Chronic Arthropathy due to Parvovirus B19: Is it a Proven Entity?

ABSTRACT & COMMENTARY

Synopsis: Synovial tissue samples from patients with chronic juvenile arthritis and a control group of healthy young adults with recent joint trauma were examined for parvovirus B19 DNA using polymerase chain reaction (PCR) analysis. A higher proportion of the controls were positive for B19 than the patients.

Source: Söderlund M, et al. Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy. Lancet 1997;349:1063-1065.

Cases that are classified as parvovirus arthropathy are usually transient, but it has also been implicated in chronic rheumatoid arthritis or juvenile chronic arthritis.

Söderlund and associates at the University of Helsinki used the polymerase chain reaction (PCR) to detect parvovirus B19 DNA from synovial tissue obtained at arthroscopy or arthrotomy. The amplified DNA was studied by southern blot hybridization.

Eight of 29 (28%) children with chronic arthritis were positive for parvovirus B19 DNA; however, an even higher proportion (13 of 28; 44%) of the non-arthropathy controls were positive. All of the individuals with B19 DNA in synovial tissue also had serum IgG antibodies to B19.

COMMENT BY PAUL McCARTHY, MD, FAAP

There is an extensive scientific literature that attempts to link various infectious agents with chronic synovitis (arthritis). Interest in this association has been sparked by selected molecular markers Class I and II molecules that are encoded by genes in the major histocompatibility complex on the short arm chromosome #6. For example, there is a strong association between HLA-DR4 (a Class II molecule) and polyarticular juvenile rheumatoid arthritis with rheumatoid factor positivity. Class II molecules are intimately involved in antigen presentation to T cells and subsequent inflammatory events. It has been speculated that the increased frequency of selected Class I and Class II molecules in patients with chronic inflammatory states, such as arthritis, may be related to molecular mimicry between the molecule and a foreign antigen, most probably an infectious agent. Because of this mimicry, the immune system may not recognize the infecting agent; hence, the agent may produce chronic inflammation. An intriguing report of a putative prolonged infection causing chronic arthritis in children was that of Chantler et al, in which the authors found that 37% of 19 children with juvenile chronic arthritis but 0% of controls had rubella virus isolated from mononuclear cells from blood or synovial fluid.1 However, the etiologic role of rubella in chronic childhood arthritis has not been confirmed.

There have been several previous reports of arthritis in association with clinical parvovirus B19 infection in both adults and children. The arthritis is usually, but not always, self-limited. In one report, 20 children developed arthritis in association with clinical parvovirus B19 infection. The arthritis lasted less than four months in 13 children; in the remaining seven children whose arthritis had not resolve at the time of the report, only four had arthritis for more than four months.2

Does parvovirus B19 cause chronic arthritis? Söderlund et al report evidence of parvovirus B19 DNA in the synovium of 28% of children with juvenile chronic arthritis. But, he also found such evidence in 48% of non-arthritic controls. The implications of this report are that parvovirus B19 DNA is not a marker found exclusively in the synovium of children with chronic arthritis, and parvovirus B19 DNA in the synovium does not indicate that the synovitis will be self-limited, as is seen in the majority of children with arthritis having its onset during a clinical parvovirus infection. The data do not rule out the possibility that a parvovirus infection may trigger a chronic arthritis in a susceptible host since the Class I and Class II status of the patients and controls was not analyzed. A report in 1986 of 18 patients with arthritis persisting for a median of six months following a parvovirus infection noted that 12 of the 18 patients were HLA-DR4 positive.3

As is demonstrated by this report, defining the relationship among infectious agents, host susceptibility, and chronic inflammatory problems, including arthritis, remains an intriguing but unresolved scientific challenge. It is also true that PCR is a very sensitive test for detecting minute amounts of DNA. It is possible that small amounts of viral DNA may persist for a long time in tissues and have little relationship to any clinical entity.

References

1. Chantler JK, et al. Persistent rubella virus infection associated with chronic arthritis in children. N Engl J Med 1985;313:1117-1123.

2. Nacton JJ, et al. Human parvovirus B19-arthritis in children. J Pediatr 1993;122:186-190.

3. Klouda PT, et al. HLA and acute arthritis following human parvovirus infection. Tissue Antigens 1986;28:318-319.