The Increased Levels of Fecal Calprotectin in Children With Active Enthesitis Related Arthritis and MRI Signs of Sacroiliitis: The Results of a Single Center Cross-Sectional Exploratory Study in Juvenile Idiopathic Arthritis Patients.

Lovro Lamot,Rudolf Vukojević,Nora Nikolac Gabaj,Mandica Vidović,Miroslav Harjaček,Mirta Lamot,Ivana Trutin,Marijana Miler

doi:10.3389/fmed.2021.650619

Lovro Lamot, Rudolf Vukojević + Show 6 more

Open Access

https://doi.org/10.3389/fmed.2021.650619

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Abstract

Enthesitis related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA), often regarded as an undifferentiated form of juvenile spondyloarthritis (jSpA). While gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in ERA patients is largely unknown. The aim of this study was to measure the concentration of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with different subtypes of JIA, as well as to correlate the results with various demographic, clinical, laboratory, imaging, and treatment characteristics. The cross-sectional exploratory study involving 71 patients with ERA, other forms of JIA and children complaining musculoskeletal symptoms was therefore conducted. Along with fCAL assessment, a detailed clinical and laboratory examination was performed, including the calculation of a composite disease activity scores. Moreover, MRI of the sacroiliac joints was performed in all ERA and other patients complaining of low back pain. The median concentration of fCAL was highest in ERA patients (33.2 mg/kg, p = 0.02), with a significant difference between those with inactive and active disease (20.0 vs. 57.4, p = 0.01), as well as those with and without MRI signs of sacroiliitis (22.6 vs. 54.3, p = 0.04). The fCAL did not differ depending on the NSAID use (23 vs. 20, p = 0.18), although weak correlation was observed with the treatment duration (r = 0.25, p = 0.03). In conclusion, our findings indicate that a parallel inflammation in musculoskeletal system and gut can occur not just in adults with SpA, but in children with ERA as well.

Highlights

During the past decades, several studies have shown that a substantial number of children with juvenile idiopathic arthritis (JIA) have some kind of gastrointestinal (GI) symptoms, while up to 85% of JIA patients with significant GI symptoms have histological evidence of mild non-specific inflammation [1,2,3,4,5]
Along with fecal calprotectin (fCAL) assessment, a detailed clinical and laboratory examination was performed for each patient, including the calculation of a composite juvenile arthritis disease activity score with 27-joint reduced count (JADAS-27) for those diagnosed with oligo- and polyarticular JIA and Enthesitis related arthritis (ERA), as well as juvenile spondyloarthritis disease activity for those diagnosed with ERA [33, 34]
The novel finding of our study was that fCAL concentration was significantly higher in ERA patients with MRI sign(s) characteristic for the SlJ inflammation, which adds to the growing number of evidences for a clinical association of gut inflammation and axial spondyloarthritis in adult and pediatric patients [40,41,42,43]

Summary

Introduction

Several studies have shown that a substantial number of children with juvenile idiopathic arthritis (JIA) have some kind of gastrointestinal (GI) symptoms, while up to 85% of JIA patients with significant GI symptoms have histological evidence of mild non-specific inflammation [1,2,3,4,5]. Despite some differences between spondyloarthritis (SpA) in children and adults, mostly in tendency to involve axial joints which is more remarkable in adults, there are emerging views that spondyloarthritis (SpA) surpasses this arbitrary age-based divide [13] It is still unclear if clinically silent macroscopic and microscopic gut inflammation which occurs in about 60% of adult patient with ankylosing spondylitis (AS) is present in children with ERA as well [14]. This is largely due to the challenges imposed by the use of endoscopy, the gold standard for detailed assessment of the inflammation in the gut, which are considerably important in children [15]. Non-invasive tests such as blood and fecal biomarkers are increasingly used in clinical practice to help select patients who might benefit from endoscopies and other more detailed investigations

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