Management of psoriasis in pregnancy

INTRODUCTION — Psoriasis is a chronic skin disorder characterized by well-demarcated erythematous papules and plaques with a silver scale, although atypical or nonclassic forms also exist. It commonly occurs on the extensor surface of the elbows or knees, or the scalp (picture 1A-C). Psoriasis commonly occurs in individuals of reproductive age because three-quarters of patients develop the disease before reaching age 40 years [1]. (See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis".)

The management of psoriasis in pregnant patients will be reviewed here. The general treatment of psoriasis and pustular psoriasis of pregnancy, a severe pustular form of psoriasis, is discussed separately. (See "Treatment of psoriasis in adults" and "Dermatoses of pregnancy".)

SPECIAL CONSIDERATIONS — The presence of psoriasis in a woman who is pregnant raises unique considerations. Examples include the impact of maternal psoriasis on the fetus, therapeutic restrictions during pregnancy, and the effects of pregnancy on psoriasis severity [2]:

●Impact of psoriasis on pregnancy outcomes – Few studies have investigated the impact of psoriasis on pregnancy outcomes, leaving the relationship between psoriasis and pregnancy outcomes unclear [3,4]. A 2016 systematic review of observational studies that evaluated the relationship between psoriasis and pregnancy outcomes found that four of the nine included studies reported increased risk for at least one adverse fetal outcome (spontaneous abortion, caesarean delivery, low birth weight, macrosomia, large-for-gestational age, or a composite outcome that included prematurity and low birth weight) [3]. However, study results were inconsistent.

●Impact of pregnancy on treatment choices – Choosing drug therapies that pose the least risk to the fetus is the major issue in managing the pregnancies of affected patients. Ideally, patients should try to plan pregnancy when they are in remission and they are off medication or are taking the minimum effective dose of medications that have the best fetal safety profiles. Because many patients with moderate to severe psoriasis do not achieve complete remissions, postponing pregnancy until a period of remission is often unrealistic in this population. The selection of treatments with good fetal safety profiles is particularly important for these patients. (See 'Treatment principles' below.)

●Impact on severity of psoriasis – Psoriasis improves during pregnancy in 40 to 60 percent of patients, worsens in 10 to 20 percent, and remains stable in the remainder. Improvement may be dramatic. In a prospective study, among 16 women with greater than 10 percent body surface area involvement with psoriasis who experienced improvement in psoriasis during pregnancy, the mean reduction in psoriatic lesions between 10 and 30 weeks gestation was 84 percent [5]. In the postpartum period, psoriasis severity remains the same or worsens in most patients [5-7].

●Impact on risk of psoriasis in biologic children – Children of individuals with psoriasis have an increased risk for the development of the disorder. (See "Psoriasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Genetic factors'.)

TREATMENT PRINCIPLES — Treatment of psoriasis in nonpregnant individuals can be divided into three broad categories: topical therapy, phototherapy, and systemic therapy. Choice of therapy is based upon the severity of the disease and its impact on the patient's overall sense of well-being, relevant comorbidities, patient preference (including cost and convenience), efficacy, and evaluation of individual patient response. Psoriasis involving limited areas of skin (eg, less than 5 to 10 percent the body surface area) can often be managed topically. Phototherapy or systemic therapy is usually necessary for adequate treatment of more extensive disease. Topical therapy and phototherapy is generally preferred over systemic therapy for the treatment of pregnant patients because of concern for safety. (See "Treatment of psoriasis in adults".)

The treatment paradigm is the same for both pregnant and nonpregnant patients, except that some medications are avoided in pregnancy and the risk/benefit ratio may be calculated differently because fetal risk must also be taken into account [8]. We agree with a recommendation from the Medical Board of the National Psoriasis Foundation that topical treatment with emollients or moisturizers and a low- or medium-potency topical corticosteroid is the first-line medical intervention for pregnant patients with limited psoriasis [9]. Ultraviolet B (UVB) phototherapy (particularly narrowband ultraviolet B [NBUVB]) is the preferred treatment for pregnant patients with more severe symptoms.

When patients receiving systemic therapy for psoriasis become pregnant, the decision must be made whether to continue treatment or to transition to topical therapy or phototherapy. Although contraindicated therapies (eg, acitretin, methotrexate) must be discontinued, the appropriate action is less definitive for patients receiving other systemic treatments. Because many patients with psoriasis improve during pregnancy, patients may be able to switch to phototherapy during the prenatal period. Biologic tumor necrosis factor (TNF) inhibitors and cyclosporine are occasionally used during pregnancy for patients with severe disease who cannot transition to topical therapy or phototherapy. In these situations, the potential risks and benefits of therapy must be considered carefully. (See 'Third-line therapy' below and 'Contraindicated therapies' below.)

Treatment of nonpregnant individuals is reviewed separately. (See "Treatment of psoriasis in adults" and "Treatment of psoriatic arthritis" and "Treatment selection for moderate to severe plaque psoriasis in special populations".)

First-line therapy — Many pregnant patients with limited psoriasis (nondebilitating psoriasis that involves less than 5 to 10 percent of the body surface area) can be managed sufficiently with topical therapy. Emollients, moisturizers, and low- to medium-potency topical corticosteroids are the preferred topical therapies for this population based upon safety considerations (table 1) [9].

Emollients and moisturizers — The simplest topical therapies are emollients or moisturizers, which may control bothersome scale. Use of these agents is well tolerated, lacking significant adverse effects.

Topical corticosteroids — For limited psoriasis, intermittent topical corticosteroids may control disease with no or minimal maternal or fetal risk [10,11]. (See "Treatment of psoriasis in adults", section on 'Corticosteroids'.)

A systematic review did not find sufficient evidence to link topical corticosteroid use to increased risk for congenital abnormalities, preterm delivery, or stillbirth [12]. However, there may be an association between use of potent topical corticosteroids and low birthweight [12]. In particular, a retrospective study found a correlation between low birth weight and high levels of potent or very potent topical corticosteroid use [13]. (See "Topical corticosteroids: Use and adverse effects", section on 'Use during pregnancy or lactation'.)

Therefore, for pregnant patients who will be treated with topical corticosteroids for psoriasis, the use of low- or medium-potency topical corticosteroids is preferred (table 1) [9]. We reserve the use of high-potency topical corticosteroids for patients who fail treatment with lower-potency topical corticosteroids.

Of note, the development of striae (stretch marks) is common in pregnancy and use of topical corticosteroids may increase risk for striae in sites of application. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Second-line therapy — When topical therapy with emollients, moisturizers, or topical corticosteroids is insufficient or impractical due to resistant disease or extensive skin involvement, NBUVB phototherapy is often useful for treatment.

Ultraviolet B phototherapy — Phototherapy can be used to treat localized psoriasis or the entire cutaneous surface area. NBUVB phototherapy at wavelength 311 nm appears to be a safe and often effective treatment of psoriasis in pregnant patients [10,11]. The major disadvantage of this approach is the need to travel to a clinic three days per week for treatment. Broadband UVB (290 to 320 nm) is a slightly less effective alternative that can be used if NBUVB is not available. Localized disease can be treated with a laser device that emits UVB (eg, 308 nm excimer laser) [11]. (See "UVB phototherapy (broadband and narrowband)".)

Patients receiving phototherapy generally require adjuvant therapy with emollients, moisturizers, or low- to medium-potency topical corticosteroids for symptomatic relief.

Common adverse effects of UVB phototherapy include erythema, skin dryness, and pruritus. Exacerbation of melasma, a photosensitive skin disorder commonly associated with pregnancy, also is a potential risk of phototherapy [9]. Melasma is characterized by the development of hyperpigmentation on sun-exposed skin (picture 2) (see "Melasma: Management"). To minimize risk of melasma, shielding of the face during phototherapy is advised [2]. Additional adverse effects associated with phototherapy are reviewed separately. (See "UVB phototherapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Maternal folate deficiency has been associated with an increased risk for fetal neural tube defects. Concerns regarding the effect of ultraviolet light exposure decreasing serum folate levels are discussed separately.

Third-line therapy — Most pregnant patients with psoriasis can be managed effectively with the therapies described above. Patients who cannot be managed effectively with the topical moisturizers, topical corticosteroids, or phototherapy may require systemic therapy to achieve sufficient improvement in symptoms. Biologic TNF inhibitors and cyclosporine can be effective for these patients. However, data on safety in pregnant individuals are limited, and the need for systemic treatment should be considered carefully.

Anti-tumor necrosis factor biologic agents — Although data on the use of anti-tumor necrosis factor (TNF) biologic agents in pregnancy are limited, there is a growing body of literature demonstrating that the biologic TNF inhibitors used for psoriasis may be used safely during pregnancy. Increased risk for preterm birth and small for gestational age infants have been reported, but effects of underlying, inflammatory diseases are also postulated to contribute [14,15].

Transfer of certolizumab pegol, a pegylated, Fc-free anti-TNF biologic agent used for psoriasis, across the placenta is minimal and less than other anti-TNF biologic agents. Limited data support low risk for immunosuppression in the newborn and teratogenicity for this agent [16,17]. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

Because adalimumab, etanercept, and infliximab can cross the placenta and can be detected in infants for up to several months or longer after birth [18,19], there is concern for the possibility of postpartum effects on infants born to treated individuals. Although the best approach is unconfirmed, discontinuation of these drugs prior to the end of gestation and postponement of live vaccine administration to infants has been suggested. For infliximab, drug discontinuation is suggested at 30 weeks gestation (based upon the knowledge that transmission across the placenta primarily occurs in the third trimester), and avoidance of live vaccine administration to infants born to treated individuals is suggested until the age of seven months [20,21]. Similar precautions may be appropriate for adalimumab and etanercept. An infant exposed to infliximab in utero died from disseminated Bacillus Calmette-Guérin (BCG) infection after receipt of the BCG vaccine at the age of three months [22].

The manufacturers of all the biologic medications for psoriasis and psoriatic arthritis manage ongoing registries of drug-exposed pregnant patients and encourage enrollment of all such cases. The safety of these drugs in pregnant individuals is discussed in detail separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Tumor necrosis factor inhibitors' and "Fertility, pregnancy, and nursing in inflammatory bowel disease", section on 'Anti-tumor necrosis factor agents'.)

Cyclosporine — Cyclosporine is a calcineurin inhibitor.

Teratogenicity data in humans are derived primarily from organ transplant recipients. The risk of teratogenicity among the offspring of women treated with cyclosporine appears to be low, but premature labor and infants who are small for gestational age have been reported. Such findings may be related to the underlying medical condition rather than to the drug and could also be related to both the medical condition and the drug. Another concern is that, in some studies, newborns whose mothers consumed cyclosporine had a decrease in T and B cells [11]; however, it is not clear that this change had any clinical significance. The use of cyclosporine in pregnancy is discussed in detail separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Cyclosporine'.)

CONTRAINDICATED THERAPIES — Several therapies useful for the treatment of psoriasis in nonpregnant individuals are contraindicated in pregnant patients because of teratogenicity. These include topical tazarotene, methotrexate, and acitretin.

Tazarotene — Tazarotene is a retinoid approved for the topical treatment of psoriasis. Tazarotene is contraindicated in pregnancy [23,24].

Less than 1 percent of the dose is absorbed on psoriatic skin [25]. However, tazarotene is avoided during pregnancy based on good data that another retinoid (oral isotretinoin) is associated with a significant increase in major congenital malformations. First trimester oral isotretinoin exposure is strongly associated with embryopathy, including craniofacial, cardiac, thymic, and central nervous system malformations. (See "Treatment of psoriasis in adults", section on 'Tazarotene' and "Oral isotretinoin therapy for acne vulgaris", section on 'Teratogenicity'.)

Methotrexate — Methotrexate is a folate antagonist and is contraindicated in pregnancy. It should not be used for treatment of psoriasis in a pregnant or lactating woman because it is teratogenic and may interfere with cellular metabolism in a nursing infant [24]. Conception should be avoided for three months after the last dose because the drug can persist in the liver for several months. This drug is discussed in detail separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Methotrexate'.)

Acitretin — Acitretin is contraindicated in pregnancy, given that there is good evidence that retinoids significantly increase the incidence of severe congenital anomalies in experimental animals and humans [26]. It should not be used for treatment of psoriasis in a pregnant or lactating woman. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Teratogenicity'.)

Acitretin can be metabolized to etretinate in the body, and etretinate has been identified in body fat as long as 52 months after stopping acitretin [27]. For this reason, experts recommend that pregnancy be avoided for three years after the last dose of acitretin.

OTHER PSORIASIS THERAPIES — Several other psoriasis therapies, while not deemed contraindicated for patients with psoriasis, are less favorable options for the treatment of pregnant patients due to safety concerns or lesser efficacy.

Topical calcineurin inhibitors — Topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus) are not particularly effective in psoriasis; however, they are occasionally used when topical corticosteroids must be avoided.

Based on experimental animal studies and human case reports, these drugs do not appear to increase the risk of congenital anomalies. Treatment with oral tacrolimus may be associated with increased risk for low birth weight and premature delivery [9]. However, it is unclear whether similar effects occur with the low systemic absorption associated with topical administration. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

Coal tar — Safety data for coal tar in pregnancy are limited. Although there is concern for potential mutagenic properties of coal tar based upon animal studies, a case series including 23 women who used coal tar products during pregnancy did not detect an increase in congenital anomalies [28]. Topical coal tar can be considered for use in the second and third trimesters of pregnancy [10,11]. As a precaution, coal tar is often avoided in the first trimester of pregnancy. (See "Treatment of psoriasis in adults".)

Calcipotriol — Calcipotriol (calcipotriene) and calcitriol are vitamin D derivatives. Studies in rats and rabbits have not reported an increased risk of congenital anomalies [26]. Hypercalcemia has been reported with excessive topical use [29], and excessive vitamin D intake can lead to skeletal abnormalities in offspring [26]; however, this is unlikely with limited topical use [11,23,24]. (See "Treatment of psoriasis in adults", section on 'Topical vitamin D analogs'.)

Anthralin — The risks of anthralin therapy during pregnancy are unknown. Therefore, use of anthralin in pregnant patients is not recommended [9].

Psoralen plus ultraviolet A phototherapy — Use of systemic psoralen plus ultraviolet A (PUVA) phototherapy during pregnancy is more controversial than use of ultraviolet B (UVB) phototherapy. Some experts suggest it can be used if the psoralen is applied topically [11]. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

Sulfasalazine — Case series have found no increase in the incidence of adverse pregnancy outcomes with sulfasalazine exposure during pregnancy. Since sulfasalazine binds albumin, there is a theoretic risk that sulfasalazine will displace bilirubin from albumin and thereby increase the risk of kernicterus; however, there is no evidence that clinically significant displacement of bilirubin occurs. Although the safety profile of sulfasalazine is reassuring, it is minimally effective for treatment of psoriasis. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Sulfasalazine'.)

Systemic glucocorticoids — Systemic glucocorticoids are not recommended for the treatment of psoriasis because of the potential for severe flaring of psoriasis upon drug withdrawal. An exception is pustular psoriasis of pregnancy (impetigo herpetiformis), for which systemic glucocorticoids are a mainstay of therapy. (See "Dermatoses of pregnancy", section on 'Pustular psoriasis of pregnancy'.)

Ustekinumab — Ustekinumab is a monoclonal antibody that targets interleukin (IL) 12 and IL-23. Data on the safety of ustekinumab in pregnancy are primarily limited to animal studies. Individual cases of uncomplicated delivery of a healthy infant [30-34] and spontaneous abortion [35] have been reported in patients treated with ustekinumab during pregnancy. Pending further study, anti-tumor necrosis factor (TNF) biologic therapy is preferred over ustekinumab for psoriasis in the pregnant population.

Other biologic agents and apremilast — There are insufficient data regarding fetal exposure to ixekizumab, secukinumab, and brodalumab, newer IL-17 inhibitors approved for the treatment of moderate to severe psoriasis. An analysis of the manufacturer's global safety database for secukinumab through June 2017 identified no safety signals with regard to spontaneous abortions or congenital malformations [36].

There are insufficient data regarding the IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab. Similarly, there are insufficient data regarding apremilast, an oral phosphodiesterase type 4 inhibitor. A moderate level of caution should be employed with use of these medications in the setting of pregnancy.

Fumaric acid — Fumaric acid esters are used to treat psoriasis in Europe. Although animal studies do not show any teratogenicity, there are very limited data in humans. Therefore, the use of fumaric acid esters is not recommended in a pregnant woman [37].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis".)

SUMMARY AND RECOMMENDATIONS

●Overview – The effect of maternal psoriasis on pregnancy outcomes remains uncertain. Choosing drug therapies that pose the least risk to the fetus is the major issue in managing the pregnancies of affected patients. (See 'Special considerations' above and 'Treatment principles' above.)

●Timing of pregnancy – Ideally, patients should plan pregnancy when they are in remission and off medication or taking the minimum effective dose of medications that have the best fetal safety profiles. However, postponing pregnancy until a period of remission is often unrealistic. The selection of treatments with good fetal safety profiles is particularly important for these patients. (See 'Special considerations' above.)

●Impact of pregnancy on psoriasis – Psoriasis improves during pregnancy in 40 to 60 percent of patients, worsens in 10 to 20 percent, and remains stable in the remainder. In patients who improve, the degree of improvement can be dramatic. In the postpartum period, psoriasis severity remains the same or worsens in most patients. (See 'Special considerations' above.)

●Approach to treatment:

•Patients with limited psoriasis – For pregnant patients with limited psoriasis (ie, nondebilitating psoriasis that involves less than 5 to 10 percent of the body surface area), we suggest topical rather than systemic therapy (Grade 2C). Emollients and moisturizers are useful for reducing bothersome scale. Our first-line medical treatment is a low- to medium-potency topical corticosteroid (table 1). (See 'First-line therapy' above.)

•Patients with topical therapy-resistant or extensive psoriasis – For patients with psoriasis that cannot be managed adequately with topical therapy (ie, resistant or extensive disease), we suggest narrowband ultraviolet B (NBUVB) phototherapy rather than systemic therapies because of the safety and efficacy of phototherapy in pregnancy (Grade 2C). Because psoriasis often improves during pregnancy, patients who required systemic treatment prior to pregnancy may be able to transition to phototherapy. (See 'Ultraviolet B phototherapy' above.)

●Contraindicated therapies – Topical tazarotene, methotrexate, and acitretin are contraindicated during pregnancy. (See 'Contraindicated therapies' above.)