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Cosmetic aspects of pregnancy
Clinics in Dermatology (2006) 24, 133 – 141
Cosmetic aspects of pregnancy Rachel Nussbaum, MDa, Anthony V. Benedetto, DOb,c,* a
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA Department of Dermatology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA c Dermatologic SurgiCenter, Philadelphia, PA 19167, USA b
Abstract There are a vast number of changes to the female body that occur during pregnancy, to which any pregnant woman will attest. The changes, although considered, for the most part, physiological and not pathological, are quite distressing to many women. This chapter serves to review those changes and comment on their physiological origins. Most of these changes can be definitively or inferentially linked to the dramatic hormonal changes that take place to support a pregnancy. Comments are also made about treatment as they pertain to pregnant women. In addition, a brief discussion about performing cosmetic procedures during pregnancy is included. D 2006 Elsevier Inc. All rights reserved.
The hormonal changes in pregnancy The hormonal changes that occur in the pregnant women are quite dramatic and are not limited to ovarian or placental derived hormones. Estrogen production from the placenta as well as the ovary increases gradually from the second month of pregnancy until term. Progesterone is also predominantly placental in origin, and it rises to a peak during the fifth month of pregnancy. The placenta is also a source of human chorionic gonadotropin, which increases dramatically during the first trimester and drops dramatically once estrogen and progesterone increase.1 Other endocrine organs undergo dramatic changes in pregnancy as well. The anterior pituitary gland increases in weight by more than two-fold during pregnancy with a concomitant increase in gonadotropin hormone secretion.2 The adrenal cortex undergoes significant hypertrophy with increased production and secretion of hormones. The
4 Corresponding author: 1200 Locust Street, Philadelphia, PA 19107, USA. Tel.: +1 215 546 3666; fax: +1 215 546 6060. E-mail address: [email protected] (A.V. Benedetto). 0738-081X/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2005.10.007
adrenal hormones include the glucocorticoid cortisol, the mineralocorticoid aldosterone, and the sex steroid hormone dehydronepiandrosterone.1 Changes in the thyroid gland are observed as well: it increases in volume and hormone secretion beginning in the second trimester, and one of the many effects is an increase in basal metabolic rate.1,2 The endocrine changes in pregnancy are protean; it is no surprise that there are subsequent changes to the skin, eccrine, apocrine, pilosebaceous, and vascular systems (Fig. 1). Hormonal receptors can be found throughout the skin, its appendages, and vasculature, and the changes that occur are likely mediated primarily via these receptors.
Pigmentary changes in pregnancy A variety of pigmentary changes occur in 90% of pregnant women.3 It is well known that benign nevi and freckles become hyperpigmented during pregnancy.4 Scars that are fairly new can also become similarly hyperpigmented.4 There is usually a generalized mild hyperpigmentation of the skin with pregnancy (Figs. 2 and 3). In anatomic
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Fig. 1
Telangiectasia associated with pregnancy.
regions that are already pigmented in the nonpregnant state, such as the nipples, areola, and external genitalia, the hyperpigmentation that occurs with pregnancy is more intense. In addition, the linea alba, which is a tendinous median line on the anterior abdominal wall, becomes hyperpigmented predominantly during the first trimester of pregnancy. It is thereafter referred to as the linea nigra. Hyperpigmentation can also occur in the axillae as well as the upper inner aspects of the thighs, although this occurs in a smaller proportion of women.4 These pigmentary changes begin early in pregnancy, gradually increase during the pregnancy, and often decrease postpartum. Anatomic areas that are already hyperpigmented (areolae, nipples, and genitalia), however, generally do not return to their prepregnancy color.5 Groups have hypothesized that the darkening in these areas occurs because of a greater sensitivity to hormonal stimulation in anatomic regions with a higher concentration of melanocytes.6,7 Shizume and Lerner,8 in 1954, found an increase in serum and urinary melanocyte-stimulating hormone during pregnancy that then rapidly decreased after parturition. This finding, however, does not explain the entire story: Thody et al9 found that plasma b–melanocytestimulating hormone levels were not significantly different in late pregnancy or after delivery. These findings appear to conflict; however, the control of different subtypes of
Fig. 2
Hyperpigmentation.
Fig. 3
Mottled pigmentation.
melanocyte-stimulating hormone may be varied and lead to differential end organ effects. Furthermore, estrogen and progesterone are known to be strong stimulators of melanocytes, which might explain how hyperpigmentation occurs without a detectable increase in melanocyte-stimulating hormone early in pregnancy.10 Recent studies have demonstrated that the placenta is rich in bioactive molecules other than estrogen and progesterone that can induce pigmentation both in vitro in human cells and in vivo in animal models.11 These molecules include human placental lipids, which stimulate melanocytes by up-regulating tyrosinase activity.11 Another pigmentary change is melasma (chloasma), also known as bthe mask of pregnancy,Q which occurs in greater than 50% of pregnant women (Fig. 4). Clinically, melasma appears as blotchy, irregularly shaped patches of light- to dark-brown hyperpigmentation with very well demarcated borders. It typically affects the cheeks and upper lip but can occur anywhere on the face as well as the upper extremities. Its onset is usually in the second half of pregnancy, and dark complexioned women are more often affected.5,6,12 The centrofacial pattern is the most common, occurring in 63% of women. The malar pattern is seen in 21% of cases, and the mandibular type occurs in 16% of women.4 Melasma has two main histological patterns, the epidermal and dermal types. The epidermal type is the most common and is characterized histologically by increased numbers of melanocytes and increased melanin deposition in basal as well as suprabasal keratinocytes. The
Fig. 4
Melasma.
Cosmetic aspects of pregnancy dermal type has numerous melanophages both in the superficial and deep dermis. Seventy-two percent of cases seem to be purely epidermal melasma, whereas 13% have a purely dermal histological phenotype. Mixed types occur in five percent of pregnant women. Wood’s lamp examination helps demonstrate the difference between epidermal and dermal melasma, as only the epidermal subtype will enhance the color contrast between the affected and normal skin.13 The cause of melasma has not been entirely elucidated; studies point to hormonal changes being important.14 Sunlight appears to play a major role because areas affected are usually those with maximal sun exposure, and patients often describe an exacerbation of melasma with exposure to sunlight.14 Finally, there does appear to be a genetic component as well. Fortunately, melasma associated with pregnancy typically completely disappears within a year of delivery, but one study showed persistence of melasma in 30% of postpartum women, with presence of melasma as long as 10 years after delivery.5,8 Treatment of melasma is routinely deferred until after delivery for obvious reasons. Firstly, the hormonal trigger for melasma persists throughout pregnancy, making melasma more resistant to treatment. Secondly, most women have a significant improvement in melasma after parturition, making therapy unnecessary. Thirdly, the mainstay of therapy for melasma is relatively contraindicated during pregnancy. Although a comprehensive review of the therapeutic options is beyond the scope of this chapter, several common treatment options will be reviewed. Hydroquinone, for example, is in the US Food and Drug Administration pregnancy category C because studies have never been conducted to see whether hydroquinone causes fetal harm when applied topically.15,16 Tretinoin has also been shown to be effective in treating melasma; however, it is pregnancy category C in the United States and category D in the Australian equivalent administration. There are several reports of fetal malformations when mothers used tretinoin during pregnancy; nonetheless, causation cannot be definitely determined.17 Glycolic acid has not received a US Food and Drug Administration pregnancy rating, but epidemiological studies have failed to demonstrate any fetal abnormalities from its use during pregnancy.18,19 Lasers and light sources have also been used and are effective for melasma; however, use during pregnancy has not been studied.20 Most physicians are extremely cautious with pregnant patients and assume a minimalist approach, deferring therapy until the postpartum period, and it is the impression of the authors that most pregnant women prefer to delay treatment until that time as well.
The pilosebaceous unit and pregnancy Hirsutism is defined as excessive hair growth in both a normal and abnormal distribution (Fig. 5). It occurs to some
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Fig. 5
Hirsutism.
degree in all pregnant women, usually early in pregnancy. Women who already have dense dark hair tend to have a greater degree of hirsutism with pregnancy, and it is most pronounced on the upper lip, chin, and cheeks, although generalized hair growth may occur as well.4 In addition to increases in facial hair, hypertrichosis overlying the midsuprapubic area is common. Within six months of parturition, most of the fine lanugo hairs disappear, but coarse terminal hairs tend to remain.4 There are now numerous permanent and nonpermanent options for treating hirsutism. These include shaving, waxing, electrolysis, and laser epilation. Lasers have become very popular and effective in recent years.20 Once again, treatment is typically deferred until after parturition because the effects of lasers during pregnancy have not been definitively determined. It is the opinion of the authors to take a conservative approach and defer treatment until after delivery. Scalp hair becomes fuller during pregnancy, which correlates with an increase in the mean hair shaft diameter when compared with the nonpregnant state.21 Lynfield22 studied the histological characteristics of hair during pregnancy and found an increase in the proportion of anagen to telogen hairs during pregnancy. The mean percentage of anagen hairs in the first trimester was 85%, which was similar to nonpregnant controls. By the second trimester, the percentage increased to 95%, and this proportion was maintained through the first week postpartum.22 This phenomenon is probably due to estrogen’s effect on prolonging the anagen phase.6 There are abundant estrogen receptors (b-type) expressed within the hair follicle, and it is likely that higher levels of estrogen binding to these receptors induces changes that keep follicles in the anagen phase of the hair growth cycle.23 Coincident with the abrupt decrease in estrogen upon parturition, there is a dramatic shift of the recruited anagen hairs to telogen hairs. Lynfield22 found that the percentage of anagen hairs dropped dramatically to 76% shortly after parturition. Clinically, the telogen effluvium that ensues appears as a dramatic loss of hair that begins four to 20 weeks postpartum and can continue for up to one year. Telogen effluvium that occurs postpartum is considered a
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Fig. 6
Telogen effluvium.
normalization of scalp hair follicles to the prepregnancy state, and complete hair regrowth occurs within 15 months (Fig. 6).22 Nonetheless, women often complain that the density is not that of prepregnancy.4,6,12 Other changes to the pilosebaceous unit are not as well understood. For example, the effect of pregnancy on acne has not been extensively reviewed and anecdotal reports are conflicting (Fig. 7). Some women report improvement in acne with pregnancy, whereas others report worsening. Ratzer24 reviewed the effect of pregnancy on acne in more than 400 women and found that pregnancy improved acne in 58% of women surveyed. She also found that after delivery, 75% of women reported improvement in acne, 13% reported no change, and 12% reported worsening of their acne. In an attempt at studying mechanisms, Burton found that sebum excretion in the forehead increases during pregnancy and remains high postpartum in nursing women.25 Whether this finding correlates with clinical worsening of acne is unclear.26
Connective tissue changes in pregnancy Of pregnant women, 55% to 90% will develop striae distensae.4,27 The body areas typically involved are the abdomen, hips, buttocks and breasts. The striae begin as pink-purple linear streaks oriented perpendicular to skin tension lines. Occasionally, striae are pruritic. With time, as with all striae, they become more pale and less noticeable. Etiologies include hormonal influences (adrenocorticosteroids, estradiol, and relaxin), as well as the physical stretch
Fig. 7
Acne secondary to pregnancy.
and distension associated with increased abdominal girth. Liu28 discussed that during pregnancy, two factors are necessary for the production of striae. The first is the priming of the skin by increased levels of estrogen and relaxin. Together, these hormones increase the production of collagen and nonsulfated mucopolysaccharides. The abundance of mucopolysaccharide in the dermis attracts water, which acts to decrease the cohesive forces between collagen fibers, leading to easy separation. The second factor is the physical stretch upon the primed dermis, causing breaks in collagen. He proposed that without priming the dermis, no striae would form when the skin is stretched. Others feel stretch alone promotes the development of striae and that tearing of collagen as well as elastic fibers contributes to their appearance.29,30 More recently, Watson et al31 commented that changes in the elements of the skin necessary for tensile strength and elasticity are suspected in the development of striae gravidarum (Fig. 8). These extracellular matrix components include fibrillin, elastin, and collagen. A study was done on skin biopsies from striae and adjacent normal skin in pregnant women. The differences found included looser dermal matrix, increased glycosaminoglycans, reduced fibrillin and elastic fibers, and alterations in the orientation of elastin and fibrillin in the dermis. The striae examined in this study were early erythematous striae, and the techniques used were electron microscopy, light microscopy, and immunohistochemistry. The group posed the question of whether the constant stretch of pregnancy might lead to remodeling of the dermis. This question remains unanswered. In addition to understanding the mechanism of striae formation, several groups have attempted to delineate the predictors for developing striae gravidarum. In 1959, a study linked the association between maternal obesity and weight gain during pregnancy to the development of striae gravidarum.32 In support, another group found that striae gravidarum were associated with body mass index as well as baby weight. Interestingly, they found that advancing age was inversely proportional to the development of striae.33
Fig. 8
Striae gravidarum.
Cosmetic aspects of pregnancy A recent large study found that 50% of patients with striae gravidarum had mothers with striae gravidarum, but the strongest association was made between striae gravidarum and the presence of breast and thigh striae. Among women with striae gravidarum, 81% had preexisting striae on the breasts and thighs. In contrast, only 31% of women without striae gravidarum had striae in these locations. This group did not find that body mass index or degree of weight gain correlated with striae gravidarum development, which does contradict previously published series. The authors do comment that very few women in the study were obese and that this may have skewed the results. Overall, from this study, genetics as well as possible variations in the ultrastructural composition of the dermis seem to play a major role in the development of striae gravidarum.27 No therapy has proven definitively to decrease the development of striae gravidarum. Physicians and patients have toted using olive oil or taking vitamin and mineral supplements to prevent striae gravidarum; however, none have been verified by large prospective trials. One physician’s personal success in preventing striae gravidarum in all of his pregnant patients with a combination of zinc, ascorbic acid, pyridoxal, and flaxseed oil is fascinating and should prompt a prospective, controlled study to evaluate this observation.34 Regarding treatment of striae postpartum, an open-label study with 0.1% tretinoin cream showed a decrease in the severity of striae gravidarum after three months of application.35 Nonetheless, a double-blind placebo-controlled trial of 0.025% tretinoin cream applied for seven months to striae gravidarum failed to demonstrate significant improvements over placebo.36 It is unclear whether the patients in this study were underdosed or if there is truly no effect on striae. Currently, therapies to decrease the appearance of striae include using vascular lasers on pink-purple striae.37 In addition, surgical excision of striae with abdominoplasty has favorable results when there is accompanying redundant abdominal skin. Another well-known connective tissue change in pregnancy is the development of acrochordons. In 1906, Brickner first described small, pigmented, sessile or pedunculated growths concentrated around the neck that appear in the fourth to sixth month of pregnancy and often spontaneously regress after delivery.38 He called them fibroma molluscum gravidarum, although now we know them as skin tags or achrocordons that are simply outgrowths of the epidermis and dermis with a fibrovascular connective tissue core.3 Templeton observed and described their increased incidence in postmenopausal women and concluded that the hormonal changes that occur in these two phases of life are important in the development of achrocordons.38,39 Breast changes are prominent during pregnancy and include enlargement, tenderness, erectile nipples, hyperpigmentation of the nipples and areolae, prominence of veins, striae, and enlargement of Montgomery’s tubercles.4 These
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Fig. 9
Facial puffiness.
are elevated brown papules of sebaceous origin associated with lactiferous ducts on the areolae of the breasts. Causes for all of these changes include increases in hormones of adrenal, pituitary, ovarian, and placental origin, as well as sodium and fluid retention.4 During late pregnancy, nonpitting edema occurs in 50% of women. There is a visible puffiness in the eyelids, face, and hands of pregnant women. Carpal tunnel syndrome is a common complication of this edema (Fig. 9).4,40 Pitting edema occurs in dependent areas such as the feet and legs in 70% of pregnancies, and these findings are not related to preeclampsia or eclampsia. Fluid shifts are thought to be secondary to both increased sodium and water retention, as well as increased vascular permeability, which are affected by the high levels of hormones in pregnancy. These changes almost always reverse shortly after delivery.4
Sweat glands and pregnancy Eccrine sweating gradually increases during pregnancy, and this can lead to complications such as miliaria.4 Potential etiologies include thyroid overactivity and the increased weight of pregnancy. In contrast, palmoplantar perspiration is decreased near late pregnancy, and this is thought to be related to increased adrenocorticotropic activity.41 Apocrine gland activity commonly decreases during pregnancy, and there have been reports of improvement in apocrine-driven dermatoses such as hidradenitis suppurativa and Fox-Fordyce disease. Hormonal effects are suspected in this phenomenon as well, although further study of the subject is lacking.42
The vascular changes of pregnancy Vascular changes in pregnancy are well described and are related to two major factors: hormonal changes and increases in intravascular pressure. The palmar erythema occurring in pregnancy has two distinct clinical presentations (Figs. 10 and 11). The first is diffuse mottling of the entire palm with accompanying cyanosis and pallor.5,6,12 The second is a mottled erythema of the palms that is most pronounced over the thenar and hypothenar eminences, near the metacarpophalangeal
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Fig. 12
Fig. 10
Palmar erythema.
joints, and the tips of the fingers. The former is most common, morphologically mimicking the palmar erythema seen in hyperthyroidism and hepatic cirrhosis.4 In a large study by Bean et al,43 62.5% of white and 35% of AfricanAmerican pregnant women developed palmar erythema. One third of the white women developed the erythema by the second month of pregnancy, and there was a steady increase in the incidence as the ninth month approached. Of those with palmar erythema, 91% saw resolution by the seventh week postpartum. Etiologies include increases in blood volume and blood flow that normally occur during pregnancy, genetic factors, as well as increased circulating estrogen. Another common vascular change in pregnancy is the spider angioma (Fig. 12). Corbett44 first described the appearance of spider angiomata during pregnancy and their subsequent resolution upon parturition. Spider angiomata are characterized by three clinical features: the central pulsating arteriole, the fine radiating branches, and the surrounding erythema. The surrounding erythema extends several millimeters beyond the visible vessels. Spider angiomata appear bright red, and the temperature of the skin overlying them is warmer than the adjacent skin. Bean et al43 found that 67% of white pregnant women had spider angiomata; conversely, they were only present in 11% of African-American pregnant women. The study also found that 14% of white women had spider angiomata by the second month of pregnancy, but African-American women developed them only after the fourth month of
Fig. 11
Palmar erythema.
Spider hemangiomas of left cheek.
pregnancy. As in the case of palmar erythema, 75% of spider angiomata in this series resolved by the seventh week after parturition. Spider angiomata are most commonly present in areas drained by the superior vena cava: the neck, throat, face (especially the periorbital area), and arms.5,12 Regarding the etiology of these vascular changes, no hepatic abnormalities were found in any of these women, and they were no more likely to occur in women with toxemia or hypertension. Although morphologically identical to the angiomata appearing in liver disease, impaired liver function is not thought to play a role in the development of spider angiomata in pregnancy. The conclusion was that estrogen, in particular, had effects on vasculature, and it is likely that elevated estrogen is the shared metabolic factor that is causative in the vascular lesions of pregnancy and liver failure.43 Treatment of spider angiomata includes cryosurgery, electrocautery, and vascular lasers. These procedures are probably safe during pregnancy, but one must weigh the potential risks and benefits of any treatment. Fortunately, most resolve spontaneously, never needing treatment. It is our impression that most patients and their physicians would prefer to treat these benign lesions after delivery. Vascular changes occur on a larger scale as well. Of pregnant women, 40% develop varicosities (Fig. 13), most commonly occurring in the legs; however, hemorrhoidal and vulvar varicosities are also prevalent.4 Pressure from the gravid uterus leads to partial obstruction of the inferior vena cava; this causes an increase in venous pressure. Data point to decreased vessel wall strength during pregnancy as well. Together, these factors probably lead to the development of
Fig. 13
Varicose and spider veins secondary to pregnancy.
Cosmetic aspects of pregnancy varicosities.5,7,12 It is interesting, however, to point out that varicosities are commonly seen toward the end of the first trimester of pregnancy, a time when intrapelvic pressure is not significant. This observation suggests that vascular fragility in pregnancy may play an important role.5 In addition, it is clear that local factors are not the only contributors, but genetics as well as behavioral factors play a key role. Behavioral factors that may exacerbate varicosities or increase the risk of developing them include prolonged sitting or standing or wearing tight belts or girdles (all activities that obstruct venous return).4 Prevention or minimizing the risk of developing varicosities is the aim of intervention during pregnancy. These measures include leg elevation, sleeping in a Trendelenburg position, lying in the left lateral decubitus position, and avoiding tight-fitting clothing. These measures theoretically help improve venous return and decrease venous hypertension. In addition, wearing elastic compression stockings also aids in compressing the superficial vasculature without impairing circulation.4,42 Although these measures are commonly recommended, there are no studies to prove definitively that these measures actually decrease venous hypertension, improve venous return, or decrease the occurrence of varicosities. Treatment of varicose veins (Fig. 13) include vein stripping, endovascular ablation, endovascular sclerotherapy, and radiofrequency techniques, among others.45 A comprehensive review of these techniques is beyond the scope of this chapter. For the treatment of telangiectasia, lasers, light sources, and sclerotherapy are available. These treatments are effective but are generally not done during pregnancy because the risks are unknown.46 These treatments can be performed safely after parturition, when they will likely be more effective, and the authors strongly recommend that treatment be avoided during pregnancy. There are other vascular changes that occur less commonly in pregnancy but are worth mentioning. Five percent of pregnant women develop small superficial or subcutaneous cavernous hemangiomas. Elevated estrogens are thought to be responsible. These occur toward the end of the first trimester and gradually increase in size as the pregnancy continues.5 Cutis marmorata is a bluish mottling of the skin upon exposure to cold. This is seen occasionally on the lower extremities during pregnancy.5,12 Of course, should this persist after delivery, secondary causes other than a hyperestrogen state must be ruled out. Purpura of the lower extremities is also a common finding in pregnancy and is speculated to be due to increased capillary fragility in the face of higher venous pressures.5
The oral mucosa and pregnancy Changes in the gingiva occur commonly during pregnancy as well. These changes have been termed stomatitis gravidarum, hypertrophic gingivitis of pregnancy, prolifera-
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Fig. 14
Pyogenic granuloma.
tive gingivitis of pregnancy, epulis gravidarum, or pregnancy tumor.38 The most common gingival change in pregnancy is edema of the gums, changing their color from dark red to blue. There is also an increased tendency for the gums to bleed. These changes usually occur during the fourth month of pregnancy and subside in the weeks after delivery. A curious phenomenon occurring commonly in pregnancy is the pregnancy tumor or epulis gravidarum.47 It occurs in approximately two percent of pregnancies and appears during the second through fifth months of pregnancy. The pregnancy tumor appears on the gingiva and is histologically indistinguishable from a pyogenic granuloma (Fig. 14).4 The lesion is typically smooth, soft to semifirm, with a shiny, red-purple or red-pink hue. The lesion can be pedunculated or sessile, and the classic location is the interdental papilla, but other common locations include the buccal or lingual surfaces of the gingiva.47 Usually, these tumors regress spontaneously with parturition, although minor trauma can lead to hemorrhage and ulceration. The pregnancy tumor often occurs in women who have extensive gingivitis of pregnancy.4 Removal of the pregnancy tumor is typically deferred until several months postpartum because of the high rate of spontaneous regression, unless there is extensive bleeding, pain, difficulty eating, or if the patient feels that the cosmetic appearance of the tumor is too disruptive.
Cosmetic procedures during pregnancy The question whether cosmetic procedures can be performed on pregnant patients often arises. It is our impression that most dermatologists and cosmetic surgeons prefer to avoid performing procedures that are medically unnecessary in this setting. The motivation behind this practice is likely mostly a medicolegal one. As most medications and devices are not tested on pregnant patients, the effects on the fetus are unknown. Many medications, as already discussed, are rated by the US Food and Drug Administration as Pregnancy Category C.48 Most often, medications receive this rating because the manufacturing companies choose not to study these drugs in pregnancy. To
140 perform these procedures or use these medications, therefore, might put the practitioner at risk for litigation. Botulinum toxin A (Allergan, Irvine, Calif) is a cosmetic drug that does have some literature supporting its use in pregnancy because of its initial medical indication to treat cervical dystonia and blepharospasm. Upon review of the literature, several case reports are found about its use in pregnancy. One patient was treated during her four pregnancies. To date, the longest follow-up is five years, and none of her children have demonstrated any apparent developmental abnormalities.49 Furthermore, there have been no cases of abnormal deliveries or floppy babies as reported by 396 physicians responding to a survey about botulinum toxin injections in pregnant patients.50 There are several cases of maternal botulism with normal outcomes in the newborns.51,52 In one case of maternal botulism, there were undetectable levels of botulinum toxin present in the infant’s serum, suggesting that the neurotoxin may not cross the placenta.53 Subsequent to these reports, one group described a pregnant women who received 500 U of botulinum toxin for cervical dystonia.54 At 10 weeks gestation with twins, no fetal heartbeat could be detected. Clearly there is no definitive association between the fetal demise and botulinum toxin, and the patient had several risk factors for fetal demise. Nonetheless, the general consensus is to be conservative and avoid administering botulinum toxin for cosmetic purposes to pregnant women. Collagen injections have not been studied in pregnancy; however, there is a report of one woman being treated with collagen for urinary stress incontinence and had a normal pregnancy.55 No adverse effects have been reported to date from collagen injections in pregnancy, but if the injection is for cosmetic purposes, the authors advise against its use during pregnancy. Hyaluronic acid gels for soft tissue augmentation have not been studied in pregnant patients as they are relatively new on the market. There are no case reports of outcomes in pregnant patients treated with hyaluronic acid. The consensus among hyaluronic acid gel manufacturers is to avoid use during pregnancy, although theoretically, no adverse events are predicted to occur because the composition is identical to human hyaluronic acid.56 More invasive cosmetic surgical procedures are considered too risky during pregnancy because of the need for general anesthesia; therefore, these are best left for the postpartum period.
Conclusions Pregnancy is associated with dramatic physiological changes to the female body, many of which manifest as cosmetic changes. It is quite impressive just how many of these changes regress with parturition. Despite these changes essentially being cosmetic in nature and not harmful, they do cause distress to many women. By educating patients
R. Nussbaum, A.V. Benedetto regarding what to expect and promoting a healthy lifestyle during pregnancy, perhaps we can alleviate some of the anxiety associated with the appearance of these physiological changes. As the understanding of the endocrine changes and the effects on end organs progresses, perhaps we can further elucidate why all these changes indeed occur. With regard to performing cosmetic procedures in pregnancy, it is the opinion of the authors that a conservative approach be followed if the purpose is purely cosmetic in nature.
References 1. Braude P, Hamilton-Fairley D. Hormonal changes during puberty, pregnancy, and the menopause. In: Black M, McKay M, Braude P, et al, editors. Obstetric and gynecologic dermatology. 2nd ed. London7 Mosby; 2002. p. 1 - 8. 2. Hill BHR. The skin and its normal and abnormal states in pregnancy. N Z J Med 1953;53:151 - 6. 3. Errickson CV, Matus NR. Skin disorders of pregnancy. Am Fam Physician 1994;49:605 - 10. 4. Wong RC, Ellis CN. Physiologic changes in the skin during pregnancy. J Am Acad Dermatol 1984;10:929 - 40. 5. Hellreich PD. The skin changes of pregnancy. Cutis 1974;13:82 - 6. 6. Wade TR, Wade SL, Jones HE. Skin changes and diseases associated with pregnancy. Obstet Gynecol 1978;52:233 - 42. 7. Lawley TJ, Yancey KB. Skin changes and diseases in pregnancy. In: Freedberg IM, Eisen AZ, Wolff K, et al, editors. Fitzpatrick’s dermatology in general medicine. 6th ed. New York7 McGraw Hill; 2003. p. 1361 - 6. 8. Shizume K, Lerner AB. Determination of melanocyte-stimulating hormone in urine and blood. J Clin Endocrinol Metab 1954;14: 1491 - 510. 9. Thody AJ, Plummer NA, Burton JL. Plasma beta-melanocyte– stimulating hormone levels in pregnancy. J Obstet Gynaecol Br Commonw 1974;81:875 - 7. 10. Snell RS, Bischitz PB. The effect of large doses of estrogen and estrogen and progesterone on melanin pigmentation. J Invest Dermatol 1960;35:73 - 82. 11. Mallick S, Singh SK, Sarkar C, et al. Human placental lipid induces melanogenesis by increasing the expression of tyrosinase and its related proteins in vitro. Pigment Cell Res 2005;18:25 - 33. 12. Winton GB, Lewis CW. Dermatoses of pregnancy. J Am Acad Dermatol 1982;6:977 - 98. 13. Spielvogel RL, Kantor GR. Pigmentary disorders of the skin. In: Elder D, Elenitsas R, Jaworsky C, et al, editors. Lever’s histopathology of the skin. 8th ed. Philadelphia7 Lippincott Williams & Wilkins; 1997. p. 617 - 24. 14. Pathak MA, Riley FC, Fitzpatrick TB. Melanogenesis in human skin following exposure to long wave ultraviolet and visible light. J Invest Dermatol 1962;39:435 - 43. 15. Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch Dermatol 1995;131:1453 - 7. 16. Hydroquinone. Reprotox. [Online]. [Cited 26 August 2005]. Available from: URL: http://www.thomsonhc.com/hcs/librarian/PFPUI/ DN45xM0UUBHVO/ND_PG/PRIH/CS/CC00C3/ND_T/HCS/ND_P/ Main/DUPLICATI ONSHIELDSYNC/21F8D5/ND _ B / H CS / PFActionId/hcs.main.FollowLink/cgiexe/:mdxcgi:display.exe/scid/ 51756867/cgiparm/CTL=:production:ocmcontent:ocmcontent: 2 0 _ Q 2 : m d x c g i : M E G AT. S Y S & S E T = 4 3 0 F 5 C 7 A 8 D C B E 0 & SYS = 8&T = 1526&D = 1&Q = 0. 17. Tretinoin. TERIS. [Online]. [Cited 26 August 2005]. Available from: U R L : h t t p : / / w w w. t h o m s o n h c . c o m / h c s / l i b r a r i a n / P F P U I /
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24. 25. 26. 27. 28. 29. 30. 31.
32. 33.
DN45xM0UUCcAC/ND_PG/PRIH/CS/CC00C3/ND_T/HCS/ND_P/ M a i n/ D U P L I C AT I O NS H I E L D S Y N C / 21 F 8 D 5 / N D _ B/ HC S / PFActionId/hcs.main.FollowLink/cgiexe/:mdxcgi:display.exe/scid/ 51756867/cgiparm/CTL=:production:ocmcontent:ocmcontent: 2 0 _ Q 2 : m d x c g i : M E G AT. S Y S & S E T = 4 3 0 F 5 D 6 2 7 A F 6 B 0 & SYS = 9&T = 1108&D = 1&Q = 0. Glycolic acid. TERIS. [Online]. 2001 [Cited 26 August 2005]. Available from: URL: http://www.thomsonhc.com/hcs/librarian/ PFPUI/DN45xM0UUCyu5/ND_PG/PRIH/CS/CC00C3/ND_T/HCS/ ND _P/Main/DUPLICATIONSHIELDSYNC/21F8D5/ND_ B/HCS/ PFActionId/hcs.main.FollowLink/cgiexe/:mdxcgi:display.exe/scid/ 51756867/cgiparm/CTL=:production:ocmcontent:ocmcontent: 2 0 _ Q 2 : m d x c g i : M E G AT. S Y S & S E T = 4 3 0 F 5 D B 6 D 6 7 F 6 0 & SYS = 9&T= 472&D =1&Q = 0. Glycolic acid. Reprotox. [Online]. [Cited 26 August 2005]. Available from: URL: http://www.thomsonhc.com/hcs/librarian/PFPUI/ DN45xM0UUCyu5/ND_PG/PRIH/CS/CC00C3/ND_T/HCS/ND_P/ Main/DUPLICATIONSHIELDSYNC/21F8D5/ND_B/HCS/PFActionId/hcs.main.FollowLink/cgiexe/:mdxcgi:display.exe/scid/51756867/ cgiparm/CTL=:production:ocmcontent:ocmcontent:20_Q2:mdxcgi: M E G AT. S Y S & S E T = 4 3 0 F 5 D B 6 D 6 7 F 6 0 & S Y S = 8 & T = 1406&D = 1&Q = 0. Tanzi EL, Lupton JR, Alster TS. Lasers in dermatology: four decades of progress. J Am Acad Dermatol 2003;49:1 - 31. Nissimov J, Elchalal U. Scalp hair diameter increases during pregnancy. Clin Exp Dermatol 2003;28:525 - 30. Lynfield YL. Effect of pregnancy on the human hair cycle. J Invest Dermatol 1960;35:323 - 7. Thornton MJ, Taylor AH, Mulligan K, et al. Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin. Exp Dermatol 2003;12:181 - 90. Ratzer MA. The influence of marriage, pregnancy and childbirth on acne vulgaris. Br J Dermatol 1964;76:165 - 8. Burton JL, Shuster S, Cartlidge M. The sebotropic effect of pregnancy. Acta Derm Venereol 1975;55:11 - 3. Van Pelt HP, Juhlin L. Acne conglobata after pregnancy. Acta Derm Venereol 1999;79:169. Chang ALS, Agredano YZ, Kimball AB. Risk factors associated with striae gravidarum. J Am Acad Dermatol 2004;51:881 - 5. Liu DT. Letter: striae gravidarum. Lancet 1974;1:625. Williams B. Letter: aetiology of striae gravidarum. Lancet 1974;1:307. Shuster S. The cause of striae distensae. Acta Derm Venereol Suppl 1979;59:161 - 9. Watson REB, Parry EJ, Humphries JD, et al. Fibrillin microfibrils are reduced in skin exhibiting striae distensae. Br J Dermatol 1998;138: 931 - 7. Poidevin LOS. Striae gravidarum: their relationship to adrenal cortical hyperfunction. Lancet 1959;274:436 - 9. Thomas RG, Liston WA. Clinical associations of striae gravidarum. J Obstet Gynaecol 2004;24:270 - 1.
141 34. Levin WM. Striae gravidarum: folklore and fact. Arch Fam Med 1995;4:98. 35. Rangel O, Arias I, Garcia E, et al. Topical tretinoin 0.1% for pregnancy-related abdominal striae: an open-label, multicenter, prospective study. Adv Ther 2001;18:181 - 6. 36. Pribanich S, Simpson FG, Held B, et al. Low-dose tretinoin does not improve striae distensae: a double-blind, placebo-controlled study. Cutis 1994;54:121 - 4. 37. Jimenez GP, Flores F, Berman B, et al. Treatment of striae rubra and striae alba with the 585-nm pulsed-dye laser. Dermatol Surg 2003;29: 362 - 5. 38. Kern AB. Cutaneous changes associated with pregnancy. R I J Med 1950;33:525 - 8. 39. Templeton HJ. Cutaneous tags of the neck. Arch Dermatol Syph 1936;33:495 [as cited in Ref 33]. 40. Parmley T, O’Brien TJ. Skin changes during pregnancy. Clin Obstet Gynecol 1990;33:713 - 7. 41. MacKinnon PCB, MacKinnon IL. Palmar sweating in pregnancy. J Obstet Gynaecol Br Commonw 1955;62:298 - 9. 42. Cornbleet T. Pregnancy and apocrine gland diseases: Hidradenitis, Fox-Fordyce disease. AMA Arch Dermatol Syphilol 1952;65:12 - 9. 43. Bean WB, Cogswell R, Dexter M, et al. Vascular changes of the skin in pregnancy. Surg Gynecol Obstet 1949;88:739 - 52. 44. Corbett D. Br J Dermatol Syph 1914;26:200 [as cited in Ref 38]. 45. Weiss RA, Feied CF, Weiss MA. Vein diagnosis and treatment: a comprehensive approach. New York7 McGraw-Hill; 2001. p. 304. 46. Coles CM, Werner RS, Zelickson BD. Comparative pilot study evaluating the treatment of leg veins with a long pulse Nd:YAG laser and sclerotherapy. Lasers Surg Med 2002;30:154 - 9. 47. Barak S, Oettinger-Barak O, Oettinger M, et al. Common oral manifestations during pregnancy: a review. Obstet Gynecol Surv 2003;58: 624 - 8. 48. Key to FDA use-in-pregnancy – ratings. In: Murray L, editor. Physician’s desk reference. 59th ed. New Jersey7 Oradell; 2005. p. 217. 49. Newman WJ, Davis TL, Padaliya BB, et al. Botulinum toxin type A therapy during pregnancy. Mov Disord 2004;19:1384 - 5. 50. Moser E, Ligon KM, Singer C, et al. Botulinum toxin A (Botox) therapy during pregnancy. Neurology 1997;48(Suppl E):399. 51. Long SS. Epidemiologic study of infant botulism in Pennsylvania: report of the infant botulism study group. Pediatrics 1985;75:928 - 34. 52. Polo JM, Martin J, Berciano J. Botulism and pregnancy. Lancet 1996;348:195. 53. St Clair EH, DiLiberti JH, O’Brien ML. Observation of an infant born to a mother with botulism. J Pediatr 1975;87:658. 54. Bodkin CL, Maurer KB, Wszolek ZK. Botulinum toxin type A therapy during pregnancy. Mov Disord 2005;20:1081 - 2. 55. Carr LK, Herschorn S. Periurthral collagen injection and pregnancy. J Urol 1996;155:1037. 56. Restylane. [Online] 2005. [Cited 26 Aug 2005]. Available from: URL: http://www.restylane.com.
Cosmetic aspects of pregnancy Rachel Nussbaum, MDa, Anthony V. Benedetto, DOb,c,* a
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA Department of Dermatology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA c Dermatologic SurgiCenter, Philadelphia, PA 19167, USA b
Abstract There are a vast number of changes to the female body that occur during pregnancy, to which any pregnant woman will attest. The changes, although considered, for the most part, physiological and not pathological, are quite distressing to many women. This chapter serves to review those changes and comment on their physiological origins. Most of these changes can be definitively or inferentially linked to the dramatic hormonal changes that take place to support a pregnancy. Comments are also made about treatment as they pertain to pregnant women. In addition, a brief discussion about performing cosmetic procedures during pregnancy is included. D 2006 Elsevier Inc. All rights reserved.
The hormonal changes in pregnancy The hormonal changes that occur in the pregnant women are quite dramatic and are not limited to ovarian or placental derived hormones. Estrogen production from the placenta as well as the ovary increases gradually from the second month of pregnancy until term. Progesterone is also predominantly placental in origin, and it rises to a peak during the fifth month of pregnancy. The placenta is also a source of human chorionic gonadotropin, which increases dramatically during the first trimester and drops dramatically once estrogen and progesterone increase.1 Other endocrine organs undergo dramatic changes in pregnancy as well. The anterior pituitary gland increases in weight by more than two-fold during pregnancy with a concomitant increase in gonadotropin hormone secretion.2 The adrenal cortex undergoes significant hypertrophy with increased production and secretion of hormones. The
4 Corresponding author: 1200 Locust Street, Philadelphia, PA 19107, USA. Tel.: +1 215 546 3666; fax: +1 215 546 6060. E-mail address: [email protected] (A.V. Benedetto). 0738-081X/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2005.10.007
adrenal hormones include the glucocorticoid cortisol, the mineralocorticoid aldosterone, and the sex steroid hormone dehydronepiandrosterone.1 Changes in the thyroid gland are observed as well: it increases in volume and hormone secretion beginning in the second trimester, and one of the many effects is an increase in basal metabolic rate.1,2 The endocrine changes in pregnancy are protean; it is no surprise that there are subsequent changes to the skin, eccrine, apocrine, pilosebaceous, and vascular systems (Fig. 1). Hormonal receptors can be found throughout the skin, its appendages, and vasculature, and the changes that occur are likely mediated primarily via these receptors.
Pigmentary changes in pregnancy A variety of pigmentary changes occur in 90% of pregnant women.3 It is well known that benign nevi and freckles become hyperpigmented during pregnancy.4 Scars that are fairly new can also become similarly hyperpigmented.4 There is usually a generalized mild hyperpigmentation of the skin with pregnancy (Figs. 2 and 3). In anatomic
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Fig. 1
Telangiectasia associated with pregnancy.
regions that are already pigmented in the nonpregnant state, such as the nipples, areola, and external genitalia, the hyperpigmentation that occurs with pregnancy is more intense. In addition, the linea alba, which is a tendinous median line on the anterior abdominal wall, becomes hyperpigmented predominantly during the first trimester of pregnancy. It is thereafter referred to as the linea nigra. Hyperpigmentation can also occur in the axillae as well as the upper inner aspects of the thighs, although this occurs in a smaller proportion of women.4 These pigmentary changes begin early in pregnancy, gradually increase during the pregnancy, and often decrease postpartum. Anatomic areas that are already hyperpigmented (areolae, nipples, and genitalia), however, generally do not return to their prepregnancy color.5 Groups have hypothesized that the darkening in these areas occurs because of a greater sensitivity to hormonal stimulation in anatomic regions with a higher concentration of melanocytes.6,7 Shizume and Lerner,8 in 1954, found an increase in serum and urinary melanocyte-stimulating hormone during pregnancy that then rapidly decreased after parturition. This finding, however, does not explain the entire story: Thody et al9 found that plasma b–melanocytestimulating hormone levels were not significantly different in late pregnancy or after delivery. These findings appear to conflict; however, the control of different subtypes of
Fig. 2
Hyperpigmentation.
Fig. 3
Mottled pigmentation.
melanocyte-stimulating hormone may be varied and lead to differential end organ effects. Furthermore, estrogen and progesterone are known to be strong stimulators of melanocytes, which might explain how hyperpigmentation occurs without a detectable increase in melanocyte-stimulating hormone early in pregnancy.10 Recent studies have demonstrated that the placenta is rich in bioactive molecules other than estrogen and progesterone that can induce pigmentation both in vitro in human cells and in vivo in animal models.11 These molecules include human placental lipids, which stimulate melanocytes by up-regulating tyrosinase activity.11 Another pigmentary change is melasma (chloasma), also known as bthe mask of pregnancy,Q which occurs in greater than 50% of pregnant women (Fig. 4). Clinically, melasma appears as blotchy, irregularly shaped patches of light- to dark-brown hyperpigmentation with very well demarcated borders. It typically affects the cheeks and upper lip but can occur anywhere on the face as well as the upper extremities. Its onset is usually in the second half of pregnancy, and dark complexioned women are more often affected.5,6,12 The centrofacial pattern is the most common, occurring in 63% of women. The malar pattern is seen in 21% of cases, and the mandibular type occurs in 16% of women.4 Melasma has two main histological patterns, the epidermal and dermal types. The epidermal type is the most common and is characterized histologically by increased numbers of melanocytes and increased melanin deposition in basal as well as suprabasal keratinocytes. The
Fig. 4
Melasma.
Cosmetic aspects of pregnancy dermal type has numerous melanophages both in the superficial and deep dermis. Seventy-two percent of cases seem to be purely epidermal melasma, whereas 13% have a purely dermal histological phenotype. Mixed types occur in five percent of pregnant women. Wood’s lamp examination helps demonstrate the difference between epidermal and dermal melasma, as only the epidermal subtype will enhance the color contrast between the affected and normal skin.13 The cause of melasma has not been entirely elucidated; studies point to hormonal changes being important.14 Sunlight appears to play a major role because areas affected are usually those with maximal sun exposure, and patients often describe an exacerbation of melasma with exposure to sunlight.14 Finally, there does appear to be a genetic component as well. Fortunately, melasma associated with pregnancy typically completely disappears within a year of delivery, but one study showed persistence of melasma in 30% of postpartum women, with presence of melasma as long as 10 years after delivery.5,8 Treatment of melasma is routinely deferred until after delivery for obvious reasons. Firstly, the hormonal trigger for melasma persists throughout pregnancy, making melasma more resistant to treatment. Secondly, most women have a significant improvement in melasma after parturition, making therapy unnecessary. Thirdly, the mainstay of therapy for melasma is relatively contraindicated during pregnancy. Although a comprehensive review of the therapeutic options is beyond the scope of this chapter, several common treatment options will be reviewed. Hydroquinone, for example, is in the US Food and Drug Administration pregnancy category C because studies have never been conducted to see whether hydroquinone causes fetal harm when applied topically.15,16 Tretinoin has also been shown to be effective in treating melasma; however, it is pregnancy category C in the United States and category D in the Australian equivalent administration. There are several reports of fetal malformations when mothers used tretinoin during pregnancy; nonetheless, causation cannot be definitely determined.17 Glycolic acid has not received a US Food and Drug Administration pregnancy rating, but epidemiological studies have failed to demonstrate any fetal abnormalities from its use during pregnancy.18,19 Lasers and light sources have also been used and are effective for melasma; however, use during pregnancy has not been studied.20 Most physicians are extremely cautious with pregnant patients and assume a minimalist approach, deferring therapy until the postpartum period, and it is the impression of the authors that most pregnant women prefer to delay treatment until that time as well.
The pilosebaceous unit and pregnancy Hirsutism is defined as excessive hair growth in both a normal and abnormal distribution (Fig. 5). It occurs to some
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Fig. 5
Hirsutism.
degree in all pregnant women, usually early in pregnancy. Women who already have dense dark hair tend to have a greater degree of hirsutism with pregnancy, and it is most pronounced on the upper lip, chin, and cheeks, although generalized hair growth may occur as well.4 In addition to increases in facial hair, hypertrichosis overlying the midsuprapubic area is common. Within six months of parturition, most of the fine lanugo hairs disappear, but coarse terminal hairs tend to remain.4 There are now numerous permanent and nonpermanent options for treating hirsutism. These include shaving, waxing, electrolysis, and laser epilation. Lasers have become very popular and effective in recent years.20 Once again, treatment is typically deferred until after parturition because the effects of lasers during pregnancy have not been definitively determined. It is the opinion of the authors to take a conservative approach and defer treatment until after delivery. Scalp hair becomes fuller during pregnancy, which correlates with an increase in the mean hair shaft diameter when compared with the nonpregnant state.21 Lynfield22 studied the histological characteristics of hair during pregnancy and found an increase in the proportion of anagen to telogen hairs during pregnancy. The mean percentage of anagen hairs in the first trimester was 85%, which was similar to nonpregnant controls. By the second trimester, the percentage increased to 95%, and this proportion was maintained through the first week postpartum.22 This phenomenon is probably due to estrogen’s effect on prolonging the anagen phase.6 There are abundant estrogen receptors (b-type) expressed within the hair follicle, and it is likely that higher levels of estrogen binding to these receptors induces changes that keep follicles in the anagen phase of the hair growth cycle.23 Coincident with the abrupt decrease in estrogen upon parturition, there is a dramatic shift of the recruited anagen hairs to telogen hairs. Lynfield22 found that the percentage of anagen hairs dropped dramatically to 76% shortly after parturition. Clinically, the telogen effluvium that ensues appears as a dramatic loss of hair that begins four to 20 weeks postpartum and can continue for up to one year. Telogen effluvium that occurs postpartum is considered a
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Fig. 6
Telogen effluvium.
normalization of scalp hair follicles to the prepregnancy state, and complete hair regrowth occurs within 15 months (Fig. 6).22 Nonetheless, women often complain that the density is not that of prepregnancy.4,6,12 Other changes to the pilosebaceous unit are not as well understood. For example, the effect of pregnancy on acne has not been extensively reviewed and anecdotal reports are conflicting (Fig. 7). Some women report improvement in acne with pregnancy, whereas others report worsening. Ratzer24 reviewed the effect of pregnancy on acne in more than 400 women and found that pregnancy improved acne in 58% of women surveyed. She also found that after delivery, 75% of women reported improvement in acne, 13% reported no change, and 12% reported worsening of their acne. In an attempt at studying mechanisms, Burton found that sebum excretion in the forehead increases during pregnancy and remains high postpartum in nursing women.25 Whether this finding correlates with clinical worsening of acne is unclear.26
Connective tissue changes in pregnancy Of pregnant women, 55% to 90% will develop striae distensae.4,27 The body areas typically involved are the abdomen, hips, buttocks and breasts. The striae begin as pink-purple linear streaks oriented perpendicular to skin tension lines. Occasionally, striae are pruritic. With time, as with all striae, they become more pale and less noticeable. Etiologies include hormonal influences (adrenocorticosteroids, estradiol, and relaxin), as well as the physical stretch
Fig. 7
Acne secondary to pregnancy.
and distension associated with increased abdominal girth. Liu28 discussed that during pregnancy, two factors are necessary for the production of striae. The first is the priming of the skin by increased levels of estrogen and relaxin. Together, these hormones increase the production of collagen and nonsulfated mucopolysaccharides. The abundance of mucopolysaccharide in the dermis attracts water, which acts to decrease the cohesive forces between collagen fibers, leading to easy separation. The second factor is the physical stretch upon the primed dermis, causing breaks in collagen. He proposed that without priming the dermis, no striae would form when the skin is stretched. Others feel stretch alone promotes the development of striae and that tearing of collagen as well as elastic fibers contributes to their appearance.29,30 More recently, Watson et al31 commented that changes in the elements of the skin necessary for tensile strength and elasticity are suspected in the development of striae gravidarum (Fig. 8). These extracellular matrix components include fibrillin, elastin, and collagen. A study was done on skin biopsies from striae and adjacent normal skin in pregnant women. The differences found included looser dermal matrix, increased glycosaminoglycans, reduced fibrillin and elastic fibers, and alterations in the orientation of elastin and fibrillin in the dermis. The striae examined in this study were early erythematous striae, and the techniques used were electron microscopy, light microscopy, and immunohistochemistry. The group posed the question of whether the constant stretch of pregnancy might lead to remodeling of the dermis. This question remains unanswered. In addition to understanding the mechanism of striae formation, several groups have attempted to delineate the predictors for developing striae gravidarum. In 1959, a study linked the association between maternal obesity and weight gain during pregnancy to the development of striae gravidarum.32 In support, another group found that striae gravidarum were associated with body mass index as well as baby weight. Interestingly, they found that advancing age was inversely proportional to the development of striae.33
Fig. 8
Striae gravidarum.
Cosmetic aspects of pregnancy A recent large study found that 50% of patients with striae gravidarum had mothers with striae gravidarum, but the strongest association was made between striae gravidarum and the presence of breast and thigh striae. Among women with striae gravidarum, 81% had preexisting striae on the breasts and thighs. In contrast, only 31% of women without striae gravidarum had striae in these locations. This group did not find that body mass index or degree of weight gain correlated with striae gravidarum development, which does contradict previously published series. The authors do comment that very few women in the study were obese and that this may have skewed the results. Overall, from this study, genetics as well as possible variations in the ultrastructural composition of the dermis seem to play a major role in the development of striae gravidarum.27 No therapy has proven definitively to decrease the development of striae gravidarum. Physicians and patients have toted using olive oil or taking vitamin and mineral supplements to prevent striae gravidarum; however, none have been verified by large prospective trials. One physician’s personal success in preventing striae gravidarum in all of his pregnant patients with a combination of zinc, ascorbic acid, pyridoxal, and flaxseed oil is fascinating and should prompt a prospective, controlled study to evaluate this observation.34 Regarding treatment of striae postpartum, an open-label study with 0.1% tretinoin cream showed a decrease in the severity of striae gravidarum after three months of application.35 Nonetheless, a double-blind placebo-controlled trial of 0.025% tretinoin cream applied for seven months to striae gravidarum failed to demonstrate significant improvements over placebo.36 It is unclear whether the patients in this study were underdosed or if there is truly no effect on striae. Currently, therapies to decrease the appearance of striae include using vascular lasers on pink-purple striae.37 In addition, surgical excision of striae with abdominoplasty has favorable results when there is accompanying redundant abdominal skin. Another well-known connective tissue change in pregnancy is the development of acrochordons. In 1906, Brickner first described small, pigmented, sessile or pedunculated growths concentrated around the neck that appear in the fourth to sixth month of pregnancy and often spontaneously regress after delivery.38 He called them fibroma molluscum gravidarum, although now we know them as skin tags or achrocordons that are simply outgrowths of the epidermis and dermis with a fibrovascular connective tissue core.3 Templeton observed and described their increased incidence in postmenopausal women and concluded that the hormonal changes that occur in these two phases of life are important in the development of achrocordons.38,39 Breast changes are prominent during pregnancy and include enlargement, tenderness, erectile nipples, hyperpigmentation of the nipples and areolae, prominence of veins, striae, and enlargement of Montgomery’s tubercles.4 These
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Fig. 9
Facial puffiness.
are elevated brown papules of sebaceous origin associated with lactiferous ducts on the areolae of the breasts. Causes for all of these changes include increases in hormones of adrenal, pituitary, ovarian, and placental origin, as well as sodium and fluid retention.4 During late pregnancy, nonpitting edema occurs in 50% of women. There is a visible puffiness in the eyelids, face, and hands of pregnant women. Carpal tunnel syndrome is a common complication of this edema (Fig. 9).4,40 Pitting edema occurs in dependent areas such as the feet and legs in 70% of pregnancies, and these findings are not related to preeclampsia or eclampsia. Fluid shifts are thought to be secondary to both increased sodium and water retention, as well as increased vascular permeability, which are affected by the high levels of hormones in pregnancy. These changes almost always reverse shortly after delivery.4
Sweat glands and pregnancy Eccrine sweating gradually increases during pregnancy, and this can lead to complications such as miliaria.4 Potential etiologies include thyroid overactivity and the increased weight of pregnancy. In contrast, palmoplantar perspiration is decreased near late pregnancy, and this is thought to be related to increased adrenocorticotropic activity.41 Apocrine gland activity commonly decreases during pregnancy, and there have been reports of improvement in apocrine-driven dermatoses such as hidradenitis suppurativa and Fox-Fordyce disease. Hormonal effects are suspected in this phenomenon as well, although further study of the subject is lacking.42
The vascular changes of pregnancy Vascular changes in pregnancy are well described and are related to two major factors: hormonal changes and increases in intravascular pressure. The palmar erythema occurring in pregnancy has two distinct clinical presentations (Figs. 10 and 11). The first is diffuse mottling of the entire palm with accompanying cyanosis and pallor.5,6,12 The second is a mottled erythema of the palms that is most pronounced over the thenar and hypothenar eminences, near the metacarpophalangeal
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Fig. 12
Fig. 10
Palmar erythema.
joints, and the tips of the fingers. The former is most common, morphologically mimicking the palmar erythema seen in hyperthyroidism and hepatic cirrhosis.4 In a large study by Bean et al,43 62.5% of white and 35% of AfricanAmerican pregnant women developed palmar erythema. One third of the white women developed the erythema by the second month of pregnancy, and there was a steady increase in the incidence as the ninth month approached. Of those with palmar erythema, 91% saw resolution by the seventh week postpartum. Etiologies include increases in blood volume and blood flow that normally occur during pregnancy, genetic factors, as well as increased circulating estrogen. Another common vascular change in pregnancy is the spider angioma (Fig. 12). Corbett44 first described the appearance of spider angiomata during pregnancy and their subsequent resolution upon parturition. Spider angiomata are characterized by three clinical features: the central pulsating arteriole, the fine radiating branches, and the surrounding erythema. The surrounding erythema extends several millimeters beyond the visible vessels. Spider angiomata appear bright red, and the temperature of the skin overlying them is warmer than the adjacent skin. Bean et al43 found that 67% of white pregnant women had spider angiomata; conversely, they were only present in 11% of African-American pregnant women. The study also found that 14% of white women had spider angiomata by the second month of pregnancy, but African-American women developed them only after the fourth month of
Fig. 11
Palmar erythema.
Spider hemangiomas of left cheek.
pregnancy. As in the case of palmar erythema, 75% of spider angiomata in this series resolved by the seventh week after parturition. Spider angiomata are most commonly present in areas drained by the superior vena cava: the neck, throat, face (especially the periorbital area), and arms.5,12 Regarding the etiology of these vascular changes, no hepatic abnormalities were found in any of these women, and they were no more likely to occur in women with toxemia or hypertension. Although morphologically identical to the angiomata appearing in liver disease, impaired liver function is not thought to play a role in the development of spider angiomata in pregnancy. The conclusion was that estrogen, in particular, had effects on vasculature, and it is likely that elevated estrogen is the shared metabolic factor that is causative in the vascular lesions of pregnancy and liver failure.43 Treatment of spider angiomata includes cryosurgery, electrocautery, and vascular lasers. These procedures are probably safe during pregnancy, but one must weigh the potential risks and benefits of any treatment. Fortunately, most resolve spontaneously, never needing treatment. It is our impression that most patients and their physicians would prefer to treat these benign lesions after delivery. Vascular changes occur on a larger scale as well. Of pregnant women, 40% develop varicosities (Fig. 13), most commonly occurring in the legs; however, hemorrhoidal and vulvar varicosities are also prevalent.4 Pressure from the gravid uterus leads to partial obstruction of the inferior vena cava; this causes an increase in venous pressure. Data point to decreased vessel wall strength during pregnancy as well. Together, these factors probably lead to the development of
Fig. 13
Varicose and spider veins secondary to pregnancy.
Cosmetic aspects of pregnancy varicosities.5,7,12 It is interesting, however, to point out that varicosities are commonly seen toward the end of the first trimester of pregnancy, a time when intrapelvic pressure is not significant. This observation suggests that vascular fragility in pregnancy may play an important role.5 In addition, it is clear that local factors are not the only contributors, but genetics as well as behavioral factors play a key role. Behavioral factors that may exacerbate varicosities or increase the risk of developing them include prolonged sitting or standing or wearing tight belts or girdles (all activities that obstruct venous return).4 Prevention or minimizing the risk of developing varicosities is the aim of intervention during pregnancy. These measures include leg elevation, sleeping in a Trendelenburg position, lying in the left lateral decubitus position, and avoiding tight-fitting clothing. These measures theoretically help improve venous return and decrease venous hypertension. In addition, wearing elastic compression stockings also aids in compressing the superficial vasculature without impairing circulation.4,42 Although these measures are commonly recommended, there are no studies to prove definitively that these measures actually decrease venous hypertension, improve venous return, or decrease the occurrence of varicosities. Treatment of varicose veins (Fig. 13) include vein stripping, endovascular ablation, endovascular sclerotherapy, and radiofrequency techniques, among others.45 A comprehensive review of these techniques is beyond the scope of this chapter. For the treatment of telangiectasia, lasers, light sources, and sclerotherapy are available. These treatments are effective but are generally not done during pregnancy because the risks are unknown.46 These treatments can be performed safely after parturition, when they will likely be more effective, and the authors strongly recommend that treatment be avoided during pregnancy. There are other vascular changes that occur less commonly in pregnancy but are worth mentioning. Five percent of pregnant women develop small superficial or subcutaneous cavernous hemangiomas. Elevated estrogens are thought to be responsible. These occur toward the end of the first trimester and gradually increase in size as the pregnancy continues.5 Cutis marmorata is a bluish mottling of the skin upon exposure to cold. This is seen occasionally on the lower extremities during pregnancy.5,12 Of course, should this persist after delivery, secondary causes other than a hyperestrogen state must be ruled out. Purpura of the lower extremities is also a common finding in pregnancy and is speculated to be due to increased capillary fragility in the face of higher venous pressures.5
The oral mucosa and pregnancy Changes in the gingiva occur commonly during pregnancy as well. These changes have been termed stomatitis gravidarum, hypertrophic gingivitis of pregnancy, prolifera-
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Fig. 14
Pyogenic granuloma.
tive gingivitis of pregnancy, epulis gravidarum, or pregnancy tumor.38 The most common gingival change in pregnancy is edema of the gums, changing their color from dark red to blue. There is also an increased tendency for the gums to bleed. These changes usually occur during the fourth month of pregnancy and subside in the weeks after delivery. A curious phenomenon occurring commonly in pregnancy is the pregnancy tumor or epulis gravidarum.47 It occurs in approximately two percent of pregnancies and appears during the second through fifth months of pregnancy. The pregnancy tumor appears on the gingiva and is histologically indistinguishable from a pyogenic granuloma (Fig. 14).4 The lesion is typically smooth, soft to semifirm, with a shiny, red-purple or red-pink hue. The lesion can be pedunculated or sessile, and the classic location is the interdental papilla, but other common locations include the buccal or lingual surfaces of the gingiva.47 Usually, these tumors regress spontaneously with parturition, although minor trauma can lead to hemorrhage and ulceration. The pregnancy tumor often occurs in women who have extensive gingivitis of pregnancy.4 Removal of the pregnancy tumor is typically deferred until several months postpartum because of the high rate of spontaneous regression, unless there is extensive bleeding, pain, difficulty eating, or if the patient feels that the cosmetic appearance of the tumor is too disruptive.
Cosmetic procedures during pregnancy The question whether cosmetic procedures can be performed on pregnant patients often arises. It is our impression that most dermatologists and cosmetic surgeons prefer to avoid performing procedures that are medically unnecessary in this setting. The motivation behind this practice is likely mostly a medicolegal one. As most medications and devices are not tested on pregnant patients, the effects on the fetus are unknown. Many medications, as already discussed, are rated by the US Food and Drug Administration as Pregnancy Category C.48 Most often, medications receive this rating because the manufacturing companies choose not to study these drugs in pregnancy. To
140 perform these procedures or use these medications, therefore, might put the practitioner at risk for litigation. Botulinum toxin A (Allergan, Irvine, Calif) is a cosmetic drug that does have some literature supporting its use in pregnancy because of its initial medical indication to treat cervical dystonia and blepharospasm. Upon review of the literature, several case reports are found about its use in pregnancy. One patient was treated during her four pregnancies. To date, the longest follow-up is five years, and none of her children have demonstrated any apparent developmental abnormalities.49 Furthermore, there have been no cases of abnormal deliveries or floppy babies as reported by 396 physicians responding to a survey about botulinum toxin injections in pregnant patients.50 There are several cases of maternal botulism with normal outcomes in the newborns.51,52 In one case of maternal botulism, there were undetectable levels of botulinum toxin present in the infant’s serum, suggesting that the neurotoxin may not cross the placenta.53 Subsequent to these reports, one group described a pregnant women who received 500 U of botulinum toxin for cervical dystonia.54 At 10 weeks gestation with twins, no fetal heartbeat could be detected. Clearly there is no definitive association between the fetal demise and botulinum toxin, and the patient had several risk factors for fetal demise. Nonetheless, the general consensus is to be conservative and avoid administering botulinum toxin for cosmetic purposes to pregnant women. Collagen injections have not been studied in pregnancy; however, there is a report of one woman being treated with collagen for urinary stress incontinence and had a normal pregnancy.55 No adverse effects have been reported to date from collagen injections in pregnancy, but if the injection is for cosmetic purposes, the authors advise against its use during pregnancy. Hyaluronic acid gels for soft tissue augmentation have not been studied in pregnant patients as they are relatively new on the market. There are no case reports of outcomes in pregnant patients treated with hyaluronic acid. The consensus among hyaluronic acid gel manufacturers is to avoid use during pregnancy, although theoretically, no adverse events are predicted to occur because the composition is identical to human hyaluronic acid.56 More invasive cosmetic surgical procedures are considered too risky during pregnancy because of the need for general anesthesia; therefore, these are best left for the postpartum period.
Conclusions Pregnancy is associated with dramatic physiological changes to the female body, many of which manifest as cosmetic changes. It is quite impressive just how many of these changes regress with parturition. Despite these changes essentially being cosmetic in nature and not harmful, they do cause distress to many women. By educating patients
R. Nussbaum, A.V. Benedetto regarding what to expect and promoting a healthy lifestyle during pregnancy, perhaps we can alleviate some of the anxiety associated with the appearance of these physiological changes. As the understanding of the endocrine changes and the effects on end organs progresses, perhaps we can further elucidate why all these changes indeed occur. With regard to performing cosmetic procedures in pregnancy, it is the opinion of the authors that a conservative approach be followed if the purpose is purely cosmetic in nature.
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