Patients with Atopic Dermatitis Colonized with Staphylococcus aureus Have a Distinct Phenotype and Endotype

Abstract

Patients with atopic dermatitis (AD) are commonly colonized with Staphylococcus aureus (AD S. aureus⁺), but what differentiates this group from noncolonized AD patients (AD S. aureus^-) has not been well studied. To evaluate whether these two groups have unique phenotypic or endotypic features, we performed a multicenter, cross-sectional study enrolling AD S. aureus⁺ (n = 51) and AD S. aureus^- (n = 45) participants defined by the presence or absence of S. aureus by routine culture techniques and nonatopic, noncolonized control individuals (NA S. aureus^-) (n = 46). Filaggrin (FLG) genotypes were determined, and disease severity (Eczema Area and Severity Index, Rajka-Langeland Severity Score, Investigator's Global Assessment score, Numerical Rating Scale, and Dermatology Life Quality Index) was captured. Skin physiology was assessed (transepidermal water loss [TEWL], stratum corneum integrity, hydration, and pH), and serum biomarkers were also measured. We found that AD S. aureus⁺ patients had more severe disease based on all scoring systems except itch (Numerical Rating Scale), and they had higher levels of type 2 biomarkers (eosinophil count, tIgE, CCL17, and periostin). Additionally, AD S. aureus⁺ patients had significantly greater allergen sensitization (Phadiatop and tIgE), barrier dysfunction (TEWL and stratum corneum integrity), and serum lactate dehydrogenase (LDH) than both the AD S. aureus^- and NA S. aureus^- groups. FLG mutations did not associate with S. aureus⁺ colonization. In conclusion, adult patients with AD who are colonized on their skin with S. aureus have more severe disease, greater type 2 immune deviation, allergen sensitization, barrier disruption, and LDH level elevation than noncolonized patients with AD.

Figure 1

Skin Barrier Measurements by diagnostic group and the absence or presence of S. aureus skin colonization. (a) TEWL AUC was highest in ADS. aureus+ group and distinguished all three groups from each other. (b) Basal TEWL was highest in the ADS. aureus+ group compared to the ADS. aureus− and NAS. aureus− groups. AD S. aureus− was not different than NAS. aureus− group. (c) A borderline trend for lower SC hydration was observed in ADS. aureus+ group compared to the ADS. aureus− group and both AD groups were lower than the NAS. aureus− group. (d) Skin pH was not different between the three patient groups. Means (or geometric means for plots on the log scale) are displayed as black diamonds. Box plots are displayed. Comparisons of values (or log₁₀ values for plots on the log scale) are computed using a generalized linear mixed model adjusting for gender, age, site and FLG mutation status.

Figure 2

Peripheral Blood Biomarkers by diagnostic group and the absence or presence of S. aureus skin colonization. (b) Serum total IgE (c) peripheral eosinophil counts and (d) TARC (CCL17) were highest in the ADS. aureus+ group and distinguished all three groups from each other. (a) Serum LDH and (f) sIL-2R were highest in the ADS. aureus+ group compared to the ADS. aureus− and NAS. aureus− groups. ADS. aureus− and NAS. aureus− groups did not differ. (e) Periostin (OSF-2) was greater in the ADS. aureus+ than the ADS. aureus− group and had a borderline trend for greater values compared to the NAS. aureus− group. Means (or geometric means for plots on the log scale) are displayed as black diamonds. Box plots are displayed. Comparisons of values (or log₁₀ values for plots on the log scale) are computed using a generalized linear mixed model adjusting for gender, age, site and FLG mutation status. For serum total IgE, 1 kAU/mL = 1000 kAU/L.

Figure 2

Peripheral Blood Biomarkers by diagnostic group and the absence or presence of S. aureus skin colonization. (b) Serum total IgE (c) peripheral eosinophil counts and (d) TARC (CCL17) were highest in the ADS. aureus+ group and distinguished all three groups from each other. (a) Serum LDH and (f) sIL-2R were highest in the ADS. aureus+ group compared to the ADS. aureus− and NAS. aureus− groups. ADS. aureus− and NAS. aureus− groups did not differ. (e) Periostin (OSF-2) was greater in the ADS. aureus+ than the ADS. aureus− group and had a borderline trend for greater values compared to the NAS. aureus− group. Means (or geometric means for plots on the log scale) are displayed as black diamonds. Box plots are displayed. Comparisons of values (or log₁₀ values for plots on the log scale) are computed using a generalized linear mixed model adjusting for gender, age, site and FLG mutation status. For serum total IgE, 1 kAU/mL = 1000 kAU/L.

Figure 3

Relationship between serum LDH and skin barrier measurements in ADS. aureus+ and ADS. aureus− participants. LDH is strongly associated with (a) Basal TEWL, (b) SC hydration and (c) trends toward an association with TEWL AUC. The estimated geometric mean ratio (95% CI) reflects a percent change ([1-estimate] x 100) in the response variable for a 10 unit increase in LDH for Basal TEWL and TEWL AUC. The estimate for SC Hydration represents a .94 unit decrease in SC Hydration for every 10 unit increase in LDH. All estimates are computed using a generalized linear mixed model adjusting for diagnostic group, age, site, gender and FLG genotype. The regression line represents an ADS. aureus+ male of median age (38 years old) with wild-type filaggrin status from the URMC study site.