Parvovirus B19 and chronic arthritis--causal or casual association?

Since its identification in asymptomatic blood donors in 1975, human parvovirus B19 has been associated with a variety of clinical manifestations including erythema infectiosum,l aplastic crises,2 hydrops fetalis,3 certain vasculitides4 5 and an acute arthropathy.6 7 Nikkari et al8 propose in this issue that parvovirus B 19 could be a trigger for rheumatoid arthritis in some patients. The spectrum of outcome was demonstrated in a controlled epidemiological study,9 varying from an asymptomatic infection, a flulike illness often with a rash, to an acute arthropathy in 60% of women and 30% of men, and lasting more than two months in 20%. Some of these patients, and others reported,6 9 had an arthropathy at times clinically indistinguishable from rheumatoid arthritis, a few are seropositive for rheumatoid factor,'0 and patients have been reported who developed erosive disease.81 Studies have therefore looked at the possible relationship between parvovirus B 19 and rheumatoid arthritis. There are two principal difficulties in this line of enquiry: first, proving a causal relationship and second, the limitations of the methods of detection of recent or past parvovirus B 19 infection. Chronic diseases caused by infectious agents, such as reactive arthritis, do not meet the Henle-Koch postulates,'2 as they represent an unusual host response to a common infection. Controlled or long term prospective studies are required. Seroepidemiology is of limited value. The usefulness of B 19 IgG assay in patients whose symptoms are long standing is not great, because more than 50% of adults in the United Kingdom have this antibody whether or not they have a history of arthritis, and the seroprevalence increases to more than 75% in those older than 50 years. '3 One early study did find a greater prevalence of B 19 IgG in chronic arthfritis patients compared with controls,'4 but this was not confirmed by others, '5 and needs to be repeated using the newer B 19 IgG assays available. A negative B 19 IgG result excludes a past infection with B 19 virus, but a positive result may have no pathological significance, merely reflecting past acquisition of antibody, mostly likely as a result of erythema infectiosum or asymptomatic infection in childhood. Nikkari et al detected parvovirus B 19 specific gene sequences by polymerase chain reaction (PCR) in two patients with early arthritis fulfilling criteria for rheumatoid arthritis, but the disease was progressive and erosive in only one case. Caution must be exerted in interpreting these results. Positive PCR findings in serum are not limited to the acute phase, but can be made for many months afterwards, even in completely resolving B19 infection in immunocompetent hosts without clinical sequelae. '6 The presence of B19 DNA at this stage of convalescence may merely reflect the stochastic decay'6 of a biological entity, B19 virus, which is both stable and initially present at an extremely high concentration in the blood. The persistence of B 19 DNA at other sites of the body, especially in synovial material, may have greater significance, but does not prove causation as it may be a mere passenger in one of the cell populations attracted to the inflamed synovium. Preliminary PCR studies targeted on these areas have been performed,'7 18 but have so far been limited by lack of suitable control samples. It would be helpful in future PCR investigations to develop assays that are both quantitative (so that a clinically significant level of B 19 DNA can be determined) and discriminatory between replicating forms of B19 DNA or RNA and virion associated DNA. This might allow current B 19 infection to be differentiated from a recent acute infection. The question ofwhether B 19 virus is a persistent infection or a trigger in chronic arthritis may then be addressed. Until then, the role of B 19 in rheumatoid arthritis remains speculative. There is, however, a clear role of B 19 in acute arthropathy, which may initially present as indistinguishable from rheumatoid arthritis, and it is important to appreciate the limitations of presently available diagnostic procedures. Here the diagnosis rests on demonstrating B 19 specific IgM, but as this marker is only present for two to three months after onset ofsymptoms it is only useful when early presenting cases are being examined. Specific IgM serology is not worthwhile in patients presenting more than three months after disease onset and may be complicated by the presence ofrheumatoid factor, which generates nonspecific reactions in some B19 IgM assays. Caution must also be shown with some recent commercial B 19 IgM assays which have unproven specificity and sensitivity; results should be confirmed by a reference B 19 IgM assay or by some other procedure, for example, IgG avidity assay. '9 As the majority of cases have a good outcome,9 diagnosis of parvovirus B 19 arthropathy will allow reassurance of the patient and appropriate conservative treatment.