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Systemic Comorbidities of Keloid and Hypertrophic Scars: A Phenome-Wide Association Study in a Multiethnic U.S.
Fatemeh Vahidnezhad1,2,3, Noosha Samieefar4,5, Mahdi Akbarzadeh6
1Division of Genetic and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Insights
Excessive scarring (ES) in children is linked to various health issues beyond skin problems, including respiratory and sensory disorders. This highlights potential systemic immune and developmental dysregulation, requiring further investigation.
Area of Science:
- Pediatric Health
- Dermatology
- Genetics
Background:
- Excessive scarring (ES), encompassing keloids and hypertrophic scars, significantly impacts children's physical function, appearance, and quality of life.
- The full spectrum of pediatric comorbidities associated with ES is not well-defined, hindering effective anticipatory guidance and multidisciplinary care strategies.
Purpose of the Study:
- To investigate the comorbidity spectrum of excessive scarring (ES) in a diverse pediatric cohort.
- Utilize a phenome-wide association study (PheWAS) approach to identify associated health conditions.
Main Methods:
- A population-based study using longitudinal electronic health record (EHR) data from The Children's Hospital of Philadelphia (CHOP) starting in 2006.
- Diagnosis codes (ICD-9-CM, ICD-10-CM) were mapped to 3109 phenotype codes (PheCodes).
- Phenome-wide association studies (PheWAS) were performed using logistic regression with Bonferroni correction for multiple testing.
Main Results:
- Out of 86,092 pediatric participants, 662 (0.77%) had ES. PheWAS identified 154 significant associations across 16 disease categories, with 105 novel findings.
- Dermatologic phenotypes (18%) were most common, including acne, eczema, and infections.
- Significant associations were also found in respiratory (14%), sense organ (12%), and infection-related (9%) categories, including asthma, hearing impairment, and susceptibility to viral/fungal infections.
Conclusions:
- Pediatric excessive scarring (ES) suggests localized wound-healing issues and potential systemic immune, developmental, and proliferative dysregulations.
- Further genetic and mechanistic studies are crucial to understand causal pathways.
- Emphasizes the need for multidisciplinary surveillance extending beyond dermatology for comprehensive pediatric care.
Background:
Excessive scarring (ES), including keloids and hypertrophic scars, impairs function, appearance, and quality of life in children. Its pediatric comorbidity spectrum is not well defined, limiting anticipatory guidance and multidisciplinary care. This research aims to investigate comorbidities of ES in a diverse pediatric cohort using a phenome-wide association study (PheWAS).
Methods:
This population-based study leveraged longitudinal electronic health record (EHR) data from participants enrolled in the Children's Hospital of Philadelphia (CHOP) from 2006. Diagnosis codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] and Tenth Revision [ICD-10-CM]) were mapped to 3109 phenotype codes (PheCodes). PheWAS analyses were conducted using logistic regression, with Bonferroni correction applied to account for multiple testing.
Results:
Among 86,092 pediatric participants, 662 (0.77%) were identified with ES; the remaining served as controls. Multivariable PheWAS screening identified 154 significant associations across 16 disease categories, of which 105 were not reported previously to our knowledge. Dermatologic phenotypes (n = 28; 18%) were most enriched, including acne and other follicular disorders, eczema, pigmentary changes, papulosquamous and granulomatous disorders, and cutaneous infections. Respiratory phenotypes (n = 21; 14%) included respiratory failure, pneumonia, asthma, allergic rhinitis, pharyngitis, and tonsillar hypertrophy. Sense organ disorders (n = 19; 12%) comprised conjunctivitis, refractive errors, otitis, and hearing impairment. Infection-related phenotypes (n = 14; 9%) highlighted susceptibility to viral (influenza, human papillomavirus [HPV], molluscum contagiosum), fungal (candidiasis, dermatophytosis), and bacterial infections.
Conclusions:
These findings suggest that ES in children indicates not only localized wound-healing impairment, but also systemic immune, developmental, and proliferative dysregulations, emphasizing the need for genetic and mechanistic studies to clarify causal pathways and multidisciplinary surveillance beyond dermatologic care.
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