JAMA Dermatology

<jats:sec id="ab-doi220066-4"><jats:title>Importance</jats:title><jats:p>Keloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.</jats:p></jats:sec><jats:sec id="ab-doi220066-5"><jats:title>Objective</jats:title><jats:p>To 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).</jats:p></jats:sec><jats:sec id="ab-doi220066-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This 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.</jats:p></jats:sec><jats:sec id="ab-doi220066-7"><jats:title>Exposures</jats:title><jats:p>Keloid or hypertrophic scar diagnoses.</jats:p></jats:sec><jats:sec id="ab-doi220066-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Previously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.</jats:p></jats:sec><jats:sec id="ab-doi220066-9"><jats:title>Results</jats:title><jats:p>Of 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; <jats:italic>P</jats:italic> &amp;amp;lt; .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; <jats:italic>P</jats:italic> = .02) and with vitamin D deficiency in Asian participants (OR, 2.24; 95% CI, 1.26-3.97; <jats:italic>P</jats:italic> = .006). The association with uterine leiomyoma was borderline significant in Black women (OR, 1.93; 95% CI, 1.00-3.71; <jats:italic>P</jats:italic> = .05), whereas the association with atopic eczema was significant in White participants (OR, 1.68; 95% CI, 1.34-2.12; <jats:italic>P</jats:italic> &amp;amp;lt; .001) and showed a similar trend in Asian (OR, 2.17; 95% CI, 1.01-4.67; <jats:italic>P</jats:italic> = .048) and Black participants (OR, 1.89; 95% CI, 0.83-4.28; <jats:italic>P</jats:italic> = .13). The PheWAS identified 110 significant associations across disease systems; of the nondermatological, musculoskeletal disease and pain symptoms were prominent.</jats:p></jats:sec><jats:sec id="ab-doi220066-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>This 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.</jats:p></jats:sec>

Keloid disorder: fibroblast differentiation and gene expression profile in fibrotic skin diseases.

Exp Dermatol

IL-6 signaling pathway in keloids: a target for pharmacologic intervention?

J Invest Dermatol

Decorin, versican, and biglycan gene expression by keloid and normal dermal fibroblasts: differential regulation by basic fibroblast growth factor.

Exp Cell Res

Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars.

Clinical challenge and call for research on keloid disorder: meeting report from the 3rd International Keloid Research Foundation Symposium, Beijing 2019.

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Arch Dermatol Res

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Am J Clin Dermatol

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J Drugs Dermatol

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Front Physiol

Risk of cancer development in patients with keloids.

Sci Rep

The increased prevalence of keloids in atopic dermatitis patients with allergic comorbidities: a nationwide retrospective cohort study.

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BMJ Open

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Does vitamin D deficiency predispose to keloids via dysregulation of koebnerisin (S100A15)? a case-control study.

Wound Repair Regen

The TaqI gene polymorphisms of VDR and the circulating 1,25-dihydroxyvitamin D levels confer the risk for the keloid scarring in Chinese cohorts.

Cell Physiol Biochem

A case-control study analyzing the association of keloids with hypertension and obesity.

Int J Dermatol

Keloids and ultrasound detected fibroids in young African American women.

PLoS One

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PLoS Med

Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: a scientific statement from the American Heart Association.

Circulation

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J Stat Softw

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BJOG

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J Epidemiol Community Health

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J Clin Endocrinol Metab

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Am J Clin Nutr

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Ann Nutr Metab

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J Open Source Softw

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Bioinformatics

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Lancet

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Prog Cardiovasc Dis

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Best Pract Res Clin Obstet Gynaecol

Does keloid pathogenesis hold the key to understanding Black/White differences in hypertension severity?

Hypertension

RNA sequencing keloid transcriptome associates keloids with Th2, Th1, Th17/Th22, and JAK3-skewing.

Front Immunol

Periostin is induced by IL-4/IL-13 in dermal fibroblasts and promotes RhoA/ROCK pathway-mediated TGF-ß1 secretion in abnormal scar formation.

J Plast Surg Hand Surg

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J Pharmacol Exp Ther

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J Clin Periodontol

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Arthritis Rheum

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Neurol Neuroimmunol Neuroinflamm

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Keloid disease: clinical relevance of single versus multiple site scars.

Keloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.
To 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).
This 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.
Keloid or hypertrophic scar diagnoses.
Previously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.
Of 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.
This 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.

Comorbidities of Keloid and Hypertrophic Scars Among Participants in UK Biobank.

Comorbidities of Keloid and Hypertrophic Scars Among Participants in UK Biobank

Comorbidities of Keloid and Hypertrophic Scars Among Participants in UK Biobank

Clinical Summary

What was studied

Key findings

Study limitations

Clinical implications

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