Wrinkles

Abstract

Introduction

Skin disorders associated with photodamage from ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in people with white compared with other skin types. Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent and treat skin wrinkles? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha and beta hydroxyl acids, carbon dioxide laser, chemical peel, dermabrasion, facelifts, isotretinoin, natural cartilage polysaccharides (oral or topical), retinyl esters, sunscreens, tazarotene, tretinoin, variable pulse erbium:YAG laser, and vitamin C or E (topical).

Key Points

Skin disorders associated with damage by ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in white people compared with other skin types.

• Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease.

We don't know whether sunscreens or topical vitamins C or E prevent wrinkles, as no studies were found.

Exposure to ultraviolet light may be associated with photodamage to the skin. Guidelines suggest that avoiding direct sunlight, either by staying indoors or in the shade, or by wearing protective clothing, is the most effective measure for reducing exposure to ultraviolet light.

We don't know whether topical vitamins C or E improve the appearance of wrinkles, as studies have been small. These vitamins may cause stinging and erythema.

Topical tretinoin improves fine wrinkles compared with placebo cream in people with mild to moderate photodamage, but its effect on coarse wrinkles is unclear.

• Topical tretinoin may cause itching, burning, erythema, and skin peeling.

• Isotretinoin cream improves fine and coarse wrinkles compared with vehicle cream in people with mild to severe photodamage, but causes severe irritation of the face in 5%–10% of people.

• We don't know whether tazarotene is more effective than tretinoin at improving fine and coarse wrinkles in people with moderate photodamage, as studies have given inconclusive results. It can cause burning of the skin.

We don't know whether retinyl esters, topical or oral natural cartilage polysaccharides, alpha or beta hydroxyl acids, or chemical peels are beneficial.

We don't know whether dermabrasion is more effective at improving wrinkles compared with carbon dioxide laser treatment, as studies have given inconclusive results, but adverse effects are common with both treatments, especially erythema.

• We don't know whether variable pulse erbium:YAG laser treatment or facelifts improve wrinkles, as few studies were found.

About this condition

Definition

Wrinkles are visible creases or folds in the skin. Wrinkles less than 1 mm in width and depth are defined as fine wrinkles and those greater than 1 mm as coarse wrinkles. Most RCTs have studied wrinkles on the face, forearms, and hands.

Incidence/ Prevalence

We found no information on the incidence of wrinkles alone; only on the incidence of skin photodamage — which includes a spectrum of features such as wrinkles, hyperpigmentation, tactile roughness, and telangiectasia. The incidence of skin disorders associated with ultraviolet light increases with age and develops over several decades. One Australian study (1539 people, aged 20–55 years, living in Queensland) found moderate to severe photodamage in 72% of men and 47% of women under 30 years of age. Severity of photodamage was significantly greater with increasing age, and was independently associated with solar keratoses and skin cancer. Wrinkling was more common in people with white skin (especially skin phototypes I and II). We found few reports of photodamage in black skin (phototypes V and VI). One study reported that the incidence of photodamage in European and North American populations with Fitzpatrick skin types I, II, and III is about 80%–90%. As Asian skin is more pigmented (Fitzpatrick skin types III–V), wrinkling is not readily apparent until approximately the age of 50 years, with wrinkles being less severe than in white skin of similar age. A prospective study (85 white women living in North America and 70 Japanese women living in Tokyo, aged 20–69 years) comparing age-related changes in wrinkles in eight areas of the facial skin (forehead, glabella, upper eyelid, corner of the eye, lower eyelid, nasolabial groove, cheek, and corner of the mouth) and sagging in the subzygomatic area found more wrinkle formation in all areas of the face in younger age groups of white women than in Japanese women (aged 20–29 years). Another prospective study (160 Chinese women and 160 French women, aged 20–60 years) found that wrinkle onset was delayed by about 10 years in Chinese women compared with French women.

Aetiology/ Risk factors

Wrinkles may be caused by intrinsic factors (e.g., ageing, hormonal status, and intercurrent diseases) and by extrinsic factors (e.g., exposure to ultraviolet radiation, and cigarette smoke). These factors contribute to epidermal thinning, loss of elasticity, skin fragility, and creases and lines in the skin. The severity of photodamage varies with skin type, which includes skin colour, and the capacity to tan. It is becoming increasingly clear that brief incidental sun exposures that occur during the activities of daily living add significantly to the average individual's daily exposure to ultraviolet light. One review of five observational studies found that facial wrinkles in men and women were more common in smokers than in non-smokers. It also found that the risk of moderate to severe wrinkles in lifelong smokers was more than twice that in current smokers who had been smoking for a shorter period (RR 2.57, 95% CI 1.83 to 3.06). The effects of pregnancy and menopause on facial wrinkling have also been investigated by some researchers. In postmenopausal women, oestrogen deficiency is thought to be an important contributory factor for development of wrinkles. One observational study (186 Korean women, aged 20–89 years) found that facial wrinkling increased significantly with an increase in the number of full-term pregnancies (OR 1.84, 95% CI 1.02 to 3.31) and the number of years since menopause (OR 3.91, 95% CI 1.07 to 14.28). However, postmenopausal women who had HRT had significantly less facial wrinkling compared with postmenopausal women who had no history of HRT (OR 0.22, 95% CI 0.05 to 0.95).

Prognosis

Wrinkles cannot be considered a medical illness requiring intervention but concerns about changes in physical appearance brought on by aging can have a detrimental effect on quality of life. In some cases, concerns about physical appearance can affect personal interactions, occupational functioning, and self-esteem. Geographical differences, culture, and personal values potentially influence a person's anxieties about ageing. In societies in which the maintenance of a youthful appearance is valued, the demand for interventions that ameliorate visible signs of ageing grows as ageing populations expand.

Aims of intervention

To prevent skin wrinkling; to improve fine and coarse wrinkling in adults; and to improve quality of life, with minimal adverse effects of treatment.

Outcomes

Wrinkle improvement includes physician and patient evaluation of improvement in skin texture that reduces the visibility of wrinkles; quality of life; and adverse effects of treatment. We excluded RCTs based solely on non-clinical outcomes, such as histological assessment, photography, or optical profilometry.

Methods

Clinical Evidence search and appraisal April 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2008, Embase 1980 to April 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 1. Additional searches were carried out using NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single-blinded, and containing more than 20 people of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. Most RCTs in the review recruited people with moderate to severe photodamage and wrinkles, rather than people with wrinkles alone. To aid readability of the numerical data in our reviews, we round percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Wrinkles.

Important outcomes	Adverse effects, Quality of life, Wrinkle improvement
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatments for skin wrinkles?
2 (912)	Wrinkle improvement	Tazarotene versus vehicle cream	4	–1	–1	0	0	Low	Quality point deducted for incomplete reporting of results. Consistency point deducted for inconsistent effect with different doses
2 (291)	Wrinkle improvement	Tazarotene versus tretinoin	4	–2	–1	0	0	Very low	Quality points deducted for uncertainty about randomisation and allocation concealment, and inconsistent assessment of results. Consistency point deducted for conflicting results
13 (1480)	Wrinkle improvement	Tretinoin versus placebo	4	–3	0	0	0	Very low	Quality points deducted for uncertainty about randomisation and allocation concealment, inconsistent assessment of results, and short-term follow-up in some RCTs. Consistency point deducted for conflicting results, but added for dose response
2 (1099)	Wrinkle improvement	Isotretinoin versus placebo	4	–3	0	0	0	Very low	Quality points deducted for poor follow-up, no intention-to-treat analysis, and incomplete reporting of results
2 (149)	Wrinkle improvement	Glycolic acid versus vehicle cream	4	–2	0	–1	0	Very low	Quality points deducted for sparse data, and incomplete reporting of results. Directness point deducted for uncertainty about clinical significance of the outcome. Consistency point deducted for conflicting results, but added for possible dose response
1 (74)	Wrinkle improvement	Lactic acid versus vehicle cream	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for uncertainty about clinical significance of the outcome
3 (55)	Wrinkle improvement	Carbon dioxide laser versus dermabrasion	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
3 (55)	Adverse effects	Carbon dioxide laser versus dermabrasion	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
2 (44)	Wrinkle improvement	Carbon dioxide laser versus chemical peel	4	–3	–1	0	0	Very low	Quality points deducted for sparse data, inadequate blinding and incomplete reporting of results. Consistency point deducted for contradictory results
2 (44)	Adverse effects	Carbon dioxide laser versus chemical peel	4	–3	–1	0	0	Very low	Quality points deducted for sparse data, inadequate blinding and incomplete reporting of results. Consistency point deducted for contradictory results
3 (55)	Wrinkle improvement	Carbon dioxide laser versus erbium:YAG laser	4	–3	–1	–1	0	Very low	Quality points deducted for sparse data, incomplete blinding, and incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for different outcomes assessed
3 (55)	Adverse effects	Carbon dioxide laser versus erbium:YAG laser	4	–2	0	0	0	Low	Quality points deducted for sparse data, and incomplete reporting of results
1 (20)	Wrinkle improvement	Carbon dioxide laser versus carbon dioxide laser plus variable pulse erbium:YAG laser	4	–3	0	0	0	Very low	Quality point deducted for sparse data, incomplete blinding, and incomplete reporting of results
2 (174)	Wrinkle improvement	Oral natural cartilage polysaccharides versus placebo	4	–3	–1	0	0	Very low	Quality points deducted for sparse data, flawed assessment of outcome and incomplete reporting of results. Consistency point deducted for conflicting results
1 (30)	Wrinkle improvement	Oral natural cartilage polysaccharides versus each other	4	–2	0	0	0	Low	Quality points deducted for sparse data and flawed outcome assessment
1 (30)	Wrinkle improvement	Topical natural cartilage polysaccharides versus placebo	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and flawed allocation concealment. Directness point deducted for uncertainty about clinical significance of outcome
1 (28)	Wrinkle improvement	Vitamin C versus placebo	4	–3	0	0	0	Very low	Quality points deducted for sparse data, poor follow-up, and no intention-to-treat analysis

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Erbium:YAG laser

An yttrium aluminium garnet laser.

Fitzpatrick skin phototype classification

I = always burns easily, never tans; II = always burns easily, tans minimally; III = burns moderately, tans gradually (light brown); IV = burns minimally, always tans well (brown); V = rarely burns, tans profusely (dark brown); VI = never burns, deeply pigmented (black).

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Mild/moderate/severe photodamage

A spectrum of features including wrinkles, hyperpigmentation, tactile roughness, and telangiectasia. Usually measured on a scale from 0–9 (0 = none, 1–3 = mild, 4–6 = moderate, and 7–9 = severe).

Very low-quality evidence

Any estimate of effect is very uncertain.

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