Current Recommendations for the Systemic Treatment of Cutaneous Lupus Erythematosus During Pregnancy
Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease of the skin that commonly affects women of childbearing age. Some of the medications used in the treatment of CLE are safe in pregnancy, whereas others are contraindicated based on their teratogenic effects. We describe the most recent recommendations for the use of commonly prescribed CLE medications for those who are pregnant or plan on becoming pregnant.
Practice Points
- Patients should consult their primary dermatologist when discussing medication options for cutaneous lupus erythematosus (CLE) prior to pregnancy.
- Hydroxychloroquine is a first-line medication for maintenance treatment of CLE, while oral steroids are effective for CLE flares in pregnancy. Second-line medications include dapsone and intravenous immunoglobulin. These classes of medications are considered safe in pregnancy.
- Cutaneous lupus erythematosus medications contraindicated in pregnancy include oral retinoids, mycophenolate mofetil, thalidomide, and methotrexate.
Azathioprine—Although azathioprine has been shown to provide relief of discoid lupus erythematosus symptoms,48 it currently is only utilized for refractory disease, largely due to notable side effects that particularly affect the gastrointestinal tract and liver.4 Moreover, azathioprine use during pregnancy has been associated with prematurity, congenital anomalies, fetal cytopenia, and low birth weight.49 With that said, and although not recommended, if patients decide to continue treatment, experts recommend limiting the dose to 2 mg/kg daily to reduce potential adverse events.
Category X
Oral Retinoids—According to the American Academy of Dermatology, retinoids such as isotretinoin and acitretin are considered second-line therapy for CLE.50 With that being said, there are well-documented effects on fetal development associated with oral retinoid use, including central nervous system, cardiovascular system, and craniofacial abnormalities.51 Therefore, its use is contraindicated during pregnancy. To prevent pregnancy while taking isotretinoin, patients must enroll in an online monitoring program called iPLEDGE. This program requires monthly updates by both the physician and the patient, including a negative pregnancy test every month for female patients actively taking the medication.52
The half-lives of the oral retinoids isotretinoin and acitretin are 10 to 20 hours and 50 to 60 hours, respectively.53,54 However, alcohol consumption converts acitretin into the metabolite etretinate, which can remain in tissue for up to 120 days.54,55 Therefore, women are advised to avoid alcohol while taking acitretin and avoid conception for 2 to 3 years after cessation of the medication.55 For those wishing to restart retinoids after pregnancy, studies show the medication can be safely reinstated 35 days after delivery for those interested in continued treatment.56
Thalidomide—Although low-dose thalidomide can treat refractory CLE, its use is restricted because of its known teratogenicity, most notably limb deformities.57 If prescribed thalidomide, women will need to enroll in the System for Thalidomide Education and Prescribing Safety program, similar to the iPLEDGE program, and use 2 forms of contraception when sexually active.58 Contraception should be continued for 4 weeks following the last dose of thalidomide. After this point, conception is considered safe.59
Methotrexate—For nonpregnant patients, low-dose methotrexate (MTX) with folate supplementation is a treatment option for CLE.60 However, for those who are pregnant, low-dose MTX is an abortive agent and has been associated with aminopterin syndrome, which includes skull deficits, craniofacial abnormalities, and limb deformities in live births.19,61 Therefore, MTX is not recommended in pregnancy. Of note, MTX can affect sperm; male patients also should be counselled.
