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Cross-sectional study of fecal calprotectin in children with various forms of arthritis and non-inflammatory musculoskeletal disorders: a single centre experience

Introduction: Although gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in juvenile SpA (jSpA) patients is still largely unknown, mostly due to the lack of reliable non-invasive tests. Objectives: We performed a cross-sectional study of fecal calprotec- tin (fCAL), a surrogate marker of gut inflammation, in patients with jSpA, other forms of juvenile idiopathic arthritis (JIA) and non- inflammatory (NI) conditions. Methods: fCAL was measured by commercially available assay in stool samples of enthesitis related (ErA), psoriatic (PsA) and patients with other JIA subtypes (oligo- and poly- articular) who fulfilled ILAR criteria, as well as in children with NI causes of musculoskeletal pain (NI-MSD), regardless of the gastrointestinal (GI) symptoms (Table 1). fCAL was compared among different groups of patients and correlated with demographic data, clinical characteristics, treatment modalities and disease activity measured by jSpADA. The values were also dichotomized to <50 mg/kg, 50-200 mg/kg, and >200 mg/kg, which was regarded as normal, slightly increased and increased, respectively. Ileocolono- scopy was performed in one patient. Results: The median fCAL levels were highest in ErA patients (p= 0.04). Moreover, in ErA patients moderate correlation between fCAL levels and MRI signs of SI inflammation (r=0.4, p= 0.39) was found, while the patients with inflammation had higher fCAL concentrations than those without (22.6 vs 54.3, p=0.048). There was no significant difference in fCAL concentration between ErA patients with inactive (jSpADA ≤1) or active (jSpADA ≥ 1) disease (39.7 vs 30.9, p=0.66). In all patients, NSAID use was not associated with increased fCAL (20 vs 23, p=0.18), although weak correlation was found with the duration of the use (r=0.25, p=0.03). No correlation was observed between fCAL level and age at the time of sampling, duration of the disease, CRP or ESR, number of active joints and/or enthesis, physician global assesment, morning stiffnes, uveitis, back mobility, abdominal pain, diarrhea, B27 presence in a patinet or a faimly and disease activity in ErA and other JIA patients measured by jSpADA and JADAS, respectively. Microscopic gut inflammation was observed in one ErA patient with fCAL concentration of 839 mg/kg. Conclusion: Our study has shown that fCAL levels are significantly higher in ErA patients compared to other JIA (p=0.03) and/or NI-MSD (p=0.03) patients. Moreover, almost a third of patients with ErA had levels of fCAL above the range regarded as normal, which adds to the number of evidences for a gut inflammation in this particular type of JIA. Besides, the fCAL levels were higher in those with axial involve- ment, which further suppots the association of gut and axial inflamma- tion in children with ErA. Although endoscopy remains a gold standard for the diagnosis of gut inflammation, fCAL can help to select children with ErA who might benefit from this invasive procedure, regardless of the GI symptoms, as shown in one patient with the highest fCAL con- centration in our study. Moreover, fCAL levels seems not to be influ- enced by disease characteristic and/or concomitant therapy intake. Therefore, fCAL should be a part of diagnostic workup in children with any type of JIA, but most importantly in those with ErA.

faecal calprotectin ; fCAL ; juvenile idiopathic arthritis ; JIA

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