In an adult with moderate‑to‑severe palmoplantar (including pustular) psoriasis and no contraindications, what is the recommended acitretin dosing, monitoring schedule, and alternative systemic therapies if acitretin is unsuitable?

Acitretin for Moderate-to-Severe Palmoplantar (Including Pustular) Psoriasis

For adults with moderate-to-severe palmoplantar psoriasis, initiate acitretin at 25–30 mg once daily with food for 2–4 weeks, then escalate to a maintenance dose of 25–50 mg daily, with intensive monitoring of liver function tests and lipids every 2–4 weeks for the first 2 months, then every 3 months thereafter. 1

Dosing Strategy

Initial Dosing

• Start with 25–30 mg once daily taken with the main meal to optimize absorption and assess tolerability over the first 2–4 weeks 1
• For pustular variants (including palmoplantar pustular psoriasis), acitretin produces rapid and impressive responses, often within 3 weeks, with 84% of patients showing improvement 2, 3
• The FDA-approved range is 10–50 mg daily, but clinical practice for severe disease typically begins at 25–50 mg 1

Dose Escalation and Maintenance

• After the initial period, gradually escalate to a maintenance dose of 25–50 mg daily for 6–8 weeks to achieve optimal response 1
• Maximum dose of 75 mg daily may be required in refractory cases, though higher doses substantially increase mucocutaneous side effects 1
• Hyperkeratotic (plaque-type) palmoplantar psoriasis responds well to acitretin as monotherapy or in combination with phototherapy 2

Combination Therapy Considerations

• When combining acitretin with phototherapy (NB-UVB or PUVA), use lower doses (≤25 mg daily) to minimize adverse effects 1
• Begin with 2 weeks of acitretin monotherapy before adding phototherapy 2
• Reduce initial UVB dose by 30–50% when adding phototherapy to prevent excessive erythema, then gradually increase as tolerated 2, 1
• Acitretin 25 mg daily plus phototherapy achieves efficacy comparable to 35 mg monotherapy 2

Monitoring Schedule

Baseline Assessment (Before Starting)

• Fasting lipid profile (cholesterol and triglycerides) 1
• Complete blood count (CBC) 1
• Liver function tests (LFTs) 1
• Renal function (serum creatinine, eGFR) 1
• Pregnancy test in all women of childbearing potential 1
• Comprehensive history focusing on hepatic disease, lipid disorders, diabetes, and alcohol use 1

Intensive Monitoring Phase (First 2 Months)

• LFTs and lipid profile every 2–4 weeks 1
• If abnormalities arise, increase monitoring to weekly and adjust dose 1

Maintenance Monitoring Phase (After 2 Months)

• LFTs and lipid profile every 3 months 1
• CBC and renal function every 3 months 1
• Pregnancy testing every 3 months when indicated 1
• For diabetic patients, monitor blood glucose at the same intervals and advise more frequent capillary checks during the first few weeks 1

Critical Safety Management

Hepatotoxicity Thresholds

• Discontinue acitretin if transaminases rise to >3× upper limit of normal 1
• Refer to gastroenterology if bilirubin exceeds 50 µmol/L or ALT exceeds 200 IU/L 1
• Continue hepatic monitoring for ≥3 months after discontinuation 1

Lipid Management

• Triglycerides >5 mmol/L: Refer to lipid specialist and evaluate secondary causes (alcohol, diabetes, hypothyroidism) 1
• Triglycerides ≥10 mmol/L: Immediately discontinue acitretin and arrange urgent lipidology referral due to pancreatitis risk 1
• If therapeutic response is satisfactory but lipids remain elevated, initiate dietary modifications before adding lipid-lowering agents 1

Absolute Contraindications

• Pregnancy – multiple malformations occur, especially with exposure between weeks 3–6 of gestation (skeletal, craniofacial, CNS, auditory, ocular, cardiovascular abnormalities) 2, 1
• Women of childbearing potential must use effective contraception for 3 years after stopping acitretin due to possible conversion to etretinate (half-life 168 days) 2, 1
• Alcohol ingestion promotes conversion of acitretin to etretinate, extending teratogenic risk; advise complete alcohol avoidance 2
• Severe hepatic or renal impairment 1
• Chronically elevated blood lipids 1
• Concurrent tetracycline use (risk of pseudotumor cerebri) 1

Drug Interactions to Avoid

• Methotrexate – additive hepatotoxicity; use with extreme caution 1
• Vitamin A supplements – risk of hypervitaminosis A 1
• Tetracyclines – increased intracranial pressure 1
• Glyburide – acitretin may alter glucose-lowering effect 1

Expected Timeline and Efficacy

For Pustular Palmoplantar Psoriasis

• Response typically seen within 3 weeks, with 84% of patients showing improvement 2, 3
• This is substantially faster than the 2–3 months required for plaque-type disease 1, 3

For Hyperkeratotic (Plaque-Type) Palmoplantar Psoriasis

• Clinical response is gradual, typically requiring 3–6 months to reach peak efficacy 1
• After 6 and 12 months of continuous treatment, 75% and 88% of patients, respectively, reach PASI 50 2

Alternative Systemic Therapies if Acitretin is Unsuitable

First-Line Alternatives

Methotrexate is the preferred alternative for palmoplantar psoriasis with significant disease burden:

• More effective than acitretin for palmoplantar disease – achieves 75% reduction in modified PPPASI in 24% of patients vs. 8% with acitretin at 12 weeks 4
• Dose: 0.4 mg/kg weekly (typically 15–25 mg weekly in adults) 4
• Particularly useful when psoriatic arthritis is present 5
• Requires baseline and ongoing monitoring of CBC, LFTs, and renal function 4

Cyclosporine for rapid control or crisis management:

• Dose: 2.5–5.0 mg/kg/day in two divided doses 2
• Achieves clearance in approximately 4 weeks 3
• Not recommended for long-term use due to nephrotoxicity and hypertension 2
• Requires intensive monitoring: blood pressure and renal function every 2 weeks for first 3 months, then monthly 2

Biologic Therapies for Refractory Disease

Secukinumab (IL-17A inhibitor) – most investigated biologic for palmoplantar pustular psoriasis:

• Effective for severe or treatment-resistant cases 5
• Particularly useful when concurrent psoriatic arthritis is present 6

Ustekinumab (IL-12/23 inhibitor):

• 90 mg dose shows 67% clearance rate in palmoplantar pustular psoriasis 6
• Alternative when IL-17 inhibitors are unsuitable 5

TNF inhibitors (infliximab, adalimumab, etanercept):

• Infliximab 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks for severe pustular psoriasis 3
• Consider for rapidly progressive disease or acitretin failure 3

Topical Therapy as Adjunct or Monotherapy for Localized Disease

• Combination of vitamin D analogue (evening) + high-potency topical corticosteroid (morning) for 4–8 weeks 6
• Fixed combination products (calcipotriol/betamethasone) are particularly convenient 6
• Avoid salicylic acid with calcipotriene – acidic pH inactivates calcipotriene 6

Common Pitfalls and How to Avoid Them

• Underestimating the teratogenic window: Women must avoid pregnancy for 3 years, not the drug's 49-hour half-life, due to etretinate conversion 2, 1
• Inadequate lipid monitoring: Triglycerides ≥10 mmol/L require immediate discontinuation due to pancreatitis risk 1
• Premature discontinuation: Plaque-type palmoplantar psoriasis requires 3–6 months to reach peak efficacy; counsel patients on this timeline 1
• Combining with phototherapy without dose adjustment: Always reduce UVB dose by 30–50% initially to prevent severe erythema 2, 1
• Using acitretin as monotherapy when arthritis is present: Methotrexate or biologics are more appropriate for patients with psoriatic arthritis 5