What is the recommended treatment for a patient with pustular psoriasis?

Treatment of Pustular Psoriasis

For generalized pustular psoriasis (GPP), acitretin is the first-line systemic therapy, with infliximab reserved for severe, rapidly progressive cases requiring urgent control. 1, 2

Initial Assessment and Treatment Selection

Localized Pustular Psoriasis (Palms and Soles)

• Start with moderately potent topical corticosteroids (British National Formulary grade III) for symptom relief 1
• Topical coal tar and dithranol may provide additional benefit, though response is often limited 3, 1
• Avoid TNF antagonists (etanercept, infliximab, adalimumab) as they may paradoxically exacerbate chronic palmoplantar pustulosis 1
• For acropustulosis with major quality of life impact, TNF antagonists are reasonable options 1

Generalized Pustular Psoriasis (GPP)

Hospital admission is required for initial management of GPP, as this is a potentially life-threatening condition requiring systemic therapy 3

First-Line Systemic Therapy: Acitretin

• Dose: 0.1-1 mg/kg/day orally 1, 2
• Response typically seen within 3 weeks, with 84% efficacy in pustular psoriasis 2, 4
• Particularly advantageous as it is not immunosuppressive 2
• Absolute contraindication: Pregnancy or women planning pregnancy within 2 years of stopping treatment 1
• Requires contraception for at least 2 years after discontinuation due to teratogenic potential 3
• Monitor: Liver function tests and fasting serum lipids every 6 weeks initially 3

Rapid-Acting Therapy for Severe GPP: Infliximab

• Dose: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 1, 5
• Demonstrates rapid and often complete disease clearance in severe cases 1
• Grade C recommendation from the American Academy of Dermatology for pustular psoriasis subtypes 1
• May require dose intensification to 10 mg/kg or more frequent intervals (every 4 weeks) for better control 1
• Avoid in chronic palmoplantar pustulosis due to risk of exacerbation 1
• Relapse is common but not universal upon discontinuation 1

Alternative Systemic Options

Methotrexate:

• Especially useful in acute generalized pustular psoriasis and psoriatic erythroderma 3
• Efficacy: 76.2% in Japanese multicenter study 4
• Contraindications: Pregnancy, breastfeeding, significant hepatic damage, anaemia, leucopenia, thrombocytopenia 3
• Requires weekly monitoring of full blood count and liver function tests initially 3
• Critical drug interactions: Avoid alcohol, NSAIDs, co-trimoxazole, trimethoprim, salicylates 3

Cyclosporine:

• Initial dose: 2.5 mg/kg/day divided twice daily 1, 5
• Efficacy: 71.2% in generalized pustular psoriasis 4
• Contraindications: Abnormal renal function, uncontrolled hypertension, previous/concomitant malignancy 3, 1
• Monitor serum creatinine and blood pressure every 2 weeks for first 3 months 3
• Reduce dose if creatinine increases >30% from baseline 3
• Avoid: Aminoglycosides, amphotericin, trimethoprim, ketoconazole, NSAIDs 3

Etanercept (for GPP with psoriatic arthritis):

• Dose: 50 mg subcutaneously twice weekly for 12 weeks, then 50 mg weekly 3
• Grade B recommendation for pustular/erythrodermic psoriasis subtypes 3
• Clinical efficacy demonstrated in case series with maintenance of response up to 48 weeks 1

Phototherapy Considerations

PUVA (Psoralens plus UVA):

• Generally considered first-choice systemic treatment with least toxicity 1
• Efficacy: 45.7% in generalized pustular psoriasis 1, 4
• Use with extreme caution as it may exacerbate pustular psoriasis 3, 6
• Contraindications: Pregnancy, significant cataracts, age <18, previous cutaneous malignancy 1

Ultraviolet B:

• May be helpful but must be used cautiously as it can exacerbate pustular disease 3, 1, 6

Combination Therapy Strategies

Acitretin + Narrowband UVB:

• Provides synergistic effects for pustular psoriasis 1, 2

Infliximab + Methotrexate:

• Grade B recommendation for augmenting efficacy 1
• Particularly beneficial for long-term management of GPP 1

Infliximab + High-potency topical corticosteroids ± Vitamin D analogues:

• Grade B recommendation 1

Critical caveat: Combination therapy toxicity is at least additive; approach with extreme caution 1, 2

Systemic Corticosteroids: Critical Warnings

Systemic corticosteroids are contraindicated as primary therapy in pustular psoriasis 1, 2, 5

Why They Must Be Avoided:

• Precipitate life-threatening complications including erythrodermic psoriasis, generalized pustular psoriasis, or very unstable psoriasis upon withdrawal 3, 2, 5
• Create severe rebound phenomena 5

Extremely Limited Exceptions (Only Three Scenarios):

1. Persistent uncontrollable erythroderma causing metabolic complications
2. Generalized pustular psoriasis of von Zumbusch type when all other drugs are contraindicated
3. Hyperacute psoriatic polyarthritis threatening severe irreversible joint damage 3, 2

If Patient Already on Steroids:

• Do not abruptly discontinue during a flare 1
• Initiate acitretin (0.1-1 mg/kg/day) while slowly tapering steroids 1
• For severe cases, consider adding infliximab during taper 1

Monitoring Requirements for GPP

Daily assessment during acute phase:

• Body surface area involvement
• Pustule formation and distribution
• Systemic symptoms (fever, hypotension, weakness)
• Metabolic complications (hypocalcemia is common) 5, 6
• Serial clinical photography 5

Laboratory monitoring (frequency depends on agent):

• Full blood count
• Liver function tests
• Serum creatinine
• Electrolytes
• Blood pressure (for cyclosporine) 3, 1

Common Pitfalls to Avoid

1. Never use fluoridated hydrocortisone in pustular psoriasis—risk of exacerbation 2
2. Do not use TNF antagonists for palmoplantar pustulosis—may worsen disease 1
3. Avoid phototherapy during acute pustular flares—can exacerbate pustulation 3, 6
4. Do not combine multiple systemic agents without careful consideration—toxicity is additive 1, 2
5. Ensure 2-year contraception after acitretin in women of childbearing potential 3, 1
6. Monitor for superinfections—most common complication requiring approximately one-fourth of patients to need additional treatment 6

Emerging Therapies

Spesolimab (IL-36 receptor inhibitor):

• Shows promising results in GPP with rapid onset of action 7, 8
• May be combined with apremilast for maintenance therapy after acute control 8
• Represents future direction for GPP-specific targeted therapy 7, 9