Original Paper
Dermatology 2018;234:31–36
DOI: 10.1159/000489879
Pityriasis Rosea during Pregnancy:
Major and Minor Alarming Signs
Francesco Drago Giulia Ciccarese Astrid Herzum Alfredo Rebora
Aurora Parodi
DISSAL, Section of Dermatology, Policlinico San Martino, Genoa, Italy
Keywords
Pityriasis rosea · Pregnancy · Human herpesvirus 6 · Human
herpesvirus 7
Abstract
Background: Pityriasis rosea (PR) is a self-limiting exanthem-
atous disease associated with human herpesvirus (HHV)-6
and/or HHV-7 reactivation. In pregnant women, PR may be
associated with pregnancy complications. Objective: To de-
termine relevant risk factors in the development of negative
pregnancy outcome in PR. Methods: Between 2005 and
2017 at the Department of Dermatology, University of Ge-
noa, we recruited 76 women who developed PR during preg-
nancy. In 60 patients without known risk factors for intra-
uterine fetal death (30 with pregnancy complications and 30
without) we analyzed the pregnancy week of PR onset, pres-
ence of enanthem and of constitutional symptoms, PR body
surface area involvement, age, and in 50 patients (20 with
pregnancy complications and 30 without), the viral load of
HHV-6 and HHV-7 (copies/mL). Results: In logistic regression
analysis, early onset of PR (p = 0.0017) and enanthem (p =
0.0392) proved to be significantly associated with pregnancy
complications. HHV-6 viral load (copies/mL) (p < 0.0001),
© 2018 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/drm
Received: March 17, 2018
Accepted after revision: May 7, 2018
Published online: June 22, 2018
constitutional symptoms (p < 0.001), and PR body surface
area involvement (p < 0.004) were also significantly associ-
ated with pregnancy complications. Conclusion: The onset
of PR before week 15 and enanthem may be considered ma-
jor risk factors that should alarm the dermatologist. Consti-
tutional symptoms and involvement of > 50% of the body
area may be considered minor risk factors.
© 2018 S. Karger AG, Basel
Introduction
Pityriasis rosea (PR) is a self-limiting exanthematous
disease associated with human herpesvirus (HHV)-6
and/or HHV-7 reactivation [1–3] which is more fre-
quent in pregnant women than in the general population
[4]. The exanthem typically begins with a single, round
or oval erythematous scaly plaque (herald patch) usually
situated on the trunk, the thigh, the upper arm, or the
neck. After an interval of about 2 weeks, a general erup-
tion appears in crops consisting of smaller oval erythem-
atous-squamous lesions symmetrically distributed
mainly on the trunk, the neck, and the limbs. The lesions
follow the lines of cleavage of the skin forming a “theatre
155.247.166.234 - 7/31/2018 2:08:11 PM
Astrid Herzum
DISSAL, Section of Dermatology, Policlinico San Martino
Largo Rosanna Benzi 10
IT–16132 Genoa (Italy)
Temple University
Downloaded by:
E-Mail astridherzum @ yahoo.it
 Color version available online
b

a c

Fig. 1. Pityriasis rosea in a pregnant patient. a Oval erythematous scaly plaque (herald patch) on the right shoul-
der and similar smaller lesions on the back. b Oval erythematous-squamous lesions on the abdomen. c Erythem-
atous-squamous lesions on the lines of cleavage of the skin forming a “theatre curtain” pattern.

Color version available online

From 2005 to 2017:
76 pregnant women with PR

Women with known risk

factors for intrauterine fetal
death were excluded

60 patients without known risk factors

for intrauterine fetal death

30 women developed 30 women did not develop

pregnancy complications pregnancy complications

Collection of clinical and laboratory data: age, PR body

surface area involvement, pregnancy week of PR onset,
presence of enanthem and constitutional symptoms, HHV-6
and HHV-7 viral load in plasma
Fig. 2. Flowchart of Patients and Methods.
PR, pityriasis rosea.

curtain” pattern (Fig. 1). Usually, the face, scalp, palms,
and soles are spared. In addition to classic PR, different
forms have been described and classified according to
the pathogenesis and course of the disease: pediatric PR,
relapsing PR, persistent PR, PR in pregnancy, and PR-
like eruptions. Several patterns of enanthems may be
present and usually follow the course of the skin erup-
tion, disappearing with it or a few days later. They are
frequently associated with forms of PR different from
the classic one [1–4].
The occurrence of PR during pregnancy may be asso-
ciated with a negative outcome, such as premature deliv-
155.247.166.234 - 7/31/2018 2:08:11 PM

32 Dermatology 2018;234:31–36 Drago/Ciccarese/Herzum/Rebora/Parodi

DOI: 10.1159/000489879
Temple University
Downloaded by:
Table 1. Risk factors possibly associated with pregnancy complications as assessed by logistic regression analysis
Patients with
complications
Onset, weeks 14.80±3.65
Enanthem 26 (87)
Body area involvement >50% 11 (37)
Constitutional symptoms 26 (87)
Age, years 29.13±2.49
Values are presented as mean ± SD or n (%). ns, not significant.
ery and fetal demise. The onset of PR within the first 15
weeks of gestation, especially if associated with severe
constitutional symptoms and a widespread diffusion of
the eruption, has been indicated as an alarming sign for
the outcome of pregnancy [5, 6].
We studied a large cohort of patients with PR occur-
ring during pregnancy to determine, by applying statisti-
cal methods, which risk factors could compromise the
course of the pregnancy. We also aimed to evaluate which
were the most significant risk factors to distinguish be-
tween the major and the minor ones.
Patients and Methods
For further details, see the supplementary material (for all on-
line suppl. material, see www.karger.com/doi/10.1159/000489879
[7] (Fig. 2).
Results
Seventy-six patients with PR occurring during preg-
nancy were recruited during the study period: 60 were
healthy women whereas 16 had known risk factors for
intrauterine fetal death and were therefore excluded.
Overall, 30 patients (39%) developed pregnancy compli-
cations and 46 (61%) (30 healthy women and 16 women
with known risk factors for intrauterine fetal death) had
a normal pregnancy outcome. The pregnancy complica-
tions were miscarriage (n = 8 patients) and hydramnios
(n = 3); the neonatal complications recorded at birth were
neonatal hypotonia (n = 15), low birth weight (n = 17),
low Apgar score (n = 8), and patent foramen ovale (n =
4). Some patients suffered from more than one complica-
tion. No further neonatal impairment was recorded dur-
ing follow-up. Follow-up of the 44 babies with birth com-
Pityriasis Rosea during Pregnancy
Patients without p OR (95% CI)
complications
24.83±3.64 0.0017 0.4880 (0.3115–0.7645)
7 (23) 0.0392 19.3284 (1.1584–322.4902)
1 (3) ns ns
9 (30) ns ns
29.0±2.55 ns ns
plications lasted 24 months: 6 of the 17 babies with low
birth weight had difficulty recovering age-appropriate
percentiles; all the other babies with and without compli-
cations at birth developed normally. Of the 76 recruited
women, we studied and assessed the clinical and labora-
tory features of the 60 pregnant patients with PR who had
no known risk factors for intrauterine fetal death. The
mean age (±standard deviation, SD) at onset of PR was
29.1 ± 2.49 years in the patients with pregnancy or new-
born complications and 29.0 ± 2.55 years in those without
(Table 1). The difference was not statistically significant
(t = 0.154; p = 0.878). The mean week of PR onset during
pregnancy was 14.8 ± 3.65 in patients with pregnancy or
newborn complications and week 24.8 ± 3.64 in those
without. The difference was highly significant (t = 10.625;
p < 0.001). Enanthem affected 26 patients with pregnancy
or newborn complications (86.7%) and 7 without. The
difference was highly significant (χ2 = 21.813; p < 0.001).
The presence of constitutional symptoms was noted
by 26 patients with pregnancy or newborn complications
(86.7%) and by 9 patients without (30%). The difference
was highly significant (χ2 = 17.554; p < 0.001).
PR lesions involved >50% of the body area in 11 pa-
tients with pregnancy or newborn complications (36.7%)
and only in 1 patient (3.3%) without. The difference was
highly significant. All patients denied any previous preg-
nancy complication or fetal demise. Furthermore, in 50
patients (20 with pregnancy complications and 30 with-
out) we obtained blood samples to assess both HHV-6
and HHV-7 viral DNA loads (copies/mL) in the plasma,
using calibrated quantitative real-time polymerase chain
reaction (PCR) as previously described [7]. The mean vi-
ral load of HHV-6 was 585.15 ± 459.17 copies/mL in the
20 patients with pregnancy or newborn complications
versus 73.73 ± 67.82 in the 30 patients without complica-
tions. The difference was highly significant (t = 6.033; p <
0.001).
155.247.166.234 - 7/31/2018 2:08:11 PM
Dermatology 2018;234:31–36 33
DOI: 10.1159/000489879
Temple University
Downloaded by:
 Color version available online
Onset of PR during >15 weeks Enanthem
HHV-6 plasma viral load pregnancy
(if possible)

<585 copies/mL ≥585 copies/mL ≤15 weeks Yes No

PR body surface area involved >50%

and/or constitutional symptoms

Yes, at least one No

Undetermined risk
pregnancy

Lower-risk pregnancy High-risk pregnancy Lower-risk pregnancy

HHV-6 plasma viral load
≥585 copies/mL <585 copies/mL

Follow-up Rest: at least 2 weeks

Follow-up
Careful clinical and laboratory follow-up (ultrasound)
Possible therapy

Fig. 3. Laboratory and clinical algorithm in pregnant pityriasis rosea (PR) patients. HHV-6 plasma viral load
identifies high- or lower-risk pregnancy. If HHV-6 plasma viral load was not tested, proceed with the clinical
algorithm; undetermined risk pregnancies will need an HHV-6 plasma viral load test to assign high or lower risk.

The mean viral load of HHV-7 was 42.15 ± 162.44 cop-
ies/mL in patients with pregnancy or newborn complica-
tions and 14.30 ± 24.10 in those without. The difference
was not significant (t = 0.929; p = 0.358).
With the logistic regression, we analyzed all parame-
ters already studied with the t test and the χ2 test, with the
exception of HHV-6 and HHV-7 viral loads, which were
not studied because we had determined them in only 50
patients. The logistic regression analysis examined the re-
lationship between risk factors and pregnancy complica-
tions when all risk factors were considered together. This
analysis provides the most influential risk factors [8]. Ear-
ly onset of PR (p = 0.0017) and the presence of enanthem
(p = 0.0392) proved to be significantly associated with
pregnancy or newborn complications. The odds ratio for
early onset was 0.4880 (95% CI: 0.3115–0.7645). The odds
ratio for enanthem was 19.3284 (95% CI: 1.1584–
322.4902). No statistical associations were found between
the presence of constitutional symptoms, age of the preg-
nant woman, involvement of >50% of the body area, and
pregnancy or newborn complications.
Discussion
In our study we found a number of risk factors that
may be related to an adverse pregnancy or birth out-
come. The current findings are consistent with our pre-
vious studies, but seem more significant, because the
number of patients is higher and further statistical pro-
cessing of data, such as the logistic regression, has been
added [1, 5].
We discovered that the most important risk factor
threatening the successful outcome of pregnancy was the
high viral load of HHV-6. PR is associated with an endog-
enous systemic reactivation of HHV-6 and/or HHV-7,
either individually or in combination [7]. We showed
previously that if PR occurs during pregnancy, intrauter-
ine fetal infection may happen, causing pregnancy com-
plications or birth defects [5, 6].
The current study confirms that only systemic active
infection with HHV-6, especially during the first weeks of
gestation, is a major risk factor for complications during
pregnancy. In fact, we failed to find any evidence that
155.247.166.234 - 7/31/2018 2:08:11 PM

34 Dermatology 2018;234:31–36 Drago/Ciccarese/Herzum/Rebora/Parodi

DOI: 10.1159/000489879
Temple University
Downloaded by:
HHV-7 is associated with pregnancy complications in PR
patients, confirming previous findings [5, 6].
HHV-6 is probably an underestimated cause of fetal
infection [9], though Caserta et al. [10] have shown al-
most 40 years ago that HHV-6 may cause fetal infection.
They demonstrated HHV-6 reactivation or reinfection in
17% of pregnant women identifying active placental in-
fection and congenital HHV-6 infection. Later, Ashshi et
al. [11] detected HHV-6 DNA in 25% of fetuses with fetal
hydrops, and Al-Buhtori et al. [12] found HHV-6 in 2.7%
of cases of fetal demise, suggesting that viral infection
may be more common in fetal death than previously
thought. Lastly, Gervasi et al. [13] studied, in 729 women
undergoing midtrimester amniocentesis, the prevalence
of viral infections in the amniotic fluid through quantita-
tive real-time PCR. Considering a large series of viruses,
including adenoviruses, herpes simplex virus, varicella
zoster virus, HHV-6, human cytomegalovirus, Epstein-
Barr virus, parvovirus B19, and enteroviruses, they found
HHV-6 to be the most frequently detected virus in amni-
otic fluid (7 cases, 1.0%) followed by human cytomegalo-
virus (0.8%), parvovirus B19 (0.3%), and Epstein-Barr vi-
rus (0.1%) [13].
Before performing an expensive study on viral loads,
physicians should take into consideration some elemen-
tary clinical signs that can guide them in defining the de-
gree of risk in a pregnant woman with PR. The onset of
PR before week 15 and enanthem are major risk factors
that should alarm the dermatologist. Constitutional
symptoms and involvement of >50% of the body area may
be considered minor risk factors (Fig. 3). Furthermore, it
is important to distinguish PR-like eruption caused by
concomitant therapies, a condition with which it is suf-
ficient to stop the involved drug [14, 15].
As HHV-6 infection is the main risk factor for PR oc-
curring during pregnancy [14–18], some precautions
should be taken. Pregnant PR patients should rest at
home up to their recovery, as with all severe viral infec-
tions. Antiviral therapies, such as acyclovir or valacyclo-
vir, may be contemplated when the degree of risk for the
pregnancy or birth outcome are very high. Acyclovir is
effective in HHV-6 infection [19] and gives symptomatic
relief in PR [20]. Regrettably, acute renal failure second-
ary to acyclovir is a well-described side effect, with the
most common mechanism being crystal nephropathy,
and a case of nephrotoxicity has been reported in a wom-
an at 32 weeks of pregnancy who had been treated for
possible chickenpox [21]. As regards the treatment of PR
during pregnancy, there are no specific guidelines. In-
deed, we prescribed oral acyclovir treatment (800 mg
Pityriasis Rosea during Pregnancy
thrice daily for 7 days) only in 5 women presenting with
early PR onset (during the first 20 weeks of pregnancy),
particularly widespread and itchy lesions, systemic symp-
toms, and a state of great anxiety due to their illness.
However, the antiviral regimen did not shorten the dura-
tion of the illness nor did it prevent complications in 3 of
the treated patients. We therefore suggest considering a
low-dosage antiviral treatment only when PR in pregnan-
cy has an early onset and is associated with systemic
symptoms, or when a state of anxiety is so intense that it
may significantly lower the patient’s quality of life. Rest
and reassurance are probably the best cure.
In conclusion, in all the pregnant PR patients, and es-
pecially in the patients at high risk, it is mandatory to per-
form a careful follow-up with available instrumental
techniques such as ultrasound scans that can promptly
detect pregnancy or fetal complications.
Key Message
Physicians should take clinical signs and HHV-6 viral load into
consideration in pregnant women with pityriasis rosea.
Statement of Ethics
Patients were asked to sign a written informed consent to the
study. The institute’s committee on human research approved the
study protocol.
Disclosure Statement
The authors have no conflict of interest or financial support to
declare.
References   1 Drago F, Ciccarese G, Rebora A, Broccolo F,
Parodi A: Pityriasis rosea: a comprehensive
classification. Dermatology 2016; 232: 431–
437.
  2 Drago F, Broccolo F, Ciccarese G, Rebora A,
Parodi A: Persistent pityriasis rosea: an un-
usual form of pityriasis rosea with persistent
active HHV-6 and HHV-7 infection. Derma-
tology 2015;230:23–26.
  3 Drago F, Ciccarese G, Gasparini G, Cogorno
L, Javor S, Toniolo A, Broccolo F: Contempo-
rary infectious exanthems: an update. Future
Microbiol 2017;12:171–193.
 4 Corson EF, Luscombe HA: Coincidence of
pityriasis rosea with pregnancy. AMA Arch
Derm Syphilol 1950;62:562–564.
155.247.166.234 - 7/31/2018 2:08:11 PM
Dermatology 2018;234:31–36 35
DOI: 10.1159/000489879
Temple University
Downloaded by:
  5 Drago F, Broccolo F, Zaccaria E, Malnati M,
Cocuzza C, Lusso P, Rebora A: Pregnancy
outcome in patients with pityriasis rosea. J
Am Acad Dermatol 2008;58:S78–S83.
  6 Drago F, Broccolo F, Javor S, Drago F, Rebora
A, Parodi A: Evidence of human herpesvi-
rus-6 and -7 reactivation in miscarrying
women with pityriasis rosea. J Am Acad Der-
matol 2014;71:198–199.
  7 Broccolo F, Drago F, Careddu AM, Foglieni
C, Turbino L, Cocuzza CE, Gelmetti C, Lusso
P, Rebora AE, Malnati MS: Additional evi-
dence that pityriasis rosea is associated with
reactivation of human herpesvirus-6 and -7. J
Invest Dermatol 2005;124:1234–1240.
  8 Bland M: An Introduction to Medical Statis-
tics, ed 4. Oxford, Oxford University Press,
2015.
  9 Flamand L, Komaroff AL, Arbuckle JH, Med-
veczky PG, Ablashi DV: Review, part 1: Hu-
man herpesvirus-6-basic biology, diagnostic
testing, and antiviral efficacy. J Med Virol
2010;82:1560–1568.
36 Dermatology 2018;234:31–36
DOI: 10.1159/000489879
10 Caserta MT, Hall CB, Schnabel K, Lofthus G,
McDermott MP: Human herpesvirus (HHV)-
6 and HHV-7 infections in pregnant women.
J Infect Dis 2007;196:1296–1303.
11 Ashshi AM, Cooper RJ, Klapper PE, Al-Jiffri
O, Moore L: Detection of human herpes virus
6 DNA in fetal hydrops. Lancet 2000; 355:
1519–1520.
12 Al-Buhtori M1, Moore L, Benbow EW, Coo-
per RJ: Viral detection in hydrops fetalis,
spontaneous abortion, and unexplained fetal
death in utero. J Med Virol 2011;83:679–684.
13 Gervasi MT, Romero R, Bracalente G, Chai-
worapongsa T, Erez O, Dong Z, Hassan SS,
Yeo L, Yoon BH, Mor G, Barzon L, Franchin
E, Militello V, Palù G: Viral invasion of the
amniotic cavity (VIAC) in the midtrimester
of pregnancy. J Matern Fetal Neonatal Med
2012;25:2002–2013.
14 Drago F, Ciccarese G, Rebora A, Parodi A:
Pityriasis rosea and pityriasis rosea-like erup-
tion: can they be distinguished? J Dermatol
2014;41:864–865.
15 Drago F, Broccolo F, Agnoletti A, Drago F,
Rebora A, Parodi A: Pityriasis rosea and pity-
riasis rosea-like eruptions. J Am Acad Derma-
tol 2014;70:196.
16 Ciccarese G, Broccolo F, Rebora A, Parodi A,
Drago F: Oropharyngeal lesions in pityriasis
rosea. J Am Acad Dermatol 2017;77:833–837.
17 Drago F, Ciccarese G, Rebora A, Parodi A: Re-
lapsing pityriasis rosea. Dermatology 2014;
229:316–318.
18 Drago F, Ciccarese G, Broccolo F, Ghio M,
Contini P, Thanasi H, Parodi A: The role of
cytokines, chemokines, and growth factors in
the pathogenesis of pityriasis rosea. Media-
tors Inflamm 2015;2015:438963.
19 Wagstaff AJ, Faulds D, Goa KL: Aciclovir. A
reappraisal of its antiviral activity, pharmaco-
kinetic properties and therapeutic efficacy.
Drugs 1994;47:153–205.
20 Fölster-Holst R, Zawar VP, Chuh A: Paraviral
exanthems. Expert Rev Anti Infect Ther 2016;
14:601–611.
21 Chang YH, Tseng JY, Chen CY, Sung PL, Yeh
CC, Yang MJ: Acyclovir-induced nephrotox-
icity in a pregnant woman with chickenpox.
Taiwan J Obstet Gynecol 2016;55:618–619.
155.247.166.234 - 7/31/2018 2:08:11 PM
Drago/Ciccarese/Herzum/Rebora/Parodi
Temple University
Downloaded by: