PEER REVIEWED FEATURE 2 CPD POINTS Managing the skin in pregnancy Part 1. Pregnancy-related skin concerns NINA WINES BSc, MB BS, DRANZCOG, FACD

Pregnancy-associated skin concerns range from regnant women with skin concerns usually present first common benign conditions such as stretch marks to their GPs, who play a major role in their diagnosis, and skin pigmentation to rarer specific dermatoses management and timely referral when required. Skin of pregnancy, some of which are associated with concerns in pregnant women can be broadly divided Pinto benign conditions related to the pregnancy, potentially more maternal and fetal risk. Management requires knowledge of which treatments are safe and serious pregnancy-specific skin rashes and pre-existing or practical while a woman is pregnant or incident skin diseases that require management during preg- nancy. Postpartum, women may also present to their GP with breastfeeding. skin concerns. Management of these conditions requires knowl- edge of which treatments are safe and practical while a woman is pregnant or breastfeeding. KEY POINTS This is the first article in a short series that discusses the • Benign pregnancy-related skin concerns are common and management of skin conditions during pregnancy and are mostly treatable either during the pregnancy or, if they breastfeeding. This article focuses on the management of persist, after the birth. pregnancy-related skin concerns, including benign conditions • Specific dermatoses of pregnancy such as intrahepatic such as stretch marks and pigmentation and more severe cholestasis of pregnancy and pemphigoid gestationis are pregnancy- specific skin rashes, some of which pose fetal and associated with maternal and fetal risk. maternal risk. It also summarises the safety during pregnancy • Topical medications are usually the first-line choice for and breastfeeding of topical and systemic medications used to treatment of most skin conditions during pregnancy treat skin conditions. Future articles in the series will discuss (estimated percutaneous absorption 4 to 25%). the management of pre-existing skin diseases, such as acne, • Selected systemic medications may be used after consideration of their safety and the high-risk periods psoriasis and atopic dermatitis, and skin cancer during preg- during pregnancy. nancy, as well as common postpartum skin problems. • Referral to a dermatologist is recommended when the diagnosis is unclear or the condition does not respond to treatment or is associated with potential fetal or maternal MedicineToday 2016; 17(7): 25-34 risk. Dr Wines is Principal Consultant Dermatologist at Northern Sydney JPC-PROD/SHUTTERSTOCK

© Dermatology; and a Visiting Medical Officer at The Skin Hospital, Sydney, NSW.

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when used on a small surface area.2 Sun protection is important as all hyper- pigmenting conditions are e xacerbated by sun exposure. GPs are involved in the early treatment of melasma. Daily sun avoidance and sun protection should be recommended, as well as avoidance of rubbing, abrasive treatments or scrubs, friction, perfumed products or any product that stings, as Figures 1a and b. Stretch marks. a (left). Early stretch marks (red stage). These respond well to vascular laser therapy. b (right). Old stretch marks leave white or silvery lines. These irritation can encourage pigmentation. respond well to fractionated laser therapy. The importance of avoiding waxing affected areas should be explained as waxing promotes inflammation and Benign pregnancy-related skin After pregnancy, the best time to treat worsens melasma. Topical azelaic acid is concerns stretch marks is when they are still red. safe to use during pregnancy and has a Stretch marks Once the lesions are white or silver, frac- gradual lightening effect.2 Superficial peels Stretch marks occur when the skin is tional laser therapy can be effective. Referral containing low concentrations of salicylic subjected to continuous and progressive to a dermatologist with experience in laser acid or glycolic acid are likely to be safe stretching. They are more frequent in management can be helpful for manage- during pregnancy.2 Referral to an experi- women with large babies in comparison ment of both early and old stretch marks. enced dermatologist may be beneficial if with their size, multiple pregnancies or There is evidence that topical retinoids may this resource is not available. obesity. Common locations for stretch also help.1 However, in practice I have found Women should be reassured that marks in pregnant women include the them only partially effective. melasma is not permanent and in most abdomen, breasts and thighs. At their cases fades gradually over six to 12 months onset the skin initially becomes pink, Skin pigmentation after the birth. To hasten postpartum occasionally itchy and then purple. Over Darkening of the skin around the nipples, resolution, an additional bleaching agent time the stretch marks become white or genitalia and in a line from the umbilicus can be c ommenced. Many formulas are silvery (Figures 1a and b). to the pubis (linea nigra) is common and reported to be effective. In my clinical Unfortunately, there are no truly effec- normal in pregnancy, especially in women practice, I have found a compounded tive ways of preventing stretch marks in with dark skin (Figure 2). Scars may also formula containing hydroquinone 2 to 4%, those who are vulnerable to them. There darken. tretinoin 0.5%, hydrocortisone 1% in aque- is no evidence that topical agents or Melasma (also known as chloasma) is a ous delivers the best results. Hydroquinone moisturising oils prevent them, but oils distressing form of facial pigmentation that and tretinoin are considered moderately may relieve the itch that can sometimes affects many pregnant women (Figure 3). safe in lactation on a small surface area.2 be present. Daily massage with olive oil Conventional lightening products such as I advise using a pea-sized amount with a possibly helps. Control of excessive weight hydroquinone and tretinoin are contra- moisturiser initially every alternate night, gain may assist in preventing their indicated in pregnancy, although they are gradually working up to daily application development. likely to be safe during breastfeeding to help avoid irritation. Avoid using hydro- quinone in high concentrations for long periods as this may result in permanent bluish discolouration of the skin. Laser therapy has been reported to be helpful for melasma, but in practice I find this delivers disappointing results and sometimes worsens the condition. In addition, there is little point advising patients to make a large investment in treat- ment if they plan to have more children, as Figure 2. Linea nigra. Figure 3. Melasma. melasma will probably recur in subsequent pregnancies.

26 MedicineToday JULY 2016, VOLUME 17, NUMBER 7 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2016. Skin tags Skin tags (fibroma pendulum) are small skin growths that appear in areas of fric- tion, such as under the arms and breasts. Most resolve spontaneously after the pregnancy. If they persist and bother the patient, I offer a variety of treatments, such as liquid nitrogen spray, snip excision, electrodesiccation or shave excision. The choice of treatment depends on the size of the skin tag and the thickness of its base. If the tag and its base are tiny then snip Figures 4a and b. A pyogenic granuloma in a pregnant patient (a, left) before curettage and excision using spring scissors with or with- (b, right) two weeks after curettage. out local a naesthesia is helpful and easy. (Snip excision of a tiny skin tag typically screen investigating for anaemia, iron defi- referral to a dermatologist experienced in causes less pain than local anaesthesia.) If ciency and thyroid abnormality is benefi- laser therapy may be helpful. Patients should the base is larger, I tend to infiltrate a local cial. Reassurance that the hair should be be instructed not to wax or pluck for six anaesthetic and then use forceps to assist back to normal by the baby’s first birthday weeks before laser therapy as the shaft of shave excision. Cryotherapy is quick but is important. Simple measures, such as the hair bulb is needed as a target for the can leave residual surrounding post- using a thickening shampoo, avoiding laser. Patients should shave in the lead up inflammatory pig menta tion or erythema, aggressive treatments to the hair and avoid- to laser. This can seem foreign to patients, and multiple treatments are sometimes ing tight hair styling may be helpful. In especially on the face. Multiple laser treat- required. addition, microfibre treatments are safe, ments (approximately four depending on relatively inexpensive and effective in giving the location of the hair) are required at six Hair and pregnancy the appearance of thicker hair. A healthy to eight-week intervals. Darker, thicker hair Hair thinning balanced diet and stress reduction strategies responds best to laser therapy, whereas Scalp hair continuously goes through may also prevent ongoing shedding. white or blonde hair does not respond. If growth, resting and shedding cycles. If hair loss continues after 12 months the patient cannot access laser therapy then Throughout pregnancy more hair follicles postpartum then referral to a dermatol- waxing and electrolysis are options during stay in the growth and resting phase, so that ogist is warranted for investigation and breastfeeding. hair shedding is reduced and the hair feels consideration of systemic therapy. thicker. Postpartum, the hair cycle returns Spider veins to normal, and approximately three months Hirsutism Spider veins are common during preg- after the birth hair shedding is temporarily Pregnant women may experience excessive nancy and are found predominantly on increased. This phenomenon is termed hair growth in locations such as the lip, the chest, face and neck and occasionally ‘telogen effluvium gravidarum’. chin, cheeks and suprapubic area. This is on the arms and abdomen. They often have This hair loss can cause great distress more common in women who have a central point surrounded by radiating to women and GPs are usually the first to pre- existing abundant body hair or very tiny dilated vessels or telangiectasia. When deal with the emotional and physical dark hair. Fine hair may disappear after the spider vein is compressed, it is emptied effects. The increased shedding is usually pregnancy, but thicker hairs can remain.3 of blood, and when the pressure is released, complete by six to 12 months after delivery, During pregnancy, waxing or plucking it refills. About 75% of spider veins fade by and hair returns to its pre-pregnancy state.3 may help the woman feel better and more the seventh week postpartum.3 However, However, some women feel that their hair confident. they can persist, recur and enlarge in the is not as thick as before the pregnancy and Postpartum, I find that the most effective same site in subsequent pregnancies. If they may also report a change in hair texture, treatment for hirsutism with more perma- are cosmetically concerning then postpar- curliness or even colour. It is important to nent results is laser therapy. This is safe tum management is warranted. Spider acknowledge the distress that hair loss can during breastfeeding. Laser hair reduction naevi are extremely responsive to therapy cause women, especially as it is established has become much more affordable and with a 595 nm vascular laser. In experi- that around 25% of scalp hair must be lost readily available. As women vulnerable to enced hands, they may resolve after one before identifiable thinning occurs.2 hirsutism often have darker skin, the type treatment, but occasionally a second treat- If hair loss is severe then a systemic of laser needs to be carefully chosen, and ment may be required.

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Pyogenic granulomas granuloma.4 However, its safety during The gold standard for managing super- Pyogenic granulomas are reactive vascular pregnancy and lactation is not certain. ficial veins and small surface thread vessels lesions that present as rapidly growing red is sclerotherapy. Some patients can be man- lumps at sites of local trauma (Figure 4a). Leg veins aged nonsurgically with endovascular laser They are annoying and uncomfortable The growing uterus places pressure on the and radiofrequency occlusion laser therapy. and often bleed. They gradually increase large veins behind it, which may lead to Laser therapy is not as effective as sclero- in size until the birth and then undergo ankle swelling and in some patients to the therapy for leg vein problems but can be involution. formation of varicose and thread veins and used as an alternative and may also help in If these granulomas are a problem and a skin rash from gravitational eczema. ‘tidying up’ tiny superficial thread veins treatment is considered necessary then Treatments to reduce these problems dur- that are too small to inject with a sclerosant. my favoured approach during pregnancy ing pregnancy include leg elevation, sup- Multiple treatments are required at six to is serial curettage and electrodesiccation portive stockings and exercise. eight-week intervals. Postinflammatory after local anaesthesia, with care to remove After pregnancy, many women are con- pigmentation can occur. the proliferating dermal base to prevent cerned by the appearance of their leg veins. recurrence (Figure 4b). Histopathological However, unless a woman has extreme Specific dermatoses of confirmation of the diagnosis is reassuring symptoms, it is sensible to defer treatment pregnancy to exclude rare differential diagnoses. If of leg veins until she has completed her The specific dermatoses of pregnancy are the lesion recurs then curettage or excision family as the lesions are likely to worsen or a group of rare rashes unique to pregnancy. can be repeated or the lesion can be mon- recur in subsequent pregnancies. If leg veins Despite their rarity, it is essential for GPs itored until the birth. Topical imiquimod are causing symptoms or cosmetic con- to be familiar with these dermatoses as 5% (category B1) has also been reported cerns then referral for imaging of the super- some can be associated with maternal and to be effective in management of pyogenic ficial and deep venous system is useful. fetal risk.

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proves difficult to control. In severe cases TABLE 1. RECENT CLASSIFICATION OF SPECIFIC DERMATOSES OF PREGNANCY5 systemic corticosteroids or antihistamines New classification Previous synonym(s) may be required. UVB phototherapy is used for resistant cases. Atopic eruption of Prurigo of pregnancy pregnancy Prurigo gestationis Polymorphic eruption of pregnancy Polymorphic eruption of pregnancy (PEP; Papular dermatitis of pregnancy formerly known as pruritic urticarial Pruritic folliculitis of pregnancy papules and plaques of pregnancy or PUPPPs) is a benign, self-limiting itchy Eczema in pregnancy inflammatory disorder affecting women Polymorphic eruption of Pruritic urticarial papules and plaques of pregnancy who are primigravidas in the third t rimester pregnancy (PUPPPs) of pregnancy or immediately in the post- 7,8 Toxic erythema of pregnancy partum period. The cause is not known but it has been suggested that it could be due Pemphigoid gestationis Herpes gestationis to a combination of hormones and an Intrahepatic cholestasis Cholestasis of pregnancy immune response to stretched skin.7,9 It is of pregnancy not associated with fetal risk. Pruritus/prurigo gravidarum PEP usually begins as an itchy rash in Obstetric cholestasis the stretch marks on the abdomen and tends to spare the umbilicus. It may resem- Jaundice of pregnancy ble hives or appear as a red rash that can sometimes be scaly (Figure 6). The appear- Because of their rarity and the clinical 80%, they occur for the first time during ance changes as the disease progresses and overlap between these dermatoses, there pregnancy or after a long period of remis- becomes polymorphic; it may appear as is ongoing discussion about their classifi- sion.5 Two-thirds of patients with AEP circular hive-like lesions, red patches and cation. A recent simplified classification develop red scaly itchy patches in sites sometimes as small blisters. system for the specific dermatoses of preg- typically affected by atopic eczema (termed Referral to a dermatologist may be nancy is shown in Table 1.5 They comprise eczematous or E-type AEP). The other needed to confirm the diagnosis and atopic eruption of pregnancy, polymorphic third of patients have tiny red raised spots exclude other pregnancy-specific derma- eruption of pregnancy, intrahepatic (1 to 2 mm) or slightly larger raised skin toses. The histological appearance is not cholestasis of pregnancy and pemphigoid lumps (at times with scratch marks) on the especially characteristic but biopsy may be gestationis. Their characteristics are sum- abdomen, back and limbs, termed prurigo helpful to exclude pemphigoid gestationis, marised in Table 2. or P-type AEP (Figures 5a and b). Patients which may be associated with fetal risk. At a practical level, it is most likely that often have an elevated serum IgE level, a Treatment is symptomatic. As the itch pregnant women with a specific derma- positive allergy test result for allergens and can be unbearable, topical moisturisers, tosis of pregnancy will present with an a family history of atopic diseases.6 corticosteroids (sometimes with wet itch. A conceptual approach to the causes AEP has no effect on the fetus and usu- dressings) and oral antihistamines are of itch in pregnancy is shown in the Flow- ally disappears after delivery. Treatment needed. Rarely, a short burst of oral chart. If a woman is suspected to have a depends on severity, but moistu risers, top- corticosteroid is needed. specific dermatosis of pregnancy then ical moderately potent corticosteroids with PEP resolves spontaneously within referral to a dermatologist can be helpful short bursts of a potent corticosteroid, and weeks after the birth, with no scarring. It for diagnosis. oral anti histamines (chlorpheniramine, is rare for it to recur during subsequent diphenhydramine, loratadine or cetirizine) pregnancies. Atopic eruption of pregnancy are usually enough. Secondary infection Atopic eruption of pregnancy (AEP) is the can develop from scratching and can be Pemphigoid gestationis most common specific dermatosis of preg- managed with antibiotics (see below for Pemphigoid gestationis is a rare, itchy nancy. It usually presents before the third safe drugs during pregnancy). autoimmune blistering eruption that trimester. In 20% of affected patients, the Referral to a dermatologist may be usually presents in the second or third atopic skin changes represent an exacer- needed if wet dressings or light therapy are trimester. However, patients presenting in bation of pre-existing atopy.5 In the other considered necessary or the condition the first trimester or postpartum have been

30 MedicineToday JULY 2016, VOLUME 17, NUMBER 7 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2016. reported.5,10,11 The cause is not fully under- resulting in a rash, itch and eventual blister it starts in the periumbilical area and then stood but it is believed that antib odies formation. spreads to the rest of the abdomen and produced to the placenta form circulating Clinically, pemphigoid gestationis sometimes the thighs, palms and soles. It immune complexes, which in turn react presents as itchy lesions or annular plaques is intensely itchy, interfering with sleep, and with the basement membrane of the skin that usually form blisters. Characteristically continues throughout the pregnancy. After

TABLE 2. CHARACTERISTICS OF THE SPECIFIC DERMATOSES OF PREGNANCY

Condition Onset Features Maternal risk Fetal risk Recurrence in Treatment subsequent pregnancies

Atopic eruption Before third 20% have personal No No Yes Moisturisers of pregnancy trimester or family history of Oral anti- (previously atopy (eczema, histamines prurigo of asthma, hayfever) Mid-potency pregnancy) 80% have first corticosteroids episode of eczema Antibiotics if in pregnancy infected Ig E elevated (20 to Light treatment 70%)

Polymorphic Third trimester Itchy rash starting No No Rare Oral anti- eruption of in in stretch marks on histamine pregnancy primigravidas abdomen Mid-potency (PEP; 10 to 15% of Sparing of corticosteroids previously cases occur umbilicus and Systemic known as immediately usually face corticosteroids if PUPPPs) postpartum Biopsy to rule out extreme pemphigoid gestationis

Pemphigoid Second, third Itchy lumps and Long-term Small for Yes Oral anti- gestationis trimesters blisters, initially increased gestational histamine 25% of cases involving umbilicus, risk of age Topical occur then generalising thyroid Prematurity corticosteroids disease immediately Specific biopsy Oral (Graves’ postpartum findings corticosteroids disease) May flare (subepidermal postpartum blister with linear with menses IgG and C3 along or oral basement contraceptives membrane)

Intrahepatic Late second and Severe itch Early Prematurity Yes Oral cholestasis of third trimesters Can start on palms induction of Meconium- antihistamines pregnancy and soles, then labour stained Urodeoxycholic generalise Intra-partum amniotic fluid acid if severe Total serum bile haem- Respiratory Early delivery if acids raised orrhage distress over 36/40 Long-term Intrauterine weeks’ gestation risk of death Vitamin K hepatobiliary Vitamin K disease deficiency and coagulopathy in mother and newborn

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A CONCEPTUAL APPROACH TO THE CAUSES OF ITCH IN PREGNANT WOMEN

Pregnant woman presents with itch

No rash Rash

Intrahepatic cholestasis of Related to pregnancy Unrelated to pregnancy pregnancy • Skin shows scratches only • Increased serum bile acid level • After third trimester • Before third trimester Other (e.g. scabies, • Affects mainly • Affects mainly trunk drug rash) abdomen and limbs

Periumbilical involvement Periumbilical sparing

Atopic eruption of pregnancy Pemphigoid gestationis Polymorphic eruption • 20% have • Linear C3 deposition along of pregnancy history of atopy basement membrane • Onset in stretch • Increased IgE • Subepidermal blisters marks level

Fetal risk No fetal risk the birth, the course is variable; it may immunosuppressant such as cyclosporin Pemphigoid gestationis can be associated resolve immediately, flare in the postnatal A, dapsone or azathioprine. with other autoimmune diseases in the period or continue for months, flaring with GPs need to be aware of the potential mother, such as Graves’ disease, Hashimoto’s each menstrual period.11 It may also worsen fetal risks in women with pemphigoid ges- thyroiditis and pernicious anaemia.11 GPs with the use of oral contraceptives. Most tationis. There is a small risk of premature may need to monitor for the adverse effects cases eventually remit spontaneously in birth and small-for-gestational-age babies, of topical or systemic corticosteroids and for the weeks or months after the birth. Pem- and 10% of newborns may develop a mild associated autoimmune diseases. Oral pred- phigoid gestationis tends to recur in sub- urticarial or hive-like rash or blisters.5 nisone is considered safe during lactation. sequent pregnancies. Referral to a dermatologist may be required for confirmation of the diagnosis and management. Skin biopsy specimens show classic histopathological features (subepidermal blister formation), and direct immunofluorescence shows linear depositions of IgG and C3 complement along the basement membrane.10,11 Women with mild disease may be treated with a moisturiser and a potent topical cortico- steroid, but most require a systemic corti- costeroid 0.5 mg/kg. Those with very severe Figures 5a and b. Atopic eruption of pregnancy in a woman at 13 weeks’ gestation. or persistent disease may require a systemic

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absolutely contraindicated throughout the 1. AUSTRALIAN CATEGORISING SYSTEM FOR PRESCRIBING entire pregnancy and should be ceased MEDICINES DURING PREGNANCY before conception (to be discussed in more detail in a future article of this series). A = Safety established in human The safety of many skin medications studies during pregnancy and breastfeeding is B = Human data minimal (B1 – studies sum marised in the Appendix (included in animals show no problems; B2 – in the website version of this article, studies in animals lacking, but available www.medicinetoday.com.au).2,13 data show no increased occurrence of Figure 6. Polymorphic eruption of pregnancy. fetal damage; B3 – studies in animals have shown risk and significance of this Conclusion in humans is uncertain) Women who are pregnant or breastfeeding Intrahepatic cholestasis of C = Drugs which have caused or may be may develop a variety of skin conditions, pregnancy suspected of causing harmful effects ranging from benign conditions associated Intrahepatic cholestasis of pregnancy (ICP) D = Unsafe – evidence of risk that may with the pregnancy to pregnancy-specific is characterised by severe itch with no rash in certain clinical circumstances be skin rashes that may present maternal or but rather secondary signs of scratching. justified fetal risks. GPs play a pivotal role in the diag- It begins in the third trimester of preg- X = Contraindicated nosis, management and timely referral when nancy, often starting on the palms and soles required of pregnant women with skin con- and spreading to the rest of the body. It is itch. Ursodeoxycholic acid can be used and ditions. A confident understanding of skin diagnosed by the finding of elevated serum has been shown to improve pregnancy medications and their safety ratings assists bile acid and aminotransferase levels. It is outcomes.12 Phototherapy is sometimes in the management of skin conditions dur- a significant condition to be aware of as it used. Cholestyramine, antihistamines and ing pregnancy and breastfeeding. MT is associated with fetal risks, the most com- oral corticosteroids have also been tried as mon being premature birth (in 20 to 60% treatments but are not supported by current References of cases), intrapartum fetal distress (20 to evidence and can have side effects. Early A list of references is included in the website version 30%) and stillbirth (1 to 2%).7 In women delivery may be required. of this article (www.medicinetoday.com.au). with severe or prolonged ICP, cholestasis can cause vitamin K deficiency and coag- Skin medications in pregnancy COMPETING INTERESTS: None. ulopathy in both the woman and the new- and breastfeeding born.5 These pregnancies should be For most skin conditions, topical medica- carefully monitored by an obstetrician. tions are the safest choice and the first-line ONLINE CPD JOURNAL PROGRAM ICP usually resolves one to two days treatment. Percutanous absorption of top- after the birth but in some cases can persist ical medications is estimated to be 4 to Which pregnancy-related skin for one to two weeks.7 Up to 50 to 70% of 25%.10 Selected systemic treatments may conditions can be associated with cases recur during subsequent pregnancies be used after consideration of their safety fetal risk? and with the use of oral contraceptives. ratings and the high-risk periods during Treatment of ICP aims to lower the level pregnancy (Box 1 and Table 3). Isotreti- of serum bile acid and to alleviate the severe noin, acitretin and methotrexate are

TABLE 3. PERIODS OF FETAL DEVELOPMENT13

Development stage Time after conception

Preimplantation 0 to 2 weeks

Embryonic/organogenesis* Until 12 weeks OBE.COM D A Fetal From 13 weeks Review your knowledge of this topic and earn CPD points by taking part in MedicineToday’s Online CPD Journal Peripartum Last month of gestation OTO/STOCK. F Program. Log in to I

* Most important time to avoid teratogenic medications. Brain, teeth and bones remain susceptible after 9 weeks DNO R

www.medicinetoday.com.au/cpd I of fetal development. Note that home pregnancy tests may not give a positive result until 5 weeks after conception. B ©

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Managing the skin in pregnancy Part 1. Pregnancy-related skin concerns NINA WINES BSc, MB BS, DRANZCOG, FACD

References

1. Kang SM, Kim KJ, Griffiths CE, et al. Topical tretinoin (retinoic acid) risk and therapy. Ann Dermatol 2011; 23: 265-275. improves early stretch marks. Arch Dermatol 1996; 132: 519-526. 9. Rudolph CM, Al-Fares S, Vaughan-Jones SA, Mullegger M, Kerl M, Black M. 2. Murase J, Heller M, Butler D. Safety of dermatological medications in Polymorphic eruption of pregnancy: clinicopathology and potential pregnancy and lactation. Part 1 Pregnancy. J Am Acad Dermatol 2014; trigger factors in 181 patients. Br J Dermatol 2006; 154: 54-60. 401: e1-e13. 10. Lipozencic J, Ljubojevic S, Bukvic-Mokos Z. Pemphigoid gestationis. Clin 3. Ingber A. Obstetric dermatology. A practical guide. Springer-Verlag; 2009. Dermatol 2012; 30: 51-55. 4. Tritton SM, Smith S, Wong LC, Zagarella S, Fisher G. Pyogenic granuloma 11. I ntong LR, Murrell D. Pemphigoid gestationis: pathogenesis and clinical in ten children treated with topical imiquimod. Paediatr Dermatol 2009; features. Dermatol Clin 2011; 29: 447-452. 26: 269-272. 12. Kondrackien J, Beuers U, Kupcinskas L. Efficacy and safety of 5. Ambros-Rudolph CM, Müllegger RR, Vaughan-Jones SA, Kerl H, Black MM. ursodeoxycholic acid versus cholestyramine in intra-hepatic cholestasis of The specific dermatoses of pregnancy revisited and reclassified: results of a pregnancy. Gastroenterology 2005; 129: 894-901. retrospective two-center study on 505 pregnant patients. J Am Acad Dermatol 13. A ustralian Government Department of Health Therapeutic Goods 2006; 54: 395-404. Administration. Prescribing medicines in pregnancy database. Available online 6. Sävervall C, Sand FL, Thomsen SF. Dermatological diseases associated with at: https://www.tga.gov.au/prescribing-medicines-pregnancy-database pregnancy: pemphigoid gestationis, polymorphic eruption of pregnancy, (accessed July 2016). intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. 14. McCormack WM, George H, Donner A, et al. Hepatotoxicity of erythromycin Dermatol Res Pract 2015; 2015: 979635. estolate during pregnancy. Antimicrob Agents Chemother 1977; 12: 630-635. 7. Roth M. Pregnancy dermatoses: diagnosis, management, and 15. Lund M, Pasternak B, Davidsen RB, et al. Use of macrolides in mother and controversies. Am J Clin Dermatol 2011; 12: 25-41. child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort 8. Ambros-Rudolph CM. Dermatoses of pregnancy – clues to diagnosis, fetal study. BMJ 2014; 348: g1908.

Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2016. MedicineToday 2016; 17(7): 25-34 Managing the skin in pregnancy Part 1. Pregnancy-related skin concerns NINA WINES BSc, MB BS, DRANZCOG, FACD Appendix

TGA RECOMMENDATIONS ON USE OF SKIN MEDICATIONS DURING PREGNANCY AND LACTATION2,13-15

Category Medication Pregnancy* Lactation

Topical anti- Topical A, except mometasone (B3) and Can apply to nipple; apply after inflammatories corticosteroids methylprednisolone aceponate (C) breastfeeding; ointments preferred Topical corticosteroids are safe in pregnancy over creams (avoid large amounts of high potency corticosteroids for prolonged periods)

Calcipotriol B1 <100 g/week; use on small area only Safe; use on <20% body surface area; do not apply to chest area to prevent infant consumption

Calcipotriol B1 Avoid to prevent infant consumption 50 µg/g + betamethasone 500 µg/g

Pimecrolimus B3; do not use in pregnancy Not known if secreted in milk; do not apply to nipple as oral absorption high

Desonide B3 Caution in lactation

Dithranol B2 Avoid

Topical Clindamycin A Not recommended antibiotics Erythromycin A Caution

Azelaic acid B1 Safe

Metronidazole B2 Safe

Mupirocin B1 Safe

Benzyl benzoate B2 Safe

Antibiotics Amoxicillin A Detected in breast milk

Azithromycin B1 No data; use if no alternative

Cephalosporins A, B1–2 Safe

Erythromycin (not A (erythromycin estolate may cause maternal Excreted in breast milk; linked to erythromycin hepatotoxicity in second trimester14) increased probability of pyloric estolate) stenosis in infants15

Topical Nystatin A Caution antifungals Clotrimazole A Safe

Miconazole A Safe

Terbinafine B1 Safe

Selenium sulfide Not categorised; local application acceptable Safe; cases of lactate suppression reported

continued on next page

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Category Medication Pregnancy* Lactation

Systemic Griseofulvin B3; avoid Avoid antifungals Ketoconazole B3; avoid Avoid

Itraconazole B3; avoid Avoid

Terbinafine B1; avoid; postpone treatment of onychomycosis Avoid

Antipruritics – Chlorpheniramine A (preferred over second generation antipruritics; Safe; observe for sedation first generation† avoid in first trimester)

Diphenhydramine A Safe; observe for sedation

Antipruritics – Loratadine B1 (first-line second-generation antihistamine) Safe; observe for sedation, second tachycardia, dry mouth generation Cetirizine B2 (second-line to loratadine) Safe; observe for sedation

Fexofenadine B2 (use alternatives as minimal data) Safe; observe for sedation

Systemic Aciclovir B3 (first line) Caution; use only if benefits outweigh antivirals risks Valciclovir B3 (second line)

Famciclovir B1 (third line)

Systemic anti- Corticosteroids A; short courses (around 2 weeks) are safe; Safe; penetrates breast milk poorly; inflammatories doses >10 mg/day for over 2 weeks during first small doses, short periods; if dose 12 weeks of pregnancy have been associated >20 mg then use prednisolone rather with oral/palate clefts; longer courses of oral than prednisone; defer feeding for corticosteroids may affect growth rate; monitor 4 hours after dose if possible maternal blood pressure and urine for diabetes

Dapsone B2; associated with hyperbilirubinaemia and Excreted in breast milk in substantial haemolytic anaemia; reserved for specific cases amounts

Ciclosporin C; avoid unless severe disease; risk of fetal Avoid or monitor infant levels growth restriction or prematurity and maternal hypertension

Biologics TNF alpha inhibitors Can be used with caution for severe recalcitrant Insufficient data to address safety psoriasis, but it is uncertain whether routine use is advisable

Wart treatments Trichloroacetic acid Not categorised; second line after destructive Probably safe treatment

Imiquimod B1 (minimal data, no teratogenicity) Not recommended, no data

Salicylic acid Not categorised; use on small areas for short Likely safe time is acceptable

Scabies + lice Permethrin B2; first line for scabies Safe treatments Pyrethrin B2; second line Safe

Malathion B2

Precipitated sulfur Likely safe Likely safe

Ivermectin B3; use in compelling circumstances only If topical permethrin fails then ivermectin can be used, but discontinue breastfeeding

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ii Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2016. APPENDIX. TGA RECOMMENDATIONS ON USE OF SKIN MEDICATIONS DURING PREGNANCY AND LACTATION2,13 continued

Category Medication Pregnancy* Lactation

Acne treatments Tretinoin (topical) D (large studies indicate it is safe, but most Likely safe; unlikely absorbed in large experts do not recommend it) quantities

Benzoyl peroxide Unclassified; may be used on small areas; Likely safe metabolised to benzoic acid, a food additive

Hair, cosmetic Minoxidil (topical) C Safe treatments Eflornithine B3 Caution

Spironolactone B3; avoid male feminisation Possible suppression of lactation

Hydroquinone Avoid; uncategorised Probably safe

Botulinum toxin A B3; unlikely to cross placenta as high molecular Not recommended weight, but cosmetic use not recommended

Cosmetic Lignocaine A Safe surgery products Chlorhexidine A

Adrenaline A Excreted in breast milk (epinephrine)

EMLA (lignocaine A Safe 2.5% and prilocaine 2.5%)

* Category according to the Australian categorising system for prescribing medicines during pregnancy: A = safety established in human studies; B = human data minimal (B1 – studies in animals show no problems; B2 – studies in animals lacking, but available data show no increased occurrence of fetal damage; B3 – studies in animals have shown risk and significance of this in humans is uncertain); C = drugs which have caused or may be suspected of causing harmful effects; D = unsafe – evidence of risk that may in certain clinical circumstances be justified; X = contraindicated. † If a first-generation antipruritic is too sedating then a second-generation antipruritic can be considered. Antihistamines can be associated with an increased risk of retrolental fibroplasia in premature infants if used within two weeks of delivery.

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