Pustular Psoriasis

Generalised pustular psoriasis is a rare, potentially life threatening form of psoriasis, with sudden crops of sterile pustules on erythematous skin that coalesce into lakes of pus, with fever, malaise and neutrophilia. It runs a relapsing course.

It is rare, with a prevalence of a few cases in 100 000 people in most series and higher in East Asia. It can occur in people with or without psoriasis, and onset occurs at any age, more often in adults and with an earlier peak in carriers of IL36RN variants.

Triggers include withdrawal of systemic corticosteroids or other immunosuppressants, infection, pregnancy (including impetigo herpetiformis), hypocalcaemia, stress, and drugs such as lithium, hydroxychloroquine and terbinafine. Pathogenic variants in IL36RN, CARD14 and AP1S3 are found in a subset.

Pathophysiology.

Loss of control of interleukin-36 signalling, often through IL36RN variants, drives sustained neutrophil recruitment and keratinocyte release of chemokines. The result is spongiform pustules in the upper epidermis, systemic inflammation and neutrophilia. Interleukin-1 and interleukin-17 add to the inflammatory loop.

• Rapid appearance of non-follicular sterile pustules of 2 to 3 mm over widespread red, tender skin, merging into lakes of pus. Pustules dry in 1 to 2 weeks and desquamate.
• Fever, malaise, arthralgia, tachycardia and fatigue, often in waves of pustulation.
• Geographic tongue, nail changes and oedema of hands and feet.
• Complications: dehydration, hypocalcaemia, hypoalbuminaemia, sepsis, heart failure, acute respiratory distress, kidney and liver dysfunction and hyperuricaemia.

Red flags.

• High fever, hypotension, tachycardia or confusion.
• Rapidly spreading or widespread pustulation with erythroderma.
• Pregnancy, with risk to the foetus and mother.

• Clinical diagnosis supported by biopsy: spongiform pustules in the upper epidermis, with neutrophils in the stratum corneum and dilated dermal vessels.
• Full blood count (neutrophilia), C-reactive protein, urea and electrolytes, creatinine, liver tests, calcium, albumin, uric acid and glucose.
• Pustule swab and blood cultures to exclude infection, which cannot be separated from sterile pustules on appearance.
• Genetic testing for IL36RN when disease begins in childhood, or is recurrent or familial.
• Chest radiograph and ECG if unwell. Drug review.

Differential diagnosis. Acute generalised exanthematous pustulosis, subcorneal pustular dermatosis, bacterial folliculitis and infection, impetigo herpetiformis, pemphigus foliaceus, IgA pemphigus, disseminated herpes and drug eruption.

Immediate care.

• Admit for fever or systemic upset. Provide fluid and electrolyte replacement, temperature control, analgesia, nutrition, thromboprophylaxis and emollient care.
• Correct hypocalcaemia and hypoalbuminaemia. Treat infection with cultures and antibiotics directed by the site and sensitivities.
• Stop triggering drugs, and avoid withdrawing systemic corticosteroids abruptly. Avoid starting systemic corticosteroids.

Systemic treatment.

• Spesolimab (an interleukin-36 receptor inhibitor) 900 mg as a single intravenous infusion for an acute flare, with a second dose after 1 week if symptoms persist (licensed in some regions).
• Rapid acting alternatives: ciclosporin 2.5 to 5 mg/kg/day in two divided doses, or infliximab 5 mg/kg intravenously at weeks 0, 2 and 6, then every 8 weeks.
• Acitretin 25 to 50 mg daily, or methotrexate 7.5 to 25 mg once weekly with folic acid 5 mg weekly, for control and maintenance.
• Biologics for maintenance: secukinumab 300 mg at weeks 0, 1, 2, 3 and 4 and then every 4 weeks, ixekizumab, or adalimumab 80 mg then 40 mg every 2 weeks. Screen for tuberculosis, hepatitis B, hepatitis C and HIV before starting.
• Phototherapy is not used in the acute stage.

Monitoring. Daily temperature, fluid balance and electrolytes during admission. After discharge review at 2 weeks and monthly until stable. Monitor ciclosporin blood pressure and creatinine, acitretin lipids and liver tests, and methotrexate blood count and liver tests.

Referral and escalation. Refer to dermatology urgently, with intensive care for shock or respiratory compromise.

Special groups. In pregnancy use ciclosporin or certolizumab with specialist input. Methotrexate and acitretin are contraindicated, and acitretin requires contraception for 3 years after stopping in women of childbearing potential.