Presentation on theme: " Psoriasis affects 2% to 3% of the population, men and women equally. However, women tend to develop psoriasis earlier and the prevalence in pregnant."— Presentation transcript:
Psoriasis affects 2% to 3% of the population, men and women equally. However, women tend to develop psoriasis earlier and the prevalence in pregnant women is not known. The effect of pregnancy on psoriasis is unpredictable. Patients may or may not improve and may even worsen during pregnancy.
Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies.
Conservative skin care, such as moisturization and protecting skin from chafing, may minimize the risk of Koebnerization. When psoriasis develops despite these efforts, then low- to mid-potency topical steroids are indicated as first-line therapy in pregnant women. An updated Cochrane review on this topic concluded that there were no significant issues when using low- to mid-potency topical steroids, but high-potency steroids may be associated with low birth weight
Cochrane review that included 7 studies, including 2 cohort and 5 case-control studies, was published in 2010. One study found significant association between first-trimester use of topical corticosteroids and orofacial cleft. Another study found significant association between very potent topical corticosteroids and low birth weight.
Cohort study using United Kingdom General Practice Research Database found no associations of topical corticosteroid exposure with orofacial cleft, cleft palate alone, preterm delivery, and fetal death in 35,503 pregnant women prescribed topical corticosteroids from 85 d before last menstrual period to delivery or fetal death, in comparison with unexposed women (48,630). However, exposure to potent/very potent topical steroids shortly before and during pregnancy was significantly associated with fetal growth restriction, showing dose-response relationship.
Salicylic acid is another topical medication that is used to treat psoriasis. There is a report that describes the side effects of orally administered salicylic acid in pregnancy, but there is no literature evaluating the topical use of salicylic acid in pregnant women with or without psoriasis Because patients with psoriasis may have enhanced absorption of salicylic acid, pregnant women should avoid this medication to prevent salicylism
Studies on the use of topical tacrolimus in pregnant women are unavailable, but there are considerable data regarding oral use. In general, topical calcineurin inhibitors have demonstrated less absorption than topical corticosteroids. With repeated applications of topical calcineurin inhibitor, use on an extensive body surface area, or with long-term use, in most patients, negligible or no systemic drug accumulation has been demonstrated
In contrast, case-controlled trials, case series, and case reports on the use of oral tacrolimus in pregnant women after organ transplantation show effects similar to cyclosporine in terms of prematurity, low birth weight, and malformations with many different agents In general, topical exposure is expected to result in lower risk than oral exposure
Animal studies of oral calcipotriene show an increased incidence of skeletal abnormalities. There are limited data on the use of coal tar in pregnant women with psoriasis. One study demonstrated no statistically significant differences between patients exposed to coal tar compared with control subjects; however, the timing and dose of exposure was uncertain. Thus, because coal tar is a known teratogen in animal studies, we do not recommend its use during pregnancy.
The second-line treatment for pregnant women includes narrowband UVB phototherapy (or broadband UVB if narrowband UVB is not available). Narrowband UVB has not been associated with an increased risk of fetal abnormalities or premature delivery UV exposure (and pesticides) did not have a significant association with preterm birth, small for gestational age, or congenital malformation in pregnant farmers and gardeners in Denmark
UVB therapy may be safer after the first trimester and women with high minimal erythema dose that require substantial time in the light box may wish to monitor for overheating However, exacerbatemelasma, so pregnant women should be advised of this possible side effect.
Limited cases of premature labor and fetal abnormalities have been reported in 107 pregnant women receiving PUVA. In one study examining the effects of PUVA in pregnant women, the authors reported a case of Down syndrome and one case of syndactyly in babies of two of the women who had preconception exposure to PUVA PUVA has been more recently moved into FDA category C, so concern about its use may be waning.
Experience with TNF inhibitors during pregnancy is limited to a small number of cases described formally in the literature. Several cases have reported no maternal adverse events or fetal anomalies after the use of adalimumab throughout pregnancy
Etanercept has been detected at low levels in cord blood at delivery. Most etanercept case reports and series conclude there are no patterns of malformation or prematurity of note. The one exception to these general conclusions is a case of vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula, esophageal atresia, renal anomalies, and limb anomalies (previously known as VATER syndrome) that was reported in 2006
Larger series are available concerning outcomes of the use of infliximab during pregnancy. 5 cases of adverse outcomes were described in a large prospective study of 131 patients taking infliximab during pregnancy Low birth-weight infant who died shortly after birth secondary to intracerebral and intrapulmonary hemorrhage. Respiratory distress, jaundice, and seizure Tetralogy of Fallot Intestinal malrotation
Also of note, infliximab does appear to cross the placenta more readily in the third trimester as a result of increased IgG placental transfer during the third trimester, so use of these medications primarily in the second trimester may also reduce exposure and avoid the most sensitive developmental time of the first trimester
Systemic steroids, more commonly used in other conditions during pregnancy, have been associated with congenital abnormalities and premature delivery. Cleft lip with or without cleft palate was significantly increased in 3 large population studies when corticosteroids were given in the first trimester. Other retrospective studies have noted intrauterine growth retardation and subsequent low birth weight. A large prospective study of 184 patients showed the following: statistically significant low birth weight, low gestational age, and prematurity.
A case-control study showed that exposure to corticosteroids from 1 month before conception until 3 months’ gestation increased the risk of cleft lip, palate, or both However, in another study of 332 women given corticosteroids in the second and third trimester, no statistically significant differences in malformations were found
Systemic corticosteroids should be avoided in the first trimester and given cautiously in low doses during the second and third trimester. Systemic corticosteroids are the treatment of choice for pustular psoriasis of pregnancy (impetigo herpetiformis), which occurs most commonly in the third trimester.
Cyclosporine is associated with low birth weight and prematurity in maternal transplantation populations. A large retrospective study of 629 patients receiving cyclosporine demonstrated a range of fetal loss and malformations similar to that of the general population, but found an association with significant low birth weight and prematurity The use of cyclosporine during pregnancy be limited to patients with psoriasis who have severe disease.
Reports on the outcome of methotrexate exposure in the first trimester of pregnancy vary widely. Although there are reports of the delivery of healthy babies there are also reports of babies with multiple anomalies and developmental delays, along with spontaneous abortions
Methotrexate is both a teratogen and mutagen, it should be avoided in patients with psoriasis who are either pregnant or considering pregnancy and stopped in anyone who becomes pregnant The timing of methotrexate exposure and history of use is important in determining fetal risk
One report of 13 patients exposed before and during the first trimester early (week 1-2) or later (week > 11) revealed that none of the 9 live births developed neural tube defects or aminopterin syndrome and other congenital anomalies 4 of 9 women with past exposure to methotrexate (within 1 year of conception) experienced spontaneous abortion Many sources recommend discontinuation of methotrexate at least 3 months before attempts at conception
Retinoids are known teratogens. Multiple animal studies have shown teratogenic effects and postimplantation loss when given tazarotene topically or orally. Decreased number of implantation sites, decreased litter size, decreased number of live fetuses, decreased fetal body weights, and retinoid-related malformations were observed. However, 8 Pregnant women exposed to topical tazarotene (unknown timing and extent of exposure) all delivered healthy babies
Other congenital anomalies include meningomyelocele; meningoencephalocele; multiple synostoses; facial dysmorphia; syndactyly; absence of terminal phalanges; malformation of hip, ankle, and forearm; low-set ears; high palate; decreased cranial volume; cardiovascular malformation; and alteration of the skull and cervical vertebrae, especially with use of acitretin. Thus, retinoids, both topical and systemic, should be avoided in pregnant women.
There is a lack of information on the safety of medications while breast-feeding. Although the number of reports is small, progress has been made in this area by comparing maternal serum levels with infant levels at delivery, breast milk levels, and infant serum levels There are no known risks associated with the use of moisturization
The bioavailability of tacrolimus, cyclosporine, methotrexate, and acitretin in infants has been reported to be below that used for treatment but can vary significantly. The clearance of these drugs is unknown UVB is likely to be a safe option, but may be very inconvenient for women with young children. New data about the biologics confirm the assumption that they are unlikely to be absorbed through the infants’ gastrointestinal tract
Based on limited data, breast milk levels in nursing women taking etanercept or infliximab have been reported to be below that used for treatment and there does not appear to be significant absorption by the infant. No articles describing use in breast-feeding women were found on the following medications: adalimumab, alefacept, anthralin, calcipotriene, coal tar, topical corticosteroids, PUVA, salicylic acid, tazarotene.
Studies on topical corticosteroid use in lactating women are unavailable. However, topical corticosteroids should be considered before systemic corticosteroids (for low body surface area) when treatment of psoriasis is required. Systemic steroids can be used if necessary, because minimal amounts have been found in breast milk. The authors recommend waiting 4 hours after ingestion of systemic steroids before breast-feeding.
0.025% of prednisolone from breast milk over 6 hours after a 50-mg intravenous dose. Another study found 0.14% of the original prednisolone dose in 1 L of breast milk from 7 mothers given a radioactive dose. The peak of prednisolone recovery occurred 1 hour after ingestion of a more than 30-mg dose in a different study. Because the elimination half-life of cortisol ranges from 2.5 to 3.5 hours, Thus, multiple authors recommend waiting at least 4 hours after the last dose of corticosteroids before breast-feeding
Samples of breast milk from 6 mothers demonstrated that almost half the concentration of tacrolimus was detected in breast milk compared with maternal serum samples Higher concentrations of 0.5% of maternal dose have been found in breast milk from a 29-year- old woman after renal transplantation on tacrolimus 4 mg daily
One report on tacrolimus in a 32-year-old woman taking 0.1 mg/kg/d of tacrolimus throughout pregnancy concluded that the baby ingested approximately 0.06% of mother’s weight-adjusted dose and reported that the baby was healthy Concentration of tacrolimus in breast milk is substantial compared with maternal levels, however, overall exposure dose to baby was very low suggesting that maternal treatment with tacrolimus may be compatible with breast-feeding.
Cyclosporine is available in breast milk, and levels may vary substantially 7 Infants with mothers who had undergone kidney transplantation (5) or kidney and pancreas transplantation (2) on cyclosporine (dose unspecified) Cyclosporine levels ranged from 55-130 ng/mL in blood (12-h trough), 50-227 ng/mL in breast milk and below detection limit of 30 ng/mL in all 7 infants Although the data are limited, cyclosporine use during lactation is not recommended because of the varying results of infant exposure to this medication.
Acitretin is found minimally in breast milk Peak acitretin at 1.5-3 h. In 800 mL of milk, 4-kg infant would be exposed to approximately 1.5% of mother’s dose. FDA package insert currently recommends patients to avoid breast-feeding; however American Academy of Pediatrics classifies drug as compatible with breast-feeding although there is potential for toxicity The author suggests avoiding infant exposure because the oral bioavailability and clearance of drugs is unknown in infants, secondary to their immature renal and hepatic systems for elimination
One case report demonstrated minimal amounts of methotrexate in breast milk The highest milk to plasma ratio was obtained at 10 hours (0.08:1) Concentration of methotrexate in breast milk was substantially less than maternal levels, so methotrexate exposure to baby was presumably very small However, because there are limited data on methotrexate use in lactating mothers and long-termeffects in infants, its use is not recommended.