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Treatment of Acne in the Pregnant Patient

Jonette E. Keri, M.D., Ph.D.Associate Professor of Dermatology, University of

Miami, Miller School of Medicine Chief, Dermatology Service, Miami VA Hospital

Disclosures

• Hoffman-La Roche

Outline

• Why treat during this time• Medications and Therapies that can be used• Plan for your practice• What if…

Acne

• Acne is a common problem• Post-adolescent acne is more common in women• Acne is commonly seen in pregnant women• Causes significant psychological stress

How common is acne in pregnancy?

• Difficult to find consistent numbers• Many references say common

How Common is Acne in Pregnancy?

• 400 women surveyed

• 75% Better after delivery• 13% No change• 12% Got worse

• Nussbaum, R. Clin Derm 2006; 24:133-141

How do we treat these patients?

• Get their acne as good as you can before they start to try to conceive

• Encourage them to get in the best health they can be prior to trying to conceive

• Discuss their expectations with them

How do we treat these patients?

• Topicals first• Systemics second line

Topical Medications

• Over the counter or prescription?

• Most times by the time the patient comes to see you they have tried the over the counter medications AND they are looking for something more

• This is an important time to discuss expectations

Pregnancy Categories

• I discuss the old Food and Drug Administration (FDA) pregnancy categories

• I do this during the expectation discussion

Risk Classifications

• United States Food and Drug Administration (FDA)• New guidelines approved but still to be implemented for older drugs

(drugs approved prior to June 30, 2015)

• There are other rating systems• Australian • Swedish• German

Old FDA pregnancy categories - simplified

• A = Safety established in human studies• B = Presumed safety based on animal studies• C = Uncertain safety; no human studies and animal studies show

adverse effect• D= Unsafe - evidence of risk that may in certain clinic circumstances

be justifiable• X = Highly unsafe – risk of use outweighs any possible benefit

New FDA Labeling• New Pregnancy and Lactation Labeling Rule (PLLR)• The new rule for newly approved prescription

medications• Staggered phase-in for older prescription drugs

• Danish MJ, Murase JE. The new US Food and Drug Administration pregnancy and lactation labeling rules: Their impact on clinical practice. J Am Acad Dermatol. 2015 Aug;73(2):310-1.

New FDA labeling

• Pregnancy• Lactation (instead of Breast-feeding)• Females and Males of Reproductive Potential – NEW

• Danish MJ, Murase JE. The new US Food and Drug Administration pregnancy and lactation labeling rules: Their impact on clinical practice. J Am Acad Dermatol. 2015 Aug;73(2):310-1.

Topical Medications for Acne

Topical medications Category B versus Category C• Generally use category B medications• Topicals

• Azeleic Acid• Clindamycin• Erythromycin

• Metronidazole

How about the topical category C medications?• Benzoyl Peroxide• Salicylic Acid• Dapsone (topically)

Benzoyl Peroxide

• Benzoyl Peroxide• Most feel safe for use• Systemic Absorption is minimal• Over the counter preparations have no pregnancy warning• Benzoyl Peroxide is metabolized to benzoic acid (a food additive) in the skin*

*reviewed in: Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy J Am Acad Dermatol. 2014 Mar;70(3):401.e1-14; quiz 415.

Salicylic Acid

• Salicylic acid • Category C• Likely safe• Systemic absorption minimal over small areas• Low dose aspirin used for the treatment of pre-eclampsia in women*• Key point – concentration should be low and over limited body surface areas

• *Trivedi, N.A., J. Postgrad Med. 2011:57(2):91-5.

Dapsone - topical

• Dapsone • Category C• Likely safe but studies are lacking• Oral dapsone is used to treat dermatitis herpetiformis in pregnancy

• *Tuffanelli, DL. Ach Dermatol 1982;118(11):876.

Topical Retinoids

• Tretinoin – Category C• One case report of otocerebral anomalies*

• Adapalene – Category C• One case report of anophthalmia and agenesis of the optic chiasma**

• Tazarotene – Category X• Contraindicated in pregnancy• *Selcert, D. Otocerebral anomalies associated with topical tretinoin use. Brain Dev. 2000;22(4):218-20.• **Autret E. et al. Lancet 1997;350(9074):339.

Category N (Not Classified) Topical

• Glycolic Acid – best example and most well received

Glycolic Acid

• Glycolic Acid• Thought to be safe as only a minimal amount is absorbed

• Category - N• Up to 27% absorbed into the skin depending on pH, concentration and time*

(in vitro)• Rats have some adverse reproductive effects, but the doses were much larger

than used in humans, (300-600mg/kg/d orally)**

*Kraeling, MK, et al. In vitro percutaneous absorption of the alpha hydroxy acids in human skin J Soc Cosmet Chem 1997; 48:187-97.

** Munley, SM, etal. Developmental toxicity study of glycolic acid in rats. Drugs Chem Toxicol 1999;22(4):569-82

Systemic Medications

Systemic Medications – Category A

• Zinc supplements • Generally recommended 30-200mg a day • Gastrointestinal disturbances• 75mg/day of elemental zinc show no harm to the fetus*• Watch “overdose” – can lead to hypocupremia

*Dreno, B. Ann Dermatol Venereol. 2008;135(1):27-33.

Systemic Medications – Category B

• Cephalexin• Cefadroxil ** Severe acne patient• Amoxicillin ** Severe rosacea patient• Azithromycin• Erythromycin

• AVOID Erythromycin Estolate – can be associated with hepatotoxicity in 10-15% of pregnant patients with prolonged use*

• Unable to order/prescribe Estolate• Rare cases of pyloric stenosis in infants with other forms of erythromycin*Hale, E.K., Int J Dermatol 2002; 41:197-203**Reviewed in: Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I.

Pregnancy J Am Acad Dermatol. 2014 Mar;70(3):401.e1-14; quiz 415.

Systemic Medications - Category C

• Prednisone when the patient has severe acne/scarring • Work with the Ob/Gyn • Dosing?

• 0.5mg/kg or less in most cases• Weeks to months – duration• Combine with systemic antibiotic• Bone and Gastrointestinal prophylaxis• Work with Ob/Gyn

So in practice how do we decide?

• Discuss expectations with the patient• First grade the acne – your grading system

• Mild• Moderate• Severe – Look for scarring

• If acne is moderated to severe consider systemic medications• Document discussions

Regimen

• Mild non-abrasive washes • Washes with Glycolic Acid • Topical Azeleic acid • Topical Clindamycin• Oral Antibiotics

• Physical sunscreen

Over the Counter Controversies

• Benzoyl Peroxide or not?• Salicylic Acid as a wash or not?

• Depends on the patient• Many patients are very conservative

• Over the counter washes listed above are safe

What do I do?

• Talk to the OB/GYN• Don’t be afraid to ask for help• Consider prednisone in the severe patient

Is ThereAnything New?

Maybe not new, but not discussed in the past with respect to acne

• nbUVB• Watch folate levels

Narrow band UVB for acne

• Pregnant patients• Safe

• Zeichner, J. Narrow band UVB therapy for the treatment of acne vulgaris in pregnancy. Arch Derm 2011 147: (5); 537.

Folate reduction associated with nbUVB

• Studies using narrowband UVB showed mixed results, potentially explained by dose-dependent degradation of folate;

• Exposure >40 J/cm2 cumulatively and >2 J/cm2 per treatment were associated with 19%-27% decreases in serum folate levels, while lower doses did not affect folate levels.

• There is no evidence of decreased folate levels after UVA exposure.• A lot of variability• Zhang M, Goyert G, Lim HW. Folate and phototherapy: What should we inform our patients? J Am Acad Dermatol. 2017 Nov;77(5):958-964.

Folate supplementation in nbUVB patients

Recommend all women of childbearing age on phototherapy take 0.8 mg/day of folate supplements, as suggested by current guidelines for women of childbearing age, to reduce the risk of neural tube defects in unplanned pregnancy.

• Zhang M, Goyert G, Lim HW. Folate and phototherapy: What should we inform our patients? J Am Acad Dermatol. 2017 Nov;77(5):958-964.

Anything else new?

Case report using oral metronidazole along with prednisone for significant acne in pregnancy

• 30 year old woman• 14 weeks gestation had significant acne • treated with prednisone and then a variety of oral antibiotics

including amoxicillin, erythromycin and cephalexin• Initially got better but then got more acne, presumed steroid acne

over the trunk and her prednisone dose was lowered and her erythromycin dose was increased

• Patient improved some and then was switched to metronidazole (?) 250mg twice daily and did well, but this was at 28 weeks

• Awan SZ, Lu J. Management of severe acne during pregnancy: A case report and review of the literature. Int J Womens Dermatol. 2017 Jul 13;3(3):145-150.

Why do I bring up the gestational age?

• Recent review in Canada of data in Quebec Canada from (1998-2009).• Looked at spontaneous abortions (<20 weeks) in patients taking antibiotics• Found macrolides (excluding erythromycin), quinolones, tetracyclines,

sulfonamides and metronidazole during early pregnancy were associated with an increased risk of spontaneous abortion.

• However, residual confounding by severity of infection cannot be ruled out.

• They found cephalexin, amoxicillin, erythromycin to be safe• Muanda FT, Sheehy O, Berard A. Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ. 2017 May 1; 189(17): E625–E633.

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Cosmetic procedures - peeling

• Glycolic acid peels: Relatively safe, limited dermal penetration.

• Lactic acid peels: Reports of safe use for gestational acne, limited dermal penetration.

• (Salicylic acid peels: Pregnancy category C, significant dermal penetration, limit use to small areas of coverage.) – Caution

• Reviewed in: Trivedi MK1,2, Kroumpouzos G3,4, Murase JE1,5 A review of the safety of cosmetic procedures during pregnancy and lactation. Int J Womens Dermatol. 2017 Feb 27;3(1):6-10.

What if.....??The patient had an exposure….

Topical Retinoid Exposure

• The objective:• Does exposure to topical retinoids lead to an increase in the risk of

adverse pregnancy outcome

• Searched Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases from inception to 4 December 2014

• Kaplan YC, et al. Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis. Br J Dermatol. 2015 Nov;173(5):1132-41

Topical Retinoid Exposure• Meta-analysis• 654 pregnant women• 1375 unexposed control pregnant women• No significant differences among the studies evaluated

• Did not detect significant increases in:• congenital malformations • spontaneous abortions • stillbirth• elective termination of pregnancy • low birthweight • prematurity

• Kaplan YC, et al. Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis. Br J Dermatol. 2015 Nov;173(5):1132-41

What does this tell us?

• Use this result primarily to reassure women who may have had an inadvertent exposure.

• But…. there is not enough evidence (statistical power) to justify the use of topical retinoids during pregnancy.

• Kaplan YC, et al. Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis. Br J Dermatol. 2015 Nov;173(5):1132-41

Sulfonamide exposure

• Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed

• The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations

• Hansen C, Andrade S, Freiman H et al. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8.

Sulfonamide Exposure• METHODS: • Mother-infant pairs were selected from a cohort of

1.2 million live-born deliveries (2001-2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program.

• Hansen C, Andrade S, Freiman H et al. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8.

Sulfonamide Exposure• METHODS: • Mothers with first-trimester trimethoprim-

sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to:

• a primary comparison group (mothers exposed to penicillins and/or cephalosporins)

• a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication)

• Hansen C, Andrade S, Freiman H et al. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8.

Sulfonamide Exposure• Overall, cardiovascular defects (1.52%) were the most

common and cleft lip/palate (0.10%) the least common that were evaluated.

• TMP-SUL exposure was NOT associated with statistically significant elevated risks for:

• Cardiovascular defects• Cleft lip/palate• Clubfoot• Urinary system defects

Hansen C, Andrade S, Freiman H et al. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8.

Sulfonamide Exposure

• CONCLUSIONS:

• First-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials

• Hansen C, Andrade S, Freiman H et al. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8.

After pregnancy, then what?

•LACTATION

PEARL:Ask the Pediatrician• American Academy of Pediatrics (AAP) has guidelines

AAP guidelines for medications prescribed to lactating mothers • Medications divided into 3 groups

1) Generally compatible with breastfeeding2) May be of concern3) Used with concern

Conclusions

• Define expectations• Document discussions• Don’t be afraid to treat• Don’t be afraid to ask for help

• OB/GYN• Pediatrician • Other Dermatologists

Treating Acne During Pregnancy and Lactation

• Editorial• Significant psychological burden during these times (pregnant and

post-partum periods)• New FDA labeling may help after some initial “getting used to…”• All pregnancies have a background risk of loss, birth defect, or

adverse event

• Baldwin HE. Treating acne during pregnancy and lactation. Cutis. 2015 Jul;96(1):11-2

Thank you!