622 Ustekinumab therapy in Netherton syndrome

Netherton syndrome (NS) is a rare disorder of cornification associated with high morbidity. It is caused by bi-allelic mutations in SPINK5 encoding the serine protease inhibitor LEKTI. Previous studies have shown Th17 skewing with IL-23 upregulation in NS, raising the possibility that targeting these inflammatory pathways may alleviate disease manifestations. Ustekinumab was previously shown in one single case to exert a beneficial effect in NS. Here, we aimed to ascertain the therapeutic efficacy of ustekinumab in NS using a number of well-validated metrics. Six doses of ustekinumab were administered to each of 3 patients with NS over a period of 13 months and treatment efficacy was ascertained using the Ichthyosis Area and Severity Index (IASI), the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS) for itch and the peak-pruritus numeric rating scale (PP-NRS). Histopathology analysis including immunophenotyping using CD3, CD4, CD8 and interleukin 17 (IL-17) immunostaining, was performed at baseline and 4 weeks following the last ustekinumab dose. Total IASI scores were reduced by 28% in two patients at week 16 with sustained response by week 56. No consistent improvement in DLQI, VAS for itch and PP-NRS scores was observed. Histopathology analysis demonstrated a slight reduction in inflammatory infiltrate and acanthosis at week 56 as compared to baseline. No significant change in immunostaining of the various inflammatory markers was observed at week 56. Ustekinumab treatment was well tolerated. In conclusion, this case series suggests a lack of clinically meaningful therapeutic effect of ustekinumab in NS.