Prolonged myalgia in Sindbis virus infection: case description and in vitro infection of myotubes and myoblasts.

BACKGROUND: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. METHODS: We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes. RESULTS: In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein. CONCLUSIONS: This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.

Clinical Sindbis alphavirus infection is associated with HLA-DRB1*01 allele and production of autoantibodies.

BACKGROUND: Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection, characterized by arthropathic disease that may persist for years, is primarily reported in Northern Europe where the disease has considerable public health importance in endemic areas. The aim of this study was to investigate the role of genetic factors in the susceptibility and outcome of SINV infection and to elucidate the association between SINV infection and autoimmunity. METHODS: The study included 49 patients with serologically confirmed symptomatic SINV infection who were followed for 3 years after acute infection. Human leukocyte antigen (HLA) genes known to be associated with rheumatic and infectious diseases and complement C4 genes were determined in 35 patients. Furthermore, a set of autoantibodies was measured at the acute phase and 3 years after infection in 44 patients. RESULTS: The frequency of DRB1*01 was significantly higher among patients with SINV infection than in the reference population (odds ratio, 3.3; 95% confidence interval, 1.7-6.5; P = .003). The DRB1*01 allele was particularly frequent in patients who at 3 years postinfection experienced joint manifestations. The frequency of rheumatoid factor at 3 years postinfection was 29.5% and had increased significantly (P = .02) during the 3-year period. In addition, antinuclear and antimitochondrial antibodies were present in serum 3 years postinfection with frequencies of 15.9% and 6.8%, respectively. CONCLUSIONS: Our data show that symptomatic SINV infection is associated with the HLA system and that autoantibody titers are elevated in patients 3 years postinfection. These findings indicate that SINV-induced arthritis shares features with autoimmune diseases.

[Rheumatoid arthritis (updated Current Care guideline)]. / Nivelreuma.

Anti-citrulline antibodies are highly specific to rheumatoid arthritis (RA) and are thus helpful in differential diagnosis. Early and aggressive disease modifying anti-rheumatic drug (DMARD) therapy is essential for a positive treatment result in cases of RA. Remission during the 1st year of treatment predicts permanent remission, milder joint damage and better functional ability. It is recommended that patients with an unsatisfactory response to DMARDs, including methotrexate and a combination of DMARDs, should be treated primarily with TNF blockers, and non-responders with rituximab or abatacept. RA is an independent risk factor for cardiovascular diseases. The assessment of cardiovascular risk must not be forgotten in daily practice.

"Strawberry like" gingivitis being the first sign of Wegener's granulomatosis.

Wegener's granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small vessels, affecting vascular structures having predilection for upper airways. If untreated WG can be lethal. WG is also known to cause oral mucosal lesions. We report a case of WG that was first diagnosed on oral gingival mucosa. A 51-year old woman was referred to a specialized dentist because of consistent irritative buccal gingival hyperplasia that did not react to conservative and microbial treatment. The lesion was biopsied and the diagnosis was suggestive for WG. Patient was further referred to the Department of Rheumatology and the diagnose of WG was confirmed and treated. The oral lesions cured totally. This case emphasizes the importance to recognize the oral manifestation of WG to get proper medication as soon as possible and avoid serious systemic tissue damage.

Arthritis and arthralgia three years after Sindbis virus infection: clinical follow-up of a cohort of 49 patients.

Sindbis virus (SINV) emerges as large human outbreaks in northern Europe every 7 years. Similar to many other alphaviruses, SINV is a mosquito-borne causative agent of a rash-arthritis. Previous reports suggest that in many alphavirus infections joint symptoms might persist for years. A prospective cohort of 49 patients was physically examined 3 y after verified acute SINV infection to reveal persistent joint symptoms. We carefully searched for a temporal association between the infection and current symptoms, and took into account other medical conditions. Sera were collected and analysed with enzyme immunoassays. Arthritis (swelling and tenderness on physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness on palpation or in movement of a joint was found in 14.3% of the patients in the rheumatological examination, and an additional 10.2% complained of persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection 3 y earlier. A positive IgM antibody response persisted in 3/49 of the patients; both patients with arthritis were in this group. As one-quarter of the patients were symptomatic 3 y after infection, it seems that persistent symptoms of SINV infection have considerable public health implications in areas with high seroprevalence.

Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis.

OBJECTIVE: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. RESULTS: The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. CONCLUSION: The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.