Psoriasis is a chronic inflammatory disease that has important physical and psychological consequences(1). It is a skin condition that affects mainly the extensor surfaces of the elbows and knees and, occasionally, the intergluteal and umbilical areas. It also affects entheses and nails(2). Approximately 20-30% of the psoriasis patients will develop psoriatic arthritis. Psoriatic arthritis is an inflammatory musculoskeletal disease that is associated with cutaneous psoriasis. Comorbidities such as osteoporosis, uveitis, subclinical bowel inflammation and cardiovascular disease occur in patients with psoriatic arthritis(2).
About 65,000-107,000 deliveries take place annually in women with psoriasis, and 9000-15,000 of these women have moderate or severe disease. Pregnancy is a physiological state that can influence the severity of psoriasis and psoriatic arthritis(3).
From a physiopathological point of view, there is an uncontrolled inflammation and excess of cytokines in psoriasis. There are dysfunctional T-helper lymphocytes and proinflammatory cytokines – especially TNF-a, IL-1 and IL-6 – that cause endothelial dysfunction, with vasospasm, aggregation of platelets and coagulation activation. All these changes render in systemic and placental vasculopathy(3).
Psoriatic arthritis and pregnancy
Even though most pregnancies in women with psoriatic arthritis are uneventful(4) and, usually in pregnancy, psoriasis and psoriatic arthritis to a lesser extent improve thanks to the immunological changes, many pregnant patients still need treatment(5). Moreover, pregnancy may be a triggering factor for the articular disease in some women with psoriasis.
A worsening of psoriasis symptoms appears in the postpartum period in about 40-90% of the patients, and the onset of psoriatic arthritis can be seen in 30-40% of the patients(3).
Many women with psoriasis tend to develop associated conditions, such as obesity, hypertension, diabetes mellitus, depression and other chronic inflammatory diseases.
Obesity, diabetes, hypertension and depression tend to be more common in women with severe psoriasis and psoriatic arthritis. All these comorbidities tend to have adverse effects on pregnancy and birth outcomes(1). The fetal risk depends on the mother’s disease activity and the treatment used to alleviate symptoms(3).
Expecting mothers with psoriasis had an increased risk of gestational diabetes, gestational hypertension, and preeclampsia. Stakes were higher in women with severe psoriasis(1).
In a study performed in Danish and Swedish women with psoriasis, severe psoriasis meant using a systemic drug (any of the following: methotrexate and/or ciclosporin, and/or biologic agents antitumor necrosis factor, ustekinumab, efalizumab, abatacept, leflunomide) before or during pregnancy. Nonsevere psoriasis meant the use of antipsoriatic topical drugs only or a diagnosis of psoriasis without recorded treatment(1). Also, active disease and treatment with glucocorticoids are factors responsible for increasing some adverse pregnancy outcomes(6).
Apart from the comorbidities that can be present in pregnant women with psoriasis, studies have shown that women with psoriatic arthritis have a higher risk of pregnancy complications (i.e., preterm birth, elective or emergency caesarean delivery) than healthy pregnant patients(4). Placental vasculopathy seems to be responsible for intrauterine growth retardation and low birth weight(3). Still, it appears that there is no increased risk of preeclampsia, stillbirth or other bad fetal outcomes(4).
Treatment options for psoriasis and psoriatic arthritis in pregnancy
Preconception counseling in order to improve maternal, pregnancy and birth outcomes is beneficial in women with psoriasis and psoriatic arthritis(1).
As mentioned before, psoriasis and psoriatic arthritis tend to improve during pregnancy, but there are patients whose symptoms may worsen, and they need systemic therapy(4). Furthermore, pregnant women with psoriatic arthritis tend to have an unhealthy lifestyle that predisposes them to associated conditions, but they can be manageable(1). The stress associated with chronic and recurrent disease impacts mental health and increases the risk of alcohol abuse, smoking, weight gain and depression(3).
Topical treatment is the first-line treatment of psoriasis in pregnant and lactating women(7,8). Emollients should be used first due to the few side effects, followed by low to medium potency corticosteroids. High-potency corticosteroids must be used with caution in the second and third trimesters due to their association with low birth weight(6,9). UVB phototherapy is the second-line treatment, with limited data, but so far it is not associated with an increased risk of fetal abnormalities or prematurity(8,9). Third-line treatments of psoriasis in pregnant women include systemic medications such as corticosteroids and cyclosporine(9).
Systemic corticoids used during pregnancy are associated with low birth weight and intrauterine growth retardation. Once the placenta is developed, placental 11-b-hydroxylase inactivates them, relatively protecting the fetus. They also have an impact on the mother, associating adverse effects such as hypertension, diabetes and osteoporosis. However, they are used to treat psoriatic arthritis(3).
Methotrexate, a traditional agent used for psoriatic arthritis, is contraindicated during pregnancy due to its teratogenic effects: central nervous system, craniofacial, and limb and growth abnormalities(10). It should also be discontinued three months before conception(3).
Azathioprine can lead to premature births, but it was not associated with birth defects or low birth weight, confirming the possibility of its use in pregnancy when indicated(11).
Cyclosporine has a prevalence rate of malformations of 3%, comparable with the one of the general population(10). Most authors recommend its use in patients with severe psoriasis(3).
Tacrolimus, usually used in nonpregnant patients to treat intertriginous areas, has no studies for topical treatment during pregnancy. When administered systemically, it has proven to be associated with prematurity and low birth weight(3).
Anti-TNF agents showed increased risks of preterm birth, caesarean section, and small for gestational age. It is not fully understood if these findings are associated with the disease activity instead of these agents’ specific effects(10). Biological agents’ concentrations in the cord blood and their transfer have been investigated. Increased levels of adalimumab and infliximab have been found, in contrast to those of certolizumab and etanercept. Etanercept seems to be involved in fetal cardiac, esophageal and renal effects. Certolizumab is the preferred agent as it has no Fc portion; thus, its active FcRn-mediated transplacental transport is not expected(4,12,13).
There is new evidence that sustains that the biological treatment causes no harm during pregnancy. This is the case of secukinumab, a monoclonal antibody (IgG1 molecule) that targets interleukin-17A and which is used to treat moderate to severe psoriatic arthritis. It could cross the placenta, but most of the passage happens in the third trimester(5). Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23 p40 subunit, inhibiting them(3). There are few studies on ustekinumab, but two case reports present full-term delivery(4), even though most authors do not recommend its use during pregnancy(3).
Psoriatic arthritis disease activity may worsen during pregnancy. There are only a few available approved therapeutic means. This highlights the importance of preconception counseling. Whenever pregnancy happens, disease ameliorating therapies that are compatible with pregnancy should be continued. The management of pregnant women with psoriatic arthritis implies balancing the risks of interrupting the mother’s treatment against any threat to the fetus/child being exposed to drugs during pregnancy or breastfeeding. The current restrictions apply to the few proven teratogenic drugs and the large proportion of medications not yet sufficiently tested.
Conflict of interests: The authors declare no conflict of interests.