Pemphigoid Gestationis at a Glance
- Acute-onset, intensely pruritic, vesiculobullous eruption of pregnancy or the immediate postpartum period.
- Rare, occurring in roughly 1 in 50,000 pregnancies.
- Histopathology: dermal–epidermal separation with numerous eosinophils.
- Direct immunofluorescence: linear deposition of C3, with or without immunoglobulin (Ig) G, along the basement membrane zone of the epidermal fragment of salt-split skin.
- Enzyme-linked immunosorbent assay for pemphigoid gestationis antibody (BP180) commercially available.
- No significant maternal morbidity or mortality.
- Associated with a slight increase in premature and small-for-gestational-age births.
Pemphigoid gestationis (PG) is the least common, yet best-characterized, dermatitis specific to pregnancy.1 It classically presents as an intensely pruritic, urticarial rash during the later part of pregnancy or the immediate postpartum period, then rapidly progresses to a pemphigoid-like, vesiculobullous eruption. The rash may wax and wane during pregnancy, only to flare during labor and delivery. PG appears to be mediated by a specific immunoglobulin (Ig) G directed against the cutaneous basement membrane zone (BMZ).
PG occurs in approximately 1 in 50,000 pregnancies.2,3 It is associated with HLA-DR3 and -DR4, and it appears likely that the incidence in various ethnic groups parallels the frequency of these genes in different populations.4
PG appears to be caused by an anti-BMZ antibody that induces C3 deposition along the dermal–epidermal junction. The PG autoantibody (formerly called HG factor) is an IgG that is infrequently found by direct immunofluorescence (IF), although indirect, complement-added IF reveals the circulating IgG in the majority of patients. In salt-split skin, staining remains with the epidermal fragment. An enzyme-linked immunosorbent assay (ELISA) for the PG antibody is commercially available, and when this highly sensitive test is used, antibody titers appear to correlate with disease activity.5 The PG autoantibody appears to belong to the IgG1 subclass and fixes complement via the classical complement pathway.6 T cells also show selective NC16A reactivity in PG, although their role in disease development remains to be elucidated.7
Nearly all patients with PG [and most patients with bullous pemphigoid (BP)] have demonstrable antibodies to BP180 (type XVII collagen), a 180-kDa transmembrane protein with its N-terminal end embedded within the intracellular component of the hemidesmosome and its C-terminal end located extracellularly (see Chapter 53). The extracellular section contains a series of 15 collagenous components alternating with 16 short, noncollagenous domains. The sixteenth noncollagenous segment closest to the plasma membrane of the basal keratinocyte is designated NC16A and contains the BP180 immunoreactive site.8,9 The PG autoantibody is assumed to be pathogenic for several reasons: (1) It is found in essentially all patients. (2) In vitro, purified antibodies to BP180 cause chemoattraction to the dermal–epidermal junction with subsequent degranulation and dermal–epidermal separation.10 (3) BP180 antibodies cause keratinocytes to lose cell adhesion in tissue culture.11 (4) Rabbit antibodies to BP180 in animal models induce subepidermal blisters when infused into neonatal mice or hamsters.12,...