Secukinumab in the management of generalized pustular psoriasis comorbidity with nephrotic syndrome in a toddler with IL36RN variant

Abstract Purpose To summarize the clinical feature, genetic variants of IL-36RN and biologic agent therapy in a toddler with generalized pustular psoriasis (GPP) with literature review. Methods Clinical data, family history, urine samples, and skin biopsy specimens were collected. Gene sequencing was performed. IL-36Ra expression in urine cells and skin was detected by Western blotting and immunofluorescence staining, respectively. Results A 1.5-year-old girl presented with eyelid and lower limb edema, her urine protein was 3+. Nephrotic syndrome was diagnosed, which was steroid-responsive but in a frequently relapse. At 1 year 9 months, red, ring-shaped plaques with silvery-white scales appeared on her trunk, later extending to face, limbs, and perineum, with development of pinpoint pustules. Inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, interleukin-6 and tumor necrosis factor-α) were markedly elevated. Whole-exome sequencing identified a homozygous variant of IL36RN (c.115 + 6T > C). Her mother was a heterozygous carrier, while her father had homozygous variant as well and presented with toe skin lesions and nail damage since his young age. Protein analysis indicated absent IL-36Ra expression in skin and reduced expression in urinary epithelial cells. Erythema and pustules resolved after the administration of secukinumab at 2 years and 2 months of age. Conclusion We report a case of GPP with a co-morbidity disease of idiopathic nephrotic syndrome in a toddler who harbored a homozygous IL36RN variant. Reduced IL-36Ra expression was evidenced in the involved skin and urine cells. The IL‑17 inhibitor appeared to be associated with clinical improvement in GPP-related manifestations. Clinical trial number Not applicable.