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.

Pathophysiology²

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 (BP). The trigger for development of autoantibodies is unknown but cross-reactivity between placenta and skin may play a role.

Epidemiology

PG is rare and affects about 1 in 50,000 pregnancies in the United States of America.³ The association with HLA-DR3 and HLA-DR4 haplotypes is reflected in a higher incidence in Caucasians.

Presentation

• Lesions may appear at 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. 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.
• Symptoms usually subside at delivery but dramatic flares can occur immediately postpartum.
• It usually resolves within weeks to months after delivery and possibly more quickly with breast-feeding. 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

Differential diagnosis

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

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

Investigation³

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-DR3, HLA-DR4 compared with 3% of the general population)

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

Associated diseases

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.

Management

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.

Complications

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

Prognosis

• 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 anaemia.

Document references

1. Al, Galadari I, Oumeish I, et al; Herpes gestationis (Pemphigoid gestationis). Clin Dermatol. 2006 Mar [abstract]
2. Yancey KB; The pathophysiology of autoimmune blistering diseases. J Clin Invest. 2005 Apr;115(4):825 [abstract]
3. Freiman A; Pemphigus gestationalis; emedicine, 2008. Includes pictures
4. Jenkins RE, Hern S, Black MM; Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp Dermatol. 1999 Jul;24(4):255-9. [abstract]
5. Tunzi M, Gray GR; Common skin conditions during pregnancy. Am Fam Physician. 2007 Jan 15;75(2):211 [abstract]
6. Chan L; Bullous pemphigoid; emedicine, 2008. Includes pictures
7. Khumalo N, Kirtschig G, Middleton P, et al; Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002292. [abstract]
8. Patton T, Korman NJ; Bullous pemphigoid treatment review. Expert Opin Pharmacother. 2006 Dec;7(17):2403-11. [abstract]
9. Fontaine J, Joly P, Roujeau JC; Treatment of bullous pemphigoid. J Dermatol. 2003 Feb;30(2):83-90. [abstract]
10. Marinkovitch MP; Epidermolysis bullosa; emedicine, 2008. Includes pictures
11. Sinemus K, Zillikens D, Lehmann P;

Internet and further reading

• Pemphigoid gestationis; Derm Net NZ - images
• Freiman A; Pemphigus gestationalis; emedicine, 2008. Includes pictures

Acknowledgements