Generalized Pustular Psoriasis

• Rare, severe, potentially life-threatening systemic inflammatory disease, now recognized as distinct from plaque psoriasis.
• Characterized by macroscopically visible sterile pustules on erythematous skin, not restricted to acral areas or within psoriatic plaques.
• Flares may develop rapidly over hours, with widespread superficial non-follicular pustules.
• Pustules may coalesce into “lakes of pus.”
• Systemic inflammation is common but is not required for diagnosis under recent international criteria.
• May occur with or without previous plaque psoriasis.
• The IL-36 pathway plays a major role in its pathogenesis.
• Severe acute flares constitute a dermatologic emergency.

TRIGGERS

• Abrupt systemic corticosteroid withdrawal +++.
• Infections.
• Medications.
• Pregnancy - historically termed impetigo herpetiformis.
• Hypocalcemia.
• Physiological or psychological stress may contribute.
• Some flares occur without an identifiable trigger.

• Often rapid onset, sometimes within hours.
• Painful erythema followed by numerous small superficial pustules.
• Burning and skin tenderness/pain.
• Fever, chills, fatigue, and malaise may occur.
• Tachycardia, nausea, anorexia, or headache may accompany systemic inflammation.
• Pustules subsequently dry with diffuse desquamation, while new crops may continue to develop.

COMPLICATIONS

• Dehydration.
• Electrolyte disturbances, including hypocalcemia.
• Hypoalbuminemia.
• Renal or hepatic dysfunction.
• Temperature dysregulation.
• Secondary bacterial infection and sepsis.
• Pulmonary involvement.
• Progression to erythroderma.

• Diffuse inflammatory erythema.
• Numerous 2-3 mm superficial, non-follicular sterile pustules.
• Pustules may coalesce into “lakes of pus.”
• Subsequent diffuse scaling/desquamation.
• Painful, tender skin.
• Edema may occur.
• Mucosal involvement may include cheilitis and geographic or fissured tongue.
• Ocular involvement may include conjunctivitis, iritis, or uveitis.

• Diffuse inflammatory erythema.
• Numerous 2–3 mm superficial, non-follicular sterile pustules.
• Pustules may coalesce into “lakes of pus.”
• Subsequent diffuse scaling/desquamation.
• Painful, tender skin.
• Edema may occur.
• Mucosal involvement may include cheilitis and geographic or fissured tongue.
• Ocular involvement may include conjunctivitis, iritis, or uveitis.

• Homogeneous erythematous background.
• Multiple superficial white-yellow pustules.
• Dotted vessels may be visible.
• White scaling during the desquamative phase.
• Dermoscopy is adjunctive rather than required for diagnosis.

• Primarily clinical: macroscopically visible sterile pustules on erythematous skin, not restricted to acral sites or psoriatic plaques.
• Skin biopsy when diagnosis is uncertain.
• Histology: subcorneal neutrophilic pustules, spongiform pustules of Kogoj, parakeratosis ± Munro microabscesses.
• CBC frequently demonstrates leukocytosis/neutrophilia.
• CRP/ESR may be elevated.
• Check electrolytes, calcium, renal/liver function, and albumin to assess systemic involvement.
• Pustule culture when infection needs to be excluded.
• Blood cultures when systemic infection/sepsis is suspected.

• Acute generalized exanthematous pustulosis (AGEP) +++.
• Generalized bacterial pustular infection.
• Subcorneal pustular dermatosis (Sneddon-Wilkinson disease).
• IgA pemphigus.
• Pemphigus foliaceus.
• Dermatitis herpetiformis.
• Other generalized pustular drug eruptions.

• Urgent dermatology assessment; hospitalization is usually required for significant acute flares.
• IV fluids and correction of electrolyte abnormalities as required.
• Monitor temperature, renal function, fluid balance, and hemodynamic status.
• Bland emollients and supportive skin care.
• Analgesia.
• Antibiotics only for suspected or confirmed secondary infection.
• Spesolimab, targeting the IL-36 receptor, is a GPP-specific targeted therapy that has changed contemporary management of acute GPP.
• Other systemic options include cyclosporine, acitretin, methotrexate, and selected TNF-α, IL-17, or IL-23 biologics depending on clinical circumstances and availability.
• Phototherapy is generally not practical for an acutely unstable flare but may have a role later in selected patients.
• Pregnancy requires coordinated dermatology-obstetric management.