Background/Purpose
Delayed puberty and decreased final length has been reported in chronic diseases like Crohn’s disease and JIA with a disease onset at prepubertal age. This may be due to systemic effects of inflammation, undernutrition or medication, for example glucocorticoids or MTX. Treatment with anti TNF has shown to restore delayed growth in JIA.
Nowadays patients are treated intensively with disease modifying drugs including biologicals to reach remission. Our objectives are to describe growth, onset and progression of puberty in established JIA patients who are treated intensively.
Methods
All consecutive JIA patients aged 10 -24 years were asked to participate in  this observational follow-up study. Demographic and disease related items were obtained yearly as well as Tanner puberty stages: Pubic Hair Girls (PHG), Breast stage (Bre), Menarche (Men), Pubic Hair Boys (PHB), Genital Stage (Gen). Reference Values were obtained from the Dutch National Growth Study. Median age at reaching each pubertal stage was estimated by Kaplan Meier survival estimates based on data from patients of Caucasian origin and younger than 21 years. The progression of puberty is defined as the difference in median age between the tanner stage 2&3; 3&4 and 4&5. Parametric tests are used to determine differences between patients and healthy controls, non parametric tests are used to determine differences between patient groups.
Results
138 patients were included; 91 girls (66%) and 47 boys (34%). Ten percent have systemic onset type of JIA, 24% oligo– persistent, 55% oligo-extended and polyarticular course, 11% other subtypes of JIA.
Median disease duration is 7,8 years (IQR 6,7). Median JADAS27 is 3,7 (IQR 6,7), median active joint count is 0,0 (2,0), median DAS 28 is 2,16 (1,30). MTX is used in 79% of the patients, anti TNF in 14% and systemic corticosteroids in 23%. Median SDS length is -0,29 (IQR 1,38), SDS weight -0,27 (1,46), SDS BMI -0,08 (1,71). PHG, Bre, PHB and Gen are delayed in all stages 2-5, more pronounced in stage 5. Median delay compared to healthy controls in PHG stage 5 is 3,4 years, in Bre stage 5 3,4 years, in Menarche 3,5 years, in PHB stage 5 1,6 years and in  Gen stage 5 1,7 years. The progression of puberty was delayed between all stages in both girls and boys, most markedly delay was seen between stage 4&5 of PHG and Bre. No significant differences are seen between users and non-users of systemic corticosteroids, MTX or biologicals. Subtype of JIA, disease activity and age at onset did not significantly influence results.
Conclusion
Due to intensive treatment, disease activity in JIA patients is low and growth is comparable to healthy age related persons. However, puberty is still remarkably delayed. Further investigation into clinical relevance and cause of delayed puberty is needed.

This study was funded by Dutch Arthritis Foundation