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Parvovirus infections: What’s relevant?

DII small banner By Warren R. Heymann, MD
Nov. 24, 2017

Parvovirus B19 infection. Purpuric rash on the legs (A) and hands (B) in a patient with a gloves-and-socks syndrome.
Credit: JAAD
It seems as though the expression “It could be Parvovirus” has entered our differential diagnostic discussions with increasing frequency over the past few years.

New literature suggests that many eruptions could be –—or not.
Parvovirus B19 is a single-stranded DNA virus that affects both adults and children; The majority of those infected with Parvovirus B19 are asymptomatic or have mild, nonspecific flulike symptoms. By 18 years of age, half of the population has been infected. Erythema infectiosum (“slapped cheek”, fifth disease) is seen in children, while the papular-purpuric gloves and socks syndrome usually affects adults. Arthropathy is more commonly observed in adults, where the small joints are affected; in children larger joints tend to be involved. Parvovirus B19 infection can trigger an acute transient aplastic crisis or chronic red cell aplasia. Patients with iron deficiency anemia, HIV, sickle cell disease, thalassemia, or spherocytosis are at greatest risk. (1) Infection during pregnancy puts the fetus at risk for hydrops fetalis.
The following reports of unusual exanthems have been attributed to Parvovirus B19 infection based on the presence of IgM to the virus:

*A 4-year-old girl and her 5 year-old brother with erythema infectiosum, developing cellulitic-appearing (red and swollen) lower extremities that resolved without sequelae after a few weeks. (2)

*A 3-year-old girl with a 1-week history of general malaise, fever, cough, and a cutaneous rash consisting of multiple generalized small and confluent vesicular lesions. The exanthem resolved within a week. (3)

*A 4-year-old girl presenting with a fever of 39 °C that had been present over the previous three days accompanied by an erythematous rash of two days duration. Purpuric papules on the chin and ears (with no erythema of the cheeks) were noted, as was a morbilliform rash over the trunk and limbs. Her legs, forearms, and the dorsa of her hands and feet were edematous and covered with small petechial papules; most striking were erythematous papules and plaques in a linear, flagellate pattern. (4)

*A 49 year-old woman with acute generalized exanthematous pustulosis accompanied by fever > 40°C , neutrophilia, and an ESR of 89. The rash resolved within 1 week with desquamation and hyperpigmentation. (5)

Parvovirus B19 has also been considered pathogenic in many diseases: Henoch–Schönlein purpura, erythema nodosum, erythema multiforme, keratolysis exfoliativa, dermatomyositis-like rash, systemic sclerosis, livedo reticularis, chronic urticaria, pityriasis lichenoides, psoriasis, Behçet disease, granuloma annulare, necrotizing vasculitis, Wells syndrome, Melkersson–Rosenthal syndrome, hydroa vacciniforme, Sweet syndrome and others. Aside from serology, the pathogenic association has been based on the detection of viral DNA by PCR in serum or skin biopsies.

Santonja et al sought to determine the frequency of B19V DNA detection in a large dermatopathology practice, by characterizing the histopathological patterns involved. They selected for polymerase chain reaction (PCR) detection of B19V a total of 1815 skin biopsies pertaining to entities allegedly related to B19V, as well as cases suspected clinically of representing parvoviral exanthems. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases. B19V DNA was found by PCR in 402 out of 1825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry in only three instances of papular purpuric ‘gloves-and-socks’ syndrome. As the virus has the capacity to persist in different tissues (including the skin) for long periods, the authors contend that it could represent merely an innocent bystander, They concluded that no pathogenic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatological conditions studied. (6)
Söderlund-Venermo (7) is spot on in an editorial that accompanies the article by Santonja et al:

This huge work, analysing almost 2000 skin biopsies to find B19V DNA in a wide variety of dermatological entities, is perhaps the last nail in the coffin for any claims of pathogenic significance of the mere presence of B19V DNA in a particular skin manifestation. As excellently reviewed by Evans already four decades ago, additional evidence is needed to prove the causality of a microbe. For B19V, a human-specific pathogen, such evidence could be a temporal relation to seroconversion, as in the case of erythema infectiosum, or for the more complex chronic manifestations, viral gene expression exclusively in the diseased tissue. The paper by Santonja et al is thus a good reminder for us all of the need to follow the modernized Henle–Koch postulates and to interpret our biological findings with caution.

1. Admani S, et al. Cutaneous infectious diseases: Kids are not just little people. Clin Dermatol 2015; 33: 657-71.
2. Neri I, et al. Cellulitis-like lesions: An unusual manifestation of a Parvovirus B19 infection. J Pediatr 2016; 175: 239.
3. Martín J, et al. Parvovirus B19-associated microvesicular eruption. Pediatr Dermatol 2015; 32: e303-4.
4. Miguélez A, et al. Flagellate erythema in Parvovirus B19 infection. Int J Dermatol 2014; 53: e583-5.
5. Lee D, et al. Acute generalized exanthematous pustulosis induced by parvovirus B19 infection. Ann Dermatol 2014; 399-400.
6. Santonja C, et al. Detection of human parvovirus B19 DNA in 22% of 1815 cutaneous biopsies of a wide variety of dermatological conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance. Br J Dermatol 2017; 177: 1060-5.
7. Söderlund-Venermo M. Clinical significance of parvovirus B19 DNA in cutaneous biopsies. Br J Dermatol 2017; 177: 900-1.

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