The Skin and Pregnancy

Pigmentary Changes

Hyperpigmentation occurs in at least 90% of pregnant women. Much of it is presumed to result from the effects of increased levels of melanocyte-stimulating hormone (MSH), beta-endorphin, estrogen, and progesterone on the melanocytes in the epidermis (see Chapter 10 ). Other bioactive molecules, such as placental lipids, can stimulate tyrosinase activity, which increases pigmentation. Pigmentation is typically most accentuated in the areolar and genital skin. The neck and axillae can become hyperpigmented, but if those areas become velvety or papillomatous, the physician should consider acanthosis nigricans associated with diabetes mellitus and other endocrinopathies. Hyperpigmentation of the linea alba, the longitudinal demarcation line on the midline of the abdomen, is called linea nigra . Pigmentary demarcation lines (i.e., Voigt or Futcher lines) may also appear on the legs and other locations. All of these pigmentary changes typically regress after delivery.

Melasma is diffuse macular hyperpigmentation of the face, usually involving the forehead, cheeks, and bridge of the nose. Although the antiquated term chloasma has often been used as a synonym, it was typically restricted to cases occurring during pregnancy (i.e., mask of pregnancy). Melasma occurs in about 70% of pregnant women but can occur in women who are not pregnant, especially those using oral contraceptives, hormonal creams, and other hormones. Increased expression of α-MSH has been found in lesional skin. The hyperpigmentation is usually blotchy and poorly demarcated, and it is bilaterally symmetric. It usually resolves after delivery, although it persists for months or years in about 30% of patients.

Avoidance of exposure to sun during pregnancy helps prevent or minimize the formation of melasma. Topical sunscreen lotions with sun protective factor (SPF) ratings of 15 or greater should be used. For troublesome hyperpigmentation that persists after delivery, topical hydroquinone bleaching creams and solutions (US Food and Drug Administration [FDA] pregnancy category C drugs), such as Lustra, Alustra, Melanex, or Solaquin, are sometimes useful. In the United States, 4% hydroquinone cream is available as a generic prescription medication, and many other brands with lower concentrations are available over the counter. The FDA had been considering removing hydroquinone from the market; it is banned in some countries because it is carcinogenic in rodents, but dermatologists opposed such a ban. Treatment is frequently prolonged for months. A combination of topical hydroquinone, tretinoin, and hydrocortisone (Kligman solution) has been claimed to be more effective, and a similar FDA-approved combination of these three drugs, substituting fluocinolone for the hydrocortisone, has been commercially marketed (Tri-Luma cream). Cosmetics (such as Covermark or Dermablend) are useful for covering irregular pigmentation. Additional therapeutic options for melasma persisting after pregnancy include daily topical retinoic acid (tretinoin [Retin-A, Avita]), salicylic acid (SalAc cleanser), or azelaic acid (Azelex, Finacea). Chemical peels with trichloroacetic acid, phenol, glycolic acid, Jessner solution (i.e., lactic acid, resorcinol, and salicylic acid in ethanol), or kojic acid may be effective. All of these treatments are more effective if the pigmentation is epidermal rather than dermal. Although the Q-switched lasers (i.e., yttrium-aluminum-garnet, ruby, or alexandrite) have been useful for many other pigmentary problems, they provide little help for melasma. Intense pulsed light (IPL) and the fractionated photolysis laser (Fraxel) produced good results in some patients. Oral tranexamic acid has been used in nonpregnant women in uncontrolled trials, but there is a risk for thromboembolism.

Pregnancy can produce new melanocytic nevi or enlarge preexisting nevi, but the incidence of changes in nevi and the formation of melanoma seems to be no greater than for nonpregnant women. Most melanomas exhibit asymmetry, an irregular border, variegated colors (i.e., red or white in addition to black or blue), and a diameter greater than 6 mm. Suspicious lesions should be excised immediately. Local anesthetic agents, such as lidocaine, are regarded as safe (FDA pregnancy category B). The use of epinephrine in low doses along with lidocaine can expedite surgery, but it is classified as pregnancy category C, as high doses can lead to uterine artery spasm. The subject of melanoma during pregnancy is addressed in Chapter 56 .

Vascular Changes

Pregnancy induces dilation and proliferation of blood vessels. Although this is thought to result largely from estrogen, the mechanism is not completely understood. Telangiectasias (i.e., persistently dilated blood vessels) that resemble those seen with chronic sunlight or radiation exposure can occur during pregnancy. Spider angioma (i.e., nevus araneus) is characterized by a central arteriole with radiating vascular “legs” resembling those of a spider and is most prevalent in sun-exposed areas. Multiple spider angiomas also can occur in persons with liver disease (resulting from decreased hepatic estrogen catabolism), with estrogen therapy, and in normal, nonpregnant women. These lesions can regress spontaneously. Persistent lesions are best treated with low-energy electrocoagulation or laser ablation.

Palmar erythema occurs in many normal pregnant women and can be associated with liver disease, estrogen therapy, and collagen vascular diseases. These vascular changes require no therapy and usually resolve after delivery.

Pyogenic granuloma is a misnomer for a red, nodular, often pedunculated, exuberant proliferation of blood vessels and inflammatory cells. This granulation tissue is not a granuloma, which is a nodular aggregate in which macrophages predominate. The surface is often ulcerated, with yellowish purulence (i.e., pyogenic appearance). These lesions can be found anywhere on the skin but most commonly occur on the scalp, upper trunk, fingers, and toes. They are especially common on the gums, often resulting from gingivitis or trauma, and have been called epulis gravidarum . The terms lobular capillary hemangioma, pregnancy tumor, and granuloma gravidarum are other synonyms for pyogenic granuloma. ^,

Therapy consists of surgical excision or electrosurgical destruction, but it can often be delayed until after delivery because some lesions regress spontaneously. Regression is associated with apoptosis of endothelial cells and a dramatic decrease in expression of vascular endothelial growth factor (VEGF), mediated by a decline in estrogen and progesterone levels. Immediate biopsy should be performed if there is problematic bleeding or if the clinical diagnosis is in doubt because some neoplasms, such as amelanotic melanomas, can resemble pyogenic granulomas.

Venous congestion and increased vascular permeability during pregnancy commonly cause gingivitis and edema of the skin and subcutaneous tissue, particularly of the vulva and lower legs. Severe labial edema has occasionally been reported during pregnancy, and a search for other causes is sometimes warranted. Varicosities are common on the legs and around the anus (i.e., hemorrhoids). They may regress after delivery but usually not completely.

Connective Tissue Changes

The mechanisms by which collagen and other connective tissue elements are influenced during pregnancy are poorly understood. Striae (i.e., stretch marks) represent linear tears in dermal connective tissue and appear as red or purple, atrophic bands over the abdomen, breasts, thighs, buttocks, groin, and axillae. They usually begin in the second or third trimester, but they sometimes occur in the first. Some lesions may be pruritic. At least a few striae occur in 50% to 80% of pregnancies, and they are severe in about 10%, especially in teenagers. ^, Risk factors for more severe striae include maternal family history of striae, young maternal age, non-White race, larger baseline and delivery body mass index (weight gain >15 kg), increased abdominal and hip girths, increased newborn weight, higher altitudes, and larger fetal height and head circumference. ^, Women with striae have an increased incidence of subsequent pelvic relaxation (i.e., prolapse).

Despite numerous anecdotal claims of therapeutic efficacy, no topical therapy prevents or affects the course of striae, which ordinarily become less apparent as the red or purple color fades after delivery. There are numerous testimonials and limited evidence regarding the value of diet, exercise, centella, bitter almond oil, hyaluronic acid, olive oil, cocoa butter, vitamin E, tretinoin, and nutritional therapy, but none of these has proved consistently valuable in controlled studies. The pulsed dye laser has been helpful, particularly in obliterating the red color of early lesions, but it is difficult to determine whether the short-term improvement is better than that after long-term observation.

Skin tags (i.e., acrochordons, soft fibromas, fibroepithelial polyps, or molluscum fibrosum gravidarum) are soft, papular, or pedunculated growths of fibrous and epithelial tissue that are common in obesity and in pregnancy. They are usually skin colored to dark brown and usually appear on the neck, axillae, or groin. Skin tags often persist after delivery and can easily be electrocoagulated or snipped off with scissors.

Hair and Nail Changes

The hair growth cycle is divided into three phases: anagen, catagen, and telogen. The duration of the growing phase (i.e., anagen) of each scalp hair follicle persists 3 to 4 years, with an average daily growth rate of approximately 0.34 mm. Growth activity is followed by a transitional (i.e., catagen) phase that lasts about 2 weeks, followed by a resting phase (i.e., telogen) that lasts several weeks. When the next hair cycle starts, newly forming hair causes shedding of the older telogen hairs.

Activity of each of the approximately 100,000 follicles on the human scalp cycles randomly and independently from the activity of neighboring follicles. At any given time, approximately 10% to 15% of hair follicles are in the telogen phase. If the average duration of growth of each follicle is approximately 1000 days (3 years), it can be calculated that about 100 hairs are shed normally each day.

In late pregnancy, hormones appear to increase the number of anagen hairs and decrease those in telogen. Estrogen receptors found in hair follicles may play a role in this. After hormone withdrawal in the postpartum period, telogen hairs can increase to 35% or more of scalp hairs, resulting in a transient hair loss peaking about 3 to 4 months after parturition. This diffuse hair loss has been called telogen effluvium, whether it occurs after delivery, surgery, illness, crash dieting, or some other stressful event. The severity varies greatly, and it takes a total hair loss of 40% to 50% to become noticeable. Telogen effluvium usually is easy to distinguish from other causes of hair loss, and patients should be reassured that regrowth is likely to occur by 9 months after delivery without any treatment.

Hirsutism of the lower facial or sexual skin areas is uncommon, but occasionally occurs in the second half of pregnancy and can be accompanied by acne. It is presumed to result from the effects of ovarian and placental androgens on the pilosebaceous unit. The possibility of underlying androgen secretion by a tumor of the ovary, a luteoma, or a lutein cyst should be considered, although polycystic ovary disease appears to be the most frequent cause. Options for hair removal include waxing, electrolysis, and laser ablation. Shaving does not increase the coarseness or growth of hair, but many women are not inclined to want to treat increased hair by this method.

Several types of nail changes have been reported during pregnancy but do not occur regularly. These changes include transverse or longitudinal grooving, increased brittleness, softening, and distal onycholysis.

General Treatment

The same treatment principles apply to all of the specific dermatoses of pregnancy. Few drugs have been proved safe during pregnancy, and the risk-benefit ratio must be considered. Milder disease is treated with topical emollients, calamine lotion, cool compresses or baths, and topical corticosteroids. Topical corticosteroids (e.g., hydrocortisone, triamcinolone) are classified as FDA pregnancy category C drugs, but they are still widely used during pregnancy when the possible benefits outweigh the risks for minimal percutaneous absorption. Some of the very-high-potency topical corticosteroids, such as clobetasol, have potential for significant absorption on large body surface areas.

Many oral antihistamines, including the nonsedating fexofenadine (Allegra) and desloratadine (Clarinex), are classified as FDA pregnancy category C drugs because available data are insufficient. Hydroxyzine (Atarax) is not recommended in the first trimester because it has been associated with a slightly increased rate (5.8%) of congenital malformations, but otherwise, it is classified as pregnancy category C. Oral antihistamines classified as pregnancy category B drugs (e.g., cetirizine [Zyrtec], chlorpheniramine, cyproheptadine [Periactin], diphenhydramine [Benadryl], loratadine [Claritin]) may be worth trying in patients with bothersome pruritus. Cetirizine and loratadine are relatively nonsedating agents. The most commonly used antihistamine in pregnancy appears to be diphenhydramine, even though it produces annoying drowsiness. One study associated diphenhydramine with cleft palate, but this finding has been disputed in other studies. An increased rate of retrolental fibroplasia has been reported for premature infants whose mothers took antihistamines within 2 weeks of delivery. No antihistamines are recommended during lactation by the manufacturers, but diphenhydramine is probably safe because levels in breast milk are low.

Use of systemic corticosteroids (e.g., prednisone, prednisolone), which are classified as FDA pregnancy category C drugs, appears to be relatively safe in humans when their use is warranted because of severe disease, but a modest increase in birth defects was reported in the Michigan Medicaid Birth Defects Study of 229,101 pregnancies. Fluorinated corticosteroids such as betamethasone or dexamethasone should be avoided in favor of nonfluorinated drugs, since the former lead to higher concentrations of active drug reaching the fetus. Cleft palates have occurred in offspring of pregnant rabbits undergoing such therapy, with a moderate increased risk for oral clefts in the first trimester of human pregnancy. Infants of mothers treated with systemic corticosteroids in high doses and for long duration should be monitored for evidence of adrenal insufficiency. Ultraviolet phototherapy can be offered to pregnant women with severe pruritus if the benefits outweigh the risks for burning and excessive heat.

Pruritus Gravidarum

Pruritus gravidarum is generalized itching during pregnancy without the presence of a rash, although excoriations can occur. Up to 14% of pregnant women complain of itching, but pruritus associated with cholestasis (i.e., intrahepatic cholestasis of pregnancy [see Chapter 64 ]) occurs in only about 1.5% to 2% of pregnant women, with onset usually occurring in the third trimester. Some authorities seem to confuse definitions by reserving the term pruritus gravidarum for patients with cholestasis of pregnancy. Frank clinical jaundice occurs in only 0.02% of pregnancies. Pruritus limited to the anterior abdominal wall is common and is usually caused by skin distention and development of striae rather than cholestasis. Pruritus usually disappears shortly after delivery but recurs in approximately 50% of subsequent pregnancies.

Cholestatic itching correlates better with elevated serum bile acid levels than with the results of other biochemical liver function tests such as alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. An elevated level of glutathione S -transferase-α, a specific marker of hepatocellular integrity, identifies women with intrahepatic cholestasis and distinguishes them from those with benign pruritus gravidarum. Abnormal plasma lipid profiles are common in those with cholestasis. Biliary obstruction in pregnancy is discussed in more detail in Chapter 64 . Because some patients with skin lesions indicative of one of the other pregnancy rashes described in this chapter have coexisting cholestasis of pregnancy, screening with liver function tests may be reasonable for patients with pregnancy-related rashes and for those experiencing pruritus without rash. Pruritus can precede abnormal findings of liver function tests or total serum bile acids, and follow-up testing for obstetric cholestasis may be needed for itchy pregnant patients with initially normal findings.

Pruritus gravidarum is associated with twin pregnancies, fertility treatments, diabetes mellitus, and nulliparity, but it is not associated with adverse perinatal outcomes for patients without cholestasis. Reported increases in rates of premature delivery and perinatal mortality appear to be restricted to those in whom frank clinical jaundice develops and in cases of intrahepatic cholestasis of pregnancy.

Treatment is symptomatic, and mild cases usually respond to adequate skin lubrication and topical antipruritics. Oral antihistamines can be of some benefit. Ultraviolet light treatment or judicious sun exposure can decrease pruritus. For more severe cases of pruritus in the setting of cholestasis, see Chapter 64 . ^,