Article

Safety of skin care products during pregnancy

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Abstract

Question: Many of my female patients complain about acne, unwanted hair growth, and other skin problems that have only developed since they became pregnant. Are products used for these types of benign skin conditions safe to use in pregnancy, as it is understandable that women want to look their best at this important time in their lives? Answer: With the exception of hydroquinone, which has a relatively high systemic absorption rate, and tretinoin, for which the evidence is controversial, these products act locally and therefore produce minimal systemic levels. Consequently, in most cases women can deal with these cosmetically unappealing skin conditions without compromising the safety of their unborn children.

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... Post-adolescent acne has been consistently shown in studies to predominate in females [1], and acne is a common problem faced by pregnant women. During pregnancy, acne often worsens because of a rise in serum androgen levels [4], which results in an increase in sebum production and secretion. Acne is well known to result in significant psychosocial morbidity [5], and this is particularly significant during the perinatal period, during which time post-natal blues and depression may develop and have serious consequences. ...
... Older formulations include topical erythromycin (FDA category B), clindamycin (B) and metronidazole (B), which are generally thought to be safe for use in pregnancy and lactation [10]. When applied topically, systemic absorption of erythromycin and clindamycin has also been found to be negligible, once again implying its safety [4]. The manufacturer of topical metronidazole, however, recommends caution in its use during pregnancy as there have been reports of tumorigenicity in animal studies [11]. ...
... Tretinoin and adapalene are probably compatible with lactation because of the low levels of systemic absorption [4,21,22]. The safety of tazarotene in breastfeeding is uncertain. ...
Article
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Acne vulgaris is a common problem encountered by pregnant and lactating women. Unfortunately, in clinical practice, treatment is often not optimized as a result of the lack of safety data and unified recommendations on the use of the various anti-acne therapies. In this narrative review, current data on their safety is summarized. We recommend the use of topical medications as first-line treatment for acne vulgaris in pregnant and lactating women. These include antibiotics (erythromycin, clindamycin, metronidazole and dapsone), benzoyl peroxide, azelaic acid and salicylic acid. Oral agents and/or light-based therapy may be considered as second-line treatment. The former consists of oral macrolides (erythromycin and azithromycin), cephalexin or zinc compounds. Blue-violet or red light phototherapy may be used as monotherapy or in addition to topical and/or oral therapies. Hormonal therapy, antibiotics consisting of tetracyclines, co-trimoxazole and fluoroquinolones, and both oral and topical retinoids should be avoided.
... Do wykonania zabiegów polecanych dla ciężarnej nie stosuje się kosmetyków, które zawierają składniki wymienione w tabeli 1. Różne źródła zawierają jednak sprzeczne informacje (15,16), podstawą rozstrzygania wątpliwości zawsze powinna być ostrożność. ...
... przewlekłe schorzenia skórne), a jeszcze inne, które występują powszechnie, nazywane są fizjologicznymi zmianami skórnymi. Te ostatnie zazwyczaj nie wpływają negatywnie na zdrowie matki lub płodu, ale niektóre z nich mogą mieć znaczenie kosmetyczne i/lub dermatologiczne (15). Intensywne zmiany pigmentacyjne mogą występować od początku ciąży (24). ...
Article
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Introduction. Pregnancy is a period of continuous change. Physiological, anatomical and biochemical changes, including fluctuations in the endocrine system, cause the occurrence of many disorders also within the skin and its appendages. They can occur at various stages of pregnancy and, depending on the subjective assessment, create a smaller or more complex problem. Aim. The aim of the study was to determine the most common cosmetic problems in pregnant women and to give them a subjective rank of severity, to show the means and ways women take to fight against these problems. Material and methods. 102 pregnant women took part in this survey study. It was conducted from November 2017 to March 2018 in gynecological clinics and pregnancy pathology wards in Krakow and Dabrowa Tarnowska. Results. The major and most common skin problem was stretch marks (98% of respondents). The problem of skin firmness loss concerned 34.31% of respondents, while 33.33% indicated the occurrence of pruritus, the appearance of acne and/or rashes was declared by 31.37% of respondents. Less frequently appearing changes were: dilated capillaries (20.58%), discoloration (16.66%) and excessive hair growth. The second trimester of pregnancy was considered the main moment of appearance of the changes. For most women, the skin care products used before pregnancy had to be changed. Over half of the respondents declared that they want to perform a professional cosmetic procedure. Most often, however, only after completing pregnancy. Conclusions. More emphasis should be placed on the correct interview with the client of a beauty salon and asking about a possible pregnancy. During pregnancy, the skin requires changes in the form of care, the vast majority of women will seek professional advice after childbirth.
... Jessner's solution and TCA peel: Use with caution, Jessner's contains salicylic acid, TCA in maternal urine correlated with fetal growth retardation although TCA used to treat genital condylomata in pregnancy safely. Andersen, 1998Lee et al., 2013Bozzo et al., 2011James et al., 2008Zhou et al., 2012Schwartz et al., 1988 Neuromodulators Botulinum toxin A: Multiple case reports suggest no harm to fetus in either cosmetic botulinum toxin or other medical indications (migraine prophylaxis, achalasia, cervical dystonia) in majority of patients. ...
... This acid can have significant dermal penetration of up to 25% if large areas are treated or when it is applied under occlusion (Lee et al., 2013). However, the reproductive outcomes of patients who are pregnant and treated with low doses of oral aspirin were studied and no significant effects on the health of the fetus were reported (Bozzo et al., 2011;James et al., 2008). It is recommended that if salicylic acid is used to treat patients who are pregnant, the area of coverage should be limited. ...
Article
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The safety of cosmetic procedures in patients who are pregnant and/or lactating is a complex clinical question surrounded by uncertainty. Our objective is to consolidate data on the safety of commonly requested cosmetic procedures during pregnancy and lactation after a systematic review of the current literature to guide evidence-based care in the future. A systematic search of the PubMed database was conducted for articles on cosmetic procedures during pregnancy and lactation. Due to a lack of controlled trials, case reports and series were considered. Minor procedures such as shave, punch, snipping, and electrocautery are considered safe. With respect to chemical peels, glycolic and lactic acid peels are deemed safe; however, trichloracetic and salicylic acid peels should be avoided or used with caution. Although safety data on botulinum toxin A is insufficient, the procedure may be safe because systemic absorption and placental transfer are negligible. Sclerotherapy can be safe during pregnancy but must be avoided during the first trimester and after week 36 of the pregnancy. Laser and light therapies have been considered generally safe for patients with granulomatous conditions and condylomata. Epilation should be limited to waxing, shaving, and topical treatments instead of permanent procedures. In patients who are lactating, most therapies discussed above are safe but fat transfer, sclerotherapy, and tumescent liposuction are not recommended. Better evidence is needed to make concrete recommendations on the safety of cosmetic therapy during pregnancy and lactation but preliminary evidence suggests excellent safety profiles for many commonly requested cosmetic procedures.
... 3,8,12 Sunscreens are used in pregnancy for several dermatologic conditions and adverse events have not been reported. 13 However, due to the well-known side-effects, such as atrophy, telangiectasia, and rosacea-like dermatitis, treatment should be intermittent and not exceed an application of more than a 2-4 weeks. 4 Presently, no specific studies related to efficacy and security of TCS in pregnant woman with CLE have been conducted. ...
Article
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Lupus erythematosus is an autoimmune disease that often affects the skin. Cutaneous manifestations are generally subdivided into different subtypes, including acute, subacute and chronic courses. Management of lupus erythematosus cutaneous manifestations during pregnancy remains a clinical challenge until nowadays. To date, no recommendations have been published specifically for the treatment of this condition in pregnant women, so therapeutic strategies are mainly based on recommendations for general population and other rheumatologic and dermatologic diseases during pregnancy. This challenge is compounded by a lack of evidence‐based studies, as clinical trials in pregnant women are considered unethical in many circumstances, so data are often extrapolated from low‐evidence sources. The aim of this article consists in review currently evidence of treatment of lupus erythematosus cutaneous lesion in pregnant women. This article is protected by copyright. All rights reserved.
... Since the absorption from topical application would produce even lower systemic concentrations it would be unlikely that these peels would cause adverse outcomes if used during pregnancy. However, it is still recommended that they are used with caution and coverage should be limited, and without occlusion, if used during pregnancy [14]. ...
... At least 4 case reports have been published linking congenital abnormalities with maternal use of topical tretinoin. [60][61][62][63][64] However, a retrospective study of 215 pregnant women exposed to topical tretinoin showed no increased incidence of retinoid embryopathy compared with 430 age-matched controls. 65 Furthermore, 2 prospective studies in 200 women who reported exposure to topical tretinoin during the rst trimester of their pregnancies found that this exposure was not associated with increased risk for congenital malformations or retinoid embryopathy. ...
Article
Topical tretinoin has been approved for use in dermatology for 40 years and is currently approved for the treatment of acne vulgaris and photodamage. During this time, topical tretinoin has accumulated significant efficacy and safety data in the treatment of acne and photodamaged skin and demonstrated clinical potential for treating a range of other dermatologic conditions. The diverse effects may be due to complex underlying mechanisms of action associated with tretinoin, including keratolytic activity, collagenesis, and other mechanisms associated with the activation of nuclear retinoic acid receptors (RARα, RARβ, and RARγ). In this article, we review the history of topical tretinoin use to date and outline emerging research suggesting that topical tretinoin may have potential clinical use for treating a multitude of other dermatological conditions when used either as monotherapy or in combination with other agents. We also describe newer formulations of topical tretinoin that have been designed to reduce irritation potential. In light of the substantial history of safety and efficacy of topical tretinoin in acne and photodamage, we speculate that it holds promise in treating many additional dermatological conditions, which may be explored in future research. J Drugs Dermatol. 2013;12(6):638-642, e94-e105.
... At low concentrations they reduce the cohesion of the corneal extract corneocytes, and stimulate the proliferation of cells in the epidermis. It is safe for use by pregnant women at a concentration of 10%, in the form of lotions, creams, gels, and solutions [17]. ...
... 1 One of the prominent physiological changes during pregnancy is the increase of androgens, which induce progression or worsening of acne vulgaris and increasing of hair growth in several body parts. 2 A descriptive study by Urasaki revealed that 91.1 percent of pregnant women developed skin lesions associated with pregnancy and about 67.2 percent of the skin changes has been a ecting their con dence and health. Skin pigmentation is the most common problem during pregnancy, followed by vascular changes, stretch mark, and acne vulgaris. ...
Article
Objective: We sought to know the efficacy and safety profile of topical products for use during pregnancy. Methods: We used PubMed, Embase, and Cochrane Library to review literature on topical products and pregnancy. Results: A majority of pregnant women develop skin changes, including physiological or hormonal changes, worsening of preexisting skin conditions, or the appearance of new dermatoses during pregnancy. Most pregnant women are concerned about the availability of treatments options with good safety profiles, especially for skin and hair treatments, to maintain their appearance and health. Although most of the treatments are recommended to be used after delivery, there are some alternatives to prevent and treat skin lesions during pregnancy. Conclusion: The most current and comprehensive information about the efficacy and safety profile of topical products in pregnancy are necessary.
... Thioglycolic acid Ͻ5% is often used in depilatory products. 38 There has been no evidence of mutagenicity or carcinogenicity with high oral doses in rat studies. Sodium, calcium, and potassium hydroxide in depilatory creams disassociate into the respective ions, and therefore are safe in pregnancy. ...
... Women of childbearing potential should also be asked about their plans for reproduction, and treatment should be tailored for safety, whether the patients are actively trying to conceive, pregnant, or (Table 3). Among the physiologic changes of pregnancy is a rise in serum androgen levels (Bozzo et al., 2011), which results in increased sebaceous gland activity and often worsening of the acne. Published information on the effects of acne medications on the developing fetus or breastfeeding infant is very limited (Kong and Tey, 2013). ...
Article
Full-text available
This review focuses on the treatment options for adult female patients with acne. Acne in adult female patients may start during adolescence and persist or have an onset in adulthood. Acne has various psychosocial effects that impact patients' quality of life. Treatment of acne in adult women specifically has its challenges due to the considerations of patient preferences, pregnancy, and lactation. Treatments vary widely and treatment should be tailored specifically for each individual woman. We review conventional therapies with high levels of evidence, additional treatments with support from cohort studies and case reports, complementary and/or alternative therapies, and new agents under development for the treatment of patients with acne.
... 21 This might consequently foster maternal fear and lead to termination of healthy and otherwise wanted pregnancies even though the risk of malformations from topical retinoid exposure is not considered significantly increased by many teratology information specialists. 22 The purpose of this study was to assess the frequency of a spectrum of adverse birth outcomes associated with first-trimester exposure to topical retinoids, to enrich rather scarce human data available to date. We compared the overall prevalence of major or minor birth defects at birth, the rate of spontaneous abortion, and the rate of elective termination of pregnancy after first-trimester exposure to topical retinoids with the baseline prevalence in pregnancies exposed to no known teratogen. ...
Article
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Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.
... Рецидив акне во время беременности происходит из-за повышения уровня андрогенов в сыворотке, что приводит к гиперсекреции сальных желез [6]. ...
... Yüksek oranda emilim söz konusu ise kimyasallar fetusa plasenta ile ulaşabilir (18). ...
... Of primary concern is the fact that 13% of our participants used skin bleaching products while pregnant and/or possibly breastfeeding. This finding is consistent with prior studies [6,45,46] and highlights the existence of prenatal and postnatal exposure to Hg, HQ, and other potentially harmful chemicals in skin bleaching products [27,31,32,[47][48][49], for which the neurodevelopmental and other effects on offspring remain understudied. The vulnerability of the fetus and young offspring to the adverse health effects of skin bleaching during such a sensitive period of their growth and development deserves urgent attention from the public health community, especially given the rising global incidence and prevalence of this practice. ...
Article
Full-text available
Introduction The application of skin bleaching products to inhibit melanogenesis is a common practice within the African diaspora. Despite the adverse health effects of skin bleaching, rigorous studies investigating skin bleaching behavior among these populations in the United States are limited. In our P30 pilot study, we explored predictors of skin bleaching practice intensity among African and Afro-Caribbean women. Methods In collaboration with our Community Engagement Core, we conducted a cross-sectional study to investigate the relationship between demographic and psychosocial predictors and skin-bleaching-related practice patterns among African and Afro-Caribbean women in New York City. Results Among the 76 participants recruited, the median age at the initiation of skin bleaching was 19.5 (16–25) years, yielding a median duration of 13.5 (6–23) years. Although pregnant women were not actively recruited for the study, 13.2% (n = 10) of the participants used skin bleaching products while pregnant or possibly breastfeeding. Nativeness and education were associated with various components of skin bleaching practice intensity, including duration of skin bleaching, daily use of products, and bleaching of the entire body. Participants’ perceived skin-color-related quality of life was not associated with skin bleaching practice intensity. Conclusion Skin bleaching is a habitual practice that likely requires culturally sensitive interventions to promote behavioral change. The existence of prenatal and postnatal exposure to mercury, hydroquinone, and other potentially harmful chemicals in skin bleaching products highlights an urgent need to explore the adverse effects of skin bleaching practices on birth outcomes and the growth and neurodevelopment of young babies.
... [11] During pregnancy, hydroquinone, a popular treatment for melasma, is not recommended due to its high absorption and possible adverse effects on the fetus. [12] In lieu of hydroquinone, sunscreen is a safer option. This was studied by Lakhdar et al. in 185 Moroccan women who were >3 months pregnant. ...
Article
Full-text available
Photosensitive conditions such as melasma and postinflammatory hyperpigmentation (PIH) are exacerbated by exposure to ultraviolet (UV) rays and visible light making sunscreen use an essential component of treatment. This is especially true in skin of color patients who are less likely to use photoprotection, even if diagnosed with these photoexacerbated conditions. We aimed to evaluate the body of literature to provide evidence for the use of sunscreen in the treatment of melasma and PIH. We reviewed English articles from PubMed, Journals@Ovid Full Text, and Embase using the search terms “sunscreen” and either “melasma” “PIH,” or “post-inflammatory hyperpigmentation.” Nine relevant publications provide evidence that a broad spectrum of protection, including UVA, UVB, and visible light within sunscreens can play an adjuvant role in therapy for melasma and PIH by stabilizing and improving these pigmentary disorders in skin of color patients. This review illustrates the advantages and limitations of sunscreen use, as well as practice gaps in photoprotection in the skin of color patients with melasma and PIH.
... [1][2][3] There is also evidence that certain chemicals in cosmetic products are also potential teratogens. [4][5][6][7][8] Only the medications prescribed by an obstetrician like vitamins, minerals and other supplements or medications to treat common symptoms during pregnancy should be taken. It is therefore of utmost importance that, prescription medications without the physician's prescription and over the counter medication is avoided in pregnancy. ...
Article
Full-text available
Background: Inappropriate use of drugs and certain cosmetics can cause potential harm to the mother as well as the fetus. Good knowledge about drug use can help pregnant women make informed decisions. This study was conducted to assess the knowledge and attitude among pregnant women regarding the usage of drugs and cosmetics during pregnancy. Materials and Methods: This cross-sectional study was conducted in the antenatal clinic of a tertiary care centre from August to November 2018 in 384 randomly selected pregnant women. Data were collected using an interviewer-administered questionnaire. Data analysis was done using SPSS version 21.0. Results: Around 51.56% of pregnant women believed that drugs may have an effect on them or the fetus and 11.19% believed the same for cosmetics. More than half of them feel that drugs should mainly be avoided in the third trimester. Around 25% of women believed that the irrational use of drugs could cause congenital anomalies in the fetus. About 58.07% of women were of the opinion that pregnancy requires the consumption of many drugs and 34.11% preferred to use alternative medicine during pregnancy. The primary source of information in majority of women was doctors followed by media. Around 32.03% of women had taken drugs outside a doctor's prescription during their pregnancy. A decrease in cosmetic use was reported by 4.94% women. Conclusion: The knowledge regarding the correct use of drugs and cosmetics during pregnancy is poor. The use of non-prescribed medications is high. Educational programs for women to increase their knowledge of the potential risks to them as well as the fetus are necessary.
... Regarding skin care products, except hydroquinone and topical retinoids, risk of malformations and other adverse effects do not seem to be increased with use of cosmetics. [17] With regard to chemical peeling agents, trichloroacetic and salicylic acid is preferably to be avoided or to be used with caution. Use of botulinum toxin is another controversial area. ...
Article
Acne vulgaris is a common skin condition in pregnant women. The choice of medication depends on the severity of the acne and the potential risks of the treatment. As a general rule, topical agents are safer than oral agents and should be the first choice, with oral agents and/or blue-violet or red light phototherapy considered as second-line treatments. The use of hormonal therapies, oral and topical retinoids and certain antibacterials should be avoided.
Article
Facial pigmentation remains a clinical challenge for all dermatologists due to similar appearance despite myriad of causes. Facial hyperpigmentation in women is often misdiagnosed as melasma resulting in subpar clinical outcomes due to the lack of identification of the correct cause of the pigmentation and appropriately targeted treatment. Most dermatologists will base their diagnosis on a visual examination. The characteristic appearance of melasma means that the diagnosis is usually straightforward and can be made clinically by a dermatologist. However, Wood’s lamp and dermatoscope may aid diagnosis and help determine the level of melanin deposition. More importantly, these diagnostic tools assist in ruling out differential diagnoses and facilitate appropriately targeted treatment. The article outlines the presentations of melasma, helping amalgamate the findings and rule out common differential diagnoses.
Article
The management of acne vulgaris in the setting of pregnancy raises important clinical considerations regarding the efficacy and safety of acne treatments in this special patient population. Particular challenges include the absence of safety data, discrepancy in safety data between different safety rating systems, and lack of evidence-based recommendations for the treatment of acne during pregnancy. Nonetheless, many therapeutic options exist, and the treatment of acne in pregnant women can be safely and often effectively accomplished. For mild or moderate disease, patients can be treated with topical antimicrobial agents, anti-inflammatory agents, as well as glycolic and salicylic acid. Several topical agents, notably benzoyl peroxide, previously viewed as potentially dangerous are cited by many sources as being considered safe. When necessary, systemic therapies that can be safely added include penicillins, amoxicillin, cephalosporins, erythromycin, clindamycin, and tetracyclines or sulfonamides, depending on the stage of fetal development. Adjunct therapy may include phototherapy or laser treatments. Physicians should work with this often highly motivated, safety-conscious patient population to tailor an individualized treatment regimen. This treatment regimen will likely shift throughout the different stages of fetal development, as distinct safety considerations are raised prior to conception as well as during each of the trimesters of pregnancy. Important considerations regarding acne management in breast-feeding mothers is also discussed.
Article
Adult acne is becoming recognized as a unique form of acne including either early (adolescent) acne that remains persistent or late onset acne. Women are predominantly affected in adult acne and will be focus of this review. The epidemiology and the characteristics of adult acne are discussed including clinical differences between adolescent and adult acne. We review topical therapies such as antibiotics, retinoids, dapsone, azelaic acid and combination-based therapies. We also review systemic therapeutic considerations, including antibiotics, isotretinoin, oral contraceptives, and hormonal modulators. We discuss the use of light-based therapies such as visible light and photodynamic therapy. Alternative therapies such as the use of botanical and phytochemical therapies are reviewed as well. Finally, we discuss the clinical and laboratory screening for considering polycystic ovarian syndrome when evaluating adult women with acne.
Article
This descriptive quantitative study was designed to investigate the appearance of blemishes in pregnancy, trace the condition's development, and describe its effects after childbirth. The survey was conducted in primary health care clinics in São Paulo City. The data, which form part of a broader study, were collected in the first half of 2010 using a form completed by the researchers. Of the sample of 234 women, 104(44.4%) mentioned the appearance of pregnancy blemishes. The vast majority expressed annoyance at the problem, and the emotional dimension was the most affected. Most participants adopted no preventive measures during the prenatal period, and received no guidance on this matter. The results reflect a need for greater attention and planning of interventions by health care programs for skin problems that are considered of low lethality and often neglected.
Research
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Özet: Saç protein, lipid, su ve küçük miktarda eser elementlerin karışımından oluşur. Proteinler polipeptit sarmalda aminoasit moleküllerinden oluşmuştur. Saç hücrelerinde keratin proteininin polipeptit zincirleri filamanların içinde organize olur. Son yıllarda saç kozmetikleri önemli bir değişim ve gelişim göstermiştir. Saçı temizlemek için kullanılan şampuanların içerikleri önemli ölçüde geliştirilmiştir. Saç kremleri, saç şekillendirici ürünler, pomatlar, biryantin, parlatıcı spreyler, saç koruyucu ürünler, kamuflaj ürünleri saç kozmetikleri arasında yerini alır. Saça şekil vermek için yapılan uygulamalar da saç kozmetiklerinin kullanıldığı alanlardır. (Türkderm 2014; 48: Özel Sayı 1: 64-9) Anahtar Kelimeler: Saç kozmetikleri, şampuan, saç kremi, saç spreyi, saç köpüğü, saç boyası Summary: Hair is composed of a mixture of trace elements in small quantities, proteins, lipids and water. Proteins consist of helical polypeptide aminoacid molecules. In the hair cells; polypeptide chains of keratin protein would be organized in filaments. In recent years, hair cosmetics showed a significant change and development. The content of shampoos which is used to cleanse the hair has enhanced significantly. Hair conditioner, hair styling products, pomades, brilliantine, and gloss sprays, hair protective products, camouflage products are most commonly used hair cosmetics. Hair shaping procedures are frequently applied. (Turkderm 2014; 48: Suppl 1: 64-9) Key Words: Hair cosmetics, shampoos, conditioner, hair spray, hair mousse, hair dye
Chapter
Pregnancy is a very special moment for every woman, and some physiologic changes occur in her body, including the skin. Skin treatment can be necessary to control some disease that can begin or get worse during pregnancy, and dermatologists must know what can or cannot be prescribed during this period. Clinical and side effects of many different medicaments are well studied and when correctly indicated they can be used. On the other hand, few data about the benefits and the harmfulness of cosmetics and cosmeceuticals is available. This chapter will approach what is known about cosmetics and cosmeceuticals, the indication and the contraindication of these products during pregnancy.
Article
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Background: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. Objectives: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. Search methods: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. Selection criteria: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. Main results: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). Authors' conclusions: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.
Chapter
Pregnancy is a very special moment for every woman, and some physiologic changes occur in her body, including the skin. Skin treatment can be necessary to control some disease that can begin or get worse during pregnancy, and dermatologists must know what can or cannot be prescribed during this period. Clinical and side effects of many different medicaments are well studied and when correctly indicated they can be used. On the other hand, few data about the benefits and the harmfulness of cosmetics and cosmeceuticals is available. This chapter will approach what is known about cosmetics and cosmeceuticals, the indication and the contraindication of these products during pregnancy.
Chapter
Pregnancy is a very special moment for every woman, and some physiologic changes occur in her body, including the skin. Skin treatment can be necessary to control some disease that can begin or get worse during pregnancy, and dermatologists must know what can or cannot be prescribed during this period. Clinical and side effects of many different medicaments are well studied and when correctly indicated they can be used. On the other hand, few data about the benefits and the harmfulness of cosmetics and cosmeceuticals is available. This chapter will approach what is known about cosmetics and cosmeceuticals, the indication and the contraindication of these products during pregnancy.
Article
Full-text available
Synopsis Alpha hydroxy acids (AHAs) are used in many cosmetic products as exfoliants, moisturizers, and emollients. The activity of AHAs on skin is likely influenced by their ability to be absorbed into the different layers of skin. The absorption of a homologous series of AHAs was measured through hunnan skin by using in vitro diffusion cell techniques. The (4C) radiolabeled compounds were applied to the skin in an oil-in-water emulsion vehicle. The absorption of the AHAs was measured at pH 3.0, to simulate the pH of the most acidic cosmetic formulations, and at pH 7.0, to observe the effect of complete ionization of AHAs on skin penetration. Much greater absorption of the AHAs was seen at pH 3.0. We also observed substantial absorption into the various skin layers (stratum corneum, viable epidermis and dermis) as well as the receptor fluid. Total absorption of glycolic acid and lactic acid was similar (27-30%). Absorption of the longer-chain AHAs decreased to 21.0% and 19.3%, for 2-hydroxyoctanoic and 2-hydroxydecanoic acids, respectively. At the end of the 24-h studies, these longer-chain AHAs did not form a depot in the skin. The stratum corneum was shown to have a pH gradient with an average pH near 7 at the viable epidermal layer. Therefore, the AHAs ionize to polar molecules as they enter and diffuse through the stratum corneum.
Article
Full-text available
Previous studies have demonstrated elevations in testosterone and androstenedione initiated within the cycle of conception in pregnant non-human primates, and minimal data in the human support the same picture. In the present study we have investigated a group of patients scheduled for artificial insemination with regular menstrual cycles. For this study all patients provided blood samples at 5 days after the luteinizing hormone (LH) surges and daily through the luteal phase and into early pregnancy (n = 12). Patients who did not become pregnant served as normal controls (n = 9). We have measured 17-hydroxyprogesterone (17-OHP) as a marker of luteal activity not obscured by progesterone within the cycle of conception and testosterone and androstenedione as the major androgens. There were no significant changes in testosterone and androstenedione in the non-pregnant controls, but both testosterone and androstenedione were significantly elevated in the pregnant luteal phase, with the first increases occurring at 15 and 14 days respectively after the LH surge. Three of 12 pregnant patients did not demonstrate a dramatic increase in either testosterone or androstenedione and when examined more carefully a corresponding lack of increase in 17-OHP in those same subjects indicated less than optimal luteal activity, suggesting that these androgens were products of the corpus luteum. In three subjects in which consecutive non-pregnant and pregnant cycles were followed there was a dramatic increase from the non-pregnant luteal phase to the pregnant luteal phase indicating that the more important observation may be the concentrations of androgens in the conceptive luteal phase compared to some baseline, either previous luteal phase or even follicular phase. We have also studied changes in dehydroepiandrosterone sulphate and found that there was no significant contribution to this increase in androgens in early conception. These studies demonstrate a significant increase in both testosterone and androstenedione presumably of ovarian, specifically luteal, origin and that adrenal androgen production is not a factor in these changes.
Article
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The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.
Article
Salicylic Acid is an aromatic acid used in cosmetic formulations as a denaturant, hair-conditioning agent, and skin-conditioning agent-miscellaneous in a wide range of cosmetic products at concentrations ranging from 0.0008% to 3%. The Calcium, Magnesium, and MEA salts are preservatives, and Potassium Salicylate is a cosmetic biocide and preservative, not currently in use. Sodium Salicylate is used as a denaturant and preservative (0.09% to 2%). The TEA salt of Salicylic Acid is used as an ultraviolet (UV) light absorber (0.0001% to 0.75%). Several Salicylic Acid esters are used as skin conditioning agents-miscellaneous (Capryloyl, 0.1% to 1%; C12-15 Alkyl, no current use; Isocetyl, 3% to 5%; Isodecyl, no current use; and Tridecyl, no current use). Butyloctyl Salicylate (0.5% to 5%) and Hexyldodecyl Salicylate (no current use) are hair-conditioning agents and skin-conditioning agents-miscellaneous. Ethylhexyl Salicylate (formerly known as Octyl Salicylate) is used as a fragrance ingredient, sunscreen agent, and UV light absorber (0.001% to 8%), and Methyl Salicylate is used as a denaturant and flavoring agent (0.0001% to 0.6%). Myristyl Salicylate has no reported function. Isodecyl Salicylate is used in three formulations, but no concentration of use information was reported. Salicylates are absorbed percutaneously. Around 10% of applied salicylates can remain in the skin. Salicylic Acid is reported to enhance percutaneous penetration of some agents (e.g., vitamin A), but not others (e.g., hydrocortisone). Little acute toxicity (LD50 in rats; >2 g/kg) via a dermal exposure route is seen for Salicylic Acid, Methyl Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate. Short-term oral, inhalation, and parenteral exposures to salicylates sufficient to produce high blood concentrations are associated primarily with liver and kidney damage. Subchronic dermal exposures to undiluted Methyl Salicylate were associated with kidney damage. Chronic oral exposure to Methyl Salicylate produced bone lesions as a function of the level of exposure in 2-year rat studies; liver damage was seen in dogs exposed to 0.15 g/kg/day in one study; kidney and liver weight increases in another study at the same exposure; but no liver or kidney abnormalities in a study at 0.167 g/kg/day. Applications of Isodecyl, Tridecyl, and Butyloctyl Salicylate were not irritating to rabbit skin, whereas undiluted Ethylhexyl Salicylate produced minimal to mild irritation. Methyl Salicylate at a 1% concentration with a 70% ethanol vehicle were irritating, whereas a 6%% concentration in polyethylene glycol produced little or no irritation. Isodecyl Salicylate, Methyl Salicylate, Ethylhexyl (Octyl) Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate were not ocular irritants. Although Salicylic Acid at a concentration of 20% in acetone was positive in the local lymph node assay, a concentration of 20% in acetone/olive oil was not. Methyl Salicylate was negative at concentrations up to 25% in this assay, independent of vehicle. Maximization tests of Methyl Salicylate, Ethylhexyl Salicylate, and Butyloctyl Salicylate produced no sensitization in guinea pigs. Neither Salicylic Acid nor Tridecyl Salicylate were photosensitizers. Salicylic Acid, produced when aspirin is rapidly hydrolyzed after absorption from the gut, was reported to be the causative agent in aspirin teratogenesis in animals. Dermal exposures to Methyl Salicylate, oral exposures to Salicylic Acid, Sodium Salicylate, and Methyl Salicylate, and parenteral exposures to Salicylic Acid, Sodium Salicylate, and Methyl Salicylate are all associated with reproductive and developmental toxicity as a function of blood levels reached as a result of exposure. An exposure assessment of a representative cosmetic product used on a daily basis estimated that the exposure from the cosmetic product would be only 20% of the level seen with ingestion of a "baby" aspirin (81 mg) on a daily basis. Studies of the genotoxic potential of Salicylic Acid, Sodium Salicylate, Isodecyl Salicylate, Methyl Salicylate, Ethylhexyl (Octyl) Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate were generally negative. Methyl Salicylate, in a mouse skin-painting study, did not induce neoplasms. Likewise, Methyl Salicylate was negative in a mouse pulmonary tumor system. In clinical tests, Salicylic Acid (2%) produced minimal cumulative irritation and slight or no irritation(1.5%); TEA-Salicylate (8%) produced no irritation; Methyl Salicylate (>12%) produced pain and erythema, a 1% aerosol produced erythema, but an 8% solution was not irritating; Ethylhexyl Salicylate (4%) and undiluted Tridecyl Salicylate produced no irritation. In atopic patients, Methyl Salicylate caused irritation as a function of concentration (no irritation at concentrations of 15% or less). In normal skin, Salicylic Acid, Methyl Salicylate, and Ethylhexyl (Octyl) Salicylate are not sensitizers. Salicylic Acid is not a photosensitizer, nor is it phototoxic. Salicylic Acid and Ethylhexyl Salicylate are low-level photoprotective agents. Salicylic Acid is well-documented to have keratolytic action on normal human skin. Because of the possible use of these ingredients as exfoliating agents, a concern exists that repeated use may effectively increase exposure of the dermis and epidermis to UV radiation. It was concluded that the prudent course of action would be to advise the cosmetics industry that there is a risk of increased UV radiation damage with the use of any exfoliant, including Salicylic Acid and the listed salicylates, and that steps need to be taken to formulate cosmetic products with these ingredients as exfoliating agents so as not to increase sun sensitivity, or when increased sun sensitivity would be expected, to include directions for the daily use of sun protection. The available data were not sufficient to establish a limit on concentration of these ingredients, or to identify the minimum pH of formulations containing these ingredients, such that no skin irritation would occur, but it was recognized that it is possible to formulate cosmetic products in a way such that significant irritation would not be likely, and it was concluded that the cosmetics industry should formulate products containing these ingredients so as to be nonirritating.
Article
This report provides a review of the safety of Glycolic Acid, Ammonium, Calcium, Potassium, and Sodium Glycolates, Methyl, Ethyl, Propyl, and Butyl Glycolates, Lactic Acid, Ammonium, Calcium, Potassium, Sodium, and TEA-Lactates, and Lauryl, Myristyl, and Cetyl Lactates. These ingredients belong to a group known as alpha-hydroxy acids (AHAs). Products containing these ingredients may be for consumer use, salon use, or medical use. This report does not address the medical use. In consumer and salon use, AHAs can function as mild exfoliants, but are also used as pH adjusters and skin-conditioning agents. AHAs are absorbed by the skin; the lower the pH, the greater the absorption. Metabolism and distribution studies show expected pathways and distribution. Consistent with these data, acute oral animal studies show oxalate-induced renal calculi, an increase in renal oxalate, and nephrotoxic effects. No systemic effects in animals were seen with dermal application, but irritation at the sight of application was produced. While many animal studies were performed to evaluate AHA-induced skin irritation, it was common for either the AHA concentration or the pH of the formulation to be omitted, limiting the usefulness of the data. Clinical testing using AHA formulations of known concentration and pH was done to address the issue of skin irritation as a function of concentration and pH. Skin irritation increased with AHA concentration at a given pH. Skin irritation increased when the pH of a given AHA concentration was lowered. Repeat insult patch tests using lotions and creams containing up to 10% Glycolic or Lactic Acid were negative. Glycolic Acid at concentrations up to 10% was not comedogenic and Lactic Acid at the same concentrations did not cause immediate urticarial reactions. Glycolic Acid was found to be nonirritating to minimally irritating in animal ocular tests, while Lactic Acid was found to be nonirritating to moderately irritating. In vitro testing to predict ocular irritation suggested Glycolic Acid would be a minimal to moderate-severe ocular irritant, and that Lactic Acid would be a minimal to moderate ocular irritant. Developmental and maternal toxicity were reported in rats dosed by gavage at the highest dose level used in a study that exposed the animals on days 7-21 of gestation. No developmental toxicity was reported at levels that were not maternally toxic. AHAs were almost uniformly negative in genotoxicity tests and were not carcinogenic in rabbits or rats. Clinical reports suggested that AHAs would enhance the penetration of hydroquinone and lidocaine. Animal and clinical tests were done to further evaluate the potential ofAHAs to enhance the skin penetration of other chemical agents. Pretreatment of guinea pig skin with Glycolic Acid did not affect the absorption of hydroquinone or musk xylol. Clinical tests results indicated no increase in penetration of hydrocortisone or glycerin with Glycolic Acid pretreatment. Because AHAs can act to remove a portion of the stratum corneum, concern was expressed about the potential that pretreatment with AHAs could increase skin damage produced by UV radiation. Clinical testing was done to determine the number of sunburn cells (cells damaged by UV radiation that show distinct morphologic changes) produced by 1 MED of UV radiation in skin pretreated with AHAs. A statistically significant increase in the number of sunburn cells was seen in skin pretreated with AHAs compared to controls. These increases, however, were less than those seen when the UV dose was increased from 1 MED to 1.56 MED. The increase in UV radiation damage associated with AHA pretreatment, therefore, was of such a magnitude that it is easily conceivable that aspects of product formulation could eliminate the effect. Based on the available information included in this report, the CIR Expert Panel concluded that Glycolic and Lactic Acid, their common salts and their simple esters, are safe for use in cosmetic products at concentrations ≤10%, at final formulation pH≥3.5, when formulated to avoid increasing sun sensitivity or when directions for use include the daily use of sun protection. These ingredients are safe for use in salon products at concentrations ≤30%, at final formulation pH ≥3.0, in products designed for brief, discontinuous use followed by thorough rinsing from the skin, when applied by trained professionals, and when application is accompanied by directions for the daily use of sun protection.
Article
Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy. Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy. Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies. Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies. Erythromycin, however, appears to be safe. Topical acne medications never have been implicated as a cause of fetal deformities in human beings. Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age. Prompt reporting of adverse effects is encouraged.
Article
To test the hypothesis that treatment with antibiotics prevents low birth weight, pregnant women whose vaginal cultures contained Ureaplasma urealyticum or Mycoplasma hominis (or both) and who gave written informed consent were treated with one of the following: identical looking capsules containing 250 mg of either erythromycin estolate or stearate (active against U urealyticum), or 150 mg of clindamycin hydrochloride (active against M hominis), or placebo, four times daily for six weeks in a randomized double-blind study. Treatment with clindamycin had no effect. Treatment with erythromycin initiated during the second trimester had no effect on mean birth weight or on the frequency of low-birth-weight infants. In contrast, women whose treatment with erythromycin was initiated in the third trimester gave birth to infants with a heavier mean birth weight (3331 g) than infants born to placebo-treated women (3187 g) (P = .042). Similarly, in women whose erythromycin was begun during the third trimester, the birth rate of infants weighing 2500 g or less was 3%, whereas in women treated with placebo, the birth rate for low-birth-weight infants was 12% (P = .047). These data suggest that treatment with erythromycin during the third trimester prevents low birth weight in mycoplasma-colonized pregnant women. Whether the effect is due solely to the action of erythromycin on U urealyticum is uncertain.
Article
24 patients suffering from papulo-pustular acne were treated with mono-therapy with 2% erythromycin-containing alcoholic solution for eight weeks. Pustular lesions responded promptly, followed by inflammatory papules. Microbiological investigations revealed a lack of propionibacteria as well as reduction of pathogenic staphylococci. Patients after extended local erythromycin treatment did not show any erythromycin serum levels.
Article
The percutaneous penetration and the metabolism of benzoyl peroxide (BPO) were assessed in vitro on human skin and in vivo on 5 patients with leg ulcers. The BPO in vitro absorbed by the skin was converted to benzoic acid preferably in the dermis. The portion penetrated through the skin was benzoic acid only. Also in patients treated with BPO, no BPO could be detected in the serum. These findings show that BPO as such is absorbed by the skin, but is systemically absorbed only after the metabolisation to benzoic acid. Therefore a systemic-toxic effect in local therapy with BPO can be excluded.
Article
The transepidermal penetration and metabolic disposition of 14C-benzoyl peroxide were assessed in vitro (excised human skin) and in vivo (rhesus monkey). In vitro, the benzoyl peroxide penetrated into the skin, through the stratum corneum or the follicular openings, or both, and was recovered on the dermal side as benzoic acid. In vivo, benzoic acid was recovered from urine in amounts equivalent to 45% and 98% of the radiolabel following, respectively, topical and intramuscular administration of small amounts of 14C-benzoyl peroxide. We conclude that benzoyl peroxide penetrates as such into the skin layers and is converted therein to benzoic acid, which, in turn is absorbed into the systemic circulation. Renal clearance of the metabolite is sufficiently rapid as to preclude its hepatic conjugation with glycine, since following topical administration to rhesus monkeys, no hippuric acid was found in the urine, as could have been expected had a significant amount of benzoic acid passed through the liver.
Article
We used information from the Group Health Cooperative of Puget Sound, Washington, USA, to evaluate the risk of birth defects in mothers exposed to topical tretinoin--a retinoid preparation used to treat acne--in the first trimester of pregnancy. We identified 215 women who delivered live or stillborn infants at Group Health Cooperative hospitals and who were exposed to topical tretinoin early in pregnancy, and 430 age-matched nonexposed women who delivered live or stillborn infants at the same hospitals. The prevalence of major anomalies among babies born to the exposed women was 1.9% and among babies born to the nonexposed women was 2.6%. The relative risk estimate for having a baby with a major congenital anomaly for exposed versus nonexposed women was 0.7 (95% CI 0.2-2.3). We conclude that topical tretinoin is not associated with an increased risk for major congenital disorders.
Article
Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3+/-11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 microg/cm2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC). Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same Rf as benzoquinone, which was decreased with azide treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.
Article
The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL(-1)) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL(-1). Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL(-1). The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake.
Article
Background: Apart from oral drug treatment, drug therapy in acne vulgaris comprises topical treatment with agents with a primarily keratolytic action (e.g. tretinoin and benzoylperoxide), and with antibiotics (clindamycin, erythromycin, and erythromycin-zinc complex). The acne grade in the particular patient usually determines the selection of the preferred route of administration, viz. topical or oral, or a combination of both, and topical treatment is usually preferred in mild to moderate acne. The fact that a topically applied compound may also become systemically available to a quantifiable extent, is not generally considered. Aim: The present paper reviews the clinical data on transdermal uptake of anti-acne agents in man, also with respect to their relevance for daily clinical practice. Outcome: The majority of published data on transdermal penetration of topical anti-acne agents focuses on the retinoid tretinoin, and on the antimicrobial agent clindamycin. This interest emerges from the fact that these agents have been associated with embryotoxicity/teratogenicity, and pseudomembranous colitis, respectively. For both compounds the extent of systemic availability after topical application is low, viz. 5-7% and 8%, respectively, at its highest. The height and variability in endogenous retinoid levels is very likely to outweigh any contribution of exogenously applied tretinoin, but a full consensus on the safe use of topical tretinoin in pregnancy is still lacking. With respect to clindamycin, the suggested association between its topical use and the occurrence of pseudomembranous colitis appears not to be of clinical relevance. In order to reduce systemic exposure to clindamycin as much as possible, topical application of clindamycin phosphate is to be preferred over clindamycin hydrochloride salt. Regarding other topical anti-acne agents, it has been suggested that topical zinc-erythromycin is to be preferred over erythromycin, both from clinical efficacy and safety viewpoints. With respect to the currently used compounds like benzoylperoxide, azelaic acid, and adapalene, available clinical pharmacokinetic data are scarce, and significant safety concerns did not emerge as yet. Conclusion: The limited transdermal uptake of topical anti-acne agents underpins their safe use in daily clinical practice. With respect to topical retinoids, formal consensus is lacking regarding their use in pregnancy.
Article
This is a retrospective study on the epidemiology of 205 patients with melasma seen in a tertiary dermatological referral centre in Singapore. The mean age of the 205 patients with melasma was 42.3 years with a female preponderance of 21:1 female to male ratio. There were proportionally more Chinese with melasma than the other races compared to the racial distribution of patients attending our clinic. Ninety percent of our patients had skin type III or IV. The mean age of onset of melasma was 37.6 years. Most sought treatment only 5 years after the appearance of their melasma. Forty-six percent of melasma were light brown, the majority of which were distributed on the malar areas (89%). More than 2/3 had epidermal melasma. Eighty-eight percent had mild localised melasma (occurring on < 20% of the total facial area). Only 26.8% of our patients reported sun exposure, 25 (12.1%) reported pregnancy and 27 (13.1%) reported oral contraceptives as precipitating factors. A positive family history of melasma was observed in 21 (10.2%) patients. Sunscreen forms the backbone in the treatment of melasma in our patients. Most patients were prescribed a sunscreen together with hydroquinone containing bleaching cream (54%) as first line treatment. Patients with epidermal type of melasma responded slightly better to treatment than those with dermal type of melasma (28% experienced > 25% reduction in pigmentation compared to 16% respectively (n.s.)). Overall, 53% of our patients experienced some reduction of pigmentation with 28% experiencing > 25% reduction and 7% experiencing > 75% reduction. In 40%, the pigmentation remained stable with treatment. Treatment of melasma remains an enigma. More studies need to be undertaken to improve treatment response to alleviate the psychosocial impact melasma has on the patient.
Article
Topical preparations of tretinoin are used for the treatment of various skin conditions and for rejuvenation of the skin. Published information on pregnancy outcome following maternal exposure to topical tretinoin is limited to three case reports. We report a case of a patient with anomalies involving the ear and central nervous system with exposure to topical tretinoin during the first trimester. Though the potential link between the use of topical tretinoin and the existence of fetal malformations remains to be further documented by animal as well as epidemiological studies, we strongly recommend that the use of topical tretinoin during pregnancy should be discouraged, and effective contraception should be used in patients of childbearing age.
Article
Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat. Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.
Article
The purpose of the present study was to develop a reverse-phase high-performance liquid chromatographic (HPLC) assay for quantifying four common sunscreen agents, namely 2-hydroxy-4-methoxybenzophenone, 2-ethylhexyl-p-methoxycinnamate, 2-ethylhexylsalicylate (octylsalicylate) and salicylic acid 3,3,5-trimethcyclohexyl ester (homosalate) in a range of biological matrices. This assay was further applied to study the skin penetration and systemic absorption of sunscreen filters after topical application to human volunteers. Separation was achieved utilizing a Symmetry C(18) column with methanol-water as the mobile phase. The assay permits analysis of the sunscreen agents in biological fluids, including bovine serum albumin (BSA) solution, plasma and urine, and in human epidermis. The assay was linear (r2 > 0.99) with minimum detectable limits of 0.8 ng for oxybenzone, 0.3 ng for octylmethoxycinnamate, and 2 ng for homosalate and octylsalicylate. The inter- and intra-day variation for the four sunscreens was less than 3% at the upper end of the linear range and less than 6% at the lower end. Recoveries of sunscreens from plasma, 4% (w/v) BSA solution and epidermal membranes were within the range of 91-104%. Recoveries from urine of the four sunscreens, and oxybenzone with its metabolites were more than 86%. Up to approximately 1% of the applied dose of oxybenzone and its metabolites was detected in the urine. Appreciable amounts were also detected in the stratum corneum through tape stripping. The HPLC assay and extraction procedures developed are sensitive, simple, rapid, accurate and reproducible. Results from the preliminary clinical study demonstrate significant penetration of all sunscreen agents into the skin, and oxybenzone and metabolites across the skin.
Article
Topical tretinoin (Retin-A) is used to treat acne and photodamaged skin. Its teratogenic potential is of concern due to its similarity to isotretinoin (Accutane), a recognized human teratogen. Through the California Teratogen Information Service and Clinical Research Program, between 1983 and 2003, 106 pregnant women with first-trimester exposure to topical tretinoin were prospectively ascertained and followed. Birth outcomes, including pregnancy loss, major structural defects, and pre- and postnatal growth were compared to 389 similarly and prospectively ascertained women with no topical tretinoin exposure during pregnancy. Because a distinct pattern of malformation had already been described for isotretinoin, we also compared exposed (n = 62) and unexposed (n = 191) infants on the prevalence of a specific subset of minor malformations selected to represent the spectrum of defects comprising the retinoic acid embyopathy. There were no significant differences between groups in the proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs. 8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Furthermore, the prevalence of one or more retinoic acid-specific minor malformations did not differ significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51). First-trimester topical tretinoin exposure in this study was not associated with an increased risk of any adverse pregnancy outcome evaluated. Specifically, there was no indication that topical tretinoin is associated with an increased risk for minor malformations that are consistent with the retinoic acid embryopathy. Although it is impossible to exclude the possibility that some women/infants may be uniquely susceptible to topical tretinoin exposure, this study provides further reassurance for women who are inadvertently exposed early in pregnancy.
Article
Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats. To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted. Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm(-2), and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high-performance liquid chromatography method. The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test). We show that a large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the volunteers excreted BZ-3 5 days after the last application.
Article
Many women of childbearing age from sub-Saharan Africa use topical skin lighteners, some of which present a risk of toxic systemic effects. The goals of this study were to evaluate, in this environment, the frequency of this practice during pregnancy, as well as eventual consequences on pregnancy. Ninety-nine women from 6 to 9 months pregnant were randomly selected among those attending a standard maternal centre in Dakar for a prenatal visit. Investigations consisted of questions about the use of skin lighteners, a standard clinical examination, follow-up until delivery and a morning blood sample for plasma cortisol levels. Sixty-eight of the 99 selected women used skin lighteners during their current pregnancy, the main active ingredients being hydroquinone and highly potent steroids (used by 64 and 28 women, respectively). No difference in the main outcomes of pregnancy were found between skin-lightener users and the others; however, women using highly potent steroids, when compared with those who did not, had a statistically significant lower plasma cortisol level and a smaller placenta, and presented a higher rate of low-birth-weight infants. Skin lightening is a common practice during pregnancy in Dakar, and the use of steroids may result in consequences in the mother and her child.
Article
In the late 1980s and early 1990s, researchers hypothesized that aspirin could be used to prevent or delay the onset of preeclampsia. This hypothesis was tested in numerous trials which showed limited, but positive results. Subsequently, aspirin has been used in an attempt to improve pregnancy outcomes in women who have both antiphospholipid antibodies and a history of recurrent loss, and has also been used in an attempt to improve the success of in vitro fertilization. In theory, aspirin has both positive and negative effects on reproduction. Aspirin, which suppresses cyclooxygenase, has the potential to interfere with implantation, but also has the potential to support the maintenance of pregnancy. Aspirin is prescribed with increasing frequency to reduce the risk of maternal thrombosis and reduce the risk of miscarriage and poor pregnancy outcome. Aspirin alone, however, is not considered sufficient to prevent thrombosis and even in women with the antiphospholipid syndrome, the question as to whether low-dose aspirin improves pregnancy outcomes has not been answered affirmatively. Aspirin has potential risks. Aspirin inhibits platelet function and can contribute to maternal and fetal bleeding. Aspirin crosses the placenta. Although aspirin has not been associated with other congenital anomalies, it has been associated with an increased risk of vascular disruptions, particularly gastroschisis and possibly premature closure of the ductus arteriosus. Nonetheless, large trials demonstrate low-dose aspirin's relative safety and generally positive effects on reproductive outcomes.
Article
Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1.
Metals and the skin. Topical effects and systemic absorption
  • Rh Guy
  • Jj Hosynek
  • Rs Hinz
  • Lorence
Guy RH, Hosynek JJ, Hinz RS, Lorence CR. Metals and the skin. Topical effects and systemic absorption. New York, NY: Informa Health Care; 1999.