Dermatoses of pregnancy

• Intrahepatic cholestasis of pregnancy

Ambros-Rudolph CM, Müllegger RR, Vaughan-Jones SA, et al: The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients, J AM Acad Dermatol 54(3):395–404, 2006.

Pruritic urticarial papules and plaques of pregnancy (also known as polymorphic eruption of pregnancy, or PUPPP) has an incidence of 1/200 pregnancies. The onset of PUPPP is usually in the third trimester. The pruritic, erythematous, papules and plaques are usually first seen in the abdominal striae (stretch marks) and then spread to the chest, trunk, and extremities. The papules and plaques typically spare the palms, soles, face, and mucous membranes. Large vesicles or bullae are uncommon, though pinpoint vesicles may be seen (Fig. 60-1).

Ahmadi S, Powell FC: Pruritic urticarial papules and plaques of pregnancy: current status, Austr J Dermatol 46:53–60, 2005.

Matz H, Orion E, Wolf R: Pruritic urticarial papules and plaques of pregnancy: polymorphic eruption of pregnancy (PUPPP), Clin Dermatol 24(2):105–108, 2006.

Topical corticosteroids and oral antihistamines are the most common methods of treatment. However, the efficacy of oral antihistamines in treating the pruritus of PUPPP is questionable. The use of oral corticosteroids is rare.

Matz H, Orion E, Wolf R: Pruritic urticarial papules and plaques of pregnancy: polymorphic eruption of pregnancy (PUPPP), Clin Dermatol 24(2):105–108, 2006.

Pemphigoid gestationis (also called herpes gestationis or gestational pemphigoid) is an autoimmune subepidermal bullous disorder of pregnancy that may start in the 2nd trimester, the 3rd trimester, or in the postpartum period. The skin lesions are characterized by urticarial papules and plaques, which then progress into painful bullae. The lesions of pemphigoid gestationis initially present periumbilically (Fig. 60-2A), and then spread to involve the trunk and extremities (Fig. 60-2B), usually sparing the face.

Semkova K, Black M: Pemphigoid gestationis: current insights into pathogenesis and treatment, Eur J Obstete Gynecol Reprod Biol 145(2):138–144, 2009.

Bullous pemphigoid antigen 2 (BPAG2) is a 180 kDal transcellular glycoprotein that is part of the hemidesmosome (a structure that binds epithelial cells to the basement membrane of the epidermis). IgG binds to BPAG2 and triggers the classic complement pathway leading to a deposition of C3 along the basement membrane zone (Fig. 60-3). Deposition of complement along the basement membrane zone leads to a recruitment of inflammatory cells, particularly eosinophils. This cascade ultimately leads to a release of proteolytic enzymes that cleave portions of the epidermis from the dermis.

HLA-DR3 and HLA-DR4.

Powell AM, Sakuam-OyamaY, Oyama N, et al: Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy, Arch Dermatol 141(6):705–710, 2005.

See Table 60-1.

Table 60-1. Compare and Contrast PUPPP and Pemphigoid Gestationis

	PUPPP	PEMPHIGOID GESTATIONIS
Clinical presentation	Pruritic erythematous papules and plaques Initial lesions present in the abdominal striae, spreading to the trunk and extremities; vesicles may be present Usually spares the palms and soles	Urticarial papules, plaques, and blisters Initial lesions start periumbilically and spread to the trunk and extremities The palms and soles are commonly involved
Direct immunofluorescence	Occasional complement deposition in a perivascular location or in a granular formation along the dermal–epidermal junction	Linear deposition of IgG (25% of the time) and complement (C3) at the dermal–epidermal junction. (see Fig. 60-3)
Fetal sequelae	None	Increased risk of intrauterine growth restriction and prematurity 3%–10% of newborns have lesions of neonatal pemphigus
Treatment	Topical corticosteroids Oral antihistamines	Topical or oral corticosteroids (prednisone 0.5 mg/kg/day) Oral antihistamines Dapsone, cyclosporine (results are mixed)
Recurrence in future pregnancies	Usually does not recur	Usually recurs at an earlier gestation and is typically more severe

High W, Hoang MP, Miller MD: Pruritic urticarial papules and plaques of pregnancy with unusual and extensive palmoplantar involvement, Obstet Gynecol 105(5):1261–1264, 2005.

Atopic eruption of pregnancy is classified to include eczema of pregnancy, prurigo gestationis, and folliculitis of pregnancy. According to the retrospective study by Ambros-Rudolph et al, it is the most common dermatoses of pregnancy, with a prevalence of 50.7%. In this study 20% of the patients were known to have preexisting atopic dermatitis, but 80% of the patients reviewed experienced symptoms de novo during pregnancy. It is known to start early in pregnancy, before the third trimester. The skin lesions are erythematous, excoriated papules, plaques, or nodules on the extensor surfaces of the limbs and on the trunk, and may appear crusted and eczematous. The treatment involves topical corticosteroids, and the disease usually resolves in the postpartum period.

Ambros-Rudolph CM, Müllegger RR, Vaughan-Jones SA, et al: The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients, J Am Acad Dermatol 54(3):395–404, 2006.

Intrahepatic cholestasis of pregnancy (ICP) is characterized symptomatically by an intense pruritus, most often starting on the palms and soles, and then becoming generalized. There are no other dermatologic findings except excoriations. ICP usually occurs in the third trimester of pregnancy. The etiology of intrahepatic cholestasis of pregnancy is not completely understood, but there is a strong indication that there is interplay between a rise in pregnancy hormones (estrogen and progesterone), accumulation of bile acids secondary to liver dysfunction, and genetic susceptibility contributing to development of this disease.

Geenes V, Williamson C: Intrahepatic cholestasis of pregnancy, World J Gastroenterol 15(17):2049–2066, 2009.

The main risks are to the fetus; the fetus is unable to excrete cholic acid, resulting in toxicity. Sudden intrauterine fetal death occurs in 1% to 2% of pregnancies affected by ICP. Other complications include respiratory distress syndrome, meconium staining of amniotic fluid membranes, and premature delivery. The risk of fetal complications increases with bile acids levels >40 μM/L. There are not usually any long-term maternal sequelae. The pruritus associated with ICP usually resolves within 48 hours to 2 weeks, after delivery.

Hepburn I: Pregnancy-associated liver disorders, Dig Dis Sci (53):2334–2358, 2008.

See Table 60-2.

Table 60-2. Treatment Regimens of ICP

Ursodeoxycholic acid 15 mg/kg/day	Decreases bile acid concentration Aids in transplacental transport of bile acids
S-adenosyl-methionine	Reverses estrogen induced cholestasis in experimental animals Minimally improves bile acid laboratory values and pruritus Studies show conflicting evidence regarding the efficacy of this drug
Cholestyramine	Generally not shown to be effective
Dexamethasone	Inhibits placental estrogen synthesis Does not improve pruritus or transaminase levels Repeated doses may be associated with decreased birth weight and other fetal complications
Delivery	Delivery is the cure for ICP Most authors recommend early delivery by 38 weeks (∼36 weeks for severe laboratory derangements)

Hepburn I: Pregnancy-associated liver disorders, Dig Dis Sci (53):2334–2358, 2008.

Impetigo herpetiformis is a rare disorder that typically presents in the third trimester. This disease is characterized by sterile pustules on an erythematous plaque initially presenting on the flexural and intertriginous areas, and then progressing to involve the trunk and remaining surfaces of the extremities. Impetigo herpetiformis can involve the mucous membranes. There also can be nail involvement, as well as systemic symptoms such as fever and malaise. It is associated with an increased risk of intrauterine growth restriction and stillbirth. Clinically and histologically, impetigo herpetiformis resembles pustular psoriasis, and it is debated whether or not impetigo herpetiformis is a distinct disease.

Lim KS, Tang MB, Nq PP: Impetigo herpetiformis—a rare dermatosis of pregnancy associated with prenatal complications, Ann Acad Med Singapore 34(9):565-568, 2005.

Systemic corticosteroids are the first-line treatment. Some studies have reported good outcomes with cyclosporine. The condition resolves with delivery. It is important to be aware of secondary infections of the lesions, and then to treat with appropriate antimicrobial medications.

Brightman, L, Stefanato CM, Bhawan J, et al: Third-trimester impetigo herpetiformis treated with cyclosporine, J Am Acad Dermatol 56(Suppl 2)S62–S64, 2005.

• Cutaneous tumors

Muallem MM, Rubeiz NG: Physiological and biological skin changes in pregnancy, Clin Dermatol 24(2):80–83, 2006.

• Melasma, which is hyperpigmentation of the face involving the cheeks, nose, or the chin (Fig. 60-4)

The exact mechanism is not known, but it is thought that an increase in estrogen, progesterone, and melanocyte-stimulating hormone stimulates melanogenesis.

Barankin B, Silver SG, Carruthers A: The skin in pregnancy, J Cutan Med Surg 6(3):236–240, 2002.

Melanoma accounts for 8% of malignancies in pregnancy. Pregnancy is no longer thought to worsen the prognosis of melanoma, and the survival rates for similarly staged pregnant and nonpregnant individuals are not statistically significant.

Pagés C, Robert C, Thomas L, et al: Management and outcome of metastatic melanoma during pregnancy, Br J Dermatol 162:274–281, 2009. [Epub ahead of print.]

• Palmer erythema (Fig. 60-5)

• Hemorrhoids

Muallem MM, Rubeiz NG: Physiological and biological skin changes in pregnancy, Clin Dermatol 24(2):80–83, 2006.

2. Molluscum fibrosum gravidarum are skin tags that develop on the face, neck, chest, axilla, and inframammary areas of pregnant women. They may regress spontaneously postpartum, and, if not, are easily treated through surgical removal.

Muallem MM, Rubeiz NG: Physiological and biological skin changes in pregnancy, Clin Dermatol 24(2):80–83, 2006.

• Fox-Fordyce disease

The regression of psoriasis, rheumatoid arthritis, and systemic lupus erythematosus is thought to be related to the suppressed maternal immunity of pregnancy. Improvement of hidradenitis suppurativa and Fox-Fordyce disease is possibly secondary to the decreased apocrine gland activity in pregnancy.

Oumeish OY, Al-Fouzan AW: Miscellaneous diseases affected by pregnancy, Clin Dermatol 24(2):113–117, 2006.

Raychaudhuri SP, Navare T, Gross J, et al: Clinical course of psoriasis during pregnancy, Int J Dermatol 42(7):518–520, 2003.

Yes. See Table 60-3.

Table 60-3. Mucocutaneous Diseases Exacerbated by Pregnancy

Infections Candidal vaginitis Trichomoniasis Condyloma acuminata Pityrosporum folliculitis Herpes simplex Varicella-zoster Leprosy

• Intrahepatic cholestasis of pregnancy

Ambros-Rudolph CM, Müllegger RR, Vaughan-Jones SA, et al: The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients, J AM Acad Dermatol 54(3):395–404, 2006.

Pruritic urticarial papules and plaques of pregnancy (also known as polymorphic eruption of pregnancy, or PUPPP) has an incidence of 1/200 pregnancies. The onset of PUPPP is usually in the third trimester. The pruritic, erythematous, papules and plaques are usually first seen in the abdominal striae (stretch marks) and then spread to the chest, trunk, and extremities. The papules and plaques typically spare the palms, soles, face, and mucous membranes. Large vesicles or bullae are uncommon, though pinpoint vesicles may be seen (Fig. 60-1).

Ahmadi S, Powell FC: Pruritic urticarial papules and plaques of pregnancy: current status, Austr J Dermatol 46:53–60, 2005.

Matz H, Orion E, Wolf R: Pruritic urticarial papules and plaques of pregnancy: polymorphic eruption of pregnancy (PUPPP), Clin Dermatol 24(2):105–108, 2006.

Topical corticosteroids and oral antihistamines are the most common methods of treatment. However, the efficacy of oral antihistamines in treating the pruritus of PUPPP is questionable. The use of oral corticosteroids is rare.

Matz H, Orion E, Wolf R: Pruritic urticarial papules and plaques of pregnancy: polymorphic eruption of pregnancy (PUPPP), Clin Dermatol 24(2):105–108, 2006.

Pemphigoid gestationis (also called herpes gestationis or gestational pemphigoid) is an autoimmune subepidermal bullous disorder of pregnancy that may start in the 2nd trimester, the 3rd trimester, or in the postpartum period. The skin lesions are characterized by urticarial papules and plaques, which then progress into painful bullae. The lesions of pemphigoid gestationis initially present periumbilically (Fig. 60-2A), and then spread to involve the trunk and extremities (Fig. 60-2B), usually sparing the face.

Semkova K, Black M: Pemphigoid gestationis: current insights into pathogenesis and treatment, Eur J Obstete Gynecol Reprod Biol 145(2):138–144, 2009.

Bullous pemphigoid antigen 2 (BPAG2) is a 180 kDal transcellular glycoprotein that is part of the hemidesmosome (a structure that binds epithelial cells to the basement membrane of the epidermis). IgG binds to BPAG2 and triggers the classic complement pathway leading to a deposition of C3 along the basement membrane zone (Fig. 60-3). Deposition of complement along the basement membrane zone leads to a recruitment of inflammatory cells, particularly eosinophils. This cascade ultimately leads to a release of proteolytic enzymes that cleave portions of the epidermis from the dermis.

HLA-DR3 and HLA-DR4.

Powell AM, Sakuam-OyamaY, Oyama N, et al: Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy, Arch Dermatol 141(6):705–710, 2005.

See Table 60-1.

Table 60-1. Compare and Contrast PUPPP and Pemphigoid Gestationis

[/not-level-membership-for-dermatology-category]

	PUPPP	PEMPHIGOID GESTATIONIS
Clinical presentation	Pruritic erythematous papules and plaques Initial lesions present in the abdominal striae, spreading to the trunk and extremities; vesicles may be present Usually spares the palms and soles	Urticarial papules, plaques, and blisters Initial lesions start periumbilically and spread to the trunk and extremities The palms and soles are commonly involved
Direct immunofluorescence