Background
The formation of a scar is a normal response to deep wound healing of the skin. In their meta-analysis of scar prevention and treatment Mustoe et al.1 defined a classification system to assist with scar terminology. Scars are classified as linear hypertrophic (e.g. surgical/traumatic), widespread hypertrophic (e.g. burn), minor keloid or major keloid and mature or immature. As indicated by its name, a hypertrophic scar is raised above the normal level of the skin but remains within the confines of the original wound. These scars generally increase in activity for the first six months then decrease in activity until final maturity at around 18 months postinjury.2 Hypertrophic scars commonly arise from wounds that spontaneously heal (also termed healing by secondary intention) and where wounds are managed by surgery or skin grafting.3 These subgroups of hypertrophic scars show different characteristics, one of which is the rate of transepidermal water loss (TEWL).4 Spontaneously healed scars have a higher rate of TEWL than skin grafted scars, and both have a higher TEWL than normal skin.4 Keloid scars can be differentiated from hypertrophic scars. Unlike hypertrophic scars they extend beyond the border of the original injury, have a longer course of activity, and have different pathophysiology and genetic factors.5 They also have a high rate of TEWL, and have been measured as having a higher TEWL than hypertrophic scars.6 Atrophic scars result from loss of the underlying structures that support the skin such as fat or muscle. Examples of atrophic scars are those that arise from acne or chickenpox.7 Atrophic scars have a different pathophysiology to hypertrophic scars and their resulting treatments are quite different. Therefore, atrophic scars will not be considered in this review.
Scar management becomes a vital component of the treatment plan for clinicians assisting those who acquire a hypertrophic or keloid scar. This is especially so in the field of burns, an injury which predominantly affects the skin and results in extensive hypertrophic scarring. Treatment of scars to maximize their final functional and cosmetic appearance occurs while the scar is immature.1 Once the scar is mature it is no longer re-modelling and conservative scar management is no longer considered effective.1 The most commonly utilized and accepted conservative treatments to minimize the activity of scars are pressure therapy,8 contact media,9 massage and skin care (moisturizing, sun protection and management of folliculitis).10 Pressure therapy is commonly implemented with the use of pressure garments and contact media is commonly implemented with the use of silicone gel sheets.10
Formation of a hypertrophic scar indicates there is damage or loss of deeper structures of the skin such as sweat glands, hair follicles and associated oil glands.11 A common observation is burn patients' failure to sweat or produce oils from their scars as a result of loss of sweat and oil glands in the skin, contributing to dry scars.10 For these reasons, clinicians commonly report they recommend moisturizer for "hydration" of a scar.12 After application of moisturizer, water content of the stratum corneum (the outermost layer of the skin) is increased, filling the spaces between partially desquamated skin flakes and the skin appears smoother.13
There is evidence that massage has a positive effect on scars but it is less supportive than the evidence for pressure and contact media.14 Scar massage or soft tissue mobilization facilitates the scar to become like normal skin. Scar massage alters the scar tissue matrix by breaking the strong bonds between the fibers and moving the interstitial fluid.15 Cho et al.16 found massage in conjunction with moisturizer decreased pain, itch, scar thickness, melanin, erythema, TEWL and skin elasticity. Despite using moisturizer in conjunction with the massage, this study did not evaluate the effect of the moisturizer.
Moisturizers can come in many forms, including creams, ointments, unguents, pastes, oils, lotions and salves. Creams are the most common and are usually emulsions of oil-in-water.13 Lotions are usually less viscous than creams and have a lower oil content than a cream.13 Typical ingredients in moisturizers (in order of highest to lowest amounts) include water, oils, emulsifiers and preservatives.13 Other ingredients for enhancement of biological or emotional effect include humectants, silicones, herbal extracts, fragrance, antioxidants and chelators.13 Water immediately hydrates the stratum corneum but is short lived as it quickly evaporates if not retained by the active ingredients in the moisturizer.17 Humectants increase the amount of water held by the stratum corneum and moisturizers with humectants are superior for the treatment for dry skin disorders compared with those without.17 Glycerol is the most common humectant.13 Others include propylene glycol, butylene glycol, panthenol, 2-pyrrolidone-5-carboxylic acid (pidolic acid), alpha-hydroxy acids and urea.13 However, propylene glycol is a known allergen and was found in 20% of moisturizers.18 Fragrances and preservatives are the main sensitizers to adverse reactions attributable to moisturizer use.13 Despite this, fragrances are found in almost 70% of moisturizers and parabens (a preservative) is found in over 60% of moisturizers.18
The proposed mechanism of contact media is that it reduces TEWL and results in decreased scar activity and better outcomes.19,20 Therefore, changes in TEWL caused by moisturizers may also have an effect on scar outcome; however, not all moisturizers decrease TEWL. Aqueous cream BP has been found to increase TEWL in healthy skin and decrease the thickness of the stratum corneum skin.21,22 However, aqueous cream BP is the second most commonly recommended moisturizer by burn therapists in Australia.12
Burn therapists across Australia, New Zealand, Canada and the United States of America were recently surveyed on the moisturizers they recommend to their patients and why. The survey revealed that 53 therapists recommended 29 different moisturizers.12 Responses reflected the belief that moisturizers hydrate scars with 85% of responders reporting this characteristic as the reason for recommending moisturizer. Recommendation for moisturizer use was most commonly aligned to the properties of the moisturizer and facilitation of massage. However, when the responders were asked if they were able to cite evidence regarding their choice of moisturizer, only one responder could provide a reference.12 This is not surprising when a recent systematic review assessing the effectiveness of moisturizer use with burn scars only located one eligible study.23
The aim of this systematic review is to assess all moisturizers and their effects on scars. The objective is to provide recommendations for clinicians regarding the effects of a moisturizer on the scar, the properties of the moisturizers they should be looking for, and/or specific ingredients that a moisturizer should have to result in a positive (or negative) effect on scar outcome.
A search of the Cochrane Library, The JBI Database of Systematic Reviews and Implementation Reports, Prospero and PubMed located no systematic reviews completed or currently underway on this topic. A previous systematic review that was specific for moisturizer use with burn scars located and included only one study.23 The aim of this systematic review, however, is to broaden the inclusion criteria to include keloid, linear and hypertrophic scars from any cause, such as burns, trauma and surgery.
Inclusion criteria
Types of participants
The review will consider studies that include people of any age with scarring on the skin. The scars will be classified as hypertrophic or keloid from skin grafting, healing by secondary intention, linear scars from surgery or trauma and scars from any other type of injury, for example, from chemical, thermal or radiation injury.
Scars from animal studies will be excluded. Scarring of other structures other than the skin will not be included, for example, internal scarring of connective tissue, muscle, tendon and other structures. Scars which are atrophic as a result of acne, chickenpox or stretch marks, for example, will be excluded as these occur as a result of degradation of underlying structures and exhibit different pathophysiology and therefore have different recommended treatments.7 Where studies include study participants with atrophic, keloid and hypertrophic scars, only data from the keloid and hypertrophic scar populations will be extracted. Where it is unclear what types of scars are being investigated the author/s will be contacted and asked to provide this information and the data relating to the keloid and hypertrophic scars. If authors do not provide additional clarification or data, studies will only be included where there are mixed scar samples in which the atrophic scars consist of 20% or less of the sample.
Types of interventions
The review will consider studies that evaluate the effect and properties of moisturizers, creams and their variants such as pastes, oils, lotions, unguents and salves. These may or may not be medicated. Studies on medicated creams where an effect was observed on scars as a secondary outcome will be included.
Comparisons will include a moisturizer/cream with other moisturizer/creams with or without an active ingredient or medication, or no treatment, or another scar treatment (such as laser or contact media, for example). A confounding factor may be the use of massage for application of a moisturizer. As mentioned above, massage has been found to have an effect on scars.14 Therefore, in a study where moisturizer is applied to the experimental group but not to the control group the application method of the moisturizer would need to be scrutinized to determine if there was a massage component. If there was a massage component, then the study would be excluded. In comparison, for a study where two different groups apply two different moisturizers the application method would need to be consistent to be included in this review. Such an example is Lewis et al.24 where aqueous cream was compared to a beeswax and herbal oil cream to reduce itch.
Outcomes
The review will consider studies that include the outcome measures that measure changes in scar activity, changes in the final appearance/cosmesis of the scar, improvements in patient reported features of scars (e.g. itch, tightness, range of movement) and/or by altering measurable features of the scar such as vascularity, color, height, length, pliability and/or TEWL. These characteristics may be measured by instrumentation such as spectrophotometry/colorimetry (color), tissue tonometry (pliability),25 standardized digital imaging and spectral modelling (vascularity and melanin),26 electrical hygrometers such as the Tewameter (TEWL; Courage Khazaka Electronic Gmbh, Cologne, Germany), to name a few. Alternatively, scar assessment scales such as the Vancouver Scar Scale,27 modified Vancouver Scar Scale28 and the patient and observer scar assessment scale29 are a few of the scales that could be used to assess the scar's physical characteristics.
Patient reported changes to their scar such as itch, pliability and hypersensitivity may be subjective outcome measures utilized in some studies. These may include questionnaires, visual analogue scales or be part of a scar assessment scale such as the patient and observer scar assessment scale.29 Reports on the characteristics of the moisturizer/cream such as patient acceptance, price paid by the patient, how well it spreads, fragrance, comfort, and other characteristics can be reported by studies. This subjective information will be of use to clinicians in their decision making when recommending moisturizers and will therefore be included in this review.
Types of studies
The review will consider both experimental and epidemiological study designs, including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case-control studies, case series and analytical cross-sectional studies for inclusion.
Search strategy
The search strategy aims to find both published and unpublished studies in English. The date range will be from database inception until the current date. A three-step search strategy will be utilized in this review. An initial limited search of PubMed and CINAHL was undertaken followed by analysis of the text words contained in the title and abstract and the index terms used to describe the article. Initial keywords to be used will be: cicatrix, hypertrophic cicatrix, scar, keloid, hypertrophic, emollient, moisturizer, skin cream, cream, lubricant, ointment, salve, unguent, lotion.
A second search using all identified keywords and index terms will then be undertaken across all included databases. The databases to be searched include: PubMed, CINAHL, Embase, Web of Science. The full database search planned for PubMed is:
(Scar[tw] OR Scars[tw] OR Scarring[tw] OR Cicatrix[mh] OR Cicatrix[tw] OR Cicatrization[tw] OR Cicatrisation[tw] OR Keloid[mh] OR Keloid*[tw] OR hypertrophic[mh] OR hypertrophic[tw]) AND (Moisturi*[tw] OR Emollients[mh] OR Emollient*[tw] OR Skin cream[mh] OR Skin cream*[tw] OR Cream[tw] OR Lotion*[tw] OR Ointments[mh] OR Ointment*[tw] OR Salve[tw] OR Salves[tw] OR Unguent[tw] OR Unguents[tw] OR Lubrica*[tw]) AND (English[la])
Third, the reference list of all identified reports and articles will be searched for additional studies.
The search for unpublished studies will include:
clinicaltrials.gov (US Clinical Trials Register), http://www.anzctr.org.au (Australian and New Zealand Clinical Trials Register), http://www.controlled-trials.com (European Clinical Trials Register), Open Grey (http://www.opengrey.eu), and Cochrane Central Register of Controlled Trials (CENTRAL).
Assessment of methodological quality
Studies selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using the predefined standardized critical appraisal instruments from the Joanna Briggs Institute (JBI).30 An appropriate critical appraisal tool will be selected based on the type of study being analyzed such as: randomized controlled trials, case-control studies, case series, cohort studies, quasi-experimental studies, and analytical cross-sectional studies.30
A closed question regarding the funding source will be added to the critical appraisal tool to detect funding bias, for example "Was the study funded by the manufacturer of the product being assessed? Yes/No" and "Did any of the authors have any financial interest in the product involved in the study? Yes/No." If it is found that there is a finding bias the study will be excluded. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.
Data extraction
Data will be extracted from studies included in the review using the standardized data extraction tool from JBI.30 For missing information or data that needs clarification, the authors of primary studies will be contacted. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer. The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.
Data synthesis
Quantitative data will, where possible be pooled in statistical meta-analysis using the JBI System for the Unified Management, Assessment and Review of Information (JBI-SUMARI). Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard [chi]2 and I2 and also explored using subgroup analyses based on the different study designs included in this review. Subgroups will be implemented to ensure judicious data synthesis and knowledge translation from this review. Examples of likely subgroups may be scar type (such as keloid, hypertrophic, healed by secondary intention and surgical scars), moisturizer type (such as creams, ointments, pastes, oils and lotions) and active ingredients. Where statistical pooling is not possible, the findings will be presented in narrative form, including tables and figures to aid in data presentation, wherever appropriate.
Acknowledgements
The authors would like to acknowledge Ms Maureen Bell, Barr Smith Library Librarian, University of Adelaide, for her invaluable contribution in assisting with refining the database searches.
References