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Fretzayas, Andrew MD, PhD; Douros, Konstantinos MD; Moustaki, Maria MD, PhD; Nicolaidou, Polyxeni MD, PhD

The Pediatric Infectious Disease Journal: March 2009 - Volume 28 - Issue 3 - p 250-252
doi: 10.1097/INF.0b013e31818cb289
Brief Reports

We describe the case of a 12-year-old boy with gloves and socks syndrome caused by coinfection with HHV-6 and PVB19, and review the published cases from 5 to 18 years of age to profile the disease in this age group. The review of the literature yielded 25 cases of gloves and socks syndrome. Most patients were febrile and had acute PVB19 infection.

From the Third Department of Pediatrics, Athens University Medical School, “Attikon” University Hospital, Athens, Greece.

Accepted for publication September 4, 2008.

Address for correspondence: Andrew Fretzayas, MD, PhD, 3rd Dept of Pediatrics, Attikon University Hospital, Rimini St., 12462 Haidari, Athens, Greece. E-mail:

Most patients with papular-purpuric gloves and socks syndrome (PPGSS) are young adults1 having well-described clinical and laboratory features. Childhood onset cases2–6 have been reported as well. In a series of 33 pediatric cases,7 only 1 patient aged 9 years was involved and all the others ranged in age from 11 months to 3 years. There were striking differences compared with adults. The petechial component of the acral lesions was not prominent, oral erosions were not present, and fever was absent.8 Human parvovirus B19 (PVB19) infection was seen in 4% of the patients,8 and blood irregularities rarely encountered. We report a case and review the literature, about the general characteristics of childhood and adolescent cases.

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We made a Medline search of articles published in accessible English language journals from 1990, the year the first 5 cases were described by Harms et al,1 using the term PPGSS, for pediatric and adolescent cases (<18 years). We used the terms gloves and socks syndrome, parvovirus B19 infection cross investigation of described cases, and the references within articles disclosed additional cases. The patients reviewed herein were categorized separately according to their age in 2 groups. The first group comprised patients less than 5 years of age who were considered as juvenile PPGSS type and the older ones (6–18 years) characterized as childhood and adolescent type. Patients belonging to the latter type were thoroughly scrutinized and represent the target population of the study.

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A 12-year-old previously healthy boy was admitted to our department with a rash that had erupted 5 days earlier and involved the upper and lower extremities. The parents reported that 10 days before admission the child had had an upper respiratory tract infection with fever (up to 38°C) and aphthous stomatitis which lasted about 2 days. He had been given no vaccinations or medications during the previous month.

Physical examination revealed multiple purpuric erythematous papules, partially confluent, on the dorsa and palms of the hands and on the dorsa and soles of the feet. The rash was sharply limited to a few centimeters above the wrists and the ankles. There were petechial lesions and erythema on the palate and the tongue. The spleen was palpable 1.5 cm below the costal margin. The rest of physical examination was unremarkable. The patient was afebrile in good general condition and did not report pruritus or pain.

Routine laboratory tests revealed mild leucopenia (3.6 × 103/μL) with relative neutropenia (39%), lymphopenia (31%), and eosinophilia (11%). Mild thrombocytopenia was also noticed (138 × 103 platelets/μL). Hemoglobin was 12.8 g/dL and erythrocyte sedimentation rate and C-reactive protein were 20 mm/h and 3.12 mg/dL, respectively. Renal and hepatic functions as well as coagulation tests were normal. Serologic tests for hepatitis A, B and C, cytomegalovirus, Coxsackie B1-B6, Epstein Barr, and herpes simplex were negative. Increased specific IgM and IgG antibody titers were detected for both HHV-6 and PVB19 by commercial enzyme-linked immunosorbent assay.

One day after admission the rash began to subside and it almost disappeared the following day when the patient was discharged. A blood test on the day of discharge revealed 4640 white blood cells/μL with a differential count of 63% neutrophils, 20% lymphocytes, 12% monocytes, and 5% eosinophils. The platelet cell count rose to 174 × 103/μL. No treatment was instituted during hospitalization.

The patient's clinical picture and serology established the diagnosis of PPGSS. Because the child lives in a small, remote, island of the Aegean Sea, we were unable to repeat the serologic tests for HHV-6 and PVB19.

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Search of the literature yielded 25 cases, in 6- to 18-year-old children, irrespective of the agents implicated in the infection process of the disease. Diagnostic tests for etiologic agents were not uniform. Parvovirus B19 was identified in 21 cases (84%). Details of the reviewed cases6–21 are analyzed and depicted in Table 1. Fever was recorded in 17 of 25 patients and lymphadenopathy 6 cases. There was 1 reported case of coinfection with PVB19 and HHV-7.14



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The most common and easily recognized pattern of PVB 19 infection is erythema infectiosum (fifth disease) occurring mainly in childhood. In its typical form, PPGSS presents initially with edema and erythema of the dorsal and palmar surfaces of the distal extremities. The lesions are sharply marginated at the wrists and the ankles. Before long, erythematopapular and purpuric lesions evolve in the same sites. Oral lesions4,9,10,13,14 and constitutional symptoms usually accompany the eruption of the purpuric rash. In many cases, there is mild anemia, reticulocytopenia, leucopenia, and thrombocytopenia.1–4,9,10,13 The syndrome has mainly been described in young adults, although a recent study7 suggested that it is not rare in children but it rather tends to appear with an atypical clinical picture.

PVB19 has been implicated as the major causative agent of the syndrome; however, other viruses,7,14 such as CMV, EBV, measles, and HHV-6 have been considered as causative agents for PPGSS. In addition, drugs such as thrimethoprim/sulfomethoxazole22 have been proposed as causative factors. The pathogenesis of PPGSS is not clear. Histologic findings from affected skin show lymphocytic infiltration and extravasation of erythrocytes with no evidence of vasculitis.23 PVB19 viral particles have been found in the endothelial cells of the dermal vessel walls and in the basal cells of the epidermis. Debate exists as to whether the lesions are attributable to a virus-induced pathogenetic mechanism to the consequence of immune complex formation and deposition.

Our patient presented with a typical clinical picture of the skin and the oral mucosa accompanied by hematologic abnormalities and had the usual benign course of the syndrome. This constellation of clinical and laboratory findings is rather unusual in the pediatric age group. Our patient is the first in whom PPGSS followed simultaneous acute infection from PVB19 and HHV-6. Unfortunately, a second serology that would have made our results more solid was not available. We found 1 report in the literature of PPGSS resulting from simultaneous infection by HHV-7 and PVB19.14 A dual infection with HHV-6B and PVB19 was described in an immunosuppressed child causing transient anemia, leucopenia, thrombocytopenia, renal insufficiency, and maculopapular rash.24

The most representative and descriptive series of children with the so-called juvenile type of PPGSS was published by Hsieh and Huang.7 The juvenile variant of papular-purpuric gloves and socks syndrome shows different clinical features from the adult type. Fever or palpable lymphadenopathy were not seen in juvenile PPGSS, and oral erosions were present in only 1 of 33 cases. The majority of patients had IgM antibodies to CMV or EBV and antibodies to PVB19 were detected in only 1 of 33 patients. The median age of the affected children was 23 months, with the exception of 1 child who was 9 years and 2 months old; the remaining 32 were up to 3 years and 1 month or younger.

In the older children reported in the literature, fever was found in 17 of 25 cases and lymphadenopathy was found in at least 6 of 25 cases, as it is not clearly reported in all the described patients. Evidence of acute infection with PVB19 was detected in 84% of cases versus in 4% of the aforementioned series of juvenile PPGSS. We conclude that, at this age, the disease generally presents with fever along with the eruption and that PVB19 is the main culprit.

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papular-purpuric gloves and socks syndrome; parvo-virus B19; human herpes virus 6; infection

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