Local Corticosteroids for Alopecia Areata: A Narrative Review

Abstract

Alopecia areata (AA) is an autoimmune condition of non-scarring hair loss that affects 2% of the population worldwide. Topical and intralesional (IL) corticosteroids are the two most commonly used treatments for AA. These locally acting glucocorticoid derivatives are thought to treat AA by reducing the CD8+ T-cell-mediated immune attack on hair follicles. Topical corticosteroids are safe and well tolerated with moderate efficacy in mild AA, but recurrence is common after treatment cessation. They are recommended for children and adults with mild AA who cannot tolerate IL injections. IL steroids are more effective than topical steroids given their ability to penetrate the dermis, where the hair follicle resides. Success rates are higher than topical steroids in mild-to-moderate AA. IL steroids are safe and well tolerated; however, treatment is limited by pain during the procedure. Further research is needed on ideal treatment regimens, long-term safety, preferred candidates, and the role of combination therapy to further elucidate the role of local corticosteroids for AA in clinical practice.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-025-01421-2.

Plain Language Summary

Alopecia areata is a common hair loss condition in which the immune system mistakenly attacks hair follicles, causing the hair to fall out. Topical steroids, which come in lotions, foams, ointments, and creams, as well as intralesional steroids, which are injected into the skin, are the two most commonly used treatments for alopecia areata. They are thought to treat alopecia areata by reducing the immune system attack on hair follicles. Topical steroids are moderately effective for patients with mild alopecia areata, but the disease may recur after treatment is stopped. Intralesional steroid injections are more effective than topical steroids because they are able to deliver the treatment deeper in the skin, where the hair follicle is located. Both topical and intralesional steroids are safe, with mild side effects that usually resolve once treatment is stopped. However, intralesional steroid injections can be painful, which often limits their use, especially in children or patients with complete scalp hair loss. More high-quality research studies are needed to better understand how topical and intralesional steroids should be used for safe and effective alopecia areata treatment.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-025-01421-2.

Key Summary Points

Topical and intralesional (IL) corticosteroids are the most commonly used treatments for alopecia areata (AA), but high-quality randomized controlled trials supporting their efficacy are limited.

Topical steroids are well tolerated, but efficacy is limited, and AA recurrence is common after treatment cessation.

IL steroids have greater efficacy than topical steroids, but treatment is limited by pain during the procedure.

More research is needed to elucidate the role of local corticosteroids for AA in clinical practice.

Introduction

Alopecia areata (AA) is an autoimmune condition of non-scarring hair loss that affects 2% of people worldwide [1]. There are various subtypes of AA, including patchy AA, where hair loss affects discrete areas; alopecia totalis (AT), where hair loss affects the entire scalp; and alopecia universalis (AU), where hair loss affects the entire scalp, face, and body [1]. The disease course may be self-resolving, remitting, chronic, or progressive, but it is ultimately unpredictable [1]. Beyond causing hair loss, AA is associated with impaired psychosocial functioning and decreased health-related quality of life [2–6].

AA pathogenesis is autoimmune in nature but has not been fully characterized. Existing theories postulate that there is loss of immune privilege of hair follicles through major histocompatibility complex (MHC)-induced activation of natural killer (NK) cells and cytotoxic CD8+ T cells [1]. This results in a premature shift of the hair follicle into the telogen phase with subsequent breakage and shedding [1].

Topical and intralesional (IL) corticosteroids are the two most commonly used treatments in AA [7]. These locally-acting glucocorticoid derivatives are thought to treat AA by reducing the CD8+ T-cell-mediated immune attack on hair follicles [1]. Expert-established treatment guidelines recommend potent to very potent topical corticosteroids as a first-line treatment for children and adults with scalp AA who cannot tolerate IL injections [8, 9]. IL steroids are also recommended for adults with mild-to-moderate AA and are considered for older children with mild-to-moderate AA or adults with severe AA on a case-by-case basis [8, 9]. This review aims to synthesize the current evidence for local corticosteroids as treatments for AA.

Methods

A literature search was performed on PubMed from inception to December 2024 to synthesize the literature on local corticosteroids for AA. Topical and IL corticosteroids were chosen as the focus of this study due to their common use in AA treatment and the lack of dedicated research in the literature to this topic. Other commonly used AA therapies, such as systemic corticosteroids, Janus kinase (JAK) inhibitors, systemic immunomodulators, minoxidil, phototherapy, and contact immunotherapy were beyond the scope of this study. The following search terms were included: “alopecia areata”, “topical steroids”, “topical corticosteroids”, “intralesional steroids”, and “intralesional corticosteroids”. Abstracts were screened to determine article relevance. Ultimately, clinical trials, systematic reviews, reviews, and case series were included, with relevant clinical trials the focus of the treatment efficacy section. Quality of clinical trial evidence was assessed by evaluating each study’s use of randomization, placebo-controlled design, blinding, intention-to-treat analysis, subjective versus objective treatment outcome assessment, sample size, and power.

Ethical Approval

This article is based on previously conducted research and did not involve performing research on any human participants or animals by any of the authors.

Mechanism of Action

Corticosteroids are synthetic derivatives of naturally occurring glucocorticoids from the adrenal gland [10]. At the cellular level, glucocorticoids form a complex with the cytoplasmic glucocorticoid receptor (GR), which is translocated to the nucleus [10]. There, the glucocorticoid-GR complex modulates the expression thousands of genes both directly, through binding of the glucocorticoid response element of DNA, and indirectly, through transrepression [11]. The major antiinflammatory effects of glucocorticoids result from the latter, with inhibition of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) resulting in interference with inflammatory response genes and down-regulation of proinflammatory cytokines [12, 13]. In AA, therapeutic benefit of corticosteroids is postulated to result from reduction of interleukin (IL)−2-, IL-15-, and interferon-gamma (IFN-γ)-mediated peribulbar CD8+ T-lymphocyte inflammation, allowing for restoration of hair growth [13–17].

Pharmacokinetics

Percutaneous absorption of topical steroids requires the active glucocorticoid agent to be released from its formulation, followed by penetration of the stratum corneum, epidermis, and dermis, and finally, diffusion across the cell membrane [18]. Penetration of the stratum corneum represents the rate-limiting step of percutaneous absorption, with lesser amounts of glucocorticoid reaching deeper layers of the skin [18, 19]. In AA, topical steroid efficacy is limited by the ability of the agent to reach the dermis, where the hair follicle resides [18]. However, IL steroids are injected in the upper subcutis, allowing for delivery of the medication directly to the hair follicles [20]. This deeper penetration explains the enhanced efficacy of IL steroids compared with the rate-limiting stratum corneum penetration seen with topical steroids [18, 19, 21].

Percutaneous and systemic absorption rates depend on the specific qualities of the corticosteroid used [18, 22, 23]. For topical steroids, increased penetration of the dermis can be achieved by using higher potency formulations, greater cumulative doses, and use in conjunction with plastic-wrap occlusion, laser, or microneedling [18, 22, 23]. Higher solubility formulations allow for greater immediate penetration of the stratum corneum, whereas formulations in suspension allow for sustained release over time [19]. For IL steroids, the lower solubility agent triamcinolone acetonide is the preferred agent due to its slow absorption from the injection site, maximizing local action with minimal systemic effects [20]. Once the target area is reached, corticosteroids are metabolized by intra-epidermal de-esterification; halogenation of the agent resists de-esterification to prolong activity [10].

There is limited pharmacokinetic data available on systemic absorption of local corticosteroids, as absorption varies with agent potency, concentration, cumulative dose, and application site [18]. Systemic absorption is expected to be low in comparison with systemic corticosteroid treatment modalities. However, disruption of the hypothalamic–pituitary–adrenal axis has been reported, especially with high potency agents [24, 25]. This is especially important to consider in the pediatric population, whose higher surface area-to-body weight ratio results in greater systemic absorption of topical corticosteroids [26]. This, combined with slower rates of steroid metabolism in children, puts them at higher risk of systemic adverse effects, such as adrenal suppression and stunting of growth [27, 28].

Treatment Regimens

The risk–benefit ratio is always considered when choosing the topical steroid regimen, as higher-potency steroids result in both increased efficacy and increased risk of adverse effects [18]. Potency is influenced by the agent choice, concentration, vehicle, dosage, frequency of application, and use under occlusion. The vasoconstrictive assay is used to estimate the potency and bioavailability of topical steroids in the skin (Table S1) [18]. When selecting agents, fluorinated and halogenated compounds are most potent, while esterified compounds have greater lipophilicity and are better able to penetrate the skin [10]. Of the available vehicles, ointments have the highest potency due to their occlusive nature; however, foams and solutions are better tolerated for the scalp [10]. Applying topical steroids under plastic-wrap occlusion also increases penetration [10]. Microneedling or laser treatments can also be used in conjunction with topical corticosteroids to improve dermal delivery and increase efficacy [22, 23].

Triamcinolone acetonide is the most used IL steroid for alopecia areata, though the first use of intralesional steroids came with the administration of hydrocortisone acetate [20]. Since then, triamcinolone hexacetonide and triamcinolone acetonide have both been used for the treatment of alopecia areata. The factors that have led to the predominance of triamcinolone acetonide in clinical practice and its selection as the experimental agent in all intralesional steroid clinical trials include its lower solubility, slower absorption from the injection site, and lower likelihood of atrophy [20, 29, 30]. Triamcinolone acetonide is typically prepared in concentrations ranging from 2.5 to 10 mg/mL. The agent is injected using a 0.5-inch long, 30-gauge needle fitted to an insulin syringe and delivered at 0.1 mL/cm² with a maximum dosage of 3 mL per visit [31–34]. Two small, double-blind, placebo-controlled studies showed that the 2.5 mg/mL concentration of triamcinolone acetonide is as beneficial for improving hair density and caliber as 5 mg/mL and 10 mg/mL concentrations, with the lower dose also having less adverse effects [20, 31, 32, 34]. These agents are administered every 4–6 weeks [20, 31].

Topical Corticosteroid Efficacy

A limited number of clinical trials using various topical steroid agents, vehicles, concentrations, and treatment regimens demonstrate mixed results in AA (Table 1). Efficacy rates for complete hair regrowth are reported from 20% to 61%, but recurrence rates after treatment discontinuation range from 38% to 63% [35–40]. Higher success rates are seen in mild AA [36]. One study reports that patients experiencing treatment failure with topical steroids had significantly better results when switched to IL triamcinolone [40].

Table 1.

Clinical trials evaluating topical corticosteroid efficacy in AA

Study name	Quality of evidence	Participants	Intervention	Primary outcome	Results	Adverse effects
SUPER HIGH POTENCY TOPICAL CORTICOSTEROIDS
Tosti et al. (2006) [36]	High; randomized, double-blind, right-to-left, placebo-controlled trial; intention-to-treat analysis, subjective treatment outcome assessment	Adults with moderate-to-severe alopecia areata (AA) (n = 34)	Clobetasol propionate 0.05% foam versus placebo foam (intrapatient design; right versus left) 5 days/week for 12 weeks. From 13–24 weeks, patient continued only with the treatment that resulted in greater hair regrowth	Primary outcome was regrowth scale (RGS) at weeks 12 and 24. RGS rated regrowth as follows: 0 (regrowth < 10%), 1 (11–25%), 2 (26–50%), 3 (51–75%), 4 (> 75%)	• At 12 weeks, 20% of those treated with clobetasol foam experienced an RGS of 3 or 4, while 42% achieved an RGS of 2 • At week 12, clobetasol was judged to have greater efficacy in 89% of sites, compared with only 11% of sites where placebo foam had greater efficacy (p = 0.0001) • In patients with mild-to-moderate AA at baseline, clobetasol resulted in significantly greater RGS than in those with severe AA at baseline, at both weeks 12 and 24	• Folliculitis (n = 2, clobetasol group)
Ucak et al. (2012) [41]	Moderate; randomized, placebo-controlled trial	Children and adults with AA (n = 100); alopecia totalis (AT) and alopecia universalis (AU) excluded	Patients were randomized to receive Clobetasol propionate 0.05% cream (n = 30), pimecrolimus 1% cream (n = 30), or placebo (pure Vaseline, n = 20). In an additional 20 patients, one half of the scalp was treated with clobetasol and the other pimecrolimus cream. All treatments were applied twice daily for 12 weeks	Primary outcome was pigmented terminal hair regrowth and percentage recovery of hair loss at 4, 8, and 12 weeks	• At week 12, the mean percentage of hair recovery was 47% ± 45% in the clobetasol cream group, which did not significantly differ from that of the pimecrolimus group (54% ± 44%) or placebo group (34% ± 41%) • In the intrapatient comparator group at 12 weeks, the percentage recovery score was 62% ± 39% on the clobetasol side and 48% ± 41% on the pimecrolimus side	Clobetasol only group:  • Folliculitis (n = 1)  • Telangiectasia (n = 1) Clobetasol + pimecrolimus group:  • Folliculitis (n = 7)  • Telangiectasia (n = 3)
Lenane et al. (2014) [38]	High; single-center, randomized, blind, two-arm, parallel-group, superiority trial; intention-to-treat analysis, objective treatment outcome assessment	Children aged 2–15, at least 10% of scalp affected (n = 41)	Clobetasol propionate 0.05% cream versus hydrocortisone 1% cream twice daily, 6 weeks on, 6 weeks off, for a total of 24 weeks	Primary outcome was percent reduction in surface area with hair loss, evaluated at 6, 12, 18, and 24 weeks	• The percentage of reduction of scalp surface area with hair loss from baseline to 24 weeks was significantly greater in the clobetasol group (97%; interquartile range (IQR) 64–100%) than in the hydrocortisone group (5%; IQR −444% to 81%) (p = 0.002) • 17/20 (85%) in the clobetasol group versus 7/21 (33%) in the hydrocortisone group achieved > 50% reduction in surface area with hair loss	• Atrophy (n = 1, Clobetasol group) • Abnormally low urinary cortisol levels (n = 11, no significant difference between treatment groups)
Tosti et al. (2003) [37]	Low; unblinded, right-to-left intrapatient clinical trial; intention-to-treat analysis; subjective treatment outcome measurement	Individuals age 17–42 years with severe and refractory AT or AU (n = 28)	Clobetasol propionate 0.05% ointment, under occlusion with plastic film, 2.5 g nightly to right side of scalp only, 6 days/week for 6 months. Treatment was extended to entire scalp when regrowth occurred	Primary outcome was clinical efficacy after 6 months of treatment, classified as (1) non-responders = no regrowth or regrowth of fine unpigmented hair; (2) poor responders = patchy regrowth of pigmented hair; and (3) responders = regrowth > 75% of terminal hairs	• At 6 months, 8 participants (29%) were treated successfully to over 95% regrowth, while 20 participants (71%) were classified as poor/non-responders • 3 of the 8 successfully treated participants experienced relapse in the 6-month follow-up period	• Painful folliculitis (n = 11, clobetasol side, 5/11 had to discontinue treatment) • Acne (n = 1) • Telangiectasias (n = 2) • Mild local atrophy (n = 1) • No significant differences in 24-h urinary free cortisol levels in comparison to start of study
HIGH POTENCY TOPICAL CORTICOSTEROIDS
Pascher et al. (1970) [35]	Low; randomized, intrapatient clinical trial; single-blind first part of study; 40% drop-out rate without intention-to-treat analysis; subjective treatment outcome assessment	Adults and children with AT or AU (n = 47)	Fluocinolone acetonide 0.2% cream versus placebo, randomly assigned to different patches, 1–2 g/day for 3–4 weeks, occlusion recommended	Primary outcome was treatment response after 6 months of therapy, classified as (1) excellent = total or near-total regrowth; (2) moderate = partial regrowth; (3) poor = little or no regrowth; or (4) worse = progressive hair loss	• Satisfactory to excellent response observed in 17 of 28 (61%) patients who completed fluocinolone treatment • The fluocinolone cream was superior to the control cream in 61% of patients, versus the control being more effective in 0% of patients • Both were equally effective or equally ineffective in 14% and 25% of patients, respectively • 11/17 (63%) responders experienced relapse during the treatment course or in the 3-month follow-up period	• Folliculitis/acne (n = 5) • No patients developed clinical evidence of systemic absorption
Charuwichitratana et al. (2000) [40]	Moderate: randomized, double-blind, placebo-controlled study; subjective outcome assessment; no intention-to-treat analysis, 80% power	Adults and children ages 16 and up with patchy AA (n = 70)	Desoximetasone 0.25% cream (n = 35) versus placebo (n = 35), applied to affected area twice daily for 12 weeks	Primary outcome was complete hair regrowth at 12 weeks. Patients with 25% or less regrowth were classified as “no improvement”; 25–49% regrowth was classified as “mild improvement”; 50–74% was “moderate improvement”; and > 75% was “good improvement”	• 15/26 (58%) of patients who completed desoximetasone treatment experienced complete hair regrowth (relative risk (RR) = 1.47; 95% confidence interval (CI) 0.83–2.59); no statistically significant difference compared with placebo group (11/28 (39%) with complete hair regrowth) • Proportion of participants with at least mild improvement was significantly greater in the desoximetasone group (25/26) than the control group (21/26) (p = 0.05) • At 12 weeks, participants without complete regrowth in either group were offered to switch to intralesional (IL) triamcinolone for 1–3 months. 13 of 14 (93%) IL triamcinolone-treated participants experienced complete regrowth, which was significantly greater than the response to desoximetasone	• Itching, transient burning, mild acneiform eruption (n = 3, desoximetasone group)
MODERATE POTENCY TOPICAL CORTICOSTEROIDS
Mancuso et al. (2003) [39]	High; randomized, controlled, investigator-blinded study; intention-to-treat analysis, subjective outcome assessment, 95% power	Adults with mild-to-moderate AA (n = 61)	Betamethasone valerate 0.1% foam versus betamethasone dipropionate lotion 0.05% twice daily for 12 weeks	Primary outcome was RGS at weeks 8, 12 (end-of-treatment), and 20 (follow-up). RGS rated regrowth as follows: 0 (regrowth < 10%), 1 (11–25%), 2 (26–50%), 3 (51–75%), 4 (> 75%)	• The number of patients to achieve full regrowth by 20 weeks was significantly higher in the betamethasone foam group (61%) than the betamethasone lotion group (27%) (p < 0.003) • Betamethasone valerate foam resulted in significant higher RGS than the betamethasone dipropionate lotion (3.1 ± 1.5 versus 1.8 ± 1.6, respectively; 95% CI = −2.7, −0.5)	• Folliculitis (n = 2, foam group; n = 1 lotion group)
LOWER–MID POTENCY TOPICAL CORTICOSTEROIDS
Sardesai et al. (2012) [42]	Low; open, randomized, comparative study, small sample size	Children and adults with mild AA (< 25% scalp involvement, n = 30)	Patients were randomized to the following treatment regimens (n = 6 per group): (1) IL triamcinolone acetonide 10 mg/ml once monthly (2) Topical betamethasone dipropionate 0.05% lotion twice daily (3) minoxidil 5% lotion applied twice daily (4) anthralin 1.15% + salicylic acid 1.15% + coal tar 5.3% ointment short contact therapy once daily (5) placebo solution (propylene glycol twice daily)	Primary outcomes were Severity of Alopecia Tool (SALT) score and percentage hair regrowth at 3 months	• 100% of patients in the IL triamcinolone (6/6) and in the topical betamethasone lotion groups (6/6) had > 75% regrowth at the end of 4 and 8 weeks; this response was significantly better than that of minoxidil, anthralin, and placebo groups • In all 5 treatment regimens, the mean reduction in SALT score from baseline to 3 months was statistically significant	• No adverse effects observed in topical steroid or IL steroid groups • Erythema and pruritus observed in anthralin group (n = 4)
Tiwari et al. (2023) [43]	Moderate quality: randomized, controlled, patient and assessor-blinded; subjective treatment outcome assessment; no intention-to-treat analysis; 80% power	Adults and children (age 11–50 years) with mild AA (< 4 patches and < 20% of scalp affected) (n = 120)	Group A: IL triamcinolone acetonide 10 mg/ml every 4 weeks + topical betamethasone dipropionate 0.05% lotion once nightly versus group B: IL normal saline every 4 weeks + topical betamethasone dipropionate 0.05% lotion once nightly	Primary outcome was hair regrowth at end of treatment (12 weeks) as assessed by the hair regrowth scale: • S-I = 0–25% regrowth • S-II = 26–50% regrowth • S-III = 51–75% regrowth • S-IV = 76–100% regrowth	At the end of the 12-week treatment period: • Patients with < 25% regrowth: 40% of group A versus 91% of group B (p < 0.001) • Patients with > 75% regrowth: 62% of group A versus 13% in group B (p < 0.001) At the end of a 12-week follow-up period: • Patients with < 25% regrowth: 2% group A versus 19% group B (p = 0.01) • Patients with > 75% regrowth: 87% group A versus 32% group B (p < 0.001)	• Atrophy (n = 5, group A; n = 1, group B) • Dyspigmentation (n = 3, group A)

Quality of evidence was assessed by evaluating each study’s use of randomization, placebo-controlled design, blinding, intention-to-treat analysis, subjective versus objective treatment outcome assessment, sample size, and power

AA alopecia areata, AT alopecia totalis, AU alopecia universalis, IL intralesional, RGS regrowth scale, IQR interquartile range, RR relative risk, CI confidence interval, SALT severity of alopecia tool

The Use of Super High Potency Topical Steroids for AA

Clobetasol Propionate 0.05% Foam

One randomized, double-blind, half-scalp placebo-controlled trial evaluated efficacy of clobetasol propionate 0.05% foam versus a placebo foam in 34 adults with AA and over 10% hair loss. At 12 weeks, greater hair regrowth was achieved in 89% of clobetasol-treated sites, versus only 11% of the placebo sites (p = 0.0001). After 12 and 24 weeks of treatment, 20% and 26% of clobetasol-treated sites achieved over 50% regrowth, versus 3% and 0% in the placebo group, respectively. In patients with mild-to-moderate AA at baseline, clobetasol foam resulted in significantly greater regrowth than in those with severe AA (p = 0.03) [36].

Clobetasol Propionate 0.05% Cream

A randomized, placebo-controlled trial evaluated efficacy of clobetasol propionate 0.05% cream against pimecrolimus 1% cream and placebo (Vaseline) in 100 children and adults with subtotal scalp AA. All creams were applied twice daily for 12 weeks. The mean percentage of hair recovery was 47% ± 45% in the Clobetasol cream group, which did not differ significantly from that of the pimecrolimus group (54% ± 44%) or placebo group (36% ± 41%) [41].

A single-center, randomized, blind, two-arm parallel-group superiority trial evaluated efficacy of clobetasol propionate 0.05% cream versus hydrocortisone 1% cream applied twice daily in 41 children with AA and at least 10% scalp involvement. Treatments were applied 6 weeks on and 6 weeks off for 24 weeks. At 24 weeks, 85% of the clobetasol group versus 33% of the hydrocortisone group achieved at least a 50% reduction in the surface area with hair loss. The reduction in percentage of hair loss from baseline was significantly greater in the clobetasol group (97%; interquartile range (IQR) 64–100%) than in the hydrocortisone group (4.6%; IQR −444% to 81%) (p = 0.002) [38].

Clobetasol Propionate 0.05% Ointment

A small, unblinded, right-to-left intrapatient-controlled trial evaluated efficacy of clobetasol propionate 0.05% ointment applied under occlusion 6 days per week for 6 months in 28 children and adults with severe, refractory AT and AU. Once regrowth occurred on the treated side, treatment was extended to the remainder of the scalp. Eight participants (29%) achieved over 95% regrowth at 6 months; however, 38% experienced relapse in the 6-month follow up period [37].

The Use of High Potency Topical Steroids for AA

Fluocinolone Acetonide 0.2% Cream

A small, intrapatient-controlled study with 40% dropout rate evaluated fluocinolone acetonide 0.2% cream versus placebo in 47 children and adults with AT and AU. Each cream was applied to one half of the scalp, 1–2 g per day for 3–4 weeks, with occlusion recommended. After 6 months of treatment, the fluocinolone cream was superior to the control cream in 61% of patients, versus the control cream being more effective in 0 patients. Total or near-total hair regrowth was observed in 61% (17/28) of patients who completed fluocinonide treatment; however, 63% (11/17) of those with total or near-total regrowth experienced relapse during the treatment course and the 3-month follow up period [35].

Desoximetasone 0.25% Cream

A randomized, double-blind, placebo-controlled study evaluated efficacy of desoximetasone 0.25% cream versus placebo in 70 children and adults with patchy AA. Treatment was applied twice daily for 12 weeks. In the desoximetasone group, 58% achieved complete hair regrowth at 12 weeks, however, this was not significantly different from placebo [relative risk (RR) of complete hair regrowth with desoximetasone = 1.47; 95% confidence interval (CI) 0.83–2.59]. The number of patients who achieved at least mild improvement was significantly greater in the desoximetasone group (96%) than in the placebo group (81%) (p = 0.05). After the initial 12 weeks of treatment, participants in either group without complete regrowth were offered to switch to IL triamcinolone injections for 1–3 months; 93% (13/14) of participants who switched to IL triamcinolone achieved complete hair regrowth, which was significantly better than the response to desoximetasone (p = 0.03) [40].

The Use of Moderate Potency Topical Steroids for AA

Betamethasone Valerate 0.1% Foam

A multicenter, prospective, randomized, controlled, investigator-blinded superiority trial evaluated efficacy of betamethasone valerate 0.1% foam versus betamethasone dipropionate 0.05% lotion applied topically twice daily for 12 weeks in 61 adults with mild-to-moderate AA. Betamethasone foam resulted in significantly greater regrowth than betamethasone lotion (p < 0.05), and significantly more patients achieved complete regrowth by 20 weeks in the betamethasone foam group (61%) than in the betamethasone lotion group (27%) (p < 0.003) [39].

The Use of Lower-Mid Potency Topical Steroids for AA

Betamethasone Dipropionate 0.05% Lotion

A small, open, randomized, comparative study compared the efficacy of topical betamethasone dipropionate 0.05% lotion twice daily, IL triamcinolone injections, topical minoxidil, anthralin, and a placebo solution in 30 children and adults with mild AA. The topical and IL steroids showed significantly better efficacy compared with the other treatment regimens, with 100% of participants in both groups achieving over 75% regrowth at 4 and 8 weeks [42].

A randomized, controlled, double-blinded study evaluated the efficacy of betamethasone dipropionate 0.05% lotion in combination with either IL triamcinolone or placebo (IL normal saline) in adults and children ages 11–50 with mild AA. After 12 weeks of treatment, 62% of the topical plus IL steroid achieved > 75% regrowth, versus 13% of those treated with the topical steroid alone (p < 0.001). After a 12-week follow-up period, 87% of the topical plus IL steroid group had > 75% regrowth, versus 32% of those treated with the topical steroid alone (p < 0.001) [43].

IL Corticosteroid Efficacy

Triamcinolone acetonide was used as the primary agent in all IL steroid clinical trials to date [31, 33, 34, 43, 44]. Though studies had different primary outcome measures and evaluated varying degrees of AA severity, IL triamcinolone acetonide elicited significantly improved hair regrowth, density, and caliber across all measurement means (Table 2) [31, 33, 34, 43, 44].

Table 2.

Clinical trials evaluating IL corticosteroid efficacy in AA in order of evidence quality

Study name	Quality of evidence	Participants	Treatment	Primary outcome	Results	Adverse effects
Rajan et al. (2021) [34]	High quality: randomized, double-blind, controlled trial, intention-to-treat analysis, large sample size, subjective treatment outcome assessment	Adults and children over 12 years of age with at least one scalp alopecia areata (AA) patch measuring more than 2.5 cm × 2.5 cm, less than 50% scalp involvement, and AA patch duration less than 1-year (n = 672 quadrants from 105 patients)	Patches divided into four quadrants to correspond to four treatment groups (normal saline and 2.5, 5, and 10 mg/mL of triamcinolone acetonide). Injections given every four weeks for 12 weeks	Primary outcome was hair density assessment using regrowth scale (RGS) at 12 weeks: 0: < 10% regrowth, 1: 11–25% regrowth, 2: 26–50% regrowth, 3: 51–75% regrowth, and 4: > 75% regrowth	• After 12 weeks, more than 50% of the quadrants showed RGS scores of 3 or 4 in 10 mg/mL (67%), 5 mg/mL (58%), and 2.5 mg/mL (54%) groups • There was significantly better improvement in RGS score in 2.5, 5, and 10 mg/mL groups compared with the normal saline group (p < 0.001)	• Percentage of quadrants with telangiectasia in 10 mg/mL, 5 mg/mL, 2.5 mg/mL, and NS group were 4.8%, 2.4%, 1.6%, and 2.4%, respectively • Percentage of quadrants with atrophy in 10 mg/mL, 5 mg/mL, 2.5 mg/mL, and NS groups were 33%, 23%, 18%, and 1.6%, respectively
Tiwari et al. (2023) [43]	Moderate quality: randomized, controlled, patient- and assessor-blinded; subjective treatment outcome assessment; no intention-to-treat analysis; 80% power	Adults and children (age 11–50 years) with mild AA (< 4 patches and < 20% of scalp affected) (n = 120)	Group A: intralesional (IL) triamcinolone acetonide 10 mg/ml every 4 weeks + topical betamethasone dipropionate lotion 0.05% once nightly versus group B: IL normal saline every 4 weeks + topical betamethasone dipropionate lotion 0.05% once nightly	Primary outcome was hair regrowth at end of treatment (12 weeks) as assessed by the hair regrowth scale: • S-I = 0–25% regrowth • S-II = 26–50% regrowth • S-III = 51–75% regrowth • S-IV = 76–100% regrowth	After the treatment period: • Patients with < 25% regrowth: 40% of group A versus 91% of group B (p < 0.001) • Patients with > 75% regrowth: 62% of group A versus 13% in group B (p < 0.001) At the end of a 12-week follow-up period: • Patients with < 25% regrowth: 2% group A versus 19% group B (p = 0.01) • Patients with > 75% regrowth: 87% group A versus 32% group B (p < 0.001)	• Atrophy (n = 5, group A; n = 1, group B) • Dyspigmentation (n = 3, group A)
Chu et al. (2015) [31]	Moderate quality: randomized, double-blind, placebo-controlled, intrasubject trial; objective treatment outcome assessment; small sample size	Adults with mild patchy AA (n = 4)	Patches divided into four 1.5 cm2 quadrants, randomized to receive either 2.5-, 5-, or 10 mg/ml triamcinolone acetonide or normal saline injections every 6 weeks for 6 sessions	Primary outcomes included hair density and caliber as assessed by a Folliscope imaging device at 42 weeks	• Significantly greater hair caliber and density were observed in IL triamcinolone areas compared with placebo (p < 0.04) • There were no significant differences in hair caliber or density in 2.5 mg/ml quadrants compared with 5- or 10-mg/ml quadrants	• Reversible skin atrophy (n = 4 in 10 mg/ml group, n = 1 in 2.5 mg/ml group) • Pain (similar in all groups, including IL saline)
Abell and Munro (1973) [44]	Low quality: non-randomized clinical trial, only controlled in 15 participants, subjective treatment outcome assessment	Individuals with mild AA, alopecia totalis (AT), and alopecia universalis (AU) (n = 84)	IL triamcinolone acetonide, 5 mg/ml using Porto Jet needleless injector, at weekly or biweekly intervals for three total treatments. In 15 patients with multiple areas of scalp involvement, concurrent treatment with IL saline was given in alternate areas	Primary outcome was hair regrowth at 6 and 12 weeks after completion of treatment. Satisfactory regrowth was determined by the presence of predominantly pigmented terminal hair regrowth in significant quantities	• 86% of patients showed regrowth at 6 weeks (92% with patchy AA versus 61% with AT) • By 12 weeks, 24% of patients experienced recurrent hair loss after initial regrowth (21% with patchy AA versus 33% with AT)	• Hemorrhage at injection site • Transient atrophy (resolved at 12-week follow-up) • Pain at injection site • Reduced morning cortisol levels, which normalized within 3 days (n = 1)
Ganjoo and Thappa (2013) [33]	Low quality: Hospital-based interventional study, uncontrolled, no intention-to-treat analysis, subjective treatment outcome assessment	Adults and children > 10 years of age with mild-to-moderate AA (1–3 patches, < 50% scalp involvement) (n = 60; 70 patches total)	IL triamcinolone acetonide 5 mg/ml every 4 weeks until > 75% regrowth achieved, with a maximum duration of 24 weeks	Primary outcome was regrowth at 4-week intervals scored by RGS, where 0 = regrowth < 10%, 1 = regrowth 11–25%, 2 = regrowth 26–50%, 3 = regrowth 51–75%	• Early responders (regrowth > 75% in < 12 weeks) were significantly associated with a shorter duration of disease (< 1 month) (p = 0.036) and smaller patch size (< 4 cm) (p = 0.0002) • Late (regrowth of > 75% in 12–24 weeks) and incomplete (did not achieve > 75% regrowth) responders were significantly associated with family history of AA (p < 0.0001), personal history of prior AA episodes (p = 0.0147), and presence of nail changes (p = 0.0007)	• Atrophy, telangiectasia (19%) • No systemic side effects observed

Quality of evidence was assessed by evaluating each study’s use of randomization, placebo-controlled design, blinding, intention-to-treat analysis, subjective versus objective treatment outcome assessment, sample size, and power

AA alopecia areata, AT alopecia totalis, AU alopecia universalis, IL intralesional, RGS regrowth scale

Evaluation of the Efficacy of IL Triamcinolone Acetonide

A randomized, controlled, double-blinded study evaluated the efficacy of IL triamcinolone in combination with a topical steroid in adults and children with mild AA. The two treatment regimens were either IL triamcinolone acetonide 10 mg/mL every 4 weeks plus topical betamethasone dipropionate lotion 0.05% once nightly or IL saline plus the topical steroid regimen. After 12 weeks of treatment, 62% of the IL triamcinolone group and 13% of the IL saline group had > 75% regrowth (p < 0.001). After a 12-week follow-up period, 87% of the IL triamcinolone group and 32% of the IL saline group had > 75% regrowth (p < 0.001) [43].

A non-randomized, partially-controlled clinical trial assessed hair regrowth in a cohort of 84 patients with mild-to-severe AA or AU who received 5 mg/mL triamcinolone acetonide injections via Porto Jet needleless injector every 1–2 weeks for three total treatments. The percentage of participants with pigmented terminal hair regrowth at 6 and 12 weeks post-treatment were 86% and 62%, respectively; however, 24% of participants experienced recurrent hair loss at 12 weeks [44].

Evaluation of the Optimal Concentration of IL Triamcinolone Acetonide

A randomized, controlled, double-blinded study evaluated the efficacy and adverse effects of various concentrations of IL triamcinolone acetonide in 105 patients with scalp AA. Lesions of at least 2.5 cm × 2.5 cm were subdivided into four quadrants and randomized to receive a dose of normal saline or 2.5, 5, or 10 mg/mL of triamcinolone acetonide every 4 weeks for 12 weeks. After 12 weeks, there was significantly better improvement in regrowth score in 2.5, 5, and 10 mg/mL-treated groups compared with the normal saline-treated group (p < 0.001), with comparatively better response between dosages seen in the 10 mg/mL group at the cost of increased adverse effects. More than 50% of the quadrants showed regrowth > 50% in 10 mg/mL (67%), 5 mg/mL (58%), and 2.5 mg/mL (54%) groups only [34].

Another randomized, placebo-controlled, double-blinded pilot study also compared efficacy and adverse effects of various concentrations of IL triamcinolone acetonide in four adults with mild AA. Patches were divided into four 1.5-cm² quadrants and randomized to receive either 2.5, 5, or 10 mg/mL triamcinolone acetonide or normal saline injections at 6-week intervals for six sessions. After 42 weeks, significantly greater hair caliber and density were observed in IL triamcinolone-treated regions compared with placebo (p < 0.04). Additionally, there were no significant differences in hair caliber or hair density in 2.5 mg/mL quadrants compared with 5 or 10 mg/mL quadrants, and there were fewer side effects reported with the lower dose [31].

Evaluation of Patient Attributes Predictive of IL Steroid Treatment Success Based on Time to Treatment Response

A hospital-based, uncontrolled, interventional study assessed the efficacy of IL triamcinolone acetonide in 60 participants ages 10 and up with mild-to-moderate AA. A concentration of 5 mg/mL of triamcinolone acetonide was delivered every 4 weeks until over 75% regrowth achieved, with a maximum duration of 24 weeks. Primary outcome was time to regrowth, which was assessed at 4-week intervals by the regrowth scale. Participants classified as fast-responders (regrowth over 75% in less than 12 weeks) were significantly associated with shorter disease duration (p = 0.036) and smaller patch size (p = 0.0002). Participants classified as slow-responders (regrowth over 75% in 12–24 weeks) and non-responders (did not achieve over 75% regrowth) were significantly associated with family history of AA (p < 0.0001), personal history of prior AA episodes (p = 0.0147), and presence of nail changes (p = 0.0007) [33].

Safety and Adverse Effects

Topical steroids are generally safe and well tolerated. Risk of side effects is increased with higher potency formulations, greater doses, application under occlusion, and long-term use [18]. Common side effects include transient burning, skin atrophy, pigmentation loss, and folliculitis, which generally resolve with treatment discontinuation [35–40, 44]. Severe adverse effects associated with systemic absorption are rare but include hypothalamic–pituitary–adrenal axis disruption, insulin resistance, neutrophilia, hypertension, osteoporosis, osteonecrosis, Cushingoid features, and slowed growth in children [18, 24, 38, 44, 45]. No systemic side effects were reported in any of the clinical trials evaluated in this paper [35–43]. One study reported abnormally low urine cortisol levels in 11 patients, however, this may have been confounded by prior systemic corticosteroid treatment [38]. Another study with very high potency topical corticosteroids reported no significant differences in 24-h urinary free cortisol levels between the start and end of the study [37]. Side effects of topical steroids can be minimized by using the lowest necessary dose and duration [45, 46].

IL steroids are generally well tolerated with few side effects due to local delivery and limited systemic absorption [20]. Common side effects include pain or bleeding at the injection site, skin atrophy, denting, dyspigmentation, folliculitis, and telangiectasias [31, 33, 34, 43, 44]. IL steroids for eyebrow hair loss may increase the risk of ocular pressure and cataracts [30]. Techniques to minimize common side effects include lowering the agent concentration, using smaller injection volumes, avoiding repeat injections at the same site, expanding treatment intervals, using smaller gauge needles and needleless injectors, and applying topical anesthetics before treatment [30, 31, 33, 34, 43, 44, 47]. Though systemic absorption is low, in rare cases, treatment may affect the hypothalamic–pituitary–adrenal axis [30, 38, 44]. A retrospective, cross-sectional case series studying 18 patients receiving chronic IL steroid treatment for AA showed half of the cohort to have abnormal dual-energy X-ray absorptiometry (DXA) scans, indicating a potential osteoporosis risk [48]. No systemic side effects were observed in any of the IL corticosteroid clinical trials evaluated in this study, with one study reporting a transient depression in morning cortisol levels in one patient that self-resolved [31, 33, 34, 43, 44].

A similar safety profile has been observed across topical steroid and IL steroid trials [49, 50]. Adverse effects can be limited by using the lowest possible dose for the shortest period of time. Side effects generally resolve with treatment discontinuation [30, 31, 38].

Conclusion and Place in Clinical Practice

Local corticosteroids are the most widely used therapies for AA [7]. Very high potency topical steroids are recommended as a first-line treatment for children and adults with scalp AA who cannot tolerate injections [8]. This is the strongest and most broad recommendation for topical AA therapy, with other topical therapies, such as contact immunotherapy, psoralen plus ultraviolet-A, dithranol, topical prostaglandin analogs, and topical minoxidil having stipulations or weaker recommendations (i.e., contact immunotherapy for moderate-to-severe AA only, topical minoxidil as an adjuvant treatment) [8]. However, data evaluating very high potency topical steroids in AA are limited to three randomized controlled trials with mixed results [36–38, 41]. Other topical steroid clinical trials use different treatment regimens with agents of varying potency classes, making it difficult to evaluate collective results. Further, the lack of a single, standardized outcome measure among clinical trials limits the ability to compare efficacy between treatment regimens or population cohorts. Overall, efficacy is estimated between 20–61% for complete hair regrowth, with high rates of recurrence after treatment discontinuation [35–40]. Beyond the limits in practicality and increased risk of adverse effects with use over large surface areas, topical corticosteroid efficacy is greater in patients with less AA at baseline, emphasizing this treatment’s role in mild AA [36].

IL steroids are recommended in mild-to-moderate AA for adults and older children who can tolerate injections [8]. They are also considered on a case-by-case basis for adults with severe AA [8]. IL steroids are preferred over topical steroids when tolerated, but their use is limited by pain during the procedure. Techniques to minimize pain include utilizing smaller gauge needles, needleless injectors, or applying topical anesthetics prior to treatment [30, 44]. Other common adverse effects can be minimized by prolonging treatment intervals and lowering the concentration or volume of injections [47]. Only two randomized, placebo-controlled trials exist for IL steroids in AA, one of which was limited by a sample size of four patients [31, 34]. Efficacy for over 75% regrowth is estimated to be between 54% and 87%, with one study reporting a recurrence rate of 24% after treatment discontinuation [34, 43, 44]. Patients with shorter disease duration and smaller patch size are more likely to see an early response, whereas concurrent nail changes and personal or family history of AA are predictors of worse treatment outcomes [33]. More data are needed to evaluate IL steroid efficacy with respect to different concentrations, treatment intervals, duration of treatment, and clinical response patterns.

Despite their widespread clinical use, data supporting local corticosteroid efficacy in AA is limited and variable, inhibiting the ability to draw strong conclusions on their utility. This is further confounded by high rates of spontaneous resolution in AA, especially for mild and moderate cases where these treatments are thought to be more effective [51]. Yet, the narrative review methodology limits our study’s ability to draw strong conclusions on the safety and efficacy of local corticosteroids in AA. The heterogeneity of study design and the lack of standardized outcome measures undermines our ability to perform a systematic review and meta-analysis which would allow for stronger conclusions and recommendations.

To more thoroughly understand safety and efficacy of local corticosteroids in AA, more data from randomized, placebo-controlled clinical trials are needed. This includes evaluation of preferred local corticosteroid treatment regimens for AA. Long-term data are also needed to evaluate safety of chronic local corticosteroid treatment. Future research may aim to predict ideal candidates for local corticosteroid therapy with respect to patient characteristics, including hair loss location, disease severity, duration of disease, and sensitivity to adverse effects. Other investigations could evaluate the utility of combination therapy with local corticosteroids and systemic agents.

In summary, while local corticosteroids remain a mainstay for managing non-severe AA, comprehensive long-term studies are essential to optimize their use, refine patient selection, and establish evidence-based treatment regimens tailored to individual clinical presentations.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

All authors contributed significantly to the study conception and design. Samantha Gregoire performed the literature search, data analysis, and drafted the article. Basil McIntosh performed data analysis and drafted the article. Katherine Sanchez, Ursula Biba, and Arash Mostaghimi critically revised the work and intellectual content. All authors read and approved the final manuscript.

Funding

No funding or sponsorship was received for the development or publication of this article.

Declarations

Conflict of Interest

Dr. Arash Mostaghimi is an Editorial Board member of Dermatology and Therapy; Dr. Mostaghimi was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Dr. Mostaghimi has received consulting fees from AbbVie, ACOM Health, Bioniz, Boehringer Ingelheim, Concert, Digital Diagnostics, Eli Lilly, Equillium, Hims & Hers Health, and Pfizer; equity from ACOM Health, Figure 1, and Hims & Hers Health; licensing/royalties from Concert and Pfizer; and research funding from Aclaris, Concert, Eli Lilly, and Incyte. Samantha Gregoire, Basil McIntosh, Katherine Sanchez, and Ursula Biba have no conflicts of interest to disclose.

Ethical Approval

This article is based on previously conducted research and did not involve performing research on any human participants or animals by any of the authors.