Disease exacerbation by etanercept in a mouse model of alphaviral arthritis and myositis.

OBJECTIVE: Mosquito-borne alphaviruses such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV) cause sporadic, sometimes large, outbreaks of rheumatic disease worldwide. This study was designed to test the effect of treating RRV-induced arthritis using the anti-tumor necrosis factor (anti-TNF) drug etanercept in a mouse model of rheumatic disease. METHODS: Mice were infected with RRV and treated with etanercept. Weight gain was measured, tissue viral titers were determined, and histologic changes in muscle and joint tissues were assessed. RESULTS: RRV-infected mice treated with etanercept showed decreased weight gain, higher viral titers in muscle, joints, and blood, and more tissue damage and inflammatory cell recruitment than RRV-infected mice without treatment. CONCLUSION: Anti-TNF therapy is unlikely to be useful in treating alphaviral arthritides. During alphaviral epidemics, careful monitoring of patients being treated with anti-TNF agents may be warranted.

Neurological impairment and arthritis in an immunocompetent child with human parvovirus B19 chronic infection.

Human parvovirus B19 (HPV-B19) is usually a self-limiting infection in immunocompetent children. In this case report, instead, we describe an immunocompotent child with evidence of persistent HPV-B19 infection, arthritis and neurological impairment. He was first admitted to hospital for HPV-B19 infection and sent home in good clinical condition after anti-inflammatory therapy. Eight months later he was re-admitted to hospital for episodes of arthritis and weakness, myalgia, tremors in his legs and hands, and was unable to walk unaided. In both plasma and serum, HPV-B19 DNA, detected by polymerase chain reaction, was still present. For neurological symptoms, he underwent magnetic resonance, which showed increased signal intensity at the spinal roots in the lumbar region, compatible with polyradiculoneuritis. After immunoglobulin therapy he had an excellent response in clinical and radiological terms, suggesting an association between neurological impairment and HPV-B19 infection. Eleven months after the second admission, the patient was still in good clinical condition.

[Parvovirus B19 as a cause of acute arthritis]. / Parvovirus B19 som årsak til akutt artritt.

Parvovirus B19 is known to cause erythema infection (fifth disease), acute and chronic arthritis, aplastic crises in chronic hemolytic anemia, chronic anemia in the immunocompromised host and hydrops fetalis. We present two patients with acute arthritis due to parvovirus infection. Both had symmetrical synovitis in wrists and ankles. Patient 1 presented with fever and rash before joint symptoms occurred; patient 2 had joint symptoms only. Arthritis due to parvovirus is usually self-limited, but may develop into a chronic disease similar to rheumatoid arthritis. Parvovirus should be considered one of the differential diagnoses while dealing with acute or chronic arthritis.

Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis.

OBJECTIVE: To evaluate the feasibility of direct in vivo gene transfer in an animal model of arthritis using a retroviral vector. METHODS: The timing and dose of retroviral vector was examined using very high titer retroviral vector (> or = 10(9) CFU) in rat adjuvant arthritis. Retroviral vector expressing beta-galactosidase (beta-gal) or vehicle alone was injected into the right ankle of rats with adjuvant arthritis. Ankles were injected either on Day 7 (pre-arthritis), Day 10 (early arthritis), Day 15 (accelerating arthritis), or Day 28 (chronic arthritis) after adjuvant immunization. Joints were harvested 3 days later and extracts were assayed for beta-gal activity. RESULTS: Synovial beta-gal expression was minimal in the Day 7 group and elevated in the Day 10, Day 15, and Day 28 groups. Gene transfer with retroviral vector did not exacerbate the local inflammatory response. Minimal or no beta-gal expression was observed in the contralateral uninjected paw or in the spleen, lung, liver, and kidneys. Frozen sections of retroviral vector injected joints were stained with X-gal and revealed transduced cells in the lining and superficial sublining layers. To determine the longevity of gene expression, ankle joints were injected with vector on Day 15 post-adjuvant, harvested, and assayed for beta-gal activity for up to 49 days after injection. Expression of the enzyme peaked from Day 3 to 7 and was still readily detected up to 49 days after retrovirus infection. CONCLUSION: This is the first report of successful direct in vivo gene transfer in the rat adjuvant arthritis model using a retroviral vector. Appropriate timing of administration and very high titer retroviral vector preparations are key determinants of adequate gene transduction.