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Biomedical subjects

E L Matteson

Publications and source records attributed to E L Matteson.

At least 19 recordsLinked to original sources

Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis.

OBJECTIVE: To study antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor in patients with active, severe extra-articular rheumatoid arthritis (ExRA) compared with controls without ExRA. METHODS: 35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti-nuclear antibodies (ANA) were investigated using indirect immune fluorescence. RESULTS: Anti-CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p = 0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94-604) v 73 IU/ml (not detected-165); p = 0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti-CCP or rheumatoid factor levels and these measures within the ExRA group. CONCLUSION: Rheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti-CCPs. This suggests a role for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.

Acute Disease↗

Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity. OBJECTIVE: To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis. METHODS: Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up. RESULTS: ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64). CONCLUSION: Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.

Adult↗

Citrullination in extra-articular manifestations of rheumatoid arthritis.

BACKGROUND: Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. METHODS: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. RESULTS: Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). CONCLUSION: Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.

Aged↗

Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia.

BACKGROUND: The role of mast cells in extra-articular manifestations of rheumatoid arthritis (RA) has not been studied so far. OBJECTIVE: To characterise and quantify mast cells in RA associated interstitial pneumonia (IP) by an immunohistological study. METHODS: Lung biopsy specimens from 15 patients with RA associated IP, 12 patients with idiopathic IP, and 5 control patients were stained with antibodies directed against tryptase (mast cell marker). Morphological characterisation of stained specimens was carried out and staining was quantified by computer assisted image analysis. RESULTS: Tryptase staining showed the marked presence of mast cells in idiopathic IP and in RA associated IP. A significant difference in stained tissue area was found between RA associated IP (2.6%, IQR 2.0-3.2%, p = 0.015) and idiopathic IP (3.1%, IQR 1.8-3.7%, p = 0.003) compared with control tissue specimens (1.0%, IQR 0.7-1.5%). The extent of mast cell infiltration correlated well and inversely with pulmonary function variables. CONCLUSIONS: Mast cell infiltrates are present in RA associated IP and idiopathic IP. The observed correlation of pulmonary function and mast cell numbers would be consistent with the proposed role of mast cell mediators in the promotion of fibrogenesis. The findings provide a rationale for studying functional aspects of mast cell involvement in the pathogenesis of RA associated lung disease.

Aged↗

How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial.

OBJECTIVE: To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis (RA). METHODS: Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr. None of the patients had previously received disease-modifying anti-rheumatic drugs (DMARDs). All patients were assigned to receive hydroxychloroquine (HCQ) at enrollment, and could also take non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. At any point during follow-up, patients not fulfilling the American College of Rheumatology (ACR) 50 criteria for improvement and/or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate (MTX), 7.5-20 mg/week. Clinical, laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated. RESULTS: After 24 months of follow-up, a majority of patients (56/94) were either still on solo DMARD therapy with HCQ (n = 49) or off DMARD therapy with controlled/quiescent disease (n = 4), and 38 patients were taking MTX (including 11 in combination with other DMARDs). At month 24, all but 9 patients met ACR50 criteria for treatment response. Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score, baseline rheumatoid factor titre > 1:40, higher number of swollen joints, and poor patient global assessment. The presence of HLA-C7xx at enrollment was also predictive of need for MTX therapy. CONCLUSIONS: This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA. There continue to be very few consistently reliable predictors of treatment needs in patients with this disease.

Adult↗

Localized nodular vasculitis: a new variant of localized cutaneous polyarteritis nodosa?

Cutaneous polyarteritis nodosa (PAN) was first described by Lindberg in 1931. This initial description was followed by many case reports and series, including those of Díaz-Pérez and Winkelmann, who used a strict definition based on cutaneous involvement, and Chen and Daoud who classified the condition into three well differentiated groups. The cutaneous form of PAN is distinct from the systemic form due to its chronic, recurrent, benign nature, the absence of internal organ involvement, and the presence of inflammation in medium and small vessels of the deep dermis and panniculus. In the present article we report our findings for 12 patients with a variant of cutaneous PAN consisting of painful erythematous nodular lesions not preceded or followed by livedo reticularis, that were located exclusively on the lower third of the legs and responded slowly to treatment with corticosteroids and immunosuppressants.

Adolescent↗

Testicular involvement in rheumatoid vasculitis.

We report the case of an adult with rheumatoid arthritis (RA) who developed biopsy-confirmed testicular involvement of vasculitis in the setting of mononeuritis multiplex. This unusual presentation of rheumatoid vasculitis was successfully treated with a combination of corticosteroids and cyclophosphamide.

Administration, Oral↗

Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years.

OBJECTIVE: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews. RESULTS: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity. CONCLUSION: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.

Adult↗

Open trial of methotrexate as treatment for autoimmune hearing loss.

OBJECTIVE: To assess the efficacy of low-dose methotrexate (MTX) administered for the treatment of autoimmune hearing loss. METHODS: This was a prospective, 12-month, open-label study of 17 patients with refractory autoimmune hearing loss. All patients had ongoing episodic worsening of hearing in one or both ears prior to enrollment despite traditional medical therapy. The MTX dose was 7.5-25 mg/week. Hearing loss and vertigo were evaluated at baseline and at completion of the study. Hearing improvement was defined as an improvement in pure tone threshold (PT) average of >10 dB or an increase in speech discrimination (SD) of >15%; worsening was defined as a decrease of >10 dB in PT or a decrease of >15% in SD in at least one ear. RESULTS: MTX was well tolerated. Among patients with Meniere's disease, 5 of 9 had improvement or resolution of vertigo. Equilibrium improved in all 3 patients with Cogan's syndrome and improved in 2 out of 3 patients with idiopathic hearing loss and this symptom. According to the parameters defined above, hearing improved in 11 patients (65%), was unchanged in 4 patients (23%), and worsened in 2 patients (12%). CONCLUSION: Long-term low-dose MTX therapy may be a useful therapy for at least some patients who have hearing loss with a presumptively autoimmune-mediated component that is refractory to traditional therapies.

Adult↗

Incidence of physician-diagnosed primary Sjögren syndrome in residents of Olmsted County, Minnesota.

OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. PATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. RESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. CONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.

Adult↗

Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept.

Patients with long-standing, severe, erosive rheumatoid arthritis who have extra-articular manifestations and have undergone joint replacement surgery are at increased risk for serious infection and premature mortality. New therapies, including cytokine antagonists, hold great promise for improving the course of rheumatoid arthritis. However, they have powerful anti-inflammatory effects that may mask symptoms of serious infection. We report a case of fatal pneumococcal sepsis occurring in a 37-year-old woman with rheumatoid arthritis treated with the tumor necrosis factor antagonist etanercept and suggest management strategies for early detection and management of this complication.

Adult↗

Recurrence of Susac syndrome (retinocochleocerebral vasculopathy) after remission of 18 years.

Susac syndrome (retinocochleocerebral vasculopathy) is a syndrome of unknown pathogenesis. The triad of multifocal encephalopathy, visual loss, and hearing loss is caused by microangiopathy of the brain, retina, and cochlea. The illness tends to be monophasic, and to our knowledge, recurrence after years of remission has not been reported. We describe a 51-year-old woman with symptoms, signs, and brain magnetic resonance imaging findings consistent with recurrence of Susac syndrome 18 years after remission. Clinicians should be aware of the possibility of late recurrence of Susac syndrome when evaluating patients with a distant history of the syndrome who present with complaints referable to the brain, retina, and cochlea.

Blindness↗