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WASHINGTON – With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.
But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”
As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.
The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.
Corticosteroids
These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.
In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.
Antihistamines
First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).
Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.
“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.
Immunosuppressants
Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.
“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”
Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.
Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”
She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”
Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.
Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.
Biologics
Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.
There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.
“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”
Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”
Pemphigus
Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said
Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”
Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.
“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.
She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.
WASHINGTON – With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.
But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”
As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.
The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.
Corticosteroids
These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.
In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.
Antihistamines
First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).
Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.
“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.
Immunosuppressants
Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.
“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”
Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.
Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”
She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”
Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.
Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.
Biologics
Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.
There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.
“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”
Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”
Pemphigus
Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said
Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”
Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.
“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.
She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.
WASHINGTON – With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.
But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”
As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.
The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.
Corticosteroids
These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.
In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.
Antihistamines
First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).
Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.
“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.
Immunosuppressants
Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.
“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”
Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.
Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”
She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”
Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.
Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.
Biologics
Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.
There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.
“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”
Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”
Pemphigus
Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said
Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”
Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.
“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.
She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.
EXPERT ANALYSIS FROM AAD 2019