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