Atopic Eczema Significantly Associated With Excessive Scarring in New UK Analysis

The influence of comorbidities on disfigurement from keloid and hypertrophic scars (excessive scarring) has been investigated in a new comprehensive analysis of data from the UK Biobank, with the results highlighting the need for additional research into the pathophysiology of excessive scarring. In particular, atopic eczema was found to have significant associations with excessive scarring.

Although they stem from similar causes—in both cases, cutaneous injury and irritation—keloid scars persist while hypertrophic scars can dissipate over time following skin-related wounds. The investigators of this multicenter cross-sectional population-based cohort study published in JAMA Dermatology used data on several established comorbidities of excessive skin scarring—hypertension, uterine leiomyoma, vitamin D deficiency, and atopic eczema—to validate previous findings and to potentially uncover new comorbidities.

“Understanding disease comorbidities has both biological and clinical benefits, such as highlighting novel mechanisms and offering opportunities for targeted and early clinical intervention,” the investigators wrote. “Previous studies of keloid and hypertrophic scar comorbidities have been limited to candidate diseases, based on speculated biological or demographic similarities.”

Their 230,078-patient population encompassed a study group of 972 persons with excessive scarring identified via diagnostic codes (n = 740, keloid scar; n = 110, hypertrophic scar; n = 177, either type of scar) and a control group with 229,106 healthy persons. The study group had more female patients (65% vs 55%) but fewer patients of a White ethnicity (86% vs 95%). Mean (SD) overall age was 64 (8) years.

The self-reported ethnic backgrounds of the entire patient cohort were Asian or Asian British (2.1%), Black or Black British (1.1%), Chinese (0.3%), Mixed (0.5%), White (94.9%), and other (0.7%). Among the 3 ethnicities most represented, Black patients had the highest prevalence of excessive scarring compared with Asian patients and White patients: 2.4% vs 1.1% vs 0.4%.

Across all participants, the most common comorbidity was hypertension in 37.2% of the scar-affected group and 34.3% of the control group. This was followed by uterine leiomyoma in 14.5% and 11.2%, respectively; atopic eczema in 10.2% and 5.8%; and vitamin D deficiency in 5.1% and 2.4%.

“All previously studied comorbidities (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) were more prevalent for individuals with excessive scarring,” the authors wrote. They added that differences were not seen in these primary comorbidities within the group with excessive scarring between those who did or did not receive treatment.

Two models were used to investigate independent associations with excessive scarring:

• The “minimal model” adjusted for age, sex (uterine leiomyoma was restricted to female participants), and ethnicity
• The “full model” adjusted for age; sex (except uterine leiomyoma); ethnicity; the influences of body mass index (BMI), Townsend Deprivation Index (TDI), and smoking status on hypertension, uterine leiomyoma, and vitamin D deficiency; and the influences of BMI, TDI, allergic rhinitis, and asthma on atopic eczema

The 4 comorbidities were universally associated with excessive scarring. With the minimal model, the risks were higher by 20% (odds ratio [OR], 1.20; 95% CI, 0.96-1.51) from uterine leiomyoma, 24% (OR, 1.24; 95% CI, 1.08-1.43) from hypertension, 42% (OR, 1.42; 95% CI, 1.05-1.93) from vitamin D deficiency, and 78% (OR, 1.78; 95% CI, 1.44-2.19). With the full model, the corresponding higher risks were 19% (OR, 1.19; 95% CI, 0.95-1.49), 11% (OR, 1.11; 95% CI, 0.96-1.30), 47% (OR, 1.47; 95% CI, 1.08-1.99), and 68% (OR, 1.68; 95% CI, 1.36-2.07).

However, with the minimal model, statistically significant associations were only seen between excessive scarring and hypertension (P = .002) or atopic eczema (P < .001). And with the full model, only presence of atopic eczema lent itself to a significant association (P < .001).

The authors’ subanalysis of the self-reported ethnicity data provided these findings:

• Among Black participants, there were nominally significant associations between excessive scarring and hypertension (OR, 2.05; 95% CI, 1.13-3.72; P = .02) or uterine leiomyoma (OR, 1.93; 95% CI, 1.00-3.71; P = .05)
• Among Asian participants, there was a significant association between excessive scarring and vitamin D deficiency (OR, 2.24; 95% CI, 1.26-3.97; P = .006)
• For atopic eczema: Among White participants, there was a highly significant association with excessive scarring (OR, 1.68; 95% CI, 1.34-2.12; P < .001); among Asian participants, a nominally significant association (OR, 2.17; 95% CI, 1.01- 4.67; P = .048); and among Black participants, an association that trended toward statistical significance (OR, 1.89; 95% CI, 0.83-4.28; P = .13)

A final discovery analysis of outcomes in the excessive scarring group, a phenome-wide association study, screened 1518 phecodes across 17 disease states. Within this subanalysis, the investigators found the strongest associations for excessive scarring with sebaceous cyst (P = 9.45 × 10⁻³⁰), nonepithelial skin cancer (P = 2.03 × 10⁻²⁵), diseases of hair/hair follicles (P = 1.50 × 10⁻²²), and infections of skin/subcutaneous tissue, seborrheic keratosis, actinic keratosis, acne, and atopic/contact dermatitis (all, P < 1.0 × 10⁻¹¹).

“Using currently available clinical codes within UK Biobank, we were only able to establish heterogeneous excessive scarring cases based on potentially subjective clinical assessment, without clinicopathological correlation,” the authors concluded. “Nonetheless, our results add to what is already known in the literature, as evidenced by the detection of both previously reported and novel associations.”

The generalizability of these findings to other patient populations should be investigated in future studies, they emphasized.

Reference

Ung CY, Warwick A, Onoufriadis A, et al. Comorbidities of keloid and hypertrophic scars among participants in UK Biobank. JAMA Dermatol. Published online January 4, 2023. doi:10.1001/jamadermatol.2022.5607