Postpartum pemphigoid gestationis.

Pemphigoid gestationis (PG) or herpes gestationis is a rare autoimmune subepidermal blistering disorder associated with pregnancy. The condition typically develops during the second or third trimester of pregnancy, but has been rarely reported in the first trimester and postpartum period. Here, we report a case of PG that presented for the first time in the postpartum period, associated with a low birth weight baby.

Introduction

Pemphigoid gestationis (PG) is a rare disease with a reported incidence of 1:50,000.[1] Milton coined the term herpes gestationis in 1872. Although PG is considered as a specific dermatosis of pregnancy, it has also been reported in association with hydatidiform mole and choriocarcinoma. This condition can be confused with other dermatoses of pregnancy like pruritic urticarial papules and plaques of pregnancy and other autoimmune blistering diseases like bullous pemphigoid. Direct immunofluorescence (DIF) is the preferred test for confirmation of diagnosis.[2]

Case Report

A 19-year-old housewife presented with multiple fluid-filled lesions on the body of 5 days duration. Within hours after her first delivery, pruritic reddish raised lesions appeared over the abdomen and limbs. On the next day, she noticed fluid-filled lesions over the same sites. Newer lesions started developing in the subsequent days and she was referred to our hospital.

On examination, multiple tense vesicles and bullae were present over abdomen, flexural aspects of forearms, thighs and back of trunk [Figures 1 and 2]. Urticarial plaques were also seen. Nikolsky sign and bulla spread sign were negative. Mucosal lesions were absent. Palms and soles appeared normal. Systemic examination was within normal limits. Her baby was healthy and did not show any skin lesions. However, the birth weight was only 1.8 kg (low birth weight), which could not be attributed to any other cause. We made a provisional diagnosis of PG and the patient was investigated.

Figure 1

Tense bulla over flexural aspect of the forearm

Figure 2

Intact and collapsed bullae over the forearm

Routine investigations including hemogram, liver and renal function tests, blood sugar levels, chest X-ray and urine examination were within normal limits. Tzanck smear showed both eosinophils and neutrophils. Skin biopsy showed subepidermal bulla, dermal edema and a perivascular inflammatory infiltrate composed of lymphocytes, eosinophils and plasma cells [Figure 3].

Figure 3

Subepidermal bulla with mixed inflammatory infiltrate (H and E, stain ×100)

These findings were consistent with a diagnosis of PG. DIF findings included a strong linear basement membrane zone (BMZ) band of C3 and a weak discontinuous BMZ band of IgG. IgM, IgA and fibrinogen were negative. The DIF findings were highly suggestive of PG [Figure 4].

Figure 4

Direct immunofluorescence photomicrograph showing linear band of C3 at the dermoepidermal junction (×200)

The patient was started on oral prednisolone 30 mg daily along with supportive measures. Her condition improved and she did not develop any further lesions [Figure 5].

Figure 5

Healed lesions over the abdomen

Prednisolone was gradually tapered and she was discharged after 2 weeks. During the subsequent visits, the patient did not have any lesions, and steroids were stopped after 8 weeks. Patient is under follow-up for the past 9 months and she is asymptomatic till now.

Discussion

PG is an uncommon autoimmune blistering disease with autoantibodies targeting the hemidesmosomal proteins BP180 and less commonly BP230.[3] The circulating IgG antibody, mainly of the IgG1 subclass, which fixes complement at the BMZ is known as the herpes gestationis (HG) factor. Immunogenic studies have revealed a marked increase in HLA antigens DR3 and DR4. It is considered that HLA mismatch between mother and fetus triggers an immune response which initiates an allogenic response to placental BMZ, which then cross reacts with skin. Recent immunohistochemical studies have identified a T-cell population with a prevalent T helper (Th2) phenotype in the lesional skin of PG subjects,[4] which may be implicated in the recognition of self-antigens and production of pathogenic autoantibodies.

Recurrence of the skin lesions in subsequent pregnancies and postpartum flare up may indicate the persistence of circulating autoantibodies. Satoh et al.[5] reported that antibodies to BP antigen (AG)2 were detectable for several months in the serum of patients with postpartum PG even after subsidence of skin lesions. However, the HG factor is not detected in all cases. Therefore, there may be some factors other than antibodies to BP AG2, which may contribute to blistering in PG. The finding that DIF for C3 remained positive for intervals ranging from 6 months to 4 years after the cessation of clinical activity in eight of nine patients with PG supports this speculation.[6]

Histopathology shows subepidermal bulla containing numerous eosinophils. The essential component for the diagnosis of PG is the finding of C3 with or without IgG in a linear band along the BMZ of perilesional skin on DIF. C3 and IgG deposits are seen in the placenta and fetal skin also.[7] Indirect immunofluorescence demonstrates circulating IgG autoantibodies in 20–60% of cases, but complement fixation test reveals these specific autoantibodies in 90% of PG patients.[16]

PG typically occurs during the second or third trimester of pregnancy or rarely in the immediate postpartum period and usually resolves within 3 months after delivery.[1] It starts as intensely pruritic, erythematous annular urticarial plaques on which blisters develop. The lesions are described more frequently on the abdomen, with extension to flexural areas. Face, mucus membranes, palms and soles are usually spared. The disease often resolves during the later part of gestation and flares at the time of delivery. Rarely, the disease may manifest within hours of parturition[8] as in our patient. Most patients experience spontaneous regression over weeks to months postpartum. Recurrent disease flares have been reported from 2 weeks up to 12 years postpartum.[2] Recurrence with menstruation or with subsequent use of oral contraceptives has often occurred. Fetal risks may also be present in PG and include miscarriages, prematurity, low birth weight babies and transient erythema and blistering.[9]

As HG is a rare disease, controlled studies are not available. However, systemic corticosteroids remain the mainstay of treatment.[10] Most patients respond to a dose of 0.5 mg/kg of prednisolone daily. Maintenance therapy, generally at a lower dosage, may be required throughout gestation. Dapsone, cyclosporine, methotrexate, cyclophosphamide and azathioprine have been tried in individual cases with variable results.

In conclusion, though PG is considered as a specific dermatosis of pregnancy, it can manifest for the first time in the immediate postpartum period and may be associated with fetal risks like low birth weight, as in our case.