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Review
. 2021 Mar 12;19(1):28.
doi: 10.1186/s12969-021-00521-5.

Growth and puberty in children with juvenile idiopathic arthritis

Affiliations
Review

Growth and puberty in children with juvenile idiopathic arthritis

Debora Mariarita d'Angelo et al. Pediatr Rheumatol Online J. .

Abstract

Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10-20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient's bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.

Keywords: Bone; Growth; Hormone replacement therapy; Juvenile idiopathic arthritis; Puberty.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Effects of pro- inflammatory cytokines on GH-IGF1 axis. GH (Growth Hormone); IGF-1 (Insulin-like Growth Factor-1); IGFBP-1 (Insulin-like Growth Factor Binding Protein-1); IGFBP-3 (Insulin-like Growth Factor Binding Protein-3); IL-6 (Interleukin-6); IL-1β (Interleukin-1β); TNFα (Tumor Necrosis Factor-α)
Fig. 2
Fig. 2
Effects of pro-inflammatory cytokines and of GCs on gonadotropin-gonads axis as well as on bone metabolism. IL-6 (Interleukin-6); IL-1β (Interleukin-1β); TNFα (Tumor Necrosis Factor-α); GCs (glucocorticoids); GnRH (gonadotropin releasing hormone); LH (luteinizing hormone); FSH (follicle stimulating hormone); RFRP-3 (RFamide-related peptide); Kiss-1 (kipeptin-1); OPG (osteoprotegerin); RANKL (nuclear factor kappa β ligand); DKK-1 (dickkopf-1)

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