Dermatologic Disorders During Pregnancy

Marcia S. Driscoll

Introduction

There are three general categories of dermatologic disorders during pregnancy. The first category includes cutaneous problems that arise due to physiologic changes during pregnancy. Secondly, there are dermatoses specific for pregnancy. Lastly, there are skin conditions that are unrelated to pregnancy, which present as a new problem or exacerbation of an existing disorder during pregnancy. Herein, the focus is upon the first two categories, as the latter encompasses a broad range of topics, and such cutaneous problems should be managed jointly by the dermatologist and obstetrician. A review of the literature in this area reveals that many recent studies focus upon topics that are beyond the scope of this chapter (eg, specific mutations that may occur in the pathogenesis of ICP), and therefore some references were published prior to 2009.

Physiologic cutaneous changes During Pregnancy

There are a multitude of hormonal, immunologic, and metabolic changes in the pregnant women, which are manifest in the skin by pigmentary, connective tissue, adnexal, and vascular alterations. In an observational study of 600 consecutive patients attending a university obstetrics clinic, cutaneous changes were seen in the majority patients; 99% of these were considered physiologic.¹ Hyperpigmentation and striae distensae were the most common changes, seen in 87.7% and 72.8%, respectively. Herein, we discuss the most common physiologic cutaneous changes in pregnancy, outlined in Table 41.1.

Pigmentary Changes

Hyperpigmentation is the most common skin change during pregnancy.¹^,² Although its pathogenesis in pregnancy is not completely understood, it is believed that elevated levels of estrogen, progesterone, α- and β-melanocyte-stimulating hormone, and β-endorphins stimulate the melanocytes to produce more melanin.³ It most often starts early in the second trimester, affects women of darker skin types more often, and occurs in anatomic areas that normally have darker pigmentation.¹^,³ Anatomic areas that often darken include the areola and/or nipple and the abdominal midline, known as linea alba, which now becomes the linea nigra (Figure 41.1). In addition, there may be hyperpigmentation of the periumbilical area, axillae, medial thighs, and anogenital region.³

In contrast, the melanocytes within moles (nevi) do not respond with an increase in melanogenesis because nevi do not normally darken during pregnancy, nor do they appear to increase in size (except in specific anatomic areas, such as the abdomen or breasts, where stretching of skin occurs).⁴^,⁵ Therefore, it is important that any changing nevus in the pregnant patient be biopsied, just as in any other patient.⁴ Likewise, there has been much controversy about the impact of pregnancy on melanoma, but most evidence to date suggests that pregnancy neither increases the risk of melanoma nor affects prognosis.⁶

Facial hyperpigmentation is known as melasma, or chloasma, when occurring in the pregnant patient. This may affect as many as 26% to >50% of patients during pregnancy, occurring more often in those with dark skin type, regular sun exposure, or family history.⁷^,⁸ It typically appears as brownish or blue/gray patches that are symmetrically distributed. It can occur on the face in certain patterns: centrofacial (cheeks, forehead, upper lip, nose, and chin), malar (involving the cheeks and nose), or mandibular (affecting the ramus of the mandible).⁵^,⁸ It may persist after pregnancy. Even in women in whom chloasma fades, it may recur with hormonal stimuli, such as oral contraceptive pills, with ultraviolet light exposure, and/or with subsequent pregnancies.²

Table 41.1 Cutaneous Physiologic Changes in Pregnancy

Pigmentary

Melasma (chloasma)
Linea nigra
Hyperpigmentation of areola, nipple, periumbilical region, axillae, medial thighs, and anogenital region

Connective tissue

Striae gravidarum
Skin tags (acrochordons)

Adnexal (hair, eccrine and apocrine sweat glands, and sebaceous glands)

Hirsutism
Thickening of scalp hair during pregnancy
Postpartum hair loss (telogen effluvium)
Brittle nails, more rapid nail growth
Enlargement of sebaceous glands of areola (Montgomery tubercles)
Hyperhidrosis (increased apocrine sweat gland activity)
Miliaria (“prickly heat”)

Vascular

Spider telangiectasias
Palmar erythema
Pyogenic granuloma (granuloma gravidarum, epulis gravidarum)
Venous varicosities—legs, vulva/vagina, anus (hemorrhoids)
Edema affecting lower extremities, sometimes face
Gingival hyperplasia, gingivitis

Early in pregnancy, initiation of broad-spectrum sunscreen with sun protection factor of 50 or more has been shown to prevent the development or worsening of melasma.⁹ Drugs that inhibit tyrosinase, the key enzyme in the pathway of melanin synthesis, are important in treatment.¹⁰ If a patient desires treatment during pregnancy or lactation, 20% azelaic acid cream twice daily to pigmented areas can be safely used due to minimal systemic absorption.¹¹ If a patient has persistent pigmentation in the postpartum period and is not breastfeeding, 4% hydroquinone cream alone or in combination with tretinoin and a corticosteroid cream may be more effective options.¹⁰

Connective Tissue Changes

The most common connective tissue alteration is striae distensae or, in pregnancy, known as striae gravidarum. Although the incidence during pregnancy is variable, a 2017 study of 600 pregnant women observed striae gravidarum in 73% of patients.¹ Risk factors include young maternal age, personal or family history, higher maternal weight before pregnancy and before delivery, and higher birth weight.¹² Striae initially appear as pink or red/purple linear bands (striae rubra), most often on the abdomen (Figure 41.1), but may develop on the breasts, thighs, hips, and buttocks; onset is typically in the late second trimester and early third trimester.¹^,²^,³^,¹² Over months to years, these fade to white atrophic bands (striae alba).²^,³ The pathogenesis is unclear but appears to be multifactorial and influenced by physical factors (increased mechanical stress such as rapid weight gain), alterations in cutaneous structure and function, hormonal factors, and genetic factors.¹² When biopsies of normal skin were compared to those from striae, striae showed significantly increased expression of estrogen, progesterone, and glucocorticoid receptors.¹³ Biopsies taken from striae and from adjacent normal skin in pregnant women showed both a decrease in fibrillin and elastin fibers in the papillary dermis, with a realignment of these same structures in the deep dermis.¹⁴ Therefore, it is possible that mechanical stress exerted on the extracellular matrix in pregnant women with particular risk factors may cause alteration in the elastic fiber network, manifesting clinically as striae.¹²

Figure 41.1 Linea nigra along with striae distensae on the abdomen.

(Reprinted from Goodheart H, Gonzalez M. Goodheart’s Photoguide to Common Pediatric and Adult Skin Disorders. 4th ed. Wolters Kluwer; 2015.)

There is no optimal strategy for prevention and management of striae gravidarum, and few studies have been conducted. A comprehensive Cochrane review of topical preparations to prevent striae gravidarum found no high-quality evidence to support use of a variety of topical agents.¹⁵ Nightly use of topical >0.05% tretinoin cream has shown a very modest improvement when treating striae rubra, but this should be undertaken only in the postpartum period due to potential teratogenicity.¹² Pulsed dye lasers, intense pulsed light, and both nonablative and ablative fractional lasers may have modest benefit.¹⁶

An additional common alteration is the development of skin tags (acrochordons), which are small flesh-colored pedunculated papules that arise most often on the neck, axillae, inframammary area, and inguinal folds, with onset in second half of pregnancy.²^,³ They may regress to some degree after delivery or can be treated with liquid nitrogen cryotherapy, scissor snip, or electrodesiccation.²

Adnexal Changes

Hirsutism, or increased hair growth in a male pattern, may occur on the face most commonly, but also on the extremities, back, and suprapubic region due to production of placental and ovarian androgens.¹⁷ Scalp hair may thicken due to a slowing in the progression of the hair from the growing phase (anagen) to resting phase (telogen). Within the first months postpartum, there is a prolongation of the telogen phase, and patients will note a shedding of hair (telogen effluvium). This hair loss should cease within 15 months.¹⁷

Nails may grow more quickly and become more brittle. Uncommon changes, which slowly normalize in the postpartum period, include transverse grooves of the nail (Beau lines), longitudinal melanonychia (linear pigmented streaks visible on nail), and distal onycholysis (separation of nail from nail bed).¹⁸

Sebaceous glands enlarge on the areola early in the first trimester and appear as small brownish papules (Montgomery tubercles) that regress postpartum.² Sebaceous gland activity on the face may be increased in the third trimester, but overall the development of acne is quite variable: it may worsen or improve.³^,¹⁷^,¹⁸ If mild acne arises, benzoyl peroxide wash, topical 1% clindamycin (solution, gel, or lotion), 2% erythromycin (gel or solution), or topical azelaic acid (15% gel or 20% cream) can be safely used during pregnancy.¹⁹

Eccrine sweat gland activity (excluding the palms) may increase leading to hyperhidrosis, and possible miliaria (“prickly heat”), while apocrine gland activity appears to decrease.¹⁸

Vascular Changes

Vascular cutaneous alterations are a result of decreased vascular smooth muscle tone and peripheral vascular resistance leading to vascular distention. In addition, there is intravascular volume expansion and compression from the enlarging uterus leading to venous congestion.² Spider telangiectasias (Figure 41.2) often arise between the second and fifth month of pregnancy,¹⁷ most commonly on areas of skin drained by the superior vena cava (face, neck, arms, hands).²^,³ They present as a central area of redness (dilated afferent arteriole) with capillaries radiating outward. They typically fade after delivery, but if persistent can be treated with pulsed dye laser or intense pulsed light therapy.² Other changes include palmar erythema, which can present as uniform mottled redness over the palms or in localized areas of the palms.²^,¹⁷ Vascular proliferation can result in gingival hyperplasia, sometimes leading to gingivitis in the presence of risk factors such as poor dental hygiene, local irritants, nutritional deficiencies, or periodontal disease.² Vasomotor instability may occur with episodes of facial flushing, pallor, and cutis marmorata (reticulate or lacy-appearing network of bluish erythema with intervening patches of normal skin) on exposure to cold.²^,¹⁷

Vascular neoplasms, such as pyogenic granulomas (also known as granuloma gravidarum, epulis gravidarum), are exophytic, erythematous papules or nodules that arise in the first half of pregnancy, most commonly on the anterior mandibular or maxillary gingiva or lips (Figure 41.3).¹⁸ These represent hyperplasia of the mucosal capillaries and fibroblasts. If highly symptomatic with much bleeding these can be excised, but most will at least partially regress postpartum.¹^,¹⁷^,¹⁸

Figure 41.2 Spider telangiectasias.

(Reprinted from Goodheart H, Gonzalez M. Goodheart’s Photoguide to Common Pediatric and Adult Skin Disorders. 4th ed. Wolters Kluwer; 2016.)

Figure 41.3 Pyogenic granuloma on the lip.

(Reprinted from Goodheart H, Gonzalez M. Goodheart’s Photoguide to Common Pediatric and Adult Skin Disorders. 4th ed. Wolters Kluwer; 2017.)

Venous congestion can result in varicosities of the legs, nonpitting edema of legs, and sometimes of the face, hemorrhoids, and lower extremity purpura. Varicosities of the vestibule and vagina (Jacquemier sign) and bluish tint of the vagina (Chadwick sign) are early diagnostic signs of pregnancy.² Compression stockings and leg elevation are typically recommended for lower extremity edema and varicosities.² Those with hemorrhoids should be encouraged to eat a high-fiber diet to decrease risk for constipation.² Key points concerning these changes are summarized in Table 41.2.

Specific Dermatoses of Pregnancy

Due to a lack of large prospective studies on dermatoses of pregnancy, there has been significant confusion over which dermatologic disorders are specific for pregnancy. There have been many synonyms for these dermatoses used historically. They have variable clinical presentations (but all are pruritic), are uncommon or rare, do not always have a definite diagnostic test, may have limited treatment options, and sometimes have onset in the postpartum period. Multiple classification systems have existed.²⁰ In 2006, the largest study of pruritic dermatoses of pregnancy evaluated 505 patients over 10 years from two university centers.²¹ These patients had comprehensive past medical histories, morphologic description of skin eruptions, laboratory testing, skin biopsies, and history of dermatoses during other pregnancies or postpartum. Based upon this review, these investigators created what is now accepted as our current classification of SDPs: polymorphic eruption of pregnancy (PEP), atopic eruption of pregnancy (AEP), pemphigoid gestationis (PG), and ICP. Because both PG and ICP may pose risks to both mother and fetus, it is imperative that these diagnoses be made promptly. Table 41.3 provides the current classification of the SDPs and synonyms used historically.²⁰ Key features of the SDPs are provided in Table 41.4, with a detailed description of each in the sections to follow.

Table 41.2 Key Points: Cutaneous Physiologic Changes in Pregnancy

Hyperpigmentation is the most commonly reported skin change
Melasma (chloasma) occurs more often in those with darker skin types, regular sun exposure, or family history
Broad-spectrum sunscreen used early in pregnancy may prevent melasma
Darkening in color of nevi during pregnancy is not physiologic, and biopsy should be performed as in the nonpregnant patient
Striae gravidarum risk factors include young maternal age, personal or family history, elevated body mass index, excessive weight gain during pregnancy
No specific topical preparation reliably prevents striae gravidarum
Postpartum treatment for striae: topical tretinoin has very modest benefit (for striae rubra) as do certain lasers and light therapy
Vascular changes include spider telangiectasias, vascular neoplasms of the gingiva and skin (pyogenic granulomas), venous varicosities of legs, hemorrhoids, gingival hyperplasia

Table 41.3 Classification of Specific Dermatoses of Pregnancy and Historical Synonyms

Current Terminology	Historical Synonyms
Polymorphous eruption of pregnancy (PEP)	Pruritic urticarial papules and plaques of pregnancy (PUPPP)
Atopic eruption of pregnancy (AEP)	Eczema in pregnancy Papular dermatitis of Spangler Prurigo of pregnancy Pruritic folliculitis Prurigo gestationis Nurse’s early prurigo
Pemphigoid gestationis (PG)	Herpes gestationis
Intrahepatic cholestasis of pregnancy (ICP)	Obstetric cholestasis Icterus gravidarum

Table 41.4 Key Features of the Specific Dermatoses of Pregnancy

	Onset	Diagnosis	Maternal Risk	Fetal Risk	Recurrence in Subsequent Pregnancies
AEP	before third trimester	clinical personal or family hx of atopy	No	No	Yes
PEP	third trimester in primigravidas 10%-15% immediate postpartum onset	clinical biopsy and DIF to r/o PG	No	No	No
PG	second and third trimester up to 25% immediate postpartum onset may flare postpartum especially with menses, OCPs	biopsy and DIF	long-term increased risk of Graves disease	Small for gestational age prematurity	Yes
ICP	late second and third trimester	Increased total serum bile acids	early induction of labor intrapartum hemorrhage long-term risk for hepatobiliary disease	prematurity meconium staining of amniotic fluid respiratory distress stillbirth unusual	Yes
AEP, atopic eruption of pregnancy; DIF, direct immunofluorescence; hx, history; ICP, intrahepatic cholestasis of pregnancy; OCPs, oral contraceptive pills; PEP, polymorphic eruption of pregnancy; PG, pemphigoid gestationis; r/o, rule out.

Polymorphic Eruption of Pregnancy

The key points concerning PEP are provided in Table 41.5.

Clinical Presentation of PEP

PEP presents in the late third trimester in primigravidae as pruritic urticarial edematous papules and plaques, typically starting within the striae distensae and/or on the lower abdomen. Sparing of umbilical skin is a characteristic finding (Figure 41.4).²^,²¹^,²² The proximal thighs and buttocks are commonly affected.²² It may spread to extremities and trunk (Figure 41.5) over days and usually spares the face, palms and soles, and mucosa.²¹ Although this SDP has been widely known as pruritic urticarial papules and plaques of pregnancy, the term PEP has been adopted because more than half of all cases have additional skin lesion morphologies, such as eczematous lesions, vesicles, nonurticarial erythema, and targetoid lesions. These polymorphous features occur later in the course of the eruption.²¹ The eruption last about 4 to 6 weeks and resolves spontaneously, independent of delivery.²³

Epidemiology of PEP

PEP is the second most common of the four SDPs,²¹ with an incidence ranging from about 1/120 to 1/300 pregnancies.²³^,²⁴^,²⁵ Although it most often occurs in the last few weeks of pregnancy, it can occur immediately postpartum in up to 15% of cases.²³ Risk factors include multifetal gestation, where it may present earlier, and excessive maternal weight gain.²⁶ No human leukocyte antigen (HLA) subtype associations have been observed with PEP.

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