A 24-year-old nulliparous woman initially presented to a prenatal clinic at 24 weeks of gestation for assessment of pruritic eczematous papules on her abdomen that had been present for 1 week. Her medical history was significant for Chiari malformation, for which she had undergone surgical widening of the foramen magnum.
On physical examination, a raised, erythematous, urticarial lesion was present on the abdomen. The patient was started on topical corticosteroid therapy with triamcinolone cream; however, the lesions later spread to her arms and legs, and she developed pruritus. Physical examination at follow-up 1 week later demonstrated a confluence of papular lesions on the abdomen with satellite lesions on the arms, hands, and thighs with vesicles (Figures 1 and 2).
At 24 weeks and 4 days of gestation, the woman was seen by a maternal–fetal medicine specialist, who recommended treatment with a methylprednisolone dose pack and hydroxyzine and referred her to a dermatologist for further evaluation.
The dermatologist described multiple scattered, erythematous, annular, urticarial plaques on the left thigh, coalescing into the abdomen and involving the periumbilical region. A few scattered tense blisters on an erythematous base were present on right posterior arm and left anterior thigh (Figures 3-5). The dermatologist performed a punch biopsy. Given concern for pemphigoid gestationis (PG), the patient was started on clobetasol ointment, 0.05%, twice a day.Figure 3. Figure 4. Figure 5.
At 25 weeks of gestation, the woman presented to the emergency department with throat tightening and tongue swelling. The lesions had worsened and spread to her anterior thighs (Figure 6), and she noted the development of new oral aphthous ulcers, decreased gustatory senses, and anorexia. She denied difficulty breathing but described dysphagia. She was admitted to the high-risk obstetrics service for symptomatic management.Figure 6.
She was started on intravenous (IV) diphenhydramine, and a dermatologist was consulted. She was prescribed oral prednisone, 30 mg per day, with a plan to taper the dosage when blister formation subsided. She also began using topical desonide, as well as and triamcinolone paste for her oral lesions and a proton-pump inhibitor for ulcer prophylaxis. During her stay, the oral prednisone dosage was increased to 40 mg per day. By hospital day 3, her symptoms had improved, and she was able to tolerate food. She was discharged home with scheduled outpatient follow-up.
After discharge, the biopsy results confirmed the diagnosis of PG. Enzyme-linked immunosorbent assay (ELISA) results for 180-kD bullous pemphigoid antigen (BP180) immunoglobulin G (IgG) demonstrated herpes gestationis factor (complement-fixing IgG antibodies) at a level of 63 units (positive results are indicated by a level of >9 units). Anti-basement membrane zone antibodies were positive, with a titer of greater than 1:10, which confirmed the diagnosis.
The woman was informed that she was at risk for preterm delivery and a low birth weight baby. She was advised that her disease has a likelihood of recurrence in any future pregnancies. Because her symptoms were improving, the oral prednisone dosage was tapered to a minimum dose of 10 mg per day. Antenatal testing was initiated at 32 weeks, and delivery was planned at 37 weeks, given her autoimmune disorder.
At 33 weeks of gestation, the patient presented with contractions. Her cervix was noted to be 1 cm dilated. Due to the increased risk of preterm delivery with her PG, she was started on intramuscular betamethasone for fetal lung maturation should she progress to labor.
Her condition remained stable until 36 weeks of gestation, when she presented with elevated blood pressure and received a diagnosis of preeclampsia. She was started on oxytocin for induction of labor. Because she had been on more than 10 mg of oral prednisone daily for more than 3 weeks, she was started on stress-dose corticosteroids with a 100-mg bolus of IV hydrocortisone and 50 mg of IV hydrocortisone every 8 hours for 24 hours.
She vaginally delivered a 2985-g boy, who had no evidence of rash or blisters. She was continued on magnesium for 24 hours postpartum and completed her IV corticosteroid course. She also was started on an oral antihypertensive medication for blood pressure control. She remained in the hospital for 5 days postpartum for management of preeclampsia. She was discharged home in good condition.
The woman was seen at a dermatology clinic 2 weeks postpartum. Because her BP180 IgG level had decreased to 25 units and her lesions had improved, prednisone was discontinued. She was cleared from the dermatology clinic with follow-up as needed.
PG, also called herpes gestationis, is a rare autoimmune disease of pregnancy that is caused by an antibody–antigen complex in the basement membrane of the epidermis. This immune complex disrupts the junction between the dermis and epidermis, causing mucous membrane blistering. Disease prevalence is approximately 1 in 2000 to 1 in 50,000 pregnancies.1
PG is caused by circulating IgG1 autoantibodies against BP180, a protein expressed in the basement membrane of the skin and amniotic epithelium of the placenta and umbilical cord.1 Antibodies bind to basement membrane antigens, which causes an immune cascade separating the dermis from the epidermis. While the exact mechanism is unknown, it is thought to be related to misidentification of placental proteins. Antigens, most commonly BP180, trigger inflammatory reactions in the skin and placenta, leading to painful lesions.2
The diagnosis of PG is made with clinical findings, ELISA testing for anti-BP180 antibodies, or direct immunofluorescence of complement (C3) at the basement membrane. Biopsy may also be useful to demonstrate a vesicle with eosinophilic infiltrate. Levels of anti-BP180 are diagnostic, with sensitivity and specificity from 96% to 100%. These levels also can be used to monitor response to treatment and severity of disease.3-7
PG lesions are initially pruritic and progress to vesicular lesions; the condition most often occurs in the second or third trimester.6 Most women who develop PG have complete resolution postpartum; however, the condition may recur, often with more-severe symptoms, in future pregnancies.7 Up to 75% of women who develop PG during pregnancy have postpartum flares, and at least 25% have recurrence with use of oral contraceptive pills or during menses.8
Women with PG have an increased risk of prematurity and small-for-gestational-age babies. This is thought to be related to the pathogenesis of the disease and placental insufficiency.9 Cases of newborns with neonatal PG from transplacental passage of maternal antibodies have been reported. Neonatal cases are self-resolving and cause no long-term consequences.10-12
The mainstay of treatment of women with PG is topical high-dose corticosteroids and oral antihistamines with the goal of preventing blister formation. In more-resistant cases, oral systemic corticosteroids are used, typically oral prednisone. Other therapies for resistant PG include intravenous immunoglobulin, cyclophosphamide, cyclosporine, doxycycline, rituximab, immunoelectrophoresis, and nicotinamide.13
Some studies have demonstrated that the use of oral prednisone in the first trimester is correlated with orofacial clefts, and that third-trimester use is associated with intrauterine growth retardation, gestational diabetes, preeclampsia, and premature delivery.14
Corticosteroids have both immunosuppressive and anti-inflammatory effects, and they are commonly used to treat autoimmune conditions such as lupus. Often, women treated with corticosteroids develop preeclampsia; however, this is likely related to the women’s autoimmune disease. It is possible that women without immune diseases treated with corticosteroids may develop preeclampsia from sodium retention leading to hypertension.
Several researchers have investigated corticosteroid use in pregnancy as a risk for preeclampsia. One study reported an increased incidence of preeclampsia in women with inflammatory bowel disease on corticosteroid therapy compared with women without the disease; however, no adjustment was made for disease state and severity.15 A large database in British Columbia demonstrated an elevated yet statistically insignificant rate of preeclampsia in women treated with corticosteroids who were naive prior to pregnancy compared with women who had been on corticosteroids prior to pregnancy.16 Although autoimmune disease factors were adjusted for, disease severity was not accounted for, which in itself could have predisposed women to preeclampsia.16 Therefore, while it is possible that chronic corticosteroid use predisposed our patient to preeclampsia, insufficient data exist to support this conclusion.
Several case studies have been published in which patients experienced a recurrence of PG lesions and symptoms upon cessation of corticosteroids; the mean symptom duration is 28 weeks postpartum.17 In our patient’s case, prednisone was continued for 2 weeks postpartum, at which time the patient had no evidence of lesions and reported no symptoms. Laboratory test results demonstrated decreased BP180 IgG antibodies, from 63 units to 25 units, which correlated with her clinical condition. While some women require extended treatment postpartum to prevent relapse, our patient had a significant decrease in antibodies, which prompted prednisone cessation. Over 12 months postpartum, there was no evidence of PG recurrence.
We thank Bernie Amaro, research assistant in the University of Florida Department of Obstetrics and Gynecology, for editorial assistance in preparing this case report for publication.
Kristin E. Briscoe, MD Division of Academic Specialists in General Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, Florida
Dikea Roussos-Ross, MD Associate Professor and Division Chief, Division of Academic Specialists in General Obstetrics and Gynecology, Department of Obstetrics and Gynecology, and Department of Psychiatry, University of Florida College of Medicine, Gainesville, Florida
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