Moisturizers and Ceramide-containing Moisturizers May Offer Concomitant Therapy with Benefits

| March 26, 2014

Chuck W. Lynde, MD, FRCPC; Anneke Andriessen, PhD; Benjamin Barankin, MD, FRCPC; Gillian de Gannes, MD, FRCPC; Wayne Gulliver, MD, FRCPC; Richard Haber, MD, FRCPC; Catherine McCuaig, MD, FRCPC; Poonam Rajan, MD, DABD, FRCPC(C); Sandra P. Skotnicki, MD, FRCPC; Richard Thomas, MD, FRCPC; Jack Toole, MD, FRCPC; Ron Vender, MD, FRCPC

Chuck W. Lynde, MD, FRCPC, is from University of Toronto, Toronto, Ontario, Canada; Anneke Andriessen, PhD, is from Andriessen Consultants, Malden & UMC St Radboud, Nijmegen, The Netherlands; Benjamin Barankin, MD, FRCPC, is from Toronto Dermatology Center, Toronto, Ontario; Gillian de Gannes, MD, FRCPC, is from Vancouver, British Columbia, Canada; Wayne Gulliver, MD, FRCPC, is from St. John’s, The Netherlands; Richard Haber, MD, FRCPC, is from University of Calgary, Calgary, Alberta, Canada; Catherine McCuaig, MD, FRCPC, is from Montreal, Quebec, Canada; Poonam Rajan, MD, DABD, FRCPC(C), is from Toronto, Ontario, Canada; Sandra P. Skotnicki, MD, FRCPC, is from Toronto, Ontario, Canada; Richard Thomas, MD, FRCPC, is from The University of British Columbia, Vancouver, British Columbia, Canada; Jack Toole, MD, FRCPC, is from University of Manitoba, Winnipeg, Manitoba, Canada; Ron Vender, MD, FRCPC, is from McMaster University, Hamilton, Ontario, Canada.

Disclosure: The panel consisted of 11 nationally recognized dermatologists who practice in Canada in medical dermatology. The meeting was held during the Canadian Dermatology Update 2011 conference in Montreal. The participating panel members received a stipend.

Abstract
Introduction: Ceramide-containing moisturizers may offer benefits as an adjunct to acne treatment. Methods: An expert panel of 11 Canadian dermatologists, including an international clinical scientist, used the following modified Delphi process: 1) A systematic literature review for acne treatment, dry skin, irritation, depletion of ceramides in acne, and benefits of moisturizers and ceramide-containing moisturizers was conducted; 2) panel members gave their opinion on the resulting statements, taking into account their treatment practices; 3) a panel meeting was held during the 2011 Canadian Dermatology Update to determine final statements; 4) the panel reviewed the final document. Results: The panel reached the following consensus (11/11): 1) A very important reason for nonadherence to acne treatment is dry skin and irritation; 2) skin barrier dysfunction may contribute to acne; 3) dry skin and irritation commonly results from topical acne treatment; 4) dry skin and irritation commonly results from systemic retinoid therapy; 5) moisturizers can improve dryness and irritation resulting from acne treatment; 6) ceramide-containing moisturizers may enhance adherence and complement existing acne therapies; 7) adjunctive therapy with moisturizers should be considered in acne-treated patients. Conclusion: The panel proposes that adjunctive therapy with moisturizers, particularly ceramide-containing moisturizers, should be considered in acne-treated patients.  (J Clin Aesthet Dermatol. 2014;7(3):18–26.)

Acne vulgaris is a chronic inflammatory dermatosis that consists clinically of open and closed comedones, papules, pustules, and nodules.[1] It is a common skin disease, affecting 40 to 50 million individuals of all races and ethnicities.[2–4] Acne vulgaris traditionally is thought to be related to hormonal factors producing excess sebum production leading to open and closed comedones, papules, pustules, and cysts. New developments have looked at additional pathogenic factors, such as altered sebum lipid quality, regulation of steroidogenesis in the skin, interaction with neuropeptidases, androgen activity, and nutrition.[5]

There are multiple acne therapies, including systemic and topical retinoids, antibacterials, systemic and topical antibiotics, and benzoyl peroxide (BPO).[6–9]
Many of the medications that are typically used can cause skin irritation and dry skin conditions and may lead to nonadherence and thus treatment failure.[10–13] Other reasons for nonadherence may be the complexity of the treatment and unattractive aspect of the treatment products. Optimal skin care, such as the concomitant use of moisturizers including ceramide-containing moisturizers as an adjunct to acne treatment, may offer therapeutic benefits. A modified Delphi panel procedure was used to explore this further.

Role of the panel
An expert panel was established to explore possible benefits to the use of moisturizers and ceramide-containing moisturizers for acne patients. The panel comprised 11 nationally recognized dermatologists, who practice in Canada in medical dermatology, including an advisor with an international clinical and scientific background in this field. The group included: Chuck W. Lynde, MD, FRCPC; Anneke Andriessen, PhD; Benjamin Barankin, MD, FRCPC; Gillian de Gannes, MD, FRCPC; Wayne Gulliver, MD, FRCPC; Richard Haber, MD, FRCPC; Catherine McCuaig, MD, FRCPC; Poonam Rajan, MD, DABD, FRCPC(C); Sandra P. Skotnicki, MD, FRCPC; Richard Thomas, MD, FRCPC; Jack Toole, MD, FRCPC; Ron Vender, MD, FRCPC.

The panel population is representative of the healthcare providers likely to assess and to treat patients with acne. The care described by the panel may be better than typical acne skin care because panel members treat a high proportion of patients with acne and are well-trained in this area. However, selecting a panel composed of opinion leaders was deemed appropriate to ensure that a high quality of care is established.

Methods
The procedure. A systematic literature review was carried out on PubMed and Google for topical acne treatment and skin irritation as well as dry skin conditions, depletion of ceramides in acne patients’ skin, and possible benefits of the use of moisturizers in general and ceramide-containing moisturizers in particular (Table 1). Further, a secondary analysis of related citations and references was conducted. The following keywords were used: topical acne treatment, adherence, concordance, efficacy, safety, tolerability, dry skin, skin irritation, moisturizers and acne, ceramide-containing moisturizers and acne, depletion of ceramides and acne, adjunctive treatment with ceramide-containing moisturizers.

Results of the literature search. Seventy-two studies were identified, 58 of which were selected for the panel discussion (Figure 1). The results were checked for the inclusion criteria and trial quality using a standardized literature evaluation form. Existing systematic reviews (e.g., Cochrane) and other guidelines served as additional steering for the body of evidence used. Pooling of the studies was not attempted due to the lack of common outcome measures and endpoints. A limitation was that most studies looked at acne treatment and did not specifically consider the evaluation of moisturizers as an adjunct therapy. The discarded studies were mostly poor quality or were reviews of already included studies. The literature search findings were categorized according to the level of evidence (Table 2). The results showed that in general, dry skin and skin irritation in acne treatment are reasons for acne patients not to adhere to treatment leading to poor outcomes.[10–19]

Research suggests that lipid bilayer deficiencies compromise skin barrier integrity, with dry skin being the most common adverse effect.[6–14] Furthermore, acne patients have a deficiency in total ceramides and free sphingosine.[5,20–25] Therefore, skin barrier dysfunction, coupled with various triggering events, may contribute to the signs and symptoms of acne.[3,5,22–25] There is evidence of benefits of the use of moisturizers as well as application of ceramides containing moisturizers.[18,21,26–32] The goal of use of moisturizers is to improve skin condition reducing irritation and inflammation.[33–39] This may result in a more rapid improvement in the acne and skin condition than could be achieved in other circumstances and also improve patient adherence and treatment efficacy.[34] In vitro and in vivo studies showed a strong antimicrobial effectiveness of skin-identical phytosphingosine produced by ceramides.[36–39] Both in vitro and in vivo, the phytosphingosine-containing product showed excellent clinical results in the context of skin care in acne, based on both anti-inflammatory and antimicrobial activity.[37–41]

These results demonstrate the potential of ceramide-containing products to enhance or complement existing acne therapies acting as an active cosmetic ingredient. The findings were summarized as follows: reasons for nonadherence to topical acne treatment (Table 3), skin irritation as a result of topical acne treatment (Table 4), skin barrier dysfunction in acne (Table 5), benefits of moisturizers (Table 6), and ceramide-containing moisturizers for acne (Table 7).

Modified Delphi method
After this literature review, a modified Delphi method was used to collect further information on treatment practice. Panel members gave their opinions on the statements that resulted from the search regarding their individual practice in caring for acne patients and the use of moisturizers and ceramide-containing moisturizers. A panel reviewed the document and statements and selected studies. A meeting was then held with the same panel members who previously reviewed the document during the Canadian Dermatology Update 2011 conference in Montreal to explore pros and cons of moisturizes and ceramide-containing moisturizers for acne patients.

The advisor guided the meeting, where the panel members reviewed a summary of all responses, reached a consensus as to the meaning of each question, and then provided a final response and wording about their treatment of patients with acne using moisturizers.

A modified Delphi process was also used to determine the final statements. The final document and statements were edited and reviewed by the panel after the meeting (Figure 2).

Statements for the panel discussion
The initial statements were put together as a result of a literature search, secondary analysis of related citations, and references. The panel addressed these in the meeting. They were asked to give their opinions, looking at the issues from a clinical perspective, and were given the opportunity to adapt the statements, after which the panel voted. Consensus was reached when 9 of the 11 dermatologist who participated in the panel agreed with the statement. At the end of the meeting, the panel reached a full (11/11) consensus on all seven modified statements. On the rationale of why to use a moisturizer for acne, the following was discussed and agreed: 1) moisturizers in acne patients help repair the defective moisture barrier function, help prepare the skin for treatment, and protect against further damage; 2) when moisturizers have incorporation of ceramides, components of the intercellular lipids, they are capable of protecting the skin. These moisturizers replenish ceramides and help repair the skin barrier.

Discussion
The panel agreed that there is evidence to support that a very important reason for nonadherence to acne treatment is dry skin and skin irritation.[8,16–29,42] They further agreed that dry skin and skin irritation commonly results from topical acne treatment and from systemic retinoids.[43–58]

The panel recognized that skin barrier dysfunction may contribute to the signs and symptoms of acne.[3–5,20–25] Pathogenic factors, such as altered sebum lipid quality, regulation of steroidogenesis in the skin, interaction with neuropeptidases, androgen activity, and nutrition, contribute to acne development.[3,22] In acne-affected skin, the barrier function is impaired and decreased water binding leads to a decrease in skin moisture and a reduction in skin surface lipids (ceramides).[5,22] Phytosphingosine occurs naturally in the stratum corneum, both in its free form and as a part of the major fraction of ceramides. It plays a crucial role in permeability barrier function and cutaneous antimicrobial defense. In acne-affected skin, phytosphingosine is depleted, leading to an impaired skin barrier, inflammation, and infection.[22] Furthermore, the lower amounts of sphingolipids were observed corresponding with a diminished water barrier function. This situation is proposed to lead to comedo formation, since barrier dysfunction is accompanied by hyperkeratosis of the follicular epithelium.[5,22] Cholesterol, ceramides, and fatty acid are important components of lipid bilayers. Ceramides play a crucial role in the stratum corneum structure and the regulation of skin barrier homeostasis.[36] Most skin barrier disorders in inflammatory dermatosis are therefore characterized by a decreased ceramide content.[30–32]

The skin type and stage of disease has to be taken into consideration when choosing the vehicle for topical treatments. The efficacy and safety/tolerability of topical treatments are largely influenced by the choice of vehicle. A delivery technology, which provides a controlled release of ceramides and other ingredients slowly over time, may allow the ingredients to better penetrate into the skin, preventing moisture loss. The ceramide-containing cleansers and moisturizers used in acne-prone skin are to be noncomedogenic , nonirritating, and fragrance-free.

The panel members agreed that moisturizers can improve skin dryness and skin irritation resulting from acne treatment. They further agreed that ceramide-containing moisturizers may enhance adherence and complement existing acne therapies. The panel therefore proposes that adjunctive therapy with moisturizers and ceramides containing moisturizers should be considered in acne-treated patients.

A cohort study is initiated to evaluate the clinical efficacy of moisturizers in acne patients.

Conclusion
The goal for the use of moisturizers and ceramide-containing moisturizers as an adjunctive acne therapy is to improve skin condition, reducing irritation and inflammation. This may result in a more rapid improvement in the acne and skin condition than could be achieved in other circumstances and improved adherence to the prescribed therapy.

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