Obstetrics and Gynecology

Polymorphic Eruption of Pregnancy (PEP)

1. What every clinician should know

Clinical features and incidence

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is the most common of the specific dermatoses of pregnancy, affecting approximately 0.5% of pregnancies. Adopted from the European literature, the preferred term is polymorphic eruption of pregnancy (PEP). "Bourne's toxemic rash of pregnancy," "toxemic erythema of pregnancy" and "Nurse's late prurigo of pregnancy" are historical synonyms of PUPPP.

The characteristic eruption of PEP occurs classically in primigravidas during the third trimester of pregnancy or rarely postpartum. Unlike pemphigoid gestationis (PG), an important dermatosis in PEP's differential diagnosis, PEP does not usually recur in subsequent pregnancies. The eruption of PEP classically begins in the striae of the gravid abdomen, sparing the umbilicus, and subsequently spreads to the proximal thighs, buttocks, and rarely to the extremities, breasts and face (Figure 1).

Figure 1.

Classically the urticarial papules and plaques of PUPPP appear first on the gravid abdomen within the striae distensae, sparing the umbilicus.

Erythematous urticarial papules and plaques are the most common morphology associated with PEP; however, vesicles, purpura, and targetoid or polycyclic lesions have been reported. A morphology other than urticarial papules and plaques typically occurs later in the course of the eruption and is often preceded by the typical urticarial papules and plaques.

Risk factors

Some studies have shown an association between increased maternal weight gain, fetal weight and PEP. In addition, increased frequency of PUPPP has been seen in multiple gestation pregnancies. These associations have led some to speculate that rapid abdominal wall distention in primigravidas may trigger the inflammatory response of PEP.

2. Diagnosis and differential diagnosis

Classically, the eruption of PEP occurs in primigravidas during the third trimester. The eruption of intensely pruritic urticarial papules and plaques begins in the striae, sparing the umbilicus and subsequently spreads to the proximal thighs and buttocks (Figure 1). Laboratory work up should be directed by the clinical findings. If the diagnosis is in question, laboratory evaluation to exclude cholestasis may be necessary. If the clinical findings are atypical, a skin biopsy may be helpful. If PEP is suspected, there are no specific laboratory tests to aid the diagnosis. Additionally, skin biopsy is not particularly useful to confirm the diagnosis. In other words, PEP is a clinical diagnosis.

Histopathologic examination shows a nonspecific spongiotic dermatitis with perivascular or upper dermal inflammatory infiltrate, at times with a marked number of eosinophils. Routine histopathology may not be useful to distinguish PEP from PG. In contrast to PG, direct immunofluorescence of perilesional skin is classically negative for linear deposition of c3 or IgG along the dermoepidermal junction. Direct immunofluorescence may show deposits of complement within vascular walls, but not in a linear array. Indirect immunofluorescence of serum for circulating IgG antibodies is also absent in PEP.

Drug rash and viral exanthem may mimic PEP and should be excluded. Typically these can be differentiated from PEP by historical clues and lack of associated symptoms respectively. Prurigo of pregnancy begins earlier in pregnancy, persists throughout pregnancy, may recur in subsequent pregnancies and often lacks the urticarial papules and plaques of PEP. Intrahepatic cholestasis of pregnancy (ICP) can be differentiated from PEP by the absence of primary skin lesions, laboratory evidence of cholestasis and recurrence with subsequent pregnancies. Early PG may mimic PEP but classically the urticarial papules and plaques of PEP spare the umbilicus, whereas those of PG do not.

3. Management

Commonly, topical corticosteroids are employed for treatment of PEP. Mid to low potency topical steroids are safe to use in pregnancy and usually effective for symptomatic control of pruritus. Oral antihistamines also can be used as an alternative or in conjunction with topical therapies for PEP. Other treatment modalities reported to be effective for the severe pruritus of PEP include a short course of oral prednisone (e.g. prednisone 0.5 mg/kg/day) and narrow band ultraviolet B light therapy.

4. Complications

There are no complications associated with eruption of PEP.

5. Prognosis and outcome

PEP is not an indication for early delivery. Although the pruritus of PEP may be severe and intractable, it is harmless to the fetus. The self-limited nature of PEP and time course of 4-6 weeks warrants symptomatic treatment alone.

6. What is the evidence for specific management and treatment recommendations

Lawley, TJ. "Pruritic Urticarial Papules and Plaques of Pregnancy.". JAMA. vol. 241. 1979. pp. 1696-9.

(In this case series, the authors report seven cases of a similar pruritic eruption developing in the third trimester of pregnancy characterized by urticarial papules and plaques. The authors proposed the term "pruritic urticarial papules and plaques of pregnancy" [PUPPP].)

Shornick, JK. "Dermatoses of Pregnancy". Semin Cutan Med Surg. vol. 17. 1998. pp. 172.

(In this review, the author classifies and describes the skin diseases found uniquely during pregnancy. The author includes herpes gestationis, pruritic urticarial papules and plaques of pregnancy, prurigo of pregnancy, and cholestasis of pregnancy.)

Rudolph, SM. "Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients.". Br J of Derm. vol. 154. 2006. pp. 54.

(In this retrospective review of 181 patients with polymorphic eruption of pregnancy (PEP), a synonym for PUPPP, the authors found an association between early onset of PEP and several factors. In this series, patients presenting with PEP earlier in pregnancy than classic PEP (third trimester) were more likely to have multiple gestation pregnancies, have initial eruption of non-abdominal sites and persist longer than classic PEP. The authors also recorded a high frequency of atopy, greater than 50%, among the patients with PEP.)

Cohen, LM. "Pruritic Urticarial Papules and Plaques of Pregnancy and its relationship to maternal-fetal weight gain and twin pregnancy.". Arch Dermatol. vol. 125. 1989. pp. 1534.

(In this retrospective study of 30 women with PUPPP, maternal weight gain and newborn birth weight were significantly increased compared to controls. The role of abdominal distention or a reaction to abdominal distention is a proposed mechanism of pathogenesis.)

Ambros-Rudolph, CM. "The specific dermatoses of pregnancy revisited and reclassified: Results of a retrospective two center study on 505 pregnant patients.". J Am Acad Dermatol. vol. 54. 2006. pp. 395.

(In this retrospective study, data from 505 pregnant patients that presented over a 10-year period [1994-2004] with pruritic dermatoses were analyzed. Eczema in pregnancy was the most common dermatosis and showed considerable overlap with prurigo of pregnancy and pruritic folliculitis of pregnancy. The authors suggest inclusion of these three entities under the heading atopic eruption of pregnancy. The authors found that patients with atopic eruption of pregnancy tended to present earlier in pregnancy than patients with pemphigoid gestationis, polymorphic eruption of pregnancy, and intrahepatic cholestasis of pregnancy.)

Regnier, S. "A case-control study of polymorphic eruption of pregnancy.". J Am Acad Dermatol.

(In this retrospective study of 200 pregnant women, the authors' aim was to understand what factors are associated with and complicate PEP. They used strict criteria to define the 40 cases of PEP, including classic clinical signs and negative DIF to exclude pemphigoid gestationis. This large case control study confirmed the association of PEP with multiple gestations, male fetuses, and cesarean deliveries. However, it did not find an association between PEP and excess maternal or fetal weight gain.

Ohel, I. "Pregnancy outcome of patients with pruritic urticarial papules and plaques of pregnancy.". The Journal of Maternal-Fetal and Neonatal Medicine. vol. 19. pp. 305.

In this population based study, the authors compared all pregnancies of women with and without PUPPP during the years 1988-2002. Of nearly 160,000 deliveries, PUPPP was diagnosed in 42 pregnancies (0.03%). The authors found PUPPP to be significantly associated with multiple gestation, hypertensive disorders and induction of labor. They found no difference in perinatal mortality.)

Elling, SV. "Pruritic urticarial papules and plaques of pregnancy in twin and triplet pregnancies.". JEADV. 2000. pp. 378.

(To determine the frequency of PUPPP in twin and triplet pregnancies, the authors performed a retrospective review of all the twin and triplet deliveries over an 18-month period at a busy general maternity hospital. The authors found that PUPPP occurred in 2.9% of twin pregnancies and 14% of triplet pregnancies. Compared to the reported rate of PUPPP in singlet pregnancies of 0.5%, their findings suggest PUPPP occurs more frequently in multiple gestations.)
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