Browse

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

ID PMID Title PublicationDate abstract
18839270 Cyclosporin A treatment for Japanese patients with severe adult-onset Still's disease. 2009 For over 10 years there have been no clinical studies about adult-onset Still's disease (AOSD) in Japan. We aimed to investigate recent clinical features and treatment of AOSD and to evaluate the efficacy of cyclosporin A (CyA) in the treatment of AOSD. The data from 34 patients with AOSD who were admitted to our hospital between 1994 and 2007 were analyzed retrospectively. Of several immunosuppressive agents, the efficacy of CyA given to seven patients was precisely evaluated. Clinical features observed in this study did not differ from those in our previous study, and serum ferritin levels were elevated in all the patients. Among immunosuppressive agents CyA, used concomitantly with corticosteroids (CS) for seven patients with severe AOSD, proved to be very effective. The disease was led to remission promptly by CyA in six patients, and all the patients except one experienced no recurrence. These results suggest that CyA can be one of the potent candidates to be used next to CS for patients with AOSD that is resistant to CS.
18570755 Autoinflammatory syndromes and infections: pathogenetic and clinical implications. 2008 Jan The autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of seemingly unprovoked inflammation without significant levels of autoantobodies and antigen specific T cells. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been formally established, much ongoing research is aimed towards confirmation of that hypothesis. This article will review recent advances in the study of a subset of NOD-like receptors (NLRs), which control the activation of caspase-1 through the assembly of a large protein complex called inflammasome. Moreover, we will review recent progresses in understanding of a range of autoinflammatory conditions in humans.
17701269 Adult onset Still's disease: a study of 14 cases. 2008 Jan We studied the clinical profile, laboratory parameters, disease course, and outcomes of patients with adult onset Still's disease (AOSD). A retrospective analysis of adult patients with Still's disease diagnosed from 2000 to 2004 was carried out. Their clinical features and laboratory findings at presentation, disease course, and outcomes were analyzed. Data of 14 patients with Still's disease were analyzed. The age at disease onset ranged from 16 to 59 years with a mean of 29.85, the male to female ratio being 9:5. The mean duration of illness from onset of symptoms to presentation was 14.5 months (range). The most common clinical manifestations were fever (n = 14), articular symptoms (n = 14), rash (n = 8), weight loss (n = 12), and sore throat (n = 5). Elevated ESR was present in all patients with a mean of 98.3 mm at 1 h. Hepatic enzymes were elevated in seven patients at disease onset. The mean duration of follow up was 19.14 months (range). Three patients progressed to chronic arthropathy. Cyclosporine led to dramatic recovery in five patients. Macrophage activation syndrome (MAS) was present in two patients, one after sulfasalazine therapy. One patient with MAS died. Still's disease, although uncommon, has characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of fever of unknown origin. Nonsteroidal anti-inflammatory drugs, steroids, and methotrexate may not be always effective, and cyclosporine is an effective drug in resistant cases. Sulfasalazine should be avoided in cases of AOSD.
17408137 [Sjogren syndrome: a review of the literature and a case report]. 2006 Sjögren syndrome is one of the most prevalent autoimmune diseases in which the body's immune system mistakenly attacks its own moisture producing glands. Although Sjögren syndrome occurs in all age groups in both women and men, women in their fourties are the most affected. Sjögren's syndrome can occur alone or in the presence of another connective tissue disease, respectively called primary and secundary Sjögren syndrome. When two of the three clinical hallmarks: keratoconjunctivitis sicca, xerostomia or connective tissue disease are present, Sjögren 's syndrome should be considered. To confirm the diagnosis of Sjögren's syndrome several tests are required. e.g. blood tests, ophthalmologic tests and oral tests. Rheumatologists have the primary responsibility for managing Sjögren's syndrome. Other specialists can treat the related symptoms. The incidence of lymphoma is higher in patients with Sjögren's syndrome than in the general population. Therefore patients must be monitored carefully for the development of related autoimmune diseases, lymphoma and other complications. Sjögren's syndrome is serious but generally not fatal if complications are diagnosed and treated early.
18091373 Primary Sjögren syndrome complicated by autoimmune hemolytic anemia and pure red cell apl 2007 Dec Patients with primary Sjögren syndrome frequently present hematologic abnormalities, consisting mainly of immune cytopenias. Pure red cell aplasia is a very rare complication of primary Sjögren syndrome. This is the first report in the literature describing the development of pure red cell aplasia combined with autoimmune hemolytic anemia in a 74-year-old woman with primary Sjögren syndrome. In our patient, despite administration of diverse therapeutic schemes, such as corticosteroids, immunomodulating agents (intravenous immune globulin), immunosuppressive drugs (cyclophosphamide), and novel treatment options (monoclonal antibody directed against the CD20 antigen), no response was achieved. The present case suggests that the possibility of comorbid connective tissue disease should be a diagnostic consideration in patients with acquired pure red cell aplasia and autoimmune hemolytic anemia. Although most of the hematologic abnormalities that occur in primary Sjögren syndrome are not clinically significant, serious and difficult-to-treat hematologic complications may also occur.
17181927 A proposal of new ocular items in Sjögren's syndrome classification criteria. 2006 Sep OBJECTIVE: To verify whether ocular surface tests other than those included in primary Sjögren's syndrome (SS-I) classification criteria (Schirmer I, Break up Time, vital dye staining) may contribute to SS I diagnosis. METHODS: Two hundred and sixty-two patients (78 SS-1, 91 non-SS autoimmune diseases, 93 Sicca syndrome) filled a validated questionnaire on symptoms and were evaluated by Schirmer test without (Schirmer I) and with (Jones test) topical anaesthesia, Break Up Time (BUT), corneal aesthesiometry, tear clearance rate, vital dye (lissamine green) staining, impression conjunctival cytology, concentration of tear lysozyme and lactoferrin. Thresholds were selected from Receiver Operating Curves; sensitivity, specificity, likelihood ratio (LR+), predictive values were calculated for each test. A logistic regression model was constructed representing the best diagnostic index for SS. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (LR+ 1.38) and BUT (LR+ 1.05); results from lissamine green staining may be unreliable due to incorporation bias. Tear lactoferrin (LR+ 4.52), Jones test (LR+ 6.24), tear lysozyme (LR+ 8.0), symptom questionnaire (LR+ 8.62), tear clearance rate (LR+ 18.73) and corneal aesthesiometry (LR+ 20.96) exhibited high diagnostic performance also taken together in the regression model. CONCLUSION: Because many of the tests we have screened in this study can be carried out by a trained ophthalmologist in any clinical setting, we recommend that ocular surface impairment is studied with the combination of tests proved to be helpful for the SS I diagnosis.
16935510 Acute sensory neuronopathy as the presenting symptom of Sjögren's syndrome. 2006 Oct Sensory neuronopathy associated with Sjögren's syndrome (SS) usually has a subacute or chronic onset. We report the case of a 37-year-old woman who presented with an unusual hyperacute form of SS ganglionopathy. She initially developed paresthesias of her fingertips and rapidly became severely ataxic. Nerve conduction studies revealed abnormal sensory but normal motor functions. Lip biopsy showed findings consistent with SS. Sural nerve biopsy showed severe axonal loss. The patient showed modest improvement with immunosuppressive therapies.
16490754 Incidence of cancer in a cohort of patients with primary Sjogren's syndrome. 2006 Aug OBJECTIVE: To compare the incidence of subsequent cancers in a cohort of patients with primary Sjögren's syndrome (pSS) with that of the general population in the same region of England. METHODS: A retrospective analysis was carried out on 112 patients who had attended the out-patients department at University College Hospital, London, from 1979 onwards. Patients were followed up from diagnosis of pSS to diagnosis of first subsequent cancer, death, loss to follow-up or 31 December 2003 (the censoring date) to determine the person-years at risk for each individual. The expected numbers of subsequent cancers were calculated from sex-/age-/period-specific rates for the general population of southeast England, derived from registrations at the Thames Cancer Registry. Standardized incidence ratios (SIRs) were then calculated as the ratio of observed to expected numbers of cancers, along with 95% confidence intervals (CIs). Separate analyses were performed for all malignant cancers combined, lymphomas and non-lymphoid cancers. RESULTS: Among the 112 patients with pSS, 25 developed cancer (either before or after development of pSS), with lymphoma occurring in 11 cases. Nine patients had two cancers. There was a significantly elevated incidence of lymphomas in pSS patients compared with the general population (SIR 37.5, 95% CI 20.7-67.6). For non-lymphoid cancer, the observed increase in incidence was small and not statistically significant (SIR 1.5, 95% CI 0.9-2.6). CONCLUSION: This study confirms that there is an increased incidence of lymphoma in patients with pSS. An increase in the incidence of other cancers was not proven but the observation that some patients developed more than one cancer raises the possibility that there may be a subgroup of patients who are at greater risk of developing cancer.
18466642 Role of interleukin-7 in degenerative and inflammatory joint diseases. 2008 IL-7 is known foremost for its immunostimulatory capacities, including potent T cell-dependent catabolic effects on bone. In joint diseases like rheumatoid arthritis and osteoarthritis, IL-7, via immune activation, can induce joint destruction. Now it has been demonstrated that increased IL-7 levels are produced by human articular chondrocytes of older individuals and osteoarthritis patients. IL-7 stimulates production of proteases by IL-7 receptor-expressing chondrocytes and enhances cartilage matrix degradation. This indicates that IL-7, indirectly via immune activation, but also by a direct action on cartilage, contributes to joint destruction in rheumatic diseases.
19047665 Oral involvement in primary Sjögren syndrome. 2008 Dec BACKGROUND: In small studies, investigators have described oral features and their sequelae in primary Sjögren syndrome (PSS), but they have not provided a full picture of the aspects and implications of oral involvement. The authors describe what is, to their knowledge, the first large-scale evaluation to do so. In addition, they report data regarding utilization and cost of dental care among patients with PSS. METHODS: The authors surveyed patients with primary Sjögren syndrome as identified by their physicians (PhysR-PSS), patient-members of the Sjögren's Syndrome Foundation (SSF-PSS) and control subjects who did not have PSS. They made comparisons between the three groups. RESULTS: Subjects were 277 patients with PhysR-PSS, 1,225 patients with SSF-PSS and 606 control subjects. More than 96 percent of those in the patient groups experienced oral problems. An oral complaint was the initial symptom in more than one-half of the patients. Xerostomia-associated signs and symptoms were common and severe, as evidenced by scores on an inventory of sicca symptoms. These patients' rate of dental care utilization was high, and the care was costly. CONCLUSIONS: Oral and dental disease in PSS is extensive and persistent and represents a significant burden of illness. CLINICAL IMPLICATIONS: Oral symptoms and signs are common in patients with PSS. Early recognition of the significance of these findings by oral specialists could accelerate diagnosis and minimize oral morbidities.
18799099 HTLV-I infection results in resistance toward salivary gland destruction of Sjögren's syn 2008 Jul OBJECTIVE: The role of HTLV-I infection in Sjögren's syndrome (SS) remains unclear. In this study, we clinically compared radiographic imaging with histological cellular infiltration between HTLV-I-seropositive and HTLV-I-sero-negative SS. METHODS: Sixty primary SS patients were divided into two age-matched groups based on the seropositivity of the anti-HTLV-I antibody. We evaluated the two groups through labial salivary gland biopsy-proven cellular infiltration and sialography-proven radiographic gland destruction. RESULTS: In these 60 pSS patients, the incidence of abnormalities as determined by salivary gland biopsy and sialography was 51.7% (31/60) and 76.7% (46/60), respectively. Although there was no difference in the prevalence of abnormal findings between salivary gland biopsy and sialography in the whole 60 patients, there were significantly fewer abnormalities determined by sialography in HTLV-I-seropositive SS patients in comparison with HTLV-I-seronegative SS patients. Also, these findings were strengthened by the results that none of HTLV-I-seropositive SS patients with focus score 0 had abnormal sialography findings. CONCLUSION: Our results suggest that HTLV-I infection results in resistance toward salivary gland destruction of Sjögren's syndrome.
18261992 The levels of macrophage migration inhibitory factor as an indicator of disease activity a 2008 May OBJECTIVES: This study investigated the levels of macrophage migration inhibitory factor (MIF) in adult-onset Still's disease (AOSD) and explored the role of this pro-inflammatory cytokine in the systemic inflammation of AOSD. DESIGN AND METHODS: Serum MIF levels were measured by ELISA in patients with AOSD and controls. Intracellular MIF production by peripheral blood leukocytes was detected by three-color flow cytometry. RESULTS: Serum MIF levels were significantly increased in patients with AOSD. Serum MIF levels were significantly higher in AOSD patients with sore throat, myalgias, splenomegaly, or pleuritis, and were closely correlated with clinical disease severity and activity. Examined by flow cytometry, the intracellular MIF levels in monocytes and T-lymphocytes from AOSD patients were significantly higher than those from healthy subjects. CONCLUSION: These data represent the first demonstration of increased MIF expression in AOSD, and suggest that MIF may be an important marker for disease evaluation and monitoring.
17997783 Bilateral periocular psoriasis: an initial manifestation of acute generalized pustular pso 2007 Nov A 21-year-old febrile lady presented to the emergency service with severe lid oedema, conjunctivitis, dry mouth and abdominal skin rash. Over 5 days, she developed silvery scales and pustules on the lids, and generalized pustules on an erythematous base. Multiple focal sterile corneal infiltrates were seen. Haematological investigations and a skin biopsy were done as the consulting dermatologist suspected acute generalized pustular psoriasis. In addition, secondary Sjögren's syndrome was diagnosed since she had keratoconjunctivitis sicca, xerostomia, raised erythrocyte sedimentation rate and positive antinuclear antibodies. The presence of microabscesses in the epidermis on skin biopsy confirmed the diagnosis of pustular psoriasis. With oral methotrexate 7.5 mg weekly and topical corticosteroids, the acute condition gradually resolved; however, the keratoconjunctivitis sicca is persisting. Secondary Sjögren's syndrome associated with acute generalized pustular psoriasis and ocular psoriasis is extremely rare. Awareness of the ocular and dermatological features of these two conditions would result in earlier diagnosis and institution of appropriate treatment.
17601211 Bilateral multiple sialolithiasis of the parotid gland in a patient with Sjögren's syndro 2007 Feb The presence of multiple calculi in the major salivary glands is an uncommon finding. Sjögren's syndrome is a chronic autoimmune disease characterized by lymphocyte-mediated destruction of the exocrine glands. The case is presented of a 49-year-old female with Sjogren's syndrome found to have bilateral multiple sialolithiasis in the parenchyma of the parotid glands. The patient presented with a right sided painful inflamed swelling of the parotid region. Even though she had been diagnosed with primary Sjögren's syndrome 3 years prior to admission, she did not report any previous episode of sialadenitis. Full blood count showed leukocytosis (white blood cells = 14,900/10(6) L) with neutrophilia (75%). Radiological assessment included ultrasound and computed tomography scan of the parotids which demonstrated intra-parenchymal multiple calculi of both parotid glands and obstruction of the right Stensen's duct. The patient was treated with intravenous antibiotics and anti-inflammatory drugs. On the second day of hospitalisation, she reported spontaneous extrusion of a calculus during massage of the gland, with immediate relief of symptoms. In patients with Sjögren's syndrome and radiological findings of calculi in the major salivary glands, close observation is mandatory for better control of recurrent sialadenitis and early recognition of mucosa-associated lymphoid tissue lymphomas.
16870094 A community-based cohort of 201 consecutive patients with primary Sjögren's syndrome in I 2006 May OBJECTIVE: To determine the spectrum and prevalence of the varied manifestations, associated conditions and laboratory abnormalities of patients with primary Sjögren's syndrome in Israel and compare them between individuals of Sephardic and Ashkenazi descent and with data from the literature. METHODS: A retrospective study of a cohort of 201 consecutive patients diagnosed and followed at a single academic medical center. All cases were diagnosed using stringent criteria according to the American European Concensus Group including a labial minor salivary gland biopsy in all cases. RESULTS: Patients' mean age was 57 years and 84% were women. Overall, more than 98% of patients had sicca symptoms of dry eyes and mouth. About 35% of the cohort had hematological manifestations--primarily immune cytopenias, protein immunoelectrophoresis abnormalities and lymphoma. About 20% had associated neurological conditions (not only peripheral but often central nervous system) and 15% had pulmonary involvement. In addition, thyroid disease, liver disease, vascular or cutaneous manifestations, synovitis, ocular and renal disease could be found. In fact, the presenting manifestation was extraglandular or an abnormal test result in 39% of the patients. CONCLUSION: No significant differences were found in glandular or extraglandular manifestations or laboratory test results between Ashkenazi and Sephardic patients, despite their genetic differences. A negative history of sicca symptoms effectively rules out primary Sjögren's syndrome in this cohort. These symptoms may not be volunteered by patients and the large variety of extraglandular involvement patterns and associated conditions observed may dominate the patient's presentation, and mandate physicians' awareness and a high index of suspicion for a timely diagnosis.
16821274 Epitope mapping of anti-alpha-fodrin autoantibody in juvenile Sjögren's syndrome: differe 2006 Jul OBJECTIVE: Juvenile Sjögren's syndrome (SS) is an early-onset type of SS. Autoantibody against the N-terminal 120 kDa form of a-fodrin is a specific and sensitive disease marker for both juvenile and adult SS. We investigated the initial and major determinants of a-fodrin in SS. METHODS: Sera were obtained from patients with juvenile SS, 10 with primary SS and 10 with secondary SS. Epitope specificities of IgG antibodies were examined by dot-blot analyses using overlapping fusion proteins of the N-terminal part (561 amino acid residues) of a-fodrin as antigens. RESULTS: All sera from patients with primary SS reacted with amino acid residues 1 to 98 and 36 to 150, but not with 91 to 199. Epitope mapping using fusion proteins with subfragments, each consisting of about 50 amino acid residues, showed reactivity with amino acid residues 27-80 and 79-132, suggesting that at least 2 epitopes are contained in the first 150 amino acid residues. All 3 cases with neurological complications had additional epitope specificities. Sera from patients with secondary SS showed more diversified specificities and strongly reacted with amino acid residues 1-98 and 334-432, whereas the reactivities to 36-150, a major epitope in primary SS, were minimal. CONCLUSION: Major and initial B cell epitopes specifically reside in N-terminal amino acids 36-132 and could be used as a diagnostic tool for primary SS. The epitope subsequently expands to other regions of a-fodrin in association with the development of neurological complications or disease progression. Secondary SS has distinct epitope specificities.
18037929 Psoriatic disease--from skin to bone. 2007 Dec Psoriatic arthritis is an inflammatory joint disease that is heterogeneous in presentation and clinical course. Evidence that this disease is distinct from rheumatoid arthritis and other spondyloarthropathies is based on data derived from characteristic clinical features, histopathologic analyses, immunogenetic associations and musculoskeletal imaging. Emphasis has centered previously on a dominant role for the T lymphocyte in the inflammatory process; however, studies provide support for a major contribution from monocyte-macrophages in the initiation and perpetuation of joint and skin inflammation. The occurrence of arthritis in the absence of psoriasis in a minority of patients with psoriatic arthritis, coupled with divergent genetic risk factors, indicates that psoriatic arthritis is distinct from psoriatic skin inflammation. A new terminology, psoriatic disease, has emerged that encompasses the various manifestations of tissue and organ involvement observed in many psoriasis patients, including inflammation in the joint, eye and gut. Moreover, adverse cardiovascular and metabolic outcomes in patients with psoriasis or psoriatic arthritis might be directly linked to the cutaneous and musculoskeletal manifestations of these diseases via subsets of circulating monocytes and tissue macrophages activated by inflammatory cytokine networks that arise in the skin and possibly the joint.
20476957 Adalimumab in juvenile rheumatoid arthritis/juvenile idiopathic arthritis. 2008 Sep Chronic arthritis in childhood is the most common pediatric rheumatic disease and can lead to significant short- and long-term disability. TNF-a is a cytokine involved in joint inflammation and destruction. It has been suggested that early and aggressive treatment leads to improved outcomes by ameliorating clinical signs and symptoms, inhibiting joint destruction and improving functional disability. The early and aggressive use of disease-modifying antirheumatic drugs and biologic response modifiers are key to achieving this goal. Anti-TNF agents are effective biologic modifiers that have had a major impact on the clinical course of arthritis. Adalimumab, a recombinant monoclonal antibody to TNF-alpha, is emerging as a valuable new therapy for juvenile arthritis.
17162369 Increased Fas and Bcl-2 expression on peripheral blood T and B lymphocytes from juvenile-o 2006 Jun Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal-Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.
18685219 Effects of a casein hydrolysate prepared from Aspergillus oryzae protease on adjuvant arth 2008 Aug We evaluated the effects of a casein hydrolysate (CH) prepared from Aspergillus oryzae protease on rat adjuvant arthritis, a model of human rheumatoid arthritis. CH was administered orally once a day to the animals for 22 d after the adjuvant injection. CH suppressed swelling in the adjuvant-uninjected hind paws, and a higher dose of CH suppressed the increase in arthritic score and swelling of the adjuvant-injected hind paws. A histopathological examination revealed evidence that the higher dose of CH suppressed the articular changes in the rats. In addition, CH suppressed the production of nitric oxide and prostaglandin E(2) in the plasma of the rats. These results suggest that CH had a suppressive effect on adjuvant arthritis by inhibiting the acute and chronic inflammatory reactions.