DERMATOLOGY EDUCATIONAL RESOURCE

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1 DERMATOLOGY EDUCATIONAL RESOURCE Adjunctive Skincare for Acne ABSTRACT While topical therapy remains a key therapeutic approach in the clinical management of AV, it can be associated with side effects that may compromise the stratum corneum and impair patient adherence. The use of adjunctive cleansers and moisturizers can help mitigate treatment side effects and subsequently enhance therapeutic efficacy. Providing patient-specific skin care recommendations, including product selection and proper use, is an important part of the clinical management of AV and may adjunctively augment the efficacy of topical medications in reducing acne lesions. KEYWORDS: acne vulgaris, adherence, cleansers, moisturizers Introduction Acne vulgaris (AV) is among the most common dermatological disorders seen by dermatologists, affecting approximately 85% of people between the ages of Emerging evidence suggests that acne is associated with epidermal barrier impairments, including stratum corneum (SC) barrier permeability. There is also mounting evidence to demonstrate an association between AV and inherent epidermal barrier dysfunction involving increased filaggrin expression and decreased ceramide levels.2 While topical therapy remains a key therapeutic approach in the clinical management of AV, it can be associated with side effects that may compromise the SC, and impair patient adherence. The use of adjunctive cleansers and moisturizers can help mitigate treatment side effects and subsequently enhance therapeutic efficacy. Pathophysiology and Clinical Presentation The four main pathophysiologic features of AV are listed below 3 : 1. Androgen-mediated stimulation of sebaceous gland activity 2. Abnormal keratinization leading to follicular plugging (comedone formation) ABOUT THE AUTHOR Shannon Humphrey, MD, FRCPC, FAAD, Director of Continuing Medical Education, Clinical Instructor, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada..

2 3. Proliferation of Propionibacterium acnes within the follicle 4. Inflammation Genetic factors, stress, and diet may also influence the development of acne. 3 Some data suggest that patients with AV suffer from inherently compromised facial SC barrier permeability, and that the severity of AV may correlate with the degree of SC barrier impairment, and decreased levels of free sphingosine and total ceramides, suggesting a deficiency of the intercellular lipid membrane. 2 Some medications used to treat AV can alter SC integrity and function, either via the active ingredient, the vehicle, or both. This can result in signs and symptoms of cutaneous irritation such as erythema, scaling, and a burning or stinging sensation. 2 Recent data show that the experience of just one treatment-related side effect (e.g., irritation, dryness, redness) significantly, negatively impacts adherence with acne treatment. 4 Topical Therapy Topical therapy is used for mild to moderate acne and also for maintenance therapy in all severity levels (Table 1). Evidence-based treatment guidelines recommend fixeddose combination topical BPOadapalene or benzoyl peroxide (BPO)-clindamycin for treatment of mild-moderate papulopustular acne. 5 Retinoids are comedolytic, anticomedogenic, and anti-inflammatory. BPO is an antimicrobial agent that has some keratolytic effects and does not contribute to antibiotic resistance. Also, antibiotics have antimicrobial and antiinflammatory effects. They can be used in conjunction with BPO lotion, gel, or wash to limit anti- Table 1: Topical Acne Therapies and Their Pathogenic Targets Acne Pathogenic Factors Retinoids Benzoyl Antibiotics Adapalene Peroxide Clindamycin Tazarotene Erythromycin Tretinoin Reduces production of sebum Targets Propionibacterium acnes X X Normalizes keratinization and desquamation X X Anti-inflammatory X X X Source: Reproduced with permission from: Wilford J and Humphrey S. Topical Acne Therapy Advances Vancouver, BC: Skin Therapy Letters.com. Available at: 18 Journal of Current Clinical Care Volume 5, Issue 1, 2015

3 biotic resistance. They should not be used for maintenance therapy. Additionally, topical dapsone gel is antimicrobial and antineutrophilic and new fixed-dose retinoid-based combination therapies are available; however, both topical retinoids and BPO can cause symptoms of skin irritation. Cleansers and Moisturizers The goal of cleansing for patients with acne or acne-prone skin is to remove surface dirt, sweat, excess oil, exfoliated cells, and microorganisms without irritating or disrupting the skin s protective barrier. Regular use of mild cleansers is an important component of effective acne management as it prepares the skin to receive topical medications, improving drug absorption. Routine cleansing may enhance antimicrobial activity and decrease the risk of infection. Simplified treatment and skin care regimes should be recommended, Adjunctive Skincare for Acne Stratum corneum Stratum lucidum Stratum granulosum Normal Skin Section Epidermis Stratum spinosum Dermis Stratum corneum containing surface dirt, sweat, excess oil, exfoliated cells and micro-organisms. Water rinse Cleanser containing removed dirt, oil, cells, etc. Topical medication 19 Journal of Current Clinical Care Volume 5, Issue 1, 2015

4 including the use of an appropriate moisturizer and washing with a mild, soap-free cleanser twice daily. 4 Types of Cleansers To date, limited published data exist to inform the clinical management of AV with regard to cleansers and moisturizers. Recommendations are based largely on general knowledge (e.g., non-soap). Ideally, cleansers for acne skin should be: non-comedogenic, non-acnegenic, non-irritating, and non-allergenic. 6 A wide spectrum of skin cleansing agents exist for acne ranging from lipid-free cleansers, syndets, and astringents to exfoliants and abrasives. 7 Anionic detergents (i.e., soaps) can alter the natural ph of skin, which is normally between 5.3 and 5.9. An increase in ph can result in increased transepidermal water loss (TEWL), which causes dryness. Further, an increase in ph may facilitate microbial growth, which can exacerbate AV. 8 Abrasive Stratum Corneum Barrier Permeability (Brick Wall Analogy) Healthy Skin SC Barrier Impairment Epidermal barrier is maintained by mortar between bricks Patients with deficiency of intercellular lipid membrane have less mortar between the bricks Moisture Escaping Skin Without SC Barrier Irritants Entering Skin Without SC Barrier 20 Journal of Current Clinical Care Volume 5, Issue 1, 2015

5 cleansers can promote SC barrier dysfunction and contribute to signs and symptoms of irritation. These should be avoided. Suitable cleansers for acneprone skin are generally based on mild synthetic surfactants that minimize the potential for skin barrier disturbances such as: 21 Journal of Current Clinical Care Volume 5, Issue 1, 2015 Non-ionic surface-acting agents (e.g., silicone and polysorbate) are less likely to cause irritation and are formulated to the same ph as the skin (5.5). Silicone surfactants (e.g., dimethicone) such as Spectro, are effective at eliminating surface debris without completely stripping away protective oils. Cleansers containing emollients, such as Cetaphil DermacControl, CeraVe and Spectro can minimize damage to the SC barrier by emulsifying dirt and oil for easy removal. Additionally, Cetaphil Dermacontrol and CeraVe contain ceramide lipids which work to replace those lost during washing. Cleansers that contain zinc coceth and zinc gluconate, such as Cetaphil Dermacontrol, also provide astringent properties without irritation or alteration to the ph level of the skin, and the zinc complex absorbs excess oil for a matte appearance of the skin. Types of Moisturizers Effective moisturizers combine humectants and emollients to prevent or reduce water evaporation, draw moisture up from deeper layers, alleviate xerosis, and maintain skin barrier integrity, and they should also prevent primary irritation. As well, broad-spectrum UVA/UVB protection is also important for patients with AV, particularly for those on topical and systemic retinoid therapy. 9 The different classes of moisturizers include: occlusives, humectants, emollients, protein rejuvenators, and ceramide-dominant (Table 2). Ceramide-dominant moisturizers contain lipids that are similar to the intercellular lipids found within the SC. The combinations of these lipids, specifically ceramide, cholesterol and fatty acids, aid in repairing the lipid bilayers and SC barrier function which are affected by extreme dry, cold weather conditions, soaps, solvents, and some medications, by replacing key, naturally occurring lipid components.10 The only published clinical trial data studying adjunctive moisturizer in AV patients is Cetaphil (DermaControl: CDM). It contains ceramides and an oil-absorbing zinc complex. It is non-comedogenic, non-irritating, non-acnegenic and non-greasy.

6 Table 2: Different Classes of Moisturizers Class How does it Work? Example ingredient What is it used for? Possible side effects 1. Occlusive It physically blocks Petrolatum Xerosis Messy water loss Lanolin Atopic dermatitis Some can cause Mineral Prevention of folliculitis (mineral oil) Oil irritant contact May cause pimples Zinc oxide dermatitis Some may cause contact dermatitis (lanolin) 2. Humectants Attracts water to Glycerin Xerosis Some may cause the stratum corneum Sorbitol Ichthyosis irritation (urea, lactic Urea Skin rejuvenation acid) Alpha-hydroxy acids Sugars 3. Emollients Smoothes skin by Cholesterol Reduces skin Not always effective filling the spaces Squalene roughness between skin flakes, Fatty acids with droplets of oil 4. Rejuvenators Claims to rejuvenate Collagen Skin rejuvenation Unlikely to work the skin by Keratin because the protein replenishing Elastin molecules are too essential proteins large to cross the epidermis Some may cause contact dermatitis 5. Ceramide- Replaces ceramides Ceramides, Cholesterol, Ceramide lipid Efficacy may be dominant deficient in skin barrier fatty acids replacement impaired in severe SC lipid barrier repair disease Prevention of transepidermal water loss Occlusive effect to prevent water loss, repair lipid layers, restore barrier Table adapted from acneguide.ca. 22 Journal of Current Clinical Care Volume 5, Issue 1, 2015

7 Additionally, moisturizers that contain zinc gluconate, such as CDM, may provide sebum regulation. The recent development of oleosome technology, which is also present in CDM, enables the delivery of broad-spectrum UVA/UVB sun protection (SPF 30). This technology effectively reduces the concentration of filters being applied to the skin, reducing the potential for skin sensitivity reactions. 9 Acne Therapy and Adherence Treatment adherence in patients with AV is a significant problem and is documented at approximately 50%. 4 An estimated Table 3: Strategies to Reduce Irritation Associated with Topical Acne Therapy Topical Therapy Active Topical Therapy Vehicle Application Technique Adjunctive Skincare Counseling 23 Journal of Current Clinical Care Volume 5, Issue 1, 2015 careful selection of topical therapy partially solubilized or micronized retinoid combination therapy to minimize irritation cream > gel hydrogel > alcohol gel excipients (humectants, emollients) 1g applied to DRY face QHS with emollient consider alternate days consider short contact Gentle, non comedogenic cleanser & emollient expectations application technique strategies to mitigate AEs 30 40% of patients using topical acne treatment formulations do not comply with their prescribed regimen. 11 Irritation resulting from topical medications and the emergence of bacterial resistance to both topical and oral antibiotics remain significant barriers to good treatment adherence. Recent advances in vehicle technology have improved efficacy, local tolerance, and adherence. 12 Additionally, novel delivery mechanisms, such as pumps, are convenient and preferred by patients, which may also improve adherence. 13 The appropriate selection and use of moisturizers has positive effects on treatment adherence. 4 Alleviating dryness and improving skin comfort by using a moisturizer concomitantly with retinoid therapy could enhance treatment efficacy. Data from a randomized, split-face study showed the application of a ceramide dominant moisturizer applied twice daily for 15 days by patients taking either oral isotretinoin (10 20 mg) for at least two months or topical tretinoin 0.05% for at least one month provided significant improvements, compared with baseline, in the levels of skin dryness, roughness, and desquamation induced by either drug. 14 As well, skin properties and discomfort were substantially improved. Some strategies to reduce irritation associated with topical acne therapy are outlined in Table 3.

8 SUMMARY OF KEY POINTS Irritation resulting from topical medications and the emergence of bacterial resistance to both topical and oral antibiotics remain significant barriers to good treatment adherence. Providing patient-specific skin care recommendations, including product selection and proper use, is an important part of the clinical management of AV and may adjunctively augment the efficacy of topical medications in reducing acne lesions. Alleviating dryness and improving skin comfort by using a moisturizer concomitantly with retinoid therapy could enhance treatment efficacy. The adjunctive use of appropriate gentle soap-free cleansers and non-comedogenic moisturizers that also restore SC barrier function, provide SPF protection, and reduce side effects of topical acne therapy is recommended and is preferred by patients and will likely improve treatment adherence.. A randomized, open label, investigator blinded split-face study of erythema, scaling, and dryness in patients using a ceramide dominant lotion formulated for acne prone skin with 0.05% tretinoin found a patient preference for the moisturizer. While both sides developed skin irritation, it worsened in the nonmoisturized sides. Notably, all five parameters, namely erythema, scaling, dryness, stinging/burning and pruritus were improved on sides with moisturizer. 9 Conclusion Because the skin barrier can be impaired in patients with AV, treatment can be negatively impacted, which can further exacerbate skin barrier defects and acne pathogenesis. Therefore, providing patient-specific skin care recommendations, including product selection and proper use, is an important part of the clinical management of AV and may adjunc- + CLINICAL PEARLS Topical dapsone gel is antimicrobial and antineutrophilic and new fixed-dose retinoid-based combination therapies are available and this allows us to improve adherence with therapy and target multiple pathogenic mechanisms with one treatment. Oleosome technology enables the delivery of broad-spectrum UVA/UVB sun protection (SPF 30). This technology effectively reduces the concentration of filters being applied to the skin, reducing the potential for skin sensitivity reactions. 24 Journal of Current Clinical Care Volume 5, Issue 1, 2015

9 tively augment the efficacy of topical medications in reducing acne lesions. 2 The adjunctive use of appropriate gentle soap-free cleansers and non-comedogenic moisturizers, ideally products that also restore SC barrier function, provide SPF protection, and reduce side effects of topical acne therapy, is recommended. Moreover, this approach is preferred by patients and will likely improve treatment adherence. This article was first published in Skintherapy letter online References 1. Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol 49(3 Suppl):S (2003 Sep). 2. Thiboutot D and Del Rosso JQ. Acne vulgaris and the epidermal barrier. J Clin Aesthet Dermatol 2013;6(2): Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004;292(6): Dréno B, Thiboutot D, Gollnick H, et al. Large-scale worldwide observational study of adherence with acne therapy. Int J Dermatol 2010;49(4): The Guideline Subcommittee Acne of the European Dermatology Forum. European Dermatology Forum guideline on treatment of acne. Berlin: Author; Available at: pdf. 6. Solomon BA, et al. Clin Dermatol.1996;14:95 9. <AU: Please insert article title> 7. Mukhopadhyay P. Cleansers and their role in various dermatological disorders. Indian J Dermatol 2011; 56(1):2 6. Available at: pmc/articles/pmc /. 8. Decker A and Graber EM. Over the counter acne treatments. J Clin Asthet Dermatol 2012;5(5): Available at: PMC /. 9. E. Schorr, F. Sidou, N. Kerrouche, J.Drugs in Dermatol 2012;11(9) Marino C. Skin physiology, irritants, dry skin, and moisturizers. Washington State Department of Labor and Industries (revised 2006). Available at: skin_phys.pdf. 11. Finlay AY. J Eur Acad Dermatol Venereol. 1999;12(Suppl 2):S Koo J. How do you foster medication adherence for better acne vulgaris management? Skinmed. 2003;2(4): Vender R, et al. Patient preferences in acne: a pointof-care educational initiative. Poster presentation. <AU: Please add the name, location, and date for the conference.> 14. Laquieze S, Czernielewski J, Rueda MJ. Beneficial effect of a moisturizing cream as adjunctive treatment to oral isotretinoin or topical tretinoin in the management of acne. J Drugs Dermatol 2006;5(10): Journal of Current Clinical Care Volume 5, Issue 1, 2015