Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12136914 Worldwide prevalence of juvenile arthritis why does it vary so much? 2002 Jul OBJECTIVE: To review epidemiological studies of childhood arthritis from 1966, and to identify possible reasons for the wide-ranging results for both prevalence and incidence of juvenile arthritis (JA). JA is the term used here collectively for juvenile rheumatoid arthritis, juvenile chronic arthritis, or juvenile idiopathic arthritis as defined in the respective published studies. METHODS: A review of 34 epidemiological studies of JA since 1966 was undertaken. RESULTS: Prevalence of JA is reported as 0.07 to 4.01 per 1000 children. Annual incidence is reported as 0.008 to 0.226 per 1000 children. The major factors contributing to differences in estimates include (1) factors due to diagnostic difficulties, to the development of new diagnostic criteria, and to the differing definitions of clinical cases; (2) differences in case ascertainment (community based versus clinical case studies, qualification and experience of study clinicians, definition of study population); (3) factors occurring with the passage of time, i.e., standard of living, health care resources, and increasing knowledge; and (4) small studies and hence more chance fluctuation. The major variation in reported prevalence was due to the difference between true community based studies involving children from within classrooms or homes (and not necessarily previously diagnosed with JA) compared with clinical case studies of children who (by definition) had been previously diagnosed. The highest prevalence was reported for true community based studies. CONCLUSION: Many factors contribute to the discrepancies between reported prevalence and incidence for JA. Studies based truly in the community reported the highest prevalence, as previously undiagnosed cases were included. Future studies involving standardized criteria and standardized case ascertainment done by fully trained clinicians should show greater consistency of results.
15610905 The role of plasma high molecular weight kininogen in experimental intestinal and systemic 2004 Sep Inflammation is accompanied by activation of the plasma kallikrein-kinin system (KKS). KKS activation has been demonstrated in a variety of inflammatory human diseases. To further explore the participation of KKS in arthritis and inflammatory bowel disease, we used two experimental animal models in arthritis and enterocolitis. We found that activation of KKS is associated with arthritis induced by intraperitoneal injection of peptidoglycan-polysaccharide polymers (PG-PS) as well as the enterocolitis and systemic inflammation induced also by PG-PS when injected into the intestinal wall of genetically susceptible Lewis rats. We postulated that KKS participates in the pathogenesis of inflammatory reactions involved in cellular injury, coagulation, fibrinolysis, kinin formation, complement activation, cytokine secretion, and release of proteases. We demonstrated that therapy with a specific plasma kallikrein inhibitor modulated the experimental enterocolitis, arthritis, and systemic inflammation. The fact that deficiency of plasma high molecular weight kininogen in the genetically susceptible Lewis rat results in decreased chronic enterocolitis and systemic inflammation also supports our hypothesis. We suggest that KKS plays a similar role in idiopathic human intestinal inflammatory disease and arthritis, making kallikrein-kinin system proteins appealing targets for drug therapy in chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease.
12784390 Beneficial effects of rosmarinic acid on suppression of collagen induced arthritis. 2003 Jun OBJECTIVE: To assess the therapeutic potential of rosmarinic acid (RosA) in an inflammatory autoimmune arthritis model. METHODS: Collagen induced arthritis is established in male DBA/1 mice. Mice were administered daily with 50 mg/kg/day of RosA for 15 days from Day 21 post-immunization and inspected daily to determine the progression of arthritis. After termination of injection, affected hindpaws were subjected to histopathological analyses and immunohistochemical assays for cyclooxygenase-2 (COX-2) expression. RESULTS: Repeated administration of RosA dramatically reduced the arthritic index and number of affected paws. Histopathologic observations closely paralleled clinical data, showing that RosA treated mice retained nearly normal architecture of synovial tissues, whereas control mice exhibited severe synovitis. Synovial tissues from RosA treated mice exhibited remarkably reduced frequency of COX-2-expressing cells, compared to those from untreated mice. CONCLUSION: RosA suppressed synovitis in a murine collagen induced arthritis model; this effect may be beneficial for treatment of rheumatoid arthritis in clinical settings.
15775150 [Inhibition of joint destruction by methotrexate]. 2003 Jun Methotrexate (MTX) plays an important role in treatment of rheumatoid arthritis (RA). It significantly reduce expected radiographic progression. Comparing with other traditional disease-modifying anti-rheumatic drugs (DMARDs), MTX slow radiographic progression during the first 2 years. Since combination with anti-tumor nectosis factor alpha (TNF-alpha) therapy has been shown to be effective for the early supression of disease activity, it could be usefull to minimize bone destruction in RA.
15379775 Etanercept for the treatment of psoriasis and psoriatic arthritis. 2004 Etanercept is a fully human soluble recombinant p75 TNF receptor that blocks the binding of TNF to cell surface receptors, thereby neutralizing its biologic activity. Data supporting the FDA's approval of etanercept for controlling signs and symptoms and for inhibiting XRAY progression of psoriatic arthritis will be presented. Data supporting the FDA filing of etanercept for the treatment of moderate to severe psoriasis will also be presented. Long term safety data of etanercept in the over 231,000 adults and children with rheumatoid arthritis who have been treated worldwide will be briefly summarized.
15166751 Polymorphoneutrophilic infiltration in acute interstitial nephritis of Sjögren syndrome. 2004 May Sjögren syndrome is a systemic autoimmune disease that involves the kidney as well as other organs. Tubulointerstitial nephritis secondary to monocyte, lymphocyte, and plasma cell infiltration is the characteristic lesion. The authors report a case of Sjögren related acute interstitial nephritis (AIN) with prominent neutrophilic infiltration in the interstitium. This is the first case describing predominance of neutrophilic infiltration in AIN associated with Sjögren syndrome.
12957186 Prevalences of herpesviruses DNA sequences in salivary gland biopsies from primary and sec 2003 Oct BACKGROUND: Sjögren's syndrome (SS) is an autoimmune exocrinopathy associated with multiple autoantibodies, lymphocyte infiltration of various organs, and functional deficiency of T cells. Several viruses have been implicated by PCR based studies, but their contribution to the pathophysiology of SS is still controversial. OBJECTIVES: In an attempt to explore the presence of human herpesviruses DNA sequences in salivary glands biopsies from patients suffering of SS, a recently developed strategy based on PCR with consensus degenerated primers that allowed to detect known and eventually unknown herpesviruses was used. STUDY DESIGN: Salivary glands biopsies from 55 patients suffering of primary and SS syndrome were explored by herpesviruses consensus PCR primers and all the PCR products were sequenced. RESULTS: Nine out of 55 salivary glands were positive by PCR and sequence analyses allowed to identify Epstein-Barr virus (EBV) in 6 cases and herpes simplex virus (HSV)-1 in 3 cases. We did not detect any sequences that could be related to a new herpesvirus. CONCLUSION: In view of the good sensitivity of the technique used, our study is not consistent with SS being associated with an unknown herpesvirus. However, our results suggest that EBV and HSV-1 could be implicated in a subset of SS cases and this possibility needs to be explored, to assess the potential benefit of antiviral drugs in some cases.
12599515 [A case of Sjögren's syndrome with marked lacrimal gland enlargement, atypical onset and 2002 Dec Since July, 1999, a 66 year-old man had been complaining of dry cough. He noticed submandibular swelling, lacrimal gland enlargement and dry eye. Keratoconjuctivitis sicca was detected by an ophthalmologist. Sjögren's syndrome was diagnosed based on microscopic findings of a labial salivary gland biopsy although anti-SS-A and anti-SS-B antibodies were negative. Hypergammaglobulinemia (IgG 3916 mg/dl) and IgA-M-proteinemia were pointed out. Swelling of mediastinal and abdominal lymph nodes was detected together with enlargement of salivary and lacrimal glands. We suspected the existence of malignant lymphoma, but a biopsy of lacrimal glands showed only lymphocytic and plasma cell infiltration and immunohistochemical analysis denied monoclonality of lymphoid line. An administration of corticosteroids caused rapid diminution in size of lacrimal and submandibular glands and lymph nodes. Clinical symptoms were also improved, but IgA-M proteinemia remains. The characteristics of our case were enlargement of lacrimal glands, the negativity of anti SS-A and SS-B antibodies, atypical onset and M-proteinemia. We discussed about these characteristics of Sjögren's syndrome in our case.
11906883 Diffusion-weighted echoplanar MR imaging of the salivary glands. 2002 Apr OBJECTIVE: We determined the apparent diffusion coefficients of normal and dysfunctional salivary glands. SUBJECTS AND METHODS: A diffusion-weighted single-shot spin-echo type of echoplanar MR imaging was performed on the parotid or submandibular glands, or both, in 36 healthy subjects, 20 patients with Sjögren's syndrome, and six patients with sialoadenitis. The apparent diffusion coefficient of the salivary gland was calculated using two b factors (b = 500 and 1,000 sec/mm(2)). RESULTS: The apparent diffusion coefficient was lower in the parotid glands (0.28 x 10(-3) mm(2)/sec) than that of the submandibular glands (0.37 x 10(-3) mm(2)/sec). The apparent diffusion coefficient was increased in sialoadenitis, whereas it decreased with abscess formation. The apparent diffusion coefficients of the parotid glands in patients with Sjögren's syndrome correlated with the salivary flow rates but not with the sialographic gradings of the glands. We also found a correlation of the decreases in apparent diffusion coefficients with the severity of gland damage as assessed on T1-weighted MR images. CONCLUSION: Diffusion-weighted echoplanar MR imaging may reveal diseased states of the salivary glands.
14971603 Scoring analysis of salivary gland scintigraphy in patients with Sjögren's syndrome. 2003 Dec The purpose of the present study was to evaluate the validity of a scoring system based on excretion rate of salivary gland scintigraphy in patients with Sjögren's syndrome (SjS). Total scintigraphic scores were compared with the results of the Saxon test. One hundred and twenty-four subjects who were clinically diagnosed with SjS and 11 normal ones underwent salivary gland scintigraphy and the Saxon test. In salivary gland scintigraphy, the difference between maximum and minimum counts after stimulation using vitamin C divided by maximum counts was defined as the excretion rate. We then defined a scoring system with 4 grades: severe dysfunction = 3 (excretion rate < 25%), moderate dysfunction = 2 (25% < or = excretion rate < 40%), mild dysfunction = 1 (40% < or = excretion rate < 50%) and normal function = 0 (50% < or = excretion rate). The summation of the total scintigraphic score (0-12) of all 4 salivary glands was used as a semi-quantitative index indicating total salivary gland function, and total scintigraphic scores were compared with the results of the Saxon test. A significant inverse linear correlation (R2 = 0.95) was observed between total scintigraphic scores and mean values of the Saxon test within a range of abnormal scintigraphic scores (> or = 4). The scoring system developed in the present study is a clinically available, objective, and reproducible method for evaluation of salivary gland function in patients with SjS.
14714319 [Variations of protein concentration in saliva stimulated and its effect on clinical diagn 2003 Dec OBJECTIVE: To study the variations of protein concentration in saliva stimulated and its effect on clinical diagnosis. METHODS: The saliva from 33 normal controls and 73 patients with Sjögren syndrome (SS) who were stimulated with acid and not were collected. The concentration of beta 2 microglobulin (beta 2-mG), secretory immunoglobulin A (SIgA), and pH were measured by Radioimmunoassay, Rate Nephelometry and pH Detection Paper, respectively. SPSS 10.0 was used to determine the mean statistical differences among these groups. RESULTS: In patients with SS, the concentration of beta 2-mG in saliva stimulated with Vc was significantly lower compared with that in saliva not stimulated (P < 0.01); In saliva stimulated with Vc, the concentration of beta 2-mG in patients with SS was higher than that in normal controls (P < 0.05). In normal controls, compared with that in saliva not stimulated, flow rate in saliva stimulated with 3% acetic acid and Vc was significantly higher (P < 0.01) and pH, concentration of beta 2-mG and SIgA were significantly lower (P < 0.01 and P < 0.05 respectively); there was a significant difference of flow rate, beta 2-mG, SIgA and pH in saliva between the subjects stimulated with 3% acetic acid and with Vc (P < 0.01). CONCLUSIONS: The reason for the decrease of protein concentration in saliva stimulated may be the increase of flow rate caused by the decrease of pH or the decrease of pH itself. Protein detection of saliva stimulated in patients with SS is helpful in diagnosis, but the criterion is different between the saliva stimulated and not stimulated.
12835540 New approaches to the treatment of Sjögren's syndrome: soon beyond symptomatic relief? 2003 Sjögren's syndrome (SS) is a common autoimmune disease characterized by destruction and dysfunction of the salivary and lachrymal glands. Systemic manifestations occur in almost one third of patients with SS. Treatment of SS has been long considered as disappointing, being mainly restricted to local management with artificial tears and oral lubricants or to the use of immunosuppression-based therapies for systemic disease. Better knowledge of the pathogenesis of SS, including the role of retroviruses and cytokines and the discovery of aquaporins, provides new perspectives for the local and systemic management of this disease. Our goal is to focus on these recent therapeutic progresses.
12140209 Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjög 2002 Aug AIM: To study the effect of the treatment of dry eye in Sjögren's syndrome patients with hypotonic or isotonic hyaluronate eye drops. METHODS: 40 Sjögren's syndrome patients were divided in two groups and treated as follows: group 1 with hypotonic (150 mOsm/l) 0.4% hyaluronate eye drops; group 2 with isotonic 0.4% hyaluronate eye drops. The eye drops were instilled six times a day for 90 days. Grading of subjective symptoms, break up time (BUT), corneal fluorescein staining, conjunctival rose bengal staining, Schirmer's I test, and conjunctival impression cytology were carried out at 0 and 15, 30, 90 days from the beginning of the study. Patients were examined in a blind fashion. For the statistical analysis the Student's t test, Mann-Whitney U test, and chi(2) test were performed. RESULTS: Symptoms were statistically significantly improved at day 15 in both groups but group 1 patients had a global score statistically significantly better group 2 (p=0.02). At day 15 group 1 patients had an improvement from baseline values of BUT (p=0.003), fluorescein, and rose bengal score (p=0.000001 and p=0.0004 respectively). Group 2 patients had, at day 15, an improvement of BUT and fluorescein score compared to baseline values (p=0.05 and p=0.0001 respectively). A comparison between the two groups showed better results for group 1 patients at day 15 for rose bengal stain (p=0.01) and for BUT (p=0.05) and fluorescein score (p=0.0003) at day 90. The conjunctival impression cytology showed that group 1 had a statistically significant better total score than group 2 starting from day 15 and lasting throughout the study (p<0.02). Also group 2 patients showed an improvement from baseline values starting from day 30 (p=0.000005). CONCLUSION: Hyaluronate eye drops are useful for treating severe dry eye in Sjögren's syndrome patients. The use of a formulation with pronounced hypotonicity showed better effects on corneoconjunctival epithelium than the isotonic solution.
15543470 [Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in 2004 Nov 19 HISTORY: A 21-year-old man was admitted to the hospital because of high fever, arthralgias and myalgias. One week before he was treated with penicillin G orally because of cough and sore throat. PHYSICAL EXAMINATION: The critically ill patient presented with a red throat and cervical lymphadenopathy. Lung auscultation revealed reduced respiratory sounds at both base, heart auscultation revealed a pericardial friction rub. Dermatologic examinations were normal. INVESTIGATIONS: Laboratory findings were notable for anemia, thrombopenia and leukocytosis, disseminated intravascular coagulation and markedly elevated CRP (309 mg/l). Electrogram showed inferior and lateral ST segment depression. Echocardiography showed pericardial effusion. Chest CT scan revealed bilateral pleural effusion, a left-sided small infiltrate and enlarged mediastinal lymph nodes. Abdominal ultrasound confirmed hepatosplenomegaly and ascites. TREATMENT AND CLINICAL COURSE: A diagnosis of parapneumonic bilateral pleural empyema, perimyocarditis and disseminated intravascular coagulation was made. Despite institution of empiric antibiotic therapy, no clinical improvement was observed. After exclusion of infectious, autoimmune or malignant disease, clinical and laboratory data, especially marked hyperferritinemia, helped to establish the diagnosis of adult-onset Still's disease. Immunosuppressive treatment with prednisolone and azathioprin resulted in remission. CONCLUSION: Adult-onset Still's disease is a rare inflammatory disorder of unknown origin, which may affect multiple organs. The diagnosis is based on a diagnostic score, which includes a number of clinical and laboratory findings, published by Yamaguchi in 1992. Marked hyperferritinemia represents an additional diagnostic clue to the disease.
15255131 Osteal complications as first manifestation in a patient with primary Sjögren's Syndrome 2004 Apr Renal affection is among the complications associated with the Sjögren's Syndrome. Tubulo-interstitial nephritis constitutes the most frequent renal lesion and distal tubular acidosis (Type 1) is the most important clinical manifestation of this tubular dysfunction, although the occurrence of chronic renal insufficiency is not an uncommon finding in the presence of distal renal tubular acidosis. Osteomalacia is a clinical consequence of tubular acidosis caused by buffering of H+ in the bone. We present the case of a woman with osteal complication a year before being diagnosed with primary Sjögren's Syndrome and with distal tubular acidosis and renal insufficiency associated at diagnosis.
11963219 [Lupus erythematosus and sarcoidosis--coexistence or association?]. 2002 Jan There are not many reports on simultaneous occurrence of the two rare multiorgan disorders lupus erythematosus and sarcoidosis. Since etiopathogenesis in both diseases is not yet fully defined, speculations concerning common immunological pathomechanisms as well as discussions about chance coexistence versus real association remain unsolved. As exemplified by our two patients, diagnostic problems may arise from the broad spectrum of cutaneous manifestations in both diseases as well as the similarity of extracutaneous symptomatology.
15696767 Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining 2004 Dec BACKGROUND: Previous studies have shown a poor correlation between dry eye symptoms and objective clinical signs in patients with Sjögren's syndrome. We examined the hypothesis that reduced corneal sensitivity is associated with increased ocular surface disease and reduced symptoms in patients with Sjögren's syndrome. METHODS: Eighteen subjects with a diagnosis of Sjögren's syndrome attending a Sjögren's clinic participated in the study. All participants completed the Ocular Surface Disease Index (OSDI) and the Symptom Severity of Discomfort (SSD) scale and answered a question regarding overall severity of dry eye symptoms. The subjects underwent measurement of best-corrected Snellen visual acuity, corneal sensitivity testing with the Cochet-Bonnet esthesiometer, fluorescein and lissamine green staining of the cornea, Schirmer's test I and determination of the tear film break-up time. The results were analysed using Pearson correlational analysis. RESULTS: Both fluorescein and lissamine green staining of the cornea correlated negatively with central corneal sensation (r = -0.3542, p = 0.034, and r = -0.3748, p = 0.029 respectively), indicating that corneal sensation was reduced with increased ocular surface disease. The overall symptom severity correlated negatively with lissamine green staining of the cornea (r = -0.4310, p = 0.011), suggesting reduced symptoms with increased corneal disease. INTERPRETATION: Reduced corneal sensation correlated with increased ocular surface disease. Ocular surface disease similarly demonstrated a reciprocal relation with patients' dry eye symptoms. Consequently, we found that patients with Sjogren's syndrome with advanced corneal staining tended to have fewer dry eye symptoms than patients with less corneal staining.
15012873 [Usefulness of oral pilocarpin therapy in the treatment of xerostomia and xerophthalmia in 2004 Feb 28 BACKGROUND AND OBJECTIVE: We aimed to asses the efficacy of pilocarpine tablets as a symptomatic treatment for dry mouth and dry eyes in patients with primary Sjögren's syndrome (SS). PATIENTS AND METHOD: We included 40 patients with SS (38 women and 2 men), mean age 49.2 years (range, 35-68), with severe xerostomia and xerophthalmia. Objective tests (salivary scintigraphy, Schirmer's test, break-up time, Rose Bengal staining) and subjective tests (symptoms' questionnaire) were carried out before starting treatment and 6 months later to evaluate any glandular function improvement. RESULTS: All patients initially received 15 mg daily of pilocarpine. Twelve (30%) patients received 20 mg daily. Dry mouth-related symptoms improved in 57.5% of patients and dry eyes-related ones improved in 35%. Scintigraphic studies demonstrated an objective improvement of the glandular function in 35% patients. Ocular tests showed an improvement in 30% cases. CONCLUSIONS: Pilocarpine therapy is useful to improve xerostomia and xerophthalmia in SS patients with moderate and severe glandular involvement. However, we have not observed a good correlation between subjective improvement of symptoms and the objective test results.
12949253 Cardiovascular autonomic dysfunction in primary Sjögren's syndrome. 2004 Jan OBJECTIVE: To assess the occurrence and clinical significance of a cardiovascular autonomic nervous system dysfunction in primary Sjögren's syndrome (pSS). METHODS: Fifty-one pSS patients participated in this case-control study. Heart rate and blood pressure variability measurements, spontaneous baroreflex sensitivity examinations and cardiovascular reflex tests were performed. RESULTS: The results of the heart rate and blood pressure variability measurements and also the baroreflex sensitivity parameters of the pSS patients peaked in the lowest percentile ranges of a database on 559 healthy control subjects (P < 0.05). In three of the five cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05), and the median autonomic neuropathy score was also elevated (3 vs 0 in the controls; P < 0.0001). CONCLUSION: Signs of an autonomic nervous system dysfunction involving the cardiovascular system can be discerned in the majority of pSS patients.
12928530 Painful indurated erythema suggestive of Kikuchi-Fujimoto disease in a patient with primar 2003 Aug We report a patient with primary Sjögren's syndrome who developed pyrexia, cervical lymphadenopathy, and painful indurated erythema on the forehead, back, chest, abdomen, and limbs. Laboratory data showed an elevated erythrocyte sedimentation rate, C-reactive protein and CH50 in addition to existing autoantibodies including anti-nuclear antibody, anti SS-A antibody, and anti SS-B antibody. A skin biopsy specimen showed focal infiltration of histiocytes with non-neutrophilic karyorrhetic debris in the dermis and subcutaneous fat tissue. Immunohistochemically the infiltrated cells were stained for CD68, suggesting cutaneous involvement of Kikuchi-Fujimoto disease. All symptoms and laboratory data improved within three weeks after treatment with 20 mg/day of prednisolone. The present case suggests that a pathophysiological condition similar to Kikuchi-Fujimoto disease can develop during the long-term course of Sjögren's syndrome.