Growth in Juvenile Idiopathic Arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is the most common inflammatory disease of childhood characterized by chronic synovitis and associated with a number of extra-articular manifestations. The course of JIA is highly variable, ranging from a mild, self-limiting form to a very aggressive disease. Disease subtypes are significant predictors for persistent disease activity. Children with oligoarthritis have a better outcome than those with either systemic or polyarticular disease in relation to the main outcomes such as remission, functional limitation, and radiological damage. Disturbance of growth and bone metabolism is a serious complication of JIA. Growth disturbances vary from general growth retardation to local acceleration of growth in the affected joint. Short stature is an important complication in children with JIA. Patients with a history of systemic JIA treated with glucocorticoids for at least 2 years during childhood have a final height standard deviation score (SDS) under –2 SD and a final height below their target height. Decreased bone mineral density (BMD) and osteopenia with possible bone fractures are other complications of JIA. The precise etiology of growth retardation is unknown. Multiple factors such as decreased physical activity, nutritional insufficiency, increased proinflammatory cytokines, and medications may play a role in skeletal maturation. Several hormones are important for normal postnatal longitudinal bone growth, but it is generally accepted that growth hormone (GH) is the most important hormone in bone growth. Children with JIA and severe growth retardation may have normal pulsatile GH secretion and are reported to have reduced insulin-like growth factor-1 (IGF-1) levels and IGF-binding protein-3 (IGFBP-3). Growth retardation in these children may be due to direct effects of proinflammatory cytokines on the growth plate, or increased levels of inflammatory cytokines may inhibit the effects of GH on the growth plate. Inflammation and corticosteroid therapy are major determinants of linear growth impairment. Effective control of the inflammation with earlier use of disease-modifying anti-rheumatic drugs and modulators of cytokines improves growth velocity in patients with JIA. Treatment with GH earlier after the onset of the disease may prevent growth and metabolic complications induced by chronic inflammation and long-term steroid therapy. Care of children with JIA requires a multidisciplinary team consisting of a pediatric rheumatologist, a physiotherapist, a pediatric endocrinologist, a nutritionist, a psychotherapist, and a social worker.