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.
TABLE 62-1Pregnancy-specific Dermatoses ||Download (.pdf) TABLE 62-1 Pregnancy-specific Dermatoses
|Disorder ||Frequency ||Characteristic Lesion ||Adverse Pregnancy Effects ||Treatment |
|Cholestasis of pregnancy ||Common ||No primary lesions, secondary excoriations from scratching ||Increased perinatal morbidity ||Antipruritics, cholestyramine, ursodeoxycholic acid |
|Pruritic urticarial papules and plaques of pregnancy (PUPPP) ||Common ||Erythematous pruritic papules or plaques; patchy or generalized on abdomen, thighs, buttocks, especially within striae, but with umbilical sparing ||None || |
|Atopic eruptions of pregnancy (AEP) || || ||None || |
| Eczema of pregnancy ||Common ||Dry, red scaly patches on extremity flexures, neck, face || || |
| Prurigo of pregnancy ||Common ||1–5 mm pruritic red papules on extensor surfaces, trunk || ||} Antipruritics, emollients, topical corticosteroids, oral steroids if severe |
|Pruritic folliculitis of pregnancy ||Rare ||Small red papules, sterile pustules on trunk || || |
|Pemphigoid gestationis ||Rare ||Erythematous pruritic papules, plaques, vesicles, and bullae; abdomen often with umbilical involvement, extremities ||Preterm birth, fetal- growth restriction, transient neonatal lesions || |
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).
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).
Pemphigoid gestationis. A. Bullae commonly develop within erythematous plaques. (Photograph contributed by Dr. Amit Pandya.) B. Abdominal lesions classically involve the umbilicus. C. Lesions on the wrist and forearm are shown here. (Photographs contributed by Dr. Kara Ehlers.)
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).
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).
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).
Pruritic urticarial papules and plaques of pregnancy (PUPPP) shows small papules within abdominal striae.
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).