When Conventional Therapy Fails: Interleukin-36 Inhibition for Severe Hydroxychloroquine-Induced Acute Generalized Exanthematous Pustulosis in Systemic Lupus Erythematosus - A Case Report.

INTRODUCTION

Acute generalized exanthematous pustulosis (AGEP) is a rare but severe cutaneous adverse drug reaction characterized by the sudden onset of widespread sterile pustules on an erythematous and edematous base, often accompanied by fever and neutrophilia. Over 90% of cases are drug-induced. Its management can be particularly challenging in patients with autoimmune diseases such as systemic lupus erythematosus (SLE), where cutaneous manifestations and immune dysregulation may confound clinical assessment.

CASE PRESENTATION: We report a case of severe hydroxychloroquine-induced AGEP in a patient with active SLE. The disease was refractory to systemic corticosteroids and further worsened after intravenous immunoglobulin infusion. Given the emerging role of interleukin (IL)-36 pathway dysregulation in pustular dermatoses, the patient was treated with spesolimab, a monoclonal antibody targeting the IL-36 receptor, resulting in rapid defervescence and near-complete resolution of pustules within days.

CONCLUSION

This case underscores the need for prompt recognition of drug-induced AGEP in patients receiving antimalarials or other immunomodulatory agents for connective tissue diseases. Crosstalk between IL-36 signaling and neutrophil extracellular traps may amplify inflammation, linking AGEP with autoimmune pathology. IL-36 inhibition with spesolimab represents a potential rescue therapy for severe, treatment-refractory AGEP, particularly in patients with underlying autoimmune disorders where conventional therapies fail.