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High frequency of parvovirus B19 in patients tested for rheumatoid factor

Department of Medicine, University of Edinburgh, Rheumatic Diseases Unit, Western General Hospital, Edinburgh EH4 2XU Paresh Jobanputra, lecturer. Edinburgh and South East Scotland Blood Transfusion Service, Royal Infirmary of Edinburgh, Edinburgh EH3 9HB Fiona Davidson, post-doctoral research fellow Susan Graham, research assistant Peng Lee Yap, consultant. Regional Virus Laboratory, Royal Victoria Hospital, Belfast BT12 6BN Hugh O'Neill, consultant clinical scientist. Department of Medical Microbiology, Medical School, University of Edinburgh, Edinburgh EH8 9AG Peter Simmonds, lecturer. Correspondence to: Dr Jobanputra.

Symptomatic adult parvovirus B19 infection typically causes a brief arthritis, often with a rash. Persistent symptoms may occur,¹ and B19 has been linked with many rheumatic diseases. Virus specific IgM is detectable for about three months after infection, leaving a narrow window in which to make a diagnosis when chronic symptoms arise. Since blood samples from patients with musculoskeletal disease are frequently tested for rheumatoid factor we sought B19 DNA by polymerase chain reaction in such samples in order to identify any relation between chronic symptoms and parvovirus infection.

Subjects, methods, and results

Remaining serum from 503 consecutive samples submitted for a rheumatoid factor test was collected prospectively between December 1992 and February 1993. Samples from blood donors (348) and from inpatients requiring blood transfusions (333), also collected during these months, served as controls. Clinical data were obtained retrospectively from records. B19 DNA was identified using a method for screening large numbers of samples.²

Parvovirus DNA was found in 23 test samples and two control samples. Samples submitted from general practitioners were more likely to be positive (table). All samples positive for B19 DNA and 48 negative samples were tested for IgG and IgM by an indirect fluorescent antibody technique.³ The proportion of samples positive for rheumatoid factor (>/=1/16) was similar in B19 DNA positive patients (3) to that for B19 negative patients (53) (P=0.98).

Of the 23 patients with B19 DNA 17 had typical joint pain resolving within one month (seven also had a rash); two, known to have longstanding intermittent seronegative arthritis, experienced an exacerbation and were both IgM positive; one had an illness lasting four months diagnosed as myalgic encephalitis; one had carpal tunnel syndrome; one had intermittent fatigue and neutropenia over many months; and one was lost to follow up. Clinical diagnoses for samples sent from the rheumatology department were: rheumatoid arthritis 29%; osteoarthritis 15%; no diagnosis 11%; and 45% miscellaneous disorders.

Details of patients and controls, presence of B19 DNA, and results of serological testing
---------------------------------------------------------------------------------------------
                                          Subjects         B19 DNA positive      Serology
----------------------------------------------------------------------------   (IgM: IgG) in
                                                Mean age           Mean age    DNA positive
                                        No        (yr)      No       (yr)        samples
---------------------------------------------------------------------------------------------
Patients tested for rheumatoid factor   503                 23*                   21++:23
 Men                                    156       45.6       2        30
 Women                                  347       45.0      21       35.5
Source
 General practitioners                  297                 20+                    20:20
 Rheumatology                           118                  1                  IgM and IgG
 Orthopaedics                            22                  1                   IgG only
 Others                                  66                  1                   IgG only
Blood donor samples                     348                  1
 Men                                    204        37
 Women                                  144        33
Blood transfusion samples               333                  1
 Men                                    117        61
 Women                                  216        52
---------------------------------------------------------------------------------------------
*P<0.001 when compared with controls. Odds ratio 18 (95% confidence interval 4.2 to 76.7).
+Odds ratio 5 (1.5 to 17); P=0.01 when compared with samples from other sources.
++P<0.001 when compared with 48 sera that were negative for B19 DNA (two of the negative sera
were IgM positive; both patients had an illness typical of B19 infection).

Comment

Parvovirus infection diagnosed on the basis of clinical features, IgM, and presence of DNA occurred frequently in individuals seen in general practice who were tested for rheumatoid factor. This reflects early testing for rheumatoid factor in patients who subsequently have a short lived illness. A definite clinical diagnosis was made in only one case, although in most cases the illness was recognised as viral. Failure to identify a specific infection in this situation matters since parvovirus is an important cause of fetal death in the second trimester⁴ and many patients were women of child bearing age. It may also matter for those with persistent symptoms. B19 is highly infectious and often asymptomatic.⁵ Viraemia is rarely detected in symptomatic individuals except by polymerase chain reaction, and isolation of patients is unlikely to prevent further infections.

An epidemic cannot explain the frequency of infection since only 40 infections were reported to the infectious disease surveillance unit in Scotland between December 1992 and February 1993. Two patients with parvovirus DNA and prolonged symptoms were IgM negative. It is difficult, in retrospect, to be certain that symptoms in these cases were due to persistent infection. Two patients with an established seronegative polyarthritis were IgM positive. These patients probably developed a coincidental acute parvovirus infection rather than an exacerbation of their underlying disease. It does not imply any relation between B19 and seronegative arthritis. Parvovirus was rarely found in samples sent from the rheumatology department. Since we relied on clinical records to assess symptom duration we may have underestimated chronicity. Virus specific IgM, found in some samples that were negative for B19 DNA, showed that we were underestimating the frequency of infection by polymerase chain reaction alone. It is clear that serological tests will identify most parvovirus infections and that this infection is often not recognised in general practice.

We thank Diane Anderson and her colleagues in medical microbiology at the Western General Hospital in Edinburgh and staff at the blood donor centre and blood issue department at the Royal Infirmary of Edinburgh for collecting sera and helping with data collection. We are very grateful to all general practitioners for clinical data.

Funding: FD and SG were supported by the Scottish National Blood Transfusion Service.

Conflict of interest: None.

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• Cohen, B. (1995). Fortnightly Review: Parvovirus B19: an expanding spectrum of disease. BMJ 311: 1549-1552 [Abstract] [Full text]