Deficiency of Interleukin-1 Receptor Antagonist: A Case with Late Onset Severe Inflammatory Arthritis, Nail Psoriasis with Onychomycosis and Well Responsive to Adalimumab Therapy

Necil Kutukculer,Jean-Laurent Casanova,Anne Puel,Guzide Aksu,Neslihan Edeer Karaca,Sanem Eren Akarcan,Melanie Migaud,Kunihiko Moriya

doi:10.1155/2019/1902817

Abstract

DIRA (deficiency of the IL-1Ra) is a rare condition that usually presents in the neonatal period. Patients with DIRA present with systemic inflammation, respiratory distress, joint swelling, pustular rash, multifocal osteomyelitis, and periostitis. Previously, we reported a patient with a novel mutation in IL1RN with a healthy neonatal period, a late-onset of pustular dermatosis, inflammatory arthritis, and excellent response to canakinumab treatment. Herein, we are presenting a new case of late-onset DIRA syndrome, carrying a different mutation and showing different clinical findings. This patient is the first one in the literature with the inflammatory arthritis, nail psoriasis, and onychomycosis and with her remarkable response to monoclonal antibodies. The case responded well and fully recovered after treatment with adalimumab, but not with canakinumab. The DIRA disease can lead to death from multiple organ failures and if recognized early, the treatment with replacement of the deficient protein with biologic agents induces rapid and complete remission. Therefore, clinical symptoms should be learned exactly by the pediatricians, pediatric rheumatologists, and immunologists; and molecular analysis targeting this defect must be performed as early as possible.

Highlights

Autoinflammatory diseases are a group of disorders characterized by systemic inflammation without high-titer autoantibodies or autoantigen-specific T cells [1, 2]
A severe autoinflammatory condition was found to be caused by biallelic mutations in IL1RN and named as deficiency of the IL-1 receptor antagonist (IL-1Ra) (DIRA) [5, 6]
DIRA (OMIM-612852) was first described in 2009 [2] and its etiology had been linked to loss-of-function mutations in IL1RN [1], or a major deletion that involves the IL1RN locus [3], a gene that encodes the IL-1 receptor antagonist (IL-1Ra)

Summary

Introduction

Autoinflammatory diseases are a group of disorders characterized by systemic inflammation without high-titer autoantibodies or autoantigen-specific T cells [1, 2]. Autoinflammatory diseases are clinically characterized by recurrent or persistent systemic inflammation, such as fever and organspecific manifestations, such as rashes and osteoarticular, serosal, neurologic, or ocular manifestations [1,2,3] These diseases are caused by dysregulated activation of the inflammasome, which is critical for the activation of the proinflammatory cytokine interleukin- (IL-) 1β, a powerful mediator of inflammatory responses [4]. In 2015, we reported a 12-year-old girl with a novel mutation in IL1RN with a late-onset presentation in comparison to previously reported children with DIRA [7] This case was the first reported patient with DIRA with an excellent response to canakinumab (recombinant human anti-human IL-1beta monoclonal antibody) treatment [7]. The case responded well and fully recovered after treatment with the monoclonal antibody adalimumab, but not with canakinumab

Case Report

Findings

Discussion