Atopic dermatitis AD
Atopic eruption of pregnancy AEP
Estrogen receptor ER
Intrahepatic cholestasis of pregnancy ICP
Malignant melanoma MM
Pemphigoid gestationis PG
Polymorphic eruption of pregnancy PEP
Prurigo of pregnancy PP
Pruritic folliculitis of pregnancy PFP
Psoralen with ultraviolet light A PUVA
Ultraviolet light B UVB
This chapter reviews the physiologic skin changes induced by pregnancy, along with preexisting skin diseases and tumors, and also outlines the diagnosis and treatment of melanoma, pruritis, and specific dermatoses of pregnancy. Common skin conditions discussed in the text are defined in Table 51-1 .
|Pseudoacanthosis nigricans||Hyperpigmentation of the skin folds and neck that mimic acanthosis nigricans|
|Dermal melanocytosis||Clusters of melanocytes abnormally located in the dermis that result in ill-defined bluish-gray patches|
|Vulvar melanosis||Irregularly distributed patches of pigmentation on the vulva|
|Pregnancy-associated hyperkeratosis of the nipple||Focal hyperkeratosis, at times with wartlike papules, of the apex of the nipple|
|Miliaria||Sweat retention that reflects obstruction of eccrine sweat ducts|
|Hyperhidrosis||Skin disorder characterized by increased sweat secretion|
|Dyshidrosis||Recurrent vesicular eruption of palms and soles|
|Fox-Fordyce disease||Chronic pruritic disorder of the apocrine glands characterized by blockage of the apocrine duct and sweat retention|
|Onycholysis||Detachment of the nail plate from the nail bed|
|Subungual hyperkeratosis||Deposition of keratinous material on the distal nail beds|
|Palmoplantar pompholyx eczema||See dyshidrosis above (former name for pompholyx )|
|Acne conglobata||Variant of acne vulgaris characterized by severe eruptive nodulocystic lesions without systemic manifestations|
|Pemphigus vulgaris||Autoimmune bullous disorder of the skin and oral mucosa produced by antidesmoglein-3 antibodies that cause intraepidermal acantholysis|
|Pemphigus vegetans||Variant of pemphigus vulgaris characterized by pustules that form fungoid vegetations or papillomatous proliferations|
|Pemphigus foliaceus||Autoimmune bullous skin disorder produced by antidesmoglein-3 antibodies that cause subcorneal acantholysis|
|Spitz nevi||Seen predominantly in children or young adults and characterized by prominent epithelioid and/or spindled melanocytes that can have atypical features|
Physiologic Skin Changes Induced by Pregnancy
The human skin undergoes substantial changes during pregnancy, induced by the combined effect of endocrine, metabolic, mechanical, and blood flow alterations. Although they may prompt cosmetic complaints, such physiologic changes are not associated with risks to the mother or fetus and can be expected to resolve or improve postpartum ( Box 51-1 ). However, some changes such as melasma, varicosities, and pregnancy-associated hyperkeratosis of the nipple may persist postpartum.
Hyperkeratosis of the nipple
Hair Cycle and Growth
Postpartum telogen effluvium
Postpartum male-pattern alopecia
Diffuse hair thinning (late pregnancy)
Brittleness and softening
Increased eccrine function
Increased sebaceous function
Decreased apocrine function
Skin tags ( molluscum fibrosum gravidarum )
Pyogenic granuloma ( granuloma gravidarum )
Severe labial edema
Mild forms of localized or generalized hyperpigmentation occur to some extent in up to 90% of pregnant women and are most noticeable in the areolae, nipples, genital skin, axillae, and inner thighs. Familiar examples include the darkening of the linea alba ( linea nigra ) and periareolar skin. Melasma, also termed chloasma or mask of pregnancy, refers to the facial hyperpigmentation reported in up to 70% of pregnant women. Hyperpigmented, symmetric, poorly demarcated patches are commonly seen on the malar areas ( malar pattern ) and are often distributed over the entire central face ( centrofacial pattern ; Fig. 51-1 ). In 16% of cases, hyperpigmentation occurs on the ramus of the mandible (mandibular pattern). Melasma results from melanin deposition in the epidermis (70%), dermal macrophages (10% to 15%), or both (20%). It is likely secondary to the hormonal changes of gestation with increased expression of α-melanocyte–stimulating hormone. Melasma typically is exacerbated by exposure to ultraviolet and visible light. Hyperpigmentation is often more pronounced in brunettes and women with more melanocytes than in women with lighter baseline skin tone; the use of a broad-spectrum sunscreen with a high sun protection factor (SPF) during pregnancy may decrease the severity of hyperpigmentation.
Melasma usually resolves postpartum but may recur in subsequent pregnancies or with the use of oral contraceptives. Troublesome persistent melasma can be treated postpartum with topical hydroquinone 2% to 4% and sunscreen, with or without a topical retinoid and mild topical steroid. Despite treatment postpartum, melasma persists in approximately 30% of patients, especially in women with the dermal or mixed subtypes in which the deeper level of pigmentation results in decreased efficacy of topical agents. Combination therapies including laser treatment and chemical peels may be effective in resistant cases. There have been no reports of adverse fetal effects from laser skin treatment during pregnancy. Most laser experts agree that laser radiation does not penetrate through the skin into deeper soft tissues; therefore it should not affect the fetus or the placenta. Still, because of potential liability issues, most dermatologists and plastic surgeons prefer not to perform laser procedures during gestation.
Uncommon pigmentary patterns such as pseudoacanthosis nigricans, dermal melanocytosis, vulvar melanosis, and verrucous areolar hyperpigmentation can also be seen in pregnancy (see Box 51-1 ). Postinflammatory hyperpigmentation secondary to specific dermatoses of pregnancy (see the section “ Specific Dermatoses of Pregnancy ”) is also common in women with more highly pigmented skin types.
As a result of the combination of rising estrogen levels and increased blood volume in pregnancy, blood flow to the skin increases 4 to 16 times in the first 2 months of pregnancy and doubles again during the third month; this results in significant vascular sequelae (see Box 51-1 ). Spider nevi (spider angiomata) and telangiectasias develop in approximately two thirds of white women and 10% of black women between the second and fifth months of pregnancy and usually resolve within 3 months postpartum ( Fig. 51-2, A ). Approximately 10% of women have persistent spider nevi; treatment with electrodessication or pulsed dye laser is effective in women who find these cosmetically troubling.
Palmar erythema, likely secondary to capillary engorgement, is also very common and occurs in up to 70% of white and 30% of black women. Whereas varicosities of the distal leg veins and hemorrhoidal veins develop in more than 40% of women, thrombosis within these superficial varicosities occurs infrequently (<10%). Nonpitting edema can be seen on the ankles (70%) and face (50%) and is most pronounced in the early months of gestation. Varicosities may regress postpartum but usually not completely and are likely to recur in subsequent pregnancies.
Gum hyperemia and gingivitis are common and frequently result in mild bleeding from the gums during routine oral hygiene. This is most prominent during the third trimester and resolves postpartum. Good dental hygiene will minimize symptoms. Periodontal disease has been associated with adverse pregnancy outcomes, so women without a recent dental examination should be referred.
The pyogenic granuloma of pregnancy, known as granuloma gravidarum or pregnancy epulis, is a benign proliferation of capillaries that usually occurs in the gingiva but can occasionally be identified on the lip or extramucosal sites (see Fig. 51-2, B ). Pyogenic granulomas commonly appear between the second and fifth months of pregnancy and affect up to 2% of pregnancies. Presenting as a vascular, deep red or purple, exuberant, often pedunculated nodule between the teeth or on the buccal or lingual surface of the marginal gingiva, a pyogenic granuloma may be more likely after mucosal trauma. Spontaneous shrinkage of the tumor usually occurs postpartum, and most cases do not require treatment. Surgical excision or electrosurgical destruction should be reserved for cases complicated by excessive bleeding or severe discomfort.
Connective Tissue Changes
Striae gravidarum, also called striae distensae or “stretch marks,” develop in up to 90% of white women between the sixth and seventh months of gestation. Risk factors include younger maternal age, excessive pregnancy weight gain, and concomitant use of corticosteroids; however, genetic susceptibility plays a key role. Striae are most prominent on the abdomen, breasts, buttocks, groin, and axillae; whereas usually asymptomatic, a proportion of patients complain of mild to moderate pruritus. The treatment of striae gravidarum is a challenge; at present, no optimal treatment is available. The erythema (red color) of early striae responds well to various pulsed-dye lasers or intense pulsed light. The red color tends to become pale over time, with or without treatment, but the atrophic lines never disappear completely and do not respond to laser treatment. Topical tretinoin 0.1% cream has been shown to improve the appearance of the striae, decreasing the length by 20%, and is occasionally used in combination with topical glycolic acid (up to 20%) in an effort to increase elastin content of the affected areas. Nevertheless, tretinoin can be very irritating to the skin and does not make striae completely disappear. No topical therapy prevents or affects the course of striae; they become less apparent postpartum but may never disappear.
Skin tags (molluscum fibrosum gravidarum) present as 1- to 5-mm fleshy, pedunculated, exophytic growths on the neck, axillae, inframammary region, or groin and usually appear during the later months of gestation. Treatment can be postponed until completion of the pregnancy because lesions may regress postpartum. Cryotherapy with liquid nitrogen or shave removal is effective for persistent or enlarging lesions. Skin tags do not have malignant potential, and treatment is unnecessary unless inflammation or ulceration develops.
Increased eccrine function has been reported during pregnancy and may account for the increased prevalence of miliaria, hyperhidrosis, and dyshidrosis. Conversely, apocrine activity may decrease during gestation, which contributes to the decreased prevalence of Fox-Fordyce disease and possibly hidradenitis suppurativa in pregnancy. Changes in sebaceous function are variable, and the effects of pregnancy on acne vulgaris are unpredictable. Treatment for acne vulgaris during pregnancy is discussed below. During pregnancy, the sebaceous glands on the areolae enlarge ( Montgomery’s glands or tubercles ).
Hair and Nail Changes
Most pregnant women develop mild hirsutism that affects their face, trunk, and extremities that commonly regresses within 6 months postpartum. In addition, postpartum hair shedding ( telogen effluvium ) may be noted as a greater proportion of hairs enter the telogen phase ( Fig. 51-3 ). The severity of telogen effluvium varies considerably, and the hair loss becomes noticeable when more than 40% to 50% of the hair is affected. Recovery is spontaneous, and no effective treatment is available. Patients can be counseled that hair thinning usually resolves within 1 to 5 months but that complete resolution may occasionally take up to 15 months. Frontoparietal hair recession and diffuse hair thinning in the later months of pregnancy have been noted in some women. Nail changes can be seen as early as the first trimester of gestation that include brittleness, onycholysis, subungual hyperkeratosis, and transverse grooving. No specific treatment is available for nail changes during pregnancy, and most are expected to resolve postpartum. An attempt should be made to eliminate external sensitizers, such as nail polish removers, and infections. The nails should be kept short if they are brittle or prone to onycholysis.
Preexisting Skin Diseases and Tumors Affected by Pregnancy
Pregnancy can aggravate or, less often, improve many skin conditions and primary skin tumors (see ). Diseases that may improve during pregnancy include atopic dermatitis, acne, chronic plaque psoriasis, Fox-Fordyce disease, hidradenitis suppurativa, linear immunoglobulin A (IgA) dermatosis, sarcoidosis, Behçet disease, urticaria, and autoimmune progesterone dermatitis (see Table 51-1 ).
Atopic Eczema and Dermatitis
Atopic dermatitis (AD), also known as atopic eczema, is a very common skin condition and is often exacerbated by pregnancy, although remission has been noted in up to 24% of cases. Two large studies that used diagnostic criteria established in pediatric populations indicated a high prevalence of AD in pregnancy, including “new AD” (AD presenting for the first time in pregnancy); however, the true prevalence may be revised as the criteria for gestational AD are refined. Risk factors include a history of prior atopy (27%), family history of atopy (50%), and offspring with infantile AD (19%). Other risk factors for AD include black or Asian race and tobacco use. The prevalence of intrinsic (“nonallergic”) versus extrinsic (IgE associated) AD during gestation is unknown, although a small study showed that intrinsic AD is more affected by pregnancy.
Most patients present with lesions in the flexural surfaces of the extremities, occasionally with concomitant lesions on the trunk. Less common presentations are palmoplantar pompholyx eczema and follicular and facial eczema. In pregnancy, eczematous lesions can develop bacterial or viral superinfection (i.e., eczema herpeticum secondary to herpes simplex virus); treatment with dicloxacillin or a first-generation cephalosporin should be used as necessary in these cases. Eczema herpeticum and disseminated herpetic infection, the latter of which may lead to fetal risk, should be promptly treated with intravenous (IV) acyclovir to minimize maternal and fetal risks.
AD is not associated with an increased risk of adverse fetal outcomes. The effects of breastfeeding and maternal food antigen avoidance during pregnancy on AD in the offspring are controversial. Treatment for gestational exacerbations of AD is primarily symptomatic. A moisturizer and low potency to midpotent topical steroid is the first-line treatment. Systemic antihistamines, such as chlorpheniramine or diphenhydramine, can also be used as necessary for relief of pruritus. A short course of oral steroids may be required for severe AD. Ultraviolet light B (UVB) is a safe second-line treatment for eczema in pregnancy. There is less experience with the newer topical immunomodulators (pimecrolimus, tacrolimus). Although their bioavailability is limited (<5%) and no pattern of anomalies has been reported after exposure to these drugs in utero, several infants have had neonatal hyperkalemia. Therefore these immunomodulators should be used as third-line treatment for refractory AD that has not responded to UVB. If systemic agents are needed for refractory AD, cyclosporine is the safest option.
The course of gestational AD in the postpartum period has not been studied. Irritant hand dermatitis and nipple eczema are often seen postpartum. Irritant hand dermatitis is treated with emollients and hand protection. Nipple eczema can evolve into painful fissures and can be complicated with bacterial superinfection, most commonly with Staphylococcus aureus . Superinfected nipple eczema should be treated with a topical steroid combined with a topical or systemic antibiotic.
The effects of pregnancy on acne vulgaris are unpredictable. In one study, pregnancy affected acne in approximately 70% of women, with 41% reporting improvement and 29% reporting a worsening with pregnancy. Two patients had improvement in one pregnancy and exacerbation in another. Some patients may develop acne for the first time during pregnancy or in the postpartum period ( postgestational acne ). Comedonal acne should be treated with topical keratolytic agents, such as benzoyl peroxide, whereas inflammatory acne should be treated with azelaic acid, topical erythromycin, topical clindamycin, or oral erythromycin base. Although first-trimester use of topical tretinoin has not been associated with an increased rate of congenital malformations in controlled studies, the number of reported exposures is too small to exclude a small increased risk. A theoretic concern remains, and the use of tretinoin during pregnancy is therefore not recommended (see Chapter 8 ).
Other Inflammatory Skin Diseases
Recurrent flares of urticaria may worsen in pregnancy. Of interest, these flares show common features with hereditary angioedema and may have been exacerbated in the past by oral contraceptive use or prior to menses. Chronic plaque psoriasis may develop for the first time during pregnancy. Women with existing chronic psoriasis can be counseled that between 40% and 63% of women have symptomatic improvement, compared with only 14% of women who have symptomatic deterioration ; postpartum flares are common (80%). Topical steroids and topical calcipotriene are relatively safe treatment options for localized psoriasis in pregnancy. For severe psoriasis that has not responded to topical medications, UVB or a short course of cyclosporine are considered second-line treatment options.
Autoimmune Progesterone Dermatitis
Autoimmune progesterone dermatitis is caused by hypersensitivity to progesterone through autoimmune or nonimmune mechanisms. Although this rare dermatosis can take various forms (urticarial, papular, vesicular, or pustular), the hallmark is recurrent cyclic lesions that usually appear during the luteal phase of the menstrual cycle. Limited information is available regarding the effects of pregnancy on autoimmune progesterone dermatitis. Case series report instances of both improvement and exacerbation. Increased cortisol levels and/or the gradual increase in the sex hormone levels during pregnancy with subsequent hormonal desensitization in some patients are both possible mechanisms for observed improvement. Diagnosis is based on either an immediate local urticarial reaction or, more frequently, a delayed hypersensitivity reaction following intradermal challenge with synthetic progesterone. Intramuscular administration of progesterone should be avoided in these patients because it has been associated with angioedema. Circulating antibodies to progesterone or the corpus luteum have been detected by indirect immunofluorescence in several patients. The sensitivity of this test seems to be lower than that of the intradermal progesterone challenge, therefore these antibodies are not widely used to confirm this diagnosis. No specific therapy for the condition during pregnancy has been proposed. Autoimmune estrogen dermatitis has also been reported in a patient who presented with urticaria in early pregnancy.
Impetigo herpetiformis is a rare variant of generalized pustular psoriasis that develops primarily during pregnancy, often in association with hypocalcemia or low serum levels of vitamin D. Although familial occurrence has been reported, more commonly a personal or family history of psoriasis is absent. The eruption usually develops in the third trimester but can also start in earlier trimesters and postpartum. Whereas the overwhelming majority of cases resolve postpartum, persistent cases have been reported and can be associated with oral contraceptive use. Various infections during pregnancy may also trigger a flare of pustular psoriasis in a genetically predisposed individual.
Impetigo herpetiformis is characterized by numerous grouped, discrete, sterile pustules at the periphery of erythematous patches ( Fig. 51-4, A ). Lesions typically originate in the major flexures (axillae, inframammary areas, groin, and gluteal fold) and progress onto the trunk, usually sparing the face, hands, and feet. Painful mucosal erosions may also develop. Onycholysis, or complete nail shedding secondary to subungual lesions, has been reported. Constitutional symptoms are common and include fever, malaise, diarrhea, and vomiting with resultant dehydration. Rarely, patients develop complications secondary to hypocalcemia that include tetany, convulsions, and delirium. Common laboratory findings are leukocytosis and elevated erythrocyte sedimentation rate; rarer perturbations include hypocalcemia, decreased serum vitamin D levels, and signs of hypoparathyroidism. Historically reported maternal risks such as tetany, seizures, delirium, and death from cardiac or renal failure or septicemia are uncommon. Fetal risks such as stillbirth and fetal abnormalities secondary to placental insufficiency have been reported even when the condition was well controlled. Whereas maternal prognosis is excellent with early diagnosis, aggressive treatment, and supportive care, an increased risk of perinatal mortality may persist despite maternal treatment. The risk is difficult to quantify because it is based on sparse case reports that span decades. Intensive fetal monitoring should be considered until the mother is stabilized. After acute treatment, the appropriate degree of fetal surveillance is not known; however, periodic assessment of fetal well-being is prudent after viability.
Definite diagnosis of impetigo herpetiformis is based on histopathology that shows typical features of pustular psoriasis (see Fig. 51-4, B ). Direct and indirect skin immunofluorescence is negative. Systemic steroids are first-line therapy for impetigo herpetiformis, and 20 to 40 mg/day of prednisone is usually effective. Cases of pustular psoriasis exacerbated by pregnancy have been treated with cyclosporine. Calcium and vitamin D replacement therapy should be undertaken if necessary and can lead to remission of the eruption. Systemic antibiotics should be administered if bacterial superinfection is suspected. Postinflammatory hyperpigmentation may develop, but scarring is usually absent. Impetigo herpetiformis has been treated postpartum with oral steroids, oral retinoids, and photochemotherapy (psoralen with ultraviolet light A [PUVA]) as single agents or in combination. Resistant cases can be treated with a combination of PUVA and clofazimine or methotrexate postpartum (methotrexate is contraindicated during pregnancy [category X], and both methotrexate and clofazimine are contraindicated during breastfeeding).
Cutaneous Manifestations of Autoimmune Disorders
Cutaneous lesions may be prominent in some individuals affected by autoimmune disorders, and these patients often have questions regarding how pregnancy will affect the appearance of these lesions. The cutaneous manifestations of chronic discoid lupus are not affected by pregnancy. Cutaneous flares of systemic lupus erythematosus can usually be managed with oral steroid treatment. Dermatomyositis/polymyositis may show exacerbation of the characteristic heliotrope rash in approximately half of affected individuals. The cutaneous progression of scleroderma is not significantly altered by pregnancy, and symptoms of Raynaud phenomenon may improve. Pregnant women with limited skin disease do significantly better than those with diffuse scleroderma. The medical and obstetric management of pregnancies complicated by collagen vascular disease is discussed in detail in Chapter 46 .
Bullous dermatologic disorders develop secondary to autoantibodies that target constituents of the skin and oral mucosa. Pemphigus vulgaris, vegetans, or foliaceus may develop or worsen during pregnancy, whereas linear IgA disease may improve. In more than 50% of cases of pemphigus vulgaris, lesions may initially appear within the oral cavity. Diffuse skin involvement with multiple flaccid vesicles follows with confluence of vesicles forming large eroded areas. Skin biopsy with immunofluorescence studies are needed for a definitive diagnosis. Biopsy for routine histopathology and immunofluorescence is indicated in patients with new-onset lesions, most critically to differentiate pemphigus from herpes ( pemphigoid ) gestationis (see that section below). In cases of pemphigus, fetal and neonatal skin lesions can occur secondary to transplacental transfer of IgG antibodies, but these resolve spontaneously within 2 to 3 weeks after birth. Pemphigus should be treated with oral corticosteroids, and high doses may be required. A recent study of 49 pregnancies complicated by pemphigus vulgaris showed a 12% perinatal mortality. Forty-five percent of live neonates had pemphigus lesions at birth. Increased fetal surveillance is prudent in pregnancies affected by active pemphigus, although the effectiveness of this surveillance in preventing morbidity and fetal loss is not known.
Acrodermatitis enteropathica is a rare autosomal-recessive disorder of zinc deficiency characterized by dermatitis, diarrhea, and alopecia. Vesiculobullous and/or eczematous skin lesions can develop on the extremities and at periorificial sites such as the mouth and perianal and genital areas. The disease usually flares early in gestation as serum zinc levels decrease, but it may also flare with oral contraceptive use.
Most skin neoplasms that present or enlarge during pregnancy are benign, and this includes pyogenic granuloma, hemangioma, hemangioendothelioma, glomus tumor, glomangioma, dermatofibroma, dermatofibrosarcoma protuberans, leiomyoma, keloid, desmoid tumor, and neurofibroma. Melanocytic nevi may develop, enlarge, or darken during pregnancy, but these changes are less dramatic than previously thought. A mild degree of histopathologic atypia has been reported in a few studies. Pennoyer and colleagues compared photographs of moles taken during the first trimester and again in the third trimester. Only 3% of nevi enlarged during pregnancy, and another 3% regressed. In contrast, dysplastic nevi in women with familial dysplastic nevus syndrome do have a tendency to increase in size and undergo color change during pregnancy. Spitz nevi, another class of common pigmented benign neoplasms, may also increase in size or erupt during pregnancy. Studies that used dermoscopy showed that the pigment network of nevi becomes thicker and more prominent, and the globules darken during pregnancy; these features, however, return to their original state within 1 year after delivery. Any suspicious pigmented skin lesion should prompt a dermatologic referral. The “ABCDE” clinical criteria for pigmented lesions— asymmetry, border irregularity, color variegation, diameter greater than 6 mm, and evolution (i.e., an enlarging or otherwise changing lesion)—are helpful in determining which lesions are of higher malignant potential. Seborrheic keratoses are also common and may enlarge or darken during gestation. None of these benign lesions requires treatment during pregnancy; the pregnant patient should be reassured that these changes are benign and may improve postpartum.
Malignant melanoma (MM; see Chapter 50 ) is the most common malignancy in pregnancy and accounts for 31% of all malignant tumors diagnosed in pregnancy with an overall incidence that ranges between 2.8 and 8.5 cases per 100,000 women. Some studies have shown that melanomas that develop during pregnancy are thicker than those in nonpregnant women, possibly because of a delayed diagnosis due to a shared misconception by the patient and/or her physician that darkening and changing of a nevus is normal in pregnancy. However, after correcting for tumor thickness, no effect on prognosis was apparent. Despite initial concerns, several epidemiologic studies to evaluate the effect of pregnancy status at diagnosis suggest that the 5-year survival rate is not affected after controlling for confounding factors. However, data are insufficient for stage III and IV disease. The major prognostic determinants of survival in patients with localized melanoma are tumor (Breslow) thickness and ulceration status, and level of invasion is only significant in women with tumors more than 1 mm in thickness.
Inconclusive evidence supports the role of estrogen receptors (ERs) in melanoma. Most studies did not show an increased risk of melanoma recurrence with oral contraceptives or hormone replacement therapy (HRT) use. Some studies have found melanoma cell lines that lack type I ERs, but others have demonstrated an inhibitory effect of estrogens on melanoma cell lines through type II ERs. In fact, decreased levels of ERβ expression, which antagonizes the proliferative behaviors of ERα, have been seen in more invasive MM with increased Breslow thickness. Higher levels of ERβ have been demonstrated in melanoma cells of pregnant women compared with melanoma cells in men, thus potentially implicating ERβ and female sex as a protective and prognostic factor in MM. Wide local excision of the primary melanoma should be performed in stages I through III, and conservative excision should be undertaken in stage IV. Sentinel lymph node biopsy (SLNB) is indicated for a tumor stage of T1b or greater if thickness is greater than 0.75 mm. SLNB is the most powerful prognostic factor in clinically localized melanoma. However, because allergic reactions to the isosulfan blue dye used in the procedure have been reported, Schwartz and colleagues proposed the use of radiocolloid alone for SLNB in the first trimester. The authors also proposed that wide local excision and SLNB with blue dye can be delayed until after delivery in women who are in the second half of pregnancy and have already undergone narrow excision of their MM with negative margins. Regarding other staging procedures, chest radiography with appropriate shielding and ultrasound of the abdomen and liver should be performed in stage IIB/IIIA. In stages greater than IIIA, magnetic resonance imaging (MRI) of the head and positron emission tomography (PET)/computed tomography (CT) scans should be performed; MRI carries a risk for tissue overheating and should not be used in the first trimester.
Complete lymph node dissection is warranted in stages I and II if SLNB is positive, and therapeutic lymph node dissection should be undertaken in stage III. As far as management of stage IV patients, elective termination and tailored treatment should be considered in the first trimester, whereas tailored treatment and induction when the fetus is viable should be considered in the second and third trimesters. However, termination of pregnancy in stage IV patients does not affect the outcome of MM in the mother, and the risk of fetal metastasis remains remote.
Melanoma is the most common type of malignancy to metastasize to the placenta and fetus, and it represents 31% of such metastases. However, it should be emphasized that placental and/or fetal metastases are extraordinarily rare (27 cases) and that even in the setting of placental metastasis, fetal metastasis only occurs in 17% of cases. Histologic evaluation of the placenta should be performed because of potentially microscopic placental metastasis with known association to fetal melanoma. The presence of placental metastases is associated with widespread disease and dismal maternal survival. The role of systemic therapy in preventing metastases to the placenta and fetus has not been adequately studied.
No standard guidelines are available for patients who desire to become pregnant after the diagnosis and treatment of melanoma. A nonsignificant decrease in mortality in pregnancy subsequent to a melanoma diagnosis has been reported. The primary reason to delay pregnancy following a recent diagnosis of melanoma is the time-dependent risk of tumor recurrence and subsequent maternal mortality. One study showed that 83% of stage II MM recurrences were within 2 years of initial treatment. Schwartz and colleagues suggested waiting 2 years in patients with thin melanomas and 3 to 5 years in thicker lesions before becoming pregnant again. Patients should be counseled on a case-by-case basis depending primarily on risk of recurrence, taking into account the thickness of their original tumor and other prognostic factors. Women with a significant risk of recurrence may want to delay pregnancy until they can be assured of a low recurrence risk. In women with a thin tumor with a low risk of recurrence, no delay may be necessary.