Autoimmune rheumatic disease assessments in children should include talks on puberty issues
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Given the link between puberty and autoimmune rheumatic disease, a group of researchers has recommended that clinical assessments of young patients with such conditions record pubertal issues at every encounter.
“The incidence of [systemic lupus erythematosus], autoimmune thyroid disease, and [multiple sclerosis] increases in peri- and post-pubescent females, suggests that sex hormone changes at puberty play an immunomodulatory role in triggering [autoimmune rheumatic disease (ARD)] onset and development,” Nina M. de Gruijter, BSc, a PhD student at the University College London Center for Adolescent Rheumatology Versus Arthritis, and colleagues wrote in Pediatric Rheumatology. “In addition to triggering autoimmunity, sex hormones can influence the outcome of autoimmune diseases.”
“No previous systematic reviews have addressed the impact of puberty on disease outcome measures in autoimmune rheumatic diseases, or the impact of ARDs on puberty-related outcomes,” they added. “Few studies are available that have looked at the epidemiology of ARDs during adolescence or focused on the gender bias in autoimmunity in adolescent populations. Understanding the interplay between the neuroendocrine and immune systems will provide insights into the pathogenesis of the peri-pubertal onset of ARDs, and may change the clinical approach to treatment of these patients in the long term.”
To analyze the links between puberty and autoimmune rheumatic disease outcomes, Gruijter and colleagues conducted a systematic review of endocrinology and rheumatology literature. Focusing on English-language articles published up until October 2019, the researchers identified and included 16 non-randomized studies. These included seven on the impact of puberty on autoimmune rheumatic disease outcomes, eight on the impact of autoimmune rheumatic disease on puberty outcomes, and one on both.
Among the studies on puberty’s impact on disease outcomes, one included patients with juvenile idiopathic arthritis-associated uveitis, five included patients with juvenile systemic lupus erythematosus, one featured health controls who later developed adult-onset SLE, and one included patients with non-specific symptoms. For the studies examining disease impact on puberty outcomes, four included patients with JIA and three featured those with juvenile SLE.
The researchers examined information on study design, sample sizes, demographics, puberty outcome measures, disease outcome measures and primary findings. They also analyzed the methodological quality of the studies using the Newcastle-Ottawa Scale (NOS).
According to the researchers, quality assessment of the studies demonstrated a small to moderate risk for bias overall, with NOS scores of four to nine out of nine. Due to the large heterogeneity of the studies, it was not possible to perform a meta-analysis, they wrote. However, multiple studies reported delayed puberty in patients with JIA and juvenile SLE, as well as menstrual and hormonal abnormalities and lower height and weight compared with healthy controls. In addition, pre-pubertal onset of juvenile SLE was correlated with more severe disease and more need for systemic treatment.
Considering the “limited quality of evidence” in their review, Gruijter and colleagues opted to craft a series of recommendations for feasible clinical assessments of children and adolescents with autoimmune rheumatic disease. The eight recommendations, based not only on the results of their literature review but also the experience of their multidisciplinary clinical team, are aimed at improving the understanding of disease and treatment impact on puberty-related outcomes. They include:
- Note the start of puberty in all patients to ensure appropriate action can be taken if it is delayed — older than 13years in girls and older than14 years in boys;
- Record age at menarche in every patient to establish that it is not delayed — older than 16 years;
- Record puberty progress — using patients’ history, self-assessment and growth chart, as well as clinical examination in case of concerns — at every clinical encounter until the completion of puberty, in accordance with the Childhood and Puberty Close monitoring Charts;
- Discuss menstrual abnormalities;
- Initiate patient-centered discussions about starting treatments that are likely to indirectly impact puberty, such as steroids or cyclophosphamide, and ensure puberty development is monitored in those starting such treatments;
- Propose endocrinology-rheumatology interdisciplinary assessments in selected cases of delayed puberty;
- Raise awareness of delayed puberty among patients and their families; and
- Quantify puberty-related outcomes in damage scores annually, including slowed growth, delayed puberty or infertility.
“Clinicians, patients and families will benefit from increased awareness of the relationship between puberty and ARDs,” Gruijter and colleagues wrote.
“Not only will our recommended assessments inform individualized flare management during puberty; they will also facilitate future research into treatments that minimize the negative impact of ARD on pubertal development,” they added. “Shedding light on the complex but important relationship between puberty and autoimmune rheumatic diseases allows young patients to have what all young people want: A chance to develop into the best version of themselves, without limitations.”
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