Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone.

BACKGROUND: X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies. RESULTS: Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH)2D increased dramatically under burosumab therapy. CONCLUSION: To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height.

Rhinovirus: A Narrative Review on Its Genetic Characteristics, Pediatric Clinical Presentations, and Pathogenesis.

Human rhinoviruses (HRVs) are the leading cause of common colds. With the development of new molecular methods since the 2000s, HRVs have been increasingly involved among severe clinical infections. Recent knowledge of the HRV genetic characteristics has also improved the understanding of their pathogenesis. This narrative review aims to provide a current comprehensive knowledge about this virus in the pediatric community. HRVs represent a main cause of upper and lower respiratory tract infections in children. HRV is the second virus involved in bronchiolitis and pneumonia in children, and HRV bronchiolitis has a higher risk of recurrent wheezing episode or asthma. Some recent findings described HRVs in stools, blood, or cerebrospinal fluid, thanks to new molecular techniques such as polymerase chain reaction (PCR) by detecting HRVs with high sensibility. However, the high rate of asymptomatic carriage and the prolonged excretion in postsymptomatic patients complicate interpretation. No sufficient data exist to avoid antibiotic therapy in pediatric high-risk population with HRV detection. Severe clinical presentations due to HRVs can be more frequent in specific population with chronic pathology or genetic particularity. Inflammatory response is mediated by the nuclear factor (NF)-kappa B pathway and production of interferon (IFN)-beta and IFN-gamma, interleukin 8 (IL8), and IL1b. No specific treatment or antiviral therapy exists, although research is still ongoing. Nowadays, in addition to benign diseases, HRVs are recognized to be involved in some severe clinical presentations. Recent advances in genetic knowledge or specific inflammatory response may lead to specific treatment.