ORIGINAL ARTICLES

Oropharyngeal lesions
in pityriasis rosea
Giulia Ciccarese, MD,a Francesco Broccolo, MD,b Alfredo Rebora, MD,a
Aurora Parodi, MD,a and Francesco Drago, MDa
Genoa and Monza, Italy

Background: Pityriasis rosea (PR) is an exanthematous disease associated with the endogenous systemic
reactivation of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7). Oropharyngeal lesions
may be associated with the exanthema, but anecdotal evidence suggests that few dermatologists are aware
of their occurrence.

Objective: Classifying oropharyngeal lesions in PR, establishing their prevalence, and assessing their
possible association with different PR forms.

Methods: The records of all PR cases diagnosed in the Dermatology Clinic of Genoa University between
2003 and 2016 were retrospectively reviewed to examine sex and age of the patients, PR type, presence of
enanthema, systemic symptoms, specific antieHHV-6 and or HHV-7 serology, and HHV-6 and/or HHV-7
DNA loads.

Results: The oropharyngeal mucosa was carefully examined in 527 patients with PR. Painless
oropharyngeal lesions were observed in 149 patients with PR (28%) and classified as erythematomacular,
macular and papular, erythematovesicular, and petechial lesions. The petechial and macular and papular
patterns were those most frequently observed. There was no statistically significant difference in the levels
of HHV-6 and HHV-7 viremia in the plasma of patients with enanthema and those without.

Limitations: Because this was a retrospective study, biopsies on mucosal lesions were not performed.

Conclusion: Our findings showed that enanthemas are frequently associated with forms of PR different
from the classic form. ( J Am Acad Dermatol 2017;77:833-7.)

Key words: enanthemas; human herpesvirus 6/7; oropharyngeal lesions; pityriasis rosea.

P ityriasis rosea (PR) is an acute, self-limiting

exanthematous disease associated with the
endogenous systemic reactivation of human
herpesvirus 6 (HHV-6) and/or HHV-7.1-6 The disease
Abbreviations used:
ClasPR:
HHV:
PR:
classic pityriasis rosea
human herpesvirus
pityriasis rosea
typically begins with a single, erythematous scaly PedPR: pediatric pityriasis rosea
plaque (herald patch) that is followed after about PersPR: persistent pityriasis rosea
PregPR: pityriasis rosea in pregnancy
2 weeks by smaller papulosquamous lesions on the RelPR: relapsing pityriasis rosea
cleavage lines of the trunk, giving the back the VHF: viral hemorrhagic fever
configuration of a ‘‘Christmas tree,’’1-7 or as we
prefer, the configuration of a ‘‘theatre curtain.’’ PR
lasts from 2 weeks to a few months, and constitu- PR (ClasPR), different forms of PR have been
tional symptoms may precede or accompany the skin described and classified according to the pathogen-
eruption.4 As in other exanthemas, alongside classic esis and course of the disease: pediatric PR (PedPR),8

From the DISSAL Department of Dermatology, IRCCS AOU San
Martino-IST, Genoa,a and Department of Health Sciences,
University of Milano-Bicocca, Monza.b
Funding sources: None.
Conflicts of interest: None disclosed.
Accepted for publication June 17, 2017.
Reprints not available from the authors.
Correspondence to: Giulia Ciccarese, MD, DISSAL, Department of
Dermatology, IRCCS A.O.U. San Martino-IST, Largo Rosanna
Benzi 10, 16132 Genova, Italy. E-mail: giuliaciccarese@libero.it.
Published online July 18, 2017.
0190-9622/$36.00
Ó 2017 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2017.06.033

833
834 Ciccarese et al J AM ACAD DERMATOL
NOVEMBER 2017

relapsing PR (RelPR),9 persistent PR (PersPR),10 PR in rather drug reactions resembling PR rashes.12-14

11 12-14
pregnancy (PregPR), and PR-like eruptions. All cases of PR were diagnosed by at least 1
Furthermore, PR eruptions that may be considered dermatologist of our group. Diagnosis was made
atypical from the standpoints of morphology, size, by using classical clinical criteria supported by
number, distribution, and site of the lesions have also laboratory investigations and/or histopathology
been reported.15-17 whenever needed.
Mucosal lesions (enanthemas), especially oropha-
ryngeal, may be associated with the skin lesions: they RESULTS
follow the course of the skin Between January 2003
eruption, disappearing with CAPSULE SUMMARY and December 2016, 635
it or a few days later.4 patients with different forms
They include punctate
d Oropharyngeal lesions may be
of PR were observed. The
hemorrhages, erosions or associated with exanthema in pityriasis
oropharyngeal mucosa was
ulcerations, erythematous rosea (PR).
carefully examined in 527 of
annular lesions, and macules d We report an expanded set of clinical them: 486 adults and 41
or plaques. There is no features that can be observed in PR and children between 3 and
consensus as to the fre- its variants. 9 years old. At the time of
quency of oropharyngeal d Familiarity with the typical diagnosis, 149 patients (28%)
lesions,18-21 and anecdotal oropharyngeal manifestations of PR may had oropharyngeal lesions
evidence suggests that few help clinicians distinguish it from other involving the palate and/or
dermatologists are aware of oral mucosal diseases. the pharynx, all of which
their occurrence. In addition, were painless. Among these
the accurate appraisal of 149 PR patients with oropha-
their frequency is further ryngeal lesions, 90 consented to undergo an oropha-
complicated by the presence of forms of PR that ryngeal swab for culture. The swabs showed normal
are different from the classic form.8-14 flora in all 90 cases. The remaining 378 patients
Very few studies to date have focused on with PR (72%) had no lesions on the oral mucosa
enanthemas associated with PR.18-22 The aims of (Supplemental Table I; available at http://www.jaad.
our study were to classify oropharyngeal lesions in org). Oropharyngeal lesions have been classified
PR, establish their prevalence, and assess their into 4 categories: erythematomacular, macular and
possible association with the different forms of papular, erythematovesicular, and petechial lesions
PR. More specifically, we attempted to establish (Fig 1, A-D).
whether the presence of oropharyngeal lesions was Petechial and macular and papular were the
associated with particular features of PR. patterns most frequently observed. Oropharyngeal
petechiae were found mainly in PersPR (18 of 24 cases
MATERIALS AND METHODS [75%]) and in PedPR (10 of 17 cases [59%]); macular
The present retrospective population-based papules were reported in all PR types but mainly in
cohort study included all cases of PR diagnosed in RelPR (10 of 16 cases [62%]), with erythematous
the Dermatology Clinic of the University of Genoa vesicles reported mainly in PregPR (6 of 29 cases
(Italy) between 2003 and 2016. The records of all PR [22%]) and erythematous macules mainly in ClasPR
cases were incorporated into a PR registry and (26 of 63 cases [41%]) (Supplemental Table II;
reviewed to examine the following features: sex available at http://www.jaad.org). Strawberry tongue
and age of the patients, type of PR (classic, pediatric, was observed in only 2 children with PR.10
or other variants),14 presence of enanthema, Systemic symptoms, especially prodromal or
morphology of the enanthema, systemic symptoms, accompanying symptoms during the first 7 days after
specific antieHHV-6 or antieHHV-7 serology, onset, were reported with different degrees of
and HHV-6 or HHV-7 DNA loads, which severity and duration in 68% of patients with PR
where assessed by using a calibrated quantitative with enanthema (101 of 149 patients). Symptoms
real-time polymerase chain reaction, as previously were mainly associated with oral petechiae and, to a
described,23 at the first visit. The specific cutoff value lesser extent, with oral macular papules
for viral DNA detection in plasma was 10 genome (Supplemental Table III; available at http://www.
equivalents per mL.3 jaad.org). Conversely, among the 378 patients with
Among the variants of PR, PR-like eruptions have PR without enanthema, systemic symptoms were
been excluded from the present study because they reported in 35% (132 of 378 patients). The difference
are considered not genuine forms of PR forms but between patients with enanthema and those without
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Fig 1. Oropharyngeal lesions of pityriasis rosea. A, Erythematous macules of the hard palate.
B, Macular papules of the soft palate. C, Erythematous vesicles of the hard palate. D, Petechiae
of the hard palate.
was statistically significant (chi-square value,
28.3895; P \.00001).
Among the patients with PR with enanthema who
complained of systemic symptoms, sore throat was
the most common (in 90 of 101 patients); fatigue and
headache were common in patients with PR both
with and without enanthema followed by fever,
insomnia, anorexia, pruritus, nausea, and irritability.
Among the 149 patients with PR with enanthema,
systemic symptoms were more frequent in PersPR,
RelPR, PedPR, and PregPR than in ClasPR. The
statistical analysis showed a highly significant
difference in occurrence of systemic symptoms
between patients with ClasPR and patients with
PedPR, PersPR, RelPR, and PregPR (chi-square value,
31.1; P \ .00001) (Supplemental Table IV; available
at http://www.jaad.org).
All 149 patients with PR with enanthema gave
informed consent for collection of blood samples for
measuring HHV-6 and HHV-7 plasma viremia. A total
of 65 patients (44%) were positive for HHV-6 plasma
viremia (mean viral load, 193.5 copies/mL [range,
20-760 copies/mL]), and 42 patients (28%) were
positive for HHV-7 plasma viremia in (mean viral
load, 97.2 copies/mL [range, 35-430 copies/mL]).
Nineteen patients with PR with enanthema (13%)
had both HHV-6 and HHV-7 plasma viremia. Among
the 378 patients with PR without enanthema, 87
patients gave informed consent for collection of
blood samples for measuring HHV-6 and HHV-7
plasma viremia. The results of testing for HHV-6
plasma viremia were positive in 61 patients (70%)
(mean viral load, 82.4 copies/mL [range, 10-436]),
with positive results of testing for HHV-7 plasma
viremia in 107 patients (40%) (mean viral load, 55.7
copies/mL [range, 10-140 copies/mL]). Thirty-four
patients with PR without enanthema (9%) had both
HHV-6 and HHV-7 plasma viremia. There was no
statistically significant difference in the levels of
Ciccarese et al 835
HHV-6 and HHV-7 viremia in the plasma of patients
with PR with and without enanthema.
DISCUSSION
In our study, involvement of the oral mucosa in
patients with PR was carefully investigated. The
statistical, clinical, and laboratory investigation of
826 patients with PR and healthy controls by
Bjornberg and Hellgren in 196224 did not mention
possible involvement of the oropharyngeal mucosa.
In the last 2 decades, very few studies have focused
on oropharyngeal lesions associated with PR, with
last such study dating back to 1992.18 A wide range of
lesions have been reported in the literature: oral
erosions and ulcerations are the most frequent,
followed by punctate hemorrhages, erythematous
annular lesions, and macules or plaques.18-22,25 In
contrast to what was reported previously, the most
common type of oropharyngeal lesions in our PR
series was the macular and papular and mainly
the petechial pattern lesions, which may be likened
to the punctate hemorrhages previously described
in the literature in association with the PR exan-
themas.18-22 Conversely, we failed to observed oral
erosions and ulcerations. A petechial enanthema can
be observed in association with other infectious
exanthemas. More specifically, viruses that may
cause a petechial enanthema associated with an
exanthema are arboviruses (especially Rift Valley
fever virus), other tropical viruses responsible for
viral hemorrhagic fevers (VHFs) (Junin virus,
Crimean-Congo virus, Ebola virus, and others), and
respiratory viruses (influenza A and B viruses,
respiratory syncytial virus, and parainfluenza
viruses). Moreover, coinfection with Epstein-Barr
virus/cytomegalovirus and respiratory agents may
cause macular and papular rash and palatal
petechiae, making it difficult to assign the cause of
the rash.25 However, in the case of arbovirus
836 Ciccarese et al
exanthemas and VHFs, history of travel in endemic
regions (southeastern/western/northern Africa,
Madagascar, and Yemen for both and South
America for VHFs), presence of severe systemic
symptoms (high fever, headache, photophobia,
and tachycardia), and (especially in VHF) presence
of a petechial exanthema may help in the diagnosis;
conversely, in the case of respiratory virus infections,
the presence of respiratory symptoms 1 to 2 days
before the onset of a macular and papular or
vesicular exanthema, may guide the diagnosis.25 In
addition, bacterial exanthemas caused by Neisseria
meningitides and Staphylococcus aureus may also
be associated with petechial enanthemas. In
the case of N meningitides infection, a petechial
enanthema may be associated with macular/macular
and papular/purpuric skin lesions during
meningococcemia with severe systemic symptoms
(high fever, stiffness, headache, and change in
mental status). In acute S. aureus endocarditis and
bacteremia, petechial eruptions occur in crops
affecting mainly the extremities and oral mucous
membranes and conjunctivae.25
Although the number of pediatric cases in our
series was limited, the oropharyngeal lesions proved
to be more common in children with PR (41%) than
in adults with PR (27%), confirming our previous
studies.4,10,14 In addition, the prevalence of
oropharyngeal involvement in our adult patients
(27%) was much higher than previously reported in
dark-skinned (9%)22 and white adult patients (16%).4
Globally, our findings showed that oropharyngeal
lesions are frequently associated with PersPR, RelPR,
PregPR, and PedPR but can also be observed in
ClasPR (17%) (Supplemental Table I). Moreover, in
all the variants of PR different from the classic form,
the presence of oropharyngeal lesions was strongly
associated with systemic symptoms (Supplemental
Table IV).6 On the contrary, enanthemas were not
associated with the detection of HHV-6 and/or
HHV-7 plasma viremia nor with the HHV-6 and/or
HHV-7 viral load in plasma (Fig 2). In clinical
practice, distinguishing PR oropharyngeal lesions
from mucosal lesions of different origin that may
concur with PR (aphthous lesions, herpes simplex or
other herpesvirus-related lesions, and cancerous or
precancerous lesions) allows unnecessary diagnostic
procedures (blood examinations or mucosal
biopsies) and treatments to be avoided.
Whenever painless oropharyngeal lesions are
present, the associated papulosquamous skin lesions
with a Christmas tree or theatre curtain distribution
allows a PR to be easily diagnosed. Furthermore,
when the herald patch is the sole manifestation of PR
or when PR eruption resembles drug-related rash,
J AM ACAD DERMATOL
NOVEMBER 2017
Fig 2. Plasma human herpesvirus-6 (HHV-6) and human
herpesvirus-7 (HHV-7) levels (copies per milliliter)
distribution among patients with pityriasis rosea PR with
enanthemas (box plots and filled circles and diamonds)
and without enanthemas (box plots and unfilled circles
and diamonds). Box plots display the 25th and 75th
percentiles, the median (horizontal line); points above
and below the whiskers indicate outliers outside the 10th
and 90th percentiles.
the presence of oropharyngeal lesions may help in
making the correct diagnosis.
In conclusion, dermatologists should be aware of
the presence of enanthemas in patients with PR.
Indeed, their detection can predict an atypical course
(PersPR and RelPR), requiring a closer follow-up11
and, in some instances, systemic treatment.26,27
Therefore, in patients with PR, we suggest careful
examination of not only the entire skin surface but
also the oropharyngeal mucosa.
We thank Anna Tedone for her valuable help in
collecting blood samples.
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837.e1 Ciccarese et al J AM ACAD DERMATOL
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Supplemental Table I. Type of PR in patients with enanthema and patients without enanthema
Patients with Patients without Comparison for each
PR type enanthema, n (%) enanthema, n (%) Total patients, n (%) PR type (P value)
ClasPR 63 (17%) 302 (83%) 365 (100%) e
PersPR 24 (75%) 8 (25%) 32 (100%) ClasPR vs PersPR (\.005)
RelPR 16 (59%) 11 (41%) 27 (100%) ClasPR vs RelPR (\.005)
PregPR 29 (47%) 33 (53%) 62 (100%) ClasPR vs PregRP (\.005)
PedPR 17 (41%) 24 (59%) 41 (100%) ClasPR vs PedPR (\.005)
PersPR vs RelPR (ns)
PersPR vs PregPR (.0089)
PersPR vs Ped PR (.004)
RelPR vs PregPR (ns)
RelPR vs PedPR (ns)
PregPR vs PedPR (ns)

ClasPR, Classic pityriasis rosea; ns, not significant; PedPR, pediatric pityriasis rosea; PersPR, persistent pityriasis rosea; PR, pityriasis rosea;
PregPR, pityriasis rosea of pregnancy; RelPr, relapsing pityriasis rosea.
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Supplemental Table II. Pattern of enanthemas in the different pityriasis rosea types
No. of patients No. of patients with No. of patients with No. of patients with Total patients with
with petechial erythematovesicular erythematomacular macular and papular enanthemas in
PR type enanthemas enanthemas enanthemas enanthemas different PR types
Classic PR 6 (9%) [14%] 8 (13%) [40%] 26 (41%) [65%] 23 (36%) [50%] 63 (100%) [42%]
Persistent PR 18 (75%) [42%] 2 (8.3%) [10%] 2 (8.3%) [5%] 2 (8.3%) [4%] 24 (100%) [16%]
Relapsing PR 2 (12.5%) [5%] 2 (12.5%) [10%] 2 (12.5%) [5%] 10 (62.5%) [22%] 16 (100%) [11%]
PR in pregnancy 7 (24%) [16%] 6 (22%) [30%] 8 (27%) [20%] 8 (27%) [17%] 29 (100%) [19%]
Pediatric PR 10 (59%) [23%] 2 (12%) [10%] 2 (12%) [5%] 3 (17%) [7%] 17 (100%) [12%]
Total patients with 43 (29%) [100%] 20 (13%) [100%] 40 (27%) [100%] 46 (31%) [100%] 149 (100%) [100%]
PR with enanthemas

Numbers in parentheses are percentage distribution of the different enanthema patterns in each type of PR (to be read in a horizontal
direction); numbers in brackets are percentage distribution of each enanthema pattern in the different types of PR (to be read in a vertical
direction).
PR, Pityriasis rosea.
837.e3 Ciccarese et al J AM ACAD DERMATOL
NOVEMBER 2017

Supplemental Table III. Presence or absence of systemic symptoms in patients with PR with the different
enanthema patterns
Patients with Patients with Patients with Patients with
Presence or absence petechial erythematovesicular erythematomacular macular and Total patients
of systemic symptoms enanthemas enanthemas enanthemas papular enanthemas with enanthemas
Systemic symptoms 40 (93%) 11 (55%) 16 (40%) 34 (74%) 101 (68%)
No systemic symptoms 3 (7%) 9 (45%) 24 (60%) 12 (26%) 48 (32%)
Total 43 (100%) 20 (100%) 40 (100%) 46 (100%) 149 (100%)

PR, Pityriasis rosea.

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Supplemental Table IV. Presence and absence of systemic symptoms in the different forms of PR among the
149 patients with PR with enanthemas
Presence or absence Persistent Relapsing Pediatric PR in Total Chi-square
of systemic symptoms Classic PR PR PR PR pregnancy patients P value statistic
Systemic symptoms 28 (44%) 23 (96%) 15 (94%) 12 (71%) 23 (79%) 101 (68%) \.00001 31.1285
No systemic symptoms 35 (56%) 1 (4%) 1 (6%) 5 (29%) 6 (21%) 48 (32%)
Total 63 (100%) 24 (100%) 16 (100%) 17 (100%) 29 (100%) 149 (100%)

Statistical analysis showed a significant difference in occurrence of systemic symptoms between patients with classic PR and patients with
atypical PR (persistent PR, relapsing PR, PR in pregnancy, and pediatric PR). (A P value less than .05 is significant.)
PR, Pityriasis rosea.