What is the recommended treatment protocol for severe psoriasis using Acetretin?

Acitretin Treatment Protocol for Severe Psoriasis

For severe psoriasis, initiate acitretin at 25-30 mg daily for 2-4 weeks, then titrate to a maintenance dose of 25-50 mg daily based on therapeutic response and tolerability, with optimal results typically achieved at 35 mg daily. 1, 2

Dosing Strategy

Initial Dosing

• Start with 25 mg or 30 mg daily for 2-4 weeks to allow gradual onset of tolerance to side effects 1
• Take capsules once daily with meals or milk to optimize absorption 1
• The gradual dose escalation approach is most effective for balancing efficacy with tolerability 1

Maintenance Dosing

• Target maintenance dose: 25-50 mg daily for 6-8 weeks to achieve optimal therapeutic results 1
• Evidence suggests 35 mg daily is the most efficacious dose, achieving PASI 75 in 69% of patients with better tolerability than 50 mg daily 2
• Maximum dose of 75 mg daily may be necessary in refractory cases 1
• Response is gradual, typically requiring 3-6 months to reach peak efficacy 1

Specific Psoriasis Variants

Severe Variants with Rapid Response

• Erythrodermic psoriasis, generalized pustular psoriasis, and palmoplantar psoriasis respond particularly well to acitretin 1
• Pustular psoriasis shows 84% improvement rates and can have rapid, remarkable responses 1
• For pustular variants, response may be seen within 3 weeks 3

Combination Therapy (Strongly Recommended)

With Phototherapy

• Begin with 2 weeks of acitretin monotherapy, then add UVB phototherapy 1
• Combination therapy with acitretin 50 mg daily plus BB-UVB achieves 74% improvement versus 42% with acitretin alone and 35% with BB-UVB alone 1
• Reduce initial UVB dose by 30-50% for the first week due to increased susceptibility to UVB-induced erythema, then gradually increase as tolerated 1
• Acitretin 25 mg daily plus phototherapy equals the efficacy of acitretin 35 mg daily monotherapy 1

With PUVA

• Adding acitretin to PUVA reduces photochemotherapy sessions needed and cumulative UVA dosage 1
• Critical benefit: Acitretin combined with PUVA decreases cutaneous squamous cell carcinoma incidence compared to PUVA alone 1

Mandatory Monitoring Protocol

Baseline Testing

• Pregnancy test (mandatory in women of childbearing potential) 1
• Liver function tests 1
• Fasting lipid panel (cholesterol and triglycerides) 1
• Blood glucose in diabetic patients 1

Ongoing Monitoring

• Lipids: Every 2-4 weeks for first 2 months, then every 3 months 1
• Liver function: Every 3 months 1
• Blood glucose monitoring in diabetics at similar intervals 1

Critical Lipid Management

• Triglycerides >5 mmol/L: Refer to lipidologist and investigate other causes (alcohol, diabetes, hypothyroidism, renal/hepatic problems) 1
• Triglycerides approaching or >10 mmol/L: Discontinue acitretin immediately and urgently refer to lipidologist due to acute pancreatitis risk 1
• Introduce dietary measures before lipid-lowering drugs if therapeutic response is good but lipids remain elevated 1

Absolute Contraindications and Critical Safety

Teratogenicity (Most Important Safety Concern)

• Absolutely contraindicated in pregnancy - causes multiple malformations including skeletal, craniofacial, CNS, auditory, ocular, and cardiovascular abnormalities, particularly if used between weeks 3-6 of gestation 1
• Women must use contraception for 3 YEARS after stopping acitretin 1
• Acitretin (half-life 49 hours) undergoes spontaneous transformation into etretinate (half-life 168 days), which is stored long-term 1
• Alcohol ingestion promotes conversion to etretinate, though the exact amount needed is unknown 1
• Should be avoided in female adolescents approaching childbearing potential 4, 3

Other Contraindications

• Nursing mothers 1
• Women planning pregnancy or without sufficient contraception 1

Common Side Effects (Dose-Dependent)

Mucocutaneous (Nearly Universal)

• Cheilitis, xerosis, dry eyes, nasal/oral mucosa dryness, epistaxis, brittle nails, pruritus, burning skin 1, 5
• Hair loss more common in women, especially at doses >17.5 mg daily 1
• Peeling of palms and soles 5

Management Strategy

• All mucocutaneous effects are generally mild and do not warrant discontinuation 5
• Side effects are dose-related and manageable with appropriate dosing 1

Treatment Duration and Discontinuation

• Therapy can be discontinued when lesions have improved sufficiently 1
• Most patients experience relapse after discontinuation 6
• Relapses should be treated with the same protocol as initial therapy 1
• Subsequent courses produce efficacy results similar to initial therapy 6

Common Pitfalls to Avoid

1. Do not use acitretin as monotherapy for severe whole-body psoriasis - combination with phototherapy is superior 1
2. Do not start phototherapy simultaneously with acitretin - wait 2 weeks to establish retinoid tolerance 1
3. Do not forget to reduce UVB dose initially - failure to do so causes excessive erythema 1
4. Do not prescribe to women of childbearing potential without discussing 3-year contraception requirement 1
5. Do not continue therapy with triglycerides >10 mmol/L - acute pancreatitis risk 1