Pruritic Urticarial Papules and Plaques of Pregnancy

Zenon Brzoza, MD, PhD, Alicja Kasperska-Zajac, MD, PhD, Ewa Oles, MD, and
Barbara Rogala, MD, PhD
Pruritic urticarial papules and plaques of pregnancy (PUPPP) are among the most common pruritic
dermatoses observed in pregnant women. PUPPP appears most frequently in the third trimester, in
primigravidas, and in multiple gestation pregnancies. The eruption of changes occurs initially on the
abdomen and extends over the thighs, legs, back, buttocks, arms, and breasts. Skin changes typical for PUPPP
are erythematous, urticarial plaques, and papules. Rash regression is usually observed within 6 weeks
postpartum. Immunologic mechanisms, hormonal abnormalities, and abdominal skin distension have been
suggested as etiologic mechanisms. PUPPP is thought to be harmless for the mother and fetus and usually
requires intervention only for symptom relief. In some cases, laboratory investigation, histologic examina-
tion, and immunologic study should be performed to exclude more serious disorders of pregnancy, such as
herpes gestationis or intrahepatic cholestasis of pregnancy. This article reviews the epidemiology, clinical
manifestation, etiology, differential diagnosis, and treatment of PUPPP. J Midwifery Womens Health 2007;
52:44 48 2007 by the American College of Nurse-Midwives.
keywords: dermatosis, pregnancy, pruritic urticarial papules and plaques of pregnancy, skin, urticaria

INTRODUCTION in primigravidas and in women with multiple gestation

Skin changes reflecting hormonal and metabolic changes
during pregnancy can be classified into 3 groups:
1) dermatoses that started before pregnancy; 2) physio-
logic lesions, such as hyperpigmentation, melasma, striae
gravidarum, palmar erythema, etc.; and 3) dermatoses
specific for pregnancy, such as itching in the course of
intrahepatic cholestasis of pregnancy (ICP), herpes ges-
tationis (HG), prurigo of pregnancy (PP), and pruritic
urticarial papules and plaques of pregnancy (PUPPP).1
This article reviews the epidemiology, clinical mani-
festation, etiology, diagnosis, and treatment of PUPPP in
the context of other skin disorders affecting pregnant
women. Most of available literature concerning this
problem is based on case reports or reports of small
numbers of women.
EPIDEMIOLOGY OF PUPPP
The term pruritic urticarial papules and plaques of
pregnancy was initially proposed by Lawley in 1979.2
Available literature from that time also refers to toxemic
erythema of pregnancy and late onset prurigo of
pregnancy. In the United Kingdom, the name suggested
for such dermatosis is the polymorphic eruption of
pregnancy (PEP).1 PUPPP is a self-limiting disorder, and
is supposed to be one of the most common pruritic
dermatoses observed in pregnant women. Though ap-
proximately 1 in 200 pregnant women suffers from
PUPPP, its etiology, like other urticarial changes, re-
mains unknown.1,35
PUPPP appears most frequently in the third trimester
pregnancies (incidence 2.9%16%).2,6 10 However, in a
few cases, an early (first or second trimester) or late
(postpartum period) onset has been observed.
CLINICAL PRESENTATION
Skin changes typical for PUPPP are erythematous, urti-
carial plaques, and 1 to 2 mm papules usually surrounded
by a narrow and pale halo.2 Vesicles that are not larger
than 2 mm can also occur.1 The eruption of changes in
the course of PUPPP appear initially on the abdomen,
particularly in striae atrophicae, then progresses to involve
the thighs, legs, back, buttocks, arms, and breasts.6,7,9
Aronson et al.6 observed 57 patients with the diagnosis of
PUPPP and classified PUPPP into 3 types, depending on
the type of lesion: 1) urticarial papules and plaques
(type I); 2) nonurticarial erythema, papules, or vesi-
cles (type II); and 3) a combination of the two forms
(type III). Fourteen of the 57 women developed skin
changes initially on their arms, wrists, thighs, legs, feet,
or face.6 Interestingly, no patient suffering from type I
had her face, palms, or soles involved, whereas women
with type II or type III can have lesions in such areas.
Trimester onset, parity, and direct immunofluorescence
findings did not differ significantly among the 3 groups.
In Callen and Hamos8 observation, 2 out of 15
patients had lesions on their legs only. Although the
eruption does not usually involve the face, palms, and
soles, some case studies have described patients whose
soles and palms were covered with rash.2,3,7,9,11 Mucous
membranes are usually not involved. Pruritus is charac-
teristic for PUPPP and its intensity can keep patients
awake at night.2,7

Address correspondence to Zenon Brzoza, MD, PhD, Chair and Clinical ETIOLOGY
Department of Internal Diseases, Allergology and Clinical Immunology,
Medical University of Silesia, Katowice, ul. 3 Maja 13-15, 41-800 Zabrze, There is little insight into pathogenesis of PUPPP. Some
Poland. E-mail: zbrzoza@mp.pl researchers suggest immunologic mechanisms; others

44 Volume 52, No. 1, January/February 2007

2007 by the American College of Nurse-Midwives 1526-9523/07/$32.00 doi:10.1016/j.jmwh.2006.09.007
Issued by Elsevier Inc.
point to hormonal abnormality.2,8 Distension of abdom- ies in a patient suffering from PUPPP. The immunoflu-
inal skin has also been considered. However, none of orescence tests performed by Aronson et al.6 revealed the
these mechanisms has been supported enough to prove deposition of IgM, IgA, or C3 at dermoepidermal junc-
what exactly causes PUPPP. tion or blood vessels among 15 out of 57 examined
patients. There were no cases of linear deposits of any
Abdominal Distension immune reactant at the dermoepidermal junction; indi-
rect immunofluorescence examination for circulating
Cohen et al.7 suggested that abdominal distension or
IgG antibodies was also negative.6 In Yanceys study,9
reaction to this process might play a pivotal role in the
slightly elevated IgA complexes were observed in 2 out
development of PUPPP. They observed a significant
of 10 patients.
increase in maternal weight gain and the newborn birth
Alcalay et al.14 also studied the immunologic aspects
weight in women who have PUPPP, when compared
of PUPPP pathogenesis; however, they found no specific
with women who do not have PUPPP, as well as a higher
antibodies in any of 11 patients and the autoimmune
twin rate in patients with such dermatosis as compared to
mechanism was not proved. Activation of skin immune
the general twin rate in their hospital. It was also
system was also supposed to underlie PUPPP pathogen-
suggested that lymphohistiocytic inflammatory reaction
esis.16 Activated T cells (human leukocyte antigen
in PUPPP could be provoked by collagen antigens,
[HLA]-DR, CD25, and leukocyte functioning antigen
exposed as a result of abdominal distension. This hypoth-
(LFA-1)) associated with CD1a were found in the
esis is supported by the observation that PUPPP occurs
dermis. Additionally, the number of CD54 dendritic
more frequently in women with a triplet pregnancy and in
cells and CD1a epidermal cells was increased in le-
patients suffering from polyhydraminos.12 Furthermore,
sional skin in comparison to perilesional, unaffected
in a case study of a woman with triplets described by
skin.15
Vaughan-Jones et al.,13 the rash onset occurred at 24
Some authors postulated maternal response to paternal
weeks gestation, which is earlier than it occurs in
antigens present in the fetal component of placenta as a
women who have a singleton fetus. According to the
PUPPP mechanism; others suggested that placental prod-
authors opinion, at this stage, the patients abdomen
ucts could play some role in pathogenesis of PUPPP.14,17
distension was comparable to 38-week single pregnancy,
In addition, it has been postulated that the presence of
which accounts for the early onset.
fetal DNA in maternal skin as a result of fetal cells
migration in women carrying a male fetus may be an
Immunologic Mechanisms
etiologic factor of PUPPP.18 In summary, none of the
Histopathology studies carried out in patients with evaluations of immunologic mechanisms done to date
PUPPP resulted in similar conclusions. Superficial and/or have demonstrated changes that are consistently seen in
middermal perivascular lymphohistiocytic infiltrate (pos- women with clinical manifestations of PUPPP.
sibly associated with edema); eosinophils; spongiosis, or
small vesicles in the dermis; and parakeratosis, or scale Hormonal Changes
crusts in the epidermis of some patients, have been
The suggested role of hormonal changes in the develop-
observed.6,7 Obviously, such histopathologic findings
ment of PUPPP has not been confirmed. In most studies,
were not specific for PUPPP.
the level of serum -subunit human chorionic gonado-
In most studies, direct and indirect immunofluores-
tropin (HCG), estradiol, progesterone, cortisol, and
cence tests performed in PUPPP patients proved nega-
urinary estriol in PUPPP patients did not differ from that
tive.1,2,6,14,15 In some cases, however, minimal deposits
of the control groups.2,8,14
of complement (C3) in the basement membrane zone or
perivascular C3 deposits in the dermis were found.2,9
PROGNOSIS
Trattner et al.16 found antiepidermal cell surface antibod-
The rash usually regresses within a week postpartum;
however, it can also clear at any time before birth and up
Zenon Brzoza, MD, PhD, is an assistant at the Clinical Department of to the sixth week postpartum.8 In a few cases, postpartum
Internal Diseases, Allergology and Clinical Immunology, Medical Univer- exacerbation of PUPPP has been observed.7
sity of Silesia, Katowice, Poland.
PUPPP does not usually reoccur in future pregnan-
Alicja Kasperska-Zajac, MD, PhD, is an assistant at the Clinical Depart-
ment of Internal Diseases, Allergology and Clinical Immunology, Medical cies.2,8 In Aronsons6 study, only 3 out of 57 patients
University of Silesia, Katowice, Poland. suffered from PUPPP recurrence in a subsequent preg-
Ewa Oles, MD, is an assistant at post-graduate training at the Clinical nancy.
Department of Internal Diseases, Allergology and Clinical Immunology, Most studies of women with PUPPP confirm the
Medical University of Silesia, Katowice, Poland.
absence of associated maternal and fetal morbidity and
Professor Barbara Rogala, MD, PhD, is the Head of Chair and Clinical
Department of Internal Diseases, Allergology and Clinical Immunology, mortality in patients, and it is thought that PUPPP is
Medical University of Silesia, Katowice, Poland. harmless to both the mother and the fetus.9,14 Neverthe-

Journal of Midwifery & Womens Health www.jmwh.org 45

 Table 1. Dermatoses of Pregnancy That Must be Considered in Differential Diagnostics of Pruritic Urticarial Papules and Plaques of Pregnancy
(PUPPP)

Dermatoses of Differential Diagnosis,

Pregnancy Clinical Characteristics
Herpes gestationis (HG) Abdominal urticarial lesions may
be clinically indistinguishable
from the lesions seen in
women who have PUPP,
though in HG, bullae and
larger vesicles are common.
Lesions can be situated on
palms and soles.
HG associated with
exacerbations and
reoccurrence during
pregnancy may occur
postpartum and frequently
reoccurs in subsequent
pregnancies
Pruritus gravidarum: Intense itching without primary
Intrahepatic skin eruption.
cholestasis of In some cases, symptoms such
pregnancy (ICP) as anorexia or nausea, and
jaundice may appear.
Often reoccurs in subsequent
pregnancies
Prurigo of pregnancy Grouped excoriated papules
(PP) cover extensor surface of the
extremities and rarely the
trunk. Face often involved.
Lesions can occur at any time
of pregnancy and recur in
subsequent pregnancy
DIF direct immunofluorescence assay; ELISA enzyme-linked immunosorbent assay; NST nonstress test.
*Patients placed on cholestyramine therapy need supplemental vitamin K.
Laboratory Evaluation
Autoimmune development of
antibody to the basement
membrane zone of the
epidermis. In DIF test of
lesion and perilesional
skin a linear band of C3
deposits and IgG along
the basement membrane
noted. ELISA evaluation
of skin biopsy can to be
a valuable tool in
differentiating between
HG and PUPPP.
In some patients increased
serum bile acids
concentration, increased
liver enzymes activity.
Patients with ICP may have
normal lab values.
Normal serologic tests,
nonspecific
histopathology, negative
immunofluorescence
Perinatal Outcome Treatment
Increased risk of preterm Antipruritics, topical and/or
birth, transient oral steroids.
neonatal lesions. Cyclophosphamide and
methotrexate in
refractory cases.
There is an association Emollients, topical
between ICP and antipruritics, topical or
prematurity, fetal oral steroids as needed,
distress, meconium cholestyramine,*
staining, and stillbirth ursodeoxycholic acid.
Oral antihistamines rarely
sufficient.
Weekly antenatal NST
recommended.
Induction at 38 weeks may
be recommended.
No maternal risk or fetal Symptomatic
morbidity and
mortality

less, in a few case studies, complications potentially
associated with the dermatosis have been observed. A
patient with PUPPP who delivered twins (one live birth
and one stillborn) has been described.2 In Aronsons
study,6 one out of the 57 pregnancies ended in fetal death
at 30 weeks gestation.6 Moreover, spontaneous abortion
in the 9th week was noticed in a patient whose eruption
appeared in the 7th week of gestation.6 Lowenstein
et al.19 suggested possible association of PUPPP and
severe preeclampsia with fetal death. They reported a
case of a woman with PUPPP who had a stillbirth. On the
other hand, none of the case studies mentioned above had
sufficient power or numbers of participants to ascertain a
true correlation between morbid outcomes and the pres-
ence of PUPPP during pregnancy.
DIFFERENTIAL DIAGNOSIS
PUPPP is one of numerous, difficult to differentiate pruritic
dermatoses that affect pregnant women (Table 1).20 23 It
must be stated that in all cases of unusual skin changes,
laboratory investigation, histologic examination, and im-
munologic studies should be performed to exclude more
serious pregnancy disorders.
Other skin lesions that have presentations similar to
PUPPP are superficial gyrate erythema, superficial urti-
carial allergic eruption, viral exanthema, and superficial
response to arthropod bites.2
TREATMENT
Treatment of PUPPP is focused on the relief of pruritus.
The most common agents used are antipruritic agents,
skin emollients, and topical corticosteroids (Table 2).24
Refractory cases may require oral corticosteroid ther-
apy.24
In the study by De Gaetano et al.,3 one patient with
PUPPP needed treatment with a long tapering of pred-
nisone. The authors emphasized the need for tapering
doses of steroids to treat particularly severe manifesta-

46 Volume 52, No. 1, January/February 2007

 Table 2. Medications for Treatment of PUPP
Medication Brand Name Dose Comments
High Potency Steroid
Betamethasone dipropionate* Diprolene 0.05% bid Ointment (15 or 45 grams)
Cream (15 or 45 grams)
Lotion (20 or 60 ml)
Triamcinolone acetonide* cream Aristocort, Kenalog 0.5% bid to tid Ointment (15, 20, 28, 57 grams)
Cream (15, 20, 30, 60 grams)
Medium Potency Steroid
Triamcinolone acetonide cream Aristocort, Kenalog 0.1% bid to tid Ointment (15, 20, 28, 57 grams)
Cream (15, 60, 80 grams)
Lotion (15, 60 ml)
Mometasone furoate Elocon 0.1% bidtid Ointment (15 or 45 grams)
Cream (15 or 45 grams)
Lotion (30 or 60 ml)
Low Potency Steroid
Hydrocortisone acetate Cortaid, Corticaine 0.5% or 0.1% bid Ointment 0.5% (15, 30 grams)
Ointment 0.1% (30 grams)
Cream 0.5% (15, 20, 30 grams)
Cream 0.1% (15, 20, 30 grams)
Nonsteroid Medication
Calamine lotion Calamine apply tid to qid Lotion (120, 240 ml)
Oatmeal Aveeno apply bid to tid Over the counter packets or lotion
Sarna lotion Sarna Lotion apply tid to qid Made of 0.5% camphor, 0.5% menthol, and
0.5% phenol. Effect is cooling of skin
Diphenhydramine Benadryl 20 50 mg PO Tablets (25, 50 mg)
Maximum of 300 mg per day
Hydroxyzine Atarax 25100 mg PO qd to qid Tablets (10, 25, 50 mg)
*High-potency steroids should be used with caution in pregnancy and for no more than 2 weeks. Known teratogens in animal studies when ingested in the first trimester. Prescribe
with physician consultation.

The ointment provides the most percutaneous absorption. Do not use ointments on skin that is weepy or broken from scratching.

tions of the disease, especially if unresponsive to topical
steroids. There are some risks associated with corticoste-
roid treatment: maternal hyperglycemia, increased risk of
infections, fetal intrauterine growth restriction, and an
increased risk of early-onset neonatal sepsis. These
adverse outcomes are rare, and the use of oral cortico-
steroids has been shown to be relatively safe in the
treatment of maternal asthma, inflammatory bowel dis-
ease, and autoimmune disorders.13
In two studies, atypical PUPPP patients were pre-
sented, who, despite intensive local and systemic
treatment, suffered from intense, resistant, and inca-
pacitating pruritus, which led to premature cesarean
delivery. Symptoms were relieved a few days after
delivery.25,26
CONCLUSION
Though PUPPP is the most common skin condition seen
during pregnancy, many questions pertaining to this
disease remain unanswered. This review points to
PUPPP as a well-defined entity, the diagnosis of which is
based mainly on the clinical presentation (onset, typical
localization, and appearance of changes). In women who
have unusual presentations, laboratory investigation, his-
tologic examination, and immunologic studies can be
performed to exclude more serious pregnancy disorders.
These persons should be referred to a dermatologist for
diagnostic work-up.
Treatment of PUPPP focuses on the mitigation of
pruritus. Antihistamines, skin emollients, and topical
steroids are the primary agents used. In some cases, a
short course of oral corticosteroids may be of value.
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Volume 52, No. 1, January/February 2007