What are the treatment options for pustular psoriasis?

Treatment of Pustular Psoriasis

Immediate Treatment Approach Based on Disease Subtype

For generalized pustular psoriasis (GPP), acitretin, cyclosporine, methotrexate, and infliximab are first-line systemic therapies, with hospital admission typically required for initial management. 1, 2, 3

Localized Pustular Psoriasis (Palms and Soles)

• Apply moderately potent topical corticosteroids (British National Formulary grade III) as first-line therapy for symptom relief 1, 2
• Topical coal tar and dithranol may provide additional benefit, though efficacy is limited 1, 2
• Acitretin (0.1-1 mg/kg/day) can be considered for refractory cases 1
• Avoid TNF antagonists (infliximab, etanercept, adalimumab) in chronic palmoplantar pustulosis as they may paradoxically exacerbate the condition 2

Generalized Pustular Psoriasis (GPP)

First-Line Systemic Therapies

Acitretin:

• Particularly effective for pustular psoriasis with response as early as 3 weeks; 84% of patients show improvement 1, 2, 4
• Dose: 0.1-1 mg/kg/day (10-50 mg daily in adults) 1
• Major advantage: not immunosuppressive, making it suitable for patients with infection risk or organ transplants 1, 4
• Absolutely contraindicated in pregnancy or women planning pregnancy within 2 years of stopping treatment 2
• Can be combined with narrowband UVB for synergistic effects 1, 2, 4

Cyclosporine:

• Initial dose: 2.5 mg/kg/day divided twice daily, can increase by 0.5 mg/kg/day every 2 weeks to maximum 4 mg/kg/day 5
• Contraindicated in abnormal renal function, uncontrolled hypertension, and previous/concomitant malignancy 2
• Requires monitoring of serum creatinine and blood pressure; reduce dose by 25-50% if creatinine rises ≥25% above baseline 5
• Response typically seen within 2-4 weeks 5

Methotrexate:

• Contraindicated in pregnancy, breastfeeding, significant hepatic damage, and blood disorders 2
• Requires regular monitoring of liver function tests and complete blood counts 2
• Can be combined with infliximab to augment efficacy and maintain long-term control 2

Infliximab:

• Demonstrates rapid and often complete disease clearance in severe GPP, making it the preferred biologic for acute severe presentations 2, 3
• Standard dosing: 5 mg/kg infused at weeks 0,2, and 6, then every 8 weeks 2
• Dose intensification up to 10 mg/kg and/or more frequent intervals (every 4 weeks) may be needed 2
• Grade C recommendation from the American Academy of Dermatology for pustular psoriasis subtypes 2
• Can be combined with methotrexate for enhanced long-term efficacy 2

Second-Line Therapies

• Adalimumab and etanercept: Etanercept at 50 mg biweekly showed clinical efficacy with maintenance of response up to 48 weeks in case series 2, 3
• PUVA (psoralen plus ultraviolet A): 45.7% efficacy rate in GPP, but contraindicated in pregnancy, age <18, and previous cutaneous malignancy 2, 3
• Ultraviolet B radiation: May be helpful but use with extreme caution as it can exacerbate pustular psoriasis 1, 2

Critical Management Principles

What to Absolutely Avoid

Never use systemic corticosteroids as routine treatment for pustular psoriasis:

• Systemic corticosteroids can precipitate erythrodermic psoriasis, generalized pustular psoriasis, or very unstable psoriasis when discontinued 2, 6, 4
• Fluoridated hydrocortisone should not be used due to risk of disease flares 4
• Rare exceptions where short-term systemic corticosteroids may be considered: persistent uncontrollable erythroderma causing metabolic complications, von Zumbusch type GPP when other drugs are contraindicated, or hyperacute psoriatic polyarthritis threatening irreversible joint damage 2, 4
• If a patient is already on oral steroids during a flare, do not abruptly discontinue—initiate acitretin while slowly tapering steroids 2

Monitoring Requirements

• All systemic treatments require pretreatment assessment and ongoing monitoring including regular blood tests, liver function tests, and serum creatinine 2, 4
• For cyclosporine: monitor blood pressure and creatinine every 2 weeks initially, then monthly 5
• For methotrexate: baseline and regular liver function tests, complete blood counts 2
• For biologics: screen for active or latent tuberculosis, hepatitis B, and fungal infections before initiation 6

Combination Therapy Considerations

• Combination therapy should be approached with extreme caution as toxicity is at least additive 2, 4
• Acitretin combined with narrowband UVB shows synergistic effects and is a reasonable approach 1, 2, 4
• Infliximab may be combined with methotrexate or topical high-potency corticosteroids 2

Emerging Therapies

• Spesolimab (IL-36 receptor inhibitor) has shown promising results in placebo-controlled randomized trials for GPP and is now approved in multiple regions including the USA, EU, Japan, and China 7, 8
• Spesolimab demonstrated rapid improvement in severe GPP flares resistant to conventional treatments 7
• This represents the only treatment with high-quality randomized controlled trial data specifically for GPP 8

Common Pitfalls

• Do not mistake treatment failure for true tachyphylaxis with topical corticosteroids—poor adherence is often the culprit 6
• Avoid switching from chronic plaque psoriasis treatments to pustular psoriasis protocols without confirming the diagnosis, as 13 cases of transformation from chronic plaque to pustular forms have been reported with cyclosporine 5
• Upon discontinuation of infliximab, relapse is common but not universal—two of three patients relapsed in case series 2
• Long-term continuous cyclosporine treatment beyond one year is not recommended; alternation with other treatments should be considered 5