Pemphigoid Gestationis (PG)

Pemphigoid gestationis (PG) is an autoimmune bullous disease of pregnancy characterised by deposition of complement (and sometimes immunoglobulin) in the lamina lucida of the cutaneous basement membrane. PG is very rare and affects only about 1 person in 2 million per year. It was, rather confusingly, named herpes gestationis because the blisters had herpetiform features.¹ However there is no connection with herpes virus infection.

Patients develop circulating antibodies of the immunoglobulin G1 subclass which bind to basement membrane and trigger an immune response causing subepidermal vesicles and blisters. There is antigenic overlap with the antibodies of bullous pemphigoid. The trigger for development of autoantibodies is unknown but cross-reactivity between placenta and skin may play a role.

PG is rare and affects about 1 in 50,000 pregnancies in the United States.³ The association with HLA-DR-3 and DR-4 haplotypes is reflected in a higher incidence in caucasians.

• Lesions may appear any time during pregnancy, but they most commonly develop during the second and third trimesters.⁴
• There is sudden onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk. Pruritis is severe and unrelenting.
• Lesions start with erythematous urticarial patches and plaques around the umbilicus. They progress to tense vesicles and blisters. Sometimes urticarial plaques may never develop blisters. They differ from true urticaria because they are relatively fixed in nature.
• The rash spreads peripherally, often sparing the face, palms, and soles. Mucosal lesions occur in less than 20% of cases.
• Symptoms usually subside at delivery but dramatic flares can occur immediately post partum.
• It usually resolves within weeks to months after delivery and possibly quicker with breastfeeding. Disease persisting for years after delivery has been reported.
• It may recur with the resumption of menstruation, use of oral contraception, and subsequent pregnancies. This is unaffected by a change in partner.⁴

It is an uncommon condition and shares some features with other skin diseases of pregnancy.⁵ As a result diagnosis can be difficult.

• Bullous pemphigoid^6,7,8,9
• Cicatricial pemphigoid
• Urticaria
• Linear IgA dermatosis
• Dermatitis herpetiformis
• Erythema multiforme
• Papular dermatitis of pregnancy
• Pruritic folliculitis of pregnancy

Routine investigations are not helpful in diagnosis. The diagnosis is made according to:

• The characteristic clinical presentation.
• Characteristic histology (subepidermal blistering)
• Direct immunofluorescence (DIF) tests
• Indirect immunofluorescence (IDIF) tests
• HLA testing (45% have HLA-DR-3, DR-4 compared to 3% of the general population)

The DIF test is important, but gives similar results in bullous pemphigoid and epidermolysis bullosa acquisita.¹⁰

PG has been described in association with hydatiform mole or choriocarcinoma.¹¹ Affected patients are more likely to get other autoimmune diseases. For example Hashimoto's thyroiditis and Pernicious anaemia.

Medication is kept to a minimum in view of the pregnancy. Corticosteroids and antihistamines are used. Shared care involving obstetrician, dermatologist and paediatrician is appropriate.

• Premature labour
• Lifetime risk of autoimmune disease
• Transient blistering disease in the infants

• There is no increased maternal or child mortality
• There is a greater prevalence of premature or small for dates babies
• 5-10% of infants may have transient cutaneous involvement that clears as the maternal antibodies wane
• Patients are more susceptible to other autoimmune diseases, including Hashimoto's thyroiditis, Graves' disease, and pernicious anemia.