Skin disorders of pregnancy
Carla V. Errickson
The dermatologic disorders that can occur during pregnancy fall into three broad categories: physiologic changes, specific skin disorders of pregnancy, and certain skin tumors. Most of these disorders are benign and resolve postpartum, but several can be harmful or even fatal to the fetus.
Almost all women, especially those with dark complexions, note some degree of hyperpigmentation during pregnancy. These pigmentary changes usually affect such areas as the areolae, axillae and genitalia, but scars and nevi also may darken. Hyperpigmentation in pregnancy is most likely related to high levels of progesterone and estrogen, since these hormones stimulate melanogenesis. The areas of hyperpigmentation almost always lighten after delivery.
Melasma is a form of hyperpigmentation that affects the face. Also known as chloasma or the “mask of pregnancy,” melasma appears as symmetric, blotchy, tan-to-brown patches, most often on the forehead and chin. Like other forms of hyperpigmentation, melasma tends to occur more frequently in dark-skinned persons.
Melasma occurs in 50 to 70 percent of pregnant women and in 5 to 34 percent of women using oral contraceptives. While the exact cause of this form of hyperpigmentation is unknown, its association with oral contraceptives suggests that hormones have a role in its etiology. Sunlight, a known precipitating factor in melasma, often exacerbates the condition. The pigmented patches of melasma usually fade within one year after delivery.
Striae gravidarum, often called “stretch marks,” occur in 90 percent of pregnant white women but are less common in Asian and black women. Striae generally develop late in the second trimester, when they appear as atrophic lines that are pink to violet in color. The skin on the abdomen, breast, buttocks, arms and thighs is most frequently affected (Figure 1).
The cause of striae gravidarum is obscure, although genetic predisposition, hormones and weight gain during pregnancy each appear to have a role in the etiology. Histologic examination reveals that elastic fibers are absent in the area of the defect and are curled and clumped at the periphery.
No treatment is available for striae gravidarum. In the postpartum period, the striae become flesh-colored, but the skin defect persists.
High levels of estrogen contribute to most, if not all, of the vascular changes that occur during pregnancy. Such changes include vessel proliferation and congestion, as well as vasomotor instability. Because of these vascular changes, the water content of the dermis increases, which contributes to edema.
One of the more common vascular changes noted during pregnancy is the spider angioma, which is characterized by a central arteriole with many fine, radiating vessels. The angioma blanches with pressure. Spider angiomas appear toward the end of the first trimester in 70 percent of white women and 10 percent of black women. Most common on the arms, face and neck, these angiomas fade postpartum but tend to recur with subsequent pregnancies.
Palmar erythema, another common vascular change in pregnancy, affects two-thirds of white women and one-third of black women. The disorder is characterized by diffuse mottling of the entire palm (Figure 2) or by localized erythema of the thenar and hypothenar eminences. Palmar erythema generally resolves one to two weeks postpartum.
Varicosities develop in up to 40 percent of pregnant women and primarily affect the saphenous, vulvar and hemorrhoidal veins. These vascular changes result from increased venous pressure in the pelvic and femoral veins, as well as decreased vessel tone. Varicosities are complicated by thrombosis in 10 percent of pregnancies.3
Cutis marmorata and pregnancy gingivitis are two other vascular changes that can occur during pregnancy. Cutis marmorata, or “marble skin,” is an exaggerated response to cold. This condition primarily affects the lower extremities and is characterized by a bluish discoloration of the skin. Gingivitis is common in pregnancy and is most likely related to vascular proliferation. In patients with swelling and erythema of the gingiva, bleeding may occur with minor trauma or ulceration.
During pregnancy, the normal cyclic stages of hair growth are altered. As a result, the number of follicles in the anagen (growing) phase is increased, and the number of follicles in the telogen (resting) phase is decreased. Because of these changes, which occur during the second and third trimester, many women note a thickening of their scalp hair. Following delivery, the situation reverses and there is a telogen effluvium, with increased shedding of hair beginning four to 20 weeks postpartum.
Pregnant women with a preexisting tendency toward a male pattern of hair distribution may develop more generalized hirsutism, with darker, coarser hair appearing on the upper lip, chin, lower abdomen and extremities. Stimulation of hair growth is probably secondary to adrenal and ovarian hormones. After delivery, coarse hairs do not regress, but fine ones often do.
Specific Skin Disorders of Pregnancy
Pruritic urticarial papules and plaques of pregnancy (PUPPP), also known as late prurigo of pregnancy and polymorphic eruption of pregnancy, is a common, benign skin disorder that occurs primarily in primigravidas.[6,7] The rash appears during the third trimester as erythematous papules that coalesce into plaques, usually starting on the abdominal striae and spreading to the thighs, buttocks and arms (Figure 3). The rash is intensely pruritic and occasionally is accompanied by small vesicles. PUPPP produces no systemic symptoms, and the disorder is not associated with oral contraceptives.
Laboratory tests are normal. Histologic examination reveals a nonspecific, perivascular mononuclear infiltrate with a variable number of eosinophils; epidermal changes, when present, include focal spongiosis and parakeratosis with mild acanthosis. Immunofluorescence studies are almost uniformly negative, with a minority of patients showing faint C3 deposition along the basement membrane.
The etiology of PUPPP is unknown, and studies of hormonal mechanisms and au- toantibodies have not found a causal relationship. One study reported that patients with PUPPP had excess maternal weight gain and an increased incidence of twin pregnancies, compared with control subjects. These findings and the fact that PUPPP mainly affects primigravidas suggest a relationship between skin distention and the development of this skin disorder of pregnancy.
The prognosis for patients with PUPPP is good. Symptoms resolve 10 to 14 days postpartum, and the disease generally does not recur with subsequent pregnancies.
Pruritus gravidarum is a generalized itching that occurs without primary skin pathology during pregnancy. The incidence of this condition varies from 0.02 to 2.40 percent and is reported to be as high as 10 percent in Scandinavia and Chile. A family history of the disorder is often present. In two-thirds of cases, the disorder begins in the third trimester, but it may appear earlier.
Pruritus gravidarum is secondary to intrahepatic cholestasis and presents with excoriations on the trunk and extremities. Jaundice may or may not be present. Nausea, vomiting and abdominal pain are absent. Liver function values are often within normal limits. Histologic findings are nonspecific.
The pathogenesis of cholestasis involves high levels of estrogen and progesterone, which interfere with biliary secretion and inhibit glucuronyl transferase. The degree of pruritus does not correlate with serum levels of bile acids but, instead, correlates with the bile acid concentration in the skin. However, the mechanism by which the level of bile acids in the skin produces pruritus is not understood.
In the absence of skin lesions, pruritus gravidarum may be confused with atopic dermatitis, but the disorders may be differentiated by the history. Other causes of generalized pruritus without primary dermatopathology are liver disease, renal failure, anemia, hypothyroidism and hyperthyroidism.
The prognosis for the pregnant woman with pruritus gravidarum is good. In most cases, the condition can be managed with topical corticosteroids and oral antihistamines, and the pruritus subsides shortly after delivery. The prognosis for the fetus is less favorable, with reports indicating increased rates of mortality and prematurity, especially in patients with severe cholestasis. Pruritus gravidarum tends to occur with subsequent pregnancies and with the use of oral contraceptives.
Pemphigus gestationis is an uncommon autoimmune disorder, occurring in one of 50,000 pregnancies. Rarely, it has been reported in association with hydatidiform mole and choriocarcinoma. The first episode of pemphigus gestationis usually occurs in primigravidas during the second or third trimester. Recurrences with subsequent pregnancies are common; these episodes occur earlier and tend to be more severe.
The disorder presents as erythematous plaques and papules that progress to vesicles and bullae (Figure 4). The lesions usually appear first on the abdomen, most commonly near the umbilicus; they are intensely pruritic and tend to spread centrifugally. The rash resolves several months postpartum, although exacerbations may occur with the menses and with the use of oral contraceptives.
Laboratory tests most commonly show leukocytosis with eosinophilia. The erythrocyte sedimentation rate may be elevated. Histologic examination reveals subepidermal bullae that are similar to the lesions in bullous pemphigoid. Immunofluorescence studies most consistently show C3 deposited along the basement membrane.
The etiology of pemphigus gestationis involves an autoantibody that reacts with a basement membrane antigen in both the mother’s skin and the placenta. The antibody most likely develops in response to aberrant expression of major histocompatibility complex class II molecules by the placenta during the second trimester. The antibody fixes C3 to the basement membrane, causing damage to both the skin and the placenta. Like many other autoimmune disorders, pemphigus gestationis is strongly associated with the DR3 and DR4 gene locus in the mother.
Prior to bullae formation, pemphigus gestationis may be confused with PUPPP. Once bullae develop, the differential diagnosis includes bullous erythema multiforme, bullous drug reaction, dermatitis herpetiformis and bullous pemphigoid.
The prognosis for the mother with pemphigus gestationis is good, while that of the fetus is controversial. Earlier studies on this skin disorder of pregnancy found increased rates of fetal morbidity and mortality. More recent studies have found that the fetal mortality rate is no different from that in control populations, but that the incidence of both small-for-gestational-age infants and premature infants is increased. Since pemphigus gestationis affects not only the skin but also the placenta, clinical evidence of placental insufficiency, such as low birth weight and prematurity, is not an unexpected finding.
Impetigo herpetiformis is a rare skin disorder that occurs primarily in pregnant women, although it has also been reported in men and postmenopausal women. The disorder has many similarities to pustular psoriasis, and some investigators consider it to be a variant of that disease.
Impetigo herpetiformis presents during the third trimester. The skin lesions begin as erythematous patches, most commonly affecting the abdomen and the inframammary and inguinal areas; the face, hands and feet are usually spared. The patches develop many small pustules less than 2 mm in diameter. Later, these pustules become crusted. The lesions may or may not be pruritic.
Patients with impetigo herpetiformis often have systemic symptoms, including fever, nausea, vomiting, diarrhea, chills, malaise and arthralgias. The disease may be associated with hypocalceniia; in such cases, tetany and convulsions can occur. Impetigo herpetiformis tends to be cyclic, in that periods of active disease alternate with periods of relative quiescence.
Laboratory findings include leukocytosis, an elevated erythrocyte sedimentation rate and, occasionafly, hypocalcemia. Histologically, impetigo herpetiformis is similar to pustular psoriasis and demonstrates epidermal vesicles filled with neutrophils (spongiform pustules). Immunofluorescence studies are negative.
The differential diagnosis of impetigo herpetiformis includes subcorneal pustular dermatosis and impetigo. Rarely, the disease may be confused with pemphigus gestationis, but the two conditions are easily differentiated by skin biopsy and immunofluorescence studies.
The prognosis for the mother with impetigo herpetiforniis is good, although the condition recurs with increasing severity in subsequent pregnancies. High rates of stillbirth have been reported.
PRURIGO OF PREGNANCY
Prurigo of pregnancy, also known as prurigo gestationis of Besnier, is a relatively common skin disorder with an incidence of one case per 300 pregnant women. The disorder appears during the second trimester.
Prurigo of pregnancy is characterized by small groups of discrete pruritic papules on the extensor surfaces of the arms and legs and on the dorsal aspects of the hands and feet. Lesions may spread to the chest and back. Laboratory studies are normal.
The pathogenesis of this disorder is not well understood, but it may be related to pruritus and subsequent scratching. The lesions respond well to topical corticosteroids, and no maternal or fetal complications occur.
Papular dermatitis of pregnancy is a rare, papular eruption that was first reported in 1962. Controversy surrounds the disease as a clinical entity, because the original study did not include histologic examination, reported high fetal mortality rates and used poorly defined diagnostic criteria to exclude other diseases. Some investigators believe that this skin eruption may be a severe form of prurigo of pregnancy.
The lesions of papular dermatitis of pregnancy are small erythematous papules with hemorrhagic crusts. The papules are pruritic and are not specific to any one trimester. The rash is widely scattered and often demonstrates postinflammatory hyperpigmentation. Lesions clear rapidly postpartum but may return with subsequent pregnancies.
The prognosis for the mother is good, and the dermatitis responds to systemic corticosteroids. The original study revealed a 30 percent fetal mortality rate. However, this mortality rate is probably an overestimation, since it was obtained by including data from the previous pregnancies of women in the study who were diagnosed with papular dermatitis.
Skin Tumors in Pregnancy
MOLLUSCUM FIBROSUM GRAVIDARUM
Molluscum fibrosum gravidarum is a condition characterized by small, fleshy skin growths, also known as acrochordons or skin tags. These skin tags are usually 1 mm to 1 cm in diameter, and they have a fibrovascular connective tissue core that is covered by stratified squamous epithelium. The lesions develop during the third trimester in the skin of the neck, chest, axillae, face and inframammary areas (Figure 5). The skin tags occasionally regress postpartum.
Pyogenic granulomas most commonly develop in the gingiva, and they occur in up to 2 percent of pregnancies. The lesion is usually a violaceous mass arising from the gum, which may bleed or be painful. Often, an associated pregnancy gingivitis is present. Histologically, the lesion consists of granulation tissue with an inflammatory infiltrate, and it is covered by squamous epithelium. Most pyogenic granulomas involute postpartum, although surgical intervention occasionally is necessary.[1,3]
The effect of pregnancy on melanoma continues to be disputed. Since estrogen affects melanogenesis and melanocyte proliferation, it is possible that pregnancy could influence the clinical course of melanoma. However, the literature has not come to a conclusion on the role of estrogen in the development and prognosis of melanoma.
Recent studies[18,20] indicate that long-term survival rates in pregnant women with melanoma are close to the survival rates in the general population and that the prognosis is best predicted by Breslow skin-thickness parameters. These studies also report that although long-term survival is relatively unchanged, the disease-free interval is reduced and nodal metastases occur earlier and more frequently in pregnant women.[18,19] Because of the risk of recurrence, the current recommendation is that pregnancy should be avoided for three years after excision of a melanoma.
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