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ID PMID Title PublicationDate abstract
17538564 Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis 2007 Jun Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.
17721292 Keratoconjunctivitis sicca in juvenile rheumatoid arthritis. 2007 Sep PURPOSE: To compare the symptoms, signs, and results of objective tests for keratoconjunctivitis sicca (KCS) in patients with juvenile rheumatoid arthritis (JRA) and controls. METHODS: Sixty-four patients with JRA and 64 age- and sex-matched controls were compared in terms of symptoms, signs, and results of objective tests for KCS. Relation between tear film breakup time (TBUT), Schirmer test results, and JRA-related variables such as age of onset, duration, and type of JRA; presence of antinuclear antibodies (ANAs); and history of uveitis were evaluated. Analysis of variance, multivariate regression analysis, Kruskall-Wallis, Student t tests, and chi tests were used for statistical analysis. RESULTS: Twelve and a half percent of patients with JRA complained of dry eye symptoms compared with 1.5% of the controls (P = 0.031). Dry eye signs were detected in 10.9% of patients with JRA compared with 1.5% of controls (P = 0.038). TBUT and Schirmer test results were lower in the JRA group than in controls (P = 0.032 and P = 0.029, respectively). Seven patients (10.9%) had definite and 1 (1.5%) had probable diagnosis of KCS in the JRA group compared with no children in the control group (P = 0.034). Within the JRA group, Schirmer test and TBUT results were significantly lower in male patients and ones with longer duration of disease. CONCLUSIONS: The prevalence of symptoms, signs, and definite diagnosis of KCS is higher and basal tear secretion and tear film stability are lower in children with JRA than in controls. Among children with JRA, male sex and longer duration of disease are independent risk factors for having decreased basal tear secretion and tear film stability.
16511937 A case-control sleep study in children with polyarticular juvenile rheumatoid arthritis. 2006 Apr OBJECTIVE: To investigate the relationship between clinical manifestations and sleep abnormalities in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-one patients with active polyarticular JRA and 20 healthy controls were enrolled consecutively. Pain and functional impairment were assessed with standardized, validated Brazilian questionnaires. Sleep evaluation was based on parent reporting of their child's sleep habits and polysomnography; subjects underwent an adaptation night in the sleep laboratory. Sleep architecture was analyzed and spectral analysis of non-rapid eye movement (REM) sleep was carried out by electroencephalography. RESULTS: Patients with JRA exhibited higher indexes of periodic leg movements (PLM; p = 0.02), isolated leg movements (LM), and arousals, as well as increases in alpha activity in non-REM sleep (all p < 0.01), in spite of similar frequency of sleep complaints in comparison to controls. Among JRA patients, greater alpha activity in non-REM sleep was observed in the participants with greater joint involvement assessed by the Escola Paulista de Medicina-Pediatric Range of Motion Scale (p = 0.03) or joint count (p = 0.02). Correlation was observed between morning stiffness and PLM and/or LM (rS = 0.75, Sr = 0.74, p < 0.001 for both), and between self-rating scores of pain and alpha activity in non-REM sleep (rS = 0.74, p < 0.001). CONCLUSION: Pain symptoms and disability are related to sleep fragmentation in patients with active polyarticular JRA.
17511858 Inhibition of indoleamine 2,3-dioxygenase-mediated tryptophan catabolism accelerates colla 2007 Indoleamine 2,3-dioxygenase (IDO) is one of the initial and rate-limiting enzymes involved in the catabolism of the essential amino acid tryptophan. In cultured cells, the induction of IDO leads to depletion of tryptophan and tryptophan starvation. Recent studies suggest that modulation of tryptophan concentration via IDO plays a fundamental role in innate immune responses. Induction of IDO by interferon-gamma in macrophages and dendritic cells results in tryptophan depletion and suppresses the immune-mediated activation of fibroblasts and T, B, and natural killer cells. To assess the role of IDO in collagen-induced arthritis (CIA), a model of rheumatoid arthritis characterized by a primarily Th1-like immune response, activity of IDO was inhibited by 1-methyl-tryptophan (1-MT) in vivo. The results showed significantly increased incidence and severity of CIA in mice treated with 1-MT. Activity of IDO, as determined by measuring the levels of kynurenine/tryptophan ratio in the sera, was increased in the acute phase of arthritis and was higher in collagen-immunized mice that did not develop arthritis. Treatment with 1-MT resulted in an enhanced cellular and humoral immune response and a more dominant polarization to Th1 in mice with arthritis compared with vehicle-treated arthritic mice. The results demonstrated that development of CIA was associated with increased IDO activity and enhanced tryptophan catabolism in mice. Blocking IDO with 1-MT aggravated the severity of arthritis and enhanced the immune responses. These findings suggest that IDO may play an important and novel role in the negative feedback of CIA and possibly in the pathogenesis of rheumatoid arthritis.
17905954 Arthrodesis after failed total ankle replacement. 2007 Sep We present a series of 16 patients treated between 1993 and 2006 who had a failed total ankle replacement converted to an arthrodesis using bone grafting with internal fixation. We used tricortical autograft from the iliac crest to preserve the height of the ankle, the malleoli and the subtalar joint. A successful arthrodesis was achieved at a mean of three months (1.5 to 4.5) in all patients except one, with rheumatoid arthritis and severe bone loss, who developed a nonunion and required further fixation with an intramedullary nail at one year after surgery, before obtaining satisfactory fusion. The post-operative American Orthopaedic Foot and Ankle Society score improved to a mean of 70 (41 to 87) with good patient satisfaction. From this series and an extensive review of the literature we have found that rates of fusion after failed total ankle replacement in patients with degenerative arthritis are high. We recommend our method of arthrodesis in this group of patients. A higher rate of nonunion is associated with rheumatoid arthritis which should be treated differently.
22478712 The impact of rheumatoid arthritis and biologics on employers and payers. 2008 Jul Paresh Chaudhari, PharmD, MPH, frames the business case for employers to look beyond the direct medical costs of treatment of RA and consider employee health benefits as an investment.
16528134 [Xerostomia: clinic, etiology, diagnosis and treatment]. 2006 The aim of this article is to review the problem of xerostomia considering its clinical, etiological, diagnostic and treatment features, basing on the today's tutorials and scientific articles found in databases on the Internet. Recent epidemiologic data on the prevalence of xerostomia in different countries are introduced. There are analyzed the main aspects of clinical manifestations of xerostomia, according to the different etiology analyzed. The most common etiological factors causing xerostomia, especially the main three of them: radiation therapy, Sjögren's syndrome, and drugs, are pointed out. The most popular and accepted clinical and laboratory assays for measuring and evaluating the function of salivary glands are represented. Attention is paid to xerostomia as substantiation of the separate diagnosis and its role in diagnosing other diseases. The concept of possible treatment modalities and prognosis are discussed. The main and most common problems concerning xerostomia are revealed.
17827869 Tranilast suppresses the disease development of the adjuvant- and streptococcal cell wall- 2007 Sep This study explores the effects of the anti-allergic and anti-fibrotic agent tranilast on adjuvant- and streptococcal cell wall-induced arthritis in rats, animal models of rheumatoid arthritis in humans. Tranilast (150 or 300 mg/kg, twice daily) or vehicle only was administered orally to the two arthritis models, from 17 days before sensitization. As a comparative control, methotrexate (0.1 mg/kg, once daily) was given to another group. Tranilast suppressed the increase in foot volumes, paw thicknesses, clinical scores, and histopathological scores of the ankle joints in both models dose-dependently. In addition, the fibrosis indices of the ankles were dramatically decreased by tranilast in both of the models. Compared to the effects of methotrexate, tranilast seemed to work more effectively in the streptococcal cell wall-induced arthritis model than in the adjuvant-induced arthritis model. From these observations, it can be concluded that tranilast suppresses the development of arthritis in multiple models and is potentially a novel therapeutic agent for human rheumatoid arthritis.
18980853 Sternoclavicular septic arthritis in a previously healthy patient: a case report and revie 2009 May Sternoclavicular septic arthritis is an unusual event in healthy patients. Cases have been reported in diabetes mellitus patients, intravenous drug abusers and patients affected by rheumatoid arthritis. We report a case of this unique infection that occurred in a patient who was not at risk of septic arthritis. Through this case and a review of the literature, we discuss the difficulty of diagnosing this disorder, and the consequences of delayed treatment in terms of life-threatening outcomes and therapeutic options.
18835272 Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regu 2009 Mar Various experimental and epidemiological studies have demonstrated that helminth infections affect outcomes of allergic or autoimmune disorders. Here, we examined the effects of Schistosoma mansoni infection on mouse collagen-induced arthritis, one of the most widely used animal models for rheumatoid arthritis. Male DBA/1 mice were infected with S. mansoni 2 weeks prior to being immunized with type II collagen (IIC). Cytokine mRNA expression in mouse paws, cytokine production by ConA-stimulated spleen cells, and anti-IIC antibodies were evaluated in addition to the severity of arthritis. S. mansoni infection significantly reduced the severity of arthritis. Anti-IIC IgG and IgG2a levels were lower in infected than uninfected mice. With regard to cytokine producing potentials in the infected mice, the down-regulation of Th1 (IFNgamma) and pro-inflammatory cytokines (TNFalpha and IL-17A), and up-regulation of Th2 (IL-4) and an anti-inflammatory cytokine (IL-10) were observed.In addition, real-time PCR revealed that the augmentation of pro-inflammatory mediators such as IL-1 beta, IL-6 and receptor activator of NFkappaB ligand in inflamed paws was abrogated by S. mansoni infection [corrected]. In conclusion, schistosome infection reduced the severity of autoimmune arthritis via systemic and local suppression of pro-inflammatory mediators, suggesting the potential of parasite-derived materials as therapeutic agents against rheumatoid arthritis.
16816921 Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen- 2006 Macrophage colony-stimulating factor (M-CSF) is a key factor for osteoclastogenesis at the bone-pannus interface in patients with rheumatoid arthritis as well as a receptor activator of NF-kappaB ligand (RANKL). Imatinib mesylate inhibits the phosphorylation of c-fms, a receptor for M-CSF. The present study investigates the effect of imatinib mesylate on joint destruction in rats with collagen-induced arthritis (CIA) and on osteoclastogenesis in vitro. Imatinib mesylate (50 or 150 mg/kg), dexamethasone, or vehicle was administered daily to CIA rats for 4 weeks from the onset of arthritis. Hind-paw swelling and body weight were measured weekly. At weeks 2 and 4, the metatarsophalangeal (MTP) joints and the ankle and subtalar joints were radiographically and histologically assessed. The effect of imatinib mesylate on osteoclast formation from rat bone marrow cells with M-CSF and soluble RANKL (sRANKL) in vitro was also examined. Radiographic assessment showed that 150 mg/kg imatinib mesylate suppressed the destruction of the MTP and the ankle and subtalar joints at week 2, and MTP joint destruction at week 4 in CIA rats, although hind-paw swelling was not suppressed. The number of TRAP-positive cells at the bone-pannus interface was significantly reduced in the group administered with 150 mg/kg imatinib mesylate compared with that given vehicle at week 4. Imatinib mesylate dose-dependently inhibited the proliferation of M-CSF-dependent osteoclast precursor cells in vitro as well as osteoclast formation induced by M-CSF and sRANKL. These findings suggest that imatinib mesylate could prevent joint destruction in patients with rheumatoid arthritis.
18467606 "Regulating" rheumatoid arthritis via autotransplantation. 2008 May 15 Using a mouse model of inducible autoimmune arthritis that mimics some aspects of the human disease, Roord and colleagues identify a role for regulatory T cells (Tregs) both for modulation of disease and as a therapeutic component of autologous bone marrow transplantation (aBMT).
17162381 Subpopulations within juvenile psoriatic arthritis: a review of the literature. 2006 Jun The presentation of juvenile psoriatic arthritis (JPsA) has long been recognized to be clinically heterogeneous. As the definition of JPsA expanded to accommodate atypical manifestations of psoriasis in young children, studies began to reflect an increasingly clear biphasic distribution of age of onset, with peaks in the first few years of life and again in early adolescence. These two subpopulations differ in gender ratio, pattern of joint involvement, laboratory findings and potentially response to therapy. Intriguingly, a similar distribution of age of onset has been observed in juvenile rheumatoid arthritis (JRA), and correlates with patterns of HLA association. While a secure classification of subpopulations within JPsA awaits improved pathophysiologic understanding, future research must consider the possibility that different disease mechanisms may be operative in distinct subsets of patients with this disorder.
18626304 Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients. 2008 Jul We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.
17543161 Dermatopathic lymphadenopathy in a patient with adult onset Still's disease. 2007 Mar Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown cause characterized by high fever accompanied by systemic manifestations. Since AOSD consists of heterogeneous symptoms and has no definite diagnostic tool, the diagnosis is based upon exclusive criteria. Dermatopathic lymphadenopathy (DL) is characterized by a localized paracortical proliferation of histiocytes and deposition of melanin in the lymph nodes. DL is not only a reactive hyperplasia of the lymph nodes, but has also been reported to be associated with hematological malignancies such as cutaneous T cell lymphoma (CTCL) and Hodgkin's lymphoma. It is therefore important to evaluate CTCL or Hodgkin's lymphoma in a patient with DL, in order to both rule out hematological malignancy and diagnose AOSD. In this report, we first describe a 37-year-old patient with AOSD whose biopsy of lymph node was proved to be DL.
16485224 [Discrepancy between objective measurement and subjective recognition of sicca syndrome be 2006 Feb BACKGROUND: This study was designed to examine if patients undergoing the same operative procedure (blepharochalasis operation) have different subjective recognition of dry eye problems depending n whether they had he operation for cosmetic or medical reasons. PATIENTS AND METHOD: The study included 32 patients (25 women, 7 men, mean age 57.8 +/- 12.1 years), who underwent blepharochalasis operation between 1/2005 and 5/2005. In 17 patients (group 1) the operation was done for cosmetic reasons, in 15 patients we found a medical indication (group 2). We evaluated the subjective discomfort from the lid problems as well as the satisfaction with the operation in general and pre- or postoperative recognition of dry eye problems (all done by scales). Additionally we measured tear secretion by Schirmer's test and break-up time before and after operation. RESULTS: The subjective recognition of a dry eye was stronger in group 1 than in group 2 before and after operation (p < 0.005), but objective data were nearly identically (BUT, Schirmer's test). CONCLUSION: When operated due to cosmetic reasons the stronger recognition of sicca problems (while objectively lacking) is may be caused by a stronger fixation on the lid disease itself. It seems necessary to document objective data for that reason.
16739213 Quality of life and psychological status in patients with primary Sjögren's syndrome and 2006 Jun 15 OBJECTIVE: To compare pain, fatigue, and sicca symptoms; quality of life; and psychological status between patients with primary Sjögren's syndrome (SS) and those with sicca symptoms but no autoimmune features (sicca asthenia polyalgia syndrome [SAPS]), and to determine whether a psychological pattern can be detected in patients with SAPS, which could suggest psychological distress as the cause. METHODS: This cross-sectional, prospective study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies. Pain, fatigue, and sicca symptoms were assessed using visual analog scales; quality of life was assessed using the Short Form 36 (SF-36); and psychological distress by the Symptom Checklist-90-Revised (SCL-90-R) questionnaire. RESULTS: No difference was observed between primary SS and SAPS patients for pain, fatigue, sicca symptoms, quality of life, and psychological status. Fatigue and pain, but not dryness, were correlated with both quality of life and psychological distress in both groups. For primary SS patients, physical and mental composite scores on the SF-36 correlated well with global severity index (GSI) scores of the SCL-90-R (r = -0.29, P = 0.006 and r = -0.61, P < 0.0001, respectively). CONCLUSION: Patients with primary SS and SAPS do not differ in quality of life or psychological status. Although both diseases probably have a different origin, they may require the same psychological support or psychiatric care. The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36.
19028363 Adult-onset Still disease. 2008 Oct Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown origin typically characterized by four main (cardinal) symptoms: spiking fever > or =39 degrees C, arthralgia or arthritis, skin rash and hyperleucocytosis (> or =10,000 cells/mm3) with neutrophils > or =80%. As many other manifestations are possible, diagnosis is potentially challenging. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. The disease evolution of AOSD can be monocyclic, polycyclic or chronic. In chronic disease, joint involvement is often predominant and erosions are noted in one-third of patients. No prognostic factors have been identified to date. Therapeutic strategies are from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy with agents blocking interleukin-1 (anakinra) and then those blocking interleukin-6 (tocilizumab) seem the most promising.
18587227 [Sjögren's syndrome associated with childhood-onset systemic lupus erythematosus]. 2008 Jun Sjögren syndrome (SS) is a common autoimmune disease that exhibits broad organ-specific and systemic manifestations, the most prevalent being decreased lacrimal and salivary gland function, xerostomia, and keratoconjunctivitis sicca. Secondary SS occurs associated with autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Thirty-four childhood-onset SLE patients (2 boys and 32 girls, mean onset age 11.5+/-2.6 years) were evaluated for the presence of secondary SS using the classification criteria for SS revised by Japanese Ministry of Welfare in 1999. Clinical manifestations, serological findings, and renal pathology in SLE patients complicated with SS (SLE+SS, n=14) were compared with those in SLE with no SS autoantibodies (Ro/SS-A or La/SS-B) (SLE-no SS antibodies, n=14). Of all 34 cases, 20 (58.8%) were with positive Ro/SS-A or La/SS-B antibody. Fourteen of the 20 (70.0%) were diagnosed as having secondary SS and all of them were subclinical SS with no sicca symptoms. However, findings of Schirmer test, salivary flow test and minor salivary gland biopsy were positive in 2 of 16 (13.3%), 5 of 16 (31.3%), and 14 of 17 (82.4%) patients, respectively. Compared with the SLE-no SS antibodies group, patients with SLE+SS showed higher level of serum IgG and had higher frequency of anti-U1 RNP antibody and significantly more severe renal involvement. The revised criteria is useful for diagnosis of SS in early stage before the development of exocrine gland damage and appears to be helpful for long term follow-up in childhood-onset SLE associated with SS.
18068857 Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neo 2007 Dec Sjögren's syndrome is a chronic inflammatory process that primarily involves the exocrine glands. Its clinical manifestations range from autoimmune exocrinopathy to extraglandular (systemic) involvement affecting the lungs, kidneys, blood vessels, and muscles; it can occur alone (primary Sjögren's syndrome) or in association with other autoimmune diseases (secondary Sjögren's syndrome). In recent years, clinical and laboratory observations have highlighted the central role of the epithelial cell and it has been suggested that the etiological name of the disease should be 'autoimmune epithelitis'. The extraglandular manifestations of the disease are divided in two groups: (1) lung, kidney (interstitial nephritis), and liver involvement as a result of lymphocytic invasion in epithelial tissues; and (2) skin vasculitis, peripheral neuropathy, and glomerulonephritis, with low C4 levels, which is the result of immune complex disease, are associated with increased morbidity and high risk for lymphoma. The diagnosis of the disease is based on the classification criteria, raised by the American-European Study Group and which have been built on the European preliminary classification criteria, developed in 1992. The association of Sjögren's syndrome with lymphoma is well documented as in approximately 5% of patients the benign autoimmune process is transformed into a lymphoid malignancy. The salivary extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue type are the most common lymphoma in Sjögren's syndrome. These tumors are antigen-stimulated B-cell lymphomas and are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Among the clinical and serological parameters that have been associated with lymphoma development in patients with Sjögren's syndrome, the presence of palpable purpura, low C4 and mixed monoclonal cryoglobulinemia constitute the main predictive markers; patients displaying these risk factors should be monitored closely. The purpose of this review is to discuss the clinical picture, the diagnostic procedure, and the malignant lymphoproliferation in the disease.