Abstract

Dear editor,

Adult patients with new onset polyarthritis may present a diagnostic challenge; differential diagnosis between primarily rheumatic conditions with viral arthritis such as those caused by parvovirus (PV)-B19 is one of the concerns.

Infection by PV-B19, a single stranded DNA virus, is very common, affecting more than 50% of adults in the United Kingdom and with a prevalence that rises with age reaching 75% in individuals older than 501,2. In children the characteristic skin rash (slapped face) is common and articular involvement is rare following the pattern of large joints oligoarthritis1. In adults the rash is usually absent and articular symptoms are common (80%) taking a polyarticular pattern that involves wrists, metacarpophalangeal and interphalangeal joints symmetrically1. So, in adults the differential diagnosis with early rheumatoid arthritis (RA) is mandatory. Moreover, these patients may present important morning stiffness3 and develop autoantibodies such as rheumatoid factor and antinuclear antibody at low titers creating further difficulties1. The polyarticular PV-B19 arthritis has usually a self-limited pattern but can also become chronic developing erosions as well2. This has led to the question of whether PV-B19 chronic arthritis is a persistent infection with articular involvement or a trigger for RA in genetically predisposed individuals.  A study done in Taiwan, in 100 patients with RA and 94 controls showed that RA patients had more PV-B19 infections (24% IgM anti-B19 in RA vs. 16% in controls; and 34% of B19DNA in serum or synovial material of RA patients versus 6.4% in control sera) showing a possible link between these two entities4. The same observation was done in a study in RA patients from Taiwan, which also showed that RA patients HLA-DR4 positives had higher prevalence of HP-B19 infections than those HLA-DR4 negatives suggesting a synergistic effect between HLA-DR4 and PV-B19 infection.

From the practical point of view, being able to differentiate these two situations helps the clinician to choose a treatment: while in chronic PV-B19 infections immunoglobulin has been used, in RA synthetic disease modifiers and/or biologics are indicated.

Herein we describe a patient that illustrates the difficulties in the differential diagnosis between these two situations and that responded well to antimalarials and methotrexate.

She was a 55-year-old woman, smoker of 10 packs-year, with a negative past medical history that came with a trigger first left finger and bilateral wrist arthritis. At that time the investigation showed C-reactive protein of 0.17 mg/L, erythrocyte sedimentation rate of 18 mm and a positive IgM for PV-B19 with negative IgG. Antinuclear antibodies (ANA), anti-CCP and rheumatoid factor (RF) were negative; complements were normal. Serology for syphilis, HIV, and HTLV I and II, hepatitis B and C; cytomegalovirus, Epstein-Barr, and herpes simples 1 and 2 were negative.  Hand X-Rays were normal. She was treated with a single injection of betamethasone depot and with antimalarials and became asymptomatic. A follow-up visit done 1 year later showed that she was well and the IgM HPV-B19 was absent with positive IgG. The patient remained well using antimalarial until 4 years later when she developed bilateral synovitis of all metacarpophalangeal and proximal interphalangeal joints with flexors tenosynovitis confirmed by ultrasound. ANA, RF and anti CCP remained negatives. Methotrexate (15 mg/week) was added to treatment with good response. She is currently on a 1-year follow-up after starting methotrexate and in remission.

This patient’s initial presented picture pointed to HP-B19 infection.  Then, she had a 5-year period of remission and the later manifestations of the disease were highly suggestive of seronegative RA. It is possible she had the two diseases or that the HPV-B19 became chronic, being quiescent during 5 years because of antimalarial use. It is also thinkable that the HPV-B19 triggered the later appearance of a true RA. While a definite answer seems impossible, it is interesting to note that the patient answered to methotrexate. The literature suggests immunoglobulin use in cases of chronic HP-B19 infection, but it is also worthwhile to note that, in other viral infections triggered arthritis such as of chikungunya, methotrexate and antimalarial have been used with success1,6.

Further studies in the role of viral infections in autoimmunity are needed to clarify this fascinating link between PV-B19 infections and RA.