Pregnancy dermatoses

Published on 18/03/2015 by admin

Filed under Dermatology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 2588 times

Pregnancy dermatoses

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

image

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

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.

Management strategy

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.

Specific Investigations

First-line therapies

image Topical corticosteroids B
image Antihistamines C

Second-line therapies

image Systemic corticosteroids D

Third-line therapies

image Early delivery E

Pemphigoid gestationis

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.

Management strategy

Although pemphigoid gestationis is a rare disorder, correct diagnosis and optimal management are essential. It occurs only in the presence of paternally derived tissue (fetus, hydatidiform mole, or choriocarcinoma). Once it has manifested, its course may be significantly modulated by changes in estrogen and progesterone levels. Exacerbations may occur postpartum, with oral contraceptives, and during the menstrual cycle post partum, and is commonly more severe in subsequent pregnancies. Circulating autoantibodies are directed against the same target antigens as in bullous pemphigoid, more commonly against BP180 than BP230 antigen. The autoantibodies react with the basement membrane of amnion placenta, resulting in the findings of immune activation in the placenta and evidence of placental insufficiency. Thus skin biopsies for dermatohistopathology and direct immunofluorescence, and serum for indirect immunofluorescence investigations or ELISA to confirm the diagnosis and to differentiate non-bullous pemphigoid gestationis from PUPPP are recommended. This is especially important because most patients with pemphigoid gestationis need treatment with systemic corticosteroids, at least for a while, and are therefore at risk of side effects from this treatment. Most cases resolve within a few months postpartum, with just a few urticarial eruptions during the year after delivery. However, some cases have been reported with recurrences more than 10 years postpartum. Even more important is the fetal prognosis. The current view is that pemphigoid gestationis is associated with premature delivery and a risk of low birth weight. Thus pregnancies of mothers with pemphigoid gestationis should be carefully followed in special units.

The goal of treatment is to suppress blister formation and to give the patients relief from the intense pruritus. In mild cases of pemphigoid gestationis, topical potent corticosteroids combined with a systemic antihistamine may be sufficient. First-generation antihistamines are favored over second-generation antihistamines. Chlorpheniramine, cyproheptadine, tripelennamine, loratidine, and levocetrizine may be used (see also discussion above about the use of antihistamines in PUPPP). However, most patients require systemic corticosteroid treatment during the course of their disease. Initially doses of prednisolone or its equivalent in the range of 20–40 mg daily may be tried, and then adjusted depending on the response. In severe cases 1 mg/kg body weight or even higher doses of prednisolone may be necessary to prevent blister formation. If the eruption resolves well the prednisolone can be reduced fairly rapidly in steps, initially twice weekly, later once a week, to a much lower maintenance dose. Some patients then respond to doses of prednisolone of 5–10 mg daily or every second day. Frequently the eruption flares immediately postpartum, and then a temporary increase in prednisolone treatment can be anticipated (for the use of systemic corticosteroids during pregnancy see also the discussion of their use in PUPPP above).

Newborns of mothers suffering from pemphigoid gestationis may develop bullous lesions similar to those of their mother by passive transfer of the antibasement membrane zone antibody across the placenta. These lesions are transient and require no therapy. If the mother has received high doses of prednisolone for a longer time the infant should be carefully examined by a neonatologist for evidence of adrenal insufficiency.

In severe cases of pemphigoid gestationis that do not respond satisfactorily to prednisolone alone or in cases where prolonged treatment with corticosteroids is contraindicated, plasmapheresis or intravenous immuneglobulins may be considered. Postpartum treatment may cause difficulties for several reasons:

image If the mother wishes to breastfeed, the drugs pass into the breast milk. Antihistamines may cause drowsiness in the baby, and corticosteroids may cause adrenal suppression. The pediatrician should therefore be informed in this situation

image In general, pemphigoid gestationis tends to improve postpartum: however, it may take weeks, months, or even years until there is complete remission. In those cases alternative drugs that are contraindicated during pregnancy or while the mother is breastfeeding may be used. Owing to its close relationship to bullous pemphigoid, in this situation the full range of immunosuppressive treatment may be tried as adjunctive therapy either with oral corticosteroids or alone. Other drugs that may be used are goserelin and ritodrine. High-dose intravenous immune globulin alone or in combination with cyclosporine or cyclophosphamide has been tried with success in rare cases for its corticosteroid-sparing effect

image Pemphigoid gestationis tends to exacerbate with menstruation. There may also be dramatic flares with oral contraceptives. Thus, patients should be recommended to avoid oral contraceptives as long as the disease is still active.

Specific investigations

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.

The disease most often confused with pemphigoid gestationis is PUPPP. There may be a broad clinical and histopathologic overlap between these two entities, which are immunologically distinct, with linear C3 deposits (in 100%) and linear IgG deposits (in approximately 30%) along the basement membrane zone in pemphigoid gestationis.

Clinically, pemphigoid gestationis may present either with prominent annular wheals or target lesions or with grouped vesicles, and then may be confused with either erythema multiforme or dermatitis herpetiformis. However, these two diseases should be easily distinguished from pemphigoid gestationis by histopathology and direct immunofluorescence.

First-line therapies

image Topical corticosteroids C
image Systemic corticosteroids B
image Antihistamines C

Clinical features and management of 87 patients with pemphigoid gestationis.

Jenkins RE, Hern S, Black MM. Clin Exp Dermatol 1999; 24: 255–9.

This review summarizes the clinical data on 142 pregnancies in 87 patients with pemphigoid gestationis. Most patients received chlorpheniramine to suppress the pruritus. Thirteen of 69 (18.8%) patients were treated with topical corticosteroids alone without systemic treatment. Fifty-six of the 69 (81.2%) required systemic corticosteroids with initial doses of prednisolone in the range of 5–110 mg daily, resulting in suppression of blistering in most cases.

This large series of patients provides a good overview of the clinical presentation, immunologic findings, and management strategies. Some patients have also been treated with azathioprine, dapsone, pyridoxine, sulfapyridine, androgenic steroids, and goserelin. Plasmapheresis was also used, with some temporary relief. Although topical and systemic corticosteroids alone or together are regarded as first-line treatments in pemphigoid gestationis, their use has been based only on anecdotal reports and not on controlled studies.

Third-line therapies

image High-dose intravenous immuneglobulin E
image Azathioprine E
image Cyclophosphamide E
image Cyclosporine E
image Dapsone E
image Sulfapyridine E
image Pyridoxine E
image Ritodrine E
image Goserelin E

Pruritus gravidarum

Pruritus gravidarum, also known as intrahepatic cholestasis of pregnancy, or a mild form of benign recurrent intrahepatic cholestasis, is a hepatic condition that usually occurs in late pregnancy. It first manifests with severe generalized pruritus and may be followed by the clinical appearance of jaundice. Its incidence has been estimated at 0.02–2.4% of pregnancies. It is likely that the irritation results from abnormal hepatic excretion of bile acids induced by endogenous estrogen and progesterone. The itching usually subsides rapidly after delivery.

Management strategy

The first symptom of pruritus gravidarum is itch, followed by secondary excoriations. In mild cases the diagnosis is based on exclusion by differentiating pruritus gravidarum from other itchy conditions that may occur by chance during pregnancy. Scabies, eczema, urticaria, drug eruptions, or other conditions, and early cases of PUPPP and pemphigoid gestationis, must be excluded. Liver function tests may occasionally be abnormal with a raised alkaline phosphatase. Total serum bile acid levels are markedly elevated and correlate with impaired fetal prognosis. The pruritus and the cholestasis usually remit within a few days after delivery.

The incidence of prematurity and low birth weight is increased in the offspring of patients with pruritus gravidarum, and the pregnancies should be followed carefully. Pruritus gravidarum may recur with subsequent pregnancies and the use of oral contraceptive pills. In mild disease attempts should be made to control pruritus by the frequent application of cooling lotions or creams and topical antipruritic agents. A 1% menthol lotion or the addition of 6–10% polidocanol may be helpful. In more severe cases oral antihistamines are the therapy of choice (for the use of oral antihistamines during pregnancy see also the discussion of their use in PUPPP above). From the author’s experience phototherapy with UVB (290–320 nm) or UVA (320–400 nm) may also be of benefit in some cases. Cholestyramine and, as shown in numerous recent studies, the administration of ursodeoxycholic acid (either a dose of 15 mg/kg/day or, independent of body weight, 1 g/day is administered either as a single dose or divided into two or three doses until delivery) may give adequate relief of symptoms and improves fetal prognosis (prematurity). Pregnancies should be followed carefully by an interdisciplinary management between dermatologists, hepatologists, gynecologists, and pediatricians.

Specific investigations

Second-line therapies

image Ursodeoxycholic acid A

Atopic eruption of pregnancy

Atopic eruption of pregnancy (AEP) is a benign pruritic disorder of pregnancy presenting with eczematous and/or papular lesions in patients with an atopic diathesis after exclusion of the other dermatoses of pregnancy or other itchy conditions. It is the most common dermatosis in pregnancy, accounting for 50% of patients, starts usually early, in 75% before the third trimester, and tends to recur in subsequent pregnancies due to the atopic background. Synonyms are prurigo of pregnancy, prurigo gestationis, early onset prurigo of pregnancy, pruritic folliculitis of pregnancy, and eczema in pregnancy.

Related posts:

Xanthomas Mastocytoses Scleredema Erythromelalgia Cryptococcosis Panniculitis