Introduction
Background
Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy. The disease was originally named herpes gestationis on the basis of the morphological herpetiform feature 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.
The Medscape Pregnancy Resource Center may be of interest.
Pathophysiology
Pemphigoid gestationisis a pregnancy-associated autoimmune disease. Most patients develop antibodies against 2 hemidesmosomal proteins, BP180 (BPAG2, collagen XVII) and less frequently BP230. 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 triggers an immune response, leading to the formation of subepidermal vesicles and blisters. In 1999, Chimanovitch et al1 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 (61-80%) and HLA-DR4 (52%), or both (43-50%), 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) antibodies and can thus present an immunologic target during gestation.
Frequency
United States
In the United States, pemphigoid gestationis has an estimated prevalence of 1 case in 50,000-60,000 pregnancies.
International
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 al2 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.
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. See Hashimoto Thyroiditis, Graves Disease, and Pernicious Anemia for more information on these topics.
Race
Pemphigoid gestationis is less common among blacks than whites, which might reflect its association with specific HLA haplotypes.
Sex
This condition only affects females.
Age
Pemphigoid gestationis occurs in women of childbearing age.
Clinical
History
- Pemphigoid gestationis typically manifests during late pregnancy, with an abrupt onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk. Unrelenting pruritus often interferes with daily activities.
- Lesions may appear any time during pregnancy, but they most commonly develop during the second and third trimesters.
- Symptoms may abate at the end of pregnancy; however, dramatic flares can occur at or immediately after delivery. Pemphigoid gestationis usually resolves spontaneously within weeks to months after delivery and possibly quicker with breastfeeding. The persistence of disease activity for years postpartum has been reported.
- Pemphigoid gestationis may recur with the resumption of menses, use of oral contraception, and subsequent pregnancies. The 1999 cohort study by Jenkins et al2 showed no association between change in partner and development of pemphigoid gestationis in subsequent pregnancies.
Physical
- The initial clinical manifestations are erythematous urticarial patches and plaques, which are typically periumbilical.
- These lesions progress to tense vesicles and blisters (see Media File 1 and Media File 4).
- Some patients may present with urticarial plaques and may never develop blisters (see Media File 2). These hivelike plaques differ from true urticaria because of their relatively fixed nature.
- The rash spreads peripherally, often sparing the face, palms, and soles. Mucosal lesions occur in less than 20% of cases.
- Patients may have secondary infections at blister sites.
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, BP.
- 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.
More on Pemphigoid Gestationis |
 Overview: Pemphigoid Gestationis |
| Differential Diagnoses & Workup: Pemphigoid Gestationis |
| Treatment & Medication: Pemphigoid Gestationis |
| Follow-up: Pemphigoid Gestationis |
| Multimedia: Pemphigoid Gestationis |
| References |
| Next Page » |
References
Chimanovitch I, Schmidt E, Messer G, Dopp R, Partscht K, Brocker EB, et al. IgG1 and IgG3 are the major immunoglobulin subclasses targeting epitopes within the NC16A domain of BP180 in pemphigoid gestationis. J Invest Dermatol. Jul 1999;113(1):140-2. [Medline].
Jenkins RE, Hern S, Black MM. Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp Dermatol. Jul 1999;24(4):255-9. [Medline].
Sitaru C, Powell J, Messer G, Brocker EB, Wojnarowska F, Zillikens D. Immunoblotting and enzyme-linked immunosorbent assay for the diagnosis of pemphigoid gestationis. Obstet Gynecol. Apr 2004;103(4):757-63. [Medline].
Amato L, Mei S, Gallerani I, Moretti S, Fabbri P. A case of chronic herpes gestationis: persistent disease or conversion to bullous pemphigoid?. J Am Acad Dermatol. Aug 2003;49(2):302-7. [Medline].
Ambros-Rudolph CM, Mullegger RR, Vaughan-Jones SA, Kerl H, Black MM. The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients. J Am Acad Dermatol. Mar 2006;54(3):395-404. [Medline].
Bedocs PM, Kumar V, Mahon MJ. Pemphigoid gestationis: a rare case and review. Arch Gynecol Obstet. May 28 2008;[Medline].
Boulinguez S, Bedane C, Prost C, Bernard P, Labbe L, Bonnetblanc JM. Chronic pemphigoid gestationis: comparative clinical and immunopathological study of 10 patients. Dermatology. 2003;206(2):113-9. [Medline].
Fabbri P, Caproni M, Berti S, Bianchi B, Amato L, De Pita O, et al. The role of T lymphocytes and cytokines in the pathogenesis of pemphigoid gestationis. Br J Dermatol. Jun 2003;148(6):1141-8. [Medline].
Kreuter A, Harati A, Breuckmann F, Appelhans C, Altmeyer P. Intravenous immune globulin in the treatment of persistent pemphigoid gestationis. J Am Acad Dermatol. Dec 2004;51(6):1027-8. [Medline].
Kroumpouzos G, Cohen LM. Dermatoses of pregnancy. J Am Acad Dermatol. Jul 2001;45(1):1-19; quiz 19-22. [Medline].
Lin MS, Arteaga LA, Diaz LA. Herpes gestationis. Clin Dermatol. Nov-Dec 2001;19(6):697-702. [Medline].
Lin MS, Gharia MA, Swartz SJ, Diaz LA, Giudice GJ. Identification and characterization of epitopes recognized by T lymphocytes and autoantibodies from patients with herpes gestationis. J Immunol. Apr 15 1999;162(8):4991-7. [Medline].
Powell AM, Sakuma-Oyama Y, Oyama N, Albert S, Bhogal B, Kaneko F, 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. 2005;141:705-10. [Medline].
Satoh S, Seishima M, Sawada Y, Izumi T, Yoneda K, Kitajima Y. The time course of the change in antibody titres in herpes gestationis. Br J Dermatol. Jan 1999;140(1):119-23. [Medline].
Shimanovich I, Brocker EB, Zillikens D. Pemphigoid gestationis: new insights into the pathogenesis lead to novel diagnostic tools. BJOG. Sep 2002;109(9):970-6. [Medline].
Tunzi M, Gray GR. Common skin conditions during pregnancy. Am Fam Physician. Jan 15 2007;75(2):211-8. [Medline].
Further Reading
Keywords
herpes gestationis, PG, autoimmune dermatosis of pregnancy, pregnancy-associated autoimmune disease, bullous pemphigoid antigen 2, BPAG2, herpetiform blisters, herpes gestationis factor, pruritic urticarial papules, pruritic urticarial blisters
