, Kaveh R, Yazdanpanah N, Sahaf AS, Ahramyanpour N. The Efficacy and Adverse Effects of Corticosteroid Pulse Therapy In Alopecia Areata: A Review Article. Dermatol Pract Concept. 2023;13(4):e2023255. DOI: https://doi.org/10.5826/ dpc.1304a255 Accepted: May 10, 2023; Published: October 2023 Copyright: ©2023 Rastaghi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Najmeh Ahramiyanpour, Assistant Professor of Dermatology, Department of Dermatology, Afzalipour Hospital, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Postal Code: 7616913555; Email: najme.pour@gmail.com Introduction: Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, vary- ing in severity from small round hairless patches to the total loss of scalp or body hair. As steroid pulse therapy outcomes for AA vary, this study aimed to review the related literature regarding the efficacy, relapse rates, side effects, and prognostic factors associated with the response to different pulse corti- costeroid treatments. Methods: We performed a literature search on August 29, 2022, to provide an overview of the efficacy of pulse steroid therapy in patients with AA. The terms "pulse steroid therapy AND alopecia areata" and "pulse corticosteroid therapy AND alopecia areata" were searched on PubMed and Google Scholar. Results: A total of 24 articles were assessed. There was no difference in outcomes and side effects between intravenous and oral pulse corticosteroid therapy. The relapse rate and efficacy depended on the time of AA onset, age, and AA type: improved outcomes and decreased relapse were linked with recent onset (<6 months), a younger age (<10 years), and the multifocal type of AA. Patients with a past medical history of atopy, nail pitting, or thyroid disease and those with severe forms of AA like alopecia totalis and alopecia universalis had the least improvement. ABSTRACT 2 Review | Dermatol Pract Concept. 2023;13(4):e2023255 Introduction Alopecia areata (AA) is a common, non-scarring, autoim- mune hair loss disorder with an estimated lifetime risk of ap- proximately 2% [1-3]. Genetics and environment both play essential roles in the pathology of the disease, as almost 20% of the patients have a positive family history. In addition to the suggested autoreactive T-cell-mediated pathogenesis of the disease, psychological stress may also be heavily involved. The severity of AA ranges from small round hairless patches to the total loss of scalp or body hair (alopecia totalis/alo- pecia universalis), which can cause devastating psychosocial effects, such as major depression, anxiety, mood disorders, and social phobia [4-6]. Implementing and evaluating treatment protocols for AA is challenging due to the disease's uncertain patho- genesis and unpredictable remission rates [6]. The treat- ment should also cover the patient's psychological needs, making management more difficult. Topical, intralesional, and systemic agents have been used for AA, but the ef- ficacy of the treatments varies widely [6-9]. One of the suggested treatments is corticosteroid therapy. Topical and intra-lesional corticosteroids are effective and well tolerated in patients with mild to moderate AA [4,6,10]. However, managing severe AA cases (alopecia universalis, totalis, and ophiasis) is more challenging [11]. Systemic corticosteroids are usually effective in these patients and can be administered via the intravenous, oral, or intramus- cular route [12]. Objectives In 1975, Burton and Shuster introduced corticosteroid pulse therapy for treating patients with AA to reduce the possi- ble side effects of long-term use of corticosteroids and to increase the treatment's effectiveness. Since then, many sci- entists have aimed to optimize this type of therapy [10]. As steroid pulse therapy regimens and outcomes for AA vary, this study aimed to review the related literature regarding the efficacy, relapse rates, side effects, and prognostic factors associated with the response to different pulse corticosteroid treatments. Methods A literature search was performed on August 29, 2022, to re- view the efficacy of pulse steroid therapy in patients with AA. The terms "pulse steroid therapy AND alopecia areata" and "pulse corticosteroid therapy AND alopecia areata" were searched on PubMed and Google Scholar. All types of sci- entific publications matching the keywords were transferred to EndNote version 8 (Clarivate Analytics), and duplicates were removed. Two authors reviewed the articles inde- pendently based on their titles and abstracts. Subsequently, a third author performed an eligibility assessment of the full texts based on the inclusion and exclusion criteria. Inclusion criteria consisted of relevant full-text, English-written clini- cal trials. All case reports, editorials, conferences, commen- taries, letters to editors, and review articles were excluded from the study. Poor quality trials were also excluded based on a Jadad scale of less than 3. In case of any conflicts, the senior author made the final decision and responded to each of the points raised in the screenings. After screening the data, a total of 24 articles were identified and included in this study. Then, two authors independently extracted and recorded the data in an Excel 2016 spreadsheet (Microsoft). The extracted features included the title, publication year, author names, year, sample size, mean age, type of treatment, assessments, outcomes, and side effects. Results The Efficacy of Intravenous Corticosteroid Pulse in Severe AA The efficacy of intravenous steroid pulse was studied in ten articles. Among them, seven examined intravenous meth- ylprednisolone, two assessed the combination therapy of methylprednisolone and cyclosporine, and one evaluated the combination of intravenous methylprednisolone and methotrexate. Intravenous Methylprednisolone Intravenous Methylprednisolone in Adults Intravenous methylprednisolone was introduced to decrease the side effects of prolonged use of oral corticosteroids in Conclusions: All kinds of mentioned systemic pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone pulse seems to be the most effective agent (followed by intramuscular triamcin- olone), especially in severe cases, but more side effects may accompany it. Combining this agent with other medications can reduce the dosage and side effects. Pulses of prednisolone and methylprednis- olone are less effective but safer, as they have low relapse rates and adverse effects. A combination of them with other drugs can increase their efficacy. Review | Dermatol Pract Concept. 2023;13(4):e2023255 3 AA. Four studies evaluated the efficiency of intravenous methylprednisolone pulse therapy in a total of 224 adults with severe AA. They noticed that patients with recent onset of the disease (<6 months) responded better. Most patients with plurifocal AA or scalp involvement <50% showed significant hair growth (mostly complete remission), while none with alopecia universalis, totalis, or ophiasis showed more than 50% hair growth, even after six months of follow-up. They concluded that intravenous methylprednisolone is a safe and promising treatment in adults with plurifocal or recent-onset AA, with only mild adverse effects, while it is less effective in patients with alopecia universalis, totalis, or ophiasis [13-16]. In another study, Chao-Chun Yang et al reviewed 85  patients with severe AA treated with oral prednisolone pulse or intravenous methylprednisolone pulse. They noticed that the two treatments were equally effective in treating severe AA, as more than half of the patients experienced nearly 75% hair regrowth. Better results and less relapse were reported with earlier initiation of treatment, especially during the first year of disease onset. There was no significant difference in side effects between the two groups [17]. To study the long-term efficacy of intravenous pulse of methylprednisolone in treating severe AA, Staumont-Sallé et al assessed 60 patients who had received this treatment ten years earlier. They reported that patients who initially responded to therapy during the first six months had a milder disease in the next ten years, while those who were non-responders to therapy still had severe disease. Autoim- mune thyroid disease and atopic disorders were more fre- quent in non-responders. This study considered intravenous methylprednisolone pulse therapy inefficient in treating se- vere AA and suggested other treatments for alopecia totalis and universalis [18]. Intravenous Methylprednisolone in Children Friedland assessed the efficacy of intravenous methylpred- nisolone pulse in treating children with severe AA. Nearly 70% of patients experienced partial to complete remission, and a higher rate of hair growth was seen in multifocal AA patients. Surprisingly, 81% of responders had a relapse in the first year of treatment. Age at onset of fewer than ten years, disease onset below six months, and multifocal disease were recognized as good prognostic factors. No serious side effects were reported. This article concluded that all children with AA do not benefit from steroid pulse treatment; there- fore, case selection plays a vital role in achieving optimal results and avoiding ineffective therapies [19]. Intravenous Methylprednisolone Combined With Cyclosporine In a study by Shaheedi-Dadras et al, a 500 mg dose of in- travenous methylprednisolone was administered in three consecutive doses monthly in addition to oral cyclosporine (2.5 mg/kg/day) for a treatment duration of 5–8 months. Ac- cording to the results, only a third of the patients showed a hair regrowth rate of more than 70%. Patients with nail pitting or a positive history of atopy responded poorly. They suggested that this treatment can be effective in treating some patients with severe AA with mild side effects [20]. Results of another study comparing the efficacy of high-dose corti- costeroid pulse therapy and combination therapy of cyclo- sporine plus low-dose corticosteroid in severe AA revealed that patients who received a high dose of intravenous meth- ylprednisolone experienced more than 50% improvement during six months of follow-up. Notably, 20%–26% relapse occurred in both groups without any significant difference. A  profound positive correlation between a recent disease onset and a desirable response was seen, such that 85% of patients with a disease onset of fewer than three months showed significant hair regrowth. Among all types of severe alopecia, plurifocal AA showed a better improvement than any other kind. This study indicated that intravenous meth- ylprednisolone pulse therapy was a better treatment option than combination therapy with low-dose methylprednisolone and cyclosporine in patients with severe, plurifocal AA [21]. Intravenous Methylprednisolone Combined With Methotrexate Droitcourt et al evaluated the efficacy of combining intrave- nous methylprednisolone pulse with methotrexate in treating multifocal AA. More than half of the patients experienced completed hair growth, while the rest had satisfactory in- complete responses. The mean period of hair regrowth initi- ation was 2.5 months, and relapse occurred in a few patients. The study concluded that this combination is effective and well-tolerated when treating patients with severe AA [22]. The Efficacy of Oral Corticosteroid Pulse in Treating Severe AA Fourteen studies evaluated oral steroid pulse therapy in treat- ing severe AA, including 2 on methylprednisolone, 3 on dexa- methasone, 5 on prednisolone, and 4 studies on betamethasone. Oral Methylprednisolone Two studies assessed methylprednisolone pulse efficacy in AA treatment: one evaluated oral mega-pulse efficacy, relapse, and side effects, while the other evaluated oral mini-pulse. Saif et al prescribed an oral mega-pulse of methylprednisolone for 24 weeks with different proto- cols, namely three consecutive days once every two weeks, two consecutive daily pulses every three weeks, and three consecutive daily pulses every three weeks. No significant difference was seen between the groups in efficacy, and all 4 Review | Dermatol Pract Concept. 2023;13(4):e2023255 months. Almost 60% of patients had hair regrowth of more than 50% (most had >75% regrowth). The most satisfactory results were seen in patients with plurifocal AA. Patients with a disease duration of more than 12 months needed longer treatments. No serious adverse effects were reported [27]. Prednisolone Four studies focused on the effect of prednisone pulse in treating severe AA. Among all, 3 articles studied high doses of prednisolone pulse, one study evaluated the possible path- way of the effect of prednisolone in treating AA by examin- ing serum and tissue tumor necrosis factor-alpha (TNF-α) levels, and one compared the efficacy of oral prednisolone, dexamethasone, and intramuscular triamcinolone. Oral High-dose Prednisolone Pulse To assess the efficacy of the oral prednisolone pulse, Sharma et al enrolled 32 patients with more than 40% scalp in- volvement or persistent AA and treated them with a 300 mg monthly dose of prednisolone pulse. More than half of the pa- tients had an excellent response. Patients with plurifocal alo- pecia areata had the most desirable cosmetic effects, while no improvement was seen in patients with alopecia universalis. Patients with alopecia universalis and non-responders to the 300 mg prednisolone pulse were retreated with a 1000 mg prednisolone pulse; nearly 50% regrowth was seen in this group during the follow-ups. Results showed that the 300 mg prednisolone pulse was an effective treatment for plurifocal alopecia areata with mild side effects, while the 1000 mg prednisolone pulse might be an effective choice in alopecia universalis and widespread resistant AA. The female gender, disease duration of over two years, and alopecia universalis were linked with a poor or lack of response to treatment [28]. A placebo-controlled study in a total of 43 patients re- vealed that 35% of the patients who received prednisolone pulse experienced significant hair growth at the end of three months. However, relapse occurred in 25% of them during the three months of follow-up. Patients with early age of onset, disease duration of fewer than two years, and those on their first episode responded better compared to those with atopy-related, nail involvement, multiple episodes, and prolonged duration. Mild side effects of corticosteroids were seen in 55% of the patients. However, they all eased grad- ually during the follow-up period ]. Another study by Tsai et  al tested high-dose steroid pulse therapy, 5 mg/kg oral prednisone in individuals under 12, and 500 mg intrave- nous methylprednisolone in adults with severe AA. Within four months of treatment initiation, favorable results were achieved, as all patients with multifocal AA experienced sig- nificant regrowth. However, the treatment outcomes were worse in patients with alopecia ophiasis, alopecia universa- lis, alopecia totalis, and extended disease lasting more than protocols induced a desirable response rate, as more than 50% of patients experienced more than 25% improvement in hair growth during treatment. Early age of disease on- set, hypothyroidism, and longer duration of AA (more than two years) were associated with lower response. There was a significant difference in the side effects rate between the study groups, as patients who received steroid pulse with higher doses and shorter intervals experienced greater and more severe complications like arthralgia, increased appe- tite, and stomach upset. This study suggests oral mega pulse methylprednisolone as an effective choice for treating se- vere AA, albeit with a high risk of adverse events and a high relapse rate [23]. In another study by Thi et al, patients were treated with an oral mini-pulse of methylprednisolone, 16 mg/day, for two consecutive days per week. More than 82% of patients had good regrowth over six months, while only 40% had the same experience within three months. They suggested the mini-pulse of methylprednisolone as a safe and effective treatment for AA in six months [24]. Oral Dexamethasone Among all articles, three were evaluated for dexamethasone pulse therapy effect in AA treatment: two evaluated the oral mini-pulse, and one assessed the combination of oral pulse with topical corticosteroids. Oral Mini-pulse of Dexamethasone Sánchez-Díaz described 40 patients with extensive scalp AA treated with dexamethasone oral mini-pulse (mean dose of 2.7 mg/day, two days weekly, 12 months). Higher effective- ness was reported as the treatment period increased. Oral dexamethasone pulse was relatively ineffective in patients with hypothyroidism and those aged under 15 years. No greater reduction in the Severity of Alopecia Tool (SALT) score was reported in combination therapy of dexametha- sone pulse and oral minoxidil (25). Another study by Sharma et al. on 30 patients with widespread and diffuse AA who received oral dexamethasone showed promising results, as more than 60% of patients had completed or over 75% hair growth during five months. Relapse was uncommon as it was seen only in one patient. Frequent but mild and transient side effects were reported [26]. Oral Mini-pulse of Dexamethasone Combined With Topical Corticosteroids Lalosevic et al studied 65 individuals aged 8–12 years with AA, alopecia universalis, and plurifocal AA. Oral pulse dexa- methasone (once every four weeks) was combined with top- ical clobetasol 0.05% ointment to treat patients for 6–12 Review | Dermatol Pract Concept. 2023;13(4):e2023255 5 or good response. There was, however, a relapse in one pa- tient two months after stopping therapy. Only a few patients showed an unsatisfactory or lack of response at the end of the six months of therapy. Both non-responders had alopecia universalis. They concluded that betamethasone is a safe and effective treatment for extensive AA, with only mild, revers- ible side effects [33]. To compare the efficacy of betamethasone oral mini-pulse versus weekly azathioprine pulse in treating scalp alopecia, Gupta et al. enrolled 50 patients into two groups of 25. As- sessments of the results at baseline and after four and nine months demonstrated that both methods were highly effective options in treating severe alopecia with no priority, as almost 60% of patients in each group experienced complete regrowth within the nine months. However, betamethasone consump- tion was accompanied by some severe side effects. They sug- gested azathioprine pulse as a good and safe alternative to steroid therapy in severe alopecia with minor side effects [34]. Combination of Oral Mini-pulse of Betamethasone With Other Agents Asilian et al compared 36 patients treated with either beta- methasone 3 mg/once a week, methotrexate 15 mg/once a week, or a combination of them for four months. Patients in all groups experienced a significant increase in hair re- growth; however, greater regrowth was seen in patients treated with betamethasone and combination therapy com- pared with methotrexate alone. Among all, combination therapy was the most effective, especially in the long-term period of consumption of the drugs [35]. In 2011, Deshpande et al. proposed a combination ther- apy in which the patients were treated with oral betametha- sone mini-pulse (0.1 mg/kg twice a week) along with topical minoxidil and anthralin cream of 2%-5% and 1.15%, respec- tively. Topical minoxidil was applied to the affected area twice, 12 hours apart. The anthralin cream was first applied at night, two hours apart from the minoxidil application, for 10 minutes (contact time), then the contact time gradually increased every three weeks until mild erythema appeared. There was a high response rate (80%) among the patients. The response rate was low among the patients with alopecia universalis or prolonged alopecia totalis, while all patients with ophiasis and severe AA showed cosmetic improvements. Due to the synergistic inter- actions between the drugs, this combination therapy could be used as an effective and safe treatment for patients with treatment-resistant and extensive alopecia areata [36]. Conclusions Alopecia areata (AA) is a common, non-scarring, autoim- mune hair loss disorder. It is a multifactorial disease that varies in clinical presentation from a small patch to total two years. This study suggested monthly corticosteroid pulse therapy with a mean dose of 5-10 mg/kg as an effective treat- ment for severe multifocal AA lasting less than two years, with a low relapse rate [30]. Prednisolone Possible Mechanism of Action in AA To assess the possible mechanism of action of prednisolone in the treatment of AA, Abdel Halim et al compared tissue and serum levels of TNF-α in 20 patients with AA and 20 controls. This study indicated that the disease duration significantly decreased after consuming 60 mg of prednisolone twice weekly for three months. There was a positive relationship between TNF-α level and AA lesions. Both serum and tissue levels of TNF-α were higher in the pretreatment evaluations of patients compared to the control group. Post-treatment assessments revealed a statistically significant decrease in pa- tients' serum and tissue levels of TNF-α. They suggested the prednisolone pulse as a good choice for the treatment of AA, as it reduced the disease duration and TNF-α levels [31]. Comparison of the Efficacy of Oral Prednisolone, Dexamethasone, and Intra- muscular Triamcinolone A study published in 2006 by Kurosawa et al compared the efficacy, relapse rate, and side effects between three modalities of systemic corticosteroid therapy (oral prednisolone, dexa- methasone, and intramuscular triamcinolone) in 89  patients with AA. In most patients, hair growth was evident 3-6 months after the first treatment session. According to the results, the overall response rate was significantly different only between the dexamethasone group and the intramuscular triamcino- lone group patients in each clinical subtype (mostly in multi- plex AA). To conclude, both prednisolone pulse therapy and intramuscular triamcinolone are effective treatments for AA with mild side effects. However, overall relapse rates were significantly higher in the dexamethasone group than in the prednisolone group (especially for those with alopecia tota- lis and alopecia universalis). The authors concluded that new strategies are needed to reduce relapse rates [32]. Betamethasone Four studies were done on betamethasone efficacy in severe AA. One assessed mini-pulse of betamethasone, one com- pared azathioprine pulse with betamethasone, one assessed combination therapy of betamethasone and methotrexate, and the other examined a combination of betamethasone mini-pulse and topical minoxidil and anthralin. Oral Mini-pulse of Betamethasone One study evaluated the efficacy of betamethasone oral mini-pulse therapy in patients with severe AA. According to the results, most patients (74.9%) showed an excellent 6 Review | Dermatol Pract Concept. 2023;13(4):e2023255 in relapse rate and adverse effects, as the mini-pulse of oral methylprednisolone is safer; higher doses and shorter inter- vals lead to greater and more severe complications [23,24]. Studies proposed dexamethasone as a good treatment option for AA with a low rate of relapse and side effects. They also revealed no difference between the efficacy of oral mini-pulse dexamethasone (2.7 mg/day) vs. 5 mg/day for two days a week, so it’s safer to use the lower dosage. To achieve better results in children, dexamethasone can be combined with topical clobetasol [25-27]. In the studies on betamethasone, excellent therapeutic responses can be achieved with a low relapse rate and only mild reversible side effects. Monotherapy with betametha- sone mini-pulse (0.1 mg/kg/ day to 5 mg/day for 2consecutive days a week for a mean time of 6 months) is accompanied by highly successful results but some adverse effects, while combination therapy of betamethasone with methotrexate or topical minoxidil and anthralin significantly increase hair regrowth and decrease the side effects [33-36]. Articles focused on the efficacy of prednisone pulse therapy have found prednisolone (5-10 mg/kg/month for 4-6 months) as an acceptable and effective option with a low relapse rate. Results showed that an average dose of 300 mg monthly prednisolone pulse is an effective treatment for plurifocal AA with only mild side effects, but patients with alopecia universalis or alopecia totalis are resistant to this therapy. Research suggests 1000 mg prednisolone is an effec- tive choice in alopecia universalis and resistant widespread alopecia areata [28-30]. Comparisons of the efficacy of oral dexamethasone, oral prednisolone, and intramuscular triamcinolone revealed that all methods are effective, but the best results were achieved with intramuscular triamcinolone, followed by prednisolone, with only mild reversible side effects. Patients who received dexamethasone experienced less hair regrowth with a higher relapse rate [32]. In conclusion, all mentioned systemic corticosteroid pulses effectively induce hair regrowth in alopecia areata. Both forms of intravenous and oral corticosteroids have ac- ceptable efficacy. Betamethasone pulse seems to be the most effective agent in the treatment of AA (followed by intra- muscular triamcinolone), especially in severe cases, but more side effects may accompany it. Combining this agent with other medications can reduce the dosage and side effects. Prednisolone and methylprednisolone pulse are less effective but safer options, with low relapse rates and few adverse effects. A combination of them with other drugs can increase their efficacy. scalp and body alopecia. Finding the appropriate treatment protocols for AA is challenging due to the disease's uncer- tain pathogenesis and unpredictable remission rates (6). The use of systemic pulse corticosteroids was first introduced for treating severe types of AA in 1975 by Burton and Shuster to decrease possible side effects of long-term use of cortico- steroids and increase the effectiveness of the treatment. They treated 22 patients with a single intravenous dose of methyl- prednisolone, but only 23% responded. The unsuccessful re- sults were due to poor patient selection, as most patients had severe AA for a long time [10]. Afterward, several scientists followed them and administered pulse steroid therapy in var- ious forms and doses with or without other drugs to avoid the long-term side effects of prolonged steroid therapy. In this study, we considered 24 published studies and reviewed their modalities for treating different kinds of AA. A review of the studies on the efficacy and side effects of intravenous methylprednisolone revealed that pulse ther- apy of methylprednisolone might be a promising treatment option in the severe form of AA with the routine treatment protocol of 8-10 mg/kg for three consecutive days, with one-month interval up until the clinical satisfaction achieve, either for adults or children. There is no difference in the out- comes and side effects of the routes of choice (intravenous or oral). The relapse rate and efficacy depend on the time of AA onset, patient age, and the type of AA; recent onset of AA (<6 months), younger age (<10 y/o), and multifocal type of AA (compared to alopecia universalis, totalis, and ophiasis) are linked with better results and a lower chance of relapse. Patients with a past medical history of atopy, nail pitting, or thyroid disease and those with severe forms of AA like alo- pecia universalis and totalis experienced less improvement [13-19]. A combination of intravenous pulse methylprednisolone with methotrexate (12.5 mg weekly) revealed the best effi- cacy for treating the severe type of AA, although some poor prognostic factors such as childhood onset of the disease, disease duration >6 years, and a positive history of atopy or nail pitting led to poor outcomes and increase the risk of relapse. The use of sequential intravenous pulse therapy of methylprednisolone is supposed to be better than a single dose to decrease the risk of relapse. Studies on the effect of combination therapy with cyclosporine are still controver- sial, but some articles have shown promising results [20-22]. Research on the efficacy of oral methylprednisolone pulse therapy showed that both oral mega-pulse and mini-pulse of methylprednisolone are effective in severe forms of AA, but the relapse rate is high. There is a significant difference Review | Dermatol Pract Concept. 2023;13(4):e2023255 7 R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s 1 Pu ls ed ad m in is tr at io n of co rt ic os te ro id s in th e tr ea tm en t of al op ec ia a re at a Sh ar m a, V K Pr os pe ct iv e 19 96 32 : 2 4M , 8F 14 –4 8 (m ea n  28 .5 ) W id es pr ea d al op ec ia , A T, A U A : 3 00 m g or al pr ed ni so lo ne m on th ly f or a m in im um o f 4  do se s or u nt il co sm et ic al ly ac ce pt ab le h ai r gr ow th w as ob ta in ed ; B : 1 00 0 m g pr ed ni so lo ne M on th ly ev al ua ti on an d se ri al ph ot og ra ph s; th e re su lt s w er e lis te d at 6 a nd 12  m on th s by m ea su ri ng th e pe rc en t of te rm in al h ai r gr ow th . A : 5 8. 3% h ad co m pl et e or 80 –9 5% h ai r gr ow th . B : 3 o ut o f 7  ha d co sm et ic al ly ac ce pt ab le gr ow th . In g en er al , w om en a nd pa ti en ts w it h al op ec ia f or m or e th an t w o ye ar s or A T o r A U s ho w ed p oo r or n o re sp on se . E ff ec ti ve tr ea tm en t fo r w id es pr ea d al op ec ia a re at a w it h on ly m ild si de e ff ec ts A : A m an ex pe ri en ce d na us ea ; a  w om an g ot po ly m en or rh ea . B : N o si de ef fe ct s 2 Pu ls e m et hy lp re dn is ol on e th er ap y fo r se ve re al op ec ia a re at a: a n op en p ro sp ec ti ve st ud y of 4 5 pa ti en ts A . F ri ed li O pe n, pr os pe ct iv e 19 98 45 13 –6 6 PF A A , O A , A U , a nd A T 25 0 m g IV m et hy lp re dn is ol on e, tw ic e a da y on 3  co ns ec ut iv e da ys Tw o in de pe nd en t ob se rv er s m ea su re d th e pe rc en ta ge o f ha ir r eg ro w th a t 1, 3 , 6 , a nd 1 2m . Se ri al p ho to gr ap hs an d m on th ly ex am in at io ns w er e do ne . Pa ti en ts w it h m ul ti fo ca l A A sh ow ed t he b es t re sp on se , w hi le pa ti en ts w it h O A , A U , a nd A T di d no t re sp on d w el l. R el ap se oc cu rr ed in 1 0 in 7m ; a ft er a y ea r of f ol lo w -u p, on ly 1 2 w er e st ill in r em is si on . E ff ec ti ve tr ea tm en t in pa ti en ts w it h m ul ti fo ca l A A , bu t no t in t ho se w it h A U , A T, or O A O nl y co m m on m ild t ra ns ie nt si de e ff ec ts of s te ro id s: fa ti gu e, n au se a, dy sp ne a, pa lp it at io n, a nd he ad ac he 3 Tw ic e w ee kl y 5 m g de xa m et ha so ne or al p ul se in th e tr ea tm en t of ex te ns iv e al op ec ia ar ea ta Sh ar m a V K Pr os pe ct iv e 19 99 30 : 2 0M , 10 F 6– 46 (m ea n  23 .6 ) E xt en si ve al op ec ia a nd ci rc um sc ri be d al op ec ia 5 m g de xa m et ha so ne or al ly , t w ic e w ee kl y fo r 6m o r un ti l ac ce pt ab le h ai r gr ow th M on th ly ex am in at io ns w er e do ne , a nd th e re su lt s w er e re po rt ed a t 6 an d 12  m on th s as co m pl et e (1 00 % ), ex ce lle nt (7 5- 95 % ), go od  ( 51 -7 4% ), or po or ( <5 0% ) ha ir gr ow th . A ft er 5 .3 5 m on th s, h ai r gr ow th w as co m pl et e or ex ce lle nt in 19  p at ie nt s, g oo d in 2 , p oo r in 3 , an d ab se nt in 6 . E ff ec ti ve m od al it y in tr ea ti ng s ev er e m ul ti fo ca l al op ec ia w it h on ly m ild co m m on s id e ef fe ct s. C om m on ly m ild si de e ff ec ts o f co rt ic os te ro id s w er e se en in 8  pa ti en ts ; in o nl y on e pa ti en t, th e tr ea tm en t ha d to s to p du e to th e si de e ff ec ts . 8 Review | Dermatol Pract Concept. 2023;13(4):e2023255 4 H ig h- do se s te ro id pu ls e th er ap y fo r th e tr ea tm en t of se ve re a lo pe ci a ar ea ta Y a- M in g T sa i Pr os pe ct iv e 20 02 17 : 8 M , 9F 8– 53 (m ea n  25 ) M ul ti fo ca l A A , O A , A U , an d A T C hi ld re n <1 2: 5 m g/ kg o ra l pr ed ni so ne in th re e di vi de d do se s m on th ly ; A du lt s: m on th ly 5 00 m g IV m et hy lp re dn is ol on e in fu si on o ve r tw o ho ur s (f or a m ax im um o f 6  m on th s) Se ri al p ho to gr ap hs w er e ta ke n, a nd tw o bl in de d de rm at ol og is ts ev al ua te d ha ir gr ow th . T he av er ag e of t he re su lt s w as ta bu la te d. A sa ti sf ac to ry re sp on se w as de fin ed a s m or e th an 7 5% h ai r re gr ow th . 11 p at ie nt s w it h m ul ti fo ca l A A sh ow ed p ar ti al ha ir g ro w th , w hi le 2 s ho w ed no r es po ns e. L es s ef fe ct iv e in O A , A T, A U , a nd ex te nd ed A A . E ff ec ti ve m od al it y in tr ea ti ng s ev er e m ul ti fo ca l A A la st in g le ss t ha n tw o  ye ar s 5 Pl ac eb o- co nt ro lle d or al p ul se pr ed ni so lo ne th er ap y in a lo pe ci a ar ea ta B ik as h R an ja n K ar Pl ac eb o- co nt ro lle d 20 05 G ro up A : 20 : 1 4M , 6F G ro up B : 16 : 1 2M , 4F G ro up A : 26 .3 ± 7 .3 . G ro up B : 30 .2 ± 1 0. 2 Se ve re A A G ro up A : 2 00 m g of o ra l p re dn is ol on e w ee kl y fo r 3m ; G ro up B : m at ch ed pl ac eb o ta bl et s on a n id en ti ca l sc he du le Pa ti en ts w er e ex am in ed m on th ly fo r m ar ke d (> 60 % ), m od er at e (3 1– 60 % ), or po or ( <3 0% ) re gr ow th . A : 8 h ad si gn ifi ca nt h ai r gr ow th a ft er 3m ( 2= m ar ke d, 6= m od er at e) , th ou gh 2 la te r re la ps ed . P oo r re sp on se : a to py - re la te d A A , n ai l in vo lv em en t, m ul ti pl e ep is od es , & ex te nd ed A A B : N on e re sp on de d. T hi s th er ap y is e ff ec ti ve a nd pr om is in g, bu t m or e re se ar ch n ee ds to b e do ne t o ad ju st t he d os e ne ed ed . M ild f re qu en t si de e ff ec ts o f co rt ic os te ro id s w er e se en in 5 5% o f th e pa ti en ts . H ow ev er , th ey a ll ea se d gr ad ua lly d ur in g th e fo llo w -u p pe ri od . R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s Review | Dermatol Pract Concept. 2023;13(4):e2023255 9 6 A c om pa ri so n of t he e ffi ca cy , re la ps e ra te a nd si de e ff ec ts a m on g th re e m od al it ie s of s ys te m ic co rt ic os te ro id th er ap y fo r al op ec ia a re at a M as ah ir o K ur os aw a R an do m iz ed co m pa ra ti ve - pr os pe ct iv e st ud y 20 06 89 16 -6 3 ye ar s PF A A , A T, A U D ex g ro up ( n= 19 ): or al D ex 0 .5 m g/ da y fo r 6m ; IM t ri am ci no lo ne ac et on id e (i m T A ) gr ou p (n =4 3) : i m T A 40 m g m on th ly f or 6m f ol lo w ed b y 40  m g on ce e ve ry 1. 5 m on th s fo r 1  ye ar ; PT g ro up ( n= 29 ): or al p re dn is on e 80 m g fo r 3  co ns ec ut iv e da ys ev er y 3m T he r es po ns e w as ta bu la te d m on th ly by m ea su ri ng th e pe rc en ta ge of t er m in al h ai r gr ow th . S er ia l ph ot og ra ph s w er e ta ke n at b as el in e an d af te r 3, 6 , a nd 12 m . In m os t pa ti en ts , ha ir g ro w th w as ev id en t at 3 –6 m . T he o ve ra ll re sp on se r at e w as s ig ni fic an tl y di ff er en t on ly be tw ee n th e D ex a nd im T A gr ou ps , i n ea ch cl in ic al s ub ty pe (m os tl y in m ul ti pl ex A A ). B ot h im T A a nd pu ls e th er ap y ar e ef fe ct iv e fo r A A w it h on ly m ild s id e ef fe ct s. A h ig h re la ps e ra te (e sp ec ia lly in A T a nd A U ) w as s ee n in t he D ex g ro up . 10 % o f PT gr ou p pa ti en ts : dy sm en or rh ea an d ab do m in al di sc om fo rt ; 41 % o f im T A gr ou p pa ti en ts : dy sm en or rh ea , ab do m in al di sc om fo rt , a nd w or se ni ng a cn e; 30 % o f D ex gr ou p pa ti en ts : w ei gh t ga in , ab do m in al di sc om fo rt , w ea kn es s, a nd m oo ni ng . 7 E xt en si ve a lo pe ci a ar ea ta t re at ed w it h be ta m et ha so ne or al m in i- pu ls e th er ap y: A n op en un co nt ro lle d st ud y B in od K . K ha it an O pe n, un co nt ro lle d 20 04 16 : 1 1M , 5F 14 –3 6 (m ea n  26 ) Se ve re A A A s in gl e do se o f 5  m g be ta m et ha so ne w as a dm in is te re d bi w ee kl y fo r at le as t 6m . M on th ly ex am in at io ns to a ss es s th e tr ea tm en t re sp on se a nd ad ve rs e ef fe ct s; pa ti en ts w er e fo llo w ed u p fo r 5– 8m f or r el ap se of t he d is ea se . 43 .7 % h ad an e xc el le nt re sp on se ( re la ps e oc cu rr ed in 1 pa ti en t af te r 2m ). 31 .2 % s ho w ed a go od r es po ns e, an d th er ap y w as co nt in ue d fo r an ot he r 2m in th es e pa ti en ts ( no re la ps e oc cu rr ed ). 4  pa ti en ts sh ow ed p oo r or n o re sp on se (n on -r es po nd er s ha d A U ). E ff ec ti ve th er ap eu ti c m od al it y fo r ex te ns iv e al op ec ia a re at a O nl y m ild si de e ff ec ts in cl ud in g m oo n fa ce , a cn ei fo rm er up ti on , w ei gh t ga in , an d ab do m en di sc om fo rt 10 Review | Dermatol Pract Concept. 2023;13(4):e2023255 8 E xt en si ve al op ec ia a re at a: no t ne ce ss ar ily re ca lc it ra nt t o th er ap y! D ee pa l D es hp an de Pr os pe ct iv e 20 11 15 : 1 0F , 5M 7 –4 5 E xt en si ve A A O ra l b et am et ha so ne m in i- pu ls e (0 .1 m g/ kg t w ic e a w ee k) al on g w it h 2– 5% to pi ca l m in ox id il (t w ic e a da y, 12  h ou rs a pa rt ) an d 1. 15 % a nt hr al in cr ea m ( da ily ). A ft er a ch ie vi ng a re sp on se , t he o ra l st er oi d w as t ap er ed st ep -w is e an d th en st op pe d, b ut t he to pi ca l c re am s w er e co nt in ue d as m ai nt en an ce th er ap y an d th en gr ad ua lly d ec re as ed . M on th ly ev al ua ti on by m ea su ri ng th e pe rc en t of te rm in al h ai r gr ow th . C os m et ic re sp on se : p ar ti al de ns e pa tc he s of t er m in al h ai r, ob vi at in g th e ne ed fo r a w ig /c ap ; no n- re sp on de rs o r fa ilu re : n o gr ow th or v el lu s ha ir. 80 % r es po nd ed . A m on g th e 20 % no n- re sp on de rs , 2 ha d A U an d on e ha d ex te nd ed A A w it h a du ra ti on of 8 –1 0 ye ar s. O ut o f 8 p at ie nt s w ith A U / A T: c os m et ic re sp on se =4 , pa rt ia l re sp on se =1 . C os m et ic re sp on se w as s ee n in a ll 4  pa tie nt s w ith O A a nd a ll 3  pa tie nt s w ith se ve re A A . T hi s co m bi na ti on th er ap y is a n ef fe ct iv e an d sa fe t re at m en t fo r pa ti en ts w it h tr ea tm en t- re si st an t an d ex te ns iv e A A . O nl y m ild , re ve rs ib le s id e ef fe ct s 9 E ffi ca cy a nd s af et y of o ra l m eg a pu ls e m et hy lp re dn is ol on e fo r se ve re t he ra py re si st an t al op ec ia ar ea ta G ha da A Pr os pe ct iv e ra nd om iz ed 20 12 42 : 2 0F , 22 M 12 ± 7 A U , A T, O A G ro up 1 : 1 5 m g/ kg M P, 3 d ay s ev er y 2w fo r 24 w ; G ro up 2 : 1 5 m g/ kg M P, 2 d ay s ev er y 3w fo r 24 w ; G ro up 3 : 1 5 m g/ kg M P, 3 d ay s ev er y 3w fo r 24 w Ph ot og ra ph y at b as el in e an d ev er y 2w . >7 5% r eg ro w th : ad eq ua te ; 2 5- 75 % : i na de qu at e. <2 5% : p oo r N ea rl y 30 % ha d an a de qu at e re sp on se , 2 0% in ad eq ua te , an d 50 % p oo r re sp on se a t 36 w ; no d if fe re nc e be tw ee n th e gr ou ps . O ld er ag e of in it ia ti on ha d a be tt er re sp on se . M P pu ls e th er ap y is re la ti ve ly ef fe ct iv e in se ve re A A b ut ha s a hi gh re la ps e ra te 95 % ex pe ri en ce d si de e ff ec ts . Fa ti gu e: 6 4% ; w ei gh t ga in : 45 % ; s te ro id - in du ce d ac ne : 35 .7 % ; s le ep di st ur ba nc es 33 % . O th er s: ir ri ta bi lit y, le th ar gy , st om ac h up se t, na us ea , fl us hi ng , cr am p, b on y pa in , a rt hr al gi a R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s Review | Dermatol Pract Concept. 2023;13(4):e2023255 11 10 C om bi ne d or al pu ls e an d to pi ca l co rt ic os te ro id th er ap y fo r se ve re al op ec ia a re at a in ch ild re n: a lo ng - te rm f ol lo w -u p st ud y Jo va n L al os ev ic R et ro sp ec ti ve 20 15 65 10 ± 5 >3 0% s ca lp in vo lv em en t A U , A T, P F A A O ra l de xa m et ha so ne (e qu al t o 5 m g/ kg p re dn is ol on e) on ce e ve ry 4 w ( 6, 9 , or 1 2 pu ls es ) pl us to pi ca l c lo be ta so l, 6 da ys a w ee k. A cc or di ng t o th e A A in ve st ig at io na l as se ss m en t gu id el in es , p ho to s w er e ev al ua te d by a bo ar d- ce rt ifi ed de rm at ol og is t at ba se lin e, 3 , 6 , 9 , an d 12 m . 83 % w it h PF A A ha d re gr ow th >7 5% , w hi le 35 % w it h se ve re A A h ad t he sa m e ex pe ri en ce . R el ap se : 1 6. 9% C om bi ne d to pi ca l a nd o ra l co rt ic os te ro id pu ls e is ef fe ct iv e fo r se ve re A A in c hi ld re n w it ho ut a ny se ve re s id e ef fe ct s N o se ri ou s si de ef fe ct s 11 A lt er at io n of s er um an d ti ss ue t um or ne cr os is f ac to r al ph a le ve ls : A po ss ib le m ec ha ni sm of a ct io n of o ra l pu ls e st er oi ds in th e tr ea tm en t of al op ec ia a re at a D al ia A bd el H al im Pr os pe ct iv e 20 18 40 28 ± 1 1 PF A A G ro up 1 : 6 0 m g/ da y of p re dn is ol on e, bi w ee kl y fo r 3m (a ge < 16 r ec ei ve d ha lf d os e) ; G ro up 2 : C on tr ol 3- m l b lo od sa m pl e an d 2- m m pu nc h bi op sy w er e as se ss ed fo r T N F- α le ve l be fo re a nd a ft er tr ea tm en t Se ru m a nd t is su e T N F- α le ve ls si gn ifi ca nt ly de cr ea se d af te r th e tr ea tm en t. Pr ed ni so lo ne pu ls e is a g oo d ch oi ce f or tr ea ti ng A A as it r ed uc es th e di se as e du ra ti on a nd T N F- α le ve l 12 T he e ff ec ti ve ne ss of o ra l m in i- pu ls e m et hy lp re dn is ol on e in t he t re at m en t of al op ec ia a re at a in V ie tn am Ph uo ng T ri nh T hi Pr os pe ct iv e 20 19 45 >1 6 N ot m en ti on ed O ra l m in i- pu ls e M P 16 m g/ da y bi w ee kl y fo r 6m N ot m en ti on ed 40 % h ad re gr ow th b y 3m , an d 82 % h ad re gr ow th b y 6m O ra l m in i- pu ls e of M P is a n ef fe ct iv e, s af e, an d lo w -p ri ce d tr ea tm en t fo r A A N o si de e ff ec ts 13 W ee kl y az at hi op ri ne pu ls e ve rs us be ta m et ha so ne or al m in i- pu ls e in th e tr ea tm en t of m od er at e- to -s ev er e al op ec ia a re at a Pr as ha nt G up ta O pe n- la be l, ra nd om iz ed co m pa ra ti ve 20 22 50 25 >1 0% s ca lp in vo lv em en t G ro up 1 : 3 00 m g w ee kl y az at hi op ri ne (W A P) f or 4 m ; G ro up 2 : 5 m g be ta m et ha so ne bi w ee kl y fo r 4m SA LT s co re ; av er ag e pe rc en ta ge of s ca lp h ai r re gr ow th ; ev al ua ti on s at ba se lin e an d 4  &  9 m 44 % r eg ro w th in th e W A P gr ou p an d 71 % in t he be ta m et ha so ne gr ou p; 5 0% in W A P an d 62 % in be ta m et ha so ne gr ou p ha d co m pl et e ha ir gr ow th a t 9m W A P an d or al - m in i- pu ls e of be ta m et ha so ne ar e bo th ef fe ct iv e in t re at in g A A , w it h no pr io ri ty in h ai r gr ow th , t ho ug h be ta m et ha so ne pu ls e ha s m or e si de e ff ec ts M oo n fa ce , ac ne , r efl ux , an d w ei gh t ga in w er e se en in st er oi d gr ou p, w hi le o nl y tr an si en t na us ea w as r ep or te d w it h W A P 12 Review | Dermatol Pract Concept. 2023;13(4):e2023255 14 O ra l p ul se be ta m et ha so ne , m et ho tr ex at e, an d co m bi na ti on th er ap y to tr ea t se ve re al op ec ia a re at a: a ra nd om iz ed , do ub le -b lin d, pl ac eb o- co nt ro lle d, cl in ic al t ri al A li A si lia n R an do m iz ed , do ub le -b lin d, pl ac eb o- co nt ro lle d 20 20 36 27 >5 0% s ca lp in vo lv em en t G ro up 1 : 3 m g be ta m et ha so ne w ee kl y fo r 6m ; G ro up 2 : 1 5 m g M T X w ee kl y fo r 6m ; G ro up 3 : 3 m g be ta m et ha so ne +1 5 m g M T X w ee kl y fo r 6m SA LT , V A S, & ph ot og ra ph y at ba se lin e an d 3, 6 , & 9 m Si gn ifi ca nt im pr ov em en t in SA LT , V A S, a nd ph ot og ra ph ic sc or es in a ll at 3 , 6, & 9 m ; A t 9m : a 4 3% SA LT s co re de cr ea se in G ro up 3 , 2 6% in G ro up 1 , an d 23 % in G ro up 2 , & G ro up 3 s ho w ed si gn ifi ca nt ly m or e V A S/ ph ot og ra ph ic sc or es im pr ov em en t M T X & be ta m et ha so ne al on e or in co m bi na ti on ar e ef fe ct iv e in tr ea ti ng s ev er e A A , t ho ug h be ta m et ha so ne or be ta m et ha so ne + M T X a re m or e ef fe ct iv e th an M T X al on e 1 pa ti en t in M T X g ro up an d 1 in co m bi na ti on gr ou p de ve lo pe d ga st ro in te st in al sy m pt om s, re lie ve d w it h da ily f ol ic a ci d 15 A lo pe ci a ar ea ta an d de xa m et ha so ne m in i- pu ls e th er ap y, a pr os pe ct iv e co ho rt : r ea l w or ld ev id en ce a nd fa ct or s re la te d to su cc es sf ul r es po ns e M an ue l Sá nc he z- D ía z Pr os pe ct iv e co ho rt 20 22 40 32 >2 0% S A LT sc or e O ra l D ex a t a m ea n do se o f 2. 72 m g/ da y bi w ee kl y fo r 12 m ; 2 7% o f pa ti en ts r ec ei ve d or al m in ox id il 0. 5- 1 m g/ da y fo r fe m al es , 2. 5- 5 m g/ da y fo r m al es SA LT a t ba se lin e, 3, 6 , 9 , 1 2m 50 % d ec re as e in S A LT s co re in ha lf th e pa tie nt s by 9 m . S ig ni fic an t de cr ea se in S A LT sc or e in o ve ra ll as se ss m en t. N o SA LT s co re de cr ea se in o ns et ag e < 15 y O ra l m in i- pu ls e of D ex is e ff ec ti ve in tr ea ti ng A A b ut in ef fe ct iv e fo r on se t ag e <1 5y or in t ho se w it h hy po th yr oi di sm W ei gh t ga in in 3 5% ; os te op en ia o r os te op or os is in 12 .5 % ; g ly ce m ic di so rd er in 5% ; a cn ei fo rm ra sh , h ir su ti sm , an xi et y, a nd in so m ni a in le ss th an 5 % 16 T he e ff ec t of m et hy lp re dn is ol on e pu ls e- th er ap y pl us or al c yc lo sp or in e in t he t re at m en t of al op ec ia t ot al is a nd un iv er sa lis M oh am m ad Sh ah ee di - D ad ra s Pr os pe ct iv e 20 08 18 : 9 F, 9M 20 .6 ± 4. 8 (r an ge 14 –2 9) A T, A U 50 0 m g do se o f IV M P m on th ly fo r th re e da ys + or al c yc lo sp or in e (2 .5  m g/ kg /d ay ) fo r 5– 8m . A de qu at e= h ai r re gr ow th ≥ 70 % an d in ad eq ua te = re gr ow th < 70 % . To ta l o f 6  p at ie nt s sh ow ed a de qu at e re sp on se = 33 % (3 M a nd 3 F/ 3 in pa tie nt s< 20 y an d 3 in p at ie nt s> 20 y/ 2 w ith a h is to ry of a to py , 3/ 6  w ith A T a nd 3/ 12  w ith  A U ) T hi s th er ap y ca n be be ne fic ia l i n so m e pa ti en ts w it h re si st an t an d se ve re A A . M ild hy pe rt en si on (n =1 ), hy pe rl ip id em ia (n =2 ), an d m ild ac ne ( n= 1) R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s Review | Dermatol Pract Concept. 2023;13(4):e2023255 13 17 E ar ly in te rv en ti on w it h hi gh -d os e st er oi d pu ls e th er ap y pr ol on gs di se as e- fr ee in te rv al o f se ve re al op ec ia a re at a: a re tr os pe ct iv e st ud y C ha o- C hu n Y an g R et ro sp ec ti ve 20 13 85 : 3 9M , 46 F 28 .4 (r an ge 4– 60 ) A T, A U , A O ; al op ec ia >5 0% 2. 5– 10 m g/ kg /d ay of o ra l p re dn is ol on e or I V M P fo r 3  co ns ec ut iv e da ys Ph ot og ra ph y at ba se lin e an d en d of t re at m en t; sa ti sf ac to ry re sp on se : h ai r re gr ow th m or e th an 7 5% ; s co ri ng ba se d on t he A lo pe ci a A re at a In ve st ig at io na l A ss es sm en t G ui de lin es >7 5% r eg ro w th in 5 1% o f pa ti en ts . M or e sa ti sf ac to ry re su lt s in 5 0- 70 % b al dn es s ra th er t ha n A U or A T ; b et te r re sp on se w he n tr ea te d du ri ng 1 st ye ar o f di se as e IV a nd o ra l pu ls e of st er oi ds a re sa fe o pt io ns in tr ea ti ng s ev er e A A , s ho w in g eq ua l e ffi ca cy ; in it ia ti on ti m e pl ay s an im po rt an t ro le in t he e ffi ca cy ra te M ild a nd tr an si en t si de ef fe ct s in b ot h gr ou ps : fl us hi ng , hy pe rg ly ce m ia , in cr ea se d ap pe ti te , in so m ni a, & pa lp it at io ns ; n o lo ng -t er m s id e ef fe ct 18 Pu ls e co rt ic os te ro id th er ap y fo r al op ec ia a re at a: lo ng -t er m o ut co m e af te r 10 y ea rs D . St au m on t- Sa llé R et ro sp ec ti ve 20 12 30 : 1 0M , 20 F 27 .4 (r an ge 5– 63 ) A T, A U , A O , PF A A , a nd 30 –5 0% A A 50 0 m g– 1 gr (o r 10 –2 0 m g/ kg ) IV M P fo r 3  co ns ec ut iv e da ys /m f or 3 m Ph on e in te rv ie w s; on lin e su pp le m en ta ry qu es ti on na ir e (w w w . k ar ge r.c om / do i/1 0. 11 59 /0 00 34 15 23 ); cl in ic al ex am in at io ns ; D L Q I; a ll w er e do ne 1 0 ye ar s af te r tr ea tm en t M or e th an h al f st ill h ad s ev er e A A ; t ho se w it h in it ia l re sp on se t o th er ap y du ri ng fir st 6 m h ad m ild er d is ea se in n ex t 10 y vs . no n- re sp on de rs Po or lo ng -t er m ef fic ac y of co rt ic os te ro id pu ls e in se ve re A A ; re co m m en de d ot he r ki nd s of tr ea tm en t fo r th is g ro up o f pa ti en ts 22 o ut o f 30  e xp er ie nc ed si de e ff ec ts : ti re dn es s, he ad ac he , flu sh in g, n au se a an d vo m it in g, an d tr an si en t hy pe rg ly ce m ia 19 Pu ls e co rt ic os te ro id th er ap y fo r al op ec ia ar ea ta in c hi ld re n: a re tr os pe ct iv e st ud y R iv ka Fr ie dl an d R et ro sp ec ti ve st ud y 20 13 24 : 8 M , 16 F 8 ± 4. 6 A T, A U , A O , PF A A 8– 10 m g/ kg I V M P fo r 3 co ns ec ut iv e da ys , m on th ly M on th ly c lin ic al ex am in at io n 38 % c om pl et e re sp on se , 2 9% pa rt ia l r es po ns e, 33 % n o  re sp on se , 81 % r el ap se ; G oo d pr og no st ic fa ct or s: a ge <1 0y & d is ea se in it ia ti on < 6m M P pu ls e is e ff ec ti ve in c hi ld re n w it h PF A A , w it h a hi gh re la ps e ra te b ut m in im al s id e ef fe ct s O nl y 3 pa ti en ts ha d ve ry m ild tr an si en t si de ef fe ct s R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s 14 Review | Dermatol Pract Concept. 2023;13(4):e2023255 20 C om pa ri so n of h ig h- do se co rt ic os te ro id pu ls e th er ap y an d co m bi na ti on th er ap y us in g or al c yc lo sp or in e w it h lo w -d os e co rt ic os te ro id in se ve re a lo pe ci a ar ea ta In K w on Y eo R et ro sp ec ti ve 20 15 14 2: 79 M , 6 3F 8~ 80 y ea rs (m ea n, 3 5. 1 ye ar s) PF A A , A T, A U G ro up A : I V -p um p M P 1 g/ da y, tw ic e a da y fo r 3  co ns ec ut iv e da ys fo r ad ul ts an d 10  m g/ kg / da y w ee kl y fo r 3w fo r ch ild re n + or al M P 30 m g/ da y fo r 3 da ys ;G ro up B : or al c yc lo sp or in e (2 .5  m g/ kg /d ay + M P (2 .5 –5 m g/ da y) fo r 4m H ai r re gr ow th w as e va lu at ed o n a sc al e of 0 -1 00 % . G oo d re sp on se : re gr ow th o f >5 0% of t he le si on su rf ac e G oo d re sp on se ra te w as h ig he r in G ro up A . Pa ti en ts in G ro up A w it h PF A A an d th os e w it h di se as e du ra ti on ≤3 m h ad b et te r re sp on se , w he re as in G ro up B , t he d is ea se du ra ti on /t yp e di d no t af fe ct t he re sp on se . P F = be tt er r es po ns e th an t he o th er s. Pu ls e co rt ic os te ro id th er ap y is a b et te r tr ea tm en t op ti on t ha n co m bi na ti on th er ap y in pa ti en ts w it h se ve re A A a nd PF A A G ro up A : ga st ro in te st in al di sc om fo rt , he ad ac he , di zz in es s, f ac ia l flu sh in g, a nd pa lp it at io n; G ro up B : ga st ro in te st in al di sc om fo rt , he ad ac he , a nd hy pe rt en si on 21 Pu ls e co rt ic os te ro id th er ap y fo r al op ec ia ar ea ta : s tu dy o f 13 9 pa ti en ts Ta ke sh i N ak aj im a R et ro sp ec ti ve 20 07 13 9: 43 M , 9 6F 15 –7 3 (m ea n ag e: 3 5. 1) R ec en t- on se t ex te ns iv e A A 50 0 m g IV M P ov er a n ho ur o n 3 co ns ec ut iv e da ys E va lu at io n of ha ir r eg ro w th w as m ad e m os tl y by t he a tt en di ng in ve st ig at or s (8 4. 2% ) an d by se ri al p ho to s af te r 6m R ec en t- on se t di se as e lin ke d w it h m or e re gr ow th ; pa ti en ts w it h re ce nt -o ns et an d le ss s ev er e di se as e (< 50 % ) re sp on de d be tt er th an p at ie nt s w it h re ce nt - on se t an d 10 0% ha ir lo ss ; n on e of t he p at ie nt s w it h 10 0% h ai r lo ss a nd > 6m of A A h is to ry re sp on de d; re la ps e in 16 .7 % o f go od re sp on de rs (n =6 6) d ur in g 15 .3 m m ea n fo llo w -u p T hi s th er ap y is e ff ec ti ve a nd pr om is in g in pa ti en ts w it h le ss s ev er e A A (< 50 % ) an d in pa ti en ts w it h re ce nt -o ns et o f A A , w it h on ly m ild a dv er se ef fe ct s of co rt ic os te ro id s O nl y m ild & t ra ns ie nt si de e ff ec ts : pa lp it at io ns , he ad ac he , l ow - gr ad e fe ve r, an d in so m ni a R ef er en ce N o . T it le Fi rs t au th o r T ri al t yp e Ye ar Pa ti en ts (N o ., se x) A g e (y ) A lo p ec ia ty p e Tr ea tm en t A ss es sm en t O u tc o m e C o n cl u si o n Si d e ef fe ct s Review | Dermatol Pract Concept. 2023;13(4):e2023255 15 22 M ul ti pl e co ur se s of pu ls e co rt ic os te ro id th er ap y fo r al op ec ia a re at a Ta ka sh i Y os hi m as u 20 16 55 :1 3M , 41 F 16 -6 4 A A IV M P 50 0 m g/ da y w as in fu se d ov er 2 h on 3 c on se cu ti ve da ys ( at le as t on e co ur se o f th er ap y up t o th re e co ur se s) T he d ev el op m en t of v el lu s ha ir : go od r es po ns e to s ho rt -t er m th er ap y; g oo d lo ng -t er m re sp on se ( 6m af te r th e la st pu ls e) : > 75 % ha ir r eg ro w th o n al op ec ia le si on s Fe w er c ou rs es of P T r eq ui re d fo r ve llu s ha ir to d ev el op in pa tie nt s w ith <5 0% h ai r lo ss an d <6 m d is ea se on se t; go od s ho rt - te rm a nd lo ng - te rm r es po ns e ra te (1 00 % ) i n pa tie nt s w ith <5 0% h ai r lo ss re ga rd le ss o f di se as e du ra tio n; no r es po ns e in th os e w ith 1 00 % ha ir lo ss fo r >6 m T hi s tr ea tm en t ca n be co ns id er ed an e ff ec ti ve m od al it y in tr ea ti ng r ec en t- on se t se ve re A A a nd in pa ti en ts w it h le ss e xt en si ve di se as e T ra ns ie nt m ild si de e ff ec ts in 5 p at ie nt s: m us cu la r pa in in e xt re m it ie s, fin ge r nu m bn es s, le g ed em a, an d st om ac h di sc om fo rt ; tr ea tm en t w as st op pe d 23 H ig h- do se p ul se co rt ic os te ro id th er ap y in t he tr ea tm en t of s ev er e al op ec ia a re at a Si m on e Se it er M on oc en te r, pr os pe ct iv e 20 00 30 14 –5 6 (m ea n 31 ) PF A A , O A , A T, A U IV M P (8 m g/ kg b od y w ei gh t) ov er 3 0 m in o n 3 co ns ec ut iv e da ys a t m on th ly in te rv al s R e- ex am in at io n at 1 , 3 , 6 , & 1 2m af te r co m pl et io n of a 3 -c ou rs e tr ea tm en t; s er ia l ph ot og ra ph s co m pa re d w it h th e pr et re at m en t st at us b y 2  in de pe nd en t in ve st ig at or s 40 % o f th e pa ti en ts h ad >5 0% r eg ro w th an d 13 % h ad 1 0- 50 % r eg ro w th ; 67 % o f pa ti en ts w it h PF A A ha d >5 0% h ai r gr ow th , w hi le no ne w it h O A / A T /A U s ho w ed >5 0% h ai r gr ow th IV M P is a s af e an d ef fe ct iv e tr ea tm en t op ti on f or P F A A , w hi le it is le ss e ff ec ti ve in pa ti en ts w it h A T, A U , o r O A Tr an si en t m ild si de e ff ec ts in cl ud ed he ad ac he (n = 5 ), fa tig ue (n = 3 ), pa lp ita tio ns (n = 2 ), an d na us ea (n = 1 ). 24 In te re st o f hi gh -d os e pu ls e co rt ic os te ro id th er ap y co m bi ne d w it h m et ho tr ex at e fo r se ve re al op ec ia a re at a: a re tr os pe ct iv e ca se se ri es C at he ri ne D ro it co ur ta R et ro sp ec ti ve ca se s er ie s 20 12 20 : 1 2F , 8M 14 –5 7 (m ea n 33 ) M ul ti fo ca l A A , A T 50 0 m g do se o f IV M P in 3 c on se cu ti ve do se s m on th ly fo r at le as t 3m in co m bi na ti on w it h M T X ( 12 .5 m g/ w ee k up t o 25 m g/ w ee k ov er t he n ex t 6m ) at t he e nd o f th e se co nd p ul se re gi m en M on th ly as se ss m en ts du ri ng t he fi rs t 3m of t re at m en t, an d th en e ve ry 3 m b y a de rm at ol og is t; se ri al p ho to gr ap hs w er e ta ke n du ri ng vi si ts ; h ai r gr ow th w as e va lu at ed o n a sc al e of 0 –1 00 % T he m ea n pe ri od of h ai r re gr ow th in it ia ti on w as 2. 5m . B y 18 m , m ul ti fo ca l A A re sp on de d be tt er th an A T. P at ie nt s w it h >1 2m di se as e du ra ti on re sp on de d m or e vs . p at ie nt s w it h <1 2m T hi s tr ea tm en t ca n be co ns id er ed ef fe ct iv e an d w el l t ol er at ed in t re at in g se ve re A A , th ou gh a lo ng er fo llo w -u p is re co m m en de d. N o si de e ff ec ts o f co rt ic os te ro id s w er e re co rd ed . O nl y 3 pa tie nt s ha d M T X - re la te d si de ef fe ct s (n au se a in 2 a nd ne ut ro pe ni a in  1 ) an d st op pe d tr ea tm en t a ft er 5  m on th s. A A = A lo pe ci a A re at a; A T = A lo pe ci a To ta lis ; A U = A lo pe ci a U ni ve rs al is ; F = Fe m al e; I M = I nt ra m us cu la r; I V = I nt ra ve no us ; M = M al e; m = m on th s; M P = M et hy lp re dn is ol on e; M T X = M et ho tr ex at e; w = w ee ks ; O A = O ph ia si s A lo pe ci a; PF = P lu ri fo ca l; PT = P ul se T he ra py ; T N F- α = Tu m or N ec ro si s Fa ct or -a lp ha ; W A P = W ee kl y A za th io pr in e; S A LT = S ev er it y A lo pe ci a To ol ; V A S = V is ua l A na lo gu e Sc al e; D ex = D ex am et ha so ne ; D L Q I = D er m at ol og y L if e Q ua lit y In de x. 16 Review | Dermatol Pract Concept. 2023;13(4):e2023255 References 1. FVillasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Der- matol. 2015;8:397-403. DOI: 10.2147/CCID.S53985. PMID: 26244028. PMCID: PMC4521674. 2. Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: Disease characteris- tics, clinical evaluation, and new perspectives on pathogene- sis. J Am Acad Dermatol. 2018;78(1):1-12. DOI: 10.1016/j .jaad.2017.04.1141. PMID: 29241771. 3. Price VH. Alopecia areata: clinical aspects. J Invest Dermatol. 1991;96(5):68S. DOI: 10.1111/1523-1747.ep12471869. PMID: 2022874. 4. Ruiz‐Doblado S, Carrizosa A, García‐Hernández MJ. Alopecia areata: psychiatric comorbidity and adjustment to illness. Int J Dermatol. 2003;42(6):434-437. DOI: 10.1046/j.1365-4362 .2003.01340.x. PMID: 12786868. 5. Koo JY, Shellow WV, Hallman CP, Edwards JE. Alopecia areata and increased prevalence of psychiatric disorders. Int J Dermatol. 1994;33(12):849-850. DOI: 10.1111/j.1365-4362.1994.tb01018 .x. PMID: 7883407. 6. Sladden MJ, MacDonald Hull SP, Wood ML, Hutchinson PE, Messenger AG. Alopecia areata: the need for guidelines and evi- dence‐based dermatology. Br J Dermatol. 2005;152(5):1086-1087. DOI: 10.1111/j.1365-2133.2005.06578.x. PMID: 15888188. 7. Fukumoto T, Fukumoto R, Magno E, Oka M, Nishigori C, Horita N. Treatments for alopecia areata: A systematic review and network meta‐analysis. Dermatol Ther. 2021;34(3):e14916. DOI: 10.1111/dth.14916. PMID: 33631058. 8. Alsantali A. Alopecia areata: a new treatment plan. Clin Cos- met Investig Dermatol. 2011;4:107-115. DOI: 10.2147/CCID .S22767. PMID: 21833161. PMCID: PMC3149478. 9. Barton VR, Toussi A, Awasthi S, Kiuru M. Treatment of pedi- atric alopecia areata: A systematic review. J Am Acad Derma- tol. 2022;86(6):1318-1334. DOI: 10.1016/j.jaad.2021.04.077. PMID: 33940103. PMCID: PMC8556406. 10. Burton J, Shuster S. Large doses of glucocorticoid in the treat- ment of alopecia areata. Acta Derm Venereol. 1975;55(6): 493-496. PMID: 55045. 11. Kassira S, Korta DZ, Chapman LW, Dann F. Review of treat- ment for alopecia totalis and alopecia universalis. International Int J Dermatol. 2017;56(8):801-810. DOI: 10.1111/ijd.13612 . PMID: 28378336. 12. Lintzeri DA, Constantinou A, Hillmann K, Ghoreschi K, Vogt A, Blume‐Peytavi U. Alopecia areata–Current understanding and management. J Dtsch Dermatol Ges. 2022;20(1):59-90. DOI: 10.1111/ddg.14689. PMID: 35040577. 13. Nakajima T, Inui S, Itami S. Pulse corticosteroid therapy for alope- cia areata: study of 139 patients. Dermatology. 2007;215(4):320- 324. DOI: 10.1159/000107626. PMID: 17911990. 14. Yoshimasu T, Kanazawa N, Yamamoto Y, Furukawa F. Multi- ple courses of pulse corticosteroid therapy for alopecia areata. J Dermatol. 2016;43(9):1075-1077. DOI: 10.1111/1346-8138 .13388. PMID: 27095016. 15. Seiter S, Ugurel S, Tilgen W, Reinhold U. High-dose pulse cor- ticosteroid therapy in the treatment of severe alopecia areata. Dermatology. 2001;202(3):230-234. DOI: 10.1159/000051642 . PMID: 11385229. 16. Friedli A, Labarthe M-P, Engelhardt E, Feldmann R, Salomon D, Saurat J-H. Pulse methylprednisolone therapy for severe al- opecia areata: an open prospective study of 45 patients. J Am Acad Dermatol. 1998;39(4 Pt 1):597-602. DOI: 10.1016/s0190 -9622(98)70009-x. PMID: 9777767. 17. Yang CC, Lee CT, Hsu CK, et al. Early intervention with high- dose steroid pulse therapy prolongs disease-free interval of severe alopecia areata: a retrospective study. Ann Dermatol. 2013;25(4):471-474. DOI: 10.5021/ad.2013.25.4.471. PMID: 24371395. PMCID: PMC3870216. 18. Staumont-Sallé D, Vonarx M, Lengrand F, Segard M, Delaporte E. Pulse corticosteroid therapy for alopecia areata: long-term outcome after 10 years. Dermatology. 2012;225(1):81-87. DOI: 10.1159/000341523. PMID: 22964518. 19. Friedland R, Tal R, Lapidoth M, Zvulunov A, Amitai DB. Pulse corticosteroid therapy for alopecia areata in children: a retrospective study. Dermatology. 2013;227(1):37-44. DOI: 10.1159/000351559. PMID: 24008264. 20. Shaheedi-Dadras M, Karami A, Mollaei F, Moravvej H, Malekzad F. The effect of methylprednisolone pulse-therapy plus oral cyclosporine in the treatment of alopecia totalis and univer- salis. Arch Iran Med. 2008;11(1):90-93. PMID: 18154427. 21. Yeo IK, Ko EJ, No YA, et al. Comparison of High-Dose Corti- costeroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alope- cia Areata. Ann Dermatol. 2015;27(6):676-681. DOI: 10.5021 /ad.2015.27.6.676. PMID: 26719635. PMCID: PMC4695418. 22. Droitcourt C, Milpied B, Ezzedine K, et al. Interest of high-dose pulse corticosteroid therapy combined with methotrexate for severe alo- pecia areata: a retrospective case series. Dermatology. 2012;224(4): 369-373. DOI: 10.1159/000339341. PMID: 22738995. 23. Bin Saif GA, Al-Khawajah MM, Al-Otaibi HM, et al. Efficacy and safety of oral mega pulse methylprednisolone for severe ther- apy resistant Alopecia areata. Saudi Med J. 2012;33(3):284-291. PMID: 22426909. 24. Thi PT, Lan AT, Ha PTT, Vet al. The Effectiveness of Oral Mini- Pulse Methylprednisolonein - the Treatment of Alopecia Areata in Vietnam. Open Access Maced J Med Sci. 2019;7(2):291-292. DOI: 10.3889/oamjms.2019.097. PMID: 30745983. PMCID: PMC6364712. 25. Sánchez-Díaz M, Montero-Vilchez T, Bueno-Rodriguez A, Molina-Leyva A, Arias-Santiago S. Alopecia Areata and Dexa- methasone Mini-Pulse Therapy, A Prospective Cohort: Real World Evidence and Factors Related to Successful Response. J Clin Med. 2022;11(6):1694. DOI: 10.3390/jcm11061694. PMID: 35330017. PMCID: PMC8949115. 26. Sharma VK, Gupta S. Twice weekly 5 mg dexamethasone oral pulse in the treatment of extensive alopecia areata. J Dermatol. 1999;26(9):562-565. DOI: 10.1111/j.1346-8138 .1999.tb02049.x. PMID: 10535249. 27. Lalosevic J, Gajic‐Veljic M, Bonaci‐Nikolic B, Nikolic M. Com- bined oral pulse and topical corticosteroid therapy for severe alope- cia areata in children: a long‐term follow‐up study. Dermatol Ther. 2015;28(5):309-317. DOI: 10.1111/dth.12255. PMID: 26179196. 28. Sharma VK. Pulsed administration of corticosteroids in the treat- ment of alopecia areata. Int J Dermatol. 1996;35(2):133-136. DOI: 10.1111/j.1365-4362.1996.tb03281.x. PMID: 8850047. 29. Kar BR, Handa S, Dogra S, Kumar B. Placebo-controlled oral pulse prednisolone therapy in alopecia areata. J Am Review | Dermatol Pract Concept. 2023;13(4):e2023255 17 Acad Dermatol. 2005b;52(2):287-290. DOI: 10.1016/j .jaad.2004.10.873. PMID: 15692475. 30. Tsai Y-M, Chen W, Hsu M-L, Lin T-K. High-dose steroid pulse therapy for the treatment of severe alopecia areata. J Formos Med Assoc. 2002;101(3):223-226. PMID: 12051021. 31. Abdel Halim D, Abu Zeid OM, Rashed L, Saleh MA. Alteration of serum and tissue tumor necrosis factor alpha levels: A possible mechanism of action of oral pulse steroids in the treatment of al- opecia areata. J Cosmet Dermatol. 2019;18(4):1128-1132. DOI: 10.1111/jocd.12795. PMID: 30294905. 32. Kurosawa M, Nakagawa S, Mizuashi M, et al. A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata. Derma- tology. 2006;212(4):361-365. DOI: 10.1159/000092287. PMID: 16707886. 33. BinodK K, Rashmi M, KaushalK V. Studies-Extensive alopecia areata treated with betamethasone oral mini-pulse therapy: An open uncontrolled study. Indian J Dermatol Venereol Leprol. 2004;70(6):350-353. PMID: 17642661. 34. Gupta P, Verma KK, Khandpur S, Bhari N. Weekly azathio- prine pulse versus betamethasone oral mini-pulse in the treat- ment of moderate-to-severe alopecia areata. Indian J Dermatol. 2019;64(4):292-298. DOI: 10.4103/ijd.IJD_481_16. PMID: 31516138. PMCID: PMC6714202. 35. Asilian A, Fatemi F, Ganjei Z, Siadat AH, Mohaghegh F, Siavash M. Oral Pulse Betamethasone, Methotrexate, and Combi- nation Therapy to Treat Severe Alopecia Areata: A Randomized, Double-blind, Placebo-controlled, Clinical Trial. Iran J Pharm Res. 2021;20(1):267-273. DOI: 10.22037/ijpr.2020.113868.14536. PMID: 34400956. PMCID: PMC8170764. 36. Deshpande D, Dhurat R, Saraogi P, Mishra S, Nayak C. Exten- sive alopecia areata: not necessarily recalcitrant to therapy! I Int J Trichology. 2011;3(2):80-83. DOI: 10.4103/0974-7753.90807. PMID: 22223966. PMCID: PMC3250026.