Can Parvovirus B19 Infection Cause Rheumatoid Arthritis & Is It An Autoimmune Disease?

The association between parvovirus B19 infection and arthropathy was made in 1985.(1)

Parvovirus B19 has been associated with the development of various autoimmune diseases.(2)

Can Parvovirus B19 Infection Cause Rheumatoid Arthritis?

The most common infection that parvovirus B19 causes are erythema infectiosum that leads to rashes in the body. On occasions, this rash is accompanied by acute symmetric polyarthropathy or arthritis that may mimic rheumatoid arthritis in adults. The association between B19 infection and arthropathy (joint diseases) was made only recently in 1985. The rash of erythema infectiosum is mostly followed by arthralgia (joint pain), which is more common in adults (affecting 60% women and 30% men) than in children (approximately 10%). The commonly affected joints are metacarpophalangeal (75%), knees (65%), wrists (55%), and ankles (40%). However, they are devoid of articular erosions that are mainly present in rheumatoid arthritis.(1)

B19 associated arthritis is most acute but may become chronic in some cases. Nearly 50% of patients with chronic B19 arthropathy meet American Rheumatoid Association criteria for the diagnosis of rheumatoid arthritis. Although B19 has been linked to the causation of rheumatoid arthritis, the results are inadequate and need further research for it to be considered as a definitive causative agent behind rheumatoid arthritis.

Although B19 infection mimics rheumatoid arthritis in its acute stages and there is the detection of B19 DNA in the synovial fluid and synovial biopsy specimens, there is no convincing link to consider B19 infection as the cause of rheumatoid arthritis associated with erosions of the joint and inflammatory joint disease.(1)

Is Parvovirus B19 An Autoimmune Disease?

Parvovirus B19 has been shown to initiate various autoimmune diseases that include neurological, rheumatological, hematological, metabolic, neuromuscular, cardiovascular, and nephrological diseases. Neurological diseases include transverse myelitis, cerebellar ataxia, cranial nerve palsy, Guillain-Barre syndrome, neuralgic amyotrophy, and other peripheral neuropathies. Rheumatological diseases include systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, systemic sclerosis, myositis, vasculitis, and chronic fatigue syndrome/myalgic encephalomyelitis. Hematological diseases include aplastic anemia, immune thrombocytopenia, and autoimmune neutropenia. Neuromuscular diseases include myasthenia gravis and cardiovascular diseases include myocarditis and dilated cardiomyopathy. Metabolic diseases include type 1 diabetes mellitus, Hashimoto’s thyroiditis, and Graves’ disease; whereas, nephrological diseases include glomerulonephritis.(2)

Although B19 infection has been known to produce various autoantibodies directed against various autoantigens (mitochondrial, nuclear, gastric parietal cell, smooth muscle, and phospholipid antigens) that play a key role in the pathogenesis of various systemic autoimmune diseases, its connection between autoimmunity is still not clear. Chronic B19 infection does lead to the formation of antiviral antibodies that have auto-antigen binding properties. Autoimmunity might be induced by parvovirus B19 due to molecular mimicry mechanism by cross-reacting with human proteins (autoantigens), by alteration of the apoptotic process resulting in self-antigens to T lymphocytes, and phospholipase activity of the B19 unique VP1 protein region.

B19 infection triggers certain autoantibodies in the above-mentioned autoimmune diseases, such as in rheumatoid arthritis- RF and anti-cyclic citrullinated peptide antibody; in juvenile idiopathic arthritis- anti-cardiolipin, anti-phosphatidylserine, and anti-beta2-glycoprotein 1 antibodies; in systemic lupus erythematosus- anticardiolipin antibody; in glomerulonephritis- anti-nuclear antibody, anti-cardiolipin antibody, anti-GBM antibody, proteinase-3 ANCA, myeloperoxidase-antineutrophil cytoplasmic antibody. Although parvovirus B19 is associated with triggering autoimmune responses and autoimmune diseases, it in itself is not an autoimmune disease.(2),(3)

The discovery of parvovirus B19 (B19) has only been recent in the 20th century around 1974. Among all parvoviruses, only parvovirus B19 is pathogenic to humans. It is a single-stranded DNA virus and belongs to the family Parvoviridae. B19 infection is quite common both in the immunocompetent and immunocompromised individuals depending on their immunologic and hematologic status. B19 causes erythema infectiosum and arthropathy in healthy immunocompetent people. In individuals with hemolytic disorders, B19 infection may lead to transient aplastic crisis due to their affinity for erythroid progenitor cells. It is related to pure red cell aplasia, congenital anemia and chronic anemia in immunocompromised patients and hydrops fetalis causing fetal death in utero in pregnant women.(1)

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