Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 18/03/2015
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Wolfgang Jurecka
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Skin changes during pregnancy may range from normal (physiologic) changes that occur with almost all pregnancies through common or pre-existing skin diseases that are not associated with, but are influenced by, the pregnancy, to eruptions that appear to be specifically associated with pregnancy and the puerperium. This group of well-defined dermatoses of pregnancy has recently been reclassified and include: pruritic urticarial papules and plaques of pregnancy (PUPPP), pemphigoid gestationis, pruritus gravidarum (cholestasis of pregnancy), and atopic eruption of pregnancy (AEP).
Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a common, intensely pruritic dermatosis that usually begins in the third trimester of the first pregnancy, but may be delayed until a few days postpartum. It occasionally recurs, albeit less severely, in subsequent pregnancies.
Most women who have PUPPP are relieved to learn that the condition is not serious, that all should be well with them and their baby, and that the rash will disappear at or within a few days after delivery. However, treatment is usually demanded to provide relief from the intense itching. The skin lesions may closely resemble the very early (urticarial) stage of pemphigoid gestationis. Direct and/or indirect immunofluorescence microscopy of perilesional skin or serum should be performed if pemphigoid gestationis is suspected. All similar eruptions that occur in non-pregnant women may also occur in pregnancy and should not be confused with those dermatoses that are pregnancy specific. Thus erythema multiforme, drug eruptions, contact dermatitis, urticaria, and insect bites should be considered.
In women with localized disease, frequent (several times daily) application of mid-strength topical corticosteroids provides symptomatic relief after a few days in almost all cases. Ointments containing substances such as betamethasone, mometasone, or methylprednisolone can be regarded as safe during pregnancy. New lesions usually stop appearing within 2 or 3 days, and the frequency of applications can be tapered. As the pregnancy continues many patients require therapy only once a day, or can even stop treatment before delivery. Topical antipruritic preparations are normally not useful. Oral H1 antihistamines (first generation: chlorpheniramine, cyproheptadine, tripelennamine; second generation: loratidine, levocetrizine) may offer some benefit in severely pruritic patients at bedtime. In more widespread or generalized cases and those that do not respond adequately to topical corticosteroids, a systemic corticosteroid treatment may need to be considered. Oral methylprednisolone 20–40 mg daily or its equivalent for 5 days, tapered over the following 2 weeks is very effective. For systemic treatment during pregnancy, prednisone, prednisolone, and methylprednisolone are regarded as safer than betamethasone, dexamethasone, cortisone, and hydrocortisone, which may be associated with some risk of malformation.
One striking clinical feature of PUPPP is its onset in the third trimester in association with severe striae. It usually affects first pregnancies, in which striae are more common. There have been conflicting reports questioning whether PUPPP is associated with fetal weight and maternal weight gain, resulting in excessive abdominal distension. Some patients have therefore been delivered early, with the expectation that this will terminate the PUPPP. This has appeared to be the outcome in some cases, but the resolution of PUPPP is not necessarily related to delivery.
Biopsy for direct immunofluorescence
Serum for indirect immunofluorescence
A comparative study of toxic erythema of pregnancy and herpes gestationis.
Holmes RC, Black MM, Dann J, James DC, Bhogal B. Br J Dermatol 1982; 106: 499–510.
A comparison of 30 patients with PUPPP and 24 with pemphigoid gestationis showed a broad overlap in the morphology of their skin lesions, which may lead to difficulties in the diagnosis of early (urticarial) pemphigoid gestationis. Immunofluorescence is consistently positive in pemphigoid gestationis.
A comparative histopathological study of polymorphic eruption of pregnancy and herpes gestationis.
Holmes RC, Jurecka W, Black MM. Clin Exp Dermatol 1983; 8: 523–9.
There was a broad overlap in the histopathologic changes of skin lesions in patients with PUPPP and pemphigoid gestationis, allowing a clear distinction only when pemphigoid gestationis appears with typical subepidermal blisters.
An immunoelectron microscopy study of the relationship between herpes gestationis and polymorphic eruption of pregnancy.
Jurecka W, Holmes RC, Black MM, McKee P, Das AK, Bhogal B. Br J Dermatol 1983; 108: 147–51.
This highly sensitive method showed that PUPPP and pemphigoid gestationis are clearly separate entities.
Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients.
Rudolph CM, Al-Fares S, Vaughan-Jones SA, Müllegger RR, Kerl H, Black MM. Br J Dermatol 2006; 154: 54–60.
Although pruritic urticarial papules and plaques are the main morphological features at disease onset, more than half of the patients later develop polymorphous features, including erythema, vesicles, and targetoid and eczematous lesions, favoring the term polymorphic eruption of pregnancy (PEP). Multiple-gestation pregnancies and excessive maternal weight gain, but not fetal weight and gender, were significantly associated with PEP.
Pruritic urticarial papules and plaques of pregnancy. Clinical experience in twenty-five patients.
Yancey KB, Hall RP, Lawley TJ. J Am Acad Dermatol 1984; 10: 473–80.
Of 25 patients, 22 were successfully treated with frequent applications of high-potency topical corticosteroids, providing relief from the pruritus and controlling the eruption.
Pruritic urticarial papules and plaques of pregnancy (PUPPP). A clinicopathologic study.
Callen JP, Hanno R. J Am Acad Dermatol 1981; 5: 401–5.
In 15 cases PUPPP cleared prior to delivery (five cases), within 1 week of delivery (nine cases), and at 6 weeks postpartum (one case). Treatment was performed with various potent topical corticosteroids and antihistamines, namely diphenhydramine, in all cases except one.
Dermatoses of pregnancy: clues to diagnosis, fetal risk and therapy.
Ambros-Rudolph CM. Ann Dermatol 2011; 23: 265–75.
Recent review of the pregnancy dermatoses.
Evidence-based (S3) guideline on topical corticosteroids in pregnancy.
Chi CC, Kirtschig G, Aberer W, Gabbud JP, Lipozenčić J, Kárpáti S, et al. Br J Dermatol 2011; 165: 943–52.
A significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids was found. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery, and fetal death were found.
A review of antihistamines used during pregnancy.
Kar S, Krishnan A, Preetha K, Monhankar A. J Pharmacol Pharmacother 2012; 3: 105–8.
Control studies are available for certain first generation drugs regarding their safety in pregnancy, but the newer agents require further studies to be declared safer in pregnancy. A few drugs are comparatively safer to use in pregnancy than others. Every drug used in pregnancy carries a risk for teratogenicity and careful risk/benefit assessment should be done before prescribing them.
Systemic corticosteroids were efficacious in three patients with extensive disease.
Prurigo of late pregnancy.
Cooper AJ, Fryer JA. Aust J Dermatol 1980; 21: 79–84.
Four of five patients were treated successfully with oral prednisone (20 mg daily, tapering by 5 mg every 2 days).
Pruritic urticarial papules and plaques of pregnancy (polymorphic eruption of pregnancy): two unusual cases.
Vaughan Jones SA, Dunnill MG, Black MM. Br J Dermatol 1996; 135: 102–5.
One of two cases required a short course of systemic corticosteroids.
Although only a limited numbers of cases are reported in the literature describing treatment of severe cases of PUPPP with oral corticosteroids, nowadays it is generally accepted that this treatment is effective and safe if prednisone, prednisolone, or methylprednisolone are chosen. However, larger series and prospective studies are lacking.
Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study.
Cur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Reprod Toxicol 2004; 18: 93–101.
This study, which was powered to find a 2.5-fold increase in teratogenicity, supports that glucocorticosteroids do not represent a major teratogenic risk in humans.
Severe polymorphic eruption of pregnancy occurring in twin pregnancies.
Bunker CB, Erskine K, Rustin MHA, Gilkes JJH. Clin Exp Dermatol 1990; 15: 228–30.
Early delivery was performed to terminate the PUPPP.
Pruritic urticarial papules and plaques of pregnancy: a severe case requiring early delivery for relief of symptoms.
Baltrani VP, Baltrani VS. J Am Acad Dermatol 1992; 26: 266–7.
Early delivery led to relief of symptoms.
Pruritic urticarial papules and plaques of pregnancy.
Carruthers A. J Am Acad Dermatol 1993; 29: 125.
Resolution of PUPPP is unrelated to delivery; therefore early delivery should not be performed to treat PUPPP.
Treating an uncomfortable but non-serious dermatosis by such invasive methods with a potential risk for both mother and newborn is, in the author’s view, not indicated and should not be performed, especially as other adequate treatments are available.
Pemphigoid gestationis (herpes gestationis) is a rare, intensely itchy, urticarial or polymorphic or vesiculobullous eruption. It affects approximately 1 in 60 000 pregnancies and usually appears in the second or third trimester, but it may also be associated with hydatidiform mole or choriocarcinoma. The term pemphigoid gestationis is preferable because this condition shows many clinical and immunologic similarities with bullous pemphigoid and has no relationship to herpes virus infection.
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