Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies.
BACKGROUND
Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA.


METHODS AND RESULTS
We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain.


CONCLUSION
A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature.
['de Zegher|Francis|F|', 'Reynaert|Nele|N|', 'De Somer|Lien|L|', 'Wouters|Carine|C|', 'Roelants|Mathieu|M|']
D000293:Adolescent D001171:Arthritis, Juvenile D001688:Biological Products D001827:Body Height D002648:Child D004359:Drug Therapy, Combination D005260:Female D006130:Growth Disorders D019382:Human Growth Hormone D006801:Humans D007249:Inflammation D008297:Male D012741:Sexual Maturation D016896:Treatment Outcome
Systemic juvenile idiopathic arthritis Short stature Growth hormone Puberty