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Pityriasis rosea (PR) is a common self-limiting exanthem of unknown

origin seen in children and young adults. It was first described in 1798

by the British physician Robert Willan under the name roseola annulata.1

In 1860, the French doctor Camille Melchior Gilbert appropriately named

the scaly, pink rash pityriasis rosea, after pityriasis meaning bran-like

and rosea meaning rose-colored.2 PR is also known as pityriasis rosea

of Gilbert, pityriasis maculata et circinata, pityriasis rosea of Vidal, and

pityriasis circinata et marginata.1 For nearly two centuries much has

been done to study and describe the rash of PR, yet very little is known

regarding its etiology and treatment.

Pathogenesis

The cause of PR is unknown. It has been hypothesized that PR is

viral in origin, and several of its characteristics suggest this. First,

there is an increased incidence of disease during winter months. 3,4

Second, outbreaks of PR have occurred among certain groups suchas family members and military personnel.5,6 Third, the course of

PR is nearly always the same, with the herald patch appearing at the

onset, followed by a generalized eruption several days later. Other

viral exanthems, such as measles and chicken pox, also follow very

typical courses. Lastly, the majority of people will experience PR only

once in their lifetime, suggesting acquired immunity. 3,7 There has also

been increasing evidence implicating human herpesvirus six (HHV-6)

and HHV-7 in the pathogenesis of PR, 812 although other studies have

failed to show an association.1316 Currently, the role of these viruses

remains controversial.

Various drugs are known to cause a PR-like reaction. These include

bismuth, captopril, barbiturates, gold, isotretinoin, penicillamine,

metronidazole, and others. Morphological atypia of these drug-induced

rashes is accompanied by different histopathological features from

classic PR, with interface dermatitis and eosinophils. Recently,

adalimumab (Humira), a monoclonal antibody to tumor necrosis factor-

alpha (TNF-) that is used in the treatment of psoriasis, rheumatoid

arthritis, and other inflammatory conditions, was reported to induce PR. 17

Interestingly, PR-like rashes have also been reported after vaccinations

with pneumococcus,18 hepatitis B virus,19 smallpox,20,21 diphtheria,22,23 and

bacillus Calmette-Gurin (BCG).24,25 This is an important association

because it implies the possibility of immune stimulation triggering PR.

The outcome of PR in pregnancy has recently been addressed in one

study, which found that PR during pregnancy can be very dangerous.26

Itmay foreshadow premature delivery and even fetal demise. Out of

38 pregnant women with PR, nine had a premature delivery and five

miscarried. Neonatal hypotonia, weak motility, and hyporeactivity were

noted in six cases. One woman in the study who developed PR at

10 weeks of gestation and aborted two weeks later had HHV-6 DNA

detected in plasma, skin, peripheral blood mononuclear cells (PBMCs),

and placental and embryonic tissue. The greatest risk to the fetus

occurred when PR developed in the first 15 weeks of gestation. This is

important to note so that pregnant women may be appropriately

referred to high-risk maternalfetal medicine specialists if they develop

55 T O U C H B R I E F I N G S 2 0 0 9

Pediatric Dermatology

Kathryn E Swygert , BS 1 and John C Browning , MD 2

1. Medical Student; 2. Chief, Pediatric Dermatology, and Assistant Professor of Pediatrics and Dermatology,

University of Texas Health Science Center at San Antonio

Pityriasis RoseaPathogenesis, Diagnosis, and Treatment

Abstract

Pityriasis rosea (PR) is a common self-limiting skin rash. It is most commonly characterized by scaly macules along the lines of skin cleavage on the

trunk, although other patterns also occur. Diagnosis can usually be made by clinical observation, but in certain cases biopsy and/or additional studies

may be indicated. Attempts to determine the exact etiology of PR have been inconclusive, but it is thought to be caused by a virus because of the

clustering of PR cases among contacts as well as its predilection to occur at certain times of year. Various treatments have been used, including oral

antibiotics, antivirals, topical steroids, and ultraviolet light therapy, with variable success. While reassurance and observation may be considered for

PR, it is important to differentiate PR from other skin conditions where active treatment may be indicated.

Keywords

Pityriasis rosea, viral exanthem, rash, erythromycin, syphilis, pregnancy, human herpesvirus 6 (HHV-6)

Disclosure: The authors have no conflicts of interest to declare.

Received: September 22, 2009 Accepted: December 9, 2009

Correspondence: John C Browning, MD, Assistant Professor, Pediatrics and Dermatology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive,

MSC 7808, San Antonio, TX 78229. E: [email protected]


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PR. Because of subtleties in distinguishing PR from secondary syphilis,

pregnant women with PR should have serological testing for syphilis due

to danger to the fetus when syphilis is not treated.27

Epidemiology

PR is most common between 10 and 35 years of age,28 but has been

reported in patients as young as three months29 and as old as 83 years

of age.7 PR occurs worldwide with no racial or gender predilection. The

prevalence of PR remains largely unknown, even though numerous

studies have tried to establish these data. One study estimated the

prevalence to be 1.31%,7 but this is likely underestimated given

the largely unrecognized atypical forms of PR, as well as the failure ofdiagnosis by many non-dermatologists. In a 2007 Cochrane review on

interventions for PR, data from nine studies were analyzed, with the

finding that out of every 1,000 people seen by a dermatologist, around

seven are diagnosed with PR.30 Chuangs 1982 study reported that out

of every 100,000 people in the community, about 170 will have PR in

a given year.3

Clinical Presentation

Classically, a single 210cm, round to oval, erythematous, scaly patch

signals the onset of PR (see Figure 1). This indicative lesion, known as

the herald patch, heralds the coming of numerous smaller macules and

patches that are typically around 1cm in size. The herald patch may

occur anywhere, but is most frequently located on the trunk or proximal

extremities. Occasionally, patients will not develop a herald patch prior

to the generalized rash, or they may not remember the herald patch.

This may be due to the asymptomatic nature of the patch, or an unusual

location. There have been rare reports of the herald patch located on

the plantar surface of a foot, face, scalp, and even penis.31,32 The herald

patch may be mistaken for tinea corporis; however, a simple scraping

and potassium hydroxide (KOH) examination can be performed to

exclude this diagnosis.

Days to weeks after the appearance of the hearald patch, the

generalized eruption of PR abruptly develops with numerous smaller

scaly patches usually limited to the trunk and proximal extremities.

These symmetrically oriented macules and patches present with their

long axis diagonally along the skin lines of the patients back reminiscent

of pine branches, hence the frequently used descriptor Christmas-tree

pattern33 (see Figure 2). Lesions appear pink in fair-skinned individuals

and the color varies from violet to dark gray in darker-skinned patients.

A fine scale resembling tissue paper is present inside the border of

these patches, giving the distinctive ring termed collarette scale. In

some individuals, PR affects the face and extremities more than the

trunk and is referred to as inverse PR. PR in patients with darker skin

often follows this inverse pattern and may involve the scalp and face,

usually leaving residual pigmentary changes (see Figure 3) upon

resolution of the rash in the majority of cases.34

While the classic clinical presentation is as previously mentioned,

atypical forms of PR exist, representing around 20% of all cases. 35,36

Unusual clinical presentations of PR may lead to difficulty in diagnosis

and can be differentiated by morphology, size, distribution, number,

location, severity, and course of the lesions. Atypical forms of PR

according to morphology are described as vesicular, purpuric

(hemorrhagic), or urticarial. In vesicular PR, 26mm vesicles are

present and may appear as a generalized eruption or a rosette of

vesicles.37,38 This form is more commonly seen in children and young

adults and may be extremely pruritic and extensive. When the


56 U S D E R M A T O L OG Y

Figure 1: Herald Patch Demonstrating the Presence of anErythematous Patch

Figure 2: Scaly Macules Along Lines of Skin Cleavage onthe Back (Christmas Tree Pattern)


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vesicular lesions are present on the palms, soles, or forearms,

dyshidrotic eczema or varicella may be suspected. Purpuric or

hemorrhagic PR usually presents with macular purpuric lesions and

may be accompanied by palatal petechiae.3943 Urticarial PR, also known

as PR urticata, presents with raised lesions resembling urticarial

wheals and is often extremely pruritic.32,44

PR gigantean of Darier and papular PR are atypical forms according tosize. A case report of PR gigantean of Darier from 1915 describes a

herald patch the size and shape of a pear.45 The clinical course was

noted to be similar to typical PR. In papular PR multiple small papules

12mm in size may be present alongside classic PR patches. 46 This

variant is more common in children.

Unique cases of asymmetric rash distribution have been reported, with

right- or left-sided unilateral PR.47 With regard to the variation in

symptoms, PR is often mildly pruritic, although some cases may be

highly pruritic or completely asymptomatic.33 Interestingly, there are

cases where only a single patch is present and the disease is limited to

this herald patch; conversely, there are also cases where the secondary

eruption begins without an initial herald patch.48

PR can be mistaken for other exanthems, most commonly pityriasis

lichenoides chronica (PLC), guttate psoriasis, secondary syphilis,

cutaenous lupus, capillaritis, pityriasis versicolor, and nummular

eczema. Rarely, cutaneous T-cell lymphoma may be mistaken for PR.

These diseases can be distinguished from PR in a variety of ways:

PLC has a similar distribution and morphology to PR, but can be

distinguished from PR by its chronic course. Also, unlike PR, PLC does

not begin with a herald patch.

Guttate psoriasis can be differentiated from PR by history (lack of

herald patch) and by physical exam, as the psoriasis macules have

thicker scale. Additionally, Auspitz sign can be elicited in patients with

guttate psoriasis by lifting the scale to reveal underlying bleeding

dermal capillaries.

While secondary syphilis is easily distinguished histologically from PR

by the presence of numerous plasma cells in the skin, a simple rapid

plasma reagin (RPR) and treponemal antibody test can also be used

for differentiation.

Subacute cutaneous lupus erythematosus (SCLE) can be distinguished

from PR due to the formers primarily photodistributed pattern. SCLE

characteristically spares covered areas such as the lower chest and

back, frequently affected areas in PR. SCLE can also be definitively

differentiated from PR by biopsy.

Capillaritis, an idiopathic condition in which inflammation of thecapillary vessels can lead to leakage of red blood cells into the skin, is

characterized by non-blanching erythematous patches. Schambergs

disease and eczematoid-like purpura of Doucas and Kapetanakis are

two subtypes of capillaritis that may be mistaken for PR. A skin biopsy

can easily distinguish between PR and capillaritis.

The distinction between Pityriasis versicolor (PV) and PR can be

made based on response to topical or oral antifungal agents as well

as distribution of the lesions (upper trunk, face, and neck in PV), color

(hypopigmented rather than erythematous), and the presence of

finer scale in PV.

Nummular eczema primarily involves the extremeties, whereas

classic PR involves the trunk.

Cutaneous T-cell lymphoma (CTCL), or mycosis fungoides as it is also

known, initially begins with a patch stage that can potentially be

mistaken for PR. Biopsy may be helpful, but not always. Often

multiple biopsies are required before a diagnosis of CTCL is made.

CTCL is far more common in adults than in children but should still

be considered in certain pediatric cases.49

HistologyThe histologic features of PR are non-specific. 5053 In the epidermis,

mild hyperkeratosis with focal parakeratosis, minimal acanthosis with

variable spongiosis, and a moderate exocytosis of lymphocytes with

a thinned granular layer is present. In the dermis, extravasated

red blood cells are accompanied by a perivascular infiltrate of

lymphocytes and eosinophils with occasional monocytes. Similar

findings are demonstrated in the herald patch with a deeper infiltrate

and more pronounced acanthosis. Dyskaratotic cells are present in

50% of cases.

Course

PR is a self-limiting disease. The duration of PR has been reported from

two weeks to five months, with the average extent of PR at 45 days. 45

Relapses of PR are extremely rare, with only 2.8% of patients

experiencing recurrent PR in one series of 826 patients.7 In a population

study with 939 patients, 17 patients (1.8%) had a relapse after anaverage of 4.5 years of follow-up.3 A single case of annual relapse for

five consecutive years has been reported.55 After disappearance of

lesions, post-inflammatory hypo- or hyperpigmentation may remain on

the affected skin.28

Treatment

As mentioned, PR is a self-limiting disease. Aside from the potential

risks during pregnancy, as previously discussed, PR is completely

benign. Thus, the best treatment is reassurance to the patient and

observation. However, in certain cases patients may request treatment

U S D E R M A T O L OG Y

Pityriasis RoseaPathogenesis, Diagnosis, and Treatment

57

Figure 3: Hypopigmentation at Sites ofPrevious Inflammation


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due to pruritus or cosmetic concerns. Around 50% of patients with PR

will have pruritus of moderate to severe intensity.7 It has also been

demonstrated that quality of life is significantly affected in patients with

PR.56,57 Parents of children with PR also have significant anxieties about

the disease, with concerns about the cause, course, and possible

infectious nature.57 As such, one of the most important aspects of

treatment is to inform the patient and family of the usual one- to three-

month course of the rash, educate them on its benign and non-contagious nature, and inform them that the child does not need to

stay home from school or other activities.

There has been some evidence that acyclovir may be useful.58 However,

despite its effectiveness against herpes simplex virus, several studies

have shown acyclovir to be ineffective against HHV-6 and HHV-7.59,60 This

is logical as acyclovir is a thymidine-kinase-dependent antiviral and

HHV-7 lacks the thimidine kinase gene. Moreover, there has actually

been one case report of PR occurring during acyclovir therapy. 61 The

same studies that demonstrated acyclovirs ineffectiveness against

HHV-6 and HHV-7 showed that foscarnet and ganciclovir are effective

antiviral agents. Unfortunately, there have been no studies investigating

the use of foscarnet or ganciclovir in the treatment of PR. There has

been some support for erythromycin in the treatment of PR, 62 and it is

hypothesized that the mechanism of action lies in its anti-inflammatory

and modulating effects on the immune system rather than its antibiotic

properties. Recently, another study found erythromycin to be

ineffective in the treatment of PR. 63 The use of narrow-band ultraviolet

B (UVB) phototherapy as well as natural sunlight has been supported in

several studies.64,65 UV light works by suppressing the cutaneous

immune system and is most beneficial when used within the first week

of the eruption.

A 2007 Cochrane collaboration article reviewed the literature on the

different types of treatment for PR and concluded that evidence has

been inadequate for the efficacy of topical antihistamines, emollients,

corticosteroids, sunlight, artificial UV therapy, systemic antihistamines

and corticosteroids, antiviral agents, and intravenous glycyrrhizin.30

According to this review, no treatment can be recommended on the

foundation of evidence-based medicine. Let us remember our charge as

physicians:primum non nocerefirst do no harm.

Conclusion

PR continues to be a field of interest. The future will certainly bring

greater insight regarding the etiology of PR as well as improved

treatment. More controlled studies are needed to understand its cause

and clinical trials are needed to determine the best and safest

treatment. In the meantime, reassurance and anticipatory guidance can

provide great relief to anxious patients. n

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58 U S D E R M A T O L OG Y

John C Browning, MD, is an Assistant Professor of Pediatrics

and Dermatology and Chief of Pediatric Dermatology at the

University of Texas Health Science Center at San Antonio.

He is also is Co-Medical Director of Camp Discovery, a

camp for children with severe skin disease.

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