Pemphigoid Gestationis

Updated: Mar 25, 2022
  • Author: Victor A Teran, MD; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy (see the image below). The disease was originally named herpes gestationis for the herpetiform morphology of the blisters, but this term is a misnomer because pemphigoid gestationis is not related to or associated with any active or prior herpes virus infection.

Tense bullae are present on the arms of this other Tense bullae are present on the arms of this otherwise healthy 32-year-old primigravida woman.

See Diagnosing Dermatoses in Pregnant Patients: 8 Cases to Test Your Skills, a Critical Images slideshow, for help identifying several types of cutaneous eruptions associated with pregnancy.

Causes

Pemphigoid gestationis is a pregnancy-associated autoimmune disease. The autoantibodies are deposited in the skin and detectable in the circulation, and they are predominantly specific for the hemidesmosomal protein BPAG2.

Circulating antibodies and T cells are directed against an immunodominant epitope. This epitope, located in the extracellular region of BPAG2 near the membrane, is called the MCW-1 domain. This region of BPAG2 is also an immunodominant epitope in a closely related autoimmune blistering disease, bullous pemphigoid.

The trigger for autoantibody production is still poorly understood. As described in Pathophysiology, autoantibodies to amniotic basement membrane (paternal major histocompatibility class II antigens) may cross-react with BPAG2 antigen in the skin, leading to the immune response.

Pemphigoid gestationis has also been described to occur in association with trophoblastic tumors, such as hydatiform mole or choriocarcinoma. The condition may also manifest in women with egg-donated pregnancies. [1]

Complications

Women with pemphigoid gestationis have increased incidences of premature delivery and small-for-gestational age (SGA) neonates. An increased lifetime risk of other autoimmune conditions, such as Graves disease, is documented.

Infants born to affected women rarely have transient blistering disease. These infants are at risk for infection, thermoregulatory difficulties, and fluid and electrolyte abnormalities. There is at least 1 documented case of a neonate with pemphigoid gestationis being born to an asymptomatic mother with no PG diagnosis. [2]

Treatment

The goals of treatment are to relieve pruritus and to suppress extensive blister formation. To minimize the risk for the mother and fetus, use the lowest effective dose of medication to suppress disease activity. Even with optimum control, some blisters may continue to develop, and patients may have persistent pruritus. The risks and benefits of therapy must always be evaluated for the mother and the fetus.

See Medical Care and Medication Summary.

Consultations

A dermatologist and an obstetrician must coordinate care for patients with pemphigoid gestationis. The pediatrician also must be aware of the diagnosis and the medications the mother is receiving.

Because pemphigoid gestationis is an uncommon disease, referral to immunodermatologists with expertise in the treatment of patients with severe or persistent disease is appropriate.

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Pathophysiology

Pemphigoid gestationis is a pregnancy-associated autoimmune disease. Most patients develop antibodies against the hemidesmosomal protein BP180 (BPAG2, collagen XVII), and, in some cases, antibodies also form against another hemidesmosomal protein, BP230. [3] However, whereas the role of anti-BP180 is well defined in the pathogenesis of pemphigoid gestationis, [4] BP230 is intracellular and the clinical significance of anti-BP230 is uncertain. [5] Historically known as herpes gestationis factor, these circulating antibodies belong to the heat-stable immunoglobulin G1 subclass. The binding of immunoglobulin G to the basement membrane at the dermoepidermal junction triggers an immune response by neutrophils and eosinophils, leading to the formation of subepidermal vesicles and blisters. In 1999, Chimanovitch et al [6] demonstrated that pemphigoid gestationis sera recognize 5 distinct epitopes within BP180 NC16A, 4 of which have been reported as major antigenic sites targeted by bullous pemphigoid antibodies.

The trigger for the development of autoantibodies in persons with pemphigoid gestationis remains elusive. Cross-reactivity between placental tissue and skin has been proposed to play a role. Pemphigoid gestationis has a strong association with HLA-DR3 (61%) and HLA-DR4 (52%), or both (43%), [7] and virtually all patients with a history of pemphigoid gestationis have demonstrable anti-HLA antibodies. The placenta is known to be the main source of disparate (paternal) antigens and can thus present an immunologic target during gestation. One possible mechanism for autoantibody generation is that aberrantly expressed fetal major histocompatibility complex (MHC)–II on trophoblasts and amniochorionic stromal cells permits maternal detection of paternal MHC-II. [8] BP180 is expressed on both amniotic epithelial cells of the placenta and keratinocytes at the dermoepidermal junction. [9] Thus, BP180 may be presented to maternal MHC-II in the presence of paternal MHC-II and recognized as a foreign antigen, leading to the formation of antibodies that are cross-reactive toward BP180 in the epidermis.

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Epidemiology

In the United States, pemphigoid gestationis has an estimated prevalence of 1 case in 50,000 pregnancies. [5] Findings from European studies suggest that pemphigoid gestationis has an overall incidence of 0.5 cases per million people per year. In 1999, Jenkins et al [10] described the largest cohort of 87 patients in the United Kingdom with a total of 278 pregnancies, of which 142 were complicated by pemphigoid gestationis.

Pemphigoid gestationis is less common among Blacks than Whites, which might reflect its association with specific HLA haplotypes. This condition only affects females, and pemphigoid gestationis occurs in women of childbearing age. The condition is more common in multigravida pregnancies than primigravida. [11]

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Prognosis

Pemphigoid gestationis typically regresses without scarring within weeks to months after delivery. Pemphigoid gestationis may recur in subsequent pregnancies and may be precipitated by menses and the use of oral contraceptives.

Mortality/morbidity

No increase in fetal or maternal mortality has been demonstrated. A greater prevalence of premature and small-for-gestational-age (SGA) babies is associated with pemphigoid gestationis. Of infants, 5-10% born to affected mothers may present with transient cutaneous involvement that resolves as maternal autoantibodies are cleared.

Patients with pemphigoid gestationis have a higher relative prevalence of other autoimmune diseases, including Hashimoto thyroiditis, Graves disease, and pernicious anemia, which are also associated with HLA-DR3 and DR-4 haplotypes

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Patient Education

Mothers with pemphigoid gestationis should be counseled regarding potential sequelae for their infant, such as small-for-gestational-age (SGA), prematurity, and transient blistering. Patients also should be aware that pemphigoid gestationis may recur with subsequent pregnancies, resumption of menses, and use of oral contraceptive agents.

The goals of therapy (ie, control pruritus, suppress extensive blistering but not totally eliminate blister formation) should be discussed with the patient prior to treatment. Patients should understand the benefits and potential adverse effects of all prescribed medications.

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