Management of dermatological conditions in pregnancy

20.1

Introduction

Every system in the body undergoes drastic changes during pregnancy, including the integumentary system. These dermatological changes are a result of varying factors, such as alterations in collagen formation, increase in sebaceous and eccrine gland secretion, shifts in hormone production, and increased circulatory blood volume [ ]. This can lead to the development of new or worsening of current dermatological conditions during pregnancy. While these conditions are oftentimes minor and resolve after pregnancy, some can be of significant concern for the woman during the antepartum period [ ]. This may prompt the pregnant woman to seek treatment from the health care provider, who will need to utilize sound clinical judgment on how to safely manage dermatological conditions during pregnancy and the postpartum period. Overall, management can be addressed with one of four approaches: (1) delay treatment until after pregnancy; (2) consider nonpharmacologic alternatives; (3) judiciously prescribe medications; or (4) discontinue breastfeeding during the postpartum period and prescribe accordingly.

Even when considering one of the before mentioned approaches, the clinical decision regarding medication use during pregnancy is hazed by the paucity of randomized clinical trials that include pregnant women. Furthermore, the new Federal Drug Administration (FDA) Pregnancy Category that replaced the previous A, B, C, D, and X system in 2015 has been faced with criticism for being confusing when it comes to interpreting medication safety and fetal risk assessment [ ]. This is especially alarming since findings from a large, prospective cohort study of nulliparous women suggested that more than 90% of the study participants took at least one medication while pregnant [ ]. Therefore, it is imperative that guidance be provided to health care providers with regards to the practice of prescribing medications to patients who are pregnant or breastfeeding. The choice to take medications should be a joint decision between the patient and health care provider [ ].

The purpose of this chapter is to provide direction for health care providers who are faced with the dilemma of prescribing medications for managing dermatological conditions for patients during the antepartum and postpartum periods. Although a plethora of conditions impacting the integumentary system during pregnancy exists, this chapter will focus on managing the most common alterations. These include acne, psoriasis, dermatoses, bacterial infections, viral infections, fungal infections, and parasitic infections. When describing medication safety risk for the pregnant patient, the FDA categorical method will be utilized.

20.2

Acne

Acne is a common dermatological condition that can vary from mild comedones to severe inflammation and scarring [ ]. The pregnancy state can exacerbate clinical manifestations of acne. The basis for deciding to treat acne during pregnancy and the postpartum period is based on the severity of the condition. However, prescribing medications for acne can be perplexing since there are a limited number of safe pharmacologic choices available for patients who are pregnant or breastfeeding [ ].

20.3

Psoriasis

Psoriasis is an autoimmune disease characterized by thick, pruritic, scaly plaques on the skin. The increased estrogen levels that occur during pregnancy are thought to lead to an immune tolerant state, resulting in an improvement of these symptoms for many pregnant women [ ]. Results of a study examining pregnant women with psoriasis found 55% demonstrated improvement, 21% had no change, and 23% experienced worsening of symptoms during pregnancy [ ]. For pregnant women who do require treatment, pharmacologic management can be challenging for the prescriber.

20.4

Oral agents

If psoriasis is persistent or worsens during pregnancy, systemic treatment may be warranted. Cyclosporine (category C) 2.5–5 mg/kg/day is considered the initial oral agent of choice [ ]. The drug passively crosses the placental blood barrier resulting in 10%–50% of the maternal plasma concentration and lacks mutagenic or teratogenic properties [ ]. Contrary to its acceptable use in pregnancy, oral cyclosporine should be avoided in lactating women since it possesses immunosuppressive characteristics, potentially impacting the breastfed newborn [ ].

Oral corticosteroids, such as prednisone (category D), prednisolone (category D), or methylprednisolone (category C), are not used in the treatment of common psoriasis in pregnancy due to reports indicating an association with their use and gastroesophageal reflux, low birth weight, intrauterine growth restriction, and oral clefts among neonates exposed in utero [ ]. Although a metaanalysis failed to find an increased risk for serious fetal anomalies, the authors raised concern with using oral corticosteroids during the first trimester of pregnancy [ ]. These medications may be used by lactating women with a recommended 3–4 h interval from ingestion to a breastfeeding episode [ ].

Mycophenolate mofetil (category D) has been associated with congenital anomalies and first trimester spontaneous abortion; thereby, should not be used by pregnant women or those attempting to conceive [ ]. Similarly, methotrexate (category X) and acitretin (category X) should be avoided by pregnant and lactating women. Methotrexate is an abortifacient with mutagenic and teratogenic properties, such as anencephaly, cleft palate, and ear and skeletal malformations, and should not be used by women or men for 3 months prior to conception [ ]. Due to storage in adipose tissue, stricter guidelines are used for acitretin by which pregnancy should be avoided up to 3 years after discontinuing treatment due to risks for severe fetal anomalies, such as craniofacial, ear, thymus, central nervous system, and cardiovascular system malformations [ ].

Biologic agents, such as etanercept (category B), infliximab (category B), and adalimumab (category B), are becoming an increasingly popular choice in treating psoriasis. However, severely limited data on their use in pregnancy make prescribing to the pregnant and lactation populations somewhat perplexing. The majority of studies examining the administration of these medications to pregnant women are from their use in managing irritable bowel syndrome and rheumatoid arthritis [ ]. One report indicated that newborns exposed to infliximab and adalimumab in utero had significantly higher concentrations of these drugs when compared to their mothers, with levels still detectable during the first 2–7 months of life [ ]. While the placental transfer of etanercept to the fetus is much lower [ ], there has been a case report of a neonate who developed VACTERL syndrome while exposed to etanercept in utero [ ]. This condition, which causes vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula, esophageal atresia, renal anomalies, and limb anomalies, was also observed in animal studies involving etanercept [ ]. Moreover, a study involving 41 women who took etanercept or infliximab while pregnant found 59% of their newborns displayed at least one clinical manifestation of VACTERL syndrome [ ]. A case of partial VACTERL association was also reported in an infant whose mother took adalimumab while pregnant [ , ]. It is noteworthy that there have been no other reported anomalies in newborns exposed to etanercept in utero [ , ]. A comparison of women who took infliximab while pregnant also noted no increased risk of fetal or neonatal anomalies [ ]. The potential for immunosuppression in the newborn exposed to biologic agents is also of concern, especially after an infant who was exposed to infliximab in utero died from disseminated bacillus Calmette-Guerin infection after being vaccinated [ ].

Due to the low levels of etanercept and infliximab in breast milk, evidence supports their safe use by breastfeeding women [ ]. Although evidence seemingly supports the use of these biologic agents in pregnant and nursing women, due to the lack of long-term and rigorous studies, it makes arriving at a definitive conclusion regarding their safe use difficult to determine. Further lacking are empirical data on the use of newer biologic agents, such as ustekinumab, secukinumab, and ixekizumab, with pregnant and lactating women [ ].

20.5

Dermatoses

Dermatologic conditions that only occur in pregnancy and the immediate postpartum period are referred to as dermatoses of pregnancy. In 2006, these conditions were reclassified by Ambros-Rudolph, Mullegger, Vaughan-Jones, Kerl, and Black to include four conditions: (1) pemphigoid gestationis (PG); (2) polymorphic eruption of pregnancy (PEP); (3) intrahepatic cholestasis of pregnancy (ICP); and (4) atopic eruption of pregnancy (AEP) [ ]. While there are vast differences among these conditions, the underlying commonality is the intense pruritus associated with these dermatoses. Therefore, the hallmark treatment includes the use of antihistamines since they are considered the first line of treatment in managing pruritus associated with dermatological conditions during pregnancy [ ].

Systemic antihistamines are classified as first generation and second generation, with the primary difference being that first-generation antihistamines, such as chlorpheniramine (category B), diphenhydramine (category B), dexchlorpheniramine (category B), and hydroxyzine (category C), have sedating effects, while second-generation antihistamines, such as loratadine (category B), cetirizine (category B), fexofenadine (category C), and azelastine (category C), do not [ ]. This impact on the central nervous system should be taken into consideration by prescribers since it may pose a safety risk and interfere with the patient's quality of life by producing long-lasting sedative effects associated with first-generation oral antihistamines [ ]. Even so, when prescribing a first-generation oral antihistamine, the prescriber should educate the patient to take this medication prior to sleeping.

However, more empirical data exist assessing the use of first-generation antihistamines, likely because they have been used longer when compared to newer, second-generation antihistamines. A metaanalysis of 24 studies with more than 200,000 pregnant women who took an oral first-generation antihistamine during the first trimester of their pregnancies discovered no increased fetal or maternal risk [ ]. Moreover, this result was corroborated by the findings of several studies [ ]. Nonetheless, because oral diphenhydramine has been associated with retinopathy of prematurity, formerly known as retrolental fibroplasia, it should be avoided during the last 2 weeks of pregnancy [ ]. It should also not be used during this time frame because it may cause withdrawal symptoms, such as irritability and difficulty feeding, in newborns exposed to this medication in utero [ ]. Additionally, high doses of diphenhydramine can cause uterine contractions, resulting in premature births [ ]. Another first-generation antihistamine, hydroxyzine, should not be taken in the first trimester of pregnancy due to its association with fetal anomalies [ ].

First-generation systemic antihistamines are not recommended for use by lactating women primarily due to the lack of supporting evidence [ ]. It is recognized that these drugs may lead to drowsiness and lethargy in the breast-fed newborn [ ]. It has also been proposed that first-generation oral antihistamines may cause decreased maternal milk production due to their impact on dopamine secretion [ ].

With regards to second-generation antihistamines, systemic loratadine and cetirizine are considered safe during the second and third trimesters of pregnancy and lactation [ ]. Initial concerns regarding the risk of hypospadias in newborns exposed to maternal oral use of loratadine in utero were refuted by the Centers for Disease Control and Prevention after assessing data from the National Birth Defects Prevention Study [ ]. As with first-generation antihistamines, these second-generation medications should not be taken in large doses near the time of delivery [ ].