INTRODUCTION
Psoriasis is a chronic immune-mediated inflammatory disease characterized by keratinocyte hyperproliferation and dysregulated T-cell-driven inflammation [1]. Epidemiological studies indicate that one incidence peak occurs between the ages of 20 and 29 years [2]. Consequently, psoriasis frequently affects women during their reproductive years [3]. The prevalence among women of reproductive age is estimated to be approximately 1% of the general population [1]. Data from the United States indicate that more than 100,000 births occur annually in women with psoriasis [4].
Psoriasis is associated with several systemic comorbidities, including metabolic syndrome, obesity, depression, and arthritis, as well as adverse pregnancy outcomes such as low birth weight (LBW) [3]. In addition, pregnancy-related changes in disease severity and the potential use of fetotoxic, abortifacient, or teratogenic medications must be considered when managing pregnant patients with psoriasis [5]. This review summarizes current evidence regarding psoriasis during pregnancy and provides practical guidance for the safe and effective management of the disease.
PSORIASIS IN PREGNANCY
Patients with moderate to severe psoriasis vulgaris (PV) may have an increased risk of pregnancy complications, including miscarriage, preterm birth, and premature rupture of membranes, compared with the general population. Infants born to women with severe PV are more likely to have very low birth weight. However, some studies report an increased frequency of macrosomia in this group. Regarding maternal complications, psoriasis has been associated with a higher risk of gestational diabetes and gestational hypertension. In cases of pustular psoriasis, pregnancy has been linked to an increased incidence of preterm delivery and stillbirths, regardless of the treatment administered [2].
Improvement in psoriasis during pregnancy may be related to immunological changes occurring during gestation. Psoriasis is primarily mediated by T helper 1 (Th1) and T helper 17 (Th17) lymphocytes, both of which are proinflammatory cell types, while interleukin 23 (IL-23) is required for Th17 expansion. During pregnancy, a reduction in Th17 activity may contribute to improvement in disease severity [3].
In contrast, disease worsening may result from immune dysregulation associated with psoriasis, which can negatively affect pregnancy outcomes. Proinflammatory cytokines such as Th1, IL-2, and interferon (IFN)-γ may influence implantation through their role in vascular remodeling. Increased levels of Th17 cells producing IL-17A have been detected in decidual tissue, where they may also contribute to protection against invading pathogens. Furthermore, Th cell populations may shift between functional lineages depending on the immunological environment. This balance may be altered in psoriasis, potentially affecting the immune regulation required for normal pregnancy development [4].
Carriers of the HLA-Cw6 allele have been reported to experience greater clinical improvement during pregnancy compared with non-carriers. They also demonstrate higher rates of remission during gestation, suggesting that women without the HLA-Cw6 allele may be more likely to experience persistent or worsening symptoms. These findings have increased interest in genetic testing following psoriasis diagnosis to determine HLA-Cw6 status and provide additional prognostic information [3].
Sobolev et al. reported significant differences in sex hormone levels between patients with psoriasis and healthy controls. Estradiol (E2) and progesterone (PG) levels were higher in healthy individuals, whereas testosterone levels were elevated in psoriasis patients. Similar findings have been reported in postmenopausal women with psoriasis, who exhibited lower levels of E2 and PG and higher testosterone levels compared with healthy postmenopausal controls. These observations further support the role of sex hormones in psoriasis pathophysiology [6].
CLINICAL PRESENTATION OF PSORIASIS IN PREGNANCY
Two main forms of psoriasis may occur during pregnancy: plaque PV and pustular psoriasis. Plaque PV is the most common presentation. In some women, plaque psoriasis improves during pregnancy, particularly in the second and third trimesters. This improvement may be related to increased levels of PG and E2, which can suppress inflammatory responses. Conversely, some women experience disease worsening, especially during the first trimester or in the postpartum period, when rapid hormonal changes occur. Hormones such as prolactin and cortisol may also influence disease activity [2, 3].
Pustular psoriasis of pregnancy, also known as impetigo herpetiformis, is a rare, inflammatory autoimmune condition that typically occurs during the second or third trimester. Clinically, it presents with sterile pustules developing on annular or polycyclic erythematous plaques. Lesions usually begin in the intertriginous areas and spread centrifugally, while the face, palms, and soles are often spared. Systemic symptoms may include fever, chills, malaise, nausea, diarrhea, dehydration, arthralgia, tachycardia, and seizures [5].
Although severe maternal complications are uncommon, they may occur as a result of hypocalcemia and bacterial sepsis. In rare cases, severe hypocalcemia may lead to tetany, delirium, or seizures. The most serious complication is placental insufficiency, which may result in stillbirth or neonatal death. Therefore, early induction of labor is sometimes considered [7].
Pustular psoriasis of pregnancy is generally regarded as a variant of pustular psoriasis triggered by hormonal changes during gestation. The absence of a positive family history, abrupt resolution of symptoms after delivery, and recurrence primarily in subsequent pregnancies distinguish this entity from classical pustular psoriasis. Furthermore, common triggers of pustular psoriasis, such as infection, exposure to certain medications, or abrupt withdrawal of systemic corticosteroids, are usually absent in these patients [7].
Although clinical findings are often characteristic, skin biopsy may be helpful in confirming the diagnosis. Histopathologic examination reveals the typical features of pustular psoriasis. Initial laboratory evaluation should include a complete blood count and a comprehensive metabolic panel, with particular attention to calcium levels. Common laboratory abnormalities include leukocytosis, neutrophilia, elevated erythrocyte sedimentation rate, iron deficiency anemia, and hypoalbuminemia. Decreased levels of calcium, phosphate, and vitamin D may occasionally occur, whereas serum parathyroid hormone levels are rarely reduced. Cultures of pustular contents and peripheral blood are negative unless secondary infection is present [7] (table 1).
Table 1
Differential diagnosis of pustular psoriasis of pregnancy [7]
| Most likely diagnoses Other conditions to consider Conditions that must be excluded |
MANAGEMENT OF PSORIASIS IN PREGNANCY
Non-pharmacological management
Controling factors that trigger psoriasis is important for preventing disease exacerbations. These factors include diet, physical activity, and psychological well-being. Identification and management of comorbid conditions are also essential to prevent worsening of symptoms and improve patients’ quality of life. Multidisciplinary care and consultation with other medical specialties may be required to ensure comprehensive management of pregnant patients with psoriasis [8].
Pharmacological management
Topical treatment
Topical corticosteroids (TCS) have the strongest evidence supporting their use in psoriasis during pregnancy and are therefore considered first-line therapy when treatment is required. A recent Cochrane review found no increased risk of congenital malformations (including cleft palate), preterm birth, or fetal death associated with the use of mild to moderate TCS. To date, no studies have measured fetal corticosteroid concentrations following maternal topical exposure. Several studies suggest that topical corticosteroids, such as methylprednisolone aceponate and mometasone furoate, may be preferable during pregnancy. When clinical improvement is achieved, the frequency of TCS application should be reduced. If necessary, proactive therapy (e.g., application two or three times per week) may be used to prevent relapse while minimizing cumulative exposure [2].
No studies have specifically evaluated topical calcineurin inhibitors (TCIs) in pregnant patients with psoriasis. However, extensive data exist regarding systemic calcineurin inhibitors such as tacrolimus used after solid organ transplantation during pregnancy. These studies have not demonstrated an increased risk of congenital malformations, although higher rates of preterm birth and LBW have been reported. Pharmacokinetic studies indicate that topical tacrolimus 0.1% ointment results in minimal systemic absorption due to its large molecular size. Therefore, limited use in small areas, particularly steroid-sensitive sites, is unlikely to produce systemic effects [5].
Dithranol may also be considered in selected cases, as no adverse pregnancy outcomes have been reported with its use. It may be used in patients with moderate PV involving up to 10% of body surface area for a limited period under close medical supervision to minimize adverse effects such as irritation or prolonged burning. Topical vitamin D analogues may also be used in selected cases on small treatment areas when TCS cannot be applied. The same cautious approach applies to the combination of betamethasone dipropionate and calcipotriol, which should only be used when the potential benefits outweigh potential risks [2].
Systemic treatment
Cyclosporine
No evidence of teratogenicity has been reported with cyclosporine use in rheumatology or transplantation medicine. Higher rates of preterm birth and lower birth weight compared with the general population have been described; however, these outcomes may be related to the underlying maternal disease. Cyclosporine has also been reported to be safe and effective in patients with recurrent miscarriage. A review of the literature identified 22 reports describing cyclosporine use in 23 pregnant patients with psoriasis.
Based on extensive clinical experience, cyclosporine may be continued or initiated during pregnancy when indicated. Nevertheless, the European Summary of Product Characteristics (SmPC) advises caution and recommends use only when the potential benefit to the mother outweighs potential fetal risk. In addition, the risk of hypertension should be considered, especially during pregnancy [5].
Both the SmPC and the German S3 guidelines classify pregnancy as a relative contraindication to cyclosporine therapy. However, due to long-term clinical experience and available safety data, cyclosporine remains one of the preferred systemic treatment options during pregnancy when systemic therapy is necessary. Careful monitoring is required to detect potential adverse effects [2].
Tumor necrosis factor (TNF) inhibitors
The most substantial evidence regarding systemic biologic therapy during pregnancy is available for TNF inhibitors. Certolizumab pegol may be used during pregnancy and lactation when clinically indicated. Prospective and retrospective studies demonstrate minimal placental transfer because this molecule lacks the Fc region required for active transport across the placenta. Most biologic agents cross the placenta through neonatal Fc receptors that bind the Fc fragment of IgG antibodies. As certolizumab pegol does not contain this fragment, fetal exposure is minimal. Consequently, it is generally considered the biologic treatment of choice during pregnancy and lactation.
Limited data also exist for other TNF inhibitors. The use of adalimumab in nine pregnancies in 8 patients with psoriasis did not demonstrate significant teratogenic effects. According to the SmPC, adalimumab may be administered during pregnancy if clearly indicated [2].
The European League Against Rheumatism (EULAR) recommendations prefer etanercept (as well as certolizumab pegol) for patients planning pregnancy or already pregnant. However, the SmPC does not recommend routine use of etanercept during pregnancy. Similarly, the EuroGuiDerm guidelines for systemic psoriasis therapy do not prioritize etanercept in this setting. Data from other medical fields suggest that infliximab may be used during pregnancy when a clear clinical indication exists [2].
IL-23 inhibitors
The oldest IL-23 inhibitor, ustekinumab, binds to the p40 subunit and also inhibits IL-12. An animal study showed no evidence of teratogenicity. Furthermore, phase II and III clinical trials, which included 31 pregnant women, did not reveal teratogenic effects or increased fetal risk; however, the exact number of subsequent pregnancies was not specified in the publication. In addition, a report involving 29 women with psoriasis and 34 exposed pregnancies found no teratogenic effects. Given the currently limited evidence, the SmPC recommends avoiding ustekinumab during pregnancy whenever possible as a precautionary measure [2].
IL-17 inhibitor
The largest cohort study to date evaluating pregnancy exposure to the IL-17A inhibitor secukinumab reported no increased fetal or maternal risk were observed in 238 patients with psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis, and the rates of miscarriage or congenital malformations were comparable to those of the general population. However, the study noted some heterogeneity regarding the duration of drug exposure. Overall, 177 pregnancies in women with psoriasis exposed to secukinumab have been reported. Given the limited data currently available, the SmPC recommends avoiding secukinumab during pregnancy as a precautionary measure [2].
Vitamin D and omega-3 supplementation
Hypovitaminosis D has been proposed as one of the factors associated with psoriasis, in addition to chronic immune dysregulation. For this reason, vitamin D supplementation in psoriasis has been assessed in several studies. Vitamin D may suppress dendritic cell maturation and antigen presentation, thereby reducing IL-12 and IL-23 production and attenuating Th1 and Th17 responses, which are key pathogenic pathways in psoriasis [9]. The recommended intake of vitamin D for pregnant women is the same as for non-pregnant women, namely 600 IU/day. Several studies have shown that vitamin D supplementation during pregnancy may reduce the risk of allergic conditions in offspring, including wheezing, asthma, and allergic rhinitis [10].
Despite the proposed biological rationale, the clinical benefit of vitamin D supplementation in psoriasis remains uncertain. A systematic review including 23 studies found no significant differences in Psoriasis Area and Severity Index (PASI) scores between the intervention and control groups after 3, 6, and 12 months of supplementation [9]. Another review likewise showed no meaningful improvement in PASI following vitamin D supplementation [11].
Although the effect on PASI appears limited, vitamin D supplementation may still be beneficial during pregnancy. Placental vitamin D receptor expression and local calcitriol production contribute to maternal-fetal immune regulation, and supplementation may influence maternal inflammatory biomarkers and clinical risk profiles [12]. A randomized controlled trial showed that supplementation increased serum vitamin D levels in pregnant women but did not modify immune signaling later in pregnancy, suggesting that preconception supplementation may be more relevant for influencing immune mediator responses [13]. Pregnant women receiving vitamin D supplementation may also have higher total antioxidant capacity (TAC) and lower levels of inflammatory markers such as hs-CRP, IL-8, and TNF-α, which could be beneficial in pregnant patients with psoriasis [14].
Omega-3 fatty acids target major inflammatory pathways, including eicosanoids, NF-κB, PPARγ, and specialized pro-resolving mediators, and may attenuate the inflammatory milieu that sustains psoriatic plaques. This provides a mechanistic rationale for their use, particularly as adjuncts to standard therapy. In a randomized controlled trial, fish oil or omega-3 polyunsaturated fatty acids (PUFAs) combined with conventional treatment significantly reduced PASI scores without reported adverse effects [15]. During pregnancy, omega-3 supplementation has also been shown to lower maternal inflammatory markers, such as C-reactive protein (CRP), and IL-6, and to improve metabolic and inflammatory profiles, which may be beneficial in women with inflammatory comorbidities, including psoriasis [16].
In summary, oral vitamin D and omega-3 supplementation may provide supportive benefits in psoriasis. However, evidence from randomized trials remains heterogeneous. Although some studies and pooled analyses suggest clinical improvement, at least one recent randomized controlled trial of oral vitamin D found no significant reduction in disease severity. Overall, both vitamin D and omega-3 are best regarded as adjunctive measures rather than substitutes for established topical or systemic therapies. High-quality, disease-specific randomized controlled trials in pregnant women with psoriasis are still needed.
Phototherapy
Narrowband UVB (NB-UVB) is considered a first-line treatment when systemic treatment is needed. Controlled UV phototherapy during pregnancy is generally regarded as safe. Although not formally classified within Food and Drug Administration (FDA) pregnancy categories, NB-UVB has been used without evidence of increased risk of fetal abnormalities or preterm birth. However, caution is advised due to the risk of UV-related folic acid photodegradation. Reduced serum folate levels may increase the risk of fetal neural tube defects, particularly when combined with hyperthermia, which should be avoided, especially during the first 28 days of pregnancy. Therefore, folate levels should be monitored and supported with appropriate supplementation. Several studies recommend a daily folic acid dose of 0.8 mg in pregnant patients receiving UVB therapy. Broadband UVB is less effective but may be considered when NB-UVB is unavailable [2, 17].
The safety of psoralen and ultraviolet A (PUVA) therapy during pregnancy has not been established and it is classified as FDA pregnancy category C. Psoralen, administered orally, increases skin sensitivity to UVA radiation and promotes methoxsalen binding to deoxyribonucleic acid (DNA), thereby inhibiting cell division. Due to the theoretical risk of mutagenicity and teratogenicity, PUVA therapy should be avoided during pregnancy [2, 17].
Contraindications in psoriasis during pregnancy
Methotrexate (MTX)
MTX is contraindicated in pregnant women and in those planning pregnancy due to its teratogenic effects. As a folate antagonist, it interferes with DNA synthesis and cell division, leading to fetal malformations. Although a prospective observational study of 28 women exposed to low-dose MTX during the first trimester did not demonstrate increased teratogenicity, multiple reports describe embryopathy even at low doses. Therefore, women of reproductive age receiving MTX should be counseled regarding teratogenic risk and the need for effective contraception [2].
The recommended duration of contraception after MTX discontinuation varies across guidelines: the German S3 guideline advises 3 months, the SmPC recommends at least 6 months, and the EULAR suggests a washout period of 1–3 months. In the case of unintentional pregnancy during MTX therapy, the drug should be discontinued immediately or replaced with a safer alternative, and the pregnancy should be closely monitored with ultrasound [2].
MTX is also contraindicated during breastfeeding, as it is excreted into breast milk. Although only small amounts are detected, reaching peak levels 2–6 hours after oral or subcutaneous administration and possible clearance within 24 hours, current evidence and product labeling do not support its use during lactation. Safer therapeutic alternatives are available [2].
Retinoids
Systemic retinoids (e.g., isotretinoin, acitretin) are strictly contraindicated during pregnancy due to their potent teratogenicity. They disrupt retinoic acid signaling during early embryogenesis, affecting neural crest cell migration, organogenesis, and somitogenesis, and leading to characteristic retinoic acid embryopathy, including craniofacial, cardiac, thymic, and central nervous system malformations, as well as an increased risk of pregnancy loss [18].
Due to the high risk of major congenital anomalies, strict pregnancy prevention measures are required. For isotretinoin, patients must use two forms of effective contraception for at least 1 month prior to initiation, during therapy, and for 1 month after discontinuation. In contrast, acitretin requires prolonged contraception – commonly at least 3 years – due to the persistence of its metabolites. Breastfeeding is contraindicated during systemic retinoid therapy because of potential infant exposure and limited safety data [19].
Prognosis of psoriasis in pregnancy
The course of psoriasis during pregnancy varies widely among individuals, influenced by hormonal and immunological changes. Approximately 40–60% of women with chronic plaque psoriasis experience clinical improvement, particularly during the late first and second trimesters. This effect is thought to be associated with increased progesterone levels, which downregulate T-cell-mediated immune responses. In contrast, some patients remain clinically stable, while approximately 10–20% may experience disease exacerbation requiring intensified management [17, 20].
Pregnancy and fetal outcomes
Psoriasis does not appear to adversely affect fertility or significantly increase the risk of miscarriage, congenital anomalies, or premature birth. However, severe disease has been associated with adverse outcomes, including spontaneous abortion, preterm delivery, and increased rates of cesarean section. The severity of the disease can also significantly affect the mother’s quality of life [17, 20].
The immunological mechanisms underlying pregnancy outcomes are complex. While Th2-dominant immunity has been implicated in pregnancy maintenance, dysregulation of the balance between Th1, Th2, and Th17 pathways may contribute to complications. Regulatory T cells (Tregs) play a critical role in maintaining maternal–fetal tolerance through inhibition of immune cell proliferation and cytokine production [4].
Postpartum course of psoriasis
Following delivery, many women experience a recurrence or worsening of psoriasis symptoms, typically within 6–12 weeks postpartum. New-onset PsA may also occur during this period. Additionally, the Koebner phenomenon can be triggered by skin trauma, including surgical procedures such as cesarean section [17, 20].
CONCLUSIONS
Psoriasis is a dermatological condition that can affect pregnant women in various ways. During pregnancy, hormonal changes often lead to an improvement in psoriasis symptoms in many women, although some may experience worsening. Women with severe psoriasis have a higher risk of complications such as miscarriage, preterm birth, and low birth weight. Management of psoriasis during pregnancy must carefully balance the risks and benefits of available therapies, prioritizing treatments that are safe for both the mother and the fetus. After delivery, many women experience a recurrence of psoriasis symptoms, highlighting the need for ongoing management. A clear understanding of the interaction between psoriasis and pregnancy is essential to maintain maternal and fetal health and to improve patient quality of life.
