Mucocutaneous Side Effects of Acitretin
Nearly all patients (98%) taking acitretin will experience mucocutaneous side effects, which are the most common adverse reactions and the primary reason patients discontinue therapy. 1
Universal Mucocutaneous Effects (Occur in Nearly All Patients)
The following side effects occur in the vast majority of patients and are dose-dependent 1:
- Cheilitis (lip inflammation and cracking) - occurs in >75% of patients and is the most characteristic side effect 2
- Xerosis (dry skin) - generalized dryness affecting the entire body surface 1
- Dry mucous membranes affecting eyes (xerophthalmia), nose, and oral cavity 1
- Epistaxis (nosebleeds) - secondary to nasal mucosa dryness 1
- Dry mouth and thirst 1
- Brittle nails and nail disorders 1
- Itching or burning skin sensations 1
These effects range from mild to severe depending on individual patient characteristics and acitretin dose, but are completely reversible upon dose reduction or discontinuation 1, 3.
Common Mucocutaneous Effects (25-75% of Patients)
- Alopecia (hair loss) - occurs in 25-50% of patients, with significantly higher rates in women, especially at doses exceeding 17.5 mg per day 1, 4, 5
- Skin peeling - particularly prominent on palms and soles 2, 6
- Paresthesia and hyperesthesia (altered skin sensations) 2
- Paronychia (nail fold inflammation) 2
- Skin atrophy and thinning 2
- "Sticky skin" sensation 2
- Pruritus (itching) 2
Less Common but Clinically Significant Mucocutaneous Effects
- "Retinoid dermatitis" - manifests as scaly, erythematous plaques with superficial fissuring 1
- Pyogenic granulomas - particularly in periungual (around the nail) locations, associated with long-term therapy 1
- Erythematous rash 2
- Exfoliative dermatitis/erythroderma - rare but serious, requiring drug discontinuation 2
- Skin fragility and scaling - may occur over the entire body 2
- Madarosis (loss of eyelashes or eyebrows) 2
Ocular Mucocutaneous Effects
- Conjunctivitis 1
- Photophobia (light sensitivity) 1
- Contact lens intolerance - secondary to xerophthalmia 1
Dose-Dependent Considerations
The severity and frequency of mucocutaneous side effects increase with higher doses. 1, 3, 7 In clinical trials, doses of 50-75 mg daily produced significantly more mucocutaneous adverse effects than lower doses, though even 25 mg daily caused these effects in most patients 7. Frank alopecia (severe hair loss) occurs in less than 10% of patients but is more common at higher doses and with longer treatment duration 1, 5.
Clinical Management Pitfalls
The most common reason for premature discontinuation of acitretin therapy is mucocutaneous adverse effects - 22% of patients in clinical trials left studies early primarily due to mucous membrane and skin reactions 2. These effects can be managed with:
- Dose reduction rather than complete discontinuation when possible 1
- Application of fatty ointments (such as petrolatum) for cheilitis 1
- Artificial tears for xerophthalmia 1
- Nasal saline for rhinitis and epistaxis prevention 1
All mucocutaneous side effects are reversible and typically resolve within weeks of dose reduction or discontinuation, though hair regrowth may take 3-6 months 1, 3.