British Association of Dermatologists' Guidelines for the Management of Pemphigus Vulgaris 2017

K.E. Harman; D. Brown; L.S. Exton; R.W. Groves; P.J. Hampton; M.F. Mohd Mustapa; J.F. Setterfield; P.D. Yesudian

Disclosures

The British Journal of Dermatology. 2017;177(5):1170-1201. 

In This Article

Pemphigus in Pregnancy (Level of Evidence 3)

This is a rare occurrence requiring close cooperation between dermatologist, obstetrician and neonatologist. Careful selection and monitoring of immunosuppression during pregnancy is required. Due to the passive transfer of maternal IgG autoantibodies across the placenta, the neonate may be affected by cutaneous erosions. In 2009, Kardos et al. published a review of 38 reports describing 49 pregnancies affected by pemphigus.[257] Prednisolone alone was used in 76% (37 of 49) of the cases at doses of 5–300 mg per day. Adjuvant therapies were used in eight patients: azathioprine (n = 5), plasmapheresis (n = 1), plasma exchange (n = 1) and dapsone (n = 1). Five neonatal deaths were reported. Twenty (45%) of the neonates had pemphigus lesions at birth, with all resolving within 4 weeks either spontaneously or with mild topical corticosteroids. Overall, there seems to be an increased risk of fetal morbidity with gestational PV, with higher preterm birth rates and low birthweight. There is no clear increased fetal loss.[258]

The most commonly used treatments for pemphigus in pregnancy are oral corticosteroids. Current evidence suggests that there is no significant increased risk of stillbirth, preterm delivery or congenital malformations from using prednisolone in any disease, although the usual side-effects of corticosteroid use will still occur.[258] Both systemic and very potent topical corticosteroids have been linked with intrauterine growth retardation. Corticosteroids should be the first-line systemic agent. The type of corticosteroid used is important, as prednisolone is 90% inactivated by the placenta, whereas betamethasone and dexamethasone are far less inactivated and could have a greater effect on the fetus.

There are no prospective studies of immunosuppressant therapy for pemphigus in pregnancy. Many systemic immunosuppressive agents including mycophenolate mofetil, methotrexate and cyclophosphamide should be avoided due to known risks to the fetus.

Azathioprine, in combination with corticosteroids, has been used successfully for pemphigus in pregnancy.[257] While there are risks of teratogenicity with azathioprine, these are low and azathioprine has been widely used during pregnancy in association with renal transplantation, inflammatory bowel disease and systemic lupus erythematosus.[259]

IVIg is safe in pregnancy. Ahmed and Gürcan reported eight patients with severe pemphigus in pregnancy. Seven responded well and one developed headaches and stopped treatment; none of the neonates had any erosions.[159] Finally, plasmapheresis has been used successfully, although this option is unavailable in many centres.[260]

Rituximab has been used successfully in childhood pemphigus, although its effects in pregnancy are uncertain.[261–263] Rituximab is able to cross the maternofetal barrier and the manufacturers advise against pregnancy for 1 year following rituximab therapy. The drug may potentially affect the developing immune system, and thus the risks to mother and fetus need to be considered carefully prior to treatment. If a pregnancy is exposed to rituximab the baby should avoid live vaccines for at least the first 6 months of life.[264]

Maternal IgG is excreted in human milk and women should not breastfeed while receiving rituximab and for up to 12 months following the last infusion.

Summary

Pemphigus occurring in pregnancy is rare. Data suggest that there is no increased risk of fetal loss, although some morbidity is seen especially with respect to low birthweight. Prednisolone alone is the most common treatment. Certain second-line treatments have been safely used when needed.

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