Continuing Education Activity

Moisturizers are topically applied products designed to increase the water content of the skin. Ingredients used in these products have a range of actions, including preventing transepidermal water loss and promotion of desquamation. This activity will review the role of the skin barrier function, maintenance of water balance in the skin, and how these functions relate to moisturizing agents.

Objectives:

• Review the physiology of the skin barrier and how moisturizers can improve this function.
• Identify the role of moisturizers in the management of a patient with an impaired skin barrier.
• Summarize the treatment considerations for a moisturizer when approaching a patient with dry skin.
• Identify the importance of collaboration amongst interprofessional team members to improve outcomes for a patient using moisturizers to increase their skin barrier protection in the management of atopic dermatitis.

Introduction

To discuss moisturizers of the skin, we need a brief discussion on the skin barrier structure and function and the mechanism of maintaining water balance.  The stratum corneum, the outermost layer of the epidermis, is the primary physiologic barrier of the skin and is of critical importance in maintaining water balance.[1] The role of water within the stratum corneum is pivotal to maintaining normal skin integrity and turnover.[2] Water allows for the increased flexibility of the tissues and is a crucial component of the enzymatic reactions responsible for cleavage of the corneodesmosomal connections between corneocytes during the desquamation process. Below a critical water concentration, the corneodesmosomal connections remain intact, which results in a build-up of corneocytes and the appearance of dry, flaky skin.[3]

Function

The stratum corneum contains high concentrations of osmotically active molecules, including amino acids and their derivatives, lactic acid, urea, and electrolytes. These molecules form from the breakdown of filaggrin and are referred to as natural moisturizing factor (NMF). The molecules that make up NMF are hygroscopic and absorb atmospheric water at concentrations as low as 50%. The formation of NMF from filaggrin is highly correlated with the water content of the stratum corneum and only occurs within a specific range of water concentrations. When the water content is high, filaggrin is stable, and conversion to NMF does not take place.[3]  Conversely, when the water content is too low, hydrolytic enzymes needed for this reaction are unable to function. The water content of the stratum corneum ranges from 10% to 30% in healthy skin, as compared to 75% to 85% water content of stratum basale.[4] This gradient is a key feature in its function as a barrier.

Organized in a “bricks and mortar” structure, the stratum corneum is composed of a variety of proteins and lipids.[5] Corneocytes have a tight organization in an interlocking and overlapping fashion, surrounded by a lipid lamella.[3] The major lipids involved in this structure are ceramides, cholesterol, and free fatty acids, which are synthesized by the keratinocytes, and stored in secretory granules.[6][3][1] These granules get released at a slow rate under normal conditions, but upon insult to the barrier, they undergo rapid secretion. The acute barrier disruption results in loss of the calcium gradient, which is an important regulator in the secretion of these granules.[7]

Issues of Concern

Dry skin has many causes, including frequent hand washing, exposure to harsh chemicals, low ambient humidity, and medical conditions like atopic dermatitis, ichthyosis, and psoriasis. The goals of moisturizing the skin are to improve the appearance and function of the skin. In patients with medical conditions associated with impaired barrier function of the skin, like atopic dermatitis, the diligent use of moisturizers is a fundamental component of their treatment.[8]

The choice of moisturizing agents can be adjusted to best fit the needs of a patient. Factors like acne, flaking, hyperkeratosis, itching, or sensitive skin merit consideration when making recommendations of a moisturizing agent.

Clinical Significance

Types of Moisturizers

Moisturizers divide into several categories, and their functions include preventing water loss through the skin, adding water to the skin, and reducing visible flakes.  In recent years, with a fuller understanding of the structure and function of the skin barrier, the science of moisturizer development has advanced significantly. As a result, modern moisturizers frequently combine ingredients with different mechanisms of action to achieve specific results.

Occlusive moisturizers prevent evaporation of water or reduce transepidermal water loss (TEWL) from the skin by forming a barrier. This barrier allows replenishment of the water content of the stratum corneum by the deeper layers of the epidermis and dermis.

Petrolatum is the classic example of an occlusive moisturizer, and it is the most effective. It reduces water loss through the epidermis by nearly 99%.[9] Many other substances can serve as occlusive moisturizers:

• Hydrocarbons: petrolatum, mineral oil, paraffin, squalene
• Silicones: dimethicone
• Vegetable oils: coconut oil, castor oil, olive oil, grape seed oil, soybean oil
• Animal Fats: Mink oil, emu oil, lanolin
• Wax Esters: Lanolin, beeswax
• Sterols: Cholesterol, ceramides

Humectants are compounds that attract and bind water. Some of these substances, like urea, are endogenously present and make up part of the NMF. Humectants can hydrate the skin if the humidity is more than 70%, but more commonly, they will draw water from the deeper epidermis and dermis. Without concomitant use of an occlusive moisturizer, some humectants can result in an increased transepidermal water loss and exacerbate skin dryness.  

Alpha-hydroxy acids (AHAs) are an important group of humectant molecules and have more recently focused on their use as moisturizing agents and cosmetics. AHAs include glycolic and lactic acids. These agents impact the water content of the stratum corneum by several mechanisms. They are effective humectants. They promote desquamation by reducing corneocyte cohesion and also improve the barrier function by increasing levels of ceramides.[3][10] Lactic acid has been used topically at concentrations up to 12% in the treatment of ichthyosis and dry skin for many years.[3]

Urea is a component of NMF. The addition of urea to moisturizers helps with the absorption of water into the stratum corneum. It promotes the desquamation of corneocytes and increases penetration of other topically applied medications.[10] It also improves the skin's barrier function and reduces TEWL.[3] Urea improves itching and is useful in the treatment of ichthyosis, disorders associated with hyperkeratosis, and atopic dermatitis.[8]

Glycerin is another commonly used humectant and is present in many skincare products. In addition to attracting and binding water, it has demonstrated beneficial effects in barrier repair.[10][3] Other humectants include honey, propylene glycol, sorbitol, and hyaluronic acid.

An emulsifier is another classification of ingredients commonly found in moisturizers.  It is a molecule that allows for two immiscible substances to exist as a single phase. The molecules are typically long carbon chains with a polar group. Commonly used emulsifiers are fatty acids, like stearic acid.[11] 

Formulations

When a moisturizer contains humectants, the water content of the skin more rapidly increases, but as mentioned previously, this does not necessarily reduce trans-epidermal water loss. Similarly, when using an occlusive agent, the water content of the skin takes a long time to increase, as the water must be drawn from deeper levels of the skin before an improvement takes place. The term “cream” traditionally refers to a product containing more occlusive ingredients, whereas a “lotion” contains humectants primarily.[11]

Modern moisturizers often contain both occlusives and humectants that contribute to efficacy. Understanding the physiology of the skin barrier and how a disease state or circumstance may contribute to dry skin, impaired barrier function, or flaking of the skin can help us choose the best ingredients for a patient. The specific balance and combination of ingredients will help achieve a variety of outcomes depending on the desire of the consumer.

Enhancing Healthcare Team Outcomes

Particularly in the management of chronic medical conditions, like atopic dermatitis, the liberal use of moisturizers is a fundamental component of treatment.[8][12] The application of moisturizers can be time-intensive for patients and caregivers, and as a result, is often neglected. Having consistent discussions by all members of the care teams, including dermatologists, pediatricians, and nurses, is extremely important. 

Dry skin affects millions of people and can seriously affect the quality of life. The use of moisturizers is the simplest way to obtain symptom relief. Hence, nurses, pharmacists, and primary care providers should encourage patients to use moisturizers liberally. However, patients should be educated to select moisturizers that are free of fragrance; the more chemicals in a moisturizer, the more likely it causes an allergic reaction.

The consistent use of moisturizers in atopic dermatitis can reduce symptoms and frequency of disease flares. Numerous randomized controlled trials form the basis of this recommendation. The level and strength of evidence are IA.

Physicians (MDs, DOs, NPs, PAs) need to include moisturizers in their prescribing and care instructions. Pharmacists can make recommendations on the most appropriate types of agents to the prescriber or nursing staff. Nursing will often be in charge of application in the inpatient setting and can assess the effectiveness of moisturizing therapy, or in the outpatient setting can determine compliance with the moisturizing regimen and report back to the interprofessional healthcare team on the success or failure of treatment. Moisturizing agents can be a part of the compounding process if the pharmacist needs to make a topical preparation to deliver medication, and the pharmacist should consult with the clinician on such matters on a case-by-case basis. As with any intervention, using moisturizers is most effective with an interprofessional team approach. [Level V]