Pregnancy and dermatologic therapy

Kelly H. Tyler, MD, FACOG, and Matthew J. Zirwas, MD, FAAD Columbus, Ohio
Dermatologists should be familiar with medication safety in pregnancy to be able to prescribe safely and condently to pregnant women or women who may become pregnant during the course of treatment for dermatologic conditions. Topical medications should be considered rst-line therapy for pregnant women, but certain systemic medications are safe to use in pregnancy and may be prescribed if necessary. Dermatologic surgery may be performed during the second trimester of pregnancy with proper positioning, but elective procedures should be delayed until the postpartum period. ( J Am Acad Dermatol 2013;68:663-71.) Key words: dermatologic surgery; dermatologic therapy; medication safety; pregnancy; systemic medications; topical medications.

omen present to their physicians with a variety of skin disorders in the pregnant and nonpregnant state, with certain dermatoses encountered only during pregnancy.1 These women typically present first to their obstetricians during routine visits, but they sometimes require referral to a dermatologist for continued treatment of pre-existing or new skin symptoms. Female dermatologic patients may also become pregnant during the treatment of their skin disease. It is important, therefore, for dermatologists to be able to prescribe safely and confidently to pregnant women and women who may become pregnant.

Toxicology Service (www.reprotox.org), Drugs in Pregnancy and Lactation by Briggs et al,5 US Pharmacopeial Dispensing Information,6 and case reports.3 Because the FDA can be slow to update the ratings based on the most recent data and research, sources such as the Reproductive Toxicology Service World Wide Web site may be more up to date.1

TIMELINE FOR RISK

When prescribing a medication, it is important to determine whether a patient is actively preventing pregnancy with contraception, trying to conceive or not preventing pregnancy, or is currently pregnant in a specic trimester and/or period of development (preimplantation, embryonic, or fetal).1 For sexually active women not on contraception, there is an 85% chance of becoming pregnant within 1 year.7 Avoiding potentially teratogenic agents during the embryonic period, which is the second through the eighth week after conception when organogenesis occurs, is especially important.1 Because some women will not have a positive home pregnancy test result until up to 5 weeks after conception, these patients should be treated with medications that are safe during pregnancy.1 Although the highest period of risk is during organogenesis, certain structures, such as the brain, teeth, and bones, remain susceptible after 9 weeks. Thus, some medications that do not cause harm during
Published online November 21, 2012. 0190-9622/$36.00 2012 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2012.09.034

DRUG CLASSIFICATION FOR PREGNANCY

Birth defects related to the use of diethylstilbestrol and thalidomide in the mid-20th century led to the development of the Food and Drug Administration (FDA) Pregnancy and Lactation Categories.2 One of 5 categories is assigned to each drug before it is released.3 Because of the impossibility of conducting controlled studies with medication use in pregnant women, these categories reflect a risk-benefit ratio based on animal studies or epidemiologic data.4 The classifications are included in Table I.3 Although the FDA pregnancy classications are the most widely used, other sources for determining the safety of a medication during pregnancy include Teratogen Information Service, Reproductive
From the Division of Dermatology, Ohio State University. Funding sources: None. Disclosure: Dr Zirwas has acted as a consultant for Smart Practice, Onset, Taro, and Valeant. Dr Tyler has no conflicts of interest to declare. Reprint requests: Kelly H. Tyler, MD, FACOG, 911 Neil Ave, Columbus, OH 43215. E-mail: hoskins.kelly@gmail.com.

663

664 Tyler and Zirwas

J AM ACAD DERMATOL

APRIL 2013

associated with hyperbilirubinemia, so its use is not contraindicated anytime during pregnancy.12 The nonantibacterial antiacne product benzoyl peroxide is category C because human studies have not been TOPICAL MEDICATIONS DURING conducted, but it is considered safe to use during PREGNANCY pregnancy and is a treatment of choice for acne in For most dermatologic conditions in pregnancy, pregnant patients.1,4,12 Salicylic acid, another nontopical treatments remain the safest choice antibacterial antiacne proand should be considered duct, is also category C. rst-line therapy. Table II CAPSULE SUMMARY Although this is an nonstesummarizes the pregnancy roidal anti-inflammatory classifications and risks of There are 3 distinct periods of drug, which is generally coneach topical medication. development during pregnancy: traindicated in pregnancy preimplantation (0-2 weeks), embryonic/ because of the potential for Acne and rosacea organogenesis (2-8 weeks), and fetal (9th oligohydramnios and early For acne and rosacea, a week to birth). closure of the ductus arterioplethora of topical medicaThe risk associated with any given sus in the third trimester,1 the tions are available, most of medication varies substantially over the systemic absorption is estiwhich are safe for use during course of these periods, with some mated to be between 9% pregnancy. The topical retimedications presenting risk primarily and 25%.13-15 Because of its noids tretinoin and adapaearly in pregnancy and others presenting minimal absorption, there is lene are category C. Some risk primarily late in pregnancy. a very low teratogenic potenstudies suggest that topical tial,16 and pregnant women tretinoin is teratogenic in With appropriate steps, dermatologic 8-10 should simply be advised not but anthe rst trimester, surgery and procedures can generally be to apply topical salicylic acid other study contradicts that safely performed during pregnancy for prolonged periods over finding.11 Absorption is minwhen necessary. large areas or under occluimal, and risk is unlikely, but sive dressings, which would alternative treatments should enhance systemic absorption. Azelaic acid is pregbe considered in the first trimester if they are availnancy category B because animal studies show no able.12 Adapalene, also category C, has minimal adverse effects, and less than 4% of the applied dose absorption, so use during pregnancy could be conis systemically absorbed.4,12,15 sidered once the benefits and risks have been 12 discussed with the patient. Data suggest that the Psoriasis and atopic dermatitis potential risk of teratogenicity of both agents is only For inammatory skin conditions such as psoriaduring the first trimester, and no problems have been sis, topical corticosteroids are considered rst-line reported in studies where use occurs in the second therapy in pregnant patients. A detailed review of and third trimester.12 A practical approach would be to consider treatment with these agents after the first pregnancy and psoriasis was performed by Tauscher trimester in consultation with the patients obstetriet al17 in which they outlined a stepwise approach for treatment. For localized disease in pregnancy, cian. Topical tazarotene, on the other hand, is they recommended topical corticosteroids as firstcategory X because of retinoid-like anomalies found line therapy followed by stepwise therapy with in animal studies, so it is contraindicated.12 Antibacterial topical agents used for acne and topical calcipotriene, anthralin, and tacrolimus.1 Although all of these topical medications are caterosacea include clindamycin, erythromycin, and gory C, there are many data on corticosteroid use for metronidazole, all of which are category B and safe a variety of medical conditions in pregnancy, so they throughout pregnancy.12 Topical dapsone, a category C medication, has been used safely as an oral are currently the preferred first-line therapy. medication in pregnancy for both leprosy and derThe absorption, and therefore the safety in pregmatitis herpetiformis, and no fetal risks are reported nancy, of topical corticosteroids is related to a numin the literature.12 There is a theoretical risk of ber of factors, including the vehicle of administration, neonatal hyperbilirubinemia when used near the amount applied, occlusion, and sites of application.4 A practical approach to therapy with topical corticotime of delivery, so the prescribing physician should steroids in pregnant women would be to advise them consider stopping treatment before the last month of not to apply large amounts over extensive areas or pregnancy.12 Topical sodium sulfacetamide, on the other hand, is a category C medication that is not under occlusive dressings to avoid excessive
d d d

organogenesis may cause complications later in pregnancy.1

J AM ACAD DERMATOL
VOLUME 68, NUMBER 4

Tyler and Zirwas 665

Table I. US Food and Drug Administration pregnancy risk categories

Category Description

X D C

Contraindicated in pregnancy; there is no reason to risk use of drug in pregnancy Positive evidence of risk to human fetus, but benefits may outweigh risks of drug Risk cannot be ruled out; human studies have not been performed; animal studies may or may not show risk; potential benefits may justify potential risk No risk to human fetus despite possible animal risk; or no risk in animal studies and human studies not done Controlled studies show no fetal risk

Topical antifungals are considered a safer alternative to oral antifungals during pregnancy. Of the imidazoles, the 2 preferable options are clotrimazole and oxiconazole, which are both category B.4 All other topical imidazoles, including econazole and ketoconazole, are category C because of limited data, but no specific adverse effects from the use of these topical imidazoles have been reported.12 Topical ciclopirox, naftifine, terbinafine, butenafine, and nystatin are all category B because there have been no problems reported from topical use during pregnancy.12 Topical permethrin is the drug of choice for scabies and lice occurring in pregnancy and is poorly absorbed. It has been used extensively with minimal adverse effects reported, thus it is category B.12

absorption16 because of certain studies that associate such use with a risk of low birth weight.12 In pregnancy, topical calcipotriene should be considered the next step in therapy for psoriasis. Topical calcipotriene is FDA pregnancy category C, and although skeletal abnormalities have occurred in animal studies, no such ndings have been shown in human beings.12 Practical usage limits and avoidance of occlusive dressings as described above for topical steroids will likewise help avoid systemic absorption and lower the risk of vitamin D toxicity. If both topical steroids and calcipotriene fail, alternative options for topical treatment are anthralin and tacrolimus.1 There are no studies on the use of anthralin during pregnancy in human beings or animals, but because there is also no evidence of systemic absorption after topical application, its use is not contraindicated.16 Likewise, data in human beings are limited for tacrolimus, but there have been no problems reported from topical use during pregnancy.12,16 Both anthralin and tacrolimus are pregnancy category C, and until more data are available on their use in pregnancy, they remain third- and fourth-line treatment options. Pimecrolimus is a common topical treatment for atopic dermatitis. Similar to tacrolimus, it is a category C medication and no problems have been reported from its use during pregnancy, but data are limited.12 If topical corticosteroids fail, pimecrolimus would be an acceptable topical treatment for atopic dermatitis during pregnancy. Topical antimicrobials For bacterial infections, topical antibiotics such as mupirocin, neomycin, and polymyxin B are not associated with teratogenicity.12 Large studies have not been conducted on any of these, but they are considered safe to use during pregnancy.12

SYSTEMIC MEDICATIONS DURING PREGNANCY

Although systemic medications should only be used when absolutely necessary during pregnancy, it is important to know the safety ratings of systemic treatments for common dermatologic conditions, especially for patients who may become pregnant during the course of treatment or in circumstances where delaying or interrupting treatment until pregnancy is completed is not advisable. Table III summarizes the pregnancy classifications and risks of each systemic medication. Acne Acne is a common condition that is generally unaffected by pregnancy.1 The 2 most common systemic medications used to treat acne are antibiotics and isotretinoin. Isotretinoin is category X and should be avoided during pregnancy or in those patients trying to conceive.18 Increased fetal loss may result from first-trimester use, and specific malformations including microtia, stenosis of the external ear canal, cleft palate, hydrocephalus, and cardiac outflow tract defects may occur with use later in pregnancy.1 The risks of systemic retinoid exposure during embryogenesis have been extensively reviewed, and a detailed discussion is beyond the scope of this review article. We would direct interested readers to the included references.19-28 Tetracyclines are known to deposit in developing bones and teeth during the second and third trimester, resulting in enamel hypoplasia and a yellowish staining of the teeth that will darken over time.12,29 Tetracyclines have also been associated with acute fatty liver of pregnancy, which is a potentially fatal syndrome that occurs in the third trimester.4 Interestingly, tetracyclines have not been associated with congenital anomalies during the first trimester,12 so as long as they are discontinued as soon as

666 Tyler and Zirwas

J AM ACAD DERMATOL

APRIL 2013

Table II. Pregnancy classifications and risks of topical medications for dermatologic therapy
Medication Pregnancy category High-risk period Risks/comments

Retinoids Tretinoin Adapalene Tazarotene Antibacterials Clindamycin Erythromycin Metronidazole Dapsone

C C X B B B C

First trimester First trimester Entire pregnancy None None None End of third trimester None None None None None None None Third trimester with high doses None None None None

Possible teratogen in first trimester, absorption minimal Possible teratogen in first trimester, absorption minimal Retinoid-like anomalies in animal studies

Mupirocin B Neomycin B Polymyxin B B Nonantibacterial antiacne products Sodium sulfacetamide C Benzoyl peroxide C Salicylic acid C Azelaic acid Immunosuppressants Corticosteroids Tacrolimus Pimecrolimus Antipsoriatics Calcipotriene Anthralin Antifungals Clotrimazole Oxiconazole Econazole Ketoconazole Ciclopirox Naftifine Terbinafine Butenafine Nystatin Antiparasitic Permethrin B C C C C C

Theoretical risk of neonatal hyperbilirubinemia if used near time of delivery No large studies available No large studies available No large studies available

Do not apply over large areas under occlusive dressings, 9-25% absorbed \4% Absorbed Possible risk of low birth weight in some studies with excessive absorption Data in human beings limited Data in human beings limited Skeletal abnormalities in animal studies, no such findings in human studies No evidence of systemic absorption, no studies during pregnancy in human beings or animals

B B C C B B B B B B

None None None None None None None None None None

Limited data Limited data

Has been used extensively in pregnancy

pregnancy is suspected, there is very little risk. However, because of multiple concerns with use during the second and third trimester, they are classified as category D and should be avoided during later pregnancy. Erythromycin is category B and is considered safe in pregnancy; however, hepatotoxicity may rarely occur with prolonged use of the erythromycin ethylsuccinate formulation in pregnant patients.4 In addition, 2 Swedish studies have reported an increased risk of cardiovascular malformations when

erythromycin was used early in pregnancy.30,31 Alternative antibiotics in later pregnancy are azithromycin, penicillins, and cephalosporins, all of which are pregnancy category B.5 Spironolactone, an antiandrogenic drug that competitively inhibits 5a-reductase and aldosterone, is often prescribed off-label for acne.32 Pregnancy category C, spironolactone caused feminization of male rat fetuses and delayed sexual maturation of female rat fetuses in animal studies, but those effects

J AM ACAD DERMATOL
VOLUME 68, NUMBER 4

Tyler and Zirwas 667

Table III. Pregnancy classifications and risks of systemic medications for dermatologic therapy
Medication Pregnancy category High-risk period Risks/comments

Antibiotics Tetracyclines

Second and third trimester First trimester

Erythromycin

Dental staining and enamel hypoplasia in second and third trimester, has been associated with acute fatty liver of pregnancy Hepatotoxicity rare with prolonged use in pregnancy, possible increased risk of cardiovascular malformations in early pregnancy

Azithromycin Penicillins Cephalosporins Retinoids Isotretinoin

B B B X

None None None Entire pregnancy Increased fetal loss in first trimester, microtia, external ear canal stenosis, cleft palate, hydrocephalus, cardiac outflow tract defects Craniofacial, cardiac, thymic, and central nervous system malformations Delayed sexual maturation of female rat fetuses and feminization of male rat fetuses in animal studies; risk to human fetus is only theoretical, as case reports show no adverse effects in human pregnancy Increased risk of miscarriage, micrognathia, developmental delays, craniosynostosis, small low-set ears, limb abnormalities, and growth retardation Not associated with a specific congenital malformation No specific birth defects, data on long-term outcomes lacking Potential for growth retardation and inhibition of endogenous corticosteroid production when used in high doses Increased risk of miscarriage and anomalies of distal limbs, heart, esophagus, kidney, external ear, and face Avoid overheating during therapy

Acitretin Diuretic/antiandrogenic Spironolactone

Entire pregnancy

After 8 wk

Antirheumatics/antimetabolites Methotrexate

Entire pregnancy

Hydroxychloroquine Immunosuppressants Cyclosporine Corticosteroids

None

C C

None Third trimester with high doses Entire pregnancy

Mycophenolate mofetil

Phototherapy Broadband ultraviolet B phototherapy Biologics Adalimumab Etanercept Infliximab Antihistamines Cetirizine Diphenhydramine Loratadine Chlorpheniramine Antifungals Terbinafine

First 28 d of pregnancy

B B B B B B B B

None None None None None None None None

Limited data Limited data Limited data Potential sedation of neonate in nursing mothers Potential sedation of neonate in nursing mothers Potential sedation of neonate in nursing mothers Potential sedation of neonate in nursing mothers Do not electively use to treat onychomycosis during pregnancy per manufacturer Continued

668 Tyler and Zirwas

J AM ACAD DERMATOL

APRIL 2013

Table III. Contd

Medication Pregnancy category High-risk period Risks/comments

Griseofulvin Ketoconazole Itraconazole Fluconazole Antiparasitic Ivermectin

C C C C C

Entire pregnancy Entire pregnancy None None None

Increased risk of skeletal and central nervous system anomalies and fetal loss Sexual ambiguity of a male fetus, can interfere with pregnancy implantation Lowest teratogenic potential of all imidazoles Single-dose use confirmed safe Teratogenic to animals in high doses

have not been observed in human beings.1 The differentiation of the urogenital tract does not occur until after 8 weeks, so any theoretical risk would occur after that point,1 but 2 case reports of 5 pregnancies where spironolactone was used by the mother showed no abnormalities in the 2 female and 3 male children.33,34 Psoriasis Psoriasis, a chronic inammatory skin condition, affects 2% to 3% of the population,35,36 and data show that 44% of patients with psoriasis were female and of reproductive age.17 It is expected, then, that all dermatologists will encounter pregnant patients and patients of childbearing age with psoriasis. Approximately 50% of women with psoriasis will improve during pregnancy, but it can worsen in up to 20%.1 Topical treatments are first-line therapy for psoriasis, but systemic treatments may be required for moderate to severe disease. Oral retinoids, such as acitretin, that are used to treat psoriasis cause craniofacial, cardiac, thymic, and central nervous system malformations and are contraindicated in pregnancy.16 Like all oral retinoids, acitretin is a category X medication. Methotrexate, a folic acid antagonist used to treat inammatory skin disorders such as psoriasis, is also used as an abortifacient for conditions such as ectopic pregnancy, so it is contraindicated in pregnancy. Aside from an increased risk of miscarriage, associated malformations include micrognathia, developmental delays, craniosynostosis, small low-set ears, limb abnormalities, and prenatal growth retardation.37,38 Cyclosporine, a category C medication used for moderate to severe psoriasis, acts as a selective immunosuppressant by inhibiting T lymphocytes.16 It has mainly been studied in pregnant organ transplant recipients, making it difficult to separate the effects of cyclosporine from those of other medications.16 No specific birth defect has been attributed to cyclosporine, but data on long-term outcomes are

lacking.4 For pregnant patients, its benefits outweigh any theoretical risks, and it appears to be safe for the fetus.1 Broadband ultraviolet B phototherapy is considered safe during pregnancy, with no adverse outcomes reported in studies.39,40 For extensive psoriasis during pregnancy, this appears to be the safest systemic therapy, but overheating during treatment should be avoided because of an increased risk of neural tube defects if hyperthermia occurs during neural tube formation in the first 28 days of gestation.1,2 Data are currently limited on biologic agents such as adalimumab, etanercept, and iniximab, but all are listed as pregnancy category B. Pregnancy registries have been established for these medications, but given the limited data, the benets of therapy should be carefully weighed against any unknown risk to the fetus.12 Currently, no specific congenital malformations have been attributed to any of the above medications when used at any time during the pregnancy. Atopic dermatitis For atopic dermatitis during pregnancy, topical medications should be prescribed initially, but the occasional use of systemic steroids may be considered in severe or refractory cases. Pregnancy category C, oral steroids appear to be safe when used in moderate doses and for the shortest duration possible.5 Some potential problems with high doses of systemic corticosteroid use during pregnancy include intrauterine growth retardation and inhibition of endogenous corticosteroid production.6,41-44 Some studies have shown an association between orofacial clefts and corticosteroid use in pregnancy, but a recent publication by Hviid and MolgaardNielsoen45 shows no such association. When faced with a patient with a severe atopic dermatitis flare, either systemic corticosteroids or cyclosporine would be acceptable choices, as neither is associated with an increase in congenital malformations when

J AM ACAD DERMATOL
VOLUME 68, NUMBER 4

Tyler and Zirwas 669

used in pregnancy for other conditions such as asthma and autoimmune disease.1 Mycophenolate mofetil, an immunosuppressive agent used to treat moderate to severe refractory atopic dermatitis, has been assigned a pregnancy category D because of an increased rate of spontaneous abortions and certain congenital malformations including anomalies of the distal limbs, heart, esophagus, and kidney as well as external ear and facial abnormalities such as cleft lip and palate.16 Mycophenolate mofetil should be avoided during pregnancy and in women who are not actively preventing pregnancy. For conditions such as atopic dermatitis, antihistamines may be used for itching. Most antihistamines, including cetirizine, diphenhydramine, loratadine, and chlorpheniramine are pregnancy category B and are safe to use.12 It is important to note that antihistamines should be avoided during lactation in nursing mothers if possible because of possible sedating effects on the neonate.12 Connective tissue disease For pregnant women with severe discoid lupus or systemic lupus erythematous, the systemic medication hydroxychloroquine is category C and has not been associated with a specic congenital malformation. Because stopping hydroxychloroquine can precipitate a lupus are, most experts recommend continuing therapy if it is currently in use when a patient becomes pregnant.1 When faced with a patient with cutaneous lupus who is not at risk for a systemic flare and who is either pregnant or trying for pregnancy, short-term oral steroids along with topical steroids may be a better treatment option because more data are available regarding corticosteroid use in pregnancy. Fungal and parasitic infections For fungal infections during pregnancy, oral antifungals pose greater risks than topical agents.4 That said, terbinafine is a category B medication because of a low risk for fetal harm in animal studies and is the systemic treatment of choice for a dermatophyte infection during pregnancy. The manufacturer does recommend not using oral terbinafine electively to treat onychomycosis during pregnancy.12 The other major antifungals, griseofulvin and the imidazoles, are all pregnancy category C. In animal studies, griseofulvin showed an increased risk of skeletal and central nervous system anomalies and of fetal loss.1,4 Certain studies indicate an increased risk for conjoined twins as well,1,12 so griseofulvin use during pregnancy is not recommended. Ketoconazole can inhibit androgen synthesis, increasing the risk of

sexual ambiguity of a male fetus.1 It can also impair progesterone secretion and interfere with early pregnancy and implantation,4 so it should not be used during pregnancy. The newer imidazoles itraconazole and fluconazole, both category C, have been the subject of large cohort studies that indicate neither is teratogenic.1 Some studies suggest that fluconazole should be avoided in prolonged high doses to avoid the risk of malformations, but multiple studies have confirmed the safety of a single oral dose, typically used by obstetricians to treat vaginal candidiasis.4,12 Itraconazole has the lowest teratogenic potential because it has minimal effect on the steroid hormones.12 Finally, because it is teratogenic to animals in high doses, the category C medication ivermectin should be avoided as a treatment for scabies in lieu of permethrin, a safer topical FDA category B medication.12

DERMATOLOGIC SURGERY DURING PREGNANCY

Most experts agree that nonemergent surgery during pregnancy be performed during the second trimester (weeks 13-24) or postpartum to avoid the possible risk of spontaneous abortion in the rst trimester or preterm labor in the third trimester.46 If possible, the patient should be placed in the left lateral position to avoid compression of the vena cava by the pregnant uterus, but positioning on the right side is an acceptable alternative to avoid supine positioning.46 Alcohol and chlorhexidine preparations for the surgical site are acceptable to use during pregnancy, but povidone-iodine absorption through mucous membranes has been associated with fetal hypothyroidism.47-49 and hexachlorophene has been reported to cause fetal central nervous system toxicity.47,48 Most dermatologic procedures can be performed using local anesthetics. Lidocaine and prilocaine are both category B medications, and multiple studies have shown no increased risk of adverse effects in the fetus.46 Local anesthetics do cross the placental barrier, but the only potential risk to the fetus would be in the case of injection of excessive amounts or inadvertent arterial injection.50 Risks to the fetus in that case would be central nervous system or cardiac toxicity.46 Local anesthetics such as mepivacaine and bupivacaine increase the risk of fetal bradycardia,51 so lidocaine and prilocaine would be the anesthetics of choice. Epinephrine is often added to lidocaine in small concentrations as a vasoconstrictor to reduce bleeding at the operative site. It is a category C medication because of decreased uterine blood ow with use during animal experiments.46 Considering the

670 Tyler and Zirwas

J AM ACAD DERMATOL

APRIL 2013

dilution and small amounts used during dermatologic procedures, potential risk is probably outweighed by the benefits of decreased bleeding during procedures, so epinephrine is considered safe when used judiciously.46 With regard to antibiotics and pain control, medications that are category A and B should be rst-line. Antibiotics were previously discussed in the section on systemic medications. For pain control, acetaminophen is category B and is rst-line. Opioid narcotic pain medications are all category C because of the risk of neonatal respiratory depression from high doses used near the time of delivery and the risk of neonatal withdrawal from chronic maternal use.12 If opioids are necessary for pain control, they should be used in the lowest dose and for the shortest possible duration to avoid fetal withdrawal.1 Also, pain medications including nonsteroidal antiinflammatory drugs should be avoided because of the risk of oligohydramnios and premature closure of the ductus arteriosis.1 Procedures such as cryotherapy, laser ablation, and application of trichloroacetic acid that involve local destruction of lesions without anesthetics are safe to perform during pregnancy.1 Podofilox, 5-fluorouracil cream, and interferon are not recommended during pregnancy, however, because of concerns regarding maternal and fetal safety.1

7. 8.

9. 10.

11. 12. 13.

14.

15.

16.

17. 18. 19.

SUMMARY
When choosing treatments for dermatologic conditions during pregnancy, a conservative approach is best. Topical medications are rst-line because they are minimally absorbed, but certain oral medications are safe to use when topical therapy fails or is not possible. Elective surgical procedures should be delayed until the postpartum period, but when necessary, dermatologic surgery during the second trimester using local anesthetics and proper patient positioning may be performed.
REFERENCES 1. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap LC, Wenstrom KD, editors. Williams obstetrics. 22nd ed. New York: McGraw-Hill; 2005. 2. Zip C. A practical guide to dermatological drug use in pregnancy. Skin Therapy Lett 2006;11:1-4. 3. Reed B. Dermatologic drugs, pregnancy, and lactation, a conservative guide. Arch Dermatol 1997;133:894-8. 4. Hale EK, Pomeranz MK. Dermatologic agents during pregnancy and lactation: an update and clinical review. Int J Dermatol 2002;41:197-203. 5. Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. 5th ed Baltimore: Williams & Wilkins; 1998. 6. Corticosteroids/corticotropin-glucocorticoid effects, systemic. In: US pharmacopeial dispensing information: drug Information

20.

21.

22.

23.

24.

25. 26.

27. 28.

for the Health Care Professional. Vol 1. Taunton (MA): Rand McNally; 1995. pp. 878-906. Copeland LJ, editor. Textbook of gynecology. 2nd ed. Philadelphia: WB Saunders Co; 2000. Wilhite CC, Sharma RP, Allen PV, Berry DL. Percutaneous retinoid absorption and embryotoxicity. J Invest Dermatol 1990;95:523-9. Camera G, Pregliasco P. Ear malformation in baby born to mother using tretinoin cream [letter]. Lancet 1992;339:68. Lipson AH, Collins F, Webster WS. Multiple congenital defects associated with maternal use of topical tretinoin. Lancet 1993; 341:1352-3. Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and congenital disorders. Lancet 1993;341:1181-2. Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin 2006;24:167-97. Morra P, Bartle WR, Walker SE, Lee SN, Bowles SK, Reeves RA. Serum concentrations of salicylic acid following topically applied salicylate derivatives. Ann Pharmacother 1996;30:935-40. Schwarb FP, Gabard B, Rufli T, Surber C. Percutaneous absorption of salicylic acid in man after topical administration of three different formulations. Dermatology 1999;198:44-51. Akhavan A, Bershad S. Topical acne drugs: review of clinical properties, systemic exposure, and safety. Am J Clin Dermatol 2003;4:473-92. Lam J, Polifka JE, Dohil MA. Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin disease. J Am Acad Dermatol 2008;59:295-315. Tauscher AE, Fleischer AB Jr, Phelps KC, Feldman SR. Psoriasis and pregnancy. J Cutan Med Surg 2002;6:561-70. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med 1998;338:1128-37. Cheetham TC, Wagner RA, Chiu G, Day JM, Yoshinaga MA, Wong L. A risk management program aimed at preventing fetal exposure to isotretinoin: retrospective cohort study. J Am Acad Dermatol 2006;55:442-8. Garcia-Bournissen F, Tsur L, Goldstein LH, Staroselsky A, Avner M, Asrar F, et al. Fetal exposure to isotretinoinean international problem. Reprod Toxicol 2008;25:124-8. Schwarz EB, Postlethwaite DA, Hung YY, Armstrong MA. Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women. Ann Intern Med 2007;147:370-6. Sladden MJ, Harman KE. What is the chance of a normal pregnancy in a woman whose fetus has been exposed to isotretinoin? Arch Dermatol 2007;143:1187-8. Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D. Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol 2007;63: 196-205. Goldsmith LA, Bolognia JL, Callen JP, Chen SC, Feldman SR, Lim HW, et al. American Academy of Dermatology consensus conference of safe and optimal use of isotretinoin: summary and recommendations. J Am Acad Dermatol 2004;50:900-6. Honein MA, Paulozzi LJ, Erickson JD. Continued occurrence of Accutane-exposed pregnancies. Teratology 2001;64:142-7. Schaefer C, Meister R, Weber-Schoendorfer C. Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy. Arch Gynecol Obstet 2010;281:221-7. Maloney ME, Stone SP. Isotretinoin and iPledge: a view of results. J Am Acad Dermatol 2001;65:418-9. Brinker A, Trontell A, Beitz J. Pregnancy and pregnancy rates in association with isotretinoin (Accutane). J Am Acad Dermatol 2002;47:798-9.

J AM ACAD DERMATOL
VOLUME 68, NUMBER 4

Tyler and Zirwas 671

29. Sasseville D. Dermatological therapy during pregnancy and lactation. In: Harahap M, Wallach RC, editors. Skin changes and disease in pregnancy. New York: Marcel Dekker; 1996. pp. 249-319. 30. Kallen BA, Otterblad Olausson P. Maternal drug use in early pregnancy and infant cardiovascular defect. Reprod Toxicol 2003;17:255-61. 31. Kallen BA, Otterblad Olausson P, Danielsson BR. Is erythromycin therapy teratogenic in humans? Reprod Toxicol 2005;20:209-14. 32. Newman MD, Bowe WP, Heughebaert C, Shalita AR. Therapeutic considerations for severe nodular acne. Am J Clin Dermatol 2011;12:7-14. 33. Groves TD, Corenblum B. Spironolactone therapy during human pregnancy. Am J Obstet Gynecol 1995;172:1655-6. 34. Rigo J Jr, Glaz E, Papp Z. Low or high doses of spironolactone for treatment of maternal Bartters syndrome. Am J Obstet Gynecol 1996;174:297. 35. Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 2005;141:1537-41. 36. Brandrup F, Green A. The prevalence of psoriasis in Denmark. Acta Derm Venereol 1981;61:344-6. 37. Warkany J. Aminopterin and methotrexate: folic acid deficiency. Teratology 1978;17:353-8. 38. Lloyd ME, Carr M, McElhatton P, Hall GM, Hughes RA. The effects of methotrexate on pregnancy, fertility and lactation. QJM 1999;92:551-63. 39. Stern RS, Lange R. Outcomes of pregnancies among women and partners of men with a history of exposure to methoxsalen photochemotherapy (PUVA) for the treatment of psoriasis. Arch Dermatol 1991;127:347-50.

40. Gunnarskog JG, Kallen AJ, Lindelof BG, Sigurgeirsson B. Psoralen photochemotherapy (PUVA) and pregnancy. Arch Dermatol 1993;129:320-3. 41. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton (MA): Publishing Sciences Group; 1977. pp. 389-91. 42. Warrell DW, Taylor R. Outcome for the fetus of mothers receiving prednisolone during pregnancy. Lancet 1968;1: 117-8. 43. Fine LG. Systemic lupus erythematous in pregnancy. Ann Intern Med 1981;94:667-77. 44. Lewis JH, Weingold AB, Committee on FDA-Related Matters, American College of Gastroenterology. The use of gastrointestinal drugs during pregnancy and lactation. Am J Gastroenterol 1985;80:912-23. 45. Hviid A, Molgaard-Nielsoen D. Corticosteroid use during pregnancy and the risk of orofacial clefts. CMAJ 2011;183: 796-804. 46. Sweeney SM, Maloney ME. Pregnancy and dermatologic surgery. Dermatol Clin 2006;24:205-14. 47. Gormley DE. Cutaneous surgery and the pregnant patient. J Am Acad Dermatol 1990;23:269-79. 48. Richards KA, Stasko T. Dermatologic surgery and the pregnant patient. Dermatol Surg 2002;29:248-56. 49. Bachrach LK, Burrow GN, Gare DJ. Maternal-fetal absorption of povidone-iodine. J Pediatr 1984;104:158-9. 50. Fein H, Vidimos AT. Patient evaluation, informed consent, preoperative assessment and care. In: Robinson JK, Hanke CW, Sengelmann RD, Siegel DM, editors. Surgery of the skin: procedural dermatology. Philadelphia: Elsevier; 2005. pp. 67-76. 51. Moore PA. Selecting drugs for the pregnant patient. J Am Dent Assoc 1998;129:1281-6.