Overview
Definition:
Severe acne vulgaris is a chronic inflammatory condition of the pilosebaceous unit characterized by comedones, papules, pustules, nodules, and cysts, often leading to significant disfigurement and psychological distress
Isotretinoin, a potent oral retinoid, is highly effective for severe, recalcitrant cases but carries significant teratogenic risks, necessitating strict adherence to risk management programs like iPLEDGE in the United States.
Epidemiology:
Acne affects a large proportion of adolescents, with severe forms being less common but more impactful
While exact global incidence of severe acne in pediatrics varies, it significantly impacts quality of life
Isotretinoin is typically reserved for severe nodular acne, acne that has failed conventional therapy, or acne with a high risk of scarring.
Clinical Significance:
Uncontrolled severe acne can lead to permanent scarring, hyperpigmentation, and significant psychosocial morbidity, including depression and social isolation
Effective management with isotretinoin, while requiring careful counseling due to its risks, can dramatically improve outcomes and prevent long-term disfigurement
Understanding the iPLEDGE program is crucial for safe and effective prescribing in pediatric patients who can become pregnant.
Clinical Presentation
Symptoms:
Chief complaint is extensive acne lesions
Patients may report painful nodules and cysts
Significant psychosocial distress, anxiety, and depression
Scarring and hyperpigmentation are often present at presentation.
Signs:
Numerous inflammatory papules, pustules, nodules, and cysts
Distribution often involves the face, chest, and back
Evidence of scarring (ice-pick, boxcar, hypertrophic) and post-inflammatory hyperpigmentation
Oily skin
Presence of comedones (open and closed).
Diagnostic Criteria:
Diagnosis is primarily clinical, based on the presence of characteristic acne lesions
Severity is often graded based on lesion count, type, and extent
The need for isotretinoin is typically indicated by: 1
Severe nodular acne
2
Moderate acne unresponsive to standard therapy (topical/oral antibiotics, hormonal therapy)
3
Acne with a high risk of scarring.
Diagnostic Approach
History Taking:
Detailed history of acne severity, duration, and previous treatments (including efficacy and side effects)
Assess impact on quality of life and mental health
Inquire about menstrual regularity, contraception use, and potential pregnancy in female patients
Family history of acne or isotretinoin use
Assess for any contraindications to isotretinoin (e.g., history of depression, inflammatory bowel disease).
Physical Examination:
Thorough dermatological examination to assess the type, number, and distribution of acne lesions
Document the presence and type of scarring
Examine for signs of hyperandrogenism if indicated (e.g., hirsutism, clitoromegaly).
Investigations:
Baseline laboratory tests are mandatory prior to initiating isotretinoin: 1
Complete Blood Count (CBC)
2
Liver Function Tests (LFTs) including AST, ALT
3
Renal Function Tests (RFTs) including BUN, creatinine
4
Lipid profile (fasting triglycerides and cholesterol)
5
Pregnancy test (serum or urine beta-hCG) in all females of reproductive potential
Baseline Vitamin A levels are not routinely recommended
Monitoring of CBC, LFTs, RFTs, and lipids is required periodically during treatment.
Differential Diagnosis:
Other forms of acneiform eruptions such as folliculitis (bacterial, fungal), rosacea, hidradenitis suppurativa, keratosis pilaris, and drug-induced acne
Allergic contact dermatitis can also mimic acne
Careful history and examination are key to differentiate.
Management
Initial Management:
Initiation of isotretinoin therapy after comprehensive iPLEDGE counseling for eligible patients
This involves patient and prescriber registration in the iPLEDGE program
For females of reproductive potential, confirmation of a negative pregnancy test and agreement to a REMS-compliant contraception method are mandatory.
Medical Management:
Isotretinoin (e.g., Isotretinoin 13-cis-retinoic acid) is prescribed orally, typically at a dose of 0.5-1 mg/kg/day, divided into two doses
The total cumulative dose is usually targeted between 120-150 mg/kg
Treatment duration is typically 4-6 months
Adjunctive topical treatments (e.g., benzoyl peroxide, topical antibiotics) may be used cautiously if needed, but care must be taken to avoid over-drying
Regular follow-up every 1-2 months is essential for monitoring efficacy, side effects, and laboratory values.
Surgical Management:
Surgical interventions are generally not indicated for active severe acne
However, in cases of significant scarring, procedures like chemical peels, laser resurfacing, subcision, or fillers may be considered after the acne is controlled and isotretinoin treatment is completed, or in a separate treatment plan.
Supportive Care:
Patient education regarding side effects is critical
Emollients should be recommended for dry skin and lips
Sun protection is essential due to photosensitivity
Counseling on the importance of adhering to the iPLEDGE program requirements, including pregnancy prevention, is ongoing throughout therapy.
Ipledge Counseling Details
Program Overview:
The iPLEDGE program is a Risk Evaluation and Mitigation Strategy (REMS) designed to prevent fetal exposure to isotretinoin due to its known teratogenicity
It applies to all females of reproductive potential (FRP) prescribed isotretinoin.
Key Requirements For Frp:
1
Must be registered in iPLEDGE
2
Must have two negative pregnancy tests before the first prescription: one before treatment initiation and another within 30 days prior to dispensing
3
Must commit to using two forms of contraception simultaneously for one month before, during, and one month after treatment
4
Must pick up the prescription within 7 days of being dispensed the pregnancy test
5
Must have monthly pregnancy tests and counseling visits
6
Must report any known pregnancy immediately.
Key Requirements For Male Patients:
Male patients do not need to undergo pregnancy testing or use contraception
However, they must be registered in iPLEDGE and counselled on not sharing their medication and on the potential risks of isotretinoin exposure via semen, although the risk is considered very low.
Prescriber Responsibilities:
Prescribers must be registered with iPLEDGE and ensure all program requirements are met by the patient before prescribing
They must document each step of the counseling and verification process.
Pharmacy Responsibilities:
Pharmacies must verify that the patient has a completed iPLEDGE authorization form from the prescriber before dispensing isotretinoin.
Patient And Physician Agreements:
Both the patient and the prescriber must sign specific agreements outlining their responsibilities in adhering to the iPLEDGE program guidelines.
Side Effects And Monitoring
Common Side Effects:
Dry lips (cheilitis), dry skin, dry eyes, epistaxis, dry nasal passages, elevated triglycerides, elevated liver enzymes, musculoskeletal pain, fatigue, headache.
Serious Side Effects:
Teratogenicity (severe birth defects), inflammatory bowel disease exacerbation, pseudotumor cerebri (idiopathic intracranial hypertension), depression, suicidal ideation, severe allergic reactions, vision changes, hearing impairment.
Monitoring Schedule:
Monthly visits are mandatory
Monitor for signs and symptoms of common and serious side effects
Repeat laboratory tests (CBC, LFTs, lipids) as indicated by clinical practice guidelines and drug labeling, typically every 1-2 months
Monitor for adherence to contraception and iPLEDGE requirements
Assess mental health status carefully.
Management Of Side Effects:
Symptomatic treatment for dryness (emollients, artificial tears)
If lipid elevation is significant, dose adjustment or dietary modification may be needed
If elevated LFTs persist, dose reduction or discontinuation may be considered
Any signs of depression or suicidal ideation require immediate psychiatric evaluation and potential discontinuation of therapy.
Key Points
Exam Focus:
iPLEDGE program requirements for females of reproductive potential (FRP) are critical
Understanding the two negative pregnancy tests, dual contraception, and monthly monitoring
Teratogenicity is the most severe risk
Isotretinoin is teratogenic
prevent fetal exposure at all costs
Common side effects and their management
Baseline and monitoring lab investigations.
Clinical Pearls:
Emphasize that iPLEDGE applies to ALL females of reproductive potential, even those with irregular menses or who believe they are not at risk of pregnancy
Counsel male patients on not sharing medication
Be vigilant for any signs of depression or suicidal ideation
Moisturize lips and skin aggressively to manage dryness.
Common Mistakes:
Failing to register patient/prescriber in iPLEDGE
Dispensing medication without confirming negative pregnancy tests or adequate contraception
Not adhering to the 7-day dispensing window for prescriptions
Ignoring patient reports of mood changes or depression
Not adequately counseling on the teratogenic risks.