Risk of Death, Infections, and Hyperthermia in Ectodermal Dysplasias: A Nationwide Study

Abstract

This nationwide population-based study investigated the risk of death, infections, and hyperthermia in Danish patients with ectodermal dysplasia (ED). A validated cohort of ED patients (n = 396) and matched population comparators (n = 3960) was compared to assess these risks before (case-control analysis) and after ED diagnosis (cohort analysis). Using matched comparators as a reference, the overall hazard ratio (HR) for death was 1.33 (95% confidence interval [CI] 0.70-2.55) in ED patients, and particularly high in males with hypohidrosis (HR 3.77, 95% CI 1.57-9.03) and individuals diagnosed before age 18 (HR 6.53, 95% CI 1.84-23.13). ED was associated with an increased risk of hospital-diagnosed infections before (odds ratio [OR] 2.27, 95% CI 1.81-2.85) and after (HR 2.06, 95% CI 1.74-2.45) diagnosis, varying across subtypes. Sensitivity analyses supported these findings, e.g., using antimicrobial prescriptions to identify infections. An association between hypohidrosis and previous hyperthermia (OR 7.11, 95% CI 3.26-15.51) diminished after diagnosis (HR 1.38, 95% CI 0.54-3.53). This study found an increased mortality risk in males with hypohidrosis and those diagnosed in childhood, and infection and hyperthermia risks depending on ED subtype. These data enhance understanding of ED's clinical course, informing patient management and counselling.

Fig. 1

Diagram of study design. The study design included 2 analyses. A case-control analysis investigating the occurrence of infections and hyperthermia before the date of ectodermal dysplasia (ED) diagnosis or matching date (index date) in patients with ED (cases) vs matched comparators (controls), respectively. Furthermore, a cohort design with a time-to-event analysis of the risk of death, infections, and hyperthermia after the index date in patients with ED (exposed cohort) vs matched comparators (unexposed cohort). ^aPatients’ educational status was used for patients ≥ 22 years at index date and parents’ educational status was used for patients < 22 years at index date.

Fig. 2

Unadjusted ORs from case-control analysis of the associations between ectodermal dysplasia (ED) and previous hospital-treated infections, hyperthermia, and febrile convulsions. Results are shown for (A) any ED, (B) hypohidrosis, (V) males with X-linked hypohidrotic ED, and (D) incontinentia pigmenti. Results with < 3 observations are not shown. Detailed results including number of observations, adjusted analyses, and results for additional ED subgroups are provided in Table SIV. CI: confidence interval; OR: odds ratio; XLHED: X-linked hypohidrotic ectodermal dysplasia.

Fig. 3

Unadjusted hazard ratios from cohort analysis of the associations between ectodermal dysplasia (ED) diagnosis and subsequent first-time hospital-treated infections, hyperthermia, and febrile convulsions. Results are shown for (A) any ED, (B) hypohidrosis, (C) males with X-linked hypohidrotic ED, and (D) incontinentia pigmenti. Results with < 3 observations are not shown. Detailed results including number of events, person-time at risk, incidence rates, adjusted analyses, and results for additional ED subgroups are provided in Table SV. CI: confidence interval; HR: hazard ratio; XLHED: X-linked hypohidrotic ectodermal dysplasia.