A single-centre study on predictors and determinants of pubertal delay and growth impairment in Epidermolysis Bullosa

Abstract

Background Delayed puberty is a possible complication of Epidermolysis Bullosa (EB), though the actual incidence is still unknown. In chronic illnesses delayed puberty should be correctly managed since, if untreated, can have detrimental effects on adult height attainment, peak bone mass achievement and psychological health. Aims and methods This is a single-centre study on pubertal development, growth and bone status in EB. Auxological, densitometric (areal Bone Mineral Density-aBMD Z-score, Bone Mineral Apparent Density-BMAD Z-score, Trabecular Bone Score-TBS and Bone Strain Index-BSI at Lumbar spine) and body composition data (Total Body DXA scans) were collected. Disease severity was defined according to Birmingham Epidermolysis Bullosa Severity (BEBS) score. Results Twenty-one patients (12 Recessive Dystrophic EB-RDEB, 3 Dominant Dystrophic EB, 3 Junctional EB-JEB, 2 EB Simplex and one Kindler EB) aged 13 years (females) or 14 years (males) and above were enrolled (age 16.2±2.5 years, M/F 11/10). Short stature was highly prevalent (57%, mean height -2.12±2.05 SDS) with 55% patients with height <-2SD their mid-parental height. 7/21 patients (33%, 6 RDEB and 1 JEB) had delayed puberty with a median BEBS of 50 (range 29 to 63), a height SDS of -2.59 SDS (range -5.95 to -2.22) and a median lumbar BMAD Z-score of -4.0 SDS (range -5.42 to -0.63 SDS). Pubertal status was negatively associated with BEBS, skin involvement, inflammatory state and positively with height SDS and BMI SDS. Conclusions Pubertal delay is highly prevalent in EB, especially in patients with RDEB and JEB, high severity score and inflammatory state. Moreover, pubertal delay worsens growth impairment and bone health. A study on pubertal induction is ongoing to enlighten possible beneficial effects on adult height attainment and peak bone mass accrual.

Osteoporosis and bone health in pediatric patients with epidermolysis bullosa: A scoping review

“…When compared to healthy children, BMD has been consistently low for RDEB, even when adjusted for bone age and height, 8,9,13,14,17,20 and rates of bone mineral acquisition in children with EB are slower than those of healthy peers. 14 By age 10, 29% (22/76) of those with RDEB had low lumbar spine BMD Z-scores.…”

“…Pubertal delay was found in 7/21 patients (6 with RDEB and 1 with JEB), with no preference for gender ( p = .66). 9 In another study, 33% of those with RDEB had delayed puberty, while no other EB subtype met criteria, although 65% of those with EBS or JEB were too young to observe pubertal changes. 22 BMI scores were significantly lower in RDEB 9,11 and JEB, compared to DDEB ( p < .002) and EBS (p < .02).…”

“…9 In another study, 33% of those with RDEB had delayed puberty, while no other EB subtype met criteria, although 65% of those with EBS or JEB were too young to observe pubertal changes. 22 BMI scores were significantly lower in RDEB 9,11 and JEB, compared to DDEB ( p < .002) and EBS (p < .02). 11 Few papers mentioned ethnicity/skin type and no studies correlated osteoporosis with skin color, sun exposure/ geography, and diet of patients.…”

“…Baseline clinical characteristics of patients in relation to bone health are summarized in Table 1. Children with recessive dystrophic EB (RDEB) and JEB, the more severe types, were consistently reported to have growth 3,[7][8][9]15,16,18 and pubertal delay, 9,15,22 thought to result, at least in part, from malnutrition. Pubertal delay was found in 7/21 patients (6 with RDEB and 1 with JEB), with no preference for gender ( p = .66).…”

“…8 Additionally, nutritional compromise can interfere with the maturation of the hypothalamic-pituitary-gonadal axis, causing a delay in puberty, further negatively affecting achievement of peak bone mass. 9 While weight-bearing activity is optimal for bone health, it is limited due to fatigue, 8 joint contractures, 10 and depression which may impact motivation for exercise. 11 Compromise in achieving adequate bone growth during childhood and adolescence places patients with EB at immediate and future risk for pathologic fractures, osteopenia, and osteoporosis.…”