Generalized Petechial Rashes in Children During a Parvovirus B19 Outbreak M. Bruce Edmonson, Erica L. Riedesel, Gary P. Williams and Gregory P. DeMuri Pediatrics 2010;125;e787; originally published online March 1, 2010; DOI: 10.1542/peds.2009-1488 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/125/4/e787.full.html PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 ARTICLES Generalized Petechial Rashes in Children During a Parvovirus B19 Outbreak AUTHORS: M. Bruce Edmonson, MD, MPH, Erica L. Riedesel, MD, Gary P. Williams, MD, and Gregory P. DeMuri, MD Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin KEY WORDS parvovirus, epidemiology ABBREVIATIONS IgM—immunoglobulin M IgG—immunoglobulin G PCR—polymerase chain reaction GAS— group A ␤-hemolytic Streptococcus WHAT’S KNOWN ON THIS SUBJECT: Reports about petechial or purpuric rashes that are associated with acute parvovirus infection usually describe only sporadic cases with distinctively focal (eg, “gloves and socks”) rash distributions. WHAT THIS STUDY ADDS: During a community outbreak of ﬁfth disease, parvovirus proved to be a common cause of generalized petechial rash in children. Associated fever, leukopenia, and serologic test results link this rash to the viremic phase of infection. www.pediatrics.org/cgi/doi/10.1542/peds.2009-1488 doi:10.1542/peds.2009-1488 Accepted for publication Oct 28, 2009 Address correspondence to M. Bruce Edmonson, MD, MPH, 2870 University Ave, Madison, WI 53705. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2010 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no ﬁnancial relationships relevant to this article to disclose. PEDIATRICS Volume 125, Number 4, April 2010 abstract OBJECTIVES: Human parvovirus B19 infection is associated not only with erythema infectiosum (ﬁfth disease) but also, rarely, with purpuric or petechial rashes. Most reports of these atypical rashes describe sporadic cases with skin lesions that have distinctively focal distributions. During a community outbreak of ﬁfth disease, we investigated a cluster of illnesses in children with generalized petechial rashes to determine whether parvovirus was the causative agent and, if so, to describe more fully the clinical spectrum of petechial rashes that are associated with this virus. METHODS: Systematic evaluation was conducted by general pediatricians of children with petechial rashes for evidence of acute parvovirus infection. RESULTS: During the outbreak, acute parvovirus infection was conﬁrmed in 13 (76%) of 17 children who were evaluated for petechial rash. Conﬁrmed case patients typically had mild constitutional symptoms, and most (11 [85%] of 13) had fever. Petechiae were typically dense and widely distributed; sometimes accentuated in the distal extremities, axillae, or groin; and usually absent from the head/neck. Most case patients had leukopenia, and several had thrombocytopenia. Parvovirus immunoglobulin M was detected in 8 (73%) of 11 acutephase serum specimens, and immunoglobulin G was detectable only in convalescent specimens. Parvovirus DNA was detected in all 7 tested serum specimens, including 2 acute-phase specimens that were immunoglobulin M–negative. All case patients had brief, uncomplicated illnesses, but 6 were brieﬂy hospitalized and 1 underwent a bone marrow examination. Two case patients developed erythema infectiosum during convalescence. CONCLUSIONS: During an outbreak of ﬁfth disease, parvovirus proved to be a common cause of petechial rash in children, and this rash was typically more generalized than described in case reports. Associated clinical features, hematologic abnormalities, and serologic test results are consistent with a viremia-associated illness that is distinct from and occasionally followed by erythema infectiosum. Pediatrics 2010; 125:e787–e792 Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 e787 In addition to erythema infectiosum (ﬁfth disease), acute infection with human parvovirus B19 can be associated with purpuric or petechial rashes. These parvovirus-associated hemorrhagic rashes seem to be uncommon, and published reports have described only solitary or sporadic cases (reviewed by McNeely et al1 and additionally reported by others2–7). Most case reports emphasized the distinctively focal (“gloves and socks,”8 “bathing trunk,”5,7 or “acropetechial”9) distribution of these atypical rashes, and only a few reports have described generalized petechial rashes associated with parvovirus infection.1–3,10 We could ﬁnd no description of an outbreak of parvovirus-associated petechial rash in the English-language medical literature. During a recent community outbreak of ﬁfth disease, we obtained serologic conﬁrmation of acute parvovirus infection in a 13-year-old boy with an index case of fever, generalized petechial rash, and neutropenia. After conﬁrming parvovirus infection in a second child with a similar illness, we instituted prospective case ﬁnding in our network of pediatric practices and began to evaluate systematically petechial rash illnesses for evidence of parvovirus infection. Our objectives were, ﬁrst, to determine whether additional cases of parvovirus-associated petechial rash illness might be occurring during the ﬁfth disease outbreak and, then, to describe more fully the spectrum of clinical and laboratory features of this infrequently reported illness. METHODS In early March 2007, we sent a short e-mail description of the index case to all 32 ofﬁce-based general pediatricians who are associated with the UW Health, a network of medical providers that are afﬁliated with the University of e788 EDMONSON et al Wisconsin in south central Wisconsin. To encourage case ﬁnding, network pediatricians were (1) alerted to the possible relationship between petechial rashes and parvovirus B19 infection, (2) asked to watch for any suspected case (deﬁned as a petechial rash of unknown cause in a child), and (3) informed about procedures for serologic and virologic testing for parvovirus infection. Throughout the remainder of winter and spring, network pediatricians received e-mail updates about the outbreak investigation and were encouraged to obtain parvovirus tests in suspected cases. A conﬁrmed case of parvovirusassociated petechial rash was deﬁned as an otherwise unexplained petechial rash in a child for whom there was either laboratory evidence of acute parvovirus B19 infection or, when no serum specimen was available for testing, a temporal linkage to an illness consistent with erythema infectiosum (transient “slapped cheek” appearance followed by a reticular rash on the extremities). Laboratory evidence of acute parvovirus infection was deﬁned as any of the following: (1) detectable parvovirus-speciﬁc immunoglobulin m (IgM) antibody in an acute or convalescent serum specimen; (2) speciﬁc immunoglobulin G (IgG) antibody seroconversion in paired specimens; or (3) positive polymerase chain reaction (PCR). Serologic tests for IgM- and IgGspeciﬁc parvovirus B19 antibodies were performed in the 2 reference laboratories that routinely provide serologic testing services to UW Health. The Wisconsin State Laboratory of Hygiene (Madison, WI) used an indirect ﬂuorescent antibody assay (Biotrin, Dublin, Ireland), and the ARUP Laboratories (Salt Lake City, UT) used an enzymelinked immunosorbent assay (Biotrin). Serum testing for parvovirus B19 DNA was performed by PCR by using 2 primers directed at the VP1 gene. To place conﬁrmed cases in epidemiologic context, we used administrative data from the 2 reference laboratories to calculate both the number of parvovirus B19 IgM antibody tests ordered by UW Health providers and the number of tests that were positive during each quarter of the outbreak year (2007) and the 3 preceding years (2004 –2006). Clinical data and laboratory test results from all conﬁrmed cases were obtained by retrospective medical chart review and by interviews with providers and patient families. Written consent for study participation was obtained from the families of all case patients, in accordance with a study protocol that was approved by the Health Sciences Human Subjects Committee of the University of Wisconsin-Madison. RESULTS Network pediatricians reported 17 suspected cases of initially unexplained petechial rash in Madisonarea children between February and November 2007. A total of 13 cases were eventually conﬁrmed with laboratory or clinical evidence of acute parvovirus B19 infection. Most conﬁrmed cases had onset of rash between February and April (10 cases) with a peak in March (6 cases). Conﬁrmed cases coincided with an abrupt increase in the number of serologically conﬁrmed parvovirus infections among UW Health patients of all ages during the ﬁrst 3 quarters of 2007 (Fig 1). There was no difference in the timing of conﬁrmed cases and the 4 suspected cases that were not conﬁrmed (data not shown). Table 1 provides descriptive information about conﬁrmed case patients. The median age of patients was 7 years (range: 3–16 years). Patients lived in a Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 ARTICLES TABLE 1 Selected Clinical Characteristics of 250 45 Conﬁrmed Cases Serum specimens submitted IgM-positive serum specimens IgM-positive specimens 35 Characteristic Each indicates a confirmed case of parvovirus-associated petechial rash 200 30 150 25 20 100 15 10 Specimens submitted 40 50 5 0 0 2004 2005 2006 Year 2007 Study Period FIGURE 1 Timing of conﬁrmed cases of parvovirus-associated petechial rash in children compared with secular trends in laboratory serologic testing for acute parvovirus infection, UW Health, 2004 –2007. Serologic data reﬂect specimen submission for patients of all ages, regardless of clinical indication, by providers of all specialties. Information about the timing of parvovirus-associated petechial rashes is conﬁned to cases in children that were reported by system pediatricians during the study year only. variety of urban, suburban, and rural locations in and around Dane County, Wisconsin. Only 2 patients, sisters 3 and 6 years old, had a known common household or school exposure. All but 1 patient received usual medical care at UW Health. Most (9 [69%] of 13) patients were initially evaluated in a primary physician’s ofﬁce, and the remainder were evaluated in local emergency departments or urgent care centers. In most cases, the presenting complaint was fever and petechial rash. Fever was reported in 11 (85%) of 13 cases, and body temperature was objectively measured in 8 of these 11 cases with maximum recorded values ranging from 38.6 to 40.0°C. Fever was brief, ranging from 1 to 3 days, and its onset typically just preceded or coincided with discovery of the petechial rash. Associated symptoms were common and included sore throat, headache, and fatigue. Two case-patients PEDIATRICS Volume 125, Number 4, April 2010 complained that their rash was pruritic. On physical examination, most conﬁrmed case patients appeared well, but 4 patients were reported to be mildly or moderately ill. Petechiae were described as small (1–2 mm), ﬂat, red or purple spots that were often present in large numbers (described, eg, as “100s” or “too many to count”) and did not blanch. Petechiae were generalized in all cases and locally accentuated in 7 (54%) of 13 cases (Table 1). Additional physical ﬁndings included other skin abnormalities in 5 case patients: 3 had solitary, ﬂat, ecchymotic lesions on the chin or shin; 1 had tiny, blanching, pink papules on the back; and 1 had transient pink, blanching papules on the distal extremities, palms, and soles that preceded the generalized petechial rash. No case had palpable purpura. Six case pa- Age, y 0–4 5–9 10–14 15–19 Male gender Presenting complaint Fever and rash Rash Fever Associated symptoms Headache Sore throat Fatigue Myalgia Arthralgia (elbow, shoulder) None Distribution Trunk Extremities Head/neck Local accentuation Axillae Groin, perineum, and/or buttocks Distal extremities Other physical ﬁndings Cutaneous ecchymosis (chin, shin) Intra-oral erythema, petechiae, ulcers, or papules White blood cell count, 1000 cells/␮L ⬍5.0 (range: 0.9–4.8) 5.0–8.6 Not tested Platelet count, 1000 cells/␮L ⬍150 (range: 34–144) 150–170 ⬎170 Not tested Cases (N ⫽ 13) 1 8 3 1 7 9 3 1 8 5 4 2 2 0 13 12 3 3 3 2 3 6 10 2 1 4 2 5 1 tients had at least 1 intra-oral ﬁnding: 3 had mucosal erythema, 2 had palatal petechiae, 1 had ulcers, and 1 had tongue papules. Complete blood counts were available for 12 patients with conﬁrmed cases (Table 1). Leukopenia (⬍5000 white blood cells/␮L) was found in 10 (83%) of 12 patients. Two patients had isolated neutropenia (⬍1500 neutrophils/␮L), 5 had isolated lymphopenia (⬍1500 lymphocytes/␮L), and 5 had both. Four patients had thrombocytopenia (⬍150 000 platelets/␮L) but only 1 patient had a platelet count (34 000/␮L) ⬍100 000/␮L. Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 e789 TABLE 2 Parvovirus Serum Antibody and PCR Test Results in Conﬁrmed Cases Type of Specimen Tested Cases, n IgM, n Positive/n Tested IgG, n Positive/n Tested PCR, n Positive/n Tested Unpaired acute serum Paired sera Acute Convalescent Unpaired convalescent serum 8 3 8/8 0/8 4/4 0/3 2/3 1/1 0/3 3/3 1/1 2/2 0/0 1/1 1 Serologic data were unavailable for 1 conﬁrmed case (see Results). Borderline or low hemoglobin concentrations (range: 10.9 –11.4 g/dL) were noted in 3 patients. A reticulocyte count was measured in only 1 patient and was low (0.2%). Throat cultures were negative for group A ␤-hemolytic Streptococcus (GAS) in 4 patients, and a rapid antigen test was positive for GAS in 1 (subsequently parovirus-seroconﬁrmed) patient. Acute parvovirus infection was laboratory conﬁrmed in 12 of 13 cases (Table 2). Acute serum specimens were available in 11 laboratory-conﬁrmed cases, and 3 of these cases were parvovirus IgM-negative acutely. In 2 of these IgMnegative cases, acute serum specimens were also tested for parvovirus DNA and were positive by PCR in both cases. Overall, parvovirus DNA was detectable in all 7 serologically conﬁrmed cases tested by PCR. In the single conﬁrmed case that was not laboratory conﬁrmed, no serum specimen was available; however, this case was considered to be clinically conﬁrmed because of development of classic erythema infectiosum after resolution of the petechial rash. Six of the 13 children with conﬁrmed cases were hospitalized. Initial diagnostic considerations for these patients included bacteremia, GAS infection, ehrlichiosis, pancytopenia, leukemia, and viral illness. Hospitalized stays were short (range: 2–3 days). All hospitalized case patients had blood cultures obtained. One case patient underwent bone marrow biopsy to evaluate neutropenia and e790 EDMONSON et al thrombocytopenia. Two case patients developed erythema infectiosum after their petechial rash resolved; in each case, this second rash developed 2 to 3 weeks after the appearance of the ﬁrst (petechial) rash. DISCUSSION In this investigation, parvovirus proved to be a common cause of petechial rash during a community outbreak of ﬁfth disease. Relying only on passive surveillance, we were able to identify and conﬁrm 13 cases among children and adolescents in a single health care system. This is surprising because previous English-language reports of parvovirusassociated petechial rashes described only solitary cases or small numbers of seemingly sporadic cases,1–7 although the authors of 1 report did refer (in Japanese) to an apparent cluster of 8 pediatric cases examined at a single Japanese hospital during a period of 6 months.3 Parvovirus-associated petechial rashes may be more common than generally appreciated. Illnesses that are characterized by fever and petechial rash are, themselves, not rare in children11 and can be caused by a wide variety of viral, bacterial, and rickettsial agents.12 Such illnesses are not routinely evaluated for acute parvovirus infection and, typically, are attributed to unspeciﬁed (and presumed viral) agents.11,13–15 In the past, petechial or purpuric rashes may have been overlooked during “classic” investigations of large outbreaks of erythema infectiosum reported in the 1920s to 1940s,16–18 and it is notable that 2 outbreak reports from the 1950s did describe, in passing, exceptional cases of hemorrhagic rash amid hundreds of typical cases of erythema infectiosum.19,20 Even with the advent of serologic and direct virologic methods for detecting parvovirus infection, it is still possible that cases of parvovirus-associated hemorrhagic rashes are being overlooked because previous case reports emphasized the distinctively focal nature of these rashes. Petechiae rashes in some of our cases had focal accentuation (in the distal extremities, groin, or axillae), but petechiae were widely distributed in all cases and, in this respect, more closely resembled the generalized rashes described in a few case reports.1–3,10 On the basis of the clinical characteristics of our cases, it seems that parvovirus-associated petechial rash is closely linked to the viremic phase of parvovirus infection. Our case patients typically had fever, systemic symptoms, leukopenia (and occasional thrombocytopenia), and detectable parvovirus DNA in their blood, and acutephase serum tests indicated that a speciﬁc antibody response had either not yet developed (IgM-negative) or was just developing (IgM-positive/IgGnegative). Except for the petechial rash itself, these clinical characteristics closely mimic the viremic phase described in human experimental parvovirus infection, at the point (postinoculation days 9 –10) when platelet and leukocyte counts reach a nadir and IgMspeciﬁc antibody begins to appear.21 We speculate that the pathogenesis of parvovirus-associated petechial rash is similar to that of the papularpurpuric gloves and socks syndrome, in which parvovirus antigens can be detected directly in dermal vessel walls, as well as in the cells of sweat glands and ducts and epider- Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 ARTICLES mal cells.22 Erythrocyte P antigen, the receptor on the erythrocyte progenitor cell associated with the pathogenesis of the hematologic manifestations of parvovirus infection, is also present in other cell lines, including fetal cardiac myocytes and endothelial cells, and may be responsible for its skin manifestations.23 The presence of a petechial rash during the acute phase of infection, when patients have viremia, could be explained by the binding of virus to P antigen on capillary endothelial cells, thereby causing capillary disruption and extravasation of erythrocytes into dermal tissues. Endothelial cells also express the ␣5␤1 integrin, which is a cell surface receptor necessary for infection by parvovirus B19.24 The acute petechial rash and associated illness in our cases had little in common clinically with erythema infectiosum. Erythema infectiosum is believed to be a postviremic manifestation of parvovirus infection that develops 2 to 3 weeks after infection and is attributable to immune complex deposition.6,22,25 Typically, by the time erythema infectiosum develops in the course of acute parvovirus infection, any fever or constitutional symptoms have resolved, the peripheral white blood cell and platelet counts have normalized,18,26 and speciﬁc IgG antibodies have become detectable.21 Although erythema infectiosum did de- velop in 2 of our case patients, this occurred long after disappearance of their petechial rashes. This sequence—petechial rash followed by erythema infectiosum— has been previously described3,6 and further distinguishes petechial rash in our patients from erythema infectiosum. The principal limitation of our study is that cases were detected by passive surveillance and, as a result, cannot be used to estimate the incidence of parvovirus-associated petechial rash. Although laboratory administrative data provide evidence that a community outbreak of parvovirus infection did occur during the study period, they provide no basis for accurately estimating the number of children infected. Moreover, although the majority of petechial rashes reported during the study period proved to be parvovirus-associated, it is possible that additional cases of petechial rash were unreported, either because they were unevaluated for parvovirus or because they were attributed to some other cause. It is also theoretically possible that the occurrence of petechial rashes in our cases reﬂects some variation in the strain of parvovirus that was circulating locally during the outbreak. Another limitation of our study is that diagnostic testing was not uniform in suspect cases, and results of initial acute serum tests may have inﬂuenced whether additional (PCR or antibody) tests were ordered. Thus, the apparent sensitivity of parvovirus IgM (73%) and PCR (100%) tests in conﬁrmed cases may be distorted by veriﬁcation bias.27 CONCLUSIONS Results of our investigation during an outbreak of ﬁfth disease showed that petechial rashes may be a more common manifestation of parvovirus infection in children than suggested by previous reports of isolated cases. These rashes are typically more generalized than the focal petechial or purpuric rashes described in most reports. Associated clinical features, hematologic abnormalities, and results of serologic tests are consistent with a viremic illness that is distinct from and is occasionally even followed by erythema infectiosum. ACKNOWLEDGMENTS We thank the following physicians for evaluating and reporting cases: Gail Allen, James Conway, Timothy Drews, Greg Landry, Jeffrey Meade, Amy Plumb, Jeffrey Sleeth, Melissa Stiles, Eric Warbasse, Robin Wright, and KokPeng Yu. We also thank Leanne Wheeler, UW Medical Foundation Laboratories, and David Warshauer, PhD, Wisconsin State Laboratory of Hygiene, for helping collect administrative data on parvovirus testing at UW Health and Akihiro Ikeda, PhD, for translating and reviewing Japanese medical literature. REFERENCES 1. McNeely M, Friedman J, Pope E. Generalized petechial eruption induced by parvovirus B19 infection. J Am Acad Dermatol. 2005; 52(5 suppl 1):S109 –S113 lowed by papular-purpuric gloves and socks syndrome and erythema infectiosum [in Japanese]. Kansenshogaku Zasshi. 2002;76(11):963–966 2. Shimada Y, Yagi Y, Hiraga Y, Kawano S, Terada K, Kataoka N. A case with petechiae due to human parvovirus B19 [in Japanese]. Kansenshogaku Zasshi. 1996;70(9): 976 –980 4. Chinsky JM, Kalyani RR. Fever and petechial rash associated with parvovirus B19 infection. Clin Pediatr (Phila). 2006;45(3): 275–280 3. Sato A, Umezawa R, Kurosawa R, Kajigaya Y. Human parvovirus B19 infection which ﬁrst presented with petechial hemorrhage, fol- PEDIATRICS Volume 125, Number 4, April 2010 5. Butler GJ, Mendelsohn S, Franks A. Parvovirus B19 infection presenting as ‘bathing trunk’ erythema with pustules. Australas J Dermatol. 2006;47(4):286 –288 6. Foti C, Bonamonte D, Conserva A, Grandolfo M, Casulli C, Martire B. Erythema infectiosum following generalized petechial eruption induced by human parvovirus B19. New Microbiol. 2006;29(1):45– 48 7. Huerta-Brogeras M, Aviles Izquierdo JA, Hernanz Hermosa JM, Lazaro-Ochaita P, Longo-Imedio MI. Petechial exanthem in “bathing trunk” distribution caused by parvovirus B19 infection. Pediatr Dermatol. 2005;22(5):430 – 433 8. Harms M, Feldmann R, Saurat JH. Papular- Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 e791 9. 10. 11. 12. 13. purpuric “gloves and socks” syndrome. J Am Acad Dermatol. 1990;23(5 pt 1): 850 – 854 Harel L, Straussberg I, Zeharia A, Praiss D, Amir J. Papular purpuric rash due to parvovirus B19 with distribution on the distal extremities and the face. Clin Infect Dis. 2002; 35(12):1558 –1561 Conway SP, Cohen BJ, Field AM, Hambling MH. A family outbreak of parvovirus B19 infection with petechial rash in a 7-year-old boy. J Infect. 1987;15(1):110 –112 Mandl KD, Stack AM, Fleisher GR. Incidence of bacteremia in infants and children with fever and petechiae. J Pediatr. 1997;131(3): 398 – 404 Cherry JD. Human parvovirus B19. In: Feign RD, Demmler GJ, Kaplan SL, ed. Textbook of Pediatric Infectious Diseases. 5th ed. Philadelphia, PA: WB Saunders Co; 2004: 1796 –1809 Van Nguyen Q, Nguyen EA, Weiner LB. Incidence of invasive bacterial disease in children with fever and petechiae. Pediatrics. 1984;74(1):77– 80 e792 EDMONSON et al 14. Nielsen HE, Andersen EA, Andersen J, et al. Diagnostic assessment of haemorrhagic rash and fever. Arch Dis Child. 2001;85(2): 160 –165 15. Baker RC, Seguin JH, Leslie N, Gilchrist MJ, Myers MG. Fever and petechiae in children. Pediatrics. 1989;84(6):1051–1055 16. Zuckerman SN. Erythema infectiosum, with report of an epidemic in San Francisco [in French]. Arch Pediatr. 1940;57(3):168 –176 17. Herrick TP. Erythema infectiosum: a clinical report of seventy-four cases. Am J Dis Child. 1926;31(4):486 – 495 18. Boysen G. Erythema infectiosum. Acta Paediatr. 1943;31:211–227 19. Condon FJ. Erythema infectiosum: report of an area-wide outbreak. Am J Public Health Nations Health. 1959;49(4):528 –535 20. Grimmer H, Joseph A. An epidemic of infectious erythema in Germany. Arch Dermatol. 1959;80:283–285 21. Anderson MJ, Higgins PG, Davis LR, et al. Experimental parvoviral infection in humans. J Infect Dis. 1985;152(2):257–265 22. Aractingi S, Bakhos D, Flageul B, et al. Immunohistochemical and virological study of skin in the papular-purpuric gloves and socks syndrome. Br J Dermatol. 1996; 135(4):599 – 602 23. Brown KE, Anderson SM, Young NS. Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science. 1993;262(5130):114 – 117 24. Weigel-Kelley KA, Yoder MC, Srivastava A. Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry. Blood. 2003; 102(12):3927–3933 25. Young NS, Brown KE. Parvovirus B19. N Engl J Med. 2004;350(6):586 –597 26. Balfour HH Jr. Erythema infectiosum (ﬁfth disease): clinical review and description of 91 cases seen in an epidemic. Clin Pediatr (Phila). 1969;8(12):721–727 27. Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efﬁcacy of diagnostic tests. N Engl J Med. 1978; 299(17):926 –930 Downloaded from pediatrics.aappublications.org by guest on August 22, 2014 Generalized Petechial Rashes in Children During a Parvovirus B19 Outbreak M. Bruce Edmonson, Erica L. Riedesel, Gary P. Williams and Gregory P. DeMuri Pediatrics 2010;125;e787; originally published online March 1, 2010; DOI: 10.1542/peds.2009-1488 Updated Information & Services including high resolution figures, can be found at: http://pediatrics.aappublications.org/content/125/4/e787.full.h tml References This article cites 26 articles, 9 of which can be accessed free at: http://pediatrics.aappublications.org/content/125/4/e787.full.h tml#ref-list-1 Citations This article has been cited by 2 HighWire-hosted articles: http://pediatrics.aappublications.org/content/125/4/e787.full.h tml#related-urls Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Infectious Diseases http://pediatrics.aappublications.org/cgi/collection/infectious_ diseases_sub Epidemiology http://pediatrics.aappublications.org/cgi/collection/epidemiolo gy_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://pediatrics.aappublications.org/site/misc/Permissions.xht ml Reprints Information about ordering reprints can be found online: http://pediatrics.aappublications.org/site/misc/reprints.xhtml PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from pediatrics.aappublications.org by guest on August 22, 2014