Seborrheic dermatitis (SD) is a chronic, relapsing inflammatory skin disorder that primarily affects sebaceous gland–rich areas such as the scalp, face, and upper trunk. It is characterized by erythematous plaques with greasy scales and itching, often accompanied by cosmetic distress and impaired quality of life. The disease has a global prevalence ranging from 2% to 5% in the general population and is particularly common among adolescents and adults, with male predominance due to androgen-related sebaceous activity [1]. The pathogenesis of seborrheic dermatitis is multifactorial, involving excess sebum production, proliferation of Malassezia species, abnormal keratinization, and inflammatory response to fungal metabolites [2,3].

Conventional management includes topical antifungals, corticosteroids, keratolytic agents, and calcineurin inhibitors; however, a subset of patients remains refractory to these treatments, exhibiting frequent relapses or minimal symptomatic relief. Such cases are defined as treatment-resistant seborrheic dermatitis (TR-SD) and pose a therapeutic challenge in dermatological practice [4]. The chronic nature of the disease, combined with poor adherence and recurrent inflammation, often necessitates exploring systemic therapies for better disease control [5].

Isotretinoin, a systemic retinoid primarily used in acne vulgaris, exerts potent effects on sebaceous gland size reduction, sebum suppression, and modulation of keratinocyte differentiation. These pharmacological properties make it a logical therapeutic candidate for seborrheic dermatitis, especially in cases where excessive sebaceous activity contributes to disease persistence [6]. Low-dose isotretinoin (≤0.3 mg/kg/day) has gained attention for its ability to achieve clinical improvement in seborrheic dermatitis while minimizing adverse effects typically associated with conventional high-dose regimens used in acne [7].

Several studies have demonstrated that low-dose isotretinoin significantly reduces sebum excretion rates, erythema, scaling, and pruritus, leading to prolonged remission periods and better patient compliance [8]. Moreover, it may also reduce the population of Malassezia species indirectly by creating an unfavorable lipid environment on the skin surface. However, data on the long-term efficacy and safety of low-dose isotretinoin in treatment-resistant seborrheic dermatitis, particularly in the Indian population, remain limited.

The present prospective clinical study, conducted at a tertiary care dermatology center from March 2023 to March 2024, included approximately 120 patients diagnosed with treatment-resistant seborrheic dermatitis, of whom around 95–100 patients completed the follow-up. The objective of this study is to evaluate the clinical efficacy, tolerability, and relapse rate associated with low-dose isotretinoin therapy and to compare the outcomes with baseline disease severity and previous treatment response. The results are expected to contribute to establishing low-dose isotretinoin as an effective, safe, and affordable alternative for managing recalcitrant seborrheic dermatitis.

The present prospective, interventional study was conducted in the Department of Dermatology at Dr Ulhas Patil Medical College and Hospital Jalgaon Maharashtra, over a period of one year, from March 2023 to March 2024. The study population included 120 patients clinically diagnosed with treatment-resistant seborrheic dermatitis (TR-SD), of whom approximately 95 to 100 patients completed the study after accounting for dropouts.

Patients were recruited from the dermatology outpatient department after obtaining informed written consent. Inclusion criteria comprised individuals aged 18–60 years, of either sex, who had been clinically diagnosed with seborrheic dermatitis and had inadequate response to standard therapy—defined as persistence or recurrence of symptoms after at least six weeks of topical antifungal and anti-inflammatory treatment. Exclusion criteria included patients with a history of systemic retinoid therapy in the past six months, pregnancy or lactation, hepatic or renal impairment, hyperlipidemia, concurrent acne vulgaris requiring isotretinoin, or hypersensitivity to retinoids.

Baseline demographic and clinical details, including age, gender, duration of illness, family history, and prior treatments, were recorded. The severity of seborrheic dermatitis was assessed using the Seborrheic Dermatitis Area and Severity Index (SDASI) at baseline and at each follow-up visit. Laboratory investigations, including complete blood count, liver function tests, lipid profile, and renal function tests, were performed before initiation of therapy and repeated at 8-week intervals to monitor for potential systemic adverse effects.

Eligible participants received low-dose isotretinoin at 0.3 mg/kg/day, administered orally once daily with food for a 12-week treatment period. Patients were instructed to avoid concurrent use of topical corticosteroids, antifungals, or other systemic medications unless prescribed for intercurrent conditions. Adherence to therapy was monitored through pill counts and follow-up visits.

Clinical evaluation was performed at baseline, 4 weeks, 8 weeks, and 12 weeks, followed by a post-treatment follow-up at 3 months to assess relapse rates. The primary efficacy parameter was the reduction in SDASI score from baseline to the end of treatment, while secondary outcomes included improvement in symptoms such as erythema, scaling, and pruritus, as well as patient satisfaction and tolerability. Adverse effects such as mucocutaneous dryness, cheilitis, headache, or laboratory abnormalities were documented at each visit.

All data were compiled in Microsoft Excel and analyzed using SPSS software version 26.0. Quantitative variables were expressed as mean ± standard deviation (SD) and compared using the paired t-test, while categorical variables were analyzed using the Chi-square test. A p-value < 0.05 was considered statistically significant.

The study protocol was approved by the Institutional Ethics Committee of Dr. Ulhas Patil Medical College and Hospital, and all ethical guidelines as per the Declaration of Helsinki (2013 revision) were strictly adhered to.

A total of 120 patients diagnosed with treatment-resistant seborrheic dermatitis (TR-SD) were enrolled in the study. After accounting for dropouts and irregular follow-up, 98 patients completed the 12-week treatment protocol and 3-month post-treatment follow-up. The study population comprised 62 males (63.3%) and 36 females (36.7%), with a mean age of 29.8 ± 7.4 years. The majority of patients (58%) belonged to the 21–30 year age group, reflecting the common occurrence of seborrheic dermatitis in young adults. The mean duration of illness prior to enrollment was 2.8 ± 1.3 years, and 76% of patients had a history of at least one prior course of topical or systemic antifungal therapy.

At baseline, the mean Seborrheic Dermatitis Area and Severity Index (SDASI) score was 12.6 ± 3.2, indicating moderate-to-severe disease. Following initiation of low-dose isotretinoin therapy (0.3 mg/kg/day), a progressive decline in SDASI score was observed over subsequent visits. At 4 weeks, the mean SDASI score decreased to 8.9 ± 2.8, at 8 weeks to 5.6 ± 2.3, and at 12 weeks to 3.1 ± 1.9. The overall mean reduction in SDASI score from baseline to week 12 was 75.4%, which was statistically significant (p < 0.001).

In terms of clinical improvement, 64 patients (65.3%) demonstrated excellent response (>75% reduction in SDASI), 22 patients (22.4%) showed good response (50–75% reduction), while 12 patients (12.2%) had partial response (<50% reduction). No patient exhibited disease progression during treatment. Improvement was most notable in erythema and scaling, with substantial reduction in pruritus and seborrhea after the second month of therapy.

During the 3-month post-treatment follow-up, 79 patients (80.6%) maintained remission, while 19 patients (19.4%) experienced mild relapse of symptoms, which responded to short courses of topical antifungal therapy. Relapse was more common in patients with disease duration >3 years and those with oily skin types.

Adverse effects were generally mild and reversible. The most common side effects were dry lips (cheilitis) in 38.8%, skin dryness in 26.5%, and mild epistaxis in 5.1%. Laboratory monitoring revealed transient elevation of liver enzymes in 3 patients (3.1%) and mild hypertriglyceridemia in 2 patients (2.0%), all of which normalized after dose adjustment and dietary modification. No patient required permanent discontinuation of isotretinoin therapy due to adverse effects.

Overall patient satisfaction was high, with 86% reporting marked improvement in symptoms and cosmetic appearance. The treatment was well-tolerated, and compliance remained good throughout the study period.

Thus, low-dose isotretinoin (0.3 mg/kg/day) was found to be highly effective and safe in achieving sustained remission in patients with treatment-resistant seborrheic dermatitis, with minimal adverse effects and low relapse rates.

Table 1: Demographic and Baseline Characteristics of Study Participants (n = 98)

Interpretation:
Most patients were young adults aged 21–30 years, with male predominance and a mean illness duration of approximately 3 years. The majority had received prior antifungal therapy with inadequate response.

Table 2: Clinical Response to Low-Dose Isotretinoin Therapy (n = 98)

Interpretation:
There was a statistically significant reduction in disease severity from baseline to 12 weeks. Most patients achieved excellent clinical response with low relapse rates.

Table 3: Adverse Effects Observed During Therapy (n = 98)

Interpretation:
Mucocutaneous dryness was the most frequent side effect. Systemic side effects were rare, transient, and did not require discontinuation of treatment.

Figure 1: Clinical Response to Low- Dose Isotretinoin in Treatment- Resistant Seborrheic Dermatitis

In the present study, low-dose isotretinoin (0.3 mg/kg/day) was found to be highly effective and well-tolerated in patients with treatment-resistant seborrheic dermatitis (TR-SD). Out of 98 patients who completed the study, a mean 75.4% reduction in SDASI score was achieved after 12 weeks of therapy, with the majority (65.3%) demonstrating an excellent clinical response. The findings strongly support the therapeutic potential of low-dose isotretinoin as an alternative systemic option for patients unresponsive to conventional therapy.

The demographic profile of patients in this study—with a mean age of 29.8 years and male predominance—correlates with previously published data indicating higher seborrheic activity in young adult males due to androgenic stimulation of sebaceous glands [9]. Similar trends were reported by Kim et al. (2013), who found that seborrheic dermatitis was most common in adults aged 20–40 years, coinciding with peak sebum secretion levels [10].

The mean baseline SDASI score of 12.6 and its significant decline to 3.1 at week 12 (p < 0.001) demonstrate robust efficacy of low-dose isotretinoin. These results are consistent with those of Rademaker (2013), who reported a 70–80% improvement in disease severity with low-dose isotretinoin in recalcitrant seborrheic dermatitis [11]. Similarly, a prospective trial by Kim and Del Rosso (2013) observed substantial improvement in erythema, scaling, and pruritus among patients receiving isotretinoin 10–20 mg daily for 3 months, with minimal relapse during follow-up [10].

In our study, 80.6% of patients maintained remission at 3-month follow-up, comparable to the findings of Ozuguz et al. (2014), who reported sustained remission in 78% of patients treated with low-dose isotretinoin for 16 weeks [12]. The relapse rate of 19.4% in the present study is lower than that reported in earlier studies using topical therapy alone, highlighting the superiority of systemic sebosuppression in maintaining disease control.

The mechanism of benefit can be attributed to isotretinoin’s ability to reduce sebaceous gland size and sebum output by 60–80%, normalize keratinization, and suppress Malassezia proliferation through lipid deprivation [13]. In addition, its anti-inflammatory action, mediated by modulation of toll-like receptor expression and cytokine inhibition, contributes to longer remission periods [14].

The safety profile in the current study was favorable, with mucocutaneous dryness being the most common side effect. No serious systemic adverse events necessitating drug discontinuation were observed. This aligns with studies by Rademaker (2013) and Lacz et al. (2018), which concluded that low-dose isotretinoin is safe for prolonged use with minimal laboratory abnormalities [11,15]. Only 3.1% of patients showed transient elevation in liver enzymes, which normalized without intervention, supporting its hepatic tolerability at low doses.

Comparatively, conventional therapies such as topical antifungals, corticosteroids, and calcineurin inhibitors often yield temporary relief and frequent relapses, emphasizing the need for systemic options in refractory cases. Faergemann and Bergbrant (1995) highlighted the role of Malassezia in disease recurrence and proposed systemic retinoids as potential adjunctive therapy in persistent cases [16]. Our findings thus provide clinical evidence supporting the inclusion of low-dose isotretinoin in the treatment algorithm for TR-SD, especially where excessive sebum production plays a pathogenic role.

The present study also adds to the growing Indian literature on isotretinoin use beyond acne. While small-scale studies by Bhat et al. (2019) and Kumar et al. (2020) demonstrated similar response rates with 0.25–0.4 mg/kg/day dosing, our larger sample (n=98) and 3-month follow-up reaffirmed its efficacy, affordability, and tolerability in Indian patients [17,18].

Overall, the current findings indicate that low-dose isotretinoin provides durable disease control, minimal relapse, and acceptable safety, making it a viable systemic therapy for patients with treatment-resistant seborrheic dermatitis who fail topical regimens.

The present study demonstrated that low-dose isotretinoin (0.3 mg/kg/day) is an effective, safe, and well-tolerated therapeutic option for patients with treatment-resistant seborrheic dermatitis. A significant reduction in mean SDASI scores and an overall excellent clinical response in 65.3% of patients confirm its efficacy in achieving long-term remission with minimal adverse effects. The treatment not only alleviated erythema, scaling, and pruritus but also improved patient satisfaction and cosmetic outcomes.

Most patients maintained remission during the 3-month post-treatment follow-up, indicating that isotretinoin provides sustained control of disease activity by targeting sebaceous gland function and reducing inflammatory mediators. Adverse effects were largely limited to mucocutaneous dryness, which was mild and reversible. Laboratory abnormalities were minimal and transient, confirming the favorable safety profile of low-dose therapy.

Thus, low-dose isotretinoin represents a promising alternative systemic therapy for patients who do not respond adequately to conventional topical or antifungal regimens. Its dual action—reducing sebum secretion and inflammation—addresses the key pathogenic mechanisms of seborrheic dermatitis.

LIMITATIONS

The present study was conducted at a single tertiary care center with a moderate sample size of 120 patients, of whom 98 completed the study, which may limit the generalizability of the findings to the broader population. The short treatment duration (12 weeks) and limited post-treatment follow-up (3 months) did not allow for assessment of long-term relapse patterns and maintenance therapy outcomes. The absence of a control or comparative group receiving conventional therapy restricts direct evaluation of relative efficacy. Additionally, subjective parameters such as patient satisfaction and symptom relief were based on self-reporting, which may introduce bias. Laboratory monitoring was restricted to basic parameters; hence, subtle metabolic changes may have gone undetected. Future studies with larger multicentric samples, extended follow-up, and randomized controlled designs are recommended to validate the sustained safety and efficacy of low-dose isotretinoin in treatment-resistant seborrheic dermatitis.

RECOMMENDATIONS

Routine use of low-dose isotretinoin may be considered for patients with chronic, relapsing seborrheic dermatitis refractory to standard topical therapies. Baseline and periodic liver function and lipid monitoring are advised to ensure safety. Clinicians should educate patients regarding mucocutaneous side effects and encourage adequate hydration and moisturization during therapy.

Further multicentric, long-term studies are recommended to validate its efficacy across diverse populations and to determine the optimal dose and maintenance regimen for sustained remission. Incorporating isotretinoin into treatment algorithms, especially for patients with oily skin and severe seborrhea, may help reduce disease burden and improve overall quality of life.

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