Excellent response to secukinumab in an infant with severe generalized pustular psoriasis

Abstract

Generalized pustular psoriasis (GPP) represents the rarest form of psoriasis, which may be potentially fatal. In the last decade, (likely) pathogenic variants in the IL36RN, CARD14 and AP1S3 genes have been associated with monogenic GPP forms. Despite these advances, the genetic basis of most patients with GPP remains unidentified. Treatment of GPP patients is often difficult, with no consensus about the best available options to date. We report herein an infant with severe GPP in whom the disease started at the age of 2 months. Genetic investigations identified a heterozygous pathogenic variant in the IL36RN gene associated with a heterozygous variant of uncertain significance in the CARD14 gene. After previous treatment failures with acitretin, cyclosporin and anakinra, treatment with the interleukin-17 antagonist secukinumab resulted in a dramatic and prompt positive response that persisted at 12-month follow up. According to our experience, we believe secukinumab can be an effective and safe treatment for pediatric patients with GPP even before 1 year of age.

Successful treatment of a 3‐year‐old girl with generalized pustular psoriasis using secukinumab monotherapy

“…The efficacy of secukinumab in pediatric GPP is more limited, but five studies involving a total of eight patients have reported successful use 3,4 . Six of these eight children had previously failed conventional systemic therapy, five had known IL36RN mutations, three were treated with secukinumab monotherapy, and all eight patients experienced rapid and sustained improvement, without adverse events 1‐5 …”

“…Generalized pustular psoriasis is a rare and severe form of psoriasis that is characterized by recurrent episodes of diffuse cutaneous erythema covered with pinpoint pustules and generally accompanied by fever, general malaise, and elevated inflammatory markers 1 . GPP without a history of plaque psoriasis has been reported in association with IL36RN mutations 2 . The treatment of pediatric GPP can be challenging as it may be refractory to conventional systemic therapies such as acitretin, cyclosporine, and methotrexate 3 …”

The update of treatment strategies in pediatrics with generalized pustular psoriasis in China

“…All the children had defervescence and clearance of non‐acral pustules within 72 h, and all the participants except for the one with ACH achieved an Investigator's Global Assessment (IGA) 0/1 at week 24. Secukinumab was also effective in a 4‐week‐old infant with IL36RN and CARD14 gene mutations 63 …”

“…Secukinumab is a fully human immunoglobulin‐Gκ IL‐17A monoclonal antibody and decreases IL36R activation by inhibiting IL‐17A and disturbing the inflammatory loop of GPP. Several cases and case series have described the efficacy and safety of secukinumab 19,57–66 . Our team reviewed the efficacy and adverse events of secukinumab in 20 Chinese pediatric patients with GPP, with the ages ranging from 6 to 12 years and the age of onset ranging from 2 months to 11 years 19 .…”

Psoriasis in pediatric age group

“…Secukinumab has shown good efficacy and safety profile for treating pediatric patients less than one year of age. [ 36 ] There is a lack of data for the use of infliximab in children. Apremilast, a PDE-4 inhibitor, has shown to be useful in moderate to severe plaque psoriasis in a few case series, but larger studies are required to establish its efficacy and safety profile in children.…”