Human parechoviruses (HPeVs) are small, single-stranded, positive-sense RNA viruses which, like enteroviruses, are classified as Picornaviridae. While phylogenetically distinct from enteroviruses, HPeVs exhibit similar epidemiology and clinical presentation.1 Infection, for example, is common in infants, peaks in summer and autumn and is often asymptomatic.2 Symptoms in young children, when they do occur, include fever, gastroenteritis, rash and respiratory illness. Rarely, severe manifestations like sepsis, flaccid paralysis, myocarditis, necrotizing enterocolitis, encephalitis and death have been reported.3–6
HPeV infection is often accompanied by a generalized, erythematous, maculopapular rash, occasionally concentrated on the peripheral extremities.1 We observed 2 infants with HPeV infection who developed a well-demarcated swelling and redness of the distal extremities in a “stocking and glove” distribution. These cases, along with similar cases reported sporadically in the literature, are described herein. This finding may be a unique and distinctive feature of HPeV infection.
In July 2016, a male infant developed fever, fussiness and lethargy on day of life 10 in the absence of other symptoms. Examination was significant for tachycardia (heart rate 172), mild jaundice, slight hypotonia and a small erythematous papule on the upper lip. Complete blood count and differential, C-reactive protein, urinalysis and chest radiograph were normal. Cerebrospinal fluid (CSF) showed 15 WBCs/uL (50% lymphocytes, 32% neutrophils, 16% monocytes, 2% bands), 45,000 RBCs/uL, glucose 56 mg/dL and protein 153 mg/dL; Gram stain and bacterial culture were negative. Aspartate aminotransferase increased to 143 U/L and alanine aminotransferase at 83 U/L, both decreasing before discharge. The patient was treated with ampicillin and cefotaxime until the results of blood, urine and CSF bacterial cultures were negative; empiric acyclovir was also given until herpes simplex virus infection was ruled out with polymerase chain reaction (PCR) of mucosal surfaces and serum. The child improved clinically and was afebrile by the third hospital day (Fig. 1). However, on that day, he developed scrotal edema, thought to be caused by fluid overload, as well as a distinct, intense, sharply demarcated erythema and edema of the hands and feet (Fig. 2A, B); this gradually improved over the next few days. Serum enterovirus PCR was negative, but plasma PCR for parechovirus (ARUP Laboratories, Salt Lake City, UT) was positive on the sixth day of illness.
In September 2016, a male infant developed decreased feeding, fussiness and a high-pitched cry on day of life 16 in the absence of other symptoms. Examination was significant for tachycardia (heart rate 190), tachypnea (respiratory rate 72) and mild jaundice, but was otherwise unremarkable. Complete blood count and differential, C-reactive protein, urinalysis and chest radiograph were normal. CSF showed 2 WBCs/uL (82% monocytes, 18% lymphocytes), 1 RBC/uL, glucose 48 mg/dL and protein 99 mg/dL; Gram stain and bacterial culture were negative. Aspartate aminotransferase and alanine aminotransferase were normal. The patient was treated with ampicillin and gentamicin until the results of blood, urine and CSF bacterial cultures were negative. The child improved clinically and was afebrile by the fourth hospital day (Fig. 1). However, on the sixth hospital day, he developed a distinct, intense, sharply demarcated erythema and edema of the feet (Fig. 2C); this gradually improved over the next few days. Serum enterovirus PCR was negative, but CSF PCR for parechovirus (BioFire FilmArray, Salt Lake City, UT) was positive on the sixth day of illness.
LITERATURE REVIEW AND DISCUSSION
An English language literature search was conducted in Embase (1974 to August 2018) using the terms (parechovirus OR echovirus 22 OR echovirus 23) AND (rash OR exanthema OR erythroderma) (echoviruses 22 and 23 have been reclassified as HPeVs). Articles were examined for specific discussion of skin changes on the distal extremities.
The first description of a striking palmar-plantar erythema in neonates with HPeV infection was from Japan in 2013.7 Since then, additional cases have been reported from Japan, Australia, Korea, Italy, Singapore and, now, the United States, as summarized in Table 1. In all cases, HPeV infection was diagnosed by PCR and no other bacterial or viral causes were identified. The acral findings, best described as an intense, bright red, uniform, sharply demarcated swelling of the hands and feet, were self-limited in all cases.
The acral changes described in our cases and those from the literature appear to be unique to HPeV infection, although they are reminiscent of the “papular-purpuric gloves and socks” eruption described with human parvovirus infection.14 In as much as this finding is distinctive and occurs in neonates, we propose the term “Mittens and Booties Syndrome” to describe it. Recognizing this entity may direct clinicians to include HPeV PCR in the diagnostic work-up of febrile neonates, especially in cases where the diagnosis of Kawasaki disease is being considered (while rare in neonates, Kawasaki disease shares the features of fever, rash and changes in the peripheral extremities15).
1. Esposito S, Rahamat-Langendoen J, Ascolese B, et al. Pediatric parechovirus
infections. J Clin Virol. 2014;60:84–89.
2. Renaud C, Harrison CJ. Human parechovirus
3: the most common viral cause of meningoencephalitis in young infants. Infect Dis Clin North Am. 2015;29:415–428.
3. Sainato R, Flanagan R, Mahlen S, et al. Severe human parechovirus
sepsis beyond the neonatal period. J Clin Virol. 2011;51:73–74.
4. Figueroa JP, Ashley D, King D, et al. An outbreak of acute flaccid paralysis in Jamaica associated with echovirus type 22. J Med Virol. 1989;29:315–319.
5. Verboon-Maciolek MA, Groenendaal F, Hahn CD, et al. Human parechovirus
causes encephalitis with white matter injury in neonates. Ann Neurol. 2008;64:266–273.
6. Sedmak G, Nix WA, Jentzen J, et al. Infant
deaths associated with human parechovirus
infection in Wisconsin. Clin Infect Dis. 2010;50:357–361.
7. Shoji K, Komuro H, Miyata I, et al. Dermatologic manifestations of human parechovirus
type 3 infection in neonates and infants. Pediatr Infect Dis J. 2013;32:233–236.
8. Yuzurihara SS, Ao K, Hara T, et al. Human parechovirus
-3 infection in nine neonates and infants presenting symptoms of hemophagocytic lymphohistiocytosis. J Infect Chemother. 2013;19:144–148.
9. Shoji K, Komuro H, Kobayashi Y, et al. An infant
with human parechovirus
type 3 infection with a distinctive rash
on the extremities. Pediatr Dermatol. 2014;31:258–259.
10. Khatami A, McMullan BJ, Webber M, et al. Sepsis-like disease in infants due to human parechovirus
type 3 during an outbreak in Australia. Clin Infect Dis. 2015;60:228–236.
11. Loi C, Magnano M, Ravaioli GM, et al. An erythematous palmoplantar rash
due to human parechovirus
. Arch Dis Child. 2016;101:1070.
12. Yeom JS, Park JS, Seo JH, et al. Distinctive clinical features of HPeV-3 infection in 2 neonates with a sepsis-like illness. Korean J Pediatr. 2016;59:308–311.
13. Aizawa Y, Izumita R, Saitoh A. Human parechovirus
type 3 infection: an emerging infection in neonates and young infants. J Infect Chemother. 2017;23:419–426.
14. Smith PT, Landry ML, Carey H, et al. Papular-purpuric gloves and socks syndrome associated with acute parvovirus B19 infection: case report and review. Clin Infect Dis. 1998;27:164–168.
15. McCrindle BW, Rowley AH, Newburger JW, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–e999.
Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
parechovirus; exanthema; rash; infant; pediatric