membrane pore-forming toxins termed Christie-Atkins-Munch- Petersen (CAMP) factors that may stimulate TLR-2;47-52 plasmids that promote bacterial adhesion and biofilm formation;29 lyases that degrade hyaluronic acid and the extracellular matrix, propagating inflammation;46 porphyrins that induce oxidative stress/damage;53,54 and reduced loss of clustered regularly interspaced short palindromic repeats (CRISPR) loci allowing increased horizontal acquisition of virulent traits.55 Furthermore, virulent C. acnes may also have an increased resistance to erythromycin, clindamycin, and tetracycline classes of antibiotics.56,57 This presents potential concern for indiscriminate, inadvertent eradication of commensal organisms (including C. acnes phylotype II and III) within already pathologic follicular and superficial CM, allowing any remaining phylotype IA1 to flourish.
While C. acnes typically dominates the follicular microbiome, even in AV-prone skin, it does coexist with other microbes (eg, Malassezia spp. fungi, S. epidermidis, and bacteriophages).58 Of particular interest is S. epidermidis, which has shown potential to limit C. acnes growth in vitro,59 and (C. acnes specific) bacteriophages.60-63 These bacteriophages, which are significantly more abundant in healthy skin vs. acne-prone skin (P<.05) may modulate the microbiome in vitro by facilitating the exchange of virulence factors and preferentially killing specific bacteria.14,60,61
Harnessing the natural "predator-prey" relationship of these organisms may have potential as a targeted, non-antibiotic AV therapy.59 Studies also suggest that isotretinoin may achieve its durable therapeutic response by inducing a "sebaceous drought", resetting the follicular microbiome, and allowing a more diverse CM to repopulate.64-66
Rosacea
Barrier Dysfunction
Many of the clinical signs of EBD (hyperirritability, burning, stinging, and sensitivity to common OTC skincare products) are hallmarks of rosacea.17,67,68 EBD may also explain rosacea triggers, including extreme climates and UV exposure and increased likelihood of positive patch test (and risk of allergic/ irritant contact dermatitis).67,69 This may be due in part to a significantly more alkaline central facial skin (pH 5.7 vs 5.2, P=.026) and materially different skin surface lipid composition.70
EBD in rosacea appears localized to areas of (and those adjacent to) inflammation.71-73 In a study of unaffected nasolabial-fold and volar-arm skin in rosacea patients (n=28) and age/gendermatched controls (n=32), nasolabial-fold skin in rosacea patients had materially higher TEWL than healthy controls (21.1 vs 16.8, P=0.127) and significantly lower SC hydration (SCH) (16.5 vs 24.4, P<.001); these trends were not observed in the volar forearm.71 Evaluations using topically-applied lactic acid to elicit irritation (ie, lactic acid stinger test [LAST]) have found individuals with erythematotelangiectatic-predominant (ETR) and papulopustular-predominant (PPR) rosacea to be significantly more likely to have a positive (75% vs 18.8%, P<.001) and greater LAST response (P<.001).72,74 Worsening TEWL and SCH also correlated with LAST scores and patients’ perception of sensitive skin.72
EBD may also correlate with rosacea severity. Not only does concomitant use of more physiologic pH cleansers and moisturizers minimize adverse effects of prescription therapy, but they may also have additive effects in reducing rosacea severity (Table 2).75-79 A 6-week investigative trial with oral minocycline 100 mg daily, in the absence of topical intervention, has also
While C. acnes typically dominates the follicular microbiome, even in AV-prone skin, it does coexist with other microbes (eg, Malassezia spp. fungi, S. epidermidis, and bacteriophages).58 Of particular interest is S. epidermidis, which has shown potential to limit C. acnes growth in vitro,59 and (C. acnes specific) bacteriophages.60-63 These bacteriophages, which are significantly more abundant in healthy skin vs. acne-prone skin (P<.05) may modulate the microbiome in vitro by facilitating the exchange of virulence factors and preferentially killing specific bacteria.14,60,61
Harnessing the natural "predator-prey" relationship of these organisms may have potential as a targeted, non-antibiotic AV therapy.59 Studies also suggest that isotretinoin may achieve its durable therapeutic response by inducing a "sebaceous drought", resetting the follicular microbiome, and allowing a more diverse CM to repopulate.64-66
Rosacea
Barrier Dysfunction
Many of the clinical signs of EBD (hyperirritability, burning, stinging, and sensitivity to common OTC skincare products) are hallmarks of rosacea.17,67,68 EBD may also explain rosacea triggers, including extreme climates and UV exposure and increased likelihood of positive patch test (and risk of allergic/ irritant contact dermatitis).67,69 This may be due in part to a significantly more alkaline central facial skin (pH 5.7 vs 5.2, P=.026) and materially different skin surface lipid composition.70
EBD in rosacea appears localized to areas of (and those adjacent to) inflammation.71-73 In a study of unaffected nasolabial-fold and volar-arm skin in rosacea patients (n=28) and age/gendermatched controls (n=32), nasolabial-fold skin in rosacea patients had materially higher TEWL than healthy controls (21.1 vs 16.8, P=0.127) and significantly lower SC hydration (SCH) (16.5 vs 24.4, P<.001); these trends were not observed in the volar forearm.71 Evaluations using topically-applied lactic acid to elicit irritation (ie, lactic acid stinger test [LAST]) have found individuals with erythematotelangiectatic-predominant (ETR) and papulopustular-predominant (PPR) rosacea to be significantly more likely to have a positive (75% vs 18.8%, P<.001) and greater LAST response (P<.001).72,74 Worsening TEWL and SCH also correlated with LAST scores and patients’ perception of sensitive skin.72
EBD may also correlate with rosacea severity. Not only does concomitant use of more physiologic pH cleansers and moisturizers minimize adverse effects of prescription therapy, but they may also have additive effects in reducing rosacea severity (Table 2).75-79 A 6-week investigative trial with oral minocycline 100 mg daily, in the absence of topical intervention, has also
