Pemphigus Vulgaris in Pregnancy
We report the case of a 34-year-old woman who was diagnosed with pemphigus vulgaris (PV) during pregnancy. The patient presented with widespread blistering dermatitis and associated burning and pruritus. At 6 weeks’ gestation the patient was admitted to the hospital to expedite her diagnosis and initiate treatment. A skin biopsy revealed suprabasal acantholysis, and direct immunofluorescence demonstrated diffuse intercellular IgG in the epidermis and basal intercellular C3, which confirmed the diagnosis of PV. Treatment with corticosteroids was instituted after discussions with the patient about possible adverse effects to the fetus. Pemphigus vulgaris is rare in pregnancy and active PV presents potential threats of fetal spread and transient lesion production, which is associated with increased mortality and morbidity in the fetus. Our patient had active PV and required treatment throughout her pregnancy. The pregnancy progressed to premature delivery of the neonate without skin lesions or apparent complications.
Practice Points
- Early diagnosis and appropriate treatment of pemphigus vulgaris in pregnancy is paramount in protecting the health of the mother and fetus.
- Management of autoimmune diseases during pregnancy continues to present numerous challenges for physicians due to the pathology of the diseases as well as the sensitive nature of pregnancy and lack of robust data in this patient population.
Comment
Pemphigus vulgaris is associated with infertility in its active phase; therefore, PV during pregnancy is rare.8 Pregnancy may exacerbate PV, which has been a similar finding in other well-documented autoimmune diseases.7 One review of PV in pregnancy reported that 11 of 49 patients (22%) experienced an exacerbation of the disease.8 This finding pre-sents 2 problems: (1) severe active disease during pregnancy with high antibody titers has been shown to heighten risk for morbidity and mortality for the fetus, and (2) a patient with active PV during pregnancy may require systemic therapy with doses high enough to subdue the disease. The presence of PV was a challenge throughout our patient’s pregnancy. Transient skin lesions may occasionally appear in the neonate and seem to have an increased association with severe active PV in the mother; however, neonatal PV also has been present in mild cases in the mother.7 These lesions are secondary to passive transplacental transfer of PV antibodies but do not have long-lasting clinical implications because of an antibody’s brief half-life.9 The lesions either spontaneously resolve or can be treated with a topical corticosteroid.
Treatment with high-dose systemic corticosteroids or immunosuppressants can be problematic because of the risks posed to the fetus, especially if the mother must be treated when the embryo is particularly susceptible (eg, during organogenesis).10 If a woman with known PV is planning to become pregnant, it is recommended to first control and suppress the disease so that therapy can be minimal during the pregnancy. It also is recommended to use aggressive topical therapy if possible to control PV in a pregnant woman.8 This option would not have been efficacious in our patient because of her severe widespread disease.
Prednisone is considered one of the first-line treatments of PV and has been historically successful as a treatment for pregnant patients with PV if maintained at a low dosage. Prednisone, similar to other corticosteroids, can cross the placental barrier and can increase the chance of premature birth, infection, and mortality in high doses.7 Similar to prednisone, azathioprine is not recommended during pregnancy, but if use is necessary, it is suggested to keep the dose low to prevent fetal harm.11 Inadequate treatment and control of PV can be life threatening to the patient because of the severe infection that may ensue; thus it is necessary for the health of the patient and fetus to suppress the PV. One alternative to treatment with steroids and immunosuppressants is plasma exchange, which has been successful in the clinical context of pregnancy.12 The cons of plasma exchange are repeat procedures, the need to give the patient more immunosuppressants to prevent a rejection, and the return of the autoantibody.7
Several studies have evaluated the safety and efficacy of rituximab in the treatment of refractory PV. Multiple case reports state that both 1 and 2 courses of intravenous rituximab therapy at a dosage of 375 mg per square meter of body surface area affected once weekly for 4 weeks proved to be useful in clinical improvement for patients with refractory disease.13,14 Studies are currently underway to look at the effects of rituximab on pregnancy and the fetus. Preliminary findings show neonates may have B-cell abnormalities initially yet recover fully without infectious complications or sequelae.15 Rituximab currently is a pregnancy category C drug, and women are counseled to avoid pregnancy for at least 12 months after rituximab exposure and use contraception while actively taking the drug.16
Conclusion
Contrary to traditional thinking, PV itself may be associated with poor neonatal outcome, including prematurity and fetal death. These complications seem to be restricted to pregnancies with clinically severe PV.7 Our patient decided to progress with her pregnancy despite the potential risk to the fetus from the disease and treatment. Ultimately, the infant was delivered prematurely but was free of disease.
