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Case Report

Free Access

Pityriasis Rosea in Children: Clinical Features and Laboratory Investigations

Drago F.a · Ciccarese G.a · Broccolo F.b · Cozzani E.a · Parodi A.a

Author affiliations

aDepartment of Dermatology, DISSAL, IRCCS A.O.U. San Martino-IST, Genoa, and bDepartment of Health Sciences, University of Milano-Bicocca, Monza, Italy

Corresponding Author

Giulia Ciccarese, MD

Department of Dermatology, DISSAL

IRCCS A.O.U. San Martino-IST

Largo Rosanna Benzi 10, IT-16132 Genoa (Italy)

E-Mail giuliaciccarese@libero.it

Related Articles for ""

Dermatology 2015;231:9-14

Abstract

Pityriasis rosea (PR) is a common, self-limiting exanthematous disease associated with a systemic reactivation of human herpesvirus 6 (HHV-6) and/or HHV-7. It usually occurs in the second or third decade of life whereas it is uncommon in patients younger than 10 years. We studied the clinical features and virological parameters of 31 children with PR, comparing them with those in adults. Our findings indicate that PR presents different characteristics between children and adults, mainly consisting of time lapse between herald patch and generalized eruption, duration of the exanthem, oropharyngeal involvement and persistence of HHV-6 and HHV-7 plasma viremia. Overall, these results suggest that, following HHV-6 and/or HHV-7 systemic active infection, the pathogenetic mechanisms involved in PR may at least partly be different in children and adults.

© 2015 S. Karger AG, Basel


Introduction

Pityriasis rosea (PR) is a self-limiting exanthematous disease that has been associated with systemic reactivation of human herpesvirus 6 (HHV-6) and/or HHV-7 [1,2,3]. Although some authors have not been able to demonstrate this relationship [4,5], more recent studies established a causal role for systemic active HHV-6 and HHV-7 infection in the pathogenesis of PR, based on the detection of HHV-6 and HHV-7 DNA in plasma, mRNA expression and specific antigens in skin lesions of PR patients [2,3]. In addition, herpesvirus virions in various stages of morphogenesis were detected by electron microscopy in skin lesions [6] and in the supernatant of co-cultured peripheral blood mononuclear cells (PBMCs) from PR patients [1,7]. Notably, in previous studies, HHV-6 and HHV-7 plasma viremia, a marker of systemic active infection, was demonstrated in PR and related to the presence of constitutional symptoms [2,3]. Accordingly, the cytopathic effect and syncytia formation observed in PBMC cultures from PR patients [1], HHV-6 and HHV-7 mRNA expression and antigens found in lesional skin are additional evidence of productive infection [2,3]. Remarkably, such morphological changes were not observed in the co-cultured mononuclear cells from blood samples collected from patients reassessed after the acute illness whereas the samples collected during PR recurrences showed the same changes again [1].

PR prevalence is assessed at 1.3% with a slight female preponderance, but probably largely underestimated. The age of maximum incidence is between 10 and 35 years and the disease is considered uncommon in patients younger than 10 years [8,9]. In our series of 585 consecutive PR patients recruited between January 2003 and December 2013 at the Department of Dermatology, University of Genoa (Italy), 46 (8%) were under this age. From 31 of them we obtained parental informed consent to take blood samples and studied their clinical features and virological parameters, comparing them with those of adult patients.

Patients and Samples

Thirty-one children with PR were analyzed retrospectively. The inclusion criteria were all patients younger than 10 years who sought care for a skin rash at our dermatology department between January 2003 and December 2013, whose parents gave informed consent to take blood samples for laboratory investigations and in whom a final diagnosis of PR was made. All patients had the classical clinical findings of PR and the diagnosis was made clinically and independently by at least two dermatologists belonging to the same team. One of them (F.D.) made the diagnosis in all patients. Drug-induced PR-like eruptions were excluded.

The records of the 31 pediatric patients were reviewed to examine their gender and age, the time elapsed between the herald patch (HP) and the general eruption, the duration of the exanthem, the presence of enanthem, systemic symptoms, previous infections and drug intake before eruption. All selected patients had blood sampled at the first visit for specific anti-HHV-6 and anti-HHV-7 serology and for the search of HHV-6 and HHV-7 DNA loads in plasma and PBMCs by calibrated quantitative real-time PCR (CQ-PCR), as previously described [3]. Twelve patients had blood sampled also after recovery (4-6 weeks after healing) for the same investigations. In addition, IgG and IgM antibodies to adenovirus, paramyxovirus, enteroviruses, rotavirus, Epstein-Barr virus, cytomegalovirus, parvovirus B19, HHV-8 and rubella were investigated.

Presence of virus DNA in plasma due to lysis of infected cells (i.e., cytopathic effect or inadequate handling of blood specimens before DNA extraction) and/or to contamination by latently infected leukocytes (presence of chromosomally integrated HHV-6) was excluded utilizing a CQ-PCR assay for viral load measurements in plasma together with a Q-PCR assay for quantitative detection of genomic DNA content [3]. All clinical features and laboratory investigations were compared with those of adult patients from our series.

Results

Clinical Features

Among the 31 selected patients, 19 were females and 12 males, aged between 3 and 9 years (mean age 6.9 years). At careful physical examination of the whole skin, the typical HP with elevated finely scaling borders and slightly depressed center was found in 18 patients (58%) on the trunk or the lower/upper limbs. No patients presented the HP on the head.

In the 18 cases presenting with HP, the mean time lapse between its appearance and generalized eruption was 4 days. The skin eruption was characterized by oval erythematous-squamous papules and plaques, symmetrically oriented, with their long axes following the cleavage lines of the skin of trunk and limbs (Christmas tree distribution) (fig. 1). Thirteen patients (42%) developed the skin eruption without the HP. The duration of the exanthem ranged between 12 and 21 days, with a median duration of 16 ± 4 days (time lapse between HP and secondary eruption) (table 1).

Table 1

Clinical features of the 31 children with PR studied

http://www.karger.com/WebMaterial/ShowPic/127195

Fig. 1

Oval erythematous-squamous papules and plaques, symmetrically oriented, with their long axes following the cleavage lines of the skin of trunk and limbs.

http://www.karger.com/WebMaterial/ShowPic/127191

At the time of diagnosis, 11 patients (35%) had painless oropharyngeal lesions that disappeared along with the cutaneous lesions. Vesicles were the commonest oral lesions (9/11 patients, 82%) followed by petechiae, papules and strawberry tongue (table 1). None of these patients had systemic symptoms.

Fifteen patients (48%) complained of systemic symptoms during the course of PR, especially prodromal or accompanying symptoms during the first 7 days from onset, with different degrees of severity and duration. Among symptoms, irritability was the commonest (8/15 patients, 53%) followed by headache, fatigue, crying easily, insomnia, sore throat and conjunctivitis (table 1).

Previous infections such as exanthema subitum, fifth disease, pharyngitis and tonsillitis were recorded in 7 patients (23%) (table 1). Only in 2 cases (6%) had the patients taken a drug (antibiotic) 1 month before the eruption.

Patients in whom PR began without the HP presented the same course as those who had it, but oral lesions were less common.

Laboratory Investigations

Serology. In the acute phase of the eruption, serology for HHV-6 showed IgG antibodies in 26 patients (84%) with titers ranging between 1:40 and 1:640 (mean 1:160) whereas IgM antibodies were present only in 5 patients (16%). Serology for HHV-7 revealed IgG antibodies in 19 patients (61%) with titers that ranged between 1:40 and 1:160 (mean 1:80) whereas IgM antibodies were positive only in 3 cases (10%). Among the 12 patients who had blood sampled also after recovery, IgG antibodies to HHV-6 were present in 8 (67%) with titers ranging between 1:40 and 1:320 (mean 1:160) whereas IgM antibodies remained positive only in 1 patient (8%). Serology for HHV-7 showed IgG antibodies in 8 patients (67%) with titers ranging between 1:40 and 1:160 (mean 1:80) whereas IgM antibodies resulted positive only in 1 case (table 2). Serology for other viruses was negative or indicative of past immunity, routine laboratory findings were within normal limits and Venereal Disease Research Laboratory was negative in all serum samples.

Table 2

Laboratory findings during the acute phase of PR: serology and viral loads of HHV-6 and HHV-7 in serum and PBMCs

http://www.karger.com/WebMaterial/ShowPic/127194

HHV-6 and HHV-7 Viral Load. During the acute phase, the level of plasma viremia ranged between 10 and 436 genome equivalents per ml (GEq/ml) for HHV-6 (mean viremia 239 GEq/ml) and between 10 and 208 for HHV-7 (mean viremia 136 GEq/ml) (table 2). In particular, patients who developed PR without HP presented levels of plasma viremia that were lower (138 GEq/ml for HHV-6 and 66 GEq/ml for HHV-7) compared to the global viremia in children. The PBMC viral load ranged between 15 and 1,120 GEq/106 cells for HHV-6 (mean viral load 213 GEq/106 cells) and between 10 and 1,345 for HHV-7 (mean viral load 287 GEq/106 cells). One month after recovery, the level of plasma viremia ranged between 10 and 87 GEq/ml for HHV-6 (mean viral load 32 GEq/ml) and between 10 and 95 GEq/ml for HHV-7 (mean viral load 30 GEq/ml). The PBMC viral load ranged between 20 and 615 GEq/106 cells for HHV-6 (mean viral load 145 GEq/106 cells) and between 10 and 315 GEq/106 cells (mean viral load 147 GEq/106 cells) for HHV-7 (table 3).

Table 3

Laboratory findings after recovery: serology and viral loads of HHV-6 and HHV-7 in serum and PBMCs

http://www.karger.com/WebMaterial/ShowPic/127193

Discussion

PR in children younger than 10 years is uncommon. We estimated its prevalence at 7.8%, on the basis of the number of children in our series of 585 consecutive PR patients recruited between 2003 and 2013 in our dermatology department. These data are in agreement with the percentage previously described by Björnberg and Hellgren [9] and by Burch and Rowell [10], who estimated the prevalence of PR in Caucasian children below 10 years of age at 6 and 10.5%, respectively. Conversely, PR is more frequent (26%) [11] in dark-skinned children in whom facial and scalp involvement (30 vs. 8% in Caucasian patients) as well as papular lesions and residual hyperpigmentation prevail [8].

Compared to adults, the occurrence of the HP in children does not differ greatly (50 vs. 58%) [8,9]. In contrast, the mean time lapse between the HP and the generalized eruption in children (4 days) is very short compared to adults (about 2 weeks), as is the exanthem duration, ranging between 12 and 21 days (average duration 16 days) in children whereas it lasts about 45 days in adults, ranging from 2 weeks to 5 months [8]. Among the children who experienced viral infections approximately 1 year before PR, cases number 9, 13, 21, 23 and 26, we found that the eruption had a slightly longer duration (mean 19 days) compared to the other children. This may be explained considering that their T-cell-mediated immunity, which is known to be implicated in the development of PR [12] by different mechanisms (for example by overproduction of T helper 1 cytokines), was already triggered by the other previous infections.

In our series of PR children, all Caucasians, no facial or scalp involvement nor papular lesions or residual hyperpigmentation were seen.

Oropharyngeal lesions appear to be commoner in PR children than in adults: we reported oral involvement in 35% of our patients younger than 10 years, a rate much higher than those reported in adult dark-skinned (9%) [11] and Caucasian patients (16%) [13].

Regarding the occurrence of systemic symptoms during the course of PR, they are frequently reported both in adults (69%) [8] and in children with PR (48%).

The serological findings in children with PR, showing IgG positivity against the viruses, revealed that they had previously been infected with HHV-6 in 84% of cases and with HHV-7 in 61%. In addition, 16% of them presented also IgM positivity for HHV-6 (cases 5 and 19) and 9% IgM positivity for HHV-7 (cases 8 and 16). It is noteworthy that these patients concurrently presented HHV-6/7 plasma viremia, which usually anticipate IgM appearance in blood (table 2). These data are surprising since plasma viremia fluctuates and, when it rises, this usually lasts for a very short period. Therefore, it is unlikely to find simultaneously IgM antibody and viremia in the serum. In these cases, the presence of high-avidity IgG antibodies allows us to rule out the possibility of a primary infection, suggesting that in PR children plasma viremia may persist much longer than in adults. Considering that the primary HHV-6/7 infection occurs most commonly in children under 3 years of age, it is likely that the virus infection can remain active longer than in adults. Accordingly, also in the post-acute phase, PR children maintain HHV-6/7 viremia longer than adults (table 2).

One might argue that the increase in viral load during the PR episode may be the consequence and not the cause of the PR. However, the increase in the viral load in the plasma of PR patients, a marker of systemic active infection, along with evidence of productive viral infection in the lesional skin [2,3,6] should really be considered the cause of PR. In fact, in atypical persistent PR, defined as the form that lasts uninterruptedly for over 12 weeks, HHV-6 and/or HHV-7 plasma viremia persists during all the phases of the illness and recurrences [14]. In addition, the morphological changes and syncytia formation shown in cell cultures from blood samples collected during acute PR were not observed from patients reassessed after the acute illness whereas the samples collected during PR recurrences showed the same changes again [1]. Therefore, it is unlikely that circulating viruses as active as HHV-6 and HHV-7 have been shown to be in PR are not also the actual cause of the disease.

Moreover, compared to adult PR patients [3], during the PR acute phase, children showed a higher average level of plasma viremia for both HHV-6 (median 15 vs. 239 GEq/ml, p < 0.05) and HHV-7 (median 17 vs. 136 GEq/ml, p <0.05). In conclusion, our data indicate that PR has different clinical and virological features between adults and children younger than 10 years, mainly consisting of time lapse between HP and generalized eruption, duration of the exanthem, oropharyngeal involvement and level and persistence of plasma viremia (table 4). As for most viral exanthems, our understanding of PR pathogenesis is rather limited. Nevertheless, our findings suggest that, following HHV-6 and/or HHV-7 systemic active infection, the pathogenetic mechanisms involved in PR may at least partly be different in children and adults.

Table 4

Main differences between adults and children with PR

http://www.karger.com/WebMaterial/ShowPic/127192

Acknowledgments

The authors thank Dr. Rosella Gallo for help in data processing.

Disclosure Statement

The authors declare that they have no conflict of interest or funding sources.


References

  1. Drago F, Ranieri E, Malaguti F, Battifoglio ML, Losi E, Rebora A: Human herpesvirus 7 in patients with pityriasis rosea. Electron microscopy investigations and polymerase chain reaction in mononuclear cells, plasma and skin. Dermatology 1997;195:374-378.
    External Resources
  2. Watanabe T, Kawamura T, Jacob SE, Aquilino EA, Orenstein JM, Black JB, Blauvelt A: Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6. J Invest Dermatol 2002;119:793-797.
  3. Broccolo F, Drago F, Careddu AM, Foglieni C, Turbino L, Cocuzza CE, Gelmetti C, Lusso P, Rebora AE, Malnati MS: Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005;124:1234-1240.
  4. Kempf W, Adams V, Kleinhans M, Burg G, Panizzon RG, Campadelli-Fiume G, Nestle FO: Pityriasis rosea is not associated with human herpesvirus 7. Arch Dermatol 1999;135:1070-1072.
  5. Kosuge H, Tanaka-Taya K, Miyoshi H, Amo K, Harada R, Ebihara T, Kawahara Y, Yamanishi K, Nishikawa T: Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea. Br J Dermatol 2000;143:795-798.
  6. Drago F, Malaguti F, Ranieri E, Losi E, Rebora A: Human herpes virus-like particles in pityriasis rosea lesions: an electron microscopy study. J Cutan Pathol 2002;29:359-361.
  7. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A: Human herpesvirus 7 in pityriasis rosea. Lancet 1997;349:1367-1368.
  8. Drago F, Broccolo F, Rebora A: Pityriasis rosea: an update with a critical appraisal of its possible herpesviral etiology. J Am Acad Dermatol 2009;61:303-318.
  9. Björnberg A, Hellgren L: Pityriasis rosea. A statistical, clinical, and laboratory investigation of 826 patients and matched healthy controls. Acta Derm Venereol Suppl (Stockh) 1962;42(suppl 50):1-68.
    External Resources
  10. Burch PR, Rowell NR: Pityriasis rosea - an autoaggressive disease? Statistical studies in relation to aetiology and pathogenesis. Br J Dermatol 1970;82:549-560.
  11. Jacyk WK: Pityriasis rosea in Nigerians. Int J Dermatol 1980;19:397-399.
  12. Neoh CY, Tan AW, Mohamed K, Sun YJ, Tan SH: Characterization of the inflammatory cell infiltrate in herald patches and fully developed eruptions of pityriasis rosea. Clin Exp Dermatol 2010;35:300-304.
  13. Vidimos AT, Camisa C: Tongue and cheek: oral lesions in pityriasis rosea. Cutis 1992;50:276-280.
    External Resources
  14. Drago F, Broccolo F, Ciccarese G, Rebora A, Parodi A: Persistent pityriasis rosea: an unusual form of pityriasis rosea with persistent active HHV-6 and HHV-7 infection. Dermatology 2015;230:23-26.

Author Contacts

Giulia Ciccarese, MD

Department of Dermatology, DISSAL

IRCCS A.O.U. San Martino-IST

Largo Rosanna Benzi 10, IT-16132 Genoa (Italy)

E-Mail giuliaciccarese@libero.it


Article / Publication Details

First-Page Preview
Abstract of Case Report

Received: November 10, 2014
Accepted: February 26, 2015
Published online: May 12, 2015
Issue release date: June 2015

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 4

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: https://www.karger.com/DRM


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References

  1. Drago F, Ranieri E, Malaguti F, Battifoglio ML, Losi E, Rebora A: Human herpesvirus 7 in patients with pityriasis rosea. Electron microscopy investigations and polymerase chain reaction in mononuclear cells, plasma and skin. Dermatology 1997;195:374-378.
    External Resources
  2. Watanabe T, Kawamura T, Jacob SE, Aquilino EA, Orenstein JM, Black JB, Blauvelt A: Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6. J Invest Dermatol 2002;119:793-797.
  3. Broccolo F, Drago F, Careddu AM, Foglieni C, Turbino L, Cocuzza CE, Gelmetti C, Lusso P, Rebora AE, Malnati MS: Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005;124:1234-1240.
  4. Kempf W, Adams V, Kleinhans M, Burg G, Panizzon RG, Campadelli-Fiume G, Nestle FO: Pityriasis rosea is not associated with human herpesvirus 7. Arch Dermatol 1999;135:1070-1072.
  5. Kosuge H, Tanaka-Taya K, Miyoshi H, Amo K, Harada R, Ebihara T, Kawahara Y, Yamanishi K, Nishikawa T: Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea. Br J Dermatol 2000;143:795-798.
  6. Drago F, Malaguti F, Ranieri E, Losi E, Rebora A: Human herpes virus-like particles in pityriasis rosea lesions: an electron microscopy study. J Cutan Pathol 2002;29:359-361.
  7. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A: Human herpesvirus 7 in pityriasis rosea. Lancet 1997;349:1367-1368.
  8. Drago F, Broccolo F, Rebora A: Pityriasis rosea: an update with a critical appraisal of its possible herpesviral etiology. J Am Acad Dermatol 2009;61:303-318.
  9. Björnberg A, Hellgren L: Pityriasis rosea. A statistical, clinical, and laboratory investigation of 826 patients and matched healthy controls. Acta Derm Venereol Suppl (Stockh) 1962;42(suppl 50):1-68.
    External Resources
  10. Burch PR, Rowell NR: Pityriasis rosea - an autoaggressive disease? Statistical studies in relation to aetiology and pathogenesis. Br J Dermatol 1970;82:549-560.
  11. Jacyk WK: Pityriasis rosea in Nigerians. Int J Dermatol 1980;19:397-399.
  12. Neoh CY, Tan AW, Mohamed K, Sun YJ, Tan SH: Characterization of the inflammatory cell infiltrate in herald patches and fully developed eruptions of pityriasis rosea. Clin Exp Dermatol 2010;35:300-304.
  13. Vidimos AT, Camisa C: Tongue and cheek: oral lesions in pityriasis rosea. Cutis 1992;50:276-280.
    External Resources
  14. Drago F, Broccolo F, Ciccarese G, Rebora A, Parodi A: Persistent pityriasis rosea: an unusual form of pityriasis rosea with persistent active HHV-6 and HHV-7 infection. Dermatology 2015;230:23-26.
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