Pemphigoid gestationis

What is pemphigoid gestationis?^{1 2}

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. It was named herpes gestationis because the blisters had herpetiform features. However, there is no connection with herpes virus infection. There are several ways to diagnose pemphigoid gestationis: clinical evaluation, histological findings, direct immunofluorescence (DIF) or indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and C4d immunochemistry can all be used.

Pathophysiology

Patients develop circulating antibodies of the immunoglobulin G1 subclass which bind to basement membrane and trigger an immune response causing subepidermal vesicles and blisters.³ There is antigenic overlap with the antibodies of bullous pemphigoid. The trigger for development of auto-antibodies is unknown but cross-reactivity between placenta and skin may play a role.

How common is pemphigoid gestationis? (Epidemiology)

PG is very rare and affects only about 1 person in 50,000-2 million pregnancies (depending on HLA type prevalence).⁴ The association with HLA-DR3 and HLA-DR4 haplotypes is reflected in a higher incidence in Caucasians.⁵

Pemphigoid gestationis symptoms (presentation)^{5 6}

• Lesions may appear at any time during pregnancy but they most commonly develop during the second and third trimesters.⁷

• There is sudden onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk. Pruritus 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 fewer than 20% of cases.

• Many women experience remission during late pregnancy, sometimes followed by a flare immediately after delivery. The flare usually settles over a period of 4 weeks without recurrence.¹

Differential diagnosis

It is an uncommon condition and shares some features with other skin diseases of pregnancy.⁸ As a result, diagnosis can be difficult.

• Bullous pemphigoid.

• Cicatricial pemphigoid.

• Pruritic urticarial papules and plaques of pregnancy (PUPPP).

• Linear IgA dermatosis.

• Dermatitis herpetiformis.

• Erythema multiforme.

• Papular dermatitis of pregnancy.

• Pruritic folliculitis of pregnancy.

Investigation¹

Routine investigations are not helpful in diagnosis. There are several ways to diagnose pemphigoid gestationis:

• Clinical evaluation.

• Histology shows typical features of subepidermal blistering.⁹

• Direct immunofluorescence (DIF) or indirect immunofluorescence (IIF).

• Enzyme-linked immunosorbent assay (ELISA).

• C4d immunochemistry can all be used.

Associated diseases

PG has been described in association with hydatiform mole or choriocarcinoma. Affected patients are more likely to develop other autoimmune diseases - for example, Hashimoto's thyroiditis and pernicious anaemia.⁷

Pemphigoid gestationis treatment and management¹

The aim of the treatment is to reduce pruritus and to prevent the advancement of new blisters. The treatment strategy depends on the severity of the disease.

In mild cases, topical corticosteroids are sufficient. In more severe cases, oral corticosteroids are necessary. Minimum effective doses should be used to reduce the risk of side effects.

In addition to corticosteroids, oral anti-histamines can be used to control pruritus. Ultraviolet light therapy is relatively contraindicated as it may promote new blister formation.

In unresponsive cases, patients may benefit from systemic immunoadsorption, a blood-purification technique that enables the selective removal of immunoglobulins from separated plasma through high-affinity adsorbers, and intravenous immunoglobulin (IVIG). Immunoadsorption is rare and not available in all countries. IVIG is a more standard care.

In case of persisting (postnatal) symptoms, systemic immunosuppressants such as cyclosporine A, dapsone, azathioprine, or methotrexate might be beneficial.

Complications

• Premature labour in 20%.⁴

• Lifetime risk of autoimmune disease.

Prognosis¹

There is no increased maternal or child mortality.¹⁰

• There is a greater prevalence of premature or small-for-dates babies.¹¹

• 5-10% of infants may have transient cutaneous involvement that clears as the maternal antibodies wane.⁷

• It is likely to recur in subsequent pregnancies (although it may skip a pregnancy), may be more or less severe, and the onset is likely to be earlier than in previous pregnancies.⁹

• Patients are more susceptible to other autoimmune diseases, including Hashimoto's thyroiditis, Graves' disease and pernicious anaemia.