There are a number of common skin changes in pregnancy that are thought to be related to hormonal changes.

Pigmentation

Hyperpigmentation is very common during pregnancy and occurs in up to 90% of women [4]. It is one of the most commonly recognized signs of pregnancy and may be generalized or restricted to areas of normal hyperpigmentation such as nipples, areolae, inner thighs, perineum, vulva and perianal region. The linea alba, a tendinous median line on the anterior abdominal wall, frequently hyperpigments to become the linea nigra and may extend from the symphysis pubis to the xiphisternum. Pigmentation increases in the first trimester, particularly in dark-haired, dark-complexioned women, and fades post partum, although it seldom returns to the pre-pregnancy level. Freckles and melanocytic nevi tend to darken and may increase in number. Recent scars may also hyperpigment.

Melasma

Irregular, sharply demarcated patches of facial pigmentation known as melasma (see Plate 20.1) develop in approximately 70% of women during the second half of pregnancy [4,5]. Melasma also occurs in up to 30% of women taking oral contraceptives [6] and in essentially healthy women between early adulthood and the menopause [7]. The most common pattern is centrofacial, involving the forehead, cheeks, upper lip, nose and chin. The malar pattern is limited to cheeks and nose, and the mandibular type involves the ramus of the mandible [8]. Histologically, there are two patterns of pigmentation: the epidermal type, which occurs in 72% of cases, in which the melanin is deposited mainly in the basal melanocytes, and the dermal type, which affects 13% of patients, where the melanin is mainly in the superficial and deep dermis [8]. Examination under Wood’s light shows enhancement of color contrast if melanin is primarily in the epidermis, and not if the melanin is located only in the dermis. Nearly 90% of women with chloasma due to oral contraception have a past history of melasma of pregnancy [6].

Pathogenesis

Eestrogen and progesterone are known to be strong melanogenic stimulants [9] and these hormones may be responsible for the hyperpigmentation of pregnancy. Serum and urinary melanocyte-stimulating hormone (MSH) levels have been reported as elevated during pregnancy with a rapid decrease post partum [10]. Other work has, however, demonstrated no difference in beta-MSH levels in the third trimester and after parturition [11]. Levels of beta-MSH were higher than the mean level obtained from nonpregnant controls but were within the normal range and therefore thought unlikely to be responsible for the pigmentary changes.

The patterns of pigmentation may relate to differences in end-organ sensitivity or distribution of melanocytes. Sun exposure may also exacerbate the development of melasma.

Treatment

Treatment is unsatisfactory and consists of minimizing exposure to sunlight by sun avoidance, or covering the skin with clothing when out in the sun, and avoidance of oral contraceptives. Sunscreens should be used and cosmetic camouflage with nonallergic products is helpful. Postpartum use of depigmenting agents may be effective and Kligman & Willis [12] report success in 14 out of 16 patients using twice-daily application of 5% hydroquinone, 0.1% tretinoin and 0.1% dexamethasone in ethanol and propylene glycol for 5–7 weeks. Sanchez et al. [8] recommend the use of 2% hydroquinone and 0.05% tretinoin on the epidermal type of persistent melasma and believe that the dermal types respond poorly if at all to this therapy. Depigmenting agents should always be used with caution as dermatitis, further hyperpigmentation or even hypopigmentation may ensue. Melasma usually fades within 1 year of delivery [13], although in one study 30% of cases persisted after 10 years [10].

Pruritus gravidarum

This term refers to intense pruritus that occurs as a manifestation of pregnancy, without any associated rash or clinical jaundice and usually in early pregnancy. Pruritus from all causes occurs in 17% of pregnant women [14] and may be due to conditions unrelated to pregnancy (such as dry skin, scabies, pediculosis (lice), urticaria, atopic eczema, drug eruptions, candidiasis, trichomonal vaginitis or neurodermatitis) or conditions that only occur in pregnancy (cholestasis of pregnancy, pruritic urticarial papules and plaques of pregnancy, pruritic folliculitis of pregnancy, prurigo of pregnancy and pemphigoid gestationis, also known as herpes gestationis). All of these listed conditions (with the notable exception of cholestasis of pregnancy) are associated with a typical rash that should be looked for by a careful complete skin examination.

Early scabies may be the most subtle of these rashes and should be looked for by examining the space between the fingers, the flexing surfaces of the wrists and armpits, the areolae of the breasts, along the belt line, and on the lower buttocks. The face usually does not become involved in adults. Examination in this areas may reveal only small, barely noticeable bumps that may be slightly shiny and dark in color rather than red. Initially the itching may not exactly correlate to the location of these bumps.

If no rash is found, the main differential diagnosis of persistent itch in pregnancy is obstetric cholestasis and this condition should be tested for on several occasions by obtaining a serum bile salts and liver function tests in any pregnant patient with persistent itch (see Chapter 9 where obstetric cholestasis is discussed in detail). In the absence of rash and in the presence of repeatedly normal serum liver enzymes and bile salts, patients with new-onset persistent itch in pregnancy can be presumed to have pruritus gravidarum.

Treatment

Mild forms of pruritus gravidarum may be treated with bland topical antipruritic creams such as calamine or moisturizers. Antihistamines may be a useful adjunct. However, in some patients the pruritus may be so severe that preterm delivery is necessary. Pruritus gravidarum (just like obstetric cholestasis) can recur in up to 50% of subsequent pregnancies or with oral contraceptive use. Unlike obstetric cholestasis, the condition is not associated with an increased fetal risk. It usually resolves rapidly in the postpartum period.

Vascular changes

Edema

Clinically apparent edema of the face and hands occurs in approximately 50% of pregnant women, whilst edema of the legs not associated with pre-eclampsia develops in about 80% [4]. It is usually nonpitting in nature and worse in the morning. It is probably due to several factors: increased fluid retention (approximately 2.5 L during pregnancy), increased vascular permeability, increased blood flow [15] and decreased colloid osmotic pressure of plasma. It warrants no treatment except for reassurance. In extreme cases of lower limb edema, compression stockings may be necessary.

Spider nevi

Vascular spiders (also known as spider nevi) are superficial vascular structures that consist of a central pulsating arteriole with radiating thin-walled vessels. Compression of the center causes the lesion to fade but when compression is released, the spider leg-like vessels quickly refill from the center of the lesion. Clinically they are indistinguishable from the spider nevi of chronic liver disease. Spider nevi develop between the second and fifth months of pregnancy and are present in about 57% of white women and 10% of black women by the third trimester [16]. This difference is probably due to difficulty in visualizing them on dark skin. In comparison, spider nevi are said to occur in 15% of normal nonpregnant white women. They occur in the areas drained by the superior vena cava on the upper trunk and face, increase in size and number throughout pregnancy and fade post partum. The majority (75%) have disappeared by the 7th week after delivery [16]; the remainder persist and recurrence may occur at the same sites in subsequent pregnancies. Treatment for persistent lesions is with cold point cautery or pulsed dye laser.

Palmar erythema

Palmar erythema develops during pregnancy in 70% of white women and 35% of black women [16]. Its onset is in the first trimester and it fades within 1 week of delivery. There are two clinical patterns: (i) diffuse mottling of the whole palm; and (ii) erythema confined to the thenar and hypothenar eminences. The former is the more common. It frequently occurs in patients who also have spider nevi and both are thought to be due to high estrogen levels. The increases in blood volume and blood flow are other possible factors.

Varices

Varices may affect as many as 40% of pregnant women and may involve the saphenous system or small superficial vessels in the legs, as well as the hemorrhoidal and vulvar networks. Venous congestion of the labial tissue can also lead to significant edema and pain. Factors contributing to venous congestion include increased venous pressure in femoral and pelvic vessels due to compression from the gravid uterus, increase in the blood volume, increased collagen fragility and a hereditary tendency to varicose veins. Varices tend to regress post partum, although not always completely.

Treatment is elevation of the legs and elastic support stockings. Several maxi-type pads can be placed in the undergarments to provide symptomatic relief of significant labial edema. Vulvar support garments have also been developed for this indication. Thrombosis may occur in leg varices or in hemorrhoids. Varices are a risk factor for thromboembolism which is discussed in Chapter 4.

Hemangiomata

Hemangiomata are red to purple papules on the skin that are vascular in origin. The term includes such diverse lesions as port wine stain (vascular birthmarks), Campbell de Morgan spots (nonblanching red or violet spots that appear with age, usually on the chest or trunk, and are typically less than 6 mm in diameter) and strawberry nevi (red firm dome-shaped hemangiomas present at birth or soon after that typically occur on the head or neck and grow rapidly but then regress and involute without scarring). Capillary hemangiomata develop on the head and neck in 5% of pregnant women, appearing at the end of the first trimester and enlarging until term [13]. Pre-existing hemangiomata of any type may also increase in size during pregnancy. High estrogen levels are probably an etiologic factor. Surgical removal is the treatment for lesions which persist post partum.

The “pregnancy tumor” or telangiectatic epulis is a specific pregnancy lesion composed of fibrous and vascular tissue. It is clinically and histologically similar to pyogenic granuloma (a misnamed noninfectious and nongranulomatous vascular lesion of skin and mucosa typically seen in children and young adults that appears as a solitary glistening papule or nodule prone to bleeding or ulceration). Telangiectatic epulis is sited on the oral mucosa or gingiva and arises from interdental papillae on the buccal or lingual surfaces of the gingiva. It is usually associated with extensive gingivitis and may bleed or ulcerate. It often grows rapidly and may represent a vascular and fibrous response to injury It usually develops at between 2 and 5 months gestation and affects 2% of pregnant women. Treatment is not usually necessary because these lesions typically regress after delivery. For cases with persistent bleeding in pregnancy cautery or excision may be performed.

Purpura

This may occur on the legs during the second half of pregnancy due to increased capillary permeability and fragility [13]. Vasculitis and thrombocytopenia must be excluded with a complete blood count and consideration of the need for biopsy if a systemic vascultis is suspected.

Connective tissue and collagen

Striae gravidarum (gravidarum distensae)

Striae gravidarum, commonly known as stretch marks, develop during the second half of pregnancy in most women. They occur on the abdomen, breasts and thighs. Initially they are pink or violaceous linear wrinkles, which develop perpendicular to skin tension lines. They become white and atrophic with time, although never disappear completely. They are identical to the striae associated with puberty, obesity, Cushing’s disease and steroid therapy.

The etiology of striae is multifactorial: stretching is a localizing factor and striae do tend to occur more with overweight mothers or those carrying heavier babies or with multiple pregnancy but their occurrence does not correlate directly with the degree of skin distension or weight gain [17,18]. There is also a familial tendency [19]. Rupture of collagen and elastic fibers [20] and increased adrenocortical activity have been considered important [17]. It has also been suggested that estrogen and relaxin increase the collagen and sulfate-free mucopolysaccharides and that subsequent stretching leads to easier separation of collagen [19]. Histologically, striae consist of areas of broken and curled elastic fibers in the upper dermis with parallel bands of collagen and elastic fibers in the center [21]. Fibrillin microfibrils in the elastic fiber network appear to be reduced and reorganized in skin affected by striae [22]. There is no specific treatment for striae and it is controversial as to whether emollient massage is effective in their prevention [17]. Topical tretinoin cream 0.025% does not appear to have any beneficial effect and should not be used in pregnancy because of the teratogenic effects of vitamin A compounds [23].

Skin tags or molluscum fibrosum gravidarum

Soft, fleshy, pendunculated, skin-colored or slightly pigmented papillomata (papules or plaques with fine multiple surface projections) may develop on the face, neck, upper anterior chest, axillae and under the breasts during the second half of pregnancy. They are about 1–5 mm in diameter and clinically and histologically identical to skin tags [24]. They are probably due to hormonal factors and regress post partum. Persisting lesions may be removed by electrodesiccation.

Glandular activity

Sweat and apocrine glands

Eccrine sweating (the watery sweating that can be produced by glands throughout the skin) is increased during pregnancy [25] and may be associated with milia (also known as milk spots, these are benign keratin-filled cysts under the epidermis that typically occur in the area around the nose and eyes due to occlusion of the eccrine sweat ducts) and intertrigo (inflammation of skin in the body folds, especially the inner thighs, genitalia, armpits, under the breasts and belly, behind the ears and between digits). Palmar eccrine sweating is, however, diminished [26]. Apocrine (the oily sweating that occurs only in areas such as the axilla, periareolar and pubic area) activity is also reduced with subsequent improvement of conditions such as Fox–Fordyce disease (a noninfectious inflammation behind chronically blocked sweat gland ducts which most commonly presents as a pruritic papular eruption) and hidradenitis suppurativa (a bacterial infection occurring behind chronically blocked sweat glands with the formation of pus-draining sinuses) [3], which may, however, rebound post partum.

Sebaceous glands

Sebaceous activity (sebum- or oil-producing glands usually associated with hair follicles anywhere but also occurring on the lips, areola, and genitals) increases during the third trimester, and acne occasionally develops during pregnancy. Sebaceous glands associated with lactiferous ducts on the areolae hypertrophy as early as 6 weeks gestation and appear as Montgomery’s tubercles (tiny bumps scattered around the areola). They are one of the signs of early pregnancy.

Hair changes

Telogen effluvium

Normally about 85% of scalp hairs are in the anagen (growing) phase and 15% are in the telogen (resting or nongrowing) phase. A hair usually grows in anagen phase for 4 years and then rests in telogen phase for 4 months. At the end of the telogen phase, a hair is dead, fully keratinized and falls out. The scalp end of the hair lost at the end of the telogen phase has a characteristic shape of a club or bulb while hair lost in the anagen phase has a tapered or pointed end. Typically adults lose about 100 hairs a day, with most hairs having the club-shaped end indicating the end of the hair life cycle.

During pregnancy the proportion of hairs in anagen (the growing phase) increases [27] to 95% of hair follicles, creating the thickening of scalp hair in pregnancy reported by many women. Post partum, the conversion from anagen (growing) hairs to telogen (resting) hairs is accelerated and the proportion of growing hairs drops within a few months to 75%. This creates a phenomenon of postpartum hair loss known as “telogen effluvium” that typically follows delivery by 4–20 weeks [3]. The hair loss is generally diffuse, although may be more marked in the frontoparietal hairline in women with a tendency to male-pattern baldness. Baldness seldom, if ever, occurs, and spontaneous recovery usually takes place within 6 months of delivery [28], although it may take as long as 15 months [3]. Recovery is usually complete unless the telogen effluvium is severe, repeated in several pregnancies or associated with male-pattern alopecia. With successive pregnancies hair loss tends to be less marked.

The diagnosis of telogen effluvium is made by finding large numbers of “club hairs” when hair is pulled gently or falls from the patient’s scalp. Histologically, the follicles in telogen are normal. Increased adrenocorticosteroids and ovarian androgens probably account for the increase in anagen hairs, and estrogens prolong the anagen phase [5]. Telogen effluvium is probably caused by several factors including changes in endocrine balance, the stress of delivery, difficult labor and blood loss. No specific treatment is required apart from reassurance.

Some women develop male-pattern or diffuse hair loss in late pregnancy. This is usually due to inhibition of anagen in some follicles and not to increased loss. The postpartum regrowth of hair in women with male-pattern hair loss in pregnancy is unlikely to be complete.

There is no significant change in the anagen/telogen ratio of body hair [29].

Hirsutism

Hypertrichosis (increased hair growth not localized to androgen-dependent areas of the skin), most marked on face, arms and legs, is quite common in pregnancy but marked hirsutism (male-pattern hair growth) is rare. It resolves post partum but frequently recurs in subsequent pregnancies.

Hirsutism may be accompanied by acne, deepening of the voice and clitoral enlargement and is probably due to increased adrenocorticosteroid and ovarian androgen secretion. Other causes of hirsutism, namely androgen-secreting ovarian tumors (luteomas and theca lutein cysts) and polycystic ovaries, should be excluded. Androgenization of a female fetus is unlikely in these circumstances. Treatment of the mother’s hirsutism (which will persist after the pregnancy) is with reassurance and cosmetic removal (depilatory creams, electrolysis or ruby laser).

Nails

Nail changes, consisting of transverse grooving, brittleness, distal onycholysis (separation of the distal nail plate from the underlying nail bed starting at the distal free margin and progressing proximally) and subungual keratosis (excessive proliferation of the nail bed) may occur from the 6th week of pregnancy. The pathogenesis of these changes is not known. There is no effective treatment.

Breasts and nipples

Sore nipples with cracks and fissures commonly develop in the first few days of breastfeeding. The soreness may limit sucking, and stasis, mastitis or breast abscess may follow. Nipple eczema may also develop and involve the breast. Secondary infection must be excluded. Fissures and eczema are avoided by gentle washing to remove saliva and milk and by use of emollients after each feeding session. Removal of excess emollients prior to the next breastfeeding session is important. To help heal fissures, the breasts should be left exposed if possible for 5–10 minutes after breastfeeding to allow air drying; alternatively, a hair drier on the cool, low setting can be used when in a hurry. Any secondary infection should be treated with antibiotics. Severely affected patients are often atopic.

A number of dermatoses are specific to pregnancy, to the puerperium or occur as a result of trophoblastic tumors. Severe pruritus is the leading symptom in all these dermatoses of pregnancy, and can considerably impair maternal quality of life. Intrahepatic cholestasis of pregnancy is the only condition that is also associated with significant fetal risks. Unequivocal diagnostic tests are only available for pemphigoid gestationis (indirect immunofluorescence) and intrahepatic cholestasis of pregnancy (serum bile acids with liver function tests). In the largest case series to date of pregnancy dermatoses, the following classification system was proposed with associated distribution of relative frequencies [4]:

• pemphigoid gestationis (herpes gestationis) 4.2%
  
• polymorphic eruption of pregnancy 21.6%
  
• prurigo of pregnancy 0.8%
  
• pruritic folliculitis of pregnancy 0.2%
  
• intrahepatic cholestasis of pregnancy 3%
  
• eczema in prengnacy 49.7%
  
• miscellaneous dermatoses 20.6%.

Pemphigoid gestationis

Pemphigoid gestationis (PG) (see Plates 20.2 and 20.3) (also known as herpes gestationis) is an intensely pruritic bullous eruption that occurs in one in 60,000 pregnancies [30] or in association with the trophoblastic tumors choriocarcinoma [31] and hydatidiform mole [32]. Fortunately, it is a rare cause of significant pruritius during pregnancy. Because of the connotations of the term herpes to patients and other medical providers (and the fact that it is not caused by the herpes virus), it is best to use the term pemphigoid gestationis (rather than herpes gestationis) in conversation with the patient and in the medical record.

The eruption initially consists of pruritic erythematous urticarial papules and plaques often with target lesions and ring-like (annular) patterns. Vesicles develop after a delay varying between a few days and a month and enlarge to become tense bullae. In 90% of patients the lesions begin in the periumbilical region and spread to involve thighs, breasts, palms and soles (see Plate 20.2). The face and oral mucosa are only rarely involved. PG may begin during the first or any subsequent pregnancy and typically arises during the second and third trimesters but has been reported as early as 9 weeks gestation or as late as 1 week post partum [33]. In subsequent pregnancies recurrence usually occurs with an earlier onset and more severe disease. When PG develops during the mid-trimester, there is usually a period of relative remission in the last few weeks of pregnancy followed by an abrupt postpartum flare [15]. The bullous lesions tend to resolve within a month of delivery, but the urticated plaques may persist for over a year [33].

The etiology of PG is unknown, but recent work highlights the immunopathologic findings in this disease. Paternal histocompatibility antigens (human leukocyte antigens (HLA)) were considered important following a study in which 50% of the consorts were HLA-DR2 compared to 25% of the controls [34]. However, this was not confirmed in another study in which the frequency of paternal HLA was normal [35]. A paternal factor is likely, as in some patients with pregnancies by several consorts the onset of PG has coincided with a change in partner, and in one case a patient had PG in her first and second pregnancies and then had an unaffected pregnancy by a new consort [35–37].

Maternal HLA studies have revealed a significantly increased frequency of DR3 with DR4 [34]. DR3 and DR4 are associated with other diseases with an immune pathogenesis such as Graves’ disease, rheumatoid arthritis and insulin-dependent diabetes mellitus, which suggests that their presence confers an increase in immune susceptibility in the patients with PG. One study has confirmed the association between PG and other autoimmune diseases, particularly Graves’ disease [38]. The antigenic trigger is probably paternally derived as PG occurs not only in pregnancy but also in association with hydatidiform mole and choriocarcinoma, and in these trophoblastic tumors, the chromosomes are all paternally derived. There is also evidence that DR compatibility between mother and fetus favors a spared pregnancy [39]. Once initiated, PG is undoubtedly hormonally modulated.