Expert Consensus on the Rational Approach to Isotretinoin Usage for Effective Management of Acne: ERAISE ACNE Recommendations

Abstract

Oral isotretinoin remains the gold standard for severe acne, with expanding use in broader subtypes. However, clinical practice varies across regions in terms of dosing, monitoring, and adjunctive care. A consensus was developed by 20 dermatology experts through a modified Delphi process and literature review (2000–2024) to provide practical recommendations. High consensus supported first-line isotretinoin among adults for severe acne variants (conglobata, nodulocystic, and papulopustular), acne with scarring or psychological distress, and moderate acne featuring frequent relapse, significant scarring, strong family history, and marked psychosocial burden. Similar agreement was achieved for adolescents (12–18 years). High consensus supported isotretinoin for special clinical scenarios, including treatment-resistant acne, gram-negative folliculitis, and acne fulminans. Early initiation was favored to prevent acne progression and scarring, with high agreement on quality-of-life improvement with isotretinoin use. Conventional dosing (0.5–1 mg/kg/day) was preferred for severe acne forms; low-dose (0.1–0.5 mg/kg/day) was acceptable for moderate/persistent acne. The consensus acknowledged common adverse effects, less frequent systemic effects, and the well-established teratogenic risk of isotretinoin. Laboratory monitoring, especially in metabolic risk, was advised. Low consensus persisted around cumulative dosing, laboratory testing frequency, and duration of posttreatment washout before pregnancy. The Expert consensus on the Rational Approach to ISotretinoin usage for Effective management of ACNE (ERAISE ACNE) algorithm offers a practical guide for isotretinoin use in Indian clinical practice, emphasizing early initiation, tailored dosing, safety-focused monitoring, and is applicable to settings with similar patient demographics and challenges.

Supplementary Information

The online version contains supplementary material available at 10.1007/s13555-026-01681-6.

Key Summary Points

This 20-member modified Delphi consensus (ERAISE ACNE algorithm), developed in the context of Indian clinical practice, with relevance to regions having similar patient settings, outlined first-line isotretinoin indications for severe conglobate, nodulocystic, and severe papulopustular acne in adults and adolescents and risk-based use in select moderate cases.

Early initiation of isotretinoin after failure of first-line therapy was endorsed to curb acne progression, scarring, and postinflammatory hyperpigmentation, with acknowledged benefits in quality of life.

Conventional daily dosing (0.5–1 mg/kg/day) was preferred for severe acne, while low-dose regimens were acceptable for moderate or persistent mild acne.

Risk-adapted laboratory monitoring rather than a universal approach was emphasized, with recognition of common and less frequent adverse effects, precautions, and contraindications.

There was consensus on use of procedures such as comedone extraction, chemical peels, and fractional lasers during isotretinoin therapy in appropriate candidates and on isotretinoin use for select nonacne indications.

Introduction

Globally, the prevalence of acne is estimated to be approximately 20.5% [1]. However, the prevalence varies across regions, with higher rates reported in East Asia, Latin America, and the Middle East and lower rates in Europe. The pathophysiology of acne vulgaris is multifactorial, encompassing follicular hyperkeratinization, increased sebum production, proliferation of Cutibacterium acnes (C. acnes), and associated inflammation [2, 3]. In addition, long-term sequelae such as postinflammatory hyperpigmentation (PIH) and permanent scarring are frequently observed [4]. Beyond its cutaneous manifestations, acne vulgaris imposes a substantial psychosocial burden, contributing to emotional distress, anxiety, and depression [5, 6]. Patients often face stigmatization in both social and professional contexts, exacerbating the emotional impact [7].

Regional and single-center studies have indicated that acne affects approximately 70–87% of adolescents and 0.74–1.07% of adults [8–11]. Mild and self-treated cases may often remain underreported. The epidemiological profile of acne may include persistence into adulthood, with hyperpigmentation and scarring being common outcomes, emphasizing the need for early and effective interventions [10, 12, 13]. According to the acne management algorithms proposed by the National Institute for Health and Care Excellence (NICE), the American Academy of Dermatology (AAD), and the Indian Acne Alliance (IAA), treatment is based on disease severity and risk factors [14–16]. Mild to moderate acne is managed primarily with topical combination therapies, including topical retinoids, benzoyl peroxide, and topical antibiotics (used only in combination to reduce antibiotic resistance). Moderate to severe acne requires escalation to systemic therapies, where oral antibiotics are added to topical regimens for limited durations, with hormonal agents (such as combined oral contraceptives or anti-androgens) considered in appropriate female patients, and oral isotretinoin recommended for severe, scarring, or treatment-refractory acne. Across all severity grades, both guidelines emphasize the importance of adjuvant care, including gentle cleansers, non-comedogenic moisturizers, appropriate photoprotection, and patient education regarding adherence and avoidance of lesion manipulation [17]. However, despite the available treatment options, acne management remains challenging, particularly in cases associated with a high risk of scarring, psychological distress, or relapse [18]. Rising antibiotic resistance among C. acnes strains further complicates management strategies globally [19].

Oral isotretinoin, a synthetic retinoid and vitamin A derivative, remains the most effective monotherapy for severe, recalcitrant acne vulgaris. It targets all major pathogenic pathways by reducing sebaceous gland size and sebum production, normalizing follicular keratinization, inhibiting C. acnes, and exerting anti-inflammatory effects [20]. Since its initial approval by the US Food and Drug Administration in 1982 for nodular acne and subsequent approval for severe cystic and conglobate acne vulgaris, isotretinoin has become the gold standard for severe acne management. Its use has since expanded to include moderate acne associated with scarring or psychological morbidity [21, 22].

Despite its proven efficacy, the use of isotretinoin is often associated with some concerns, including teratogenicity, mucocutaneous side effects, and laboratory abnormalities such as dyslipidemia and hepatotoxicity [23, 24]. Inconsistent dosing strategies, monitoring protocols, and patient selection criteria further contribute to variability in prescribing practices [25]. Moreover, widespread myths and misconceptions, often lacking scientific backing, continue influencing patient and physician perceptions despite evidence supporting the efficacy and safety of isotretinoin when appropriately used [26].

Multiple international acne guidelines and expert consensus statements have attempted to standardize isotretinoin use [15, 27–29]. However, in the Indian context, no updated, evidence-based guidelines have been formulated in over a decade. Given the differences in clinical presentations and patient expectations across regions, practical, region-specific guidance on the use of isotretinoin in the management of acne vulgaris is warranted.

To address this gap, a panel of dermatology experts convened to develop a structured, evidence-informed consensus on isotretinoin use in acne vulgaris using a modified Delphi methodology. This manuscript presents the consensus process, outcomes, and key recommendations that emerged, aiming to support dermatologists in optimizing isotretinoin therapy in routine clinical practice in India.

Materials and Methods

This initiative aimed to develop consensus-based recommendations on the optimal use of oral isotretinoin in acne vulgaris, focusing on patient selection, safe prescribing practices, and treatment monitoring. A modified Delphi methodology was employed based on previously published studies, and reporting was carried out in accordance with the ACcurate COnsensus Reporting Document (ACCORD) guidelines, integrating a comprehensive literature review with expert clinical insights. The ACCORD checklist is provided as Supplementary Table 1. The methodological framework included selecting an expert panel, reviewing the literature, drafting a questionnaire, and implementing a structured consensus development process. Figure 1 presents an overview of the consensus workflow. While this study was not prospectively registered, it was carried out in alignment with established consensus development practices.

Fig. 1.

Overview of the consensus workflow

Ethics and Informed Consent

This Delphi-based consensus did not involve patient data, human biological samples, or clinical interventions. It was limited to obtaining expert opinions from healthcare professionals, and as such, it was considered exempt from formal ethics committee review. All panelists were informed about the consensus objectives, methodology, and intended use of the findings. Informed consent was obtained from all panel members. Participation was entirely voluntary, and responses were anonymized to maintain confidentiality.

Expert Panel Selection

A scientific committee consisting of 20 dermatologists across India was constituted for this initiative. Panel members were selected through purposive sampling based on their clinical experience, academic contributions, and expertise in acne management. The selection ensured representation from diverse clinical settings, including private practice and academic institutions (Supplementary Table 2). One expert was designated as the moderator to oversee and facilitate the overall process.

Review of the Literature

A comprehensive search on PubMed and the Cochrane Library was conducted to identify relevant literature published between January 2000 and September 2024. A scoping literature review (in English) was conducted to make sure the available evidence informed the initial statements. Search terms included combinations of keywords such as “acne vulgaris,” “isotretinoin,” “systemic therapy,” “efficacy,” “safety,” “monitoring,” “contraindications,” and “guidelines.” Eligible articles included original research, systematic reviews, meta-analyses, practice guidelines, and consensus recommendations, all published in English. Animal studies and non-English publications were excluded. Articles deemed relevant to the consensus objectives were appraised and graded using the Oxford Levels of Evidence (2011) framework [30]. This evidence synthesis informed the development of the questionnaire. A summary of key findings was shared with the panel members as a preread document.

Formulation of the Questionnaire

Insights from the literature review were used to identify key clinical themes and existing gaps in the use of isotretinoin. Preliminary statements were considered based on available evidence. A structured questionnaire was developed and organized under broad thematic categories: patient selection (pediatric and adult), dosing and duration, laboratory monitoring, side effects, precautions and contraindications, formulation-specific considerations, procedural interventions, and dermatological indications for isotretinoin use beyond acne. For the purpose of this consensus, the IAA grading of acne severity was used [16]. Mild acne (Grade I) was defined by predominance of comedones (comedones < 30; papules < 10; no scarring); moderate acne (Grade II) was defined by predominance of papules (any number of comedones; papules > 10; nodules < 3; ± scarring); and severe acne (Grade III) was defined by presence of many nodules (any number of comedones; any number of papules; nodules/cysts > 3; scarring). These questions were used to guide the literature review and the generation of statements. The preliminary statements were refined through iterative expert input and aligned with current evidence and the panel members’ real-world clinical experience.

Survey Administration and Data Collection

The finalized questionnaire was disseminated to the expert panel via a digital platform. For each statement, the experts were asked to select either “agree” or “disagree.” Predefined thresholds of consensus were applied: high consensus (≥ 80% agreement or disagreement), moderate consensus (60–79% agreement or disagreement), and low consensus (< 60% agreement or disagreement) [31]. Statements that did not achieve high consensus in the first round were reviewed by the moderator and further modified during the virtual discussion before a second round of voting. Standardized phrasing was used for high, moderate, and low consensus statements, which included “strongly recommended,” “can be considered,” and “may be considered,” respectively, to reflect the strength of agreement. The strength of a recommendation was adapted to this consensus based on the National Institute for Health and Care Excellence guideline development manual and European Society of Human Reproduction and Embryology good practice recommendations [32, 33].

Consensus Development Process

The modified Delphi process involved two rounds of voting and one virtual discussion session. In the first Delphi round, the panelists voted on the initial set of statements. Statements that did not reach a high level of consensus were deliberated during a virtual meeting for necessary amendments. On the basis of this discussion, selected statements were revised for clarity and clinical applicability. Revised statements were then redistributed for a second round of voting.

Results

The consensus process was carried out between July and December 2024. The participants were provided 20 days to complete each round of the survey. The participation rate was 100% (n = 20) in all rounds. A preliminary preconsensus survey was conducted to gather practice insights from participating experts (n = 20). The survey revealed that in their practice, acne was commonly seen in adolescents and young adults, with prevalence peaking in the 18–29-year age group and declining thereafter. Moderate acne was most frequently encountered (reported by 75% of respondents in 30–69% of cases), followed by mild and severe forms. The key factors influencing treatment decisions included patient age, disease severity, prior treatments, psychosocial impact, and clinical effectiveness. Nearly half (45%) of the respondents reported acne relapse in 30–49% of patients within 2 years. Isotretinoin use varied: 40% prescribed it in 15–29% of cases, and another 40% in 50–69% of cases. Its benefits were recognized; the most cited improvements were in inflammation, sebum control, scarring, and bacterial load. While 75% of the respondents tailored isotretinoin use by age group, 85–95% initiated therapy in moderate-to-severe acne, with 25% also considering it in selected mild cases.

A total of 58 statements were prepared and submitted for the first round of voting. Of these, 19 statements achieved a high consensus, 18 reached a moderate consensus, and 21 reached a low consensus. Following this initial round, a virtual meeting was conducted to deliberate on the statements that achieved moderate or low consensus. On the basis of the discussion, some statements were revised, removed, or retained to reflect expert insights. This elimination followed the expert panel’s judgment that the statement relied on limited or conflicting data, overlapped substantially with better-supported recommendations. In the second round of voting, after eliminating four statements, a total of 35 statements were evaluated. At the end of the process, 35 statements reached a high consensus, 10 achieved a moderate consensus, and nine remained at a low consensus. The final list of consensus statements is provided in Table 1.

Table 1.

Finalized list of consensus statements

Statement lD no.	Consensus statement	Level of evidence	Finalized in round	Level of consensus
Patient profiles that can benefit from isotretinoin therapy
1	Systemic isotretinoin therapy is strongly recommended in patients with conglobate acne (LOC 95%), severe recalcitranta nodular cystic acne (LOC 100%), and severe recalcitranta papulopustular acne (LOC 100%)	1	1	High
2*	Systemic isotretinoin therapy is strongly recommended for moderate recalcitrant inflammatory acne with a family history of acne† (LOC 100%), treatment-resistant moderate inflammatory acne with a high tendency of atrophic scarring† (LOC 100%), moderate acne with significant psychological distress† (LOC 85%), and patients with moderate acne who relapse frequently after discontinuation of systemic antibiotics and topical therapies# (LOC 100%)	1†; 3#	2	High
3*	Systemic isotretinoin therapy is strongly recommended for patients with acne with antibiotic-resistant strains of Cutibacterium acnes# (LOC 85%), patients with gram-negative folliculitis‡ (LOC 80%), female patients with recurrent acne and no evidence of relapse due to hormonal changes (LOC 95%), and patients with strong personal history of scarring† (regardless of acne grade) (LOC 80%) However, low-dose systemic isotretinoin therapy with an initial prednisolone is strongly recommended in patients with acne fulminans. Isotretinoin can be gradually increased with a slow taper of prednisolone$ (LOC 100%)	1†; 2#; 3‡; 5$	2	High
4	Systemic isotretinoin therapy can be considered in patients with a strong family history of scarring, irrespective of acne grade (LOC 75%)	1	2	Moderate
First-line oral isotretinoin in the pediatric age group
5	Among patients in the pediatric age group (12–18 years), first-line oral isotretinoin therapy is strongly recommended for severe conglobate acne (LOC 95%), severe nodulocystic acne (nodules/cysts > 3) (LOC 95%), and severe papulopustular acne (with significant psychological distress [LOC 80%] or with a risk of scarring [LOC 100%])	1	2	High
6	First-line oral isotretinoin therapy is strongly recommended in pediatric patients (12–18 years) with moderate nodular acne (nodules < 3; LOC 95%) and moderate long-persisting papulopustular acne with significant physical scarring (LOC 95%)	3	2	High
7	First-line oral isotretinoin therapy is strongly recommended in pediatric patients (12–18 years) with persistent mild-to-moderate papulopustular acne (LOC 80%)	3	1	High
8	First-line oral isotretinoin therapy can be considered in pediatric patients (12–18 years) with moderate papulopustular acne with a risk of scarring (LOC 70%)	3	2	Moderate
Other pediatric patient profiles where oral isotretinoin can be used
9	Oral isotretinoin therapy is strongly recommended in pediatric patients (12–18 years) with severe papulopustular acne (LOC 95%) and moderate papulopustular acne with severe psychosocial distress (LOC 80%)	3	2	High
10	Oral isotretinoin therapy can be considered in pediatric patients (12–18 years) with moderate papulopustular acne (LOC 60%) and moderate papulopustular acne with a strong family history of acne (LOC 75%)	3	2	Moderate
11	Oral isotretinoin therapy may be considered in pediatric patients (12–18 years) with mild acne with a family history or personal history of scarring (LOC 55%)	3	2	Low
First-line oral isotretinoin in the adult age group
12	First-line oral isotretinoin therapy is strongly recommended in adults (> 18 years) with severe conglobate acne (LOC 100%), severe nodulocystic acne (nodules/cysts > 3; LOC 100%), and severe conglobate/nodulocystic/papulopustular acne with significant physical scarring or strong family history of scarring (LOC 100%) First-line oral isotretinoin therapy is also strongly recommended for adults with severe papulopustular acne with significant psychological distress (LOC 90%), severe papulopustular acne with a risk of scarring (LOC 100%)	1	2	High
13	First-line oral isotretinoin therapy is strongly recommended in adults with moderate nodular acne (nodules < 3) with significant physical scarring (LOC 100%), long-persisting moderate papulopustular acne with significant physical scarring (LOC 100%), moderate papulopustular acne with a risk of scarring (LOC 90%), and persistent mild-to-moderate papulopustular acne (LOC 90%)	1	2	High
14	First-line oral isotretinoin therapy is strongly recommended in female patients with acne in whom hormonal imbalances/menstrual irregularities have been ruled out (LOC 95%)	4	2	High
Other adult patient profiles where oral isotretinoin can be used
15	Oral isotretinoin therapy is strongly recommended in adult patients (> 18 years) with severe papulopustular acne (LOC 100%), moderate papulopustular acne (LOC 80%), moderate papulopustular acne with a strong family history of acne (LOC 85%), moderate papulopustular acne with severe psychosocial distress (LOC 80%)	1	2	High
16	Oral isotretinoin therapy may be considered in adult patients (> 18 years) with mild acne with a family/personal history of scarring (LOC 35%) and mixed comedonal/inflammatory acne (LOC 45%)	5	2	Low
Second-line oral isotretinoin
17	Oral isotretinoin is strongly recommended as a second-line treatment in patients with moderate (LOC 100%) and severe recalcitrant acne (LOC 100%) if there is inadequate response after completion of a treatment course with oral antibiotics plus topical combination therapy (benzoyl peroxide, retinoid, and/or antibiotic)	1	1	High
18	In patients with persistent mild-to-moderate papulopustular acne, oral isotretinoin is strongly recommended as a second-line treatment option if inadequate response is reported after topical combination therapy (benzoyl peroxide, retinoid, and/or antibiotic) (LOC 95%)	1	1	High
Early initiation of isotretinoin
19	Early initiation (i.e., after the failure of the first-line recommended therapy) of isotretinoinb is strongly recommended to prevent the incidence of acne scars (LOC 90%) and postacne hyperpigmentation (LOC 80%)	1	1	High
20*	Early initiation (i.e., after the failure of the first-line recommended therapy) of isotretinoin is strongly recommended to prevent the progression of mild-to-moderate (LOC 60%)^ and moderate-to-severe acne (LOC 95%)†	1	1	Moderate^/High†
Dosing and duration of isotretinoin therapy in acne management
21	The conventional dose (0.5–1 mg/kg/day) of oral isotretinoin is strongly recommended over the low dose (0.1–0.5 mg/kg/day) for clinical cure and prevention of relapse in conglobate acne (LOC 90%) and severe nodulocystic acne (LOC 80%)	1	2	High
22*	Low dose (0.1–0.5 mg/kg/day) of oral isotretinoin can be considered for clinical cure and prevention of relapse in severe (LOC 60%)/moderate cases of papulopustular acne† (LOC 70%) and persistent mild acne# (LOC 75%)	3†; 1#	2	Moderate
23	Cumulative dosing may be considered while prescribing isotretinoin for clinical cure and prevention of relapse (LOC 50%). Standard cumulative dosing (up to 120 mg/kg body weight) may be considered while prescribing isotretinoin for clinical cure and prevention of relapse over higher dose (150–220 mg/kg body weight) cumulative dosing (LOC 30%)	3	2	Low
24	Isotretinoin treatment may be continued until 1 month after complete remission (55%)	3	2	Low
25	It is strongly recommended to take isotretinoin along with meals (LOC 100%)	1	1	High
26	Escalating the daily dose of isotretinoin is strongly recommended to increase the response rate in slow respondersc (LOC 95%)	1	1	High
27*	Modification of isotretinoin dosage can be considered in the event of a flare-up (LOC 65%)^ during the initial phase of treatment for normal comedonal acne. Dose modification is strongly recommended for severe flare-ups during the initial phase of treatment for normal comedonal acne (LOC 80%)†	5	2	Moderate^/High†
28	A once-daily isotretinoin dose is strongly recommended as more convenient (vs. a twice-daily regimen) and is more likely to increase treatment adherence (LOC 85%)	2	2	High
29	Once-daily isotretinoin dose may be associated with a higher tendency for gastrointestinal disturbance. Splitting the dose twice daily may be considered in such cases (LOC 50%)	2	2	Low
30	Low-dose isotretinoin maintenance therapy (up to a maximum of 0.3 mg/kg/day) is strongly recommended on a case-by-case basis after the completion of the conventional dose in patients with persistent acne (severe papulopustular, severe nodulocystic, or conglobate acne) (LOC 85%)	1	2	High
31	Low-dose isotretinoin maintenance therapy may be considered for 3 months after the completion of the conventional dose in patients with persistent acne (severe papulopustular, severe nodulocystic, conglobate acne), depending on patient condition (LOC 59%)	1	2	Low
Risk of relapse and quality of life after isotretinoin therapy
32*	Family history of severe acne,† personal/family history of sinus tract lesions# (pilonidal sinus, hidradenitis, or dissecting cellulitis of the scalp), and hyperandrogenism† are the factors related to patient history that are associated with increased risk of relapse after isotretinoin therapy (LOC 100%)	2†; 5#	1	High
33	Prepubertal acne (LOC 70%), cosmetic use (LOC 70%), and smoking history (LOC 65%) are factors related to patient history that can be associated with increased risk of relapse after isotretinoin therapy	5	1	Moderate
34	Oral isotretinoin effectively improves the patient’s quality of life in terms of improvement of symptoms and emotional and functional aspects (LOC 100%)	2	1	High
Laboratory monitoring during treatment with isotretinoin
35	Routine laboratory monitoring during isotretinoin therapy depends on the patient’s medical history/risk factors (LOC 90%)	1	1	High
36	Monitoring laboratory parameters before treatment initiation (at baseline) and during isotretinoin therapy is strongly recommended in patients with acne with dyslipidemia (LOC 90%), obesity (LOC 85%), or a family history of diabetes, dyslipidemia, metabolic syndrome, and fatty liver (LOC 85%)	1	1	High
37*	Lipid profile (total cholesterol, low-density lipoproteins, high-density lipoproteins, and triglycerides) and liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) are strongly recommended before treatment initiation (at baseline) and during isotretinoin therapy (LOC 100%)	1	2	High
38	Laboratory measurement of blood glucose and creatine phosphokinase levels may be considered in patients receiving oral isotretinoin (LOC 35%)	1	2	Low
Side effects and precautions
39*	Cheilitis (LOC 100%) and dry skin (xerosis; LOC 90%)^ are the most commonly observed (≥ 1/10) side effects patients experience during isotretinoin therapy. Other side effects most commonly observed include dry eyes (LOC 75%)† and dry nose (LOC 70%)†	1	2	High^/Moderate†
40*	(A) Psychiatric symptoms, such as depressed mood, insomnia, and hallucinations, are side effects rarely observed (≥ 1/10,000 and < 1/1000) in patients during isotretinoin therapy‡ (LOC 80%) (B) Other side effects rarely observed include elevated liver enzymes‡ (LOC 70%), elevated serum lipids‡ (LOC 75%), and menstrual irregularities# (LOC 70%) from baseline	1‡; 3#	2	HighA/ModerateB
41	Gentle soap-free cleansers (LOC 100%), lip balms (LOC 100%), noncomedogenic moisturizers (LOC 95%), and noncomedogenic sunscreens (LOC 80%) are strongly recommended adjuvants in patients on isotretinoin therapy	2	1	High
42	It is strongly recommended that the prescribing dermatologist ask their patients about symptoms of depression before treatment initiation and during the isotretinoin therapy (LOC 95%)	1	1	High
43	Prescribing dermatologist can consider monitoring their patients for any indication of inflammatory bowel disease before treatment initiation and during isotretinoin therapy (LOC 75%)	1	2	Moderate
44	Patient counseling for female patients of childbearing age is strongly recommended during isotretinoin therapy (LOC 100%)	1	1	High
45	For female patients of childbearing age, pregnancy testing can be considered before initiating isotretinoin therapy (LOC 62.50%)	2	1	Moderate
46	Advise female patients of childbearing age to avoid pregnancy after isotretinoin therapy for a duration of 6 months (LOC 30%)	5	2	Low
47	Advising male patients on isotretinoin therapy for family planning is not needed (LOC 75%)	5	2	Moderate
Contraindications
48	The contraindications for isotretinoin include hypervitaminosis A (LOC 100%), significant leukopenia (LOC 95%), hyperlipidemia (LOC 85%), hepatic dysfunction (LOC 95%), pregnancy (LOC 100%), and combination with tetracyclines (LOC 90%)	1	1	High
Formulations
49	In clinical experience, there is no difference in the efficacy outcomes between the use of conventional soft gel capsule formulation and micronized formulation of isotretinoin (LOC 70%)	2	1	Moderate
50	In clinical experience, there is no difference in the safety outcomes between the use of conventional soft gel capsule formulation and micronized formulation of isotretinoin (LOC 85%)	2	1	High
Isotretinoin and procedural interventions
51	Comedone extraction (LOC 100%), superficial and medium-depth peels (LOC 85%), and laser procedures (fractional ablative and nonablative) for acne scarring (LOC 80%) can be performed in patients on isotretinoin therapy	2	1	High
52*	Laser procedures (fractional ablative and nonablative) for pigmented skin lesions (LOC 65%)^ and microdermabrasion (LOC 50%)† can also be considered in patients on isotretinoin therapy	2	1	Moderate^/Low†
Dermatological indications for the use of isotretinoin beyond acne
53	Beyond acne, isotretinoin can be used in skin conditions such as rosacea (LOC 95%), seborrheic dermatitis (LOC 90%), and hidradenitis suppurativa (LOC 90%)	1	1	High
54	Isotretinoin may be considered in pustular psoriasis (LOC 45%) and ichthyosis (LOC 35%)	4	1	Low

Portions of the statement that were supported by different levels of evidence or received varying levels of agreement have been annotated with superscripts (*, †, ‡, #, $, ^)

LOC level of consensus

^aFailed oral antibiotics in combination with topical retinoids and benzoyl peroxide treatment strategy

^bIndicated in adults and children 12 years of age and older

^cSlow responders are patients with significant active acne despite 6 months of isotretinoin treatment, ruling out hormonal disorders in female patients and acneiform eruptions (due to infections, drug reactions, medications, or chemical contact) in male and female patients

Discussion

Patient Profiles That Can Benefit from Isotretinoin Therapy (Statements 1–4)

Oral isotretinoin has long been established as the treatment of choice for severe, recalcitrant acne, particularly conglobate, nodular cystic, and severe papulopustular variants, due to its ability to target all four pathogenic factors of acne. A systematic review by Daly et al. reaffirmed its effectiveness in achieving long-term remission in patients with severe acne, especially when administered at standard cumulative doses [34]. Consistent with international guidelines such as those from the AAD and the European S3 group [15, 27], the expert panel in this Delphi study reached a high level of consensus in recommending isotretinoin as a first-line agent for patients with conglobate acne (95%), severe nodulocystic acne (100%), and severe papulopustular acne (100%) (statements 1–4 from Table 1).

While traditionally reserved for severe acne, isotretinoin is currently being increasingly used in moderate acne when associated with significant psychosocial burden, frequent relapse, or risk of scarring. European guidelines suggest that isotretinoin may be appropriate as a first-line option in such patients, particularly when prognostic markers (e.g., family history of scarring and psychological distress) are present [15, 27]. A longitudinal study by Brzezinski et al. further showed that early isotretinoin use in moderate acne reduced the risk of long-term postacne complications [35]. Reflecting this evolving perspective, the expert panel recommended systemic isotretinoin therapy for moderate acne presentations such as recalcitrant inflammatory acne, treatment-resistant forms with a high risk of atrophic scarring, moderate acne with significant psychological distress, and frequent relapsing moderate acne after systemic antibiotics or topical therapies (100% consensus). These recommendations received high consensus, reflecting the panel’s recognition of the extended indications for isotretinoin. This is particularly relevant for skin of color, which is associated with high scarring tendency and greater frequency and intensity of PIH [36, 37].

Another key consideration is the growing concern of antibiotic resistance in C. acnes, wherein isotretinoin offers a key advantage due to its nonantibiotic mechanism of action [38]. Böni and Nehrhoff showed that gram-negative folliculitis, a condition often misdiagnosed as treatment-resistant acne, responds well to isotretinoin [39]. Additionally, isotretinoin has demonstrated efficacy in female patients with recurrent acne, often representing a subset of adult acne that responds poorly to conventional therapies (which typically include topical retinoids, benzoyl peroxide, and oral or topical antibiotics) [40]. Reflecting this, the panel reached a high level of consensus on recommending systemic isotretinoin in several special scenarios, including acne with antibiotic-resistant C. acnes strains (85%), gram-negative folliculitis (80%), and recurrent acne in female patients without overt hormonal abnormalities (95%). These recommendations underscore the limitations of conventional therapies and highlight isotretinoin’s broad-spectrum, mechanism-specific efficacy. A personal or family history of scarring was also identified as an important prognostic factor, justifying early initiation of isotretinoin even in cases not clinically classified as “severe” (80% consensus).

In cases of acne fulminans, low-dose isotretinoin combined with systemic corticosteroids is the treatment of choice [41]. For such cases, the panel unanimously (100%) recommended initiating isotretinoin at low doses combined with initial prednisolone to manage the inflammatory flare, with gradual uptitration of isotretinoin and tapering of steroids. This stepwise approach is in accordance with the literature supporting corticosteroid use to mitigate the initial inflammatory exacerbation sometimes seen with isotretinoin [41].

First-Line Oral Isotretinoin in the Pediatric Population (Statements 5–11)

Evidence supports the safe and effective use of oral isotretinoin in pediatric patients aged 12–18 years with severe or select moderate acne forms [35]. Long-term follow-up has demonstrated that early intervention with isotretinoin in pediatric patients can prevent permanent scarring and reduce psychosocial morbidity [35].

Several international guidelines, including those from the AAD and the European S3 group, now endorse isotretinoin as a first-line therapy for pediatric patients (aged 12–18 years) with severe acne or a high disease burden [15, 28, 29]. In line with this, the consensus panel strongly supported first-line use of isotretinoin in pediatric patients (aged 12–18 years) with severe conglobate acne (95%), severe nodulocystic acne defined as nodules/cysts > 3 (95%), and severe papulopustular acne associated with either psychosocial distress (80%) or risk of scarring (100%).

Furthermore, isotretinoin was strongly recommended as a first-line therapy for moderate nodular acne (nodules < 3, 95%) and moderate long-standing papulopustular acne with physical scarring (95%). Clinical evidence indicates that pediatric patients with moderate papulopustular acne and elevated psychological distress scores benefit significantly from isotretinoin when topical and oral antibiotics fail [42]. Consequently, the experts reached a high level of consensus on oral isotretinoin use for pediatric patients with moderate papulopustular acne associated with severe psychosocial distress (80%), even if not used as first-line. These recommendations reinforce the importance of tailoring acne treatment in pediatric patients to individual disease burden, psychosocial impact, and risk of scarring rather than relying solely on traditional severity-based algorithms.

First-Line Oral Isotretinoin in Adults (Statements 12–16)

A network meta-analysis including 210 articles and 37 interventions revealed that the most effective treatment for acne was oral isotretinoin, followed by triple therapy (containing a topical/oral antibiotic, a topical retinoid, and benzoyl peroxide) [43]. Its disease-modifying potential and ability to induce long-term remission support its use as a first-line agent in adults with severe acne and in select moderate cases with poor prognostic markers [15, 28, 29].

Adult acne, particularly in women, is prevalent and often presents as a persistent, treatment-resistant condition. Oral isotretinoin therapy, although historically reserved for severe phenotypes, has shown benefits in adult-onset or persistent moderate acne with relapsing patterns and poor response to other treatment modalities, even when nodule counts are low [44].

The expert panel reached high consensus in recommending first-line oral isotretinoin therapy in adults (> 18 years) with severe acne conglobata (100%), severe nodulocystic acne (nodules/cysts > 3) (100%), and severe papulopustular acne (with a strong family history of acne [100%], significant physical scarring [100%], and significant psychosocial distress [90%]). Furthermore, isotretinoin was also recommended by the experts as a first-line therapy in adults with moderate nodular acne (nodules < 3) with physical scarring (100%), long-standing moderate papulopustular acne with scarring (100%), and persistent mild-to-moderate papulopustular acne (90%).

A substantial subset of adult female patients presents with recurrent or persistent acne without identifiable hormonal abnormalities such as polycystic ovary syndrome. These patients often do not respond adequately to hormonal therapies or antibiotics. Isotretinoin has shown favorable outcomes in such cases, offering long-term remission, particularly when hormonal evaluation has ruled out underlying endocrine causes [44]. There was a strong consensus among the experts (95%) for recommending first-line isotretinoin in female adult patients with acne, where hormonal imbalance and menstrual irregularities have been ruled out. This recommendation underscores the importance of timely escalation to isotretinoin in appropriate nonhormonal acne phenotypes to avoid undertreatment.

Moderate acne in adults, even without classic severe markers, can significantly affect the quality of life. Factors such as family history, psychosocial impact, and nonresponsiveness to prolonged antibiotic or topical therapy are recognized as justification for systemic therapy, especially isotretinoin [45]. Along these lines, the expert panel recommended oral isotretinoin therapy (not necessarily as first-line) for the following adult profiles: severe papulopustular acne (100%), moderate papulopustular acne (80%), and moderate papulopustular acne with a strong family history of acne (85%) or severe psychosocial distress (80%).

Second-Line Use of Oral Isotretinoin (Statements 17–18)

Clinical guidelines from the AAD and the European S3 consensus recommend oral isotretinoin as a second-line option for patients with moderate-to-severe acne who have failed to respond to standard therapies, including oral antibiotics combined with topical agents (benzoyl peroxide, retinoids, and/or topical antibiotics) [15, 27]. Several studies have demonstrated that prolonged or repeated courses of antibiotics yield diminishing therapeutic benefits while increasing the risk of antibiotic resistance, reinforcing the rationale for transitioning to isotretinoin when standard combination therapy fails [46].

In line with these principles, the expert panel reached a strong consensus in recommending oral isotretinoin as a second-line therapy in patients with moderate acne (100%) and severe recalcitrant acne (100%) who have not responded adequately to a combination regimen of oral antibiotics and topical combinations. These recommendations align with current evidence-based guidelines and underscore the importance of timely escalation to systemic retinoids to prevent disease chronicity, antibiotic overuse, and worsening psychosocial impact.

A separate yet increasingly relevant scenario involves persistent mild-to-moderate papulopustular acne that fails to respond to optimized topical combination therapy, where systemic treatment becomes necessary. It may carry a risk of progression or scarring if left inadequately treated. Emerging evidence supports the use of low-dose isotretinoin in these cases, demonstrating both efficacy and good tolerability [47].

The current expert opinion also supported a risk-adapted approach in patients with verified adherence who show poor response to topical therapy, including benzoyl peroxide with a retinoid or a topical antibiotic. This recommendation (95% consensus) highlights the need to address therapeutic failure proactively, even in nonsevere acne, when clinical resistance, recurrence, or significant psychosocial burden is evident [48]. Together, these recommendations advocate for judicious second-line use of isotretinoin in moderate and even nonsevere acne presentations, guided by clinical resistance, recurrence, or risk of complications.

Early Initiation of Isotretinoin (Statements 19–20)

Patients with skin of color are more prone to acne-induced sequelae such as scarring and PIH, which affect up to 95% of inflammatory acne cases and are difficult to reverse [37, 49–51]. These pigmentary and structural changes are problematic in darker skin types due to their propensity for long-lasting pigment alterations [50, 51]. PIH may persist long after lesion resolution, and, along with scarring, can contribute to sustained psychosocial burden. Proactive intervention, particularly through the timely initiation of isotretinoin once standard oral and topical treatments have failed, has been shown to halt disease progression, reduce inflammation, minimize both atrophic scarring and PIH, and ultimately improve overall quality of life, especially in patients with a strong family history or prior scarring [35, 44, 45, 48, 52].

Reflecting the practice patterns of the experts, the voting reached a high level of consensus on early initiation of isotretinoin to prevent the incidence of acne scars (90%) and reduce PIH (80%), underscoring the importance of identifying patients at high risk of scarring or PIH for earlier consideration of isotretinoin, even in nonsevere acne cases.

Beyond pigmentary considerations, earlier and more aggressive treatments can prevent progression to more severe, nodular forms [53]. Importantly, early isotretinoin use may also reduce the total cumulative dose needed, minimizing adverse effects while preserving long-term efficacy [54]. On the basis of this rationale, the expert panel reached a high level of consensus (95%) that starting isotretinoin promptly after first-line treatment failure can prevent the progression from moderate to severe acne. This aligns with the clinical trend toward more proactive management in cases with poor response trajectories or indicators of poor prognosis.

Beyond these high-risk scenarios, the expert opinions were more divided. Given the limited evidence, only 60% of the experts preferred early initiation of isotretinoin in their practice after the failure of first-line therapy to prevent the progression of mild-to-moderate acne. This cautious endorsement suggests that while early systemic intervention may benefit selected high-risk cases, it should be individualized and carefully weighed against potential risks.

Dosing and Duration of Isotretinoin Therapy in Acne Management (Statements 21–31)

The approach to dosing and duration of isotretinoin therapy in acne management has shifted from fixed cumulative targets to more individualized, patient-centric strategies. This section summarizes the expert consensus on daily dosing, cumulative targets, treatment duration, and strategies to optimize outcomes and minimize relapse or adverse effects.

Daily Dosing Strategies: Conventional vs. Low-Dose Approaches

The recommended conventional daily dose of isotretinoin is 0.5–1 mg/kg/day. However, low-dose regimens have gained interest in particular patient profiles, especially in those at greater risk of side effects. Research indicates that low-dose isotretinoin can be effective in moderate-to-severe acne, although relapse rates may be higher without extended or maintenance therapy [55]. The experts preferred conventional dosing (0.5–1 mg/kg/day) for conglobate acne (90%) and severe nodulocystic acne (80%) to achieve clinical cure and prevent relapse. For moderate-to-severe papulopustular acne, the experts considered low-dose isotretinoin (0.1–0.5 mg/kg/day) effective, reflecting moderate consensus (75%). For persistent mild acne, 75% of the experts favored low-dose isotretinoin, showing moderate consensus.

Cumulative Dose, Treatment Duration, and Clinical Cure

Debate continues on the optimal cumulative dosing and duration of therapy. It has been suggested that a single course of isotretinoin therapy for 15–20 weeks results in complete and prolonged remission [56]. While the traditional cumulative target is 120–150 mg/kg, it has been reported that, compared to < 220 mg/kg, a higher cumulative dose (≥ 220 mg/kg) effectively decreases relapse rates without increasing adverse effects [57]. Some emerging studies suggest that individualized dosing targets based on response and tolerability may be more effective [58]. Extending therapy beyond lesion clearance has also been proposed to improve long-term outcomes [59].

The discussion on whether achieving a specific cumulative dose is essential for all patients remained inconclusive among the expert panel. Some experts reported using cumulative dose targets in routine practice, while others emphasized clinical cure (treat-to-clear) as an endpoint. Among those who followed cumulative dosing, there were differences in opinions on preference for standard targets of up to 120 mg/kg body weight or higher cumulative dosing of 150–220 mg/kg. Regarding treatment duration, 55% of the experts suggested continuing isotretinoin until 1 month beyond full lesion clearance, while others stated that the treatment duration depends on individual daily dose (40%) or completion of the cumulative dose (30%).

Dosing Frequency and Food Considerations

The traditional isotretinoin dosage recommendation was two divided doses with food [56]. However, once-daily dosing may be preferred for patient convenience and improved adherence, especially in long-term therapy [60]. Most panelists preferred once-daily dosing (85%) to increase patient adherence. Dose splitting, proposed to mitigate gastrointestinal side effects in higher-dose regimens, received only 50% support. Although higher doses have been suggested to cause side effects that can be mitigated by dose splitting, side effects may depend on the cumulative daily dose rather than dosing frequency [60–62]. Food increases the bioavailability of isotretinoin [56]. The experts agreed (100%) that isotretinoin should be taken with meals.

Managing Slow Responders and Isotretinoin Flare-ups

Isotretinoin slow responders are patients with significant active acne despite 6 months of treatment, ruling out hormonal disorders in female patients and acneiform eruptions (due to infections, drug reactions, medications, or chemical contact) in male and female patients [63]. In slow responders, dose escalation has been shown to improve clinical outcomes, particularly for those who do not metabolize isotretinoin as well as others [44, 63]. The experts showed a strong preference for daily dose escalation in slow responders (95%).

Flare-ups during early therapy are well documented, and some authors advocate for dose modification rather than abrupt discontinuation during these periods [44]. For severe flare-ups in comedonal acne during the initial phase of treatment, dose modification was recommended (80%).

Low-Dose Maintenance Therapy

Low-dose maintenance isotretinoin (≤ 0.3 mg/kg/day) was suggested in patients with recurrent acne or relapse risk after standard therapy [64]. Eighty-five percent of the experts favored low-dose maintenance isotretinoin after conventional treatment in persistent acne (e.g., conglobate and nodulocystic), although no consensus was reached on its duration. Low-dose isotretinoin maintenance therapy was suggested to be considered for 3 months after the completion of the conventional dose in patients with persistent acne (severe papulopustular, severe nodulocystic, and conglobate acne), depending on patient condition (59%). Some experts (n = 3) did not prefer low-dose isotretinoin as maintenance and recommended topical therapy as maintenance for 6 months after completion of topical therapy.

Predictors of Relapse and Impact on Quality of Life (Statements 32–34)

Several patient factors increase the risk of relapse after isotretinoin therapy, including a family history of acne, sinus tract lesions, and untreated hyperandrogenism, particularly ovarian hyperandrogenism [65–68]. Additionally, lifestyle factors such as the use of cosmetic products and smoking may also influence recurrence [69]. On the basis of their practice, the experts identified the following as high-risk factors for relapse with clear agreement (100%): family history of severe acne, sinus tract-related conditions (e.g., pilonidal sinus and hidradenitis suppurativa), and hyperandrogenism. Additional factors with moderate consensus included prepubertal acne (70%), cosmetic use (70%), and smoking history (65%).

Finally, isotretinoin’s positive impact on quality of life is well documented, with improvements in physical symptoms, emotional well-being, and social functioning [70–73]. In agreement with such evidence, all experts (100%) agreed that oral isotretinoin improves the quality of life of patients, supporting its continued use.

Laboratory Monitoring During Treatment with Isotretinoin (Statements 35–38)

The risk of clinically significant biochemical abnormalities during isotretinoin therapy is relatively low in otherwise healthy individuals [74]. While statistically significant changes have been observed in mean laboratory values, including white blood cell count, hepatic enzymes, and lipid panels, these changes are generally not considered high risk, and only a small proportion of patients exhibit clinically abnormal results [24]. The effect of isotretinoin on liver enzymes and lipid profile is reported as rare and reversible [75]. However, laboratory monitoring remains critical in individuals with pre-existing risk factors such as obesity, dyslipidemia, metabolic syndrome, or hepatic disorders [76].

Personalized monitoring strategies based on clinical risk rather than universal strategies for all patients have been advocated to minimize patient burden and healthcare costs while ensuring safety [48, 77]. Reflecting this, 90% of the experts responded that in their practice, the frequency and scope of laboratory monitoring are tailored to the patient’s medical history and risk profile. A high consensus was also reached for routine baseline and follow-up monitoring of liver enzymes and lipid profiles in patients with acne who have dyslipidemia (90%), obesity (85%), and a family history of diabetes, dyslipidemia, metabolic syndrome, or fatty liver disease (85%).

The most clinically relevant laboratory parameters during isotretinoin therapy include liver function tests and lipid profiles, which have the strongest evidence supporting routine monitoring [78]. Although elevated creatine phosphokinase and blood glucose levels have been reported, they are not routinely monitored in the absence of clinical symptoms or specific risk factors [79, 80]. The experts unanimously agreed (100%) that the standard baseline and follow-up laboratory tests should include lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides) and liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase). However, a low consensus (35%) was observed for routine measurement of blood glucose and creatine phosphokinase levels, with the experts recommending these only in selected cases.

Regarding the frequency of laboratory testing, practices vary widely by region and clinical judgment. Some suggest monthly monitoring during the initial phase, with less frequent testing once laboratory values stabilize. In contrast, others advocate testing only at baseline and once during treatment in low-risk patients [19, 48]. Reflecting this variability, no consensus was reached on an ideal monitoring schedule, underscoring the need for clinician-driven, risk-based strategies in real-world practice settings. Such an approach may be important in the context of limited resources to address the burden of testing and reduce healthcare costs. The divided opinions included (i) baseline and every 2 months until the completion of therapy; (ii) baseline, month 1, and every 3 months thereafter; (iii) baseline and every 3 months thereafter; (iv) after month 1 and the end of the treatment; and (v) baseline and every time the isotretinoin dose is increased.

Side Effects, Precautions, and Contraindications (Statements 39–48)

Isotretinoin is associated with well-characterized, primarily mucocutaneous, dose-dependent side effects. Cheilitis, xerosis, dry eyes, and nasal dryness are the most frequent and expected side effects. Other commonly reported manifestations include nosebleeds due to nasal mucosal dryness, photosensitivity, muscle ache, and bone/joint pain [23, 81]. More severe or systemic side effects, such as mood changes, depression, inflammatory bowel disease (IBD), hepatic enzyme elevation, dyslipidemia, pancreatitis, and menstrual irregularities, are rare but clinically relevant, underscoring the need for careful patient selection and monitoring [81–86]. Nevertheless, careful clinical vigilance remains prudent. These potentially serious events may require dose reduction, temporary interruption, or discontinuation [14, 87].

Mucocutaneous side effects often stem from inadequate patient education about preventive measures, such as using mild cleansers, moisturizers, or lip balms, from the outset of treatment [88]. Proactive skincare routines are crucial for enhancing tolerability and adherence during isotretinoin therapy [89]. The study by Tahiliani et al. demonstrated that the concurrent use of a well-formulated moisturizer significantly improves skin tolerability and patient compliance without compromising efficacy [90]. On the basis of observations in their respective clinical practices, the experts reached a high level of agreement on the most common side effects, such as cheilitis (100%) and dry skin (90%), with moderate agreement on other common effects, including dry eyes (75%) and dry nose (70%). The experts uniformly recommended gentle, soap-free cleansers (100%), lip balms (100%), noncomedogenic moisturizers (95%), and noncomedogenic sunscreens (80%).

In cases where serum aminotransferase levels rise during isotretinoin therapy, the elevation is usually transient and does not require dose modification. However, rise in serum aminotransferase levels of more than five times the upper limit of normal should prompt at least temporary discontinuation, particularly if confirmed on a second sample or if accompanied by symptoms or jaundice [83]. Similarly, elevations in triglyceride levels during isotretinoin treatment may require dose reductions or discontinuation. For less marked elevations, dietary modification or therapy to lower lipid levels may be used. In this regard, adjunctive treatment with an omega-3 fatty acid supplement has been suggested to permit maximal therapeutic dosing of isotretinoin [84, 87]. Where psychiatric symptoms emerge or worsen during therapy, close monitoring and timely mental health referral are advised; dose reduction or discontinuation may be considered based on severity [14, 91]. Rarely observed side effects that achieved high consensus include psychiatric symptoms, such as depressed mood, insomnia, and hallucinations (80%), and moderate consensus included elevated liver enzymes (70%), hyperlipidemia (75%), and menstrual irregularities (70%).

Findings from a meta-analysis suggest that at a population level, isotretinoin users do not have an increased risk of suicide or psychiatric conditions. However, baseline screening and monitoring are encouraged in patients at risk of mood disorders [85]. Likewise, monitoring for gastrointestinal symptoms in patients at risk is considered a pragmatic approach. Screening for depressive symptoms before and during therapy was recommended with high consensus (95%). However, monitoring for IBD symptoms was considered reasonable, particularly in patients at risk (75%; moderate consensus).

Isotretinoin is a known teratogen and is contraindicated in pregnancy. Guidelines emphasize reliable contraception and serial pregnancy testing throughout the treatment period, followed by posttreatment pregnancy avoidance [48, 92, 93]. Exposure during pregnancy is associated with fetal malformations, highlighting the critical importance of strict pregnancy prevention measures [93]. The US iPLEDGE and the European directive specify contraception for 30–35 days after the last dose, based on its pharmacokinetics and evidence that plasma levels typically fall below detectable limits within 2 weeks [94].

By contrast, in India, the Central Drugs Standard Control Organization (CDSCO) currently advises avoiding pregnancy for 6 months after stopping isotretinoin [95]. However, it has been suggested that such a long duration may not be necessary [94]. This longer duration stems from historical regulatory precautions rather than direct pharmacokinetic evidence. Consequently, Indian dermatologists operate in a regulatory environment where a clear, evidence-based consensus on the posttreatment washout period is lacking. The expert panel, therefore, did not reach a uniform agreement on the ideal duration for pregnancy avoidance after isotretinoin. Nonetheless, there was unanimous agreement (100%) on counseling all women of childbearing potential and enforcing contraception during therapy. Several experts noted that, scientifically, a shorter interval consistent with US/European recommendations may be sufficient, but adherence to national guidelines remains essential until updated guidance is issued.

For male individuals, there is no robust evidence linking isotretinoin to male-mediated teratogenicity or impaired fertility [96]. Accordingly, family planning was deemed unnecessary for male patients by 75% of the experts (moderate consensus).

Isotretinoin has several absolute and relative contraindications due to its teratogenicity and potential for hepatotoxicity or hematologic impact. Additionally, concomitant use with tetracyclines may increase the risk of pseudotumor cerebri (benign intracranial hypertension), a potentially serious adverse event [44, 97]. There was high consensus on the following contraindications: hypervitaminosis A (100%), pregnancy (100%), hepatic dysfunction (95%), significant leukopenia (95%), hyperlipidemia (85%), and concomitant use of tetracycline (90%). These recommendations reflect international safety standards and support the development of risk-adapted protocols in clinical practice.

Formulations of Isotretinoin (Statements 49–50)

Isotretinoin is available in conventional soft-gel formulations and micronized variants. Both formulations have demonstrated comparable efficacy and safety when administered appropriately [98, 99]. The conventional formulation was approved by the US Food and Drug Administration in 1982. Extensive real-world data accumulated over the years support predictable clinical outcomes [61]. Although micronized isotretinoin may offer marginal improvements in bioavailability and is occasionally associated with fewer mucocutaneous and lipid-related side effects, it has been suggested that the difference may be minimal in practice [100]. Reflecting this, expert consensus indicated moderate agreement (70%) that there is no significant difference in efficacy between conventional and micronized formulations and high consensus (85%) that the safety profiles are equivalent, provided dosing and administration guidelines are followed.

Procedural Interventions During Isotretinoin Therapy (Statements 51–52)

Historically, isotretinoin was believed to impair wound healing and increase the risk of scarring following dermatologic procedures. This led to widespread caution in performing interventions during active treatment. However, emerging evidence suggests that interventions such as extraction of comedones, chemical peels, and laser procedures can be safely performed during isotretinoin therapy, provided appropriate techniques, patient selection, and postprocedure care are ensured [101]. Similarly, an evaluation by an Indian task force revealed insufficient evidence to support avoiding/delaying procedures and suggested it was safe in patients with concurrent or recent isotretinoin administration [102].

There was a unanimous consensus (100%) supporting the safety of comedone extraction during isotretinoin therapy [103]. High consensus supported the safety of superficial and medium-depth chemical peels (85%) and laser treatments for acne scarring, including fractional ablative and nonablative lasers (80%). Moderate consensus (65%) was observed for laser procedures targeting pigmented lesions, suggesting some hesitancy or variability in clinical practice. A low consensus (50%) was reached for microdermabrasion, reflecting ongoing concerns regarding healing variability and practitioner comfort levels with this procedure during isotretinoin use. These insights highlight a notable paradigm shift in clinical dermatology, promoting greater procedural flexibility for patients undergoing isotretinoin therapy, particularly for interventions targeting active acne lesions or postacne sequelae.

Nonacne Dermatologic Indications (Statements 53–54)

Beyond its well-established role in acne management, isotretinoin has shown potential in treating chronic inflammatory dermatoses due to its sebum-suppressive, anti-inflammatory, and immunomodulatory effects [29, 45, 104]. These conditions include rosacea, seborrheic dermatitis, psoriasis, hidradenitis suppurativa, photoaging, and lamellar ichthyosis. A high consensus was achieved for the use of isotretinoin in rosacea (95%), seborrheic dermatitis (90%), and hidradenitis suppurativa (90%). Isotretinoin may act on rosacea by modulating innate immunity and reducing the inflammatory response through negative regulation of Toll-like receptor (TLR)-2 expression in keratinocytes. The sebosuppressive action and modulation of innate immunity and inflammatory response can explain its role in seborrheic dermatitis. Similarly, TLR-2 modulation and reduced expression of genes related to keratinocyte hyperproliferation may explain the role of isotretinoin in hidradenitis suppurativa [29]. Conversely, there was low consensus for isotretinoin’s use in pustular psoriasis (45%) and ichthyosis (35%). Case reports suggest isotretinoin may be considered in pustular psoriasis when acitretin is unsuitable [105, 106] and in pediatric lamellar ichthyosis at doses of 0.6–1 mg/kg/day for 6–16 weeks [107]. However, there is a lack of randomized controlled trials in these conditions, underscoring the need for further research. These findings reflect a widening, yet selective, clinical footprint for isotretinoin beyond acne. They reinforce the need for high-quality clinical trials to validate its use, particularly in inflammatory and sebaceous dermatoses.

Expert Insights into Factors Influencing Isotretinoin Use with Oral Antibiotic, Hormonal, or Topical Therapies

Inputs from experts on combining isotretinoin with other agents were gathered through an open-ended question, allowing them to respond based on their clinical experience. Combining isotretinoin with other acne therapies often depends on patient-specific factors, clinical presentation, and treatment responses. However, due to the potential for cumulative skin irritation, topical retinoids are generally avoided during the active phase of isotretinoin therapy to reduce the risk of further disruption to the skin barrier [83]. The experts opined that the combination with other topical antibiotics (such as clindamycin or minocycline) [108, 109] and benzoyl peroxide remains a core component of acne treatment aimed at controlling microbial factors and inflammation and is commonly used alongside isotretinoin in specific clinical scenarios. When secondary infections, such as bacterial folliculitis, are present, antimicrobial topicals may offer local benefits.

Oral antibiotics such as azithromycin are sometimes co-prescribed briefly during the early stages of treatment [110]. This approach is considered when there is an infection, such as Staphylococcus aureus, or an inadequate early response, particularly in severe inflammatory papulopustular or nodulocystic acne. Factors such as acne severity, location, scarring, psychosocial impact, and hormonal status influence the decision to use isotretinoin with oral antibiotics. However, coadministration of isotretinoin and tetracyclines is contraindicated due to the risk of intracranial hypertension (pseudotumor cerebri) [92].

Experts opined that in female patients with signs of hyperandrogenism, such as hirsutism, patterned hair loss, polycystic ovary syndrome, and other hormonal irregularities, the use of isotretinoin in combination with hormonal therapies is considered. Examples of hormonal therapies include combined oral contraceptives and anti-androgenic agents such as spironolactone, which may be co-prescribed to address the underlying hormonal imbalance [111, 112]. This is especially relevant in cases where acne persists after 3 months of isotretinoin therapy, or when severe acne is associated with underlying hyperandrogenism. These regimens were viewed as both therapeutically synergistic and hormonally corrective, especially in patients with documented endocrine abnormalities.

These expert insights emphasize that the use of isotretinoin in combination with other therapeutic modalities should be individualized, taking into account disease severity, patient-specific risk factors, and treatment response.

Translating Consensus to Clinical Practice: The ERAISE ACNE Algorithm

Effective implementation of consensus recommendations in real-world practice often hinges on clear, actionable guidance. Recognizing this need, the expert panel consolidated the high- and moderate-strength recommendations from this Delphi initiative into a practical clinical pathway, known as the Expert consensus on the Rational Approach to ISotretinoin usage for Effective management of ACNE (ERAISE ACNE) algorithm. This algorithm is adaptable to diverse healthcare settings and designed to guide dermatologists in identifying suitable candidates for isotretinoin by considering key prognostic factors, including the risk of scarring, psychosocial burden, and early signs of relapse. It provides a structured approach for patient stratification, timely initiation, and optimal dosing of isotretinoin therapy. The pathway also incorporates essential components of care, including baseline screening, risk-adapted laboratory monitoring, dose-adjustment triggers, and maintenance strategies. Additional considerations, such as compatibility with procedural interventions and use beyond acne, are also integrated to support individualized treatment planning. While the algorithm is broadly applicable across regions for skin of color, it has particular relevance in Indian settings. By distilling expert-derived recommendations into a streamlined format, the ERAISE ACNE algorithm provides a ready-to-use clinical tool that supports early, risk-adapted, and contextually relevant use of isotretinoin in dermatology settings (Fig. 2, 3, 4, 5).

Fig. 2.

The ERAISE ACNE algorithm: Patient profiles that can benefit from isotretinoin use

Fig. 3.

The ERAISE ACNE algorithm: Isotretinoin for acne management in first- and second-line settings

Fig. 4.

The ERAISE ACNE algorithm: Dosage and administration of isotretinoin for acne management

Fig. 5.

The ERAISE ACNE algorithm: Side effects and laboratory monitoring during isotretinoin therapy

Strengths, Limitations, and Future Directions

This modified Delphi consensus represents a comprehensive synthesis of expert opinions in dermatology. The panel comprised professionals with extensive clinical expertise and specialized knowledge, ensuring the insights gathered were grounded in practice. The survey was developed following a thorough literature review, which helped enhance the consensus’s rigor and efficiency in eliciting informed responses. To encourage candid and unbiased feedback, anonymity was maintained throughout the survey. All experts actively participated in the consensus-building discussions, and any differences of opinion were addressed during the meeting to ensure comprehensive consideration of various viewpoints. While this reflects insights from real-world clinical practice in India, it bears contextual relevance for similar demographics.

However, it is important to note that this consensus does not include patient opinions or perspectives. While expert input is valuable in shaping clinical guidelines, the absence of direct patient opinions may be a limitation.

This work focuses on therapeutic decision-making derived using a consensus framework. Future demographic and comparative studies evaluating the influence of climate, diet, and lifestyle on acne severity could enhance understanding of disease heterogeneity and inform more comprehensive, individualized management approaches.

This consensus document provides practical, evidence-informed recommendations on the safe and effective use of oral isotretinoin for the treatment of acne vulgaris, specifically tailored to Indian clinical settings, with relevance to other regions with similar treatment challenges and patient concerns. Developed through expert consensus and supported by contemporary literature, these recommendations aim to support dermatologists in:

• Identifying appropriate patient profiles most likely to benefit from isotretinoin therapy

• Optimizing dosing strategies, including conventional and flexible regimens

• Establishing individualized monitoring protocols based on clinical risk

• Managing side effects proactively, with emphasis on patient education and skincare support

Importantly, the consensus highlights the crucial role of patient counseling in ensuring informed decision-making, adherence to treatment, and achieving long-term therapeutic success. By incorporating these expert-derived strategies into routine practice, dermatologists can optimize the therapeutic potential of isotretinoin while minimizing risks, ultimately enhancing both clinical outcomes and patient satisfaction.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Sanjiv Kandhari, Jayakar Thomas, Niti Khunger, Maya Vedamurthy, Kiran Godse, Abir Saraswat, Nina Madnani, Vijay Somani, Sushil Tahiliani, Bela Shah, C. R. Srinivas, Asit Mittal, Mukesh Girdhar, Maleeka Sachdeva, Sachin Varma, Manjunath Shenoy, Shyamanta Barua, Abhishek De, Akshay Jain, and Aseem Sharma contributed equally to the conception and design of the work; analysis and interpretation of data; drafting the article; revising it critically for important intellectual content; and final approval of the version to be published. All authors agreed to be accountable for all aspects of the work.

Funding

This study was funded by Cipla Ltd. The study sponsor also funded the journal’s Rapid Service fees.

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

Declarations

Conflict of Interest

Sanjiv Kandhari, Jayakar Thomas, Niti Khunger, Maya Vedamurthy, Kiran Godse, Abir Saraswat, Nina Madnani, Vijay Somani, Sushil Tahiliani, Bela Shah, C. R. Srinivas, Asit Mittal, Mukesh Girdhar, Maleeka Sachdeva, Sachin Varma, Manjunath Shenoy, Shyamanta Barua, Abhishek De, Akshay Jain, and Aseem Sharma have nothing to disclose.

Ethical Approval

This Delphi-based consensus did not involve patient data, human biological samples, or clinical interventions. It was limited to obtaining expert opinions from healthcare professionals, and as such, it was considered exempt from formal ethics committee review. All panelists were informed about the consensus objectives, methodology, and intended use of the findings. Informed consent was obtained from all panel members. Participation was entirely voluntary, and responses were anonymized to maintain confidentiality.