10.5826/dpc.1304a255
Introduction: Alopecia areata (AA) is a non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body hair. Steroid pulse therapy outcomes for AA vary.
Objective: 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: 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 type: improved outcomes and decreased relapse were linked with recent onset (&lt;6 months), younger age (&lt;10 years), and the multifocal type. 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.
 Conclusion: Pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone seems to be the most effective agent (followed by intramuscular 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. Pulses of prednisolone and methylprednisolone 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.
text/xml
2160-9381
3113
en
Najmeh Ahramiyanpour
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
pulse therapy
The Efficacy and Adverse Effects of Corticosteroid Pulse Therapy in Alopecia Areata
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2023-10-31
2022-12-24
2023-10-31
2024-01-16
e2023255
Dermatol Pract Concept
Introduction: Alopecia areata (AA) is a non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body hair. Steroid pulse therapy outcomes for AA vary.
Objective: 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: 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 type: improved outcomes and decreased relapse were linked with recent onset (&lt;6 months), younger age (&lt;10 years), and the multifocal type. 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.
 Conclusion: Pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone seems to be the most effective agent (followed by intramuscular 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. Pulses of prednisolone and methylprednisolone 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.
Najmeh Ahramiyanpour
2023/10/31
10.5826/dpc.1304a255
e2023255
Department of Dermatology, Afzalipoor Hospital, Kerman University of Medical Sciences, Kerman, Iran
2160-9381
pulse therapy
en
e2023255
Deshpande D, Dhurat R, Saraogi P, Mishra S, Nayak C. Extensive alopecia areata: not necessarily recalcitrant to therapy! International Journal of Trichology. 2011;3(2):80.
The Efficacy and Adverse Effects of Corticosteroid Pulse Therapy in Alopecia Areata
https://dpcj.org/index.php/dpc/article/download/3113/2395
  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




  ABSTRACT             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.




Review | Dermatol Pract Concept. 2023;13(4):e2023255                                                                                    1
                      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.




Introduction                                                        Methods
Alopecia areata (AA) is a common, non-scarring, autoim-             A literature search was performed on August 29, 2022, to re-
mune hair loss disorder with an estimated lifetime risk of ap-      view the efficacy of pulse steroid therapy in patients with AA.
proximately 2% [1-3]. Genetics and environment both play            The terms "pulse steroid therapy AND alopecia areata" and
essential roles in the pathology of the disease, as almost 20%      "pulse corticosteroid therapy AND alopecia areata" were
of the patients have a positive family history. In addition to      searched on PubMed and Google Scholar. All types of sci-
the suggested autoreactive T-cell-mediated pathogenesis of          entific publications matching the keywords were transferred
the disease, psychological stress may also be heavily ­involved.    to EndNote version 8 (Clarivate Analytics), and duplicates
The severity of AA ranges from small round hairless patches         were removed. Two authors reviewed the articles inde-
to the total loss of scalp or body hair (alopecia totalis/alo-      pendently based on their titles and abstracts. Subsequently,
pecia universalis), which can cause devastating psychosocial        a third author performed an eligibility assessment of the full
effects, such as major depression, anxiety, mood disorders,         texts based on the inclusion and exclusion criteria. Inclusion
and social phobia [4-6].                                            criteria consisted of relevant full-text, English-written clini-
    Implementing and evaluating treatment protocols for             cal trials. All case reports, editorials, conferences, commen-
AA is challenging due to the disease's uncertain patho-             taries, letters to editors, and review articles were excluded
genesis and unpredictable remission rates [6]. The treat-           from the study. Poor quality trials were also excluded based
ment should also cover the patient's psychological needs,           on a Jadad scale of less than 3. In case of any conflicts, the
making management more difficult. Topical, intralesional,           senior author made the final decision and responded to each
and systemic agents have been used for AA, but the ef-              of the points raised in the screenings. After screening the
ficacy of the treatments varies widely [6-9]. One of the            data, a total of 24 articles were identified and included in
suggested treatments is corticosteroid therapy. Topical             this study. Then, two authors independently extracted and
and intra-lesional corticosteroids are effective and well           recorded the data in an Excel 2016 spreadsheet (Microsoft).
tolerated in patients with mild to moderate AA [4,6,10].            The extracted features included the title, publication year,
However, managing severe AA cases (alopecia universalis,            author names, year, sample size, mean age, type of treatment,
totalis, and ophiasis) is more challenging [11]. Systemic           assessments, outcomes, and side effects.
corticosteroids are usually effective in these patients and
can be administered via the intravenous, oral, or intramus-
                                                                    Results
cular route [12].
                                                                    The Efficacy of Intravenous Corticosteroid
Objectives                                                          Pulse in Severe AA
                                                                    The efficacy of intravenous steroid pulse was studied in ten
In 1975, Burton and Shuster introduced corticosteroid pulse         articles. Among them, seven examined intravenous meth-
therapy for treating patients with AA to reduce the possi-          ylprednisolone, two assessed the combination therapy of
ble side effects of long-term use of corticosteroids and to         methylprednisolone and cyclosporine, and one evaluated
increase the treatment's effectiveness. Since then, many sci-       the combination of intravenous methylprednisolone and
entists have aimed to optimize this type of therapy [10]. As        methotrexate.
steroid pulse therapy regimens and outcomes for AA vary,
this study aimed to review the related literature regarding         Intravenous Methylprednisolone
the efficacy, relapse rates, side effects, and prognostic factors   Intravenous Methylprednisolone in Adults
associated with the response to different pulse corticosteroid      Intravenous methylprednisolone was introduced to decrease
treatments.                                                         the side effects of prolonged use of oral corticosteroids in



2                                                                              Review | Dermatol Pract Concept. 2023;13(4):e2023255
AA. Four studies evaluated the efficiency of intravenous            consecutive doses monthly in addition to oral cyclosporine
­methylprednisolone pulse therapy in a total of 224 adults with     (2.5 mg/kg/day) for a treatment duration of 5–8 months. Ac-
severe AA. They noticed that patients with recent onset of          cording to the results, only a third of the patients showed
the disease (<6 months) responded better. Most patients with        a hair regrowth rate of more than 70%. Patients with nail
plurifocal AA or scalp involvement <50% showed significant          pitting or a positive history of atopy responded poorly. They
hair growth (mostly complete remission), while none with            suggested that this treatment can be effective in treating some
alopecia universalis, totalis, or ophiasis showed more than         patients with severe AA with mild side effects [20]. Results
50% hair growth, even after six months of follow-up. They           of another study comparing the efficacy of high-dose corti-
concluded that intravenous methylprednisolone is a safe and         costeroid pulse therapy and combination therapy of cyclo-
promising treatment in adults with plurifocal or recent-onset       sporine plus low-dose corticosteroid in severe AA revealed
AA, with only mild adverse effects, while it is less effective in   that patients who received a high dose of intravenous meth-
patients with alopecia universalis, totalis, or ophiasis [13-16].   ylprednisolone experienced more than 50% improvement
In another study, Chao-Chun Yang et al reviewed 85 ­patients        during six months of follow-up. Notably, 20%–26% relapse
with severe AA treated with oral prednisolone pulse or              occurred in both groups without any significant difference.
­intravenous methylprednisolone pulse. They noticed that the        A profound positive correlation between a recent disease
two treatments were equally effective in treating severe AA,        onset and a desirable response was seen, such that 85% of
as more than half of the patients experienced nearly 75%            patients with a disease onset of fewer than three months
hair regrowth. Better results and less relapse were reported        showed significant hair regrowth. Among all types of severe
with earlier initiation of treatment, especially during the first   alopecia, plurifocal AA showed a better improvement than
year of disease onset. There was no significant difference in       any other kind. This study indicated that intravenous meth-
side effects between the two groups [17].                           ylprednisolone pulse therapy was a better treatment option
   To study the long-term efficacy of intravenous pulse of          than combination therapy with low-dose methylprednisolone
methylprednisolone in treating severe AA, Staumont-Sallé            and cyclosporine in patients with severe, plurifocal AA [21].
et al assessed 60 patients who had received this treatment
                                                                    Intravenous Methylprednisolone Combined
ten years earlier. They reported that patients who initially
                                                                    With Methotrexate
responded to therapy during the first six months had a
                                                                    Droitcourt et al evaluated the efficacy of combining intrave-
milder disease in the next ten years, while those who were
                                                                    nous methylprednisolone pulse with methotrexate in treating
non-responders to therapy still had severe disease. Autoim-
                                                                    multifocal AA. More than half of the patients experienced
mune thyroid disease and atopic disorders were more fre-
                                                                    completed hair growth, while the rest had satisfactory in-
quent in non-responders. This study considered intravenous
                                                                    complete responses. The mean period of hair regrowth initi-
methylprednisolone pulse therapy inefficient in treating se-
                                                                    ation was 2.5 months, and relapse occurred in a few patients.
vere AA and suggested other treatments for alopecia totalis
                                                                    The study concluded that this combination is effective and
and universalis [18].
                                                                    well-tolerated when treating patients with severe AA [22].
Intravenous Methylprednisolone in Children
Friedland assessed the efficacy of intravenous methylpred-
                                                                    The Efficacy of Oral Corticosteroid Pulse in
nisolone pulse in treating children with severe AA. Nearly
                                                                    Treating Severe AA
70% of patients experienced partial to complete remission,          Fourteen studies evaluated oral steroid pulse therapy in treat-
and a higher rate of hair growth was seen in multifocal AA          ing severe AA, including 2 on methylprednisolone, 3 on dexa-
patients. Surprisingly, 81% of responders had a relapse in          methasone, 5 on prednisolone, and 4 studies on betamethasone.
the first year of treatment. Age at onset of fewer than ten
                                                                    Oral Methylprednisolone
years, disease onset below six months, and multifocal disease
                                                                    Two studies assessed methylprednisolone pulse efficacy
were recognized as good prognostic factors. No serious side
effects were reported. This article concluded that all children     in AA treatment: one evaluated oral mega-pulse efficacy,
with AA do not benefit from steroid pulse treatment; there-         relapse, and side effects, while the other evaluated oral
fore, case selection plays a vital role in achieving optimal        mini-pulse. Saif et al prescribed an oral mega-pulse of
results and avoiding ineffective therapies [19].                    methylprednisolone for 24 weeks with different proto-
                                                                    cols, namely three consecutive days once every two weeks,
Intravenous Methylprednisolone Combined
With Cyclosporine                                                   two consecutive daily pulses every three weeks, and three
In a study by Shaheedi-Dadras et al, a 500 mg dose of in-           consecutive daily pulses every three weeks. No significant
travenous methylprednisolone was administered in three              difference was seen between the groups in efficacy, and all



Review | Dermatol Pract Concept. 2023;13(4):e2023255                                                                             3
protocols induced a desirable response rate, as more than       months. Almost 60% of patients had hair regrowth of more
50% of patients experienced more than 25% improvement           than 50% (most had >75% regrowth). The most satisfactory

in hair growth during treatment. Early age of disease on-       results were seen in patients with plurifocal AA. Patients with
                                                                a disease duration of more than 12 months needed longer
set, hypothyroidism, and longer duration of AA (more than
                                                                treatments. No serious adverse effects were reported [27].
two years) were associated with lower response. There was
a significant difference in the side effects rate between the   Prednisolone
study groups, as patients who received steroid pulse with       Four studies focused on the effect of prednisone pulse in
higher doses and shorter intervals experienced greater and      treating severe AA. Among all, 3 articles studied high doses

more severe complications like arthralgia, increased appe-      of prednisolone pulse, one study evaluated the possible path-
                                                                way of the effect of prednisolone in treating AA by examin-
tite, and stomach upset. This study suggests oral mega pulse
                                                                ing serum and tissue tumor necrosis factor-alpha (TNF-α)
methylprednisolone as an effective choice for treating se-
                                                                levels, and one compared the efficacy of oral prednisolone,
vere AA, albeit with a high risk of adverse events and a high   dexamethasone, and intramuscular triamcinolone.
relapse rate [23].
    In another study by Thi et al, patients were treated with   Oral High-dose Prednisolone Pulse
an oral mini-pulse of methylprednisolone, 16 mg/day, for        To assess the efficacy of the oral prednisolone pulse, Sharma
two consecutive days per week. More than 82% of patients        et al enrolled 32 patients with more than 40% scalp in-
had good regrowth over six months, while only 40% had           volvement or persistent AA and treated them with a 300 mg
the same experience within three months. They suggested         monthly dose of prednisolone pulse. More than half of the pa-
the mini-pulse of methylprednisolone as a safe and effective    tients had an excellent response. Patients with plurifocal alo-
treatment for AA in six months [24].                            pecia areata had the most desirable cosmetic effects, while no
                                                                improvement was seen in patients with alopecia ­universalis.
Oral Dexamethasone                                              Patients with alopecia universalis and non-responders to the
Among all articles, three were evaluated for dexamethasone      300 mg prednisolone pulse were retreated with a 1000 mg
pulse therapy effect in AA treatment: two evaluated the oral    prednisolone pulse; nearly 50% regrowth was seen in this
mini-pulse, and one assessed the combination of oral pulse      group during the follow-ups. Results showed that the 300 mg
with topical corticosteroids.                                   prednisolone pulse was an effective treatment for plurifocal
                                                                alopecia areata with mild side effects, while the 1000 mg
Oral Mini-pulse of Dexamethasone                                prednisolone pulse might be an effective choice in alopecia
Sánchez-Díaz described 40 patients with extensive scalp AA      universalis and widespread resistant AA. The female gender,
treated with dexamethasone oral mini-pulse (mean dose of        disease duration of over two years, and alopecia universalis
2.7 mg/day, two days weekly, 12 months). Higher effective-      were linked with a poor or lack of response to treatment [28].
ness was reported as the treatment period increased. Oral          A placebo-controlled study in a total of 43 patients re-
dexamethasone pulse was relatively ineffective in patients      vealed that 35% of the patients who received prednisolone
with hypothyroidism and those aged under 15 years. No           pulse experienced significant hair growth at the end of three
greater reduction in the Severity of Alopecia Tool (SALT)       months. However, relapse occurred in 25% of them during
score was reported in combination therapy of dexametha-         the three months of follow-up. Patients with early age of
sone pulse and oral minoxidil (25). Another study by Sharma     onset, disease duration of fewer than two years, and those
et al. on 30 patients with widespread and diffuse AA who        on their first episode responded better compared to those
received oral dexamethasone showed promising results, as        with atopy-related, nail involvement, multiple episodes, and
more than 60% of patients had completed or over 75% hair        prolonged duration. Mild side effects of corticosteroids were
growth during five months. Relapse was uncommon as it           seen in 55% of the patients. However, they all eased grad-
was seen only in one patient. Frequent but mild and transient   ually during the follow-up period ]. Another study by Tsai
side effects were reported [26].                                et al tested high-dose steroid pulse therapy, 5 mg/kg oral
                                                                prednisone in individuals under 12, and 500 mg intrave-
Oral Mini-pulse of Dexamethasone Combined                       nous methylprednisolone in adults with severe AA. Within
With Topical Corticosteroids                                    four months of treatment initiation, favorable results were
Lalosevic et al studied 65 individuals aged 8–12 years with     achieved, as all patients with multifocal AA experienced sig-
AA, alopecia universalis, and plurifocal AA. Oral pulse dexa-   nificant regrowth. However, the treatment outcomes were
methasone (once every four weeks) was combined with top-        worse in patients with alopecia ophiasis, alopecia universa-
ical clobetasol 0.05% ointment to treat patients for 6–12       lis, alopecia totalis, and extended disease lasting more than



4                                                                          Review | Dermatol Pract Concept. 2023;13(4):e2023255
two years. This study suggested monthly corticosteroid pulse        or good response. There was, however, a relapse in one pa-
therapy with a mean dose of 5-10 mg/kg as an effective treat-       tient two months after stopping therapy. Only a few patients
ment for severe multifocal AA lasting less than two years,          showed an unsatisfactory or lack of response at the end of
with a low relapse rate [30].                                       the six months of therapy. Both non-responders had alopecia
                                                                    universalis. They concluded that betamethasone is a safe and
Prednisolone Possible Mechanism                                     effective treatment for extensive AA, with only mild, revers-
of Action in AA
                                                                    ible side effects [33].
To assess the possible mechanism of action of prednisolone in           To compare the efficacy of betamethasone oral mini-pulse
the treatment of AA, Abdel Halim et al compared tissue and          versus weekly azathioprine pulse in treating scalp alopecia,
serum levels of TNF-α in 20 patients with AA and 20 controls.       Gupta et al. enrolled 50 patients into two groups of 25. As-
This study indicated that the disease duration significantly        sessments of the results at baseline and after four and nine
decreased after consuming 60 mg of prednisolone twice               months demonstrated that both methods were highly effective
weekly for three months. There was a positive relationship          options in treating severe alopecia with no priority, as almost
between TNF-α level and AA lesions. Both serum and tissue           60% of patients in each group experienced complete regrowth
levels of TNF-α were higher in the pretreatment evaluations         within the nine months. However, betamethasone consump-
of patients compared to the control group. Post-treatment           tion was accompanied by some severe side effects. They sug-
assessments revealed a statistically significant decrease in pa-    gested azathioprine pulse as a good and safe alternative to
tients' serum and tissue levels of TNF-α. They suggested the        steroid therapy in severe alopecia with minor side effects [34].
prednisolone pulse as a good choice for the treatment of AA,
as it reduced the disease duration and TNF-α levels [31].           Combination of Oral Mini-pulse of
                                                                    Betamethasone With Other Agents
Comparison of the Efficacy of Oral                                  Asilian et al compared 36 patients treated with either beta-
Prednisolone, Dexamethasone, and Intra-
                                                                    methasone 3 mg/once a week, methotrexate 15 mg/once a
muscular Triamcinolone
                                                                    week, or a combination of them for four months. Patients
A study published in 2006 by Kurosawa et al compared the
                                                                    in all groups experienced a significant increase in hair re-
efficacy, relapse rate, and side effects between three modalities
                                                                    growth; however, greater regrowth was seen in patients
of systemic corticosteroid therapy (oral prednisolone, dexa-
                                                                    treated with betamethasone and combination therapy com-
methasone, and intramuscular triamcinolone) in 89 ­patients
                                                                    pared with methotrexate alone. Among all, combination
with AA. In most patients, hair growth was evident 3-6 months
                                                                    therapy was the most effective, especially in the long-term
after the first treatment session. According to the results, the
                                                                    period of consumption of the drugs [35].
overall response rate was significantly different only between
                                                                        In 2011, Deshpande et al. proposed a combination ther-
the dexamethasone group and the intramuscular triamcino-
                                                                    apy in which the patients were treated with oral betametha-
lone group patients in each clinical subtype (mostly in multi-
                                                                    sone mini-pulse (0.1 mg/kg twice a week) along with topical
plex AA). To conclude, both prednisolone pulse therapy and
                                                                    minoxidil and anthralin cream of 2%-5% and 1.15%, respec-
intramuscular triamcinolone are effective treatments for AA
                                                                    tively. Topical minoxidil was applied to the affected area twice,
with mild side effects. However, overall relapse rates were
                                                                    12 hours apart. The anthralin cream was first applied at night,
significantly higher in the dexamethasone group than in the
                                                                    two hours apart from the minoxidil application, for 10 m
                                                                                                                           ­ inutes
prednisolone group (especially for those with alopecia tota-
                                                                    (contact time), then the contact time gradually increased every
lis and alopecia universalis). The authors concluded that new
                                                                    three weeks until mild erythema appeared. There was a high
strategies are needed to reduce relapse rates [32].
                                                                    response rate (80%) among the patients. The response rate was
Betamethasone                                                       low among the patients with alopecia universalis or prolonged
                                                                    alopecia totalis, while all patients with ophiasis and severe AA
Four studies were done on betamethasone efficacy in severe
                                                                    showed cosmetic improvements. Due to the synergistic inter-
AA. One assessed mini-pulse of betamethasone, one com-
                                                                    actions between the drugs, this combination therapy could
pared azathioprine pulse with betamethasone, one assessed
                                                                    be used as an effective and safe treatment for patients with
combination therapy of betamethasone and methotrexate,
                                                                    ­treatment-resistant and extensive alopecia areata [36].
and the other examined a combination of betamethasone
mini-pulse and topical minoxidil and anthralin.
                                                                    Conclusions
Oral Mini-pulse of Betamethasone
One study evaluated the efficacy of betamethasone oral              Alopecia areata (AA) is a common, non-scarring, autoim-
mini-pulse therapy in patients with severe AA. According            mune hair loss disorder. It is a multifactorial disease that
to the results, most patients (74.9%) showed an excellent           varies in clinical presentation from a small patch to total



Review | Dermatol Pract Concept. 2023;13(4):e2023255                                                                               5
scalp and body alopecia. Finding the appropriate treatment          in relapse rate and adverse effects, as the mini-pulse of oral
protocols for AA is challenging due to the disease's uncer-         methylprednisolone is safer; higher doses and shorter inter-
tain pathogenesis and unpredictable remission rates (6). The        vals lead to greater and more severe complications [23,24].
use of systemic pulse corticosteroids was first introduced for          Studies proposed dexamethasone as a good treatment
treating severe types of AA in 1975 by Burton and Shuster           option for AA with a low rate of relapse and side effects.
to decrease possible side effects of long-term use of cortico-      They also revealed no difference between the efficacy of
steroids and increase the effectiveness of the treatment. They      oral mini-pulse dexamethasone (2.7 mg/day) vs. 5 mg/day
treated 22 patients with a single intravenous dose of methyl-       for two days a week, so it’s safer to use the lower dosage.
prednisolone, but only 23% responded. The unsuccessful re-          To achieve better results in children, dexamethasone can be
sults were due to poor patient selection, as most patients had      combined with topical clobetasol [25-27].
severe AA for a long time [10]. Afterward, several scientists           In the studies on betamethasone, excellent therapeutic
followed them and administered pulse steroid therapy in var-        responses can be achieved with a low relapse rate and only
ious forms and doses with or without other drugs to avoid           mild reversible side effects. Monotherapy with betametha-
the long-term side effects of prolonged steroid therapy. In         sone mini-pulse (0.1 mg/kg/ day to 5 mg/day for 2consecutive
this study, we considered 24 published studies and reviewed         days a week for a mean time of 6 months) is accompanied
their modalities for treating different kinds of AA.                by highly successful results but some adverse effects, while
    A review of the studies on the efficacy and side effects        combination therapy of betamethasone with methotrexate
of intravenous methylprednisolone revealed that pulse ther-         or topical minoxidil and anthralin significantly increase hair
apy of methylprednisolone might be a promising treatment            regrowth and decrease the side effects [33-36].
option in the severe form of AA with the routine treatment              Articles focused on the efficacy of prednisone pulse
protocol of 8-10 mg/kg for three consecutive days, with             therapy have found prednisolone (5-10 mg/kg/month for
one-month interval up until the clinical satisfaction achieve,      4-6 months) as an acceptable and effective option with a low
either for adults or children. There is no difference in the out-   relapse rate. Results showed that an average dose of 300 mg
comes and side effects of the routes of choice (intravenous or      monthly prednisolone pulse is an effective treatment for
oral). The relapse rate and efficacy depend on the time of AA       plurifocal AA with only mild side effects, but patients with
onset, patient age, and the type of AA; recent onset of AA          alopecia universalis or alopecia totalis are resistant to this
(<6 months), younger age (<10 y/o), and multifocal type of          therapy. Research suggests 1000 mg prednisolone is an effec-
AA (compared to alopecia universalis, totalis, and ophiasis)        tive choice in alopecia universalis and resistant widespread
are linked with better results and a lower chance of relapse.       alopecia areata [28-30].
Patients with a past medical history of atopy, nail pitting, or         Comparisons of the efficacy of oral dexamethasone, oral
thyroid disease and those with severe forms of AA like alo-         prednisolone, and intramuscular triamcinolone revealed that
pecia universalis and totalis experienced less improvement          all methods are effective, but the best results were achieved
[13-19].                                                            with intramuscular triamcinolone, followed by prednisolone,
    A combination of intravenous pulse methylprednisolone           with only mild reversible side effects. Patients who received
with methotrexate (12.5 mg weekly) revealed the best effi-          dexamethasone experienced less hair regrowth with a higher
cacy for treating the severe type of AA, although some poor         relapse rate [32].
prognostic factors such as childhood onset of the disease,              In conclusion, all mentioned systemic corticosteroid
disease duration >6 years, and a positive history of atopy          pulses effectively induce hair regrowth in alopecia areata.
or nail pitting led to poor outcomes and increase the risk of       Both forms of intravenous and oral corticosteroids have ac-
relapse. The use of sequential intravenous pulse therapy of         ceptable efficacy. Betamethasone pulse seems to be the most
methylprednisolone is supposed to be better than a single           effective agent in the treatment of AA (followed by intra-
dose to decrease the risk of relapse. Studies on the effect of      muscular triamcinolone), especially in severe cases, but more
combination therapy with cyclosporine are still controver-          side effects may accompany it. Combining this agent with
sial, but some articles have shown promising results [20-22].       other medications can reduce the dosage and side effects.
    Research on the efficacy of oral methylprednisolone pulse       Prednisolone and methylprednisolone pulse are less effective
therapy showed that both oral mega-pulse and mini-pulse             but safer options, with low relapse rates and few adverse
of methylprednisolone are effective in severe forms of AA,          effects. A combination of them with other drugs can increase
but the relapse rate is high. There is a significant difference     their efficacy.




6                                                                               Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       Reference                            First                        Patients                     Alopecia
                                                          No.              Title           author      Trial type   Year (No., sex)     Age (y)         type            Treatment              Assessment           Outcome             Conclusion         Side effects
                                                       1           Pulsed               Sharma, VK Prospective      1996   32: 24M,   14–48         Widespread      A: 300 mg oral          Monthly              A: 58.3% had      Effective             A: A man
                                                                   administration of                                       8F         (mean 28.5)   alopecia, AT,   prednisolone            evaluation           complete or       treatment for         experienced
                                                                   corticosteroids in                                                               AU              monthly for a           and serial           80–95% hair       widespread            nausea;
                                                                   the treatment of                                                                                 minimum of 4 doses      photographs;         growth.           alopecia areata       a woman got
                                                                   alopecia areata                                                                                  or until cosmetically   the results were                       with only mild        polymenorrhea.
                                                                                                                                                                                                                 B: 3 out of 7 had
                                                                                                                                                                    acceptable hair         listed at 6 and                        side effects          B: No side
                                                                                                                                                                                                                 cosmetically
                                                                                                                                                                    growth was              12 months                                                    effects
                                                                                                                                                                                                                 acceptable
                                                                                                                                                                    obtained;               by measuring
                                                                                                                                                                                                                 growth.
                                                                                                                                                                                            the percent of
                                                                                                                                                                    B: 1000 mg
                                                                                                                                                                                            terminal hair        In general,
                                                                                                                                                                    prednisolone
                                                                                                                                                                                            growth.              women and
                                                                                                                                                                                                                 patients with
                                                                                                                                                                                                                 alopecia for
                                                                                                                                                                                                                 more than two
                                                                                                                                                                                                                 years or AT or




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                                                                                                                                                                                 AU showed poor
                                                                                                                                                                                                                 or no response.
                                                       2           Pulse                A. Friedli   Open,          1998   45         13–66         PF AA, OA,      250 mg IV               Two independent      Patients with        Effective          Only common
                                                                   methylprednisolone                prospective                                    AU, and AT      methylprednisolone,     observers            multifocal AA        treatment in       mild transient
                                                                   therapy for severe                                                                               twice a day on          measured the         showed the best      patients with      side effects
                                                                   alopecia areata: an                                                                              3 consecutive days      percentage of        response, while      multifocal AA,     of steroids:
                                                                   open prospective                                                                                                         hair regrowth at     patients with        but not in those   fatigue, nausea,
                                                                   study of 45 patients                                                                                                     1, 3, 6, and 12m.    OA, AU, and AT       with AU, AT,       dyspnea,
                                                                                                                                                                                            Serial photographs   did not respond      or OA              palpitation, and
                                                                                                                                                                                            and monthly          well. Relapse                           headache
                                                                                                                                                                                            examinations were    occurred in 10 in
                                                                                                                                                                                            done.                7m; after a year
                                                                                                                                                                                                                 of follow-up,
                                                                                                                                                                                                                 only 12 were still
                                                                                                                                                                                                                 in remission.
                                                       3           Twice weekly 5 mg    Sharma VK    Prospective    1999   30: 20M,   6–46          Extensive       5 mg                    Monthly              After 5.35           Effective          Commonly mild
                                                                   dexamethasone                                           10F        (mean 23.6)   alopecia and    dexamethasone           examinations         months, hair         modality in        side effects of
                                                                   oral pulse in                                                                    circumscribed   orally, twice weekly    were done, and       growth was           treating severe    corticosteroids
                                                                   the treatment of                                                                 alopecia        for 6m or until         the results were     complete or          multifocal         were seen in
                                                                   extensive alopecia                                                                               acceptable hair         reported at 6 and    excellent in         alopecia with      8 patients;
                                                                   areata                                                                                           growth                  12 months as         19 patients, good    only mild          in only one
                                                                                                                                                                                            complete (100%),     in 2, poor in 3,     common side        patient, the
                                                                                                                                                                                            excellent            and absent in 6.     effects.           treatment had
                                                                                                                                                                                            (75-95%),                                                    to stop due to
                                                                                                                                                                                            good (51-74%), or                                            the side effects.
                                                                                                                                                                                            poor (<50%) hair




7
                                                                                                                                                                                            growth.
8
                                                       Reference                            First                          Patients                   Alopecia
                                                          No.             Title            author       Trial type   Year (No., sex)     Age (y)        type           Treatment            Assessment            Outcome            Conclusion         Side effects
                                                       4           High-dose steroid     Ya-Ming      Prospective    2002   17: 8M,    8–53          Multifocal    Children <12:          Serial photographs   11 patients with    Effective
                                                                   pulse therapy for     Tsai                               9F         (mean 25)     AA, OA, AU,   5 mg/kg oral           were taken, and      multifocal AA       modality in
                                                                   the treatment of                                                                  and AT        prednisone in          two blinded          showed partial      treating severe
                                                                   severe alopecia                                                                                 three divided doses    dermatologists       hair growth,        multifocal AA
                                                                   areata                                                                                          monthly; Adults:       evaluated hair       while 2 showed      lasting less than
                                                                                                                                                                   monthly 500 mg IV      growth. The          no response.        two years
                                                                                                                                                                   methylprednisolone     average of the       Less effective in
                                                                                                                                                                   infusion over          results was          OA, AT, AU, and
                                                                                                                                                                   two hours (for         tabulated. A         extended AA.
                                                                                                                                                                   a maximum of           satisfactory
                                                                                                                                                                   6 months)              response was
                                                                                                                                                                                          defined as more
                                                                                                                                                                                          than 75% hair
                                                                                                                                                                                          regrowth.
                                                       5           Placebo-controlled    Bikash       Placebo-       2005   Group A:   Group A:      Severe AA     Group A: 200 mg        Patients were        A: 8 had            This therapy        Mild frequent
                                                                   oral pulse            Ranjan Kar   controlled            20: 14M,   26.3 ± 7.3.                 of oral prednisolone   examined monthly     significant hair    is effective and    side effects of
                                                                   prednisolone                                             6F         Group B:                    weekly for 3m;         for marked           growth after        promising,          corticosteroids
                                                                   therapy in alopecia                                      Group B:   30.2 ± 10.2                 Group B: matched       (>60%), moderate     3m (2= marked,      but more            were seen
                                                                   areata                                                   16: 12M,                               placebo tablets        (31–60%), or         6= moderate),       research needs      in 55% of
                                                                                                                            4F                                     on an identical        poor (<30%)          though 2 later      to be done to       the patients.
                                                                                                                                                                   schedule               regrowth.            relapsed. Poor      adjust the dose     However,
                                                                                                                                                                                                               response: atopy-    needed.             they all eased
                                                                                                                                                                                                               related AA, nail                        gradually during
                                                                                                                                                                                                               involvement,                            the follow-up
                                                                                                                                                                                                               multiple                                period.
                                                                                                                                                                                                               episodes, &
                                                                                                                                                                                                               extended AA
                                                                                                                                                                                                               B: None
                                                                                                                                                                                                               responded.




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       6   A comparison          Masahiro   Randomized 2006       89         16-63 years   PF AA, AT,   Dex group (n=19):   The response was       In most patients,    Both imTA and     10% of PT
                                                           of the efficacy,      Kurosawa   comparative-                                   AU           oral Dex 0.5 mg/day tabulated monthly      hair growth was      pulse therapy     group patients:
                                                           relapse rate and                 prospective                                                 for 6m;             by measuring           evident at 3–6m.     are effective     dysmenorrhea
                                                           side effects among               study                                                                           the percentage         The overall          for AA with       and abdominal
                                                                                                                                                        IM triamcinolone
                                                           three modalities                                                                                                 of terminal hair       response rate        only mild side    discomfort;
                                                                                                                                                        acetonide (imTA)
                                                           of systemic                                                                                                      growth. Serial         was significantly    effects. A high
                                                                                                                                                        group (n=43): imTA                                                                41% of imTA
                                                           corticosteroid                                                                                                   photographs were       different only       relapse rate
                                                                                                                                                        40 mg monthly for                                                                 group patients:
                                                           therapy for                                                                                                      taken at baseline      between the          (especially in
                                                                                                                                                        6m followed by                                                                    dysmenorrhea,
                                                           alopecia areata                                                                                                  and after 3, 6, and    Dex and imTA         AT and AU)
                                                                                                                                                        40 mg once every                                                                  abdominal
                                                                                                                                                                            12m.                   groups, in each      was seen in the
                                                                                                                                                        1.5 months for                                                                    discomfort, and
                                                                                                                                                                                                   clinical subtype     Dex group.
                                                                                                                                                        1 year;                                                                           worsening acne;
                                                                                                                                                                                                   (mostly in
                                                                                                                                                                                                                                          30% of Dex
                                                                                                                                                        PT group (n=29):




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                                                                                                                                                                   multiplex AA).
                                                                                                                                                                                                                                          group patients:
                                                                                                                                                        oral prednisone
                                                                                                                                                                                                                                          weight gain,
                                                                                                                                                        80 mg for
                                                                                                                                                                                                                                          abdominal
                                                                                                                                                        3 consecutive days
                                                                                                                                                                                                                                          discomfort,
                                                                                                                                                        every 3m
                                                                                                                                                                                                                                          weakness, and
                                                                                                                                                                                                                                          mooning.
                                                       7   Extensive alopecia    Binod K.   Open,          2004   16: 11M,   14–36         Severe AA    A single                Monthly            43.7% had            Effective         Only mild
                                                           areata treated with   Khaitan    uncontrolled          5F         (mean 26)                  dose of 5 mg            examinations       an excellent         therapeutic       side effects
                                                           betamethasone                                                                                betamethasone           to assess the      response (relapse    modality for      including moon
                                                           oral mini-pulse                                                                              was administered        treatment          occurred in 1        extensive         face, acneiform
                                                           therapy: An open                                                                             biweekly for at least   response and       patient after 2m).   alopecia areata   eruption,
                                                           uncontrolled study                                                                           6m.                     adverse effects;   31.2% showed                           weight gain,
                                                                                                                                                                                patients were      a good response,                       and abdomen
                                                                                                                                                                                followed up for    and therapy was                        discomfort
                                                                                                                                                                                5–8m for relapse   continued for
                                                                                                                                                                                of the disease.    another 2m in
                                                                                                                                                                                                   these patients (no
                                                                                                                                                                                                   relapse occurred).
                                                                                                                                                                                                   4 patients
                                                                                                                                                                                                   showed poor
                                                                                                                                                                                                   or no response
                                                                                                                                                                                                   (non-responders
                                                                                                                                                                                                   had AU).




9
                                                       Reference                         First                         Patients                  Alopecia




10
                                                          No.              Title        author      Trial type   Year (No., sex)     Age (y)       type          Treatment           Assessment            Outcome            Conclusion       Side effects
                                                       8           Extensive          Deepal      Prospective    2011   15: 10F,   7–45        Extensive AA Oral betamethasone     Monthly              80% responded.      This            Only mild,
                                                                   alopecia areata:   Deshpande                         5M                                  mini-pulse (0.1 mg/    evaluation           Among the 20%       combination     reversible side
                                                                   not necessarily                                                                          kg twice a week)       by measuring         non-responders,     therapy is an   effects
                                                                   recalcitrant to                                                                          along with 2–5%        the percent of       2 had AU            effective and
                                                                   therapy!                                                                                 topical minoxidil      terminal hair        and one had         safe treatment
                                                                                                                                                            (twice a day,          growth. Cosmetic     extended AA         for patients
                                                                                                                                                            12 hours apart) and    response: partial    with a duration     with treatment-
                                                                                                                                                            1.15% anthralin        dense patches        of 8–10 years.      resistant and
                                                                                                                                                            cream (daily).         of terminal hair,                        extensive AA.
                                                                                                                                                                                                        Out of 8 patients
                                                                                                                                                            After achieving a      obviating the need
                                                                                                                                                                                                        with AU/
                                                                                                                                                            response, the oral     for a wig/cap;
                                                                                                                                                                                                        AT: cosmetic
                                                                                                                                                            steroid was tapered    non-responders or
                                                                                                                                                                                                        response=4,
                                                                                                                                                            step-wise and then     failure: no growth
                                                                                                                                                                                                        partial
                                                                                                                                                            stopped, but the       or vellus hair.
                                                                                                                                                                                                        response=1.
                                                                                                                                                            topical creams
                                                                                                                                                                                                        Cosmetic
                                                                                                                                                            were continued
                                                                                                                                                                                                        response was seen
                                                                                                                                                            as maintenance
                                                                                                                                                                                                        in all 4 patients
                                                                                                                                                            therapy and then
                                                                                                                                                                                                        with OA and all
                                                                                                                                                            gradually decreased.
                                                                                                                                                                                                        3 patients with
                                                                                                                                                                                                        severe AA.
                                                       9           Efficacy and safety Ghada A    Prospective    2012   42: 20F,   12 ± 7      AU, AT, OA    Group 1: 15 mg/kg Photography              Nearly 30%          MP pulse         95%
                                                                   of oral mega pulse             randomized            22M                                  MP, 3 days every 2w at baseline            had an adequate     therapy is       experienced
                                                                   methylprednisolone                                                                        for 24w;            and every 2w.          response, 20%       relatively       side effects.
                                                                   for severe therapy                                                                                            >75% regrowth:         inadequate,         effective in     Fatigue: 64%;
                                                                                                                                                             Group 2: 15 mg/kg
                                                                   resistant alopecia                                                                                            adequate; 25-          and 50% poor        severe AA but    weight gain:
                                                                                                                                                             MP, 2 days every 3w
                                                                   areata                                                                                                        75%: inadequate.       response at 36w;    has a high       45%; steroid-
                                                                                                                                                             for 24w;
                                                                                                                                                                                 <25%: poor             no difference       relapse rate     induced acne:
                                                                                                                                                             Group 3: 15 mg/kg                          between the                          35.7%; sleep
                                                                                                                                                             MP, 3 days every 3w                        groups. Older                        disturbances
                                                                                                                                                             for 24w                                    age of initiation                    33%. Others:
                                                                                                                                                                                                        had a better                         irritability,
                                                                                                                                                                                                        response.                            lethargy,
                                                                                                                                                                                                                                             stomach upset,
                                                                                                                                                                                                                                             nausea, flushing,
                                                                                                                                                                                                                                             cramp, bony
                                                                                                                                                                                                                                             pain, arthralgia




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       10   Combined oral        Jovan       Retrospective 2015   65   10 ± 5    >30% scalp    Oral                    According to the     83% with PF AA     Combined         No serious side
                                                            pulse and topical    Lalosevic                                       involvement   dexamethasone           AA investigational   had regrowth       topical and oral effects
                                                            corticosteroid                                                       AU, AT, PF    (equal to 5 mg/         assessment           >75%, while        corticosteroid
                                                            therapy for severe                                                   AA            kg prednisolone)        guidelines, photos   35% with severe    pulse is
                                                            alopecia areata in                                                                 once every 4w (6, 9,    were evaluated by    AA had the         effective for
                                                            children: a long-                                                                  or 12 pulses) plus      a board-certified    same experience.   severe AA
                                                            term follow-up                                                                     topical clobetasol, 6   dermatologist at     Relapse: 16.9%     in children
                                                            study                                                                              days a week.            baseline, 3, 6, 9,                      without any
                                                                                                                                                                       and 12m.                                severe side
                                                                                                                                                                                                               effects
                                                       11   Alteration of serum Dalia Abdel Prospective    2018   40   28 ± 11   PF AA         Group 1: 60 mg/day      3-ml blood           Serum and tissue   Prednisolone
                                                            and tissue tumor    Halim                                                          of prednisolone,        sample and 2-mm      TNF-α levels       pulse is a good
                                                            necrosis factor                                                                    biweekly for 3m         punch biopsy         significantly      choice for




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                            alpha levels: A                                                                    (age <16 received       were assessed        decreased after    treating AA
                                                            possible mechanism                                                                 half dose);             for TNF-α level      the treatment.     as it reduces
                                                            of action of oral                                                                  Group 2: Control        before and after                        the disease
                                                            pulse steroids in                                                                                          treatment                               duration and
                                                            the treatment of                                                                                                                                   TNF-α level
                                                            alopecia areata
                                                       12   The effectiveness   Phuong       Prospective   2019   45   >16       Not           Oral mini-pulse MP Not mentioned             40% had            Oral mini-pulse No side effects
                                                            of oral mini-pulse  Trinh Thi                                        mentioned     16 mg/day biweekly                           regrowth by 3m,    of MP is an
                                                            methylprednisolone                                                                 for 6m                                       and 82% had        effective, safe,
                                                            in the treatment of                                                                                                             regrowth by 6m     and low-priced
                                                            alopecia areata in                                                                                                                                 treatment for
                                                            Vietnam                                                                                                                                            AA
                                                       13   Weekly               Prashant    Open-label,   2022   50   25        >10% scalp    Group 1: 300 mg         SALT score;          44% regrowth in    WAP and oral-      Moon face,
                                                            azathioprine         Gupta       randomized                          involvement   weekly azathioprine     average percentage   the WAP group      mini-pulse of      acne, reflux,
                                                            pulse versus                     comparative                                       (WAP) for 4m;           of scalp hair        and 71% in the     betamethasone      and weight gain
                                                            betamethasone                                                                      Group 2: 5 mg           regrowth;            betamethasone      are both           were seen in
                                                            oral mini-pulse in                                                                 betamethasone           evaluations at       group; 50%         effective          steroid group,
                                                            the treatment of                                                                   biweekly for 4m         baseline and         in WAP             in treating        while only
                                                            moderate-to-severe                                                                                         4 & 9m               and 62% in         AA, with no        transient nausea
                                                            alopecia areata                                                                                                                 betamethasone      priority in hair   was reported
                                                                                                                                                                                            group had          growth, though     with WAP
                                                                                                                                                                                            complete hair      betamethasone
                                                                                                                                                                                            growth at 9m       pulse has more
                                                                                                                                                                                                               side effects




11
                                                       Reference                            First                           Patients                     Alopecia




12
                                                          No.             Title            author        Trial type   Year (No., sex)        Age (y)       type          Treatment            Assessment            Outcome             Conclusion        Side effects
                                                       14          Oral pulse            Ali Asilian   Randomized, 2020      36         27             >50% scalp    Group 1: 3 mg         SALT, VAS, &         Significant           MTX &              1 patient in
                                                                   betamethasone,                      double-blind,                                   involvement   betamethasone         photography at       improvement in        betamethasone      MTX group
                                                                   methotrexate,                       placebo-                                                      weekly for 6m;        baseline and 3, 6,   SALT, VAS, and        alone or in        and 1 in
                                                                   and combination                     controlled                                                    Group 2: 15 mg        & 9m                 photographic          combination        combination
                                                                   therapy to                                                                                        MTX weekly for                             scores in all at 3,   are effective in   group developed
                                                                   treat severe                                                                                      6m;                                        6, & 9m;              treating severe    gastrointestinal
                                                                   alopecia areata:                                                                                                                                                   AA, though         symptoms,
                                                                                                                                                                     Group 3: 3 mg                              At 9m: a 43%
                                                                   a randomized,                                                                                                                                                      betamethasone      relieved with
                                                                                                                                                                     betamethasone+15                           SALT score
                                                                   double-blind,                                                                                                                                                      or                 daily folic acid
                                                                                                                                                                     mg MTX weekly                              decrease in
                                                                   placebo-controlled,                                                                                                                                                betamethasone
                                                                                                                                                                     for 6m                                     Group 3, 26%
                                                                   clinical trial                                                                                                                                                     + MTX are
                                                                                                                                                                                                                in Group 1,
                                                                                                                                                                                                                                      more effective
                                                                                                                                                                                                                and 23% in
                                                                                                                                                                                                                                      than MTX
                                                                                                                                                                                                                Group 2, &
                                                                                                                                                                                                                                      alone
                                                                                                                                                                                                                Group 3 showed
                                                                                                                                                                                                                significantly
                                                                                                                                                                                                                more VAS/
                                                                                                                                                                                                                photographic
                                                                                                                                                                                                                scores
                                                                                                                                                                                                                improvement
                                                       15          Alopecia areata     Manuel          Prospective    2022   40         32             >20% SALT     Oral Dex at a        SALT at baseline,     50% decrease          Oral mini-         Weight gain
                                                                   and dexamethasone Sánchez-          cohort                                          score         mean dose of 2.72    3, 6, 9, 12m          in SALT score in      pulse of Dex       in 35%;
                                                                   mini-pulse therapy, Díaz                                                                          mg/day biweekly                            half the patients     is effective in    osteopenia or
                                                                   a prospective                                                                                     for 12m; 27% of                            by 9m. Significant    treating AA but    osteoporosis in
                                                                   cohort: real world                                                                                patients received                          decrease in SALT      ineffective for    12.5%; glycemic
                                                                   evidence and                                                                                      oral minoxidil 0.5-1                       score in overall      onset age <15y     disorder in
                                                                   factors related to                                                                                mg/day for females,                        assessment.           or in those with   5%; acneiform
                                                                   successful response                                                                               2.5-5 mg/day for                           No SALT score         hypothyroidism     rash, hirsutism,
                                                                                                                                                                     males                                      decrease in onset                        anxiety, and
                                                                                                                                                                                                                age < 15y                                insomnia in less
                                                                                                                                                                                                                                                         than 5%
                                                       16          The effect of        Mohammad Prospective          2008   18: 9F,    20.6 ±4.8    AT, AU          500 mg dose of        Adequate= hair       Total of 6 patients   This therapy       Mild
                                                                   methylprednisolone Shaheedi-                              9M         (range14–29)                 IV MP monthly         regrowth ≥70%        showed adequate       can be             hypertension
                                                                   pulse-therapy plus Dadras                                                                         for three days +      and inadequate=      response= 33%         beneficial in      (n=1),
                                                                   oral cyclosporine                                                                                 oral cyclosporine     regrowth <70%.       (3M and 3F/ 3 in      some patients      hyperlipidemia
                                                                   in the treatment of                                                                               (2.5 mg/kg/day) for                        patients<20y and      with resistant     (n=2), and mild
                                                                   alopecia totalis and                                                                              5–8m.                                      3 in patients>20y/    and severe AA.     acne (n=1)
                                                                   universalis                                                                                                                                  2 with a history
                                                                                                                                                                                                                of atopy,
                                                                                                                                                                                                                3/6 with AT and
                                                                                                                                                                                                                3/12 with AU)




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       Reference                           First                         Patients                    Alopecia
                                                          No.              Title          author      Trial type   Year (No., sex)     Age (y)         type          Treatment            Assessment           Outcome             Conclusion        Side effects
                                                       17          Early intervention    Chao-Chun   Retrospective 2013   85: 39M,   28.4          AT, AU, AO;   2.5–10 mg/kg/day       Photography at      >75% regrowth        IV and oral       Mild and
                                                                   with high-dose        Yang                             46F        (range4–60)   alopecia      of oral prednisolone   baseline and end    in 51% of            pulse of          transient side
                                                                   steroid pulse                                                                   >50%          or IV MP for           of treatment;       patients. More       steroids are      effects in both
                                                                   therapy prolongs                                                                              3 consecutive days     satisfactory        satisfactory         safe options in   groups: flushing,
                                                                   disease-free                                                                                                         response: hair      results in 50-       treating severe   hyperglycemia,
                                                                   interval of severe                                                                                                   regrowth more       70% baldness         AA, showing       increased
                                                                   alopecia areata: a                                                                                                   than 75%; scoring   rather than AU       equal efficacy;   appetite,
                                                                   retrospective study                                                                                                  based on the        or AT; better        initiation        insomnia, &
                                                                                                                                                                                        Alopecia Areata     response when        time plays an     palpitations; no
                                                                                                                                                                                        Investigational     treated during 1st   important role    long-term side
                                                                                                                                                                                        Assessment          year of disease      in the efficacy   effect




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                                                                                                                                                        Guidelines                               rate
                                                       18          Pulse corticosteroid D.           Retrospective 2012   30: 10M,   27.4          AT, AU, AO,   500 mg–1 gr            Phone interviews;   More than half       Poor long-term    22 out of
                                                                   therapy for          Staumont-                         20F        (range5–63)   PF AA, and    (or 10–20 mg/          online              still had severe     efficacy of       30 experienced
                                                                   alopecia areata:     Sallé                                                      30–50% AA     kg) IV MP for          supplementary       AA; those            corticosteroid    side effects:
                                                                   long-term outcome                                                                             3 consecutive          questionnaire       with initial         pulse in          tiredness,
                                                                   after 10 years                                                                                days/m for 3m          (www. karger.com/   response to          severe AA;        headache,
                                                                                                                                                                                        doi/10.1159         therapy during       recommended       flushing, nausea
                                                                                                                                                                                        /000341523);        first 6m had         other kinds of    and vomiting,
                                                                                                                                                                                        clinical            milder disease       treatment for     and transient
                                                                                                                                                                                        examinations;       in next 10y vs.      this group of     hyperglycemia
                                                                                                                                                                                        DLQI; all were      non-responders       patients
                                                                                                                                                                                        done 10 years
                                                                                                                                                                                        after treatment
                                                       19          Pulse corticosteroid Rivka        Retrospective 2013   24: 8M,    8 ± 4.6       AT, AU, AO,   8–10 mg/kg IV MP       Monthly clinical    38% complete    MP pulse               Only 3 patients
                                                                   therapy for alopecia Friedland    study                16F                      PF AA         for 3 consecutive      examination         response, 29%   is effective           had very mild
                                                                   areata in children: a                                                                         days, monthly                              partial response,
                                                                                                                                                                                                                            in children            transient side
                                                                   retrospective study                                                                                                                      33% no response,with PF AA,            effects
                                                                                                                                                                                                            81% relapse;    with a high
                                                                                                                                                                                                                            relapse rate but
                                                                                                                                                                                                            Good prognostic
                                                                                                                                                                                                                            minimal side
                                                                                                                                                                                                            factors: age    effects
                                                                                                                                                                                                            <10y & disease
                                                                                                                                                                                                            initiation <6m




13
                                                       Reference                          First                        Patients                  Alopecia




14
                                                          No.             Title          author     Trial type   Year (No., sex)    Age (y)        type         Treatment              Assessment            Outcome             Conclusion         Side effects
                                                       20          Comparison          In Kwon     Retrospective 2015   142:     8~80 years    PF AA, AT,   Group A: IV-pump        Hair regrowth         Good response        Pulse              Group A:
                                                                   of high-dose        Yeo                              79M, 63F (mean, 35.1   AU           MP 1 g/day, twice a     was evaluated on      rate was higher      corticosteroid     gastrointestinal
                                                                   corticosteroid                                                years)                     day for 3 consecutive   a scale of 0-100%.    in Group A.          therapy            discomfort,
                                                                   pulse therapy                                                                            days for adults         Good response:        Patients in Group    is a better        headache,
                                                                   and combination                                                                          and 10 mg/kg/           regrowth of >50%      A with PF AA         treatment          dizziness, facial
                                                                   therapy using                                                                            day weekly for 3w       of the lesion         and those with       option than        flushing, and
                                                                   oral cyclosporine                                                                        for children + oral     surface               disease duration     combination        palpitation;
                                                                   with low-dose                                                                            MP 30 mg/day for                              ≤3m had better       therapy in         Group B:
                                                                   corticosteroid in                                                                        3 days;Group B:                               response,            patients with      gastrointestinal
                                                                   severe alopecia                                                                          oral cyclosporine                             whereas in Group     severe AA and      discomfort,
                                                                   areata                                                                                   (2.5 mg/kg/day +                              B, the disease       PF AA              headache, and
                                                                                                                                                            MP (2.5–5 mg/day)                             duration/type                           hypertension
                                                                                                                                                            for 4m                                        did not affect the
                                                                                                                                                                                                          response. PF =
                                                                                                                                                                                                          better response
                                                                                                                                                                                                          than the others.
                                                       21          Pulse corticosteroid Takeshi    Retrospective 2007   139:     15–73 (mean Recent-onset   500 mg IV MP            Evaluation of         Recent-onset         This therapy       Only mild
                                                                   therapy for alopecia Nakajima                        43M, 96F age: 35.1)  extensive AA   over an hour on 3       hair regrowth         disease linked       is effective and   & transient
                                                                   areata: study of                                                                         consecutive days        was made mostly       with more            promising in       side effects:
                                                                   139 patients                                                                                                     by the attending      regrowth;            patients with      palpitations,
                                                                                                                                                                                    investigators         patients with        less severe AA     headache, low-
                                                                                                                                                                                    (84.2%) and by        recent-onset         (<50%) and in      grade fever, and
                                                                                                                                                                                    serial photos after   and less severe      patients with      insomnia
                                                                                                                                                                                    6m                    disease (<50%)       recent-onset of
                                                                                                                                                                                                          responded better     AA, with only
                                                                                                                                                                                                          than patients        mild adverse
                                                                                                                                                                                                          with recent-         effects of
                                                                                                                                                                                                          onset and 100%       corticosteroids
                                                                                                                                                                                                          hair loss; none
                                                                                                                                                                                                          of the patients
                                                                                                                                                                                                          with 100% hair
                                                                                                                                                                                                          loss and >6m
                                                                                                                                                                                                          of AA history
                                                                                                                                                                                                          responded;
                                                                                                                                                                                                          relapse in
                                                                                                                                                                                                          16.7% of good
                                                                                                                                                                                                          responders
                                                                                                                                                                                                          (n=66) during
                                                                                                                                                                                                          15.3m mean
                                                                                                                                                                                                          follow-up




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       22           Multiple courses of Takashi                           2016    55:13M,      16-64           AA               IV MP 500 mg/day       The development       Fewer courses        This treatment      Transient mild
                                                                    pulse corticosteroid Yoshimasu                                41F                                           was infused over 2     of vellus hair:       of PT required       can be              side effects
                                                                    therapy for                                                                                                 h on 3 consecutive     good response         for vellus hair      considered          in 5 patients:
                                                                    alopecia areata                                                                                             days (at least one     to short-term         to develop in        an effective        muscular pain
                                                                                                                                                                                course of therapy      therapy; good         patients with        modality in         in extremities,
                                                                                                                                                                                up to three courses)   long-term             <50% hair loss       treating recent-    finger
                                                                                                                                                                                                       response (6m          and <6m disease      onset severe        numbness,
                                                                                                                                                                                                       after the last        onset; good short-   AA and in           leg edema,
                                                                                                                                                                                                       pulse): >75%          term and long-       patients with       and stomach
                                                                                                                                                                                                       hair regrowth on      term response        less extensive      discomfort;
                                                                                                                                                                                                       alopecia lesions      rate (100%) in       disease             treatment was
                                                                                                                                                                                                                             patients with                            stopped
                                                                                                                                                                                                                             <50% hair loss
                                                                                                                                                                                                                             regardless of
                                                                                                                                                                                                                             disease duration;
                                                                                                                                                                                                                             no response in
                                                                                                                                                                                                                             those with 100%
                                                                                                                                                                                                                             hair loss for >6m




Review | Dermatol Pract Concept. 2023;13(4):e2023255
                                                       23           High-dose pulse        Simone         Monocenter,     2000    30           14–56 (mean PF AA, OA,           IV MP (8 mg/           Re-examination        40% of the           IV MP is a safe     Transient mild
                                                                    corticosteroid         Seiter         prospective                          31)         AT, AU               kg body weight)        at 1, 3, 6, & 12m     patients had         and effective       side effects
                                                                    therapy in the                                                                                              over 30 min on 3       after completion      >50% regrowth        treatment           included
                                                                    treatment of severe                                                                                         consecutive days at    of a 3-course         and 13% had 10-      option for PF       headache (n = 5),
                                                                    alopecia areata                                                                                             monthly intervals      treatment; serial     50% regrowth;        AA, while it is     fatigue (n = 3),
                                                                                                                                                                                                       photographs           67% of patients      less effective in   palpitations
                                                                                                                                                                                                       compared with         with PF AA           patients with       (n = 2), and
                                                                                                                                                                                                       the pretreatment      had >50% hair        AT, AU, or OA       nausea (n = 1).
                                                                                                                                                                                                       status by             growth, while
                                                                                                                                                                                                       2 independent         none with OA/
                                                                                                                                                                                                       investigators         AT/AU showed
                                                                                                                                                                                                                             >50% hair
                                                                                                                                                                                                                             growth
                                                       24           Interest of            Catherine      Retrospective 2012      20: 12F,     14–57           Multifocal       500 mg dose of IV      Monthly               The mean period      This treatment      No side effects of
                                                                    high-dose pulse        Droitcourta    case series             8M           (mean 33)       AA, AT           MP in 3 consecutive    assessments           of hair regrowth     can be              corticosteroids
                                                                    corticosteroid                                                                                              doses monthly          during the first 3m   initiation was       considered          were recorded.
                                                                    therapy combined                                                                                            for at least 3m in     of treatment, and     2.5m. By 18m,        effective and       Only 3 patients
                                                                    with methotrexate                                                                                           combination with       then every 3m by      multifocal AA        well tolerated      had MTX-
                                                                    for severe                                                                                                  MTX (12.5 mg/          a dermatologist;      responded better     in treating         related side
                                                                    alopecia areata: a                                                                                          week up to 25 mg/      serial photographs    than AT. Patients    severe AA,          effects (nausea
                                                                    retrospective case                                                                                          week over the next     were taken during     with >12m            though a longer     in 2 and
                                                                    series                                                                                                      6m) at the end of      visits; hair growth   disease duration     follow-up is        neutropenia in 1)
                                                                                                                                                                                the second pulse       was evaluated on      responded more       recommended.        and stopped
                                                                                                                                                                                regimen                a scale of 0–100%     vs. patients with                        treatment after
                                                                                                                                                                                                                             <12m                                     5 months.
                                                       AA = Alopecia Areata; AT = Alopecia Totalis; AU = Alopecia Universalis; F = Female; IM = Intramuscular; IV = Intravenous; M = Male; m = months; MP = Methylprednisolone; MTX = Methotrexate; w = weeks; OA = Ophiasis Alopecia;




15
                                                       PF = Plurifocal; PT = Pulse Therapy; TNF-α = Tumor Necrosis Factor-alpha; WAP = Weekly Azathioprine; SALT = Severity Alopecia Tool; VAS = Visual Analogue Scale; Dex = Dexamethasone; DLQI = Dermatology Life Quality Index.
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