SYSTEMATIC REVIEW OF CHEMICAL PEELINGS

Received on 15/02/2009
Approved on 25/02/2009
We declare no conflict of interest.

Abstract

Fundaments: chemical peelings represent damage to the skin or an accelerated form of exfoliation induced by caustic agents, having several indications; they are classified as superficial, medium-depth, and deep. The number of publications on the subject is elevated, but critical analysis are necessary to achieve objective conclusions.
Objectives: verifying the efficacy and safety of chemical peelings through a systematic review of the literature.
Methods: from January 5 to February 15, 2009, searches in three data bases were performed: Cochrane Library, MEDLINE (1966 – 2009), and LILACS. Criteria for study selection were established, with emphasis on methodological quality. The best comparative or controlled studies were described individually. The remaining review articles and descriptive and experimental studies were analyzed together.
Results: we found 414 publications and reviewed 165; 129, or 78%, corresponded to descriptive (82), review (37), or experimental (10) studies. The remaining 36 (22%) represented controlled or comparative studies, of which 19 (53%) were randomized and only four had the ideal delineation, i.e., placebo-controlled, randomized, and blind. Agents mentioned more often included: glycolic acid, salicylic acid, trichloroacetic acid (TCA), and phenol. Few studies evaluated the histologic effects and/or used quantitative parameters to determine their efficacy and safety.
Limitations: the heterogeneity of the studies; few studies with good methodological quality.
Conclusions: there are no doubts related to the the benefits of chemical peelings, which are demonstrated more by the clinical experience than by well-conducted and reproducible studies that are fundamental for the elaboration of new conduct guidelines.

FUNDAMENTS

Chemical peelings represent accelerated exfoliation or skin damage induced by caustic agents that cause controlled damage, followed by the release of cytokines and inflammatory mediators, resulting in thickening of the epidermis, collagen deposits, reorganization of structural elements, and increase in dermal volume ^1-13. The depth depends on: skin type, prior treatments, anatomical location, fat removal, application technique, agent, etc ¹⁴. Thus, any classification is an approximation. The one used more often divides them in: very superficial (strata corneum and granulosus), superficial (epidermis), medium-depth (papillary dermis), and deep (reticular dermis) ^15-19.

The stability, penetration and toxicity²⁰ of most agents are well-known. Those reported for superficial peelings include:

Jessner’s solution (14% resorcinol, 14% salicylic acid, and 14% lactic acid in 95% ethanol) ^21,22; alpha-hydroxiacids: 70% glycolic acid in a gel^23-32 or other excipients³³; 92% lactic acid³⁴, and 5% madelic acid³⁵; beta-hydroxiacid, 30% salicylic acid in ethanol^36-40, or polyethylene glycol^41,42, frequently mentioned for Asian patients and phototypes IV to VI of Fitzpatrick; alpha keto acid, 50% or 60% pyruvic acid in ethanol^43-46; resorcinol or 10% to 50% resorcin paste^47,48; 5% 5-fluoruracil (5FU) cream⁴⁹ or in propylene glycol in the fluor-hydroxy pulse peel, which combines the application of Jessner’s⁵⁰ solution or 70% glycolic acid⁵¹, in a variable number of weekly or biweekly pulses⁵², for multiple actinic keratoses and related conditions⁵³; tretinoin in an ideal concentration, yet to be defined, for superficial peeling^54-56 or rapid retinization of the skin^57-59; 10% to 20% aqueous solution of trichloroacetic acid (TCA)^60-67 or in other vehicles^68-70, which has a low cost, is stable, non-toxic, and versatile. The 35% concentration is usually combined with the prior application of Jessner’s⁶³ solution or 70% glycolic acid⁶⁴ for medium-depth peeling; higher concentrations, of 50% to 90%^71-72, for localized use.

Phenol is the only agent for deep peeling, in the classical Baker-Gordon formula (3 ml of 88% phenol, 3 drops of croton oil, 8 drops of liquid soap, and 2 ml of water), known as phenol-croton oil peel^73-78, or in modified solutions^79-81; it is used in the whole face or localized in the perioral and periocular regions; it is, rarely, cardiotoxic⁸² and nephrotoxic, and preoperative evaluation and monitoring are mandatory⁸³; it is considered the gold standard in the treatment of advanced facial aging, with excellent and lasting results.

The main indications of chemical peelings include: photoaging^84-86, prevention of skin cancer in severe photoaging⁸⁷, melasma^88,89, post-inflammatory hyperpigmentation^90,91, acne and seborrhea⁹², and acne scars^93,94. In areas other than the face, serial superficial peelings are recommended, since reepitelization is more difficult due to the smaller amount of cutaneous adnexa; the results are inferior to those obtained on the face^95-99.

The complications of chemical peelings can be unpredictable and unavoidable, related to poor indication or technique, or deficient orientation^100-102. The most frequent include: severe erythema and burning, epidermolysis, delayed healing, excoriations, infections, hypo- and hyperpigmentation, demarcation lines, contact dermatitis, and atrophic or hypertrophic scars.

Chemical peelings are relatively simple procedures, except for the deep peeling with phenol applied in the whole face, mentioned in the literature since 19622 and sanctioned by the clinical practice¹⁰³. They are usually done on an outpatient basis, have several indications, used isolatedly or in combination with other techniques, such as in the treatment of acne scars^104,105 and facial rejuvenescence^106,107. A large number of studies on the subject can be found; however, a critical analysis is important for precise conclusions on the efficacy and safety of the method.

OBJECTIVE

Determining, through a systematic review of the literature, the efficacy and safety of chemical peelings for the different indications.

METHODS

SEARCH STRATEGY

A search of all known data bases, in English, Portuguese, Spanish, and French, was undertaken from January 05 to February 15, 2009. However, references were found only on the following data bases: Cochrane Library (February 2009), MEDLINE (1966 – February 2009), and LILACS. The following key words were used: chemical peeling, chemical peel, chemexfoliation, and cross references were done with the following words: history, methods, classification, agents, standards, utilization, indication, technique, application, efficacy, safety, statistics and numerical data, contraindication, adverse effects, trends, update, review, experimental, and randomized controlled trials (RCT). For cross-references, only English words were considered due to the small number of publications in LILACS.

Study selection criteria
Out of 165 articles selected, 129 were considered for description, being analyzed as a group. For the proposed objective, 36 studies, placebo-controlled (vehicle) or comparative, between the two sides of the face (split face) or right and left forearms or hands, using 2 agents, topical products, and other techniques, such as microdermabrasion, cryotherapy, dermabrasion, and laser, were analyzed individually. In this category, randomized or not, blind or opened studies were included.

Methodological quality
The methodological quality of the studies was evaluated according to the following criteria:
Was the study randomized and the randomization was adequate?
Was it a placebo-controlled study in the same patient or in parallel groups?
Was it a comparative study among same-depth agents or among chemical peelings and other skin exfoliation techniques?
Was the study blind to the patients and/or investigators?
Was the study population selected according to inclusion and exclusion criteria clearly described?
Was the technique adequately described?
Was the evaluation of efficacy and safety blind for independent observers?
Did the efficacy evaluation include quantitative methods, such as scores of clinical signs, Melasma Area Severity Index (MASI), quantitative digital analysis of pictures, or non-invasive, like profilometry, cutometry, and colorimetry; or invasive methods like skin biopsy and histological exam with special dyes, histometry and/or immune histochemical, and digital analysis?
Were tolerance and immediate and late safety adequately assessed?
Was the intention to treat (ITT) population evaluated?
Was the statistical analysis included?
Were the patients followed for a pre-determined period to assess maintenance of the results?
Was the dropout rate lower than 5%?

RESULTS

Four hundred and fourteen articles were found, 374 on MEDLINE and 17 on LILACS. In the Cochrane Library, complete systematic review or protocols were not found, and 23 controlled studies were registered.

One hundred and sixty-five articles were reviewed; 129/165, or 78%, were descriptive (82), or review (37), or experimental (10) studies. The remaining 36 articles, or 22%, consisted of controlled studies (9), or comparative studies, split face type or with parallel groups (25), and 10/36 (53%) were randomized. However, only four showed the ideal delineation, i.e., blind, placebo-controlled, randomized studies, which are described below.

Description of 28 selected studies, with good methodological quality, divided in the following categories:
Blind, randomized and controlled studies (4):
Hevia, 1991¹⁰⁸: evaluation of the pre-treatment effect, during 14 days, in 16 men, of 0.1% tretinoin cream versus placebo cream, on the left and right sides of the face, forearms, and hands, on the healing time of the skin after 35% TCA peeling; the side pre-treated with tretinoin showed significantly faster healing, with a high degree of patient satisfaction.

Burns, 1997¹⁰⁹: pilot study on the treatment of post-inflammatory hyperpigmentation in 19 patients, men and women, phototypes IV to VI, divided into 2 groups; the control group used topical treatment with 2% hydroquinone/10% glycolic acid gel, twice a day, and 0.05% tretinoin cream at night; in the peeling group, 6 serial peelings with 68% glycolic acid were added; evaluation was subjective, using colorimetry and pictures; 17 patients finished the study; both groups showed improvement, but in the peeling group, improvement was faster, greater, and clearing was greater than the normal skin.

Erbağci, 2000¹¹⁰ : treatment of atrophic acne scars in 58 women divided in 3 groups; group A was treated with serial peelings of 20%, 35%, 50%, and 70% glycolic acid every 2 weeks; group B used 15% glycolic acid cream, once or twice a day, for 24 weeks; group C used a placebo cream, twice a day for 24 weeks; photographic evaluation showed significant differences; 70% glycolic acid peeling repeated, at least, 6 times, produced visible improvement; however, the cream was better tolerated and had some effect.

Erbil , 2007¹¹¹: treatment of recalçitrant melasma, for 20 weeks, in 28 women divided in 2 groups; the control group underwent topical treatment with 20% azelaic acid and 0.1% adapalene gel at night; in the other group, serial 70% glycolic acid peelings were added; MASI was used to evaluated the results; a reduction in MASI was seen in both groups; the difference was significant only in the peeling group.

Open, randomized and controlled studies (4):
Katz, 1995⁵⁰: described the fluor-hydroxy pulse peel in the treatment of multiple actinic keratoses; it is a superficial and combined peeling in which a 5% 5-FU solution in propylene glycol is applied after Jessner’s solution, and compared with the isolated use of Jessner’s solution, in 8 weekly pulses; efficacy was evaluated by counting the number of lesions and pictures; 6-month follow-up; the difference was significant and the combined peeling cleared 86% of the lesions.

Marrero, 1998⁵¹: same type of peeling as the one before; the difference consisted on the use of 70% glycolic acid instead of Jessner’s solution; results were similar, but it showed a greater reduction in the number of lesions, 92%.

Koppel, 2000¹¹²: evaluation of the effects of 2 topical anesthetics (EMLA and ELA-MAX) versus placebo on pain relief and on clinical and histological results of 35% TCA peeling, on the face, preceded by the application of 70% glycolic acid and of the anesthetics or placebo left for 30 minutes, without occlusion; evaluation included the opinions of the patients on discomfort, clinical picture, and histological exam; both anesthetics relieved the peeling discomfort without interfering with the results.

Hantash, 2006⁸⁷: prospective study with a 5-year follow-up, to evaluate the effects of 3 techniques of facial resurfacing versus a control group, in the reduction of actinic keratoses and prophylaxis of non-melanoma skin cancer; 34 patients with a history of tumors or severe photodamage were divided in 4 groups, 1 control and 3 treatment groups (CO2 laser, 30% TCA peeling, or 5% 5-FU cream twice a day for 3 weeks; differences among treatments were not observed.

Comparative, randomized and blind studies (6):
Lawrence, 1995¹¹³: split-face randomized study with blind evaluation of the biopsy material and histological exam, with 15 patients, to evaluate the efficacy of a single peeling with Jessner’s solution and 35% TCA versus 5% 5-FU cream twice a day for 3 weeks; clinical and histological results were similar, with a 75%-reduction in the number of visible lesions; the authors considered the single peeling a useful alternative due to the convenience of the single application.

Witheiler. 1997¹¹⁴: an extension of the prior study of the same authors, since it evaluated the efficacy of the treatments after 32 months; 8 patients were followed, and an increase in the number of actinic keratoses was observed after 12 months, suggesting that reevaluation should be done 1 to 1.5 years after treatment.

Kim, 1999²²: split-face study with 26 patients with facial acne comparing the simultaneous use of 70% glycolic acid and Jessner’s solution peelings, twice a week, in 3 sessions; a system that measures the acne Cunliffe score and the opinion of the patients were used; acne improvement was observed, but without differences between both agents, just more accentuated exfoliation with Jessner’s solution; in the opinion of the authors, this would represent an advantage for the glycolic acid peeling as adjuvant in acne treatment.

Kessler, 2008¹¹⁵: comparison of the efficacy of 30% glycolic acid and 30% salicylic acid peelings as adjuvant in the treatment of mild to moderate facial acne vulgaris, in a split-face study with 20 patients, males and females, with 6 applications every 2 weeks, and a 2-month follow-up; evaluation consisted on counting the number of papules and pustules by a blind investigator; the efficacy was similar, but salicylic acid showed less adverse effects and the effects were maintained after 2 months.

Sezer, 2007¹¹⁶: treatment of solar melanosis of the hands in 25 patients, using combined 70% glycolic acid and 35% TCA versus cryosurgery; 23 patients completed the study; it consisted on the clinical evaluation 2 months after treatment by 3 blind investigators; differences between treatments were not observed, but the authors suggested the use of the chemical peeling due to the lower incidence of side effects.

Ejaz, 2008¹¹⁷: study with parallel groups comparing the efficacy and safety of 30% salicylic acid and Jessner’s solution peelings in the treatment of melasma in 60 patients, applying them every two weeks for 12 weeks; MASI was used for the evaluation; intragroup pre- and post-treatment differences were significant, but differences between peelings were not observed; adverse events were minimal and similar.

Comparative, randomized and opened studies (5):
Piacquadio, 1996²⁶: study with parallel groups of 12 patients with moderate photoaging treated with 6 peelings of 30 to 60% glycolic acid every 4 days; 6 patients also associated the daily use of a moisturizer with 10% glycolic acid twice a day; evaluation used a clinical scale; differences between treatments were not observed.

Chew, 1999¹¹⁸: treatment of upper lip rhytides in 20 women; in one side, the CO2 laser was used, while non-occluded Baker’s phenol peeling was used on the other side; evaluation consisted of a clinical score of wrinkle intensity; significantly higher improvement was seen with the phenol peeling.

Arfan, 2002¹¹⁹: study with parallel groups in which 40 patients with melasma were treated with serial, monthly, 79% glycolic peelings for 4 months; afterwards, they were divided in 2 groups; one group used 4% hydroquinone cream daily for 3 months; MASI and pictures were used for evaluation; the combined treatment showed significant increase in peeling efficacy.

Alam, 2002¹²⁰: split-face study comparing the efficacy and patient satisfaction between 20% glycolic acid peeling and low density microdermabrasion once a week during 6 weeks for facial rejuvenescence; results evaluated by the patient, investigator, and pictures; skin improvement was not seen and patients preferred the glycolic acid peeling.

Garg, 2008³⁵: study with parallel groups with 44 patients, comparing the efficacy and tolerability of 35% glycolic acid peeling and 20% salicylic acid/10% mandelic acid peelings, in 6 sessions every 4 days, for the treatment of active acne vulgaris, acne scars, and hyperpigmentation; evaluation consisted of counting the number of lesions, total severity score, and the opinion of the patient; both were effective, but the salicylic acid/mandelic acid peeling was superior for active acne and hyperpigmentation.

Non-randomized, blind and controlled study (1);
Macedo, 2006¹²¹: split-face study in 8 women with melasma; daily use of a cream containing 4% hydroquinone and 10% glycolic acid, which started 1 month before the application of 4 serial 70% glycolic acid peelings versus placebo every 15 days; blind photographic evaluation by 3 independent observers; all patients showed variable degrees of improvement, without any added benefit from the peelings.

Comparative, non-randomized and opened studies (13)^113-131
They are only descriptive studies which do not present good delineation. However, 8 deserve to be mentioned:

Humphreys, 1996 ¹²²: study on facial photoaging with 16 men; 8 underwent pre-treatment with topical tretinoin (it does not mention the concentrations) for 6 weeks, which was continued for 6 months after 40% TCA peeling; 8 patients were treated only with peelings; evaluation was done through pictures; moderate improvement, little effects on wrinkles, without differences compared to the association with tretinoin.

Reed, 1997¹²³: split-face study for the treatment of periorbital wrinkles in 24 patients; combined peeling with Jessner’s solution + 35% TCA versus CO2 laser (SilkTouch); evaluation by clinical scores of the wrinkles; significant differences, with greater improvement with the CO2 laser.

Acland, 2001¹²⁴: study with 9 patients in which two strips of skin on the forehead were treated with CO2 laser (SilkTouch) versus radiofrequency in 2 passings; clinical and histological evaluation; radiofrequency produced more superficial peeling and dermal fibrosis after 3 months.

Sarkar, 2002²⁹: study with 40 Indian women with melasma, divided in two groups, to evaluate the benefits of the association of 6 serial, mensal, 70% glycolic acid peelings and the daily use of a cream with a modified Kligman’s formula (5% hydroquinone, 0.05% tretinoin, and 1% hydrocortisone acetate) for 21 weeks; one group only used the cream and the other the combined treatment; clinical evaluation using pictures and MASI; peelings provided additional benefits to the clinical treatment, showing that superficial chemical peelings were useful in the treatment of melasma.

Khunger, 2004⁵⁶: split-face study with 10 women with melasma, using serial 1% tretinoin peelings versus 70% glycolic acid peelings once a week for 12 weeks; MASI and pictures were used for the evaluation; decrease in MASI on both sides, but differences between both agents were not observed.

El-Domyati, 2004¹²⁵: histometric, immunohistochemical, and ultrastructural study comparing the effects of 35% TCA peelings (5 patients) and dermabrasion (4 patients) on the photoaged face; the changes observed were similar, with increase in collagen I and III, and improvement of the morphological appearance of collagen and elastic fibers.

De-Rossi-Fattaccioli, 2005¹²⁶: histological study comparing the effects of deep chemical peelings with phenol (Baker-Gordon-Litton formula) and ultra pulse CO2 laser on facial rejuvenescence; biopsies were performed at different times; after 1 month, both procedures produced an area of neocollagen, which became more compact and greater after 3 months in patients treated with phenol.

Soliman, 2007¹²⁷: study with parallel groups of 30 women with melasma, divided into two groups; both groups received 20% TCA peelings once a week until complete clearing or a maximum of 6 peelings versus the association with the topical use of 5% ascorbic acid in, one group, 2 weeks before the peelings; evaluation was performed in the interval between peelings and for 6 weeks afterwards; evaluation consisted of MASI, pictures, and patients’ opinions; combined treatment lead to a more significant reduction in MASI.

Analysis of the Results and Discussion
Descriptive studies comprehend reviews and reports of specific types of peelings with the description of the indication, application technique, clinical effects (most of the time) and/or histological, and complications, with emphasis on the cardiac complications of phenol peelings⁸². Regarding efficacy and safety, in general, those studies concluded for the benefits (greater for medium-depth and deep peelings), with minimal or no complications (especially for superficial peelings). Nine animal studies were identified: comparing the histological effects between different agents^132-134, glycolic acid¹³⁵, salicylic acid^136,137, pyruvic acid¹³⁸, polyethylene glycol as a vehicle for salicylic acid¹³⁹, and the use of oral nutraceuticals to reduce the oxidative stress caused by peelings¹⁴⁰. Regarding agents, those mentioned more often included: glycolic acid, salicylic acid, TCA, and phenol, including modified formulas. It should be mentioned that only 2 studies with the isolated use of Jessner’s^21,22 solution, which is a useful and low-cost agent, were identified. The combination with 35% TCA, described by Monheit in 1989⁶³, is more frequent. There are occasional reports on: resorcinol^47,48, 5-FU^50-53, tretinoin as an agent for fast skin retinization^57-59 or peeling^54-56, lactic acid³⁴, pyruvic acid^43-46, and mandelic acid³⁵. The use of 5% 5-FU, knowingly effective on the treatment of actinic keratoses, was mentioned as an agent for chemical peelings between 1995 and 1998 with excellent results^50,51. It is a low-cost procedure, and only in 2005 and 2009^52,53, it was the subject of new studies by Brazilian authors. Tretinoin, whose daily topical use is the gold standard for photoaging and prevention of pre-malignant and malignant lesions, was reported on chemical peelings in 2001 and 2002^54,55. The elevated concentration was questioned by other authors^57-59 regarding the stability of the formulation, since in other reports it was used in much lower concentrations. Although this question has not been answered, it is known that many Brazilian dermatologists have used that and other formulations with even higher concentrations (non-published data, personal communications). The use of other alpha-hydroxiacids, besides glycolic acid, has been reported as agents for chemical peelings^34,35,43-46. The expectative is for the lower unpredictability of immediate effects and the risk of late complications observed among us. Perhaps, for this same reason, there has been an increase in the number of publications on salicylic acid^36-42. New reports on the use of TCA in areas other than the face^{70,87,95,96,116}, which are effective and safe, if the care regarding indication and application technique is observed, are impressive. Studies from Asian and Arabic countries, and India, especially on the treatment of melasma, hyperpigmentation, and acne scars^141-144, represent another aspect that should be emphasized.
The lack of reproduction of interesting studies, which would be essential to consolidate the positive results reported, should also be emphasized.
As for the methodology, little advance on the evaluation of the efficacy, which remains predominantly subjective with pictures, and opinions of patients and investigators, therefore compromising the quality of the results, has been seen.
Few studies have histological evaluation^{37,48,125,126,145,164} and usage of quantitative methods, such as morphometry and/or immunohistochemical studies with epidermal markers like protein p53^146,147 and dermal collagen.
Chemical peelings and their main agents are so well-known that give rise to innovative ideas, such as “blepharopeeling” ¹⁴⁸. They can also delay the indication of plastic surgery in the case of occluded phenol peeling on the entire face^{73,85,153,154,155,157} or the association of peelings of different depths at the same type, according to the need of each area of the photoaged face (non-published data, personal communication). Although the literature on chemical peelings is extensive, and periodically presents updates and recommendation articles^149,157, there are few studies with adequate designs and good quality. Evidence on the efficacy is limited and several controversies persist due to the scarceness of controlled, randomized studies with standardized indications versus agents and application techniques. Relevant differences among those studies refer to: population, agents, indications, application techniques, number of sessions and intervals, criteria for the evaluation of the efficacy and safety, and follow-up of results.
Therefore, the limitations for an adequate analysis and precise conclusions include the great heterogeneity and the methodological quality of the studies.

Suggestions for future clinical studies;
For high-quality methodology, studies should have the following characteristics:
- randomized, with appropriate description of the randomization;
- homogenous parallel groups, since split-face studies have been criticized by the possibility of “contamination” of the placebo side by the study agent;
- placebo-controlled, i.e., the vehicle of the formulation; or
- comparative between 2 types of peelings or other treatment modalities, including procedures or use of topical products;
- blind, preferentially double-blind, which is not always feasible due to the peculiarity of the treatments, but, at least, monoblind on the evaluation of the efficacy parameters by 2 independent observers whose results should undergo concordance statistical testing;
- updated description of the condition being treated;
- clear presentation of the study population, such as its precedence, and biographic and clinical data;
- definition and presentation of the selection criteria (inclusion and exclusion) of the study individuals;
- detailed description of intervention, or interventions, justifying its indication;
- presentation of possible adverse effects or complications and how they will be conducted;
- parameters for the evaluation of the efficacy and safety, preferentially objective, quantitative, without neglecting the opinions of patients and investigators;
- examples of quantitative methods of clinical efficacy: quality of life index; digital analysis of clinical pictures^158,159 and/or microscopic^160,161; well-defined clinical scores of severity and/or improvement; MASI for melasma; wrinkle severity index; counting the number of active acne lesions, actinic keratoses, solar melanosis etc.; non-invasive methods, such as prophilometry^162,163 for the depth of wrinkles and scars, cutometry (elasticity), sebometry (sebaceous secretion), corneometry (hydration), colorimetry (pigmentation), etc.;
- examples of quantitative methods for evaluation of the microscopic effects since, despite advances in non-invasive methods, biopsy, followed by the histopathological exam, continues to be the gold-standard: histometry; specific dyes for elastic and collagen fibers; counting the number of epidermal sunburn cells; use of biological markers for epidermal p53 protein^146,147, apoptosis, collagen I and III, and metalloproteinases etc;
- ultrastructural study, when available¹⁶⁴; and
- appropriate statistical analysis clearly presented; using ITT (intention-to-treat) and PP (per-protocol) populations, indicating the percentage of drop outs, whenever possible.
Besides methodological matters, the following are also necessary:
- declaring any conflicts of interest and financial support;
- mentioning the approval by the Ethics Committee and signing of the informed consent by the patient or legal guardian, including authorization for pictures; and
- Following the ethical principles of the 2000 Helsinki Declaration, international standards of Good Practice in Clinical Research, and all Brazilian laws and regulations pertaining clinical studies with humans, relevant aspects of those involving the use of placebo, biopsy, or comparing interventions that could determine different results.
Experimental studies: they are rare and should be stimulated, since they are useful to analyze the stability and penetration of agents¹⁶⁵, mechanisms of action, immediate and late histological effects, contributing to forfeit biopsies in humans.

CONCLUSIONS

One observes that the literature on chemical peelings is extensive, justifying its universal use and practical utility. There are no doubts on their benefits, demonstrated more by experience than by controlled studies. Most of the times proposed delineation is adequate; however, the quality of the results is inconsistent. A large number of repetitive review, update, and descriptive studies is seen, including opened clinical studies with conclusions that are, in general, favorable.
The predominance of the American literature may justify the elevated number of publications on glycolic acid, which seems to be the preferred agent for superficial peeling in that country.
The persistence of TCA can be emphasized, confirming that another agent with so many positive characteristics, particularly for medium-depth peelings, does not exist. Phenol, despite being an old agent and reported with the greatest association with complications, remains the only agent capable of producing deep peelings. However, it is known that, if it is carefully used, frequently localized, it is safe and offers excellent results, which can be superior to ablative lasers.
The wide heterogeneity of studies, with so many variables, does not allow precise statistical analysis and conclusions. Anyway, one has the impression that chemical peelings will survive the age of equipment, but further clinical studies with good methodological quality and reproducebility are necessary to establish updated guidelines.

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