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ID PMID Title PublicationDate abstract
20683439 Pathogenetic mechanisms in the initiation and perpetuation of Sjögren's syndrome. 2010 Sep Sjögren's syndrome (SS), a chronic autoimmune disorder, particularly compromises the function of exocrine glands. The involvement of these glands is characterized by focal, mononuclear cell infiltrates that surround the ducts and replace the secretory units. The pathogenetic mechanisms of this autoimmune exocrinopathy have not been fully elucidated. Immunologically-activated or apoptotic glandular epithelial cells that expose autoantigens in genetically predisposed individuals might drive autoimmune-mediated tissue injury. Alterations in several immune mediators, such as upregulation of type I interferon-regulated genes, abnormal expression of B-cell-activating factor and activation of the interleukin-23-type 17 T-helper cell pathway, have been reported. Extension of the pathological process that affects the exocrine glands into periepithelial and extraepithelial tissue can cause a considerable percentage of patients to exhibit systemic findings that involve the lungs, liver or kidneys. These manifestations develop as a result of lymphocytic invasion or an immune-complex-mediated process, or both, and present as skin vasculitis coupled with peripheral neuropathy or glomerulonephritis (or both). Patients with systemic extraepithelial manifestations display low serum levels of the complement component C4 and mixed type II cryoglobulins, and show an increased risk of developing non-Hodgkin lymphoma, thereby reflecting an overall worse prognosis with higher mortality rates than those without extraepithelial manifestations.
20517630 Efficacy and safety of orally administered pilocarpine hydrochloride for patients with juv 2010 Oct The number of patients with juvenile-onset Sjögren's syndrome (SS) has recently increased. However, there is no drug that is safe and effective for the xerostomia that occurs in patients of this age group. We evaluated the efficacy and safety of orally administered pilocarpine hydrochloride for juvenile-onset SS patients. Five female patients, aged from 9 to 16 years, received 5-10 mg/day for 4 weeks. On days 1 and 28, salivary production was measured by the Saxon test, and patients completed subjective self-evaluations of xerostomia symptoms and were asked about changes in water intake and overall improvement of dry mouth on day 28. After 4 weeks of pilocarpine administration, salivary production increased significantly in all patients, and overall status was assessed as "improved" in all patients. One patient had excessive sweating. No serious adverse events or laboratory examination abnormalities correlated with pilocarpine administration were found. In conclusion, the results of this study suggest that orally administered pilocarpine is safe and effective for treating xerostomia in juvenile-onset SS patients. This is the first report of the efficacy of pilocarpine for juvenile SS patients; further evaluations are needed to confirm our result.
20514585 Delayed ascending aortic pseudoaneurysm in an adult onset Still's disease patient with pre 2010 Jun A 59-year-old female patient with adult onset Still's disease (AOSD) presented with hemoptysis and pseudoaneurysm from an aortic root vent cannulation site that was created 4 years earlier for combined mitral and aortic valve surgery. The pseudoaneurysm was successfully repaired and the patient remained well during a follow-up period of 20 months.
20340022 Good clinical response to methotrexate treatment in a patient with fibroblastic rheumatism 2012 Jun Fibroblastic rheumatism (FR) is a rare disease first described by Chaouat (in Rev Rhum Mal Osteoartic 47:345-351, 1980) and is characterized by a combination of rheumatologic and dermatological manifestations. Rheumatologic features are symmetrical polyarthralgias with joint stiffness, associated with cutaneous nodules and sclerodactyly. Histology shows an increased number of fibroblasts and a marked dermal fibrosis. A large number of treatments have been tried, but all of them have shown an unpredictable effect on FR. We report a Brazilian case of FR showing a good clinical response to methotrexate treatment. This drug may be considered an effective treatment in FR.
19222517 New biologics for psoriasis and psoriatic arthritis. 2009 Jan The prevalence of psoriasis is estimated to be 2.2% in the United States, and 6-39% of patients with psoriasis also develop psoriatic arthritis. New advances have been made in developing treatment options. A new human tumor necrosis factor (TNF)-alpha antibody, golimumab, has been shown to significantly improve symptoms of psoriatic arthritis. In addition, clinical trials of certolizumab pegol, a PEGylated Fab' fragment of an anti-TNF-alpha monoclonal antibody, show promising results for treating rheumatoid arthritis and suggest that it may be applicable for treating psoriasis and psoriatic arthritis in the future. New biologic therapies also include antibodies to interleukin-12 and interleukin-23. Phase II studies suggest that ustekinumab is effective in alleviating symptoms of psoriasis and psoriatic arthritis. However, longer studies with radiographic evaluation will be required before their impact on joint destruction can be assessed.
19276928 The volar approach to proximal interphalangeal joint arthroplasty. 2009 Mar Proximal interphalangeal joint arthroplasty has resulted in good outcomes in patients treated for osteoarthritis, posttraumatic arthritis, and rheumatoid arthritis. Most hand surgeons complete arthroplasties of the proximal interphalangeal joint through a dorsal approach. However, for the past 7 years, we have had positive results with a volar approach. We describe this technique, which avoids injury to the extensor tendon and allows for a more simplified approach to postoperative therapy compared with the therapy regimen required after the dorsal approach.
21044444 Use of methotrexate in undifferentiated arthritis. 2010 Sep The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of 1" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients.
20147481 Composite measures in psoriatic arthritis: GRAPPA 2008. 2010 Feb At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) in Leeds, UK, members discussed the value and current status of composite measures for the assessment of psoriatic arthritis (PsA). In plenary presentations, examples of composite measures developed for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were reviewed, followed by a presentation of the assessment of disease activity in systemic lupus erythematosus. Three recently devised composite methods of assessing activity or response in PsA also were presented. Considerable discussion followed in breakout groups, and members agreed that a new composite measure specifically for PsA is necessary. The composite measure should include components that encompass the spectrum of psoriatic disease, i.e., in addition to assessment of peripheral joints, it should include assessment of sacroiliitis, spondylitis, enthesitis, and dactylitis, as well as skin and nail disease.
19685721 [Effect of electroacupuncture at "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on collagen-ind 2009 Apr OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on collagen-induced arthritis (CIA) and its underlying mechanism in regulating the secretory function of knee-joint synovial cells in CIA rats. METHODS: Thirty-six Wistar rats were equally randomized into control, model and EA groups. CIA model (rheumatoid arthritis) was duplicated by intradermal injection of Bovine type II collagen into the back of the anesthetized rats. EA (2 Hz, 2 mA) was applied to "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 30 min, once a day for 30 days. The paw volume was measured by using a Plethysmometer and hot water tail-flick tests (50 degrees C) were conducted for detecting the rats' pain threshold (PT) before and after the treatment. The contents of PGE2, IL-1beta and TNF-alpha in supernatant of the cultured joint synoviocytes were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: In comparison with control group, the swelled paw volume, the declined PT, PGE2, TNF-alpha and IL-1beta contents in knee-joint synoviocyte supernatant were significantly higher in model group (P < 0.05). Compared with model group, PT increased obviously (P < 0.05); paw volume, supernatant PGE2, TNF-alpha and IL-1beta contents decreased obviously (P < 0.05) in EA group. CONCLUSION: EA of ST 36 and SP 6 has a pronounced therapeutic effect in relieving knee joint pain and inflammation in CIA rats, which may be related to its effect in regulating the secretory function of the knee-joint synoviocytes.
20732653 Stem cells in the treatment of inflammatory arthritis. 2010 Aug Autologous haematopoietic stem cell transplantation in patients with rheumatoid arthritis (RA) resulted in a positive short-term outcome clinically with low treatment-related toxicity. However, early conditioning regimens were of low immunoablative intensity and most patients relapsed. Mechanistic studies suggest that residual lesional effector cells may have been responsible for the relapses. The introduction of biopharmaceuticals has, for the moment, reduced the need for further experimental studies. Juvenile idiopathic arthritis patients, mostly of the systemic subgroup, have shown nearly 33% durable drug-free remission, but with significant toxicity, including fatal macrophage-activation syndrome early in the programme. Later modifications to the protocol have reduced this toxicity. Mesenchymal stem cells (MSCs), derived from several sources including bone marrow and adipose tissue, are being tested as tissue-regenerative and immunomodulating agents in many autoimmune diseases and animal models of inflammatory arthritis have been positive. MSCs and other stromal cells derived from actively inflamed synovium and peripheral blood of RA patients do not always demonstrate a full range of differentiation potential compared with healthy MSCs, although their immunomodulalatory capacity is unimpaired.
20821183 [Sjögren syndrome]. 2010 Oct Sjögren's syndrome (SS) is a chronic inflammatory disorder of hitherto unknown origin. The characteristic hallmark of SS is focal lymphocytic infiltration and slow destruction of exocrine glands, such as lacrimal and salivary glands. Sicca symptoms and/or recurrent parotid gland swelling are often accompanied by fatigue. Clinically relevant extraglandular manifestations occur in more than 20% of patients with primary SS. The development of malignant B cell lymphoma is the most important complication, which affects about 5% of primary SS patients who are at higher risk to develop malignant B cell lymphoma, both when compared with the general population as well as with patients with SS secondary to other systemic autoimmune disorders. Treatment of sicca symptoms is primarily symptomatic, whereas glucocorticoids, NSAIDs and/or immunosuppressive drugs may be indicated for the treatment of extraglandular manifestations. New therapeutic strategies, such as B cell targeted therapies, are in clinical testing especially for patients with severe organ manifestations.
20809902 Clinical features of Sjogren's syndrome in patients with multiple sclerosis. 2011 Aug OBJECTIVES:   To assess the frequency of clinical features of Sjogren's syndrome (SS) in patients with multiple sclerosis (MS) receiving treatment with disease-modifying drugs (DMDs) or naïve to treatment and the possible association with clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) parameters. METHODS:   A multicentre cross-sectional observational study was designed, based on a structured neurologist-administered questionnaire to 440 patients. RESULTS:   Twenty-eight of 230 (12%) patients receiving treatment with DMDs (DMDs(+)) and 14 of 210 (6.6%) treatment-naïve patients (DMDs(-) ) showed clinical features of SS. Four primary SS were diagnosed, two of which were DMDs(+) and two were DMDs(-) . Sicca symptoms were significantly associated with higher EDSS scores (P = 0.018), a low frequency of gadolinium-enhanced MRI-positive lesions (P = 0.018) and cerebral disturbances (P = 0.001). CONCLUSIONS: Screening for the clinical features of SS should be performed in patients with MS both receiving treatment with immunomodulatory drugs and without therapy.
19162249 Classification of lupus erythematosus based upon Japanese patients. 2009 May The two dimensional classification system for lupus erythematosus (LE) is proposed. The terms for diagnoses and those for eruptions should be used separately. The terms for diagnoses are cutaneous-limited LE (CLE), intermediate LE (ILE) and systemic LE (SLE). CLE is an entity which has only cutaneous manifestations, and ILE has mild systemic manifestations. On the other hand, the terms for skin manifestations are chronic cutaneous LE (CCLE), subacute cutaneous LE (SCLE) and acute cutaneous LE (ACLE). CCLE includes discoid LE (DLE), chilblain LE and LE profundus. SCLE includes annular SCLE and papulosquamous SCLE. In this classification system, the condition of each LE patient is estimated integratedly both in systemic and cutaneous standpoints. Analyzing Japanese LE patients by this classification system, the usefulness of this system and the features of Japanese LE patients are discussed.
19568172 Pathogenesis of Sjögren's syndrome. 2009 Sep PURPOSE OF REVIEW: To summarize recent developments in our understanding of the pathogenesis of Sjögren's syndrome with a focus on the relationship between inflammation and exocrine dysfunction. RECENT FINDINGS: Animal models demonstrated the complex interactions between immunologic and nonimmunologic mechanisms in Sjögren's syndrome. Activation of the innate immune system can lead to exocrine dysfunction before or without significant inflammation, whereas in other models, salivary gland function is preserved despite intense inflammatory infiltrates. Primary or inflammation-related abnormalities in water channels contribute to the exocrinopathy. Activation of the innate immunity in patients is demonstrated by the upregulation of type-1 interferon-regulated genes (interferon signature) in peripheral blood and salivary glands and abnormal expression of B cell-activating factor and its receptors. Nonimmune mechanisms that may contribute to exocrine dysfunction include local and systemic androgen deficiency and autonomic nervous system dysfunction. Autoantibodies against the muscarinic acetylcholine receptors would provide a link between autoimmunity and exocrine dysfunction, but the data on the presence, frequency and physiologic affect of these antibodies remain controversial. SUMMARY: Recent discoveries from studies in patients with Sjögren's syndrome and animal models suggest a complex interplay between genetic factors, environmental and stochastic events that involve innate and adaptive immunity, hormonal mechanisms and the autonomic nervous system. Some of these findings suggest that exocrine gland dysfunction may precede autoimmunity or represent a process independent from inflammation in the pathogenesis of Sjögren's syndrome.
19954508 Microparticles as biomarkers in autoimmunity: from dust bin to center stage. 2009 Microparticles are small membrane-bound vesicles released from activated and dying cells. As shown in a study of primary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis, levels of microparticles in the blood, as measured by a solid-phase prothrombinase assay or flow cytometry, are increased with autoimmunity. Among patients with these conditions, however, particle numbers were inversely related to disease activity and levels of the enzyme secretory phospholipase A2 that can digest membrane lipids and perhaps cause particle loss. These findings suggest microparticles as novel biomarkers for autoimmunity, with levels reflecting events leading to their loss as well as production.
20139274 IL-33 exacerbates autoantibody-induced arthritis. 2010 Mar 1 Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and adaptive immunity. There is therefore intense interest in the factors that integrate these immunologic pathways in rheumatoid arthritis. In this paper, we report that IL-33, a novel member of the IL-1 family, can exacerbate anti-glucose-6-phosphate isomerase autoantibody-induced arthritis (AIA). Mice lacking ST2 (ST2(-/-)), the IL-33 receptor alpha-chain, developed attenuated AIA and reduced expression of articular proinflammatory cytokines. Conversely, treatment of wild-type mice with rIL-33 significantly exacerbated AIA and markedly enhanced proinflammatory cytokine production. However, IL-33 failed to increase the severity of the disease in mast cell-deficient or ST2(-/-) mice. Furthermore, mast cells from wild-type, but not ST2(-/-), mice restored the ability of ST2(-/-) recipients to mount an IL-33-mediated exacerbation of AIA. IL-33 also enhanced autoantibody-mediated mast cell degranulation in vitro and in synovial tissue in vivo. Together these results demonstrate that IL-33 can enhance autoantibody-mediated articular inflammation via promoting mast cell degranulation and proinflammatory cytokine production. Because IL-33 is derived predominantly from synovial fibroblasts, this finding provides a novel mechanism whereby a host tissue-derived cytokine can regulate effector adaptive immune response via enhancing innate cellular activation in inflammatory arthritis.
20084005 Genetic susceptibility factors for psoriatic arthritis. 2010 Mar PURPOSE OF REVIEW: Psoriatic arthritis (PsA) has a large genetic component to its heritability, yet investigation into the genetic basis of the disease has lagged behind other rheumatic diseases mainly because of the difficulty in defining classification criteria that would accurately differentiate it from other forms of inflammatory arthritis. However, using a variety of approaches, some confirmed associations have now been identified with PsA susceptibility, making a review of these recent developments timely. RECENT FINDINGS: Family studies continue to suggest a large genetic contribution to PsA. Using a candidate gene approach, genes robustly confirmed to be associated with psoriasis vulgaris (PsV) have also been found to be associated with PsA (HLA-Cw*0602, IL23R, IL12B). There is less overlap reported with rheumatoid arthritis (RA) than PsV susceptibility loci but one report suggests that the AFF3 locus may be associated with both RA and PsA. SUMMARY: Large, well powered genome-wide association studies are currently underway and should provide further insights into the cause of this common arthritic disease over the next few months. The bulk of evidence so far suggests that the genetic factors underlying PsV are also associated with PsA suggesting that future studies of PsV could include patients with PsA.
19265135 Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in 2009 Mar 15 Distinct Notch ligands possess a characteristic ability in terms of functional T cell differentiation. However, the precise role or the therapeutic potential of each Notch ligand in autoimmune diseases is largely unknown. In this study, we examined whether Jagged1 modulates a collagen-induced rheumatoid arthritis (CIA) model by altering T cell responses. The injection of a soluble Jagged1-encoding plasmid, sJag1-P, before or even after initial type II collagen (CII) immunization suppressed the disease severity of CIA. However, this treatment did not suppress CII-specific CD4(+) T cell proliferation and CII-specific Ab production. Depletion of either CD4(+) or CD8(+) T cells ameliorated CIA severity and sJag1-P further improved CIA in CD4(+) but not CD8(+) T cell-depleted mice. Injection of OVA and Jagged1-encoding plasmids inhibited proliferation of OVA-specific granzyme B-producing CD8(+) T cells, although Jagged1 could not directly inhibit CD8(+) T cell proliferation in vitro. The blockade of Jagged1 by an anti-Jagged1 Ab exacerbated CIA, whereas this effect was not observed in the absence of CD8(+) T cells. These data indicate that Jagged1 is able to deliver an indirect negative signal into CD8(+) T cells in vivo, which suggests its therapeutic potential in the treatment of CD8(+) T cell-mediated diseases, including rheumatoid arthritis.
20346888 Cotton wool spots as an indicator of methotrexate-induced blood dyscrasia. 2010 Apr BACKGROUND: The disease-modifying antirheumatic drug methotrexate (MTX) is the treatment of choice for many patients with rheumatoid arthritis. Systemic toxicity in MTX use is well documented. Side effects such as pancytopenia, myelosuppression, hepatotoxicity, and pulmonary toxicity may be life-threatening. Various ocular effects with methotrexate use have been reported; however, to the best of our knowledge, this is the first case documenting cotton wool spots as the presenting feature of systemic MTX toxicity. CASE REPORT: A 52-year-old woman presented for a routine ocular examination. Medical history was significant for rheumatoid arthritis and treatment with methotrexate for 11 years. She reported missing her most recent rheumatology follow-up examination. Fundus examinations found progressive cotton wool spots in both eyes. Systemic blood workup found severe pancytopenia (reduced white blood cell, red blood cell, and platelet counts). The MTX was tapered, cotton wool spots resolved, and the blood results normalized. CONCLUSION: Patients using MTX typically are monitored for adverse effects at scheduled intervals by their prescribing physician. Patients taking MTX and presenting with ischemic retinal findings warrant investigation for pancytopenia. Prompt workup and communication with the patient's prescribing doctor may be life-saving.
20017973 Comparison of methods for correcting population stratification in a genome-wide associatio 2009 Dec 15 Population stratification (PS) represents a major challenge in genome-wide association studies. Using the Genetic Analysis Workshop 16 Problem 1 data, which include samples of rheumatoid arthritis patients and healthy controls, we compared two methods that can be used to evaluate population structure and correct PS in genome-wide association studies: the principal-component analysis method and the multidimensional-scaling method. While both methods identified similar population structures in this dataset, principal-component analysis performed slightly better than the multidimensional-scaling method in correcting for PS in genome-wide association analysis of this dataset.