Dermatology

Pemphigoid Gestationis (herpes gestationis)

Pemphigoid Gestationis, herpes gestationis

Are You Confident of the Diagnosis?

What you should be alert for in the history

Gestational pemphigoid classically presents during the second or third trimester, but 25% of cases have been reported to occur during the immediate postpartum period. It typically presents with the sudden onset of severe pruritus, followed by urticarial lesions on the trunk, periumbilical area, and extremities. As the disease progresses within days to weeks, a generalized eruption of tense blisters occurs, sparing the face, palms, soles, and mucous membranes (Figure 1, Figure 2). The course is typically one of exacerbations and remissions, with flares occurring during delivery in 75% of patients.

Figure 1.

Erythematous and urticarial plaques not located on striae characteristic of gestational pemphigoid.

Figure 2.

Erythematous papules and plaques characterisitc of gestational pemphigoid.

Expected results of diagnostic studies

The essential component for diagnosis is obtained from a skin biopsy of perilesional skin submitted in Michel’s media for direct immunofluorescence. Gestational pemphigoid is characterized by the presence of C3, with or without IgG, in a linear band along the basement membrane zone. If the biopsy is nondiagnostic or cannot be obtained, serum samples can be obtained and tested. Indirect immunofluorescence detects a circulating anti-BMZ antibody in the serum of approximately 20% of patients with gestational pemphigoid, but complement-added indirect IF identifies the circulating anti-BMZ IgG in almost all patients. Alternatively, enzyme-linked immunosorbent assay (ELISA) provides a sensitive and specific serum test as well. It detects the anti-BP180 antibodies in 79% of herpes gestationis serum samples.

Diagnosis confirmation

The differential diagnosis includes pruritic urticarial papules and plaques of pregnancy, erythema multiforme, intrahepatic cholestasis of pregnancy, contact dermatitis, and drug reaction

Who is at Risk for Developing this Disease?

The incidence of the disorder is approximately 1 in 10,000; it is most common among Caucasians, likely due to the increased frequency of HLA-DR3 and HLA-DR4 in this group. The disease tends to recur with subsequent pregnancies.

What is the Cause of the Disease?

Etiology

Gestational pemphigoid is considered to be a hormonally-mediated autoimmune disorder caused by an anti-basement membrane zone (anti-BMZ) serum factor that induces C3 deposition along the dermal-epidermal junction.

Pathophysiology

The placentas of women with gestational pemphigoid show an increased expression of MHC class II antigens of paternal haplotype, which are thought to initiate an allogeneic response against a placental BMZ antigen, which is found in the placenta beginning in the second trimester. This antigen is a major component of both placenta and skin, and has been identified as a 180 kD transmembrane hemidesmosomal protein in the skin. Due to the placental and skin antigen similarity, there is destruction of both the skin dermal-epidermal junction and the BMZ of the fetoplacental unit, which leads to bullous disease and low-grade placental insufficiency, respectively.

Systemic Implications and Complications

As a result of the antigenic similarity between skin and placental antigens, there is destruction of both the skin dermal-epidermal junction and the BMZ of the fetoplacental unit, which leads to bullous disease and low-grade placental insufficiency, respectively. Ten percent of neonates may be affected, with mild urticarial or vesicular lesions lasting days to weeks after birth. There is an increased incidence of small-for-gestational age births and premature delivery, with 16% of babies born before 36 weeks and 32% born before 38 weeks, possibly due to low-grade placental insufficiency. No increase in fetal mortality has been noted.

Treatment Options

Systemic corticosteroids are considered the mainstay of therapy. Most patients will respond to 0.5mg/kg of prednisone per day, but doses may be decreased during quiescent phases or increased to control flares during parturition. Topical corticosteroids and antihistamines are typically considered to be ineffective in the absence of very mild (nonvesiculobullous) disease.

Alternatives to systemic corticosteroids, such as azathioprine, methotrexate, dapsone, cyclosporine, intravenous immunoglobulin (IVIG), mycophenolate mofetil, and tetracyclines with nicotinamide, are generally reserved for severe persistent postpartum disease. These agents have not been shown to be useful prior to term and carry a much higher fetal risk than the systemic corticosteroids.

Optimal Therapeutic Approach for this Disease

Prednisone is the most effective treatment. Prednisone doses range from 0.5mg/kg to 1mg/kg per day. Prednisone at dosage of 80mg/day or less during the second trimester or later for short periods of time is generally considered safe. As opposed to managing patients with bullous pemphigoid with concurrent bisphonates therapy in order to protect patients from bone loss secondary to systemic corticosteriods, such drugs are not recommended during pregnancy.

Patient Management

Women with gestational pemphigoid incur no risks from the disease itself, but tend to be at higher risk for the development of other autoimmune diseases, particularly Graves disease. As a result, such women should be monitored appropriately for signs and symptoms of these conditions.

Unusual Clinical Scenarios to Consider in Patient Management

Flares tend to occur with the use of oral contraceptives, and the use of hormonal contraceptives is generally considered contraindicated in these patients. Patients may also experience premenstrual flares up to 18 months postpartum, and prolonged disease lasting months to years after delivery has also been reported.

What is the Evidence?

Al-Fares, SI, Vaughan Jones, SA, Black, MM. "The specific dermatoses of pregnancy: a re-appraisal". JEADY. vol. 15. 2001. pp. 197-206.

(This article clarifies specific guidelines for diagnosing the dermatoses of pregnancy.)

Bremmer, M, Driscoll, MS, Colgan, R. "Six skin disorders of pregnancy: a management guide". OBG Management. vol. 22. 2010. pp. 24-33.

(This article is a brief summary for the nondermatologist of the main dermatoses of pregnancy with a user-friendly table that aids in sorting the diagostic clues and treatment pearls.)

Shornick, JK, Bolognia, JL, Jorizzo, JL, Rapini, RP. "Pregnancy Dermatoses". Mosby. 2003. pp. 425-32.

(This is a chapter in a leading dermatology textbook.)

Borthwick, GM, Holmes, RC, Stireat, GM. "Abnormal expression of class II MHC antigens in placenta from patients with pemphigoid gestationis". Placenta. vol. 9. 1988. pp. 81-94.

(This article postulates the pathophysiology in the development of autoantibodies during pregnancy.)

Shornick, JK, Black, MM. "Fetal risks in herpes gestationis". J Am Acad Dermatol. vol. 26. 1992. pp. 63-8.

(This article identifies the risks to the fetus when the mother develops pemphigoid gestationis.)

Katz, SI, Hertz, KC, Yaoita, H. "Herpes gestationis: immunopathology and characteristics of HG factor". J Clin Invest. vol. 57. 1976. pp. 1434-41.

(This article first identifies the antigen in pemphigoid gestationis.)

Sasseville, D, Wilkinson, RD, Schnader, JY. "Dermatoses of Pregnancy". Int J Dermatol. vol. 20. 1981. pp. 223-41.

(This article clarifies specific guidelines for diagnosing the dermatoses of pregnancy.)

Black, MM. "New observations of pemphigoid “herpes” gestationis". Dermatology. vol. 189. 1994. pp. 50-51.

(This article clarifies further the clinical characteristics of pemphigoid gestationis.)
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