Chapter 62: Dermatological Disorders

Normal physiological changes of pregnancy include alterations to skin, hair, and nails as discussed in Chapter 4 (Skin). In addition, several dermatoses are seen only in pregnancy. Finally, it is axiomatic that skin diseases that affect childbearing-age women are commonly encountered in pregnancy.

Four dermatoses considered unique to pregnancy include intrahepatic cholestasis of pregnancy, pruritic urticarial papules and plaques of pregnancy (PUPPP), atopic eruption of pregnancy (AEP), and pemphigoid gestationis (Table 62-1). As a group, these are diagnosed in up to 5 percent of pregnancies with the following relative occurrences: intrahepatic cholestasis 1 in 100; PUPPP, 1 in 130 to 350; atopic eruptions, 1 in 300 to 450, and pemphigoid, 1 in 50,000 (Chander, 2011). Their gross appearance may be similar to each other or to other skin disorders, and pruritus is a common feature of all four. Only intrahepatic cholestasis and pemphigoid gestationis have been linked with adverse fetal outcomes.

Intrahepatic Cholestasis of Pregnancy

Previously termed pruritus gravidarum and in contrast to the other pregnancy-specific dermatoses, intrahepatic cholestasis of pregnancy generally has no primary skin lesions. Rarely, a rash preceded pruritus (Chao, 2011). Pruritus is associated with abnormally elevated serum bile acid levels, and hepatic aminotransferase levels may also be mildly increased. Adverse fetal affects have been linked to this condition, and it is discussed in detail in Chapter 55 (Hepatic Disorders).

Pemphigoid Gestationis

This rare autoimmune bullous disease is notable for its maternal and fetal effects. Initially, pruritic papules and urticarial plaques form and are then followed in most cases after 1 to 2 weeks by vesicles or bullae. Lesions are frequently distributed periumbilically, and they often develop on other skin surfaces with sparing of mucous membranes, scalp, and face (Fig. 62-1).

Previously termed herpes gestationis, pemphigoid gestationis is not related to the herpesvirus. It is a result of a primary reaction between maternal immunoglobulin G (IgG) antibodies directed against collagen XVII found in the basement membrane of skin as well as amnionic epithelium (Kelly, 1988; Shimanovich, 2002). Collagen XVII is also termed bullous pemphigoid 180 (BP 180). Autoantibody binding to collagen XVII, either in the amnion or in the skin, activates complement to promote eosinophil chemotaxis to the antigen-antibody complexes on the basement membrane. Eosinophilic degranulation damages the dermal-epidermal junction with blister formation (Engineer, 2000).

Pregnancy

In most cases, pemphigoid gestationis develops during a first pregnancy, and it may rarely be associated with gestational trophoblastic disease (Takatsuka, 2012). Most subsequent pregnancies are also affected and usually earlier and more severely. Whites have a higher incidence, and other autoimmune diseases are common in affected women (Shornick, 1984, 1992).

Pemphigoid gestationis usually begins during the second or third trimester. The disease course is frequently marked by antepartum exacerbations and remissions and by intrapartum flares (Shornick, 1998). It is possible that there is an association of pemphigoid gestationis with preterm birth and fetal-growth restriction, especially with early-onset disease and with blistering (Chi, 2009). These theoretically may result from mild placental insufficiency stemming from IgG and complement deposition along the amnionic basement membrane (Huilaja, 2013). Because of this, antepartum surveillance of affected pregnancies may be prudent.

In approximately 10 percent of neonates, IgG antibodies passively transferred from the mother will cause similar skin lesions in the newborn (Erickson, 2002). These eruptions require only wound care and clear spontaneously within a few weeks as the passively acquired IgG levels decrease.

Slowly following delivery, maternal lesions resolve without scarring, and most women are disease-free after 6 months (Jenkins, 1999). In some, however, resolution is protracted, and disease may be exacerbated during menses or by oral contraceptives (Semkova, 2009).

Diagnosis and Treatment

Before bullae form, these lesions may resemble PUPPP (Dermatological Conditions not Specific to Pregnancy). Other diagnoses include pustular psoriasis of pregnancy, dermatitis herpetiformis, erythema multiforme, linear IgA bullous dermatosis, urticaria, allergic contact dermatitis, bullous pemphigoid, and atopic eruptions of pregnancy (Lipozenčić, 2012). Drug-induced blistering syndromes must also be excluded, as some are life-threatening. Examples include Stevens-Johnson syndrome and toxic epidermal necrolysis (Stern, 2012).

Skin biopsy and serum antibody assays may be informative (Semkova, 2009). Immunofluorescent skin tissue staining is the gold standard, and C3 complement and sometimes IgG are seen deposited along the basement membrane between the epidermis and the dermis (Katz, 1976). Also, in many cases, circulating IgG antibodies against collagen XVII may be detected in patient serum (Powell, 2005; Sitaru, 2004).

Pruritus can be severe. Early in its course, topical high-potency corticosteroids and oral antihistamines may be effective. Oral prednisone, 0.5 to 1 mg/kg daily gradually tapered to a maintenance dose, may be needed for relief and also inhibition of new lesions. Plasmapheresis or high-dose intravenous immunoglobulin (IVIG) therapy has been used in intractable cases (Gan, 2012; Van de Wiel, 1980).

Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)

This relatively common pregnancy-specific dermatosis is characterized by its intensely pruritic 1- to 2-mm erythematous papules that coalesce to form urticarial plaques and by its benign effects on pregnancy (Rudolph, 2005). Its cause is unknown, but it is not an autoimmune dermatosis. Also known as polymorphic eruption of pregnancy, PUPPP usually appears late in pregnancy, but 15 percent begin postpartum (Buccolo, 2005). The rash affects the abdomen and proximal thighs in 97 percent of women (Fig. 62-2). Lesions often initially form within striae but show periumbilical sparing. Rarely, the face, palms, and soles may be involved (High, 2005). It is more frequently seen in white and nulliparous women, those with multifetal gestation, and those carrying a male fetus (Regnier, 2008). It seldom recurs in subsequent pregnancies (Ahmadi, 2005).

Diagnosis and Treatment

PUPPP may be compared with a number of skin eruptions. Some include contact dermatitis, drug eruption, viral exanthem, insect bites, scabies infestation, pityriasis rosea, and the other pregnancy-specific dermatoses. It also may appear similar to early pemphigoid gestationis that has not yet blistered. In unclear cases, skin biopsy and negative serum collagen XVII antibody levels help to differentiate the two. Pruritus will usually respond to treatment with oral antihistamines, skin emollients, and topical corticosteroids. A small number of women will need systemic corticosteroids to relieve severe itching (Scheinfeld, 2008).

PUPPP usually resolves within several days following delivery and leaves no scarring. In 15 to 20 percent of women, however, symptoms persist for 2 to 4 weeks postpartum (Vaughan Jones, 1999).

Atopic Eruption of Pregnancy (AEP)

This umbrella term is thought by some authorities, but not all, to encompass three conditions previously considered separate: eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy (Ambros-Rudolph, 2006; Cohen, 2007; Ingber, 2010). Two thirds of women with AEP have widespread eczematous changes, whereas the other third have papular lesions. As a group, these pose no adverse risk to the fetus. Diagnosis is greatly aided by a history of atopy and by rash characteristics.

Eczema in pregnancy has the appearance of traditional eczema but with a pregnancy onset. It is the most common pregnancy-specific dermatosis, and affected skin shows dry, thickened, scaly, red patches involving extremity flexures, nipples, neck, and face. In contrast, prurigo of pregnancy, also known as prurigo gestationis, is characterized by 5- to 10-mm, itchy, erythematous papules or nodules commonly found on the extensor surfaces and trunk. Last, pruritic folliculitis of pregnancy is rare and notable for small, erythematous follicular papules and sterile pustules predominantly on the trunk. Onset for all is during the second or third trimester, although eczema in pregnancy may develop earlier than the other two. All lesions commonly resolve with delivery, but may persist for up to 3 months postpartum. Recurrence with subsequent pregnancies is variable but common.

Diagnosis is one of exclusion. Serum bile acid levels are elevated to concentrations expected for normal pregnancy, and aminotransferase levels are normal. Serology specific for pemphigoid gestationis is negative. Many women with eczema of pregnancy have elevated serum IgE levels, which are not seen with the two other AEP dermatoses (Ambros-Rudolph, 2011).

For all three manifestations, skin lesions and pruritus are usually controlled with low- or moderate-potency topical corticosteroids and oral antihistamines. For severe eczema, second-line agents include short-course ultrapotent topical corticosteroids. However, oral corticosteroids, narrow-band ultraviolet B, or cyclosporine are occasionally required (Koutroulis, 2011).

Any chronic dermatological disorders can complicate pregnancy. Acne is unpredictably affected by pregnancy and if necessary, is treated with benzoyl peroxide, azelaic acid, or topical erythromycin, which are category B drugs (Krautheim, 2003). Topical retinoids, which include tretinoin, adapalene, and tazarotene, also appear safe, but are probably best avoided during pregnancy, especially during the first trimester (Akhavan, 2003). If topical antibiotics are required, benzoyl peroxide plus erythromycin is advocated to minimize Propionibacterium acnes drug resistance (Strauss, 2007; Thiboutot, 2009). With topical salicylic acid, systemic absorption is variable, and efforts to minimize absorption are encouraged (Lam, 2008).

Psoriasis also has a variable course during pregnancy, however, postpartum flares are common with nonsevere disease (Oumeish, 2006). Emollients and low- or moderate-potency topical corticosteroids are given initially. Anthralin and ultraviolet B phototherapy can also be used (Weatherhead, 2007). In resistant cases, restrained use of topical preparations such as high-potency or ultrapotent corticosteroids, calcipotriene, and coal tar appear to be safe in the second and third trimesters, and cyclosporine also may be used (Rosmarin, 2010; Ryan, 2010). With severe disease, a small increased risk for low-birthweight neonates has been shown by some (Lima, 2012; Yang, 2011). Also, in general, psoriatic patients have higher associated rates of depression (Rieder, 2012).

Psoriasis is most commonly of the chronic plaque variety. In contrast, with generalized pustular psoriasis of pregnancy—formerly called impetigo herpetiformis—severe systemic symptoms may develop. This rare pustular form has erythematous, sometimes pruritic, plaques ringed by sterile pustules that enlarge and then crust. Lesions initially involve intertriginous areas but may spread to the torso, extremities, and oral mucosa. Constitutional symptoms are common. For accurate diagnosis, skin biopsy is typically required (Roth, 2011). Extensive lesions can lead to sepsis from secondary infection and to massive fluid loss with hypovolemia and placental insufficiency. Treatment is with systemic corticosteroids along with antimicrobials for secondary infection, and cyclosporine is used in refractory cases (Geraghty, 2011; Huang, 2011). Pustular psoriasis typically resolves quickly in the puerperium, but recurrences have been reported in subsequent pregnancies and with menstruation or oral contraceptive use.

Erythema nodosum is a cutaneous reaction associated with numerous disorders that include pregnancy, but typically it is caused by infections, sarcoidosis, drugs, Behçet’s syndrome, inflammatory bowel disease, or a malignancy (Mert, 2007; Papagrigoraki, 2010). Characteristically, 1- to 5-cm tender, red, warm nodules and plaques develop rapidly on the extensor surface of the legs and arms. Within a few days, lesions flatten and undergo the color evolution of a bruise—from dark red and purple to yellow green. Constitutional symptoms may also be present (Requena, 2007). Initial evaluation and treatment focuses on the underlying etiology.

Pyogenic granuloma are frequently seen in pregnancy. This is a lobular capillary hemangioma commonly forming on the mouth or hand in response to low-grade local irritation or traumatic injury (Fig. 62-3). They grow quickly and bleed with minimal provocation. Active bleeding can be controlled with pressure and application of a silver nitrate stick or Monsel paste (ferric subsulfate). These growths often resolve within months postpartum. But with symptomatic or postpartum lesions, or with unclear diagnosis, excision can be done using suture and scalpel, electrosurgical curettage, laser photocoagulation, or cryotherapy. Oral lesions are best referred to oral health-care specialists.

Rosacea fulminans—also known as pyoderma faciale—is characterized by facial pustules and coalescing draining sinuses. It may rarely complicate pregnancy. Topical or oral antimicrobials are primary treatment, although surgical drainage and corticosteroids have also been used (Fuentelsaz, 2011; Jarrett, 2010). Hidradenitis suppurativa has been said to improve with pregnancy, but in our experiences, it is not appreciably changed. Oral antimicrobials or clindamycin gel are initial choices. Neurofibromatosis lesions may increase in size and number as a result of pregnancy. Other skin conditions that are discussed include hirsutism and melanoma (Chap. 63, Malignant Melanoma), cutaneous lupus (Chap. 59, Systemic Lupus Erythematosus), and skin lesions seen with infections (Chaps. 64 and 65, Maternal and Fetal Immunology).

Local skin care, oral antihistamines, and topical corticosteroids are commonly used for many dermatoses. Oral antihistamines are given for pruritus. Suitable options include first-generation agents such as diphenhydramine (Benadryl), 25 to 50 mg every 6 hours, or chlorpheniramine (Chlor-Trimeton), 4 mg every 6 hours. Second-generation agents—loratadine (Claritin) 10 mg daily and cetirizine (Zyrtec) 5 or 10 mg daily—may produce less sedation and are also pregnancy category B.

Hundreds of topical corticosteroid preparations are available, and in the United States, these are categorized by potency into seven groups. For initial treatment of dermatological disorders, low- or moderate-potency agents are preferred. Low-potency agents include those in groups 6 and 7, such as 1-percent hydrocortisone or 0.05-percent desonide (DesOwen). Moderate-potency drugs are in groups 5, 4, and 3—such as 0.1-percent triamcinolone acetonide (Aristocort) or 0.1-percent mometasone furoate (Elocon). High-potency medications are in group 2, such as 0.05-percent betamethasone diproprionate (Diprolene). Ultrapotent agents in group 1, such as 0.05-percent clobetasol propionate (Temovate), are best reserved for refractory disorders and used for only 2 to 4 weeks on small surface areas.

Mild and moderate strengths are not associated with adverse pregnancy outcomes, whereas high- and ultrapotent agents pose a small risk for fetal-growth restriction if used long-term. Even then, this risk is less than that with systemic corticosteroids (Chi, 2011). Importantly, with any topical agent, factors that increase systemic absorption include a large surface area treated, compromised epidermal barrier, occlusive dressings, prolonged treatment duration, and coadministration of topical agents that increase absorption.

With some severe skin diseases, systemic immune modulating agents, such as corticosteroids and cyclosporine, may be required. Although these are not contraindicated in pregnancy, their risks must be balanced against therapeutic benefits. Of these, cyclosporine is not recommended with breast feeding (Rosmarin, 2010). Bacterial infections are a potential secondary complication of skin disorders and are treated promptly with oral antimicrobial agents with gram-positive coverage. Therapeutic agents to be avoided during pregnancy include methotrexate, psoralen plus ultraviolet A, biological agents, mycophenolate mofetil, and systemic retinoids (Lam, 2008). These are discussed in more detail in Chapter 12 (Lead).