What are the newer treatment options for a patient with localized pustular psoriasis (LPP) and a history of gastrointestinal symptoms, considering their potential history of psoriasis or psoriatic arthritis?

Newer Treatment Options for Localized Pustular Psoriasis (LPP)

For localized pustular psoriasis (palmoplantar pustulosis), newer treatment options include IL-17 inhibitors, IL-23 inhibitors, and JAK inhibitors as systemic therapies, while avoiding TNF antagonists which may paradoxically worsen the condition. 1, 2

Critical Treatment Distinction

• TNF antagonists (etanercept, infliximab, adalimumab) should be avoided in chronic palmoplantar pustulosis as they may exacerbate this specific form of localized pustular psoriasis 1, 2
• However, TNF antagonists are reasonable for acropustulosis (pustular psoriasis of fingers/toes) if it significantly impacts quality of life 1
• This represents a critical pitfall—TNF inhibitors that work well for generalized pustular psoriasis can worsen palmoplantar disease 1, 2

First-Line Systemic Therapies for LPP

Acitretin remains highly effective for pustular psoriasis variants, with substantial improvement typically within 2-3 weeks at doses of 0.1-1 mg/kg/day (typically 25 mg daily) 1, 2

• Acitretin is particularly effective for pustular subtypes and can be combined with narrowband UVB for synergistic effects 1
• Major contraindication: pregnancy or women planning pregnancy within 2 years of stopping treatment 1

Newer Biologic Options

IL-17 inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors are strongly recommended for psoriatic disease including skin manifestations, with newer agents showing higher efficacy than TNF inhibitors 3

• These agents have strong evidence for psoriatic skin disease in the context of psoriatic arthritis 3
• Selection should be influenced by head-to-head study results, comorbidities, and activity in other disease domains 3

JAK Inhibitors and PDE4 Inhibitors

JAK inhibitors and PDE4 inhibitors (apremilast) represent newer oral systemic options with strong recommendations for psoriatic disease 3, 4

• Apremilast is dosed at 30 mg twice daily after a 5-day titration schedule to reduce gastrointestinal symptoms 4
• Common early adverse effects include diarrhea, nausea, and vomiting, particularly in the first few weeks 4
• Monitor patients over 65 years or those on medications causing volume depletion more closely for GI complications 4
• JAK inhibitors showed statistical superiority to placebo in psoriatic arthritis trials with skin outcomes 3

Phototherapy Options

Soak PUVA (topical psoralen plus UVA) is effective for palmoplantar psoriasis, requiring 2-3 treatments weekly for several months with low cutaneous malignancy risk 2

• PUVA has an efficacy rate of 45.7% in generalized pustular psoriasis and is considered first-choice systemic treatment with least toxicity 1
• Contraindications include pregnancy, significant cataracts, age <18, and previous cutaneous malignancy 1
• Oral PUVA combined with acitretin shows superior response compared to either alone 3

Topical Therapy Adjuncts

Superpotent topical corticosteroids (clobetasol propionate 0.05%) under occlusion combined with calcipotriene or tazarotene remain first-line for limited disease 2

• Moderately potent topical corticosteroids (grade III) provide symptom relief in localized pustular psoriasis 1
• Clobetasol propionate spray can be added to stable biologic regimens for additional clearing 5
• Vehicle choice (ointment vs. foam vs. spray) should be based on patient preference to optimize adherence, as efficacy is similar across formulations 6

Treatment Algorithm for LPP with GI History

Given the patient's gastrointestinal symptoms history:

1. Avoid apremilast initially due to high risk of GI adverse effects (diarrhea, nausea, vomiting) 4
2. Consider IL-17 or IL-23 inhibitors as first-line systemic therapy if topicals fail 3
3. Acitretin is an excellent option if not planning pregnancy, with rapid response expected 1, 2
4. Avoid TNF antagonists specifically for palmoplantar pustulosis 1, 2
5. Soak PUVA therapy is effective with minimal systemic absorption 2

Monitoring Requirements

• All systemic treatments require pretreatment assessment and ongoing monitoring with regular blood tests, liver function tests, and serum creatinine depending on the agent used 1, 7
• Cyclosporine requires monitoring for nephrotoxicity and is contraindicated in abnormal renal function and uncontrolled hypertension 1
• Methotrexate requires monitoring for hepatotoxicity and bone marrow toxicity 2

Critical Caveat: Avoid Systemic Corticosteroids

Systemic corticosteroids are absolutely contraindicated in pustular psoriasis due to risk of severe disease exacerbation upon withdrawal, potentially precipitating life-threatening generalized pustular psoriasis 1, 2, 7

• If a patient is already on steroids during a flare, do not abruptly discontinue—initiate alternative therapy (acitretin or biologic) while slowly tapering steroids 1