Comorbidities of Keloid and Hypertrophic Scars Among Participants in UK Biobank

Abstract

ImportanceKeloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.ObjectiveTo evaluate established comorbidities of excessive scarring in European individuals, with comparisons across ethnic groups, and to identify novel comorbidities via a phenome-wide association study (PheWAS).Design, Setting, and ParticipantsThis multicenter cross-sectional population-based cohort study used UK Biobank (UKB) data and fitted logistic regression models for testing associations between excessive scarring and a variety of outcomes, including previously studied comorbidities and 1518 systematically defined disease categories. Additional modeling was performed within subgroups of participants defined by self-reported ethnicity (as defined in UK Biobank). Of 502 701 UKB participants, analyses were restricted to 230078 individuals with linked primary care records.ExposuresKeloid or hypertrophic scar diagnoses.Main Outcomes and MeasuresPreviously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.ResultsOf the 972 people with excessive scarring, there was a higher proportion of female participants compared with the 229 106 controls (65% vs 55%) and a lower proportion of White ethnicity (86% vs 95%); mean (SD) age of the total cohort was 64 (8) years. Associations were identified with hypertension and atopic eczema in models accounting for age, sex, and ethnicity, and the association with atopic eczema (odds ratio [OR], 1.68; 95% CI, 1.36-2.07; P < .001) remained statistically significant after accounting for additional potential confounders. Fully adjusted analyses within ethnic groups revealed associations with hypertension in Black participants (OR, 2.05; 95% CI, 1.13-3.72; P = .02) and with vitamin D deficiency in Asian participants (OR, 2.24; 95% CI, 1.26-3.97; P = .006). The association with uterine leiomyoma was borderline significant in Black women (OR, 1.93; 95% CI, 1.00-3.71; P = .05), whereas the association with atopic eczema was significant in White participants (OR, 1.68; 95% CI, 1.34-2.12; P < .001) and showed a similar trend in Asian (OR, 2.17; 95% CI, 1.01-4.67; P = .048) and Black participants (OR, 1.89; 95% CI, 0.83-4.28; P = .13). The PheWAS identified 110 significant associations across disease systems; of the nondermatological, musculoskeletal disease and pain symptoms were prominent.Conclusions and RelevanceThis cross-sectional study validated comorbidities of excessive scarring in UKB with comprehensive coverage of health outcomes. It also documented additional phenome-wide associations that will serve as a reference for future studies to investigate common underlying pathophysiologic mechanisms.

An updated review of the immunological mechanisms of keloid scars

“…Keloid scars are often disfiguring, profoundly impair the quality of life and cause immense physical and mental distress of affected individuals, especially in those with symptomatic (pruritic, painful) and/or hyperpigmented scars ( 2 – 4 ). Limited epidemiological data suggested a female predominance, and a higher prevalence among people of darker skin complexion, such as those of African and Asian descents ( 5 , 6 ). The prevalence of excessive scarring in Black, Asians and Caucasians was recently reported at 2.4%, 1.1% and 0.4%, respectively ( 6 ).…”

“…Limited epidemiological data suggested a female predominance, and a higher prevalence among people of darker skin complexion, such as those of African and Asian descents ( 5 , 6 ). The prevalence of excessive scarring in Black, Asians and Caucasians was recently reported at 2.4%, 1.1% and 0.4%, respectively ( 6 ). Association between excessive scarring and other systemic conditions including hypertension ( 7 – 9 ), vitamin D deficiency ( 10 , 11 ), and atopic dermatitis ( 12 , 13 ) has been suggested.…”

“…Association between excessive scarring and other systemic conditions including hypertension ( 7 – 9 ), vitamin D deficiency ( 10 , 11 ), and atopic dermatitis ( 12 , 13 ) has been suggested. A recent cohort of the UK biobank found atopic dermatitis significantly associated with excessive scarring across ethnic groups ( 6 ). Hypertension in Blacks and vitamin D deficiency in Asians also showed significant association with keloid formation ( 6 ).…”

“…A recent cohort of the UK biobank found atopic dermatitis significantly associated with excessive scarring across ethnic groups ( 6 ). Hypertension in Blacks and vitamin D deficiency in Asians also showed significant association with keloid formation ( 6 ).…”

“…Recent technologies, such as identification of differentially expressed genes via examination of RNA sequencing data sets ( 74 , 75 , 78 – 80 ), have led to more extensive analysis of keloid tissue. A skewed T helper (Th) 2 phenotype was recently characterized ( 81 – 85 ), along with a potential co-susceptibility of keloids and atopic dermatitis ( 6 , 12 , 86 ). Moreover, even in the absence of comorbid atopic dermatitis, both lesional and non-lesional skin of patients with chronic keloids exhibit Th2 predominance ( 81 ).…”