BACKGROUND

Pemphigoid gestationis (PG) is a variant of bullous pemphigoid, in which the patient has circulating autoantibodies against proteins in the basement membrane of the skin, resulting in pruritus, rash, and blisters. Previously termed herpes gestationis, PG is not infectious, and thus this old terminology has been abandoned. While PG is considered to be a dermatosis limited to pregnancy, some rare cases have been associated with either choriocarcinoma, hydatidiform moles, or trophoblastic tumors.

EPIDEMIOLOGY

PG occurs in approximately 1 out of 1700 to 50,000 pregnancies,¹ with half the cases developing in the first pregnancy. Patients with PG have an increased incidence of autoimmune diseases, particularly autoimmune thyroid disorders.² The HLA-DR3 and DR4 alleles have been associated with the development of PG.^3,4 While the role of different partners with the same mother had previously been considered to be one potential causative factor, a larger study failed to support this theory.^5,6

CLINICAL IMPLICATIONS

PG is classically characterized as a pruritic papulovesicular eruption that favors periumbilical skin. The trunk and extremities can be affected, with sparing of the mucous membranes.^1,5 Lesions typically begin as urticarial plaques and can be clinically and histologically identical to those observed in polymorphous eruption of pregnancy. Frank blistering is not a requisite.⁵

PG most commonly occurs during the second trimester of pregnancy, though it has been described as occurring from the second week of gestation to the early postpartum period.^1,5 Interestingly, with each subsequent pregnancy, the disease recurs with earlier onset, but 8% of mothers experience a skip pregnancy, where they have an unaffected pregnancy following a previously affected one.^5,7

PROGNOSIS

Development of PG at an earlier phase of fetal development is associated with an improved prognosis.⁸ Typically, the disease persists for a mean of 6 months postpartum, although active disease lasting 12 years postpartum has been described.⁵ In these unusual persistent cases, conversion to bullous pemphigoid should be suspected.⁹ In few women, relapses can occur with the use of combined oral contraceptive pills or menstruation.^2,5,6

As PG is an autoimmune disorder due to circulating immunoglobulin G (IgG) autoantibodies against the basement membrane of the skin, transfer of these antibodies to the newborn can occur. Although the fetal prognosis is usually good, the antibodies can lead to premature birth; newborn transient erythematous, papular, or bullous dermatoses; and low birth weight.^1,5,10

DIAGNOSIS

PG requires a clinical picture suggestive of the diagnosis (pruritus, urticarial plaques favoring the umbilicus, bullae) as well as a skin biopsy analyzed by direct immunofluorescence. A biopsy will demonstrate linear deposition of IgG along the basement membrane zone of skin. Clinical-pathologic correlation is a requisite, as the immunofluorescence (IF) pattern can be seen in other autoimmune mucocutaneous blistering diseases that have a different presentation. Indirect IF can be used to further aid confirmation of the diagnosis by taking the patient’s serum and placing it on normal human skin split by salt. In this case, antibodies will target the roof of this artificial blister, supporting a diagnosis of either PG or bullous pemphigoid. Likewise, enzyme-linked immunosorbent assay (ELISA) can be used to confirm the presence of circulating autoantibodies targeting the basement membrane protein BP180.

RECOMMENDATIONS FOR MANAGEMENT

In mild-to-moderate disease, topical potent corticosteroids can be used, albeit less effectively than oral glucocorticoids.² As PG flares near the intrapartum period and resolves at six months postpartum on average, oral corticosteroids are often helpful during the late stages of pregnancy and postpartum. Tapering of steroids should be matched with the expected natural history of the disease to avoid unnecessary exposure to systemic steroids for a typically self-limited disease.

Numerous immunosuppressive agents have been described in recalcitrant cases including azathioprine, cyclophosphamide, cyclosporine, dapsone, tetracyclines, and methotrexate. Given its tolerable safety profile in pregnancy, intravenous immunoglobulin (IVIG) has become a particularly useful agent.¹¹ The use of expectant rituximab early in pregnancy has been described,¹² but remains controversial, as transient hypogammaglobulinemia can occur in the newborn.^13,14

BACKGROUND

Polymorphic eruption of pregnancy (PEP), previously described as pruritic urticarial papules and plaques of pregnancy (PUPPP), is a benign, pregnancy-specific dermatosis. The cause is unclear, and there is no diagnostic confirmatory test. Of note, PEP is truly a diagnosis of exclusion and relies on clinical findings, normal laboratory testing, a nonspecific skin biopsy, and a negative indirect IF.¹⁵

EPIDEMIOLOGY

A meta-analysis revealed that 1.7% of PEP patients had multiple gestations.¹⁶ It was also found that within the multiple gestation group, PEP was more common with triplet (14%) than twin pregnancies (2.9%).¹⁷ This fact suggests increased skin distention as a risk factor for the development of PEP. Furthermore, several additional studies have shown a higher-than-normal maternal weight gain in patients with PEP.¹⁸ Women who are pregnant with male fetuses are more likely to develop PEP, with a male-to-female infant ration of 2:1.¹⁹ A smaller study in Israel demonstrated maternal hypertension and induction of labor to be associated with PEP.²⁰ PEP is also thought to be related to chimerism as a study demonstrated fetal DNA in the skin of mothers with PEP.²¹

CLINICAL IMPLICATIONS

In PEP, pruritic urticarial papules typically begin in the abdominal striae (Fig. 25-4) and spread over several days. It usually spares the face, palms, and soles of the feet. A classic skin finding is periumbilical sparing, unlike gestational pemphigoid that can involve the umbilicus. Typically, onset occurs in the latter part of the third trimester or in the immediate postpartum period. Although microvesiculation can be seen, frank blisters are not observed.¹⁵

PROGNOSIS

The prognosis for an affected patient with PEP is excellent. The eruption resolves within one to two months, and it does not tend to recur in subsequent pregnancies. However, in one study, 7% of multiparous patients with PEP endorsed a similar eruption in prior pregnancies.²² Furthermore, no mortality is associated with PEP, no systemic complications exist, and neither fetal mortality nor morbidity is increased.

DIAGNOSIS

Diagnosis is typically clinical, as described previously. Laboratory testing must be performed to exclude concomitant diseases. This workup includes liver function testing to rule out intrahepatic cholestasis as an underlying disorder. If skin biopsy is performed, it will reveal nonspecific findings like spongiosis, parakeratosis, and/or eosinophilic spongiosis. The dermis may show a perivascular lymphocytic infiltrate with dermal edema. Direct IF typically will show no abnormalities, and indirect IF will be negative. Although IF is the only way to exclude gestational pemphigoid with certainty, it is not suggested to routinely perform IF in cases of clinically consistent PEP.

RECOMMENDATIONS FOR MANAGEMENT

Often, no treatment is necessary, as PEP resolves within 1 to 2 weeks after delivery. However, symptomatic relief can be obtained with potent topical steroids and oral antihistamines. Sometimes women with PEP require systemic corticosteroids if topical treatment is insufficient.