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Dermatological medications and local therapeutics
In this chapter, the most important dermatological medications as well as other frequently used topical therapeutics will be discussed. More extensive information on individual medications can be found under the substance headings in other chapters. Anti-infectives are discussed in Chapter 2.6 .
2.17.1
Typical skin changes during pregnancy
The adaptation of the woman during pregnancy leads to typical morphological and functional changes in the skin. These are completely normal and do not require treatment. Among them are:
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Pigmentation : Particularly striking is the appearance of a spotty hyperpigmentation of the face (melasma) which usually disappears spontaneously after birth. This is intensified by exposure to UV light (i.e. to direct sunlight) and can be minimized by using a sun block. Pigmented areas like the nipples and the areola, the area around the navel (linea alba), the armpits, and the anogenital regions may get darker in pregnant women. Moles may also become darker in some women. In general, sensitivity to light is increased during pregnancy.
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Striae : During the second half of pregnancy, striae distensae appear frequently on the stomach, hips, thighs and also on the breasts. As body size increases, these become broader and more plentiful. They begin as reddish purple lines and with time, they become white atrophic (cigarette paper like wrinkled) scars. They are more frequently seen in young women and in women who are overweight and have large babies; there is probably a genetic relationship. There is no known effective medical prophylaxis. Daily massage of the skin with a simple moisturizer or olive oil may be tried and also the control of excess weight gain may partly help to prevent the development of stretch marks ( ).
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Fibroma : Soft fibromata appear more frequently especially in the neck and axillary regions.
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Blood vessel changes : Circulation in the skin is increased. The skin feels warmer, and the vasomotor excitability of the vessels in the face increases. This leads to quick blushing and blanching and to increased dermographism. In addition, the veins in the breast and stomach skin are much more visible and varicosities in the legs and the vulva as well as hemorrhoids may appear.
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Skin glands, hair and nails : Especially in early pregnancy, the secretion of the sebaceous glands can increase significantly. Existing acne frequently improves. On the other hand, an acute pregnancy acne ( acne gravidarum ) can occur from the third month forward, which disappears during the postpartum period. The growth of the nails is generally enhanced during pregnancy, and more hair goes into the resting phase. This causes diminished shedding of the hair and is perceived as thickening of the hair. Three months after delivery the hair cycle normalizes producing temporarily more loss of hair in many women ( postpartum effluvium ). This is called telogen effluvium. This process is usually completed 6 to 12 months after delivery. Thereafter, the hair will usually be the same as before pregnancy. Treatment is not required.
Topically applied substances are better absorbed during pregnancy. This applies especially to skin that has been altered by inflammation and open wounds and may lead to the exposure of the fetus to the ingredients.
2.17.2
Antiseptics and disinfectants
Disinfectants should have a strong bactericidal or bacteriostatic action, on one hand, but good local tolerance by the skin, mucosa and wounds on the other hand. In addition, they should not lead to toxic effects if absorbed.
Alcohol
No toxic effects have been observed, as yet, from topical use of alcohols during pregnancy. In practice only ethanol and isopropyl alcohol (isopropanol) are of importance.
Recommendation
Alcohol derivatives are not dangerous and can be used as disinfectants during pregnancy.
Benzoyl peroxide
Benzoyl peroxide is used, in particular, for external treatment of acne. About 5% is absorbed ( ). To some extent, it is converted to benzoic acid in the skin. Simultaneous topical therapy with retinoids increases the absorption. Benzoyl peroxide is also used in the food and plastics industries. There are insufficient epidemiological data for a risk assessment. Despite the broad use, there are no indications of any teratogenic effects.
Recommendation
Benzoyl peroxide may be used for acne treatment in pregnant women on a limited basis (i.e. the face).
Povidone iodine
When using povidone iodine as a local disinfectant on intact skin, on wounds and on the mucosa, as well as in body cavities, iodine transfer to the fetus must be assumed. This can lead to functional disturbances of the fetal thyroid. A vaginal douche during labor can lead to a temporary TSH increase in the newborn – a sign of a transient hypothyroidism ( ), but also to effects on the maternal thyroid metabolism and maternal iodine excretion ( ). A study of 42 mother–child pairs found significantly increased iodine excretion in the urine of both mother and child when povidone iodine was used as disinfectant before Caesarean section, but the TSH values of the children were not different compared with a control group disinfected with alcoholic solutions ( ). In a retrospective comparative study of children with birth defects and healthy children, there were no indications of teratogenic effects after vaginal use during pregnancy ( ). However, an undisturbed thyroid status is necessary for the differentiation of the central nervous system. Therefore, even slight imbalances should be avoided.
Recommendation
Iodine-containing disinfectants may only be used during pregnancy on small areas for a few days. Body cavities should not be cleansed with iodine-containing solutions. However, in the light of current knowledge, its use is not connected with any irreversible damage, and it is not clear what specific skin preparation may be most efficient for preventing post-caesarean wound and surgical site infection ( ).
Phenol derivatives
Phenol derivatives are used primarily in over-the-counter preparations for rinsing the mouth, disinfecting the skin, and treating perianal infections. Solutions of phenol derivatives, such as cresol and thymol as well as chlorinated phenol derivatives are viewed as relatively safe during pregnancy. They should not be used in a concentration stronger than 2% and should only be used on intact skin. With higher concentrations, incremental absorption must be assumed.
Chlorhexidine is appropriate for pregnant women to disinfect the skin and mucosa. In a study of 2,500 mother–child pairs, however, following disinfection of the vagina with chlorhexidine, no superiority in the maternal and child postpartum course was observed compared to a placebo ( ). Daily use of chlorhexidine mouthwash for the treatment of periodontal disease was associated with a reduction of preterm birth ( ).
By contrast, caution should be exercised during pregnancy with the neurotoxic phenol derivative, hexachlorophene, because, when larger areas are treated with concentrations of more than 3%, resorptive poisoning, with central nervous system symptoms, has been observed in treated patients. In some animal experiments, hexachlorophene has been shown to be teratogenic. In many publications over the last decades, workplace contact with hexachlorophene has been controversially discussed with respect to fetotoxic effects. An older study involving 3,000 pregnant women who were occupationally exposed did not find anything remarkable ( ). A further retrospective study postulated a connection between mental retardation and occupational exposure in the last trimester of pregnancy ( ).
Recommendation
Hexachlorophene should be avoided during pregnancy. However, accidental use requires no action. The other phenol derivatives such as, for instance, chlorhexidine, may be used by pregnant women for appropriate indications for disinfection of the skin and mucosa.
Mercury compounds
Mercury can be substantially absorbed after external use and is a potential developmental toxin ( ).
Recommendation
Mercury-containing disinfectants are contraindicated during pregnancy. However, their (accidental) use does not require any action ( Chapter 1.15 ).
Other antiseptics
Quinoline sulfate has shown mutagenic properties experimentally. Clioquinol is one of the iodine-containing antiseptics. Additional antiseptics are dequalinium salts, hexetidine for throat or vaginal use, gentian violet or crystal violet, pyoktanin, ethacridine and hydrogen peroxide.
There is evidence of carcinogenic properties and contradictory data on teratogenicity for gentian violet in animal studies. Hydrogen peroxide is naturally developed from bacteria of the vaginal flora. None of these substances has been systematically studied during pregnancy, but there have also been no serious indications of teratogenicity in human with any of these substances.
Recommendation
Quinoline should be avoided. Small areas and brief use of the other antiseptic substances mentioned are unobjectionable for appropriate indications during pregnancy, but their use should be critically considered.
2.17.3
Glucocorticoids and non-steroid antiphlogistics
With long-term use of glucocorticoids ( Chapter 2.15 ) and the non-steroid antiphlogistics or application to larger and, above all, inflamed skin areas, absorption and transfer to the fetus must be assumed. Topically used glucocorticoids are divided into four groups according to their potency. Among the mildly potent are hydrocortisone acetate, prednisolone and dexamethasone. Among the moderately potent are clobetasone , flumetasone , fluocinolone and prednicarbate . Among the most potent are amcinonide , fluocinonide , fluticasone , hydrocortisone17-butyrate and mometasone and a very potent topical steroid is, for example, clobetasol propionate .
Among 363 children whose mothers were treated with topical glucocorticoids during pregnancy (170 of them in the first trimester), neither an increased risk of malformations nor a difference in the birth parameters was found compared to an untreated control group ( ). Also in a review, considering the heterogeneous and, to some extent, insufficient data, there was no indication found of teratogenic effects or effects on prematurity. At most, an association with low birthweight was discussed in connection with very potent corticosteroids ( ).
There are no systematic studies on the use in pregnancy of bufexamac , levomenol and benzydamine , and there is also no indication of teratogenic action. The non-steroid antiphlogistic bufexamac was removed from the market in 2010 because of its (allergic) side-effects. Non-steroid antiphlogistic substances have also not, as yet, been shown to be teratogenic with systemic use but due to their prostaglandin antagonistic effect they could be fetotoxic in the last trimester ( Chapter 2.1 ).
Recommendation
There is no objection to occasional use of topical glucocorticoids or topical antiphlogistics in limited areas. Very potent steroids such as clobetasol propionate should be avoided during pregnancy. However, their use may be favored to systemic steroids if required because of disease severity.
2.17.4
Astringents
On mucosa and in wounds, astringents lead, through protein precipitation of the surface layers, to sealing and shriveling of tissue. They are used for local treatment of inflamed mucosa and wounds. Two groups are used therapeutically – tannin-containing preparations ( Chapter 2.5 ) and dilute solutions of metal salts, e.g. aluminum aceticum and aluminum acetate-tartrate-solution DAB) or zinc salts .
Recommendation
There is no contraindication for therapy with astringents during pregnancy as their absorption is unlikely.
2.17.5
Antipruritics and essential oils
Antiallergics and local anesthetics
Antiallergics and local anesthetics which are used as antipruritics for topical therapy are, as a rule, harmless during pregnancy ( Chapter 2.2 ).
Polidocanol
Macrogol lauryl ether (polidocanol) is used externally against itching. In addition, it is used intravenously to obliterate varicose veins, for lesions of the oral mucosa, in vaginal spermicides and in cosmetics ( ). Further, it is used in wound therapeutics, in combination with benzethonium and urea. No teratogenic effects have been published for this widely used substance to date neither in animal nor human studies. However, systematic studies are lacking.
Recommendation
Polidocanol may also be used by pregnant women against itching.
Camphor and menthol
A small amount of camphor applied to the skin has a cooling and local anesthetic effect; while rubbing it in vigorously enhances the blood flow of the skin. Because of these effects, camphor and other essential oils are included in a large number of hyperemia-causing dermatological products ( Chapter 2.19 ).
Menthol is used topically for itching.
No teratogenic action has, as yet, been published in either animal or human studies.
Recommendation
Camphor and other essential oils may be used topically during pregnancy.
2.17.6
Coal tar and slate oil preparations
Coal tar preparations, which are used primarily for the treatment of eczema, in particular atopic eczema and psoriasis, have not been suspected of having a teratogenic effect. A retrospective study of 23 exposed women revealed nothing remarkable ( ). Experimentally, coal tar products have, to some extent, shown mutagenic or carcinogenic properties. However, coal tar has been used as a dermatological treatment for decades and has not, as yet, shown any indication of this kind in humans ( ).
The slate oil extracts , ammonium bitumen sulfonate and sodium bitumen sulfonate are used topically for both (sub)acute and chronically inflamed dermatitis as well as other skin conditions. There are no systematic studies on prenatal toxicity, but also no indications of replicable teratogenic effects in humans.
Recommendation
Ideally, coal tar preparations should not be used during pregnancy. However, (accidental) use does not require any action. Topically limited use of slate oil extracts is acceptable.
2.17.7
Local immunomodulators as therapy for atopic eczema
Tacrolimus and pimecrolimus
Tacrolimus and pimecrolimus are licensed for topical treatment of atopic eczema. There are no systematic studies on topical use during pregnancy but there is considerable experience on the systemic use of tacrolimus as an immune suppressant after transplants, which do not indicate a teratogenic risk ( ).
There is insufficient experience on the use of pimecrolimus during pregnancy to assess teratogenic risk.
Recommendation
Tacrolimus may be used on small areas of the skin during pregnancy for strict indications. Due to limited experience, therapy with pimecrolimus should be avoided.
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