Disease activity and subcutaneous nodules are associated to severe periodontitis in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) was significantly associated with increased overall risk of periodontitis, both chronic, inflammatory pathologies leading to connective tissue breakdown and bone destruction. To identify clinical and/or serological variables routinely evaluated during follow-up of people with RA which are associated with the severity of their periodontal disease. An observational, cross-sectional study was carried out, which included RA patients according to ACR/EULAR 2010 criteria having chronic periodontal disease. RA clinical parameters (disease duration, erythrocyte sedimentation rate, serum C-reactive protein, disease activity (DAS28) and rheumatoid factor, presence of bone erosions and rheumatic nodules) and also corticosteroid therapy were considered. Periodontitis was evaluated according to the American Academy of Periodontology (1999) and chronic periodontitis was assessed by full mouth periapical radiographic examination, periodontal probing depth, clinical attachment level and bleeding index. A total of 110 subjects with RA and chronic periodontitis were included. The female/male relation was 5.1, and no significant differences between genres were found in rheumatic or oral variables. RA patients with longer disease duration, higher disease activity and with rheumatic nodules had significantly greater periodontitis severity. Multivariate analysis confirmed that severe periodontitis was associated with DAS283 4.1 (OR 51.4, CI 95% 9.4-281.5) and the presence of rheumatic nodules (OR 6.4, CI 95% 1.3-31.6). Disease activity and rheumatic nodules were strongly associated with severe periodontitis. Based on these findings it would be desirable to include interdisciplinary management at an early stage of RA to ensure comprehensive treatment of both pathologies.

Potential role of Anitschkow cells in cardiovascular disease in human and veterinary medicine: A review of the literature.

Anitschkow cells (AC) are a peculiar type of stromal cells observed in myocardium, cardiac valves and coronary vessels wall whose origin, characterization and role remain controversial. In human heart, they represent a histological hallmark of Aschoff nodules in rheumatic fever, but they have also been observed in other myocardial pathologies. Firstly, they have been considered a myocyte-derived cells, but light microscopy, immunohistochemical and ultrastructural studies pointed out that a macrophagic/histiocytic origin cannot be excluded. Many authors also reported extracardiac AC or an Anitschkow nuclear pattern, thus suggesting that these cells may represent a chromatin pattern rather than a specific cell type. In veterinary medicine, AC were described in myocarditis, myocardial necrosis, degenerative and inflammatory endocardial diseases of several species. Recently, AC have been observed in intramural coronary arteries of different animals (including cattle and fish) affected by arteriosclerotic processes. Stress related to the intensive livestock farming could represent a mechanotransduction promoting factor of arteriosclerotic changes allowing the development of Anitschkow chromatin pattern. Further studies both in human and veterinary medicine are needed to confirm the origin and role of these peculiar cells.

Brief Report: Association of Quantitative and Topographic Assessment of Heberden's Nodes With Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To determine whether the presence, number, and topography (digit location and symmetry) of Heberden's nodes are associated with the incidence and progression of radiographic osteoarthritis (OA) of the knee. METHODS: We analyzed 8,023 knees (with 8 years of follow-up) from the Osteoarthritis Initiative. Cox regression was performed on Heberden's node presence, total number, location, and symmetry (using 2 symmetry index models) obtained at baseline physical examination as well as self-report of Heberden's node presence for evaluation of association with radiographic knee OA incidence (development of a Kellgren/Lawrence grade of ≥2) and progression (worsening in the medial joint space narrowing score of ≥1). Covariate adjustments relevant to OA outcomes were performed. RESULTS: The presence of Heberden's nodes (in 64% of the subjects) at baseline physical examinations, but not subjective self-report of Heberden's nodes, was associated with radiographic knee OA incidence (hazard ratio [HR] 1.19 and 95% confidence interval [95% CI] 1.001-1.402 [approached statistical significance]). Each additional Heberden's node found on physical examination was associated with knee OA incidence (HR 1.03 [95% CI 1.000-1.054] [approached statistical significance]) and progression (HR 1.04 [95% CI 1.016-1.063]). Knee OA incidence and progression were associated with Heberden's nodes located on the third digit (HR 1.26 [95% CI 1.068-1.487] and 1.18 [95% CI 1.019-1.361], respectively) and first digit (HR 1.186 [95% CI 0.992-1.418] [approached statistical significance] and HR 1.26 [95% CI 1.084-1.453], respectively). Heberden's node symmetry was associated with knee OA incidence (model 1 HR 1.09 [95% CI 0.997-1.185] [approached statistical significance]) and progression (model 2 HR 1.13 [95% CI 1.035-1.234]). CONCLUSION: The number of Heberden's nodes, their locations, and symmetry were associated with knee OA incidence and progression over 8 years.

Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A Description and a Comparison of Patients from the Kuwait Registry for Rheumatic Diseases.

OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.

CHANGING CLINICAL PROFILE OF ACUTE RHEUMATIC FEVER AND RHEUMATIC RECURRENCE.

BACKGROUND: Clinical profile of acute rheumatic fever and rheumatic recurrence seems to have changed in countries where rheumatic fever is still endemic. The objectives of this study were to compare clinical profile and outcome of patients suffering initial and recurrent episodes of acute rheumatic fever in children. METHODS: This prospective study was conducted in two tertiary care hospitals from January to June 2011. The diagnosis was based on the modified Jones criteria. Sixty children were included in the study, 15 having first episode of rheumatic fever and 45 with rheumatic recurrence. The severity of carditis was assessed by Clinical and echocardiography means: RESULTS: Carditis was the commonest presentation in both first (80%) and recurrent attacks (100%). Arthritis was seen in 60% of children with first episode and in 26.7% with recurrence. The frequency of subcutaneous nodules, invariably associated with carditis, was very high (33.3% in the first and 48.3% in recurrent episodes). Carditis was generally mild during first episode (53.3%) and severe with rheumatic recurrence (55.6%). There was no death in either group. One patient with severe mitral regurgitation and rheumatic recurrence underwent mitral valve repair for intractable heart failure. CONCLUSION: Clinical profile of rheumatic recurrence and acute rheumatic fever has changed. Rheumatic recurrence is associated with severe carditis. Carditis is more common than arthritis even in the first attack. Sub-cutaneous nodules are a frequent finding invariably associated with carditis.

Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis.

OBJECTIVE: To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). METHODS: Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. RESULTS: Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti-cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08-1.85) and lung cancer (SHR 1.86, 95% CI 1.57-2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. CONCLUSION: Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.

Clinical Profile of Acute Rheumatic Fever Patients in a Tertiary Care Institute in Present Era.

INTRODUCTION: Rheumatic heart disease (RHD) is still a common cause of morbidity and mortality in India. Rheumatic fever commonly occurs between 5-15 yrs of age. Rheumatic activity is a common cause of deterioration of symptoms in a stable or undiagnosed case of RHD. MATERIAL AND METHODS: 41 consecutive patients of acute rheumatic activity were studied. Presenting symptoms were noted. Physical examination was done for major and minor Jone's criteria. Detailed cardiac examination was done. All underwent echocardiography. RESULTS: Mean age was 14.80 ± 7.01 yrs, 26 were female and 15 were male. Joint pain was the commonest present complaint (29 patients), followed by fever in 17 patients, 32 had carditis, 26 had arthritis, 13 had subcutaneous nodules, 7 had chorea and one had erythema marginatum. In patients with carditis, 30 had mitral regurgitation (MR) only, 15 had MR with aortic regurgitation (AR). Out of 32 patients with carditis, 10 patients did not have any clinical evidence of carditis and were detected by echocardiography only. Six patients were known cases of rheumatic fever but had stopped penicillin prophylaxis. CONCLUSION: Commonest complaint in patients with rheumatic fever was joint pain followed by fever. In patients with carditis, all had MR, with 1/3rd of these patients having associated AR. 1/3rd of patients with carditis were detected by echo only and therefore, echo should be included in diagnostic criteria for acute rheumatic fever. None of the patients who developed rheumatic fever was on penicillin prophylaxis.

Atypical Wegener's Granulomatosis Accompanied with Rheumatoid Arthritis: A Case Report

Wegener's granulomatosis (WG) is highly correlated with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Patients with rheumatoid arthritis (RA) rarely contract WG. Although several concurrent cases have been reported overseas, there are no known cases in Korea. Here we report a unique case of RA with atypical WG testing positive for perinuclear ANCA (p-ANCA) and negative for anti-myeloperoxidase (MPO) antibodies. The 62-yr-old female patient presented with multiple joint pain and showed typical blood test results for RA, i.e., an elevated erythrocyte sedimentation rate and C-reactive protein concentration, and positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RA was clear based on a total score of 10 when applying the classification criteria developed by the American College of Rheumatology/European League Against Rheumatism (2010). In an autoimmune target test, speckled and skeleton patterns were observed. In an ANCA test, p-ANCA was observed (titer, 1:2,560), and tests for anti-proteinase 3 (PR3) and anti-MPO antibodies were negative. After admission, multiple nodules were detected on a chest X-ray and a computed tomography scan. We suspected that she had rheumatic nodules or vasculitis and performed an open lung biopsy. We detected necrotic granulomatous vasculitis, classified as WG, thus leading to WG diagnosis. In conclusion, WG was diagnosed in an RA patient who was negative for c-ANCA (negative PR3) and positive for p-ANCA (negative anti-MPO), and this peculiar finding is likely to improve diagnosis in cases of RA with atypical WG.

Mujer con artritis reumatoidea, nódulos pulmonares cavitarios y úlcera de piel / A woman with rheumatoid arthritis,cavitary pulmonary nodules and skin ulcer

Rheumatoid arthritis (RA) more often affect women, but extra-articular manifestations ­ cardiac, cutaneous, gastrointestinal, nervous, ocular, pulmonary and renal, are predominant in men [1­7]. These changes are found in approximately 40-50% of active chronic disease [1, 5, 6, 8]. Skin nodules occur in up to 20% of cases, mainly if rheumatoid factor is positive [1-3, 5], and are related to small vessel vasculitis, similarly to digital changes and ulcers of extremities. Pulmonary nodules are associated with positive rheumatoid factor and anti-cyclic citrulinated peptide antibody; and can evolve with necrosis and central cavitations [1-3, 5-7]. The woman herein reported had longstanding seropositive RA with cavitary pulmonary nodules and indolent cutaneous ulcer in the left elbow

La artritis reumatoide (AR) afecta con mayor frecuencia a las mujeres, pero es extraarticular. manifestaciones cardíacas, cutáneas, gastrointestinales, nerviosas, oculares, Pulmonar y renal, son predominantes en los hombres [1­7]. Estos cambios se encuentran en aproximadamente el 40-50% de las enfermedades crónicas activas [1, 5, 6, 8]. Los nódulos cutáneos se producen en hasta el 20% de los casos, principalmente si el factor reumatoide es positivo [1-3, 5], y están relacionados con vasculitis de pequeños vasos, de forma similar a la digital Cambios y úlceras de extremidades. Los nódulos pulmonares están asociados. con factor reumatoide positivo y péptido citrulinado anticíclico anticuerpo; y puede evolucionar con necrosis y cavitaciones centrales [1-3, 5-7]. La mujer aquí reportada tenía una AR seropositiva de larga data con Nódulos pulmonares cavitarios y úlcera cutánea indolente en el codo izquierdo.

Conjunctival nodule in rheumatoid arthritis.

Conjunctival nodule is very rarely seen in patients with rheumatoid arthritis. Previously reported cases were associated with the use of methotrexate. Here, we report a conjunctival rheumatoid nodule without such prior treatment. A 49-year-old woman with seropositive rheumatoid arthritis, who was being treated only with oral steroids and hydroxychloroquine, developed diffuse anterior scleritis in the right eye. In addition, examination showed a focal raised yellow/tan conjunctival nodule. The nodule was within the bulbar conjunctiva with no attachments to the underlying tissue, which is different from nodular scleritis. The nodule was not tender on palpation. The patient underwent excisional biopsy of the nodule. Intraoperatively, the lesion was noted to be a firm nodule within substantia propria of the conjunctiva. Hematoxylin-eosin staining of the specimen revealed a central area of necrosis surrounded by palisades of histiocytes. Increased dosage of oral steroid after the biopsy resulted in resolution of the ocular symptoms and signs. In conclusion, rheumatoid nodules may be seen in the conjunctiva even without prior treatment with methotrexate. These nodules may show the severity of the underlying disease and the need for more aggressive treatment.

Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression--a pilot study.

BACKGROUND: Rheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD. METHODS: Endomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. RESULTS: Histomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens. IMMUNOHISTOCHEMISTRY: Moderate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8(+) cells in 77%, CD4(+) in 23.1%, and CD3(+) in 38.5% of total patients, which suggests chronicity. CONCLUSION: The nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself.