Therapeutic management in pediatric alopecia areata: a systematic review

A. Waśkiel-Burnat, M. Kołodziejak, M. Sikora, A. Stochmal, A. Rakowska, M. Olszewska, L.

Rudnicka
Accepted Article
Department of Dermatology, Medical University of Warsaw, Warsaw, Poland

Corresponding author:
Mariusz Sikora, MD, PhD
Department of Dermatology, Medical University of Warsaw
Koszykowa 82A, 02-008 Warsaw, Poland
Telephone number: +48 22 5021324
Fax: +48228242200
e-mail: msikora@wum.edu.pl

Manuscript word count: 4535

Number of tables: 2 (1 supplementary table)
Number of figures: 1
The authors have no conflict of interest to declare.
This article has no funding source

Key words: alopecia areata, children, childhood, hair loss, pediatric, young

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/JDV.17187
This article is protected by copyright. All rights reserved
Accepted Article
Abstract
Alopecia areata is the third-most-common cause of dermatology consultations in children but
the treatment of pediatric alopecia areata remains challenging. A systematic review of the
literature about the treatment of alopecia areata in children (≤ 18 years old) was performed on
11 May 2020 by searching the PubMed, Scopus and EBSCO databases. The terms used for the
search were: “alopecia areata”, “alopecia totalis” or “alopecia universalis” combined with
“pediatric”, “children” or “childhood”. A total of 89 articles were included in final evaluation.
The most commonly assessed treatment options in pediatric alopecia areata were topical
immunotherapy (response rate in monotherapy: 54%; 187/345) intralesional
glucocorticosteroids (75%; 211/280), systemic glucocorticosteroids (73%; 102/140), and
anthralin (42%; 31/74). Topical glucocorticosteroids (81%; 35/43), systemic Janus kinase
(JAK) inhibitors (90%; 27/30), topical calcineurin inhibitors (42%; 8/19), topical JAK
inhibitors (63%; 11/17), PUVA therapy (56%; 9/16) and 308-nm excimer laser (77%; 10/13)
were also evaluated. Additionally, evaluation in smaller numbers of pediatric patients included
methotrexate (100%; 10/10), topical minoxidil (44%; 4/9) and cyclosporine (83%; 5/6). There
were limited data considering children with alopecia areata treated with azathioprine,
hydroxychloroquine, topical sildenafil, topical prostaglandin analogues, fractional carbon
dioxide laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab,
botulinum toxin, and compound glycyrrhizin. On the basis of the limited data available
glucocorticosteroids (systemic, intralesional or topical) and JAK inhibitors (systemic or
topical) may be considered the best documented and most effective treatment options in
alopecia areata in children. There are no sufficient pediatric data to compare treatment safety
and relapse rates in these therapeutic modalities.

This article is protected by copyright. All rights reserved

 Introduction
Accepted Article
Alopecia areata is an autoimmune type of non-scarring hair loss.1 The prevalence of
the disease is 0.2% in the general population.1 Alopecia areata is the third most common
cause of dermatology consultations in children. It was estimated that approximately 40% of
individuals had their first episode of hair loss by age 20 and 20% of all the cases of alopecia
areata occurred in infancy.2
The course of alopecia areata is unpredictable. Spontaneous remission may occur.3
Some patients experience relapsing episodes, progression to extensive loss, and prolonged
courses with the lack of regrowth. The most important negative prognostic factors are the
extent of hair loss (extensive alopecia areata, alopecia totalis or alopecia universalis)4, the
ophiasis pattern of hair loss5 and a long duration of the disease.5 Alopecia areata occurring
before puberty is usually associated with a poorer prognosis than alopecia areata in adults.6
Moreover, atopy, a positive family history, the presence of other autoimmune diseases and
nail involvement7 are considered as negative prognostic factors.
Numerous therapies are available for the treatment of alopecia areata, including topical
and systemic modalities. There are a number of guidelines considering therapeutic
management in patients with alopecia areata.8-12 However, they are usually focused on the
adult population and do not include all therapeutic options for which literature data are
available. The most recent international Alopecia Areata Consensus of Experts11 showed that
experts differed in their approach to the treatment of alopecia areata. According to the Italian
recommendations for the treatment of alopecia areata the treatment of children above 10 years
of age should be the same as in adults.8, 12 The British Association of Dermatologists
suggested treating children at every age with a similar regimen to adults.9
The aim of the review was to summarize data concerning the treatment of pediatric
alopecia areata.

Materials and methods

A review of the literature about the treatment of alopecia areata in children (≤ 18 years old)
was performed on 11 May 2020 by searching the PubMed, Scopus and EBSCO databases.
The terms used for the search were: “alopecia areata”, “alopecia totalis” or “alopecia
universalis” combined with “pediatric”, “children” or “childhood”. In addition, the reference

This article is protected by copyright. All rights reserved

 sections of all relevant articles were searched for further publications. All of the selected
articles were published in English, with the first one dating from 1946.
For each included study, reported variables such as the author, year, the type of study, the
Accepted Article
number of patients, the type of treatment, response outcomes, the frequency of relapses and
side effects were recorded. Response to therapy was defined as any hair regrowth. In addition,
the level of evidence available for each analyzed paper was evaluated and classified according
to The Oxford 2011 Levels of Evidence as: level of evidence I, a systematic review of
randomized trials or n-of-1 trials; II, a randomized trial or observational study with a dramatic
effect; III, a non-randomized controlled cohort/follow-up study; IV, case series, case-control
studies, or historically controlled studies; V, mechanism-based reasoning. Notably, single
case reports were labeled as level of evidence V.
Studies with no primary epidemiologic data reporting the numbers of patients with alopecia
areata, animal studies, conference materials and reviews were excluded from this analysis. If
data were duplicated in more than one study, the most complete study was included in the
analysis. Moreover, we excluded studies considering adults and children together or only adults
with alopecia areata. Data flow diagram is presented in Figure 1.

Results
A summary of detailed results is presented in Table 1 and Supplementary Table 1.

Topical immunotherapy [the highest level of evidence: III; the total number of patients:
351; response rate in monotherapy: 54% (187/345); global response rate: 54%
(191/351); relapse rate: 53% (41/78)]
According to the literature, the concentration of diphenylcyclopropenone (DPCP) used in
children with alopecia areata varied between 0.0001% and 2%13, 14, while the concentration of
squaric acid dibutylester (SADBE) between 0.00001% and 1%.15 Based on literature data,
SADBE was more effective compared to DPCP in children with alopecia areata (response rate
in monotherapy: 64%,105/163 vs 46%, 85/185). The side effects of topical immunotherapy
included eczema, urticaria and cervical or occipital lymphadenopathy.16, 17 In a study
conducted by Salsberg et al.17 they were observed in 54% (58/108) of children with alopecia
areata. Orecchia et al.18 reported local lymphadenopathy in nearly all subjects which was
considered a favorable sign.

This article is protected by copyright. All rights reserved

 Intralesional glucocorticosteroids [the highest level of evidence: IV; the total number of
patients: 280; response rate in monotherapy: 75% (211/280); global response rate: 75%
(211/280); relapse rate: no data available]
Accepted Article
Only one study tackled the issue of intralesional acetonide triamcinolone in children with
alopecia areata. According to Tan et al.19, over a 50% improvement was observed after 12 and
24 weeks in 57% (160/280) and 75% (211/280) of children with alopecia areata,
respectively.19 However, 11% (32/280) of patients discontinued the therapy because of pain,
the lack of response or progression of the disease.

Systemic glucocorticosteroids [the highest level of evidence: III; the total number of
patients: 223; response rate in monotherapy: 73% (102/140); global response rate: 70%
(157/223); relapse rate: 63% (61/97)]
According to the present review, systemic glucocorticosteroids were effective as monotherapy
in 73% (102/140) of children with alopecia areata, but they were characterized by the highest
relapse rate from various therapeutic options (63%; 61/97). Oral, intravenous and
intramuscular glucocorticosteroids were used in children with alopecia areata. Pulse (5 mg/kg
or 300 mg once a month) or sustained (0.5-2 mg/kg/day or 5-10 mg/day) therapy with oral
prednisolone and intravenous methylprednisolone pulse therapy (8-30 mg/kg for three days
once a month or 500 mg for one day once a month) were prescribed the most commonly.20-22
Side effects were infrequent and included weight gain, steroid acne, muscle pain, headache,
abdominal pain, behavioral changes, Cushing syndrome, high ocular pressure, striae
distensae, dysmenorrhea, pseudoacanthosis nigricans, and hypertrichosis.22-27

Anthralin [the highest level of evidence: III; the total number of patients: 111; response
rate in monotherapy: 42% (31/74); global response rate: 52% (58/111); relapse rate:
51% (18/35)]
The frequency at which anthralin 0.5% and 1% was used in children with alopecia areata
ranged from twice a week to once daily.19, 28, 29 The side effects of anthralin included irritation
and regional lymphadenopathy.29

Topical glucocorticosteroids [the highest level of evidence: II; the total number of
patients: 52; response rate in monotherapy: 81% (35/43); global response rate: 83%
(43/52); relapse rate: 53% (9/17)]

This article is protected by copyright. All rights reserved

 A study performed by Lenane et al.30 showed that clobetasol propionate 0.05% cream was
more effective compared to hydrocortisone 1% cream. They observed a ≥50% reduction in
the affected scalp surface area in 17/20 (85%) children with alopecia areata treated with
Accepted Article
clobetasol propionate 0.05% cream once a day for 24 weeks. Conversely, in children treated
with hydrocortisone 1% cream a ≥50% reduction in the affected scalp surface area was
observed in 7/21 (33%) cases. A study performed by Pascher et al.31 revealed topical
fluocinolone acetonide to be as effective in children with alopecia totalis as in children with
patchy alopecia areata. The adverse effects of topical glucocorticosteroids were rarely
reported in children with alopecia areata.32 Lenane et al.30 reported atrophy in only 5% (1/20)
of cases treated with clobetasol propionate.

Systemic JAK inhibitors [the highest level of evidence: IV; the total number of patients:
33; response rate in monotherapy: 90% (27/30); global response rate: 91% (30/33);
relapse rate: 0% (0/2)]
Systemic JAK inhibitors were used in children with alopecia areata mainly in monotherapy.
However, a combination of systemic JAK inhibitors with topical or oral glucocorticosteroids
was also described.33-35 Tofacitinib (10 mg/day) was most commonly used.36-38 However,
ruxolitinib (80 mg/day) and baricitinib (7-11 mg/day) were also described as effective in
pediatric alopecia areata.35, 39 Systemic JAK inhibitors are characterized by high response
rates. Studies performed by Castelo-Soccio et al.40 and Dai et al.38 revealed >50% of hair
regrowth in 100% of children with alopecia areata. The adverse effects of systemic JAK
inhibitors in childhood alopecia areata were diarrhea, upper respiratory tract infection and
headaches.33-35

Topical calcineurin inhibitors [the highest level of evidence: III; the total number of
patients: 19; response rate in monotherapy: 42% (8/19); global response rate: 42%
(8/19); relapse rate: no data available]

Jung et al.41 and Sotiriou et al.42 observed hair regrowth after topical tacrolimus 0.1% in 100%
(3/3) and 44% (5/11) of children with alopecia areata, respectively. Conversely, a study
performed by Price et al.43 revealed that topical tacrolimus 0.1% was ineffective in both,
adults and children with alopecia areata. No side effects of topical calcineurin inhibitors were
described in children with alopecia areata.41-43

This article is protected by copyright. All rights reserved

 Topical JAK inhibitors [the highest level of evidence: IV; the total number of patients:
17; response rate in monotherapy: 63% (11/17); global response rate: 63% (11/17);
relapse rate: 25% (2/8)]
Accepted Article
The number of studies concerning the efficacy of topical Janus kinase (JAK) inhibitors in
children with alopecia areata is limited.44 Putterman et al.44 demonstrated that hair regrowth
was observed in 73% (8/11) of cases after therapy with topical tofacitinib 2%, while in a study
conducted by Bayart et al.45 some hair regrowth was reported in 50% (3/6) of children with
alopecia areata after topical tofacitinib 2% or ruxolitinib 1-2% therapy. Topical JAK
inhibitors were characterized by minimal side effects – to date temporary leukopenia and
increased liver enzymes have been detected in one child with alopecia areata.44

PUVA therapy [the highest level of evidence: III; the total number of patients: 16;
response rate in monotherapy: 56% (9/16); total response rate: 56% (9/16); relapse rate:
0% (0/5)]
Apart from traditional PUVA therapy, an alternative method – “Turban PUVAsol” – was
described in a study conducted by Majumdar et al.46 The patients were asked to mix 1 ml of 8-
methoxypsoralen solution in two liters of water. A cotton towel was dipped and soaked in the
prepared solution. Then, it was wrapped around the patient's head like a turban. After 30
minutes the patient was exposed to sunlight for two hours. Partial hair regrowth was observed
in 86% (6/7) of cases. The side effects of PUVA observed in children with alopecia areata
were itching, irritation, scaling and hyperpigmentation.46

308-nm excimer laser [the highest level of evidence: III; the total number of patients: 14;
response rate in monotherapy: 77% (10/13); total response rate: 79% (11/14); relapse
rate: 50% (4/8)]
Al-Mutairi et al.47 described hair regrowth on the scalp in eight out of 11 (73%) children with
alopecia areata treated with 308-nm excimer laser (50 mJ/cm2, gradually increasing) for three
months. Lesions on the upper and lower extremities did not respond. Adverse effects were
limited to mild erythema, hyperpigmentation, itching, and mild peeling of the skin.47

Systemic methotrexate [the highest level of evidence: IV; the total number of patients:
52; response rate in monotherapy: 100% (10/10); global response rate: 77% (40/52);
relapse rate: 38% (3/8)]

This article is protected by copyright. All rights reserved

 In pediatric alopecia areata, methotrexate (2.5-25 mg/week or 0.2 mg/kg/day) was usually
used in combination with glucocorticosteroids. However, it was also reported to be effective
in monotherapy with the response rate of 100% (10/10).48-50 The adverse effects of systemic
Accepted Article
methotrexate in children with alopecia areata included nausea, vomiting, abdominal
discomfort, abnormal liver function test results, neutropenia, migraine, leg weakness and
tooth sensitivity.48-53

Topical minoxidil [the highest level of evidence: III; the total number of patients: 9;
response rate in monotherapy: 44% (4/9); global response rate: 44% (4/9); relapse rate:
0% (0/1)]
The number of studies concerning the effectiveness of minoxidil separately in children with
alopecia areata is limited.11 The concentration of minoxidil used in children with alopecia
areata varied between 1% and 5%.54-56 The side effects of topical minoxidil reported in
children with alopecia areata included generalized hypertrichosis (11%; 1/9) and arrhythmia
(33%; 3/9).56, 57

Systemic cyclosporine [the highest level of evidence: III; the total number of patients:
22; response rate in monotherapy: 83% (5/6); global response rate: 86% (19/22); relapse
rate: 100% (5/5)]
Cyclosporine (100-200 mg/day or 5-7.5 mg/kg/day) was described as an effective treatment
option in children with alopecia areata in monotherapy or in combination with systemic
glucocorticosteroids or PUVA therapy.58-60 No side effects of cyclosporine were described in
children with alopecia areata.

Systemic azathioprine [the highest level of evidence: IV; the total number of patients: 4;
response rate in monotherapy: no data available; total response rate: 75% (3/4); relapse
rate: no data available]
Azathioprine (100 mg/day) combined with methotrexate or anthralin was described to be
effective in children with alopecia areata.61, 62 No side effects or relapses were reported in
children with alopecia areata treated with azathioprine.

This article is protected by copyright. All rights reserved

 Systemic hydroxychloroquine [the highest level of evidence: IV; the total number of
patients: 9; response rate in monotherapy; no data available ; global response rate: 56%
(5/9); relapse rate: no data available]
Accepted Article
One study was performed to assess the efficacy of hydroxychloroquine in children with
alopecia areata. Yun et al.3 included nine children with alopecia areata in the study. They
were treated with hydroxychloroquine at a dose of 50-400 mg daily for 4-24 months. Partial
hair regrowth was observed in 56% (5/9) of cases. No patients achieved complete hair
regrowth. The adverse effects of hydroxychloroquine included abdominal pain, headache and
viral gastroenteritis.

Topical sildenafil [the highest level of evidence: III; the total number of patients: 8;
response rate in monotherapy: 38% (3/8); global response rate: 38% (3/8); relapse rate:
no data available]
Sarifakioglu et al.63 treated eight children with alopecia areata with sildenafil 1% cream
applied twice daily for three months to the skin lesions. In 25% (2/8) of cases, vellus hairs
were detected, while in 12.5% (1/8) terminal hairs were observed. However, such hair growth
was also observed in the patches that were left untreated. No local or systemic side effects of
topical sildenafil were reported.

Topical prostaglandin analogues [the highest level of evidence: V; the total number of
patients: 1; response rate in monotherapy: 100% (1/1); global response rate: 100%
(1/1); relapse rate: no data available]
To date, one case report has been published including the description of a child with scalp
alopecia areata with complete hair regrowth after topical bimatoprost 0.03% therapy.64

Fractional carbon dioxide laser [the highest level of evidence: IV; the total number of
patients: 1; response rate in monotherapy: 100% (1/1); total response rate: 100% (1/1);
relapse rate: no data available]
In a study performed by Majid et al.65 one child with alopecia areata was treated with
fractional carbon dioxide laser (50-60 mJ/cm2) followed by the topical application of
triamcinolone spray. The patient received four sessions repeated at an interval of three to four
weeks with 90% of hair regrowth.

This article is protected by copyright. All rights reserved

 Systemic leflunomide [the highest level of evidence: V; the total number of patients: 1;
response rate in monotherapy: -; total response rate: 100% (1/1); relapse rate: 0% (0/1)]
One case revealed unsuccessful corticosteroid therapy in a child with recalcitrant partial
Accepted Article
alopecia areata. Subsequently, the patient was successfully treated with leflunomide (20
mg/day) and anthralin.62

Mesalazine [the highest level of evidence: IV; the total number of patients: 5; response
rate in monotherapy: no data available; global response rate: 100% (5/5); relapse rate:
0% (0/5)]
Kiszewski et al.66 presented data concerning five children with alopecia areata treated with
mesalazine (15-30 mg/day) and topical betamethasone/minoxidil. At baseline, oral
prednisolone was introduced in 4/5 patients for 30-90 days. Complete hair regrowth was
observed in all cases with no relapses or adverse effects.

Systemic apremilast [the highest level of evidence: V; the total number of patients: 1;
response rate in monotherapy: no data available; total response rate: 100% (1/1);
relapse rate: no data available]
Chhabra et al.67 reported a case of a child with alopecia areata who responded to the treatment
with apremilast (30 mg/day) and platelet-rich plasma.

Dupilumab [the highest level of evidence: V; the number of patients: 1; response rate in
monotherapy: 100% (1/1); global response rate: 100% (1/1); relapse rate: 100% (1/1)]
One case report was presented which described hair regrowth in a child with atopic dermatitis
and coexisting alopecia areata after dupilumab (300 mg s.c.) therapy.68

Ustekinumab [the highest level of evidence: IV; the total number of patients: 3; response
rate in monotherapy: 100% (3/3); total response rate: 100% (3/3); relapse rate: no data
available]
A case series described by Aleisa et al.69 showed hair regrowth and no side effects after
ustekinumab therapy (90 mg i.m.) in three children with alopecia areata.

This article is protected by copyright. All rights reserved

 Efalizumab [the highest level of evidence: V; the number of patients: 1; response rate in
monotherapy: 100% (1/1); global response rate: 100% (1/1); relapse rate: no data
available]
Accepted Article
Literature search retrieved one case report of a child with alopecia areata with hair regrowth
after efalizumab therapy for atopic dermatitis.70

Botulinum toxin [the highest level of evidence: III; the total number of patients: 3;
response rate in monotherapy: 0% (0/3); total response rate: 0% (0/3); relapse rate: no
data available]
A study performed by Cho et al.71 in three children was alopecia areata showed that
botulinum toxin was ineffective.

Total glucosides of paeony capsule +/- compound glycyrrhizin tablets [the highest level
of evidence: II; the total number of patients: 117; response rate in monotherapy: no data
available; total response rate: 93% (109/117); relapse rate: no data available]
Compound glycyrrhizin (75 mg/day) with vitamin B2 was described as an effective therapy in
children with alopecia areata.72 They were more effective in combination with total glucosides
of paeony compared to monotherapy. The adverse effects of compound glycyrrhizin tablets
and total glucosides of paeony observed in the study performed by Yang et al.72 included
loose stool, increased stool frequency, edema, abdominal pain, hypokalemia, weight gain and
decreased muscle strength.72

Discussion
The present study is a systematic review of all treatment options of pediatric alopecia
areata with a detailed analysis of response rate, posology, treatment duration and side effects.
A total of 89 articles were included in the final evaluation. Treatment modalities which were
evaluated in at least 15 patients and showed an over 60% response rate in pediatric alopecia
areata were topical, intralesional and systemic glucocorticosteroids, as well as systemic or
topical JAK inhibitors (tofacitinib or ruxolitinib).
The mechanism of the action of topical sensitizers has not been fully elucidated.
Numerous theories were suggested, including antigenic competition, perifollicular
lymphocyte apoptosis and the peribulbar CD4/CD8 lymphocyte ratio change.32 Contact
sensitizers assessed in children with alopecia areata included DPCP and SADBE.16 According

This article is protected by copyright. All rights reserved

 to an Australian expert consensus statement10 topical immunotherapy is considered as one of
the first therapeutic options for pediatric alopecia areata. It is especially recommended for
children with multiple patches and the ophiasis pattern of hair loss. The Alopecia Areata
Accepted Article
Consensus of Experts11 suggested offering contact immunotherapy to children with alopecia
universalis, alopecia totalis or ophiasis before systemic therapy. According to Italian
guidelines, topical immunotherapy should be reserved for children above 10 years of age with
the chronic disease (both localized or extensive).8 Indeed, based on the present analysis
topical immunotherapy was most commonly used in children with alopecia areata. However,
it was characterized by lower efficacy compared to topical glucocorticosteroids.
Intralesional glucocorticosteroids, effective in adults with alopecia areata, are less
commonly used in children because of the fear of injections and potential pain.10, 73 According
to the Alopecia Areata Consensus of Experts intralesional are recommended for children over
the age of 13 with limited scalp alopecia areata (SALT 0-30%).11 Italian guidelines suggested
intralesional glucocorticosteroids for children above 10 years of age with active patchy
alopecia areata.8 On the contrary, according to the Australian Expert Consensus statement10
intralesional corticosteroid injection are not recommended in pediatric alopecia areata because
their use is generally not feasible without sedation. To date, only one study has been
conducted to investigate the use of intralesional glucocorticosteroids in children with alopecia
areata.19
Systemic glucocorticosteroids are characterized by the most rapid response of all
systemic therapeutic options.74 According to the Alopecia Areata Consensus of Experts11, oral
glucocorticosteroids are recommended in acute alopecia areata with SALT >50% and >30%
in children aged 7-12 and 13-18, respectively. In the chronic form of the disease, oral
glucocorticosteroids are suggested in patients at the age between 13 and 18 with SALT >50%.
In children below 7 years of age systemic glucocorticosteroids are not approved. Italian
guidelines8 suggested using systemic glucocorticosteroids in children above 10 years of age
with acute patchy or severe alopecia areata. It was suggested that pulse therapy with the
suprapharmacological doses of corticosteroid was cumulatively less toxic than sustained
corticosteroid treatment at a lower quantitative dosage.75 In the present analysis,
glucocorticosteroid pulse therapy was more commonly used compared to sustained
glucocorticosteroid treatment. The most common side effect in children with alopecia areata
treated with pulse therapy was abdominal pain, while in individuals treated with sustained
glucocorticosteroid treatment weight gain was most commonly reported.

This article is protected by copyright. All rights reserved

 The usefulness of anthralin, also known as dithranol, in alopecia areata, was first
described in 1979 by Schmoekel et al.76 It was suggested that free radicals generated by
anthralin could be the mechanism of anti-inflammatory action to clear infiltrated
Accepted Article
lymphocytes.77 According to Italian guidelines8, anthralin therapy is suggested in children
who are too young to be treated with topical glucocorticosteroids. It is recommended for
children with alopecia areata under 10 years of age and over 10 years of age with chronic,
patchy hair loss. Based on the present study, anthralin was characterized by a lower response
rate compared to topical glucocorticosteroids and immunotherapy.
Because of the minimal side effects of topical glucocorticosteroids and the ease of
application, they usually constitute the first-line therapy in pediatric alopecia areata
irrespective of disease severity.10, 11 Potent or ultrapotent topical glucocorticosteroids are
usually recommended.10, 11, 16 In the published studies, clobetasol propionate was used the
most commonly in children with alopecia areata. It was more effective compared to
hydrocortisone 1% cream.30 It was hypothesized that the topical application of
glucocorticosteroids in the diffuse form of alopecia areata may increase the risk of adverse
events.30 However, it was not confirmed in the present analysis.
JAK inhibitors, both topical and systemic, are not included in therapeutic
recommendations for pediatric alopecia areata.10, 11 Moreover, according to Italian guidelines8
the safety and efficacy of JAK inhibitors should be evaluated before their use in children with
alopecia areata. Based on the present analysis, both systemic and topical JAK inhibitors were
characterized by high response rates and a low frequency of adverse effects in children with
alopecia areata. The main disadvantage of JAK inhibitors is a significant cost of the therapy.40
Calcineurin inhibitors (tacrolimus, pimecrolimus) have been used for many years as
immunosuppressants in organ transplantation and in T-cell-mediated autoimmune diseases.
They inhibit transcription following the T-cell activation of several cytokines, such as
interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α).73 Topical
calcineurin inhibitors are not included in the majority of therapeutic recommendations for
alopecia areata.8, 10, 12 According to the Alopecia Areata Consensus of Experts11 topical
calcineurin inhibitors may be applied to treat scalp, eyebrow, or beard alopecia areata but
should not be considered the first-line topical treatment. The results of the studies
concentrating on the effectiveness of topical calcineurin inhibitors in pediatric alopecia areata
are ambiguous.

This article is protected by copyright. All rights reserved

 Methotrexate is an immunosuppressant folic acid antagonist.48 According to Italian
guidelines8 systemic methotrexate may be a treatment option for children above 10 years of
age with acute, severe alopecia areata. To date, limited data have been available as regards the
Accepted Article
role of methotrexate in the treatment of pediatric alopecia areata. In majority of studies
methotrexate was combined with systemic glucocorticosteroids in the therapy of pediatric
alopecia areata. It was suggested that the effectiveness of methotrexate in children may be
maintained long-term, in contrast to other treatments with a high relapse rate, such as the
boluses of methylprednisolone or diphencyprone.78 Indeed, recurrences following
methotrexate therapy were observed less commonly compared to systemic
glucocorticosteroids, topical immunotherapy and anthralin in pediatric alopecia areata. They
were reported in 38% (3/8) of children with alopecia areata. However, long-term follow-up
was not available in the majority of studies concerning the usefulness of methotrexate in
pediatric alopecia areata.48, 49, 53
Minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxide) was first described as a
treatment option for alopecia areata in 1982.73 According to Australian experts, topical
minoxidil should be one of the first-line therapeutic options in pediatric alopecia areata.10
However, limited literature data are available as regards the efficacy of minoxidil in children
with alopecia areata.
It was established that azathioprine impaired T-cell function as well as the essential
components of T-cell activation (interleukin-2).61 The main disadvantage of azathioprine
therapy is the delayed onset of action. Its benefits may be unobservable for 2-3 months after
the introduction of the treatment.79 According to Italian guidelines8 systemic azathioprine may
be a treatment option for children above 10 years of age with acute, severe alopecia areata. To
date, azathioprine has been used only in combination therapy with methotrexate or anthralin
in children with alopecia areata.
Prostaglandin analogues such as bimatoprost and latanoprost have been reported to
cause the hypertrichosis of the eyelashes. The mechanism of the action of prostaglandin
analogues in alopecia areata is unclear. According to the Alopecia Areata Consensus of
Experts, topical prostaglandin analogues may be prescribed as the first-line topical treatment
to treat eyelash alopecia areata.11 To date, only one case report has been published including
the description of a child with scalp alopecia areata with complete hair regrowth after topical
bimatoprost therapy.64

This article is protected by copyright. All rights reserved

 Furthermore, literature data were limited as regards the role of PUVA therapy, 308-nm
excimer laser, cyclosporine, hydroxychloroquine, topical sildenafil, fractional carbon dioxide
laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab, botulinum
Accepted Article
toxin and compound glycyrrhizin tablets in the treatment of pediatric alopecia areata. These
therapeutic options were not included in therapeutic guidelines for pediatric alopecia areata.8,
11

The evaluation of treatment efficacy in alopecia areata may be difficult because of

occasional spontaneous remissions and the heterogeneity of the disease. Individual response
to therapy is also a hindering factor.80 Some patients are prescribed combined treatment with
two or more established therapies, so the assessment of various drug efficacies may be
difficult. Another limitation is associated with the paucity of studies concerning the treatment
of pediatric alopecia areata with a high level of evidence.
Based on this systematic review, it may be suggested that the adverse effects of both topical
and systemic therapies are not commonly observed in children with alopecia areata. However,
long-term follow-up and safety were the topics of a limited number of studies in children with
alopecia areata.
It is worth emphasizing that pediatric alopecia areata is associated with the increased rates of
depression and anxiety.73 Therefore, psychological support and/or psychiatric treatment may
be beneficial in addition to dermatological therapy.81
It needs to be highlighted that treatment in pediatric alopecia areata should be selected
individually in every child. Therapeutic management in children with alopecia areata cannot
be based on drug efficacy only, as outcomes reported in individual studies are variable.
Potential short-term and long-term adverse events should be taken into consideration.

Conclusion
In conclusion, numerous treatment options are available for children with alopecia
areata. However, the number of randomized clinical trials and prospective studies considering
the therapy of pediatric alopecia areata is very limited.
Basing on available data, glucocorticosteroids (systemic, intralesional or topical) and JAK
inhibitors (systemic or topical) may be considered the best documented and most effective
treatment options in alopecia areata in children. Methotrexate in monotherapy was effective in
all pediatric patients reported, but the number of cases was insufficient to draw conclusions

This article is protected by copyright. All rights reserved

 for clinical practice. These treatment modalities may not be compared in terms of treatment
safety and relapse rates due to the paucity of pediatric data.
Accepted Article

This article is protected by copyright. All rights reserved

 References:
1. Alkhalifah A. Alopecia areata update. Dermatol Clin 2013;31:93-108.
Accepted Article
2. Rangu S, Rogers R, Castelo-Soccio L. Understanding alopecia areata characteristics in
children under the age of 4 years. Pediatric Dermatology 2019;36:854-858.
3. Yun D, Silverberg NB, Stein SL. Alopecia areata treated with hydroxychloroquine: A
retrospective study of nine pediatric cases. Pediatr Dermatol 2018;35:361-365.
4. Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long term follow-up study of 191
patients. J Am Acad Dermatol 2006;55:438-441.
5. Lew BL, Shin MK, Sim WY. Acute diffuse and total alopecia: A new subtype of alopecia
areata with a favorable prognosis. J Am Acad Dermatol 2009;60:85-93.
6. Hubiche T, Leaute-Labreze C, Taieb A et al. Poor long term outcome of severe alopecia
areata in children treated with high dose pulse corticosteroid therapy. Br J Dermatol
2008;158:1136-1137.
7. Madani S, Shapiro J. Alopecia areata update. J Am Acad Dermatol 2000;42:549-566; quiz
567-570.
8. Rossi A, Muscianese M, Piraccini BM et al. Italian Guidelines in diagnosis and treatment
of alopecia areata. G Ital Dermatol Venereol 2019;154:609-623.
9. Messenger AG, McKillop J, Farrant P et al. British Association of Dermatologists'
guidelines for the management of alopecia areata 2012. Br J Dermatol 2012;166:916-926.
10. Cranwell WC, Lai VW, Photiou L et al. Treatment of alopecia areata: An Australian
expert consensus statement. Australas J Dermatol 2019;60:163-170.
11. Meah N, Wall D, York K et al. The Alopecia Areata Consensus of Experts (ACE) study:
Results of an international expert opinion on treatments for alopecia areata. J Am Acad
Dermatol 2020.
12. Trüeb RM, Dias M. Alopecia Areata: a Comprehensive Review of Pathogenesis and
Management. Clinical reviews in allergy & immunology 2018;54:68-87.
13. Hull SM, Pepall L, Cunliffe WJ. Alopecia areata in children: response to treatment with
diphencyprone. Br J Dermatol 1991;125:164-168.
14. Schuttelaar ML, Hamstra JJ, Plinck EP et al. Alopecia areata in children: treatment with
diphencyprone. Br J Dermatol 1996;135:581-585.
15. Tosti A, Guidetti MS, Bardazzi F et al. Long-term results of topical immunotherapy in
children with alopecia totalis or alopecia universalis. J Am Acad Dermatol 1996;35:199-201.

This article is protected by copyright. All rights reserved

 16. Strazzulla LC, Wang EHC, Avila L et al. Alopecia areata: An appraisal of new treatment
approaches and overview of current therapies. J Am Acad Dermatol 2018;78:15-24.
17. Salsberg JM, Donovan J. The safety and efficacy of diphencyprone for the treatment of
Accepted Article
alopecia areata in children. Arch Dermatol 2012;148:1084-1085.
18. Orecchia G, Malagoli P, Santagostino L. Treatment of severe alopecia areata with squaric
acid dibutylester in pediatric patients. Pediatr Dermatol 1994;11:65-68.
19. Tan E, Tay YK, Giam YC. A clinical study of childhood alopecia areata in Singapore.
Pediatr Dermatol 2002;19:298-301.
20. Smith A, Trueb RM, Theiler M et al. High Relapse Rates Despite Early Intervention with
Intravenous Methylprednisolone Pulse Therapy for Severe Childhood Alopecia Areata.
Pediatr Dermatol 2015;32:481-487.
21. Seiter S, Ugurel S, Tilgen W et al. High-dose pulse corticosteroid therapy in the treatment
of severe alopecia areata. Dermatology 2001;202:230-234.
22. Sharma VK, Muralidhar S. Treatment of widespread alopecia areata in young patients
with monthly oral corticosteroid pulse. Pediatr Dermatol 1998;15:313-317.
23. Michalowski R, Kuczynska L. Long-term intramuscular triamcinolon-acetonide therapy in
alopecia areata totalis and universalis. Arch Dermatol Res 1978;261:73-76.
24. Sharma VK, Gupta S. Twice weekly 5 mg dexamethasone oral pulse in the treatment of
extensive alopecia areata. J Dermatol 1999;26:562-565.
25. Gensure RC. Clinical response to combined therapy of cyclosporine and prednisone. J
Investig Dermatol Symp Proc 2013;16:S58.
26. Camacho FM, Garcia-Hernandez MJ. Zinc aspartate, biotin, and clobetasol propionate in
the treatment of alopecia areata in childhood. Pediatr Dermatol 1999;16:336-338.
27. Kiesch N, Stene JJ, Goens J et al. Pulse steroid therapy for children's severe alopecia
areata? Dermatology 1997;194:395-397.
28. Ozdemir M, Balevi A. Bilateral Half-Head Comparison of 1% Anthralin Ointment in
Children with Alopecia Areata. Pediatr Dermatol 2017;34:128-132.
29. Wu SZ, Wang S, Ratnaparkhi R et al. Treatment of pediatric alopecia areata with
anthralin: A retrospective study of 37 patients. Pediatr Dermatol 2018;35:817-820.
30. Lenane P, Macarthur C, Parkin PC et al. Clobetasol propionate, 0.05%, vs hydrocortisone,
1%, for alopecia areata in children: a randomized clinical trial. JAMA Dermatol 2014;150:47-
50.

This article is protected by copyright. All rights reserved

 31. Pascher F, Kurtin S, Andrade R. Assay of 0.2 percent fluocinolone acetonide cream for
alopecia areata and totalis. Efficacy and side effects including histologic study of the ensuing
localized acneform response. Dermatologica 1970;141:193-202.
Accepted Article
32. Shapiro J. Current treatment of alopecia areata. J Investig Dermatol Symp Proc
2013;16:S42-44.
33. Brown L, Skopit S. An Excellent Response to Tofacitinib in a Pediatric Alopecia Patient:
A Case Report and Review. J Drugs Dermatol 2018;17:914-917.
34. Rachubinski AL, Estrada BE, Norris D et al. Janus kinase inhibition in Down syndrome: 2
cases of therapeutic benefit for alopecia areata. JAAD Case Rep 2019;5:365-367.
35. Jabbari A, Dai Z, Xing L et al. Reversal of Alopecia Areata Following Treatment With the
JAK1/2 Inhibitor Baricitinib. EBioMedicine 2015;2:351-355.
36. Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and
variants in adolescents. J Am Acad Dermatol 2017;76:29-32.
37. Craiglow BG, King BA. Tofacitinib for the treatment of alopecia areata in preadolescent
children. J Am Acad Dermatol 2019;80:568-570.
38. Dai YX, Chen CC. Tofacitinib therapy for children with severe alopecia areata. J Am
Acad Dermatol 2019;80:1164-1166.
39. Peterson DM, Vesely MD. Successful treatment of alopecia totalis with ruxolitinib in a
preadolescent patient. JAAD Case Rep 2020;6:257-259.
40. Castelo-Soccio L. Experience with oral tofacitinib in 8 adolescent patients with alopecia
universalis. J Am Acad Dermatol 2017;76:754-755.
41. Jung KE, Gye JW, Park MK et al. Comparison of the topical FK506 and clobetasol
propionate as first-line therapy in the treatment of early alopecia areata. Int J Dermatol
2017;56:1487-1488.
42. Sotiriou Elena PA, Fotiadou Christina, Sotiriadis Dimitrios, Panagiotidou Dimitrios.
Tacrolimus ointment 0.1% in the treatment of active patchy alopecia areata of childhood. Eur
J Pediat Dermatol 2007;17:227-230.
43. Price VH, Willey A, Chen BK. Topical tacrolimus in alopecia areata. J Am Acad
Dermatol 2005;52:138-139.
44. Putterman E, Castelo-Soccio L. Topical 2% tofacitinib for children with alopecia areata,
alopecia totalis, and alopecia universalis. J Am Acad Dermatol 2018;78:1207-1209 e1201.
45. Bayart CB, DeNiro KL, Brichta L et al. Topical Janus kinase inhibitors for the treatment
of pediatric alopecia areata. J Am Acad Dermatol 2017;77:167-170.

This article is protected by copyright. All rights reserved

 46. Majumdar B, De A, Ghosh S et al. "Turban PUVAsol:" A Simple, Novel, Effective, and
Safe Treatment Option for Advanced and Refractory Cases of Alopecia Areata. Int J
Trichology 2018;10:124-128.
Accepted Article
47. Al-Mutairi N. 308-nm excimer laser for the treatment of alopecia areata in children.
Pediatr Dermatol 2009;26:547-550.
48. Landis ET, Pichardo-Geisinger RO. Methotrexate for the treatment of pediatric alopecia
areata. J Dermatolog Treat 2018;29:145-148.
49. Batalla A, Florez A, Abalde T et al. Methotrexate in Alopecia Areata: A Report of Three
Cases. Int J Trichology 2016;8:188-190.
50. Royer M, Bodemer C, Vabres P et al. Efficacy and tolerability of methotrexate in severe
childhood alopecia areata. Br J Dermatol 2011;165:407-410.
51. Phan K, Lee G, Fischer G. Methotrexate in the treatment of paediatric alopecia areata:
Retrospective case series and updated meta-analysis. Australas J Dermatol 2019.
52. Droitcourt C, Milpied B, Ezzedine K et al. Interest of high-dose pulse corticosteroid
therapy combined with methotrexate for severe alopecia areata: a retrospective case series.
Dermatology 2012;224:369-373.
53. Chong JH, Taieb A, Morice-Picard F et al. High-dose pulsed corticosteroid therapy
combined with methotrexate for severe alopecia areata of childhood. J Eur Acad Dermatol
Venereol 2017;31:e476-e477.
54. Khoury EL, Price VH, Abdel-Salam MM et al. Topical minoxidil in alopecia areata: no
effect on the perifollicular lymphoid infiltration. J Invest Dermatol 1992;99:40-47.
55. Tosti A, De Padova MP, Minghetti G et al. Therapies versus placebo in the treatment of
patchy alopecia areata. J Am Acad Dermatol 1986;15:209-210.
56. Herskovitz I, Freedman J, Tosti A. Minoxidil induced hypertrichosis in a 2 year-old child.
F1000Res 2013;2:226.
57. Georgala S, Befon A, Maniatopoulou E et al. Topical use of minoxidil in children and
systemic side effects. Dermatology 2007;214:101-102.
58. Constantopoulos A, Tsoumacas C, Tsivitanidou T. Cyclosporine in severe alopecia areata
in children. Journal of the European Academy of Dermatology and Venereology 1996;7:190-
192.
59. Kim BJ, Min SU, Park KY et al. Combination therapy of cyclosporine and
methylprednisolone on severe alopecia areata. J Dermatolog Treat 2008;19:216-220.

This article is protected by copyright. All rights reserved

 60. Park KY, Jang WS, Son IP et al. Combination therapy with cyclosporine and psoralen
plus ultraviolet a in the patients with severe alopecia areata: a retrospective study with a self-
controlled design. Ann Dermatol 2013;25:12-16.
Accepted Article
61. Mascia P, Milpied B, Darrigade AS et al. Azathioprine in combination with methotrexate:
a therapeutic alternative in severe and recalcitrant forms of alopecia areata? J Eur Acad
Dermatol Venereol 2019;33:e494-e495.
62. Sardana K, Gupta A, Gautam RK. Recalcitrant alopecia areata responsive to leflunomide
and anthralin-Potentially undiscovered JAK/STAT inhibitors? Pediatr Dermatol 2018;35:856-
858.
63. Sarifakioglu E, Degim IT, Gorpelioglu C. Determination of the sildenafil effect on
alopecia areata in childhood: An open-pilot comparison study. J Dermatolog Treat
2006;17:235-237.
64. Li AW, Antaya RJ. Successful Treatment of Pediatric Alopecia Areata of the Scalp Using
Topical Bimatoprost. Pediatr Dermatol 2016;33:e282-283.
65. Majid I, Jeelani S, Imran S. Fractional Carbon Dioxide Laser in Combination with Topical
Corticosteroid Application in Resistant Alopecia Areata: A Case Series. J Cutan Aesthet Surg
2018;11:217-221.
66. Kiszewski AE, Bevilaqua M, De Abreu LB. Mesalazine in the Treatment of Extensive
Alopecia Areata: A New Therapeutic Option? Int J Trichology 2018;10:99-102.
67. Chhabra G, Verma P. Steroid-resistant alopecia totalis in a child successfully treated with
oral apremilast and platelet-rich plasma therapy. Dermatologic therapy 2019;32:e13082.
68. Penzi LR, Yasuda M, Manatis-Lornell A et al. Hair Regrowth in a Patient With Long-
standing Alopecia Totalis and Atopic Dermatitis Treated With Dupilumab. JAMA Dermatol
2018;154:1358-1360.
69. Aleisa A, Lim Y, Gordon S et al. Response to ustekinumab in three pediatric patients with
alopecia areata. Pediatr Dermatol 2019;36:e44-e45.
70. Price VH, Hordinsky MK, Olsen EA et al. Subcutaneous efalizumab is not effective in the
treatment of alopecia areata. J Am Acad Dermatol 2008;58:395-402.
71. Cho HR, Lew BL, Lew H et al. Treatment effects of intradermal botulinum toxin type A
injection on alopecia areata. Dermatol Surg 2010;36 Suppl 4:2175-2181.
72. Yang D, Zheng J, Zhang Y et al. Total glucosides of paeony capsule plus compound
glycyrrhizin tablets for the treatment of severe alopecia areata in children: a randomized
controlled trial. Evid Based Complement Alternat Med 2013;2013:378219.

This article is protected by copyright. All rights reserved

 73. Peloquin L, Castelo-Soccio L. Alopecia Areata: An Update on Treatment Options for
Children. Paediatr Drugs 2017;19:411-422.
74. Jahn-Bassler K, Bauer WM, Karlhofer F et al. Sequential high- and low-dose systemic
Accepted Article
corticosteroid therapy for severe childhood alopecia areata. J Dtsch Dermatol Ges
2017;15:42-47.
75. Friedland R, Tal R, Lapidoth M et al. Pulse corticosteroid therapy for alopecia areata in
children: a retrospective study. Dermatology 2013;227:37-44.
76. Schmoeckel C, Weissmann I, Plewig G et al. Treatment of alopecia areata by anthralin-
induced dermatitis. Arch Dermatol 1979;115:1254-1255.
77. Tang L, Cao L, Pelech S et al. Cytokines and signal transduction pathways mediated by
anthralin in alopecia areata-affected Dundee experimental balding rats. J Investig Dermatol
Symp Proc 2003;8:87-90.
78. Lucas P, Bodemer C, Barbarot S et al. Methotrexate in Severe Childhood Alopecia
Areata: Long-term Follow-up. Acta Derm Venereol 2016;96:102-103.
79. Farshi S, Mansouri P, Safar F et al. Could azathioprine be considered as a therapeutic
alternative in the treatment of alopecia areata? A pilot study. Int J Dermatol 2010;49:1188-
1193.
80. Wang E, Lee JS, Tang M. Current treatment strategies in pediatric alopecia areata. Indian
J Dermatol 2012;57:459-465.
81. Teshima H, Sogawa H, Mizobe K et al. Application of psychoimmunotherapy in patients
with alopecia universalis. Psychother Psychosom 1991;56:235-241.

This article is protected by copyright. All rights reserved

 Figure legends

Figure 1. PRISMA flow diagram.

Accepted Article

This article is protected by copyright. All rights reserved

Accepted Article
Records identified through database
Identification

searching

(n=3474)

(n = )

Records after duplicates removed

(n = 1746)
Screening

Records screened Records excluded

(n = 1746) (n = 1542)

Full-text articles assessed Full-text articles excluded,

for eligibility with reasons
(n = 204) (n = 115 *)
Eligibility

Studies included in qualitative

synthesis
(n = 89)

Studies included in
Included

quantitative synthesis
(n = 89**)

* Excluded articles: 8 studies considered only adults; 92 studies considered together children and
adults; 1 study was conference material; 1 study was review; 8 did not contain necessary data; 5
studies were duplications

** 2 randomized clinical trials; 32 prospective cohort studies; 21 retrospective cohort studies; 14

case series; 20 case reports

This article is protected by copyright. All rights reserved

 Table 1. Treatment options used in children with alopecia areata

Treatment option Highest level Total number Response rate in Global response Relapse rate
Accepted Article
of evidence of patients monotherapy rate No (%)
No (%) No (%)

Topical corticosteroids II 52 35/43 (81) 43/52 (83) 9/17 (53)

Intralesional IV 280 211/280 (75) 211/280 (75) NA

corticosteroids
Topical JAK inhibitors IV 17 11/17 (63) 11/17 (63) 2/8 (25)
Topical minoxidil III 9 4/9 (44) 4/9 (44) 0/1 (0)
Topical calcineurin III 19 8/19 (42) 8/19 (42) NA
inhibitors
Topical prostaglandin V 1 1/1 (100) 1/1 (100) NA
analogues
Topical sildenafil III 8 3/8 (38) 3/8 (38) NA
Topical immunotherapy III 351 187/345 (54) 191/351 (54) 41/78 (53)
Anthralin III 111 31/74 (42) 58/111 (52) 18/35 (51)
Fractional Carbon IV 1 1/1 (100) 1/1 (100) NA
Dioxide Laser
308-nm Excimer Laser III 14 10/13 (77) 11/14 (79) 4/8 (50)
PUVA therapy III 16 9/16 (56) 9/16 (56) 0/5 (0)
Systemic corticosteroids III 223 102/140 (73) 157/223 (70) 61/97 (63)
Systemic methotrexate IV 52 10/10 (100) 40/52 (77) 3/8 (38)
Systemic cyclosporine III 32 5/6 (83) 19/32 (59) 5/5 (100)
Systemic azathioprine IV 4 NA 3/4 (75) NA
Systemic leflunomide V 1 NA 1/1 (100) 0/1 (0)
Systematic mesalazine IV 5 NA 5/5 (100) 0/5 (0)
Systemic IV 9 NA 5/9 (56) NA
hydroxychloroquine
Systemic apremilast V 1 NA 1/1 (100) NA
Systemic JAK inhibitors IV 33 27/30 (90) 30/33 (91) 0/1 (0)
Ustekinumab IV 3 3/3 (100) 3/3 (100) NA
Dupilumab V 1 1/1 (100) 1/1 (100) 1/1 (100)
Efalizumab V 1 1/1 (100) 1/1 (100) NA
Botulinum toxin III 3 0/3 (0) 0/3 (0) NA
Compound glycyrrhizin II 117 NA 109/117 (93) NA
tablets
NA – No data available

This article is protected by copyright. All rights reserved