Background
Polymorphic eruption of pregnancy (PEP), first described as pruritic urticarial papules and plaques of pregnancy (PUPPP), refers to a benign dermatosis that usually arises late in the third trimester of a first pregnancy.[1, 2] It can also manifest immediately postpartum.[3] The entity previously had been reported as toxemic rash of pregnancy,[4] toxemic erythema of pregnancy, and late-onset prurigo of pregnancy. See the image below.
View Image | Papules within prominent striae distensae. Courtesy of Jeffrey P. Callen, MD of Louisville, Kentucky. |
Following atopic eruption of pregnancy, which occurs earlier in gestation, PEP is the second most common pruritic dermatosis of pregnancy.[5] One European author proposes that early gestational papular dermatoses (usually atopic eruption of pregnancy) be referred to as "early-onset PEP," distinguished from "late-onset PEP".[6]
Epidemiology
Polymorphic eruption of pregnancy (PEP) occurs in 1 out of 160 pregnancies.[6, 7] The condition may be less common in Blacks.
Etiology
The cause and pathogenesis of polymorphic eruption of pregnancy (PEP) are not known. A meta-analysis revealed that 11.7% of patients with PEP had multiple gestation pregnancies.[8] Within that group, a higher PEP risk for triplet (14%) over twin (2.9%) pregnancies was found,[9] suggesting a relationship between skin distention and the development of PEP. Most studies have revealed increased maternal weight gain in patients with PEP when compared with normal pregnancies, further supporting the role of increased skin distention.[2, 7, 10]
A study from Israel also found maternal hypertension and induction of labor to be significantly associated with the condition.[11] One large series of cases revealed a male-to-female infant ratio of 2:1.[12]
Investigators identified fetal deoxyribonucleic acid (DNA) in the skin of mothers with PEP, suggesting that chimerism may be relevant to the pathogenesis of this disorder.[13] Additionally, another suggested cause is the maternal immune reaction to the fetal antigens within the maternal bloodstream.[14] Finally, a case-control study from France confirmed previously documented associations with multiple gestations, cesarean deliveries, and male fetuses, although no relationship to maternal or fetal weight gain was noted.[15]
One case report identifies PEP that occurred simultaneously with COVID-19 symptoms, such as fever, headache and diarrhea, in the postpartum period. This association could suggest that SARS-CoV-2 plays a role in the pathogenesis of PEP.[16]
Another case reports a coexistence of PEP superimposed on junctional epidermolysis bullosa. The patient likely had PEP, and the pruritus caused her to scratch, leading to bullae and erosions.[17]
A study from Japan found that the development of PEP may be linked to an immune response characterized by an increased activity of Th2 cytokines, such as interleukin 33 (IL-33) and IL-9.[18]
Another study from Turkey indicated that PEP was more common in in vitro fertilization (IVF) pregnancies than in spontaneous pregnancies, even in singleton pregnancies. Similarly, increased doses of progesterone or prolonged use of progesterone may contribute to the pathogenesis of PEP.[19]
Prognosis
The prognoses for the affected patient and the newborn are excellent in polymorphic eruption of pregnancy (PEP). It typically resolves within 4-6 weeks, independent of delivery,[7] and the condition does not tend to recur in subsequent pregnancies. Only 7% of multiparous PEP patients described a similar rash with prior pregnancies.[5] Patients who have had PEP will not precipitate a return of the condition through the subsequent use of oral contraceptives.
No mortality is associated with PEP. The mere appearance of an unusual skin eruption in pregnancy can provoke anxiety, but the pruritus is the most distressing feature. The later weeks of pregnancy can be associated with many physical symptoms, and the severe itching of PEP may further debilitate and aggravate sleep loss in the weeks prior to delivery. No known systemic complications exist for affected patients, and fetal mortality or morbidity does not increase.
Patient Education
The patient should understand that PEP is a benign disorder and has not been shown to have adverse consequences for the fetus. Fully explain the side effects of corticosteroids and antihistamines (which are used in the treatment of PEP). Reassure the affected patient that PEP does not usually recur with subsequent pregnancies and will not be triggered by future use of oral contraceptives.
History
Polymorphic eruption of pregnancy (PEP) typically begins with intensely pruritic papules arising within striae distensae late in the third trimester of a first pregnancy. Of all cases, 73% are seen in primigravidae pregnancies.[5] Additionally, 11.7% of affected patients have multiple-gestation pregnancies.[8]
As many as 15% of PEP cases arise in the immediate postpartum period,[5] and in one case report 2 weeks postpartum.[20] In a few days, the eruption spreads to the buttocks and proximal thighs and may generalize. Patients present for a diagnosis of their unusual skin eruption and seek relief from the intense itching.
Physical Examination
In classic polymorphic eruption of pregnancy (PEP), papules occur within prominent striae distensae, as shown in the images below.
View Image | Papules within prominent striae distensae. Courtesy of Jeffrey P. Callen, MD of Louisville, Kentucky. |
View Image | Papules within prominent striae distensae. Courtesy of Jeffrey P. Callen, MD of Louisville, Kentucky. |
Similar lesions are often found on the buttocks and proximal thighs and may generalize elsewhere over the trunk and extremities, although the periumbilical area is characteristically spared. Small vesicles often are noted, but larger bullae, although documented in two cases, typically do not occur and would suggest the possibility of pemphigoid gestationis.[21, 22, 23] Less commonly, target lesions[24] and annular and polycyclic wheals may be present. PEP usually does not affect the face, palms, or soles.
In patients with skin of color (SOC), the presentation may differ from that seen in patients of European or Arab ancestry. The postinflammatory hyperpigmentation may be more prounounced with more subtle erythema.[25]
Although the eruption is intensely pruritic, excoriations rarely are found. One report described a case of PEP that progressed to involve the neck, arms, and legs in a photosensitive distribution as the initial abdominal involvement settled.[26]
A fever can be present in patients with PEP, but it is not a specific symptom. If a fever is present, infectious and hematologic causes must be considered.[27]
Approach Considerations
Laboratory studies
No blood or urine laboratory tests are diagnostic of polymorphic eruption of pregnancy (PEP) and are not typically performed. One large series of cases showed a significant reduction of serum cortisol levels in patients with PEP compared with normal pregnant controls.[12]
Serum submitted for indirect immunofluorescence or NC16a enzyme-linked immunosorbent assay may help to differentiate between PEP and pemphigoid gestationis when the clinical diagnosis is unclear.[30] Both studies detect autoantibodies that are present in persons with pemphigoid gestationis but are not present in those with PEP.
Direct immunofluorescence
In punch biopsy specimens of the skin, direct immunofluorescence (DIF) characteristically is negative in PEP. DIF results differentiate PEP from pemphigoid gestationis when the clinical diagnosis is unclear. The latter disorder is a rare, autoimmune blistering disease characterized by linear deposits of C3 along the basement membrane zone.
Histologic findings
Skin biopsy is rarely necessary. Routine biopsy specimens from patients with PEP usually reveal a normal epidermis, but focal spongiosis, parakeratosis, and hyperkeratosis may be seen.[31] Within the papillary dermis and mid dermis, a lymphohistiocytic infiltrate with a variable number of eosinophils and dermal edema is present.[32]
Approach Considerations
Treatment is directed at relieving the pruritus associated with polymorphic eruption of pregnancy (PEP). Topical corticosteroids are the mainstay of treatment.[33] High-potency topical (class I or II), or even systemic, steroids may be required to alleviate symptoms. Oral antihistamines are only mildly effective.
General treatment measures include the use of cool, soothing baths; emollients; wet soaks; and light cotton clothing. PEP tends to resolve spontaneously shortly after delivery or within 4-6 weeks.[7] Continue symptomatic care until resolution.
Morbidity is not increased for the fetus born to an affected mother. An older case report described early cesarean delivery to relieve a severe case of PEP.[34]
For patients who strive to avoid the use of any medications when pregnant or breastfeeding, PEP has been successfully treated with intramuscular injection of autologous whole blood in three cases.[35]
Consultations
The healthcare provider responsible for the patient's obstetric care should be made aware of the diagnosis, treatment, and favorable prognosis of PEP.
Medication Summary
As previously mentioned, topical corticosteroids are the mainstay of treatment for polymorphic eruption of pregnancy (PEP).[33] Symptom alleviation may require high-potency topical (class I or II) steroids, such as fluocinonide, or even systemic steroids. Oral antihistamines are only mildly effective.
Diphenhydramine, an antihistamine, has a sedative effect that may help patients to sleep better; it is also an effective agent against pruritus resulting from histamine release during inflammatory reactions.
Medications may need to be used into the postpartum period. Pay attention to potential adverse effects with breastfeeding.
Fluocinonide (Lidemol, Lidex, Lyderm)
Clinical Context:
Fluocinonide is a class II, high-potency, topical corticosteroid that inhibits cell proliferation. It is immunosuppressive and anti-inflammatory.
Fluticasone topical (Cutivate)
Clinical Context:
Fluticasone is a high-potency, topical corticosteroid that inhibits cell proliferation. It is immunosuppressive and anti-inflammatory.
Prednisolone (FloPred, Millipred, Millipred DP)
Clinical Context:
This glucocorticosteroid occurs naturally and synthetically. It is used for both acute and chronic asthma. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Prednisone (Deltasone, Prednisone Intensol, Rayos)
Clinical Context:
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Use systemic steroids for severe, refractory cases only.
Diphenhydramine (Alka-Seltzer Plus Allergy, Benadryl, Benadryl Allergy Dye-Free LiquiGels)
Clinical Context:
Diphenhydramine is used for the symptomatic relief of pruritus caused by the release of histamine in inflammatory reactions.
Hydroxyzine (Vistaril)
Clinical Context:
Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity and subsequently relieve pruritus.
Class Summary
Antihistamines have a sedative effect that may improve sleep.
Author
Joseph C Pierson, MD, Dermatology Residency Program Director, University of Vermont College of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Christine C Tam, MD, Managing Member, Certified Dermatologists
Disclosure: Nothing to disclose.
Natasha Salmen, BS, Medical Student, Northeast Ohio Medical University College of Medicine
Disclosure: Nothing to disclose.
Chief Editor
William D James, MD, Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.
Acknowledgements
David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Abdul-Ghani Kibbi, MD Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon
Disclosure: Nothing to disclose.
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