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ID PMID Title PublicationDate abstract
18184026 Sjögren's syndrome: diagnosis and therapeutic challenges in the elderly. 2008 Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease characterized by keratoconjunctivitis sicca and xerostomia as a result of lymphocytic infiltration of the lacrimal and salivary glands. Extra-glandular manifestations occur in about one-third of patients with SS. The diagnosis of SS in the geriatric population is not straightforward and consideration needs to be given to exclusion of other conditions that may have similar presenting symptoms. The presence of autoantibodies, in particular anti-Ro and anti-La antibodies, may aid in the diagnosis of SS. Salivary gland biopsy findings represent one of the objective criteria included in the widely accepted American-European classification diagnostic criteria. However, SS-like histological changes can also be present in the healthy elderly, adding to the dilemma in diagnosing this condition in the geriatric population. Management of SS involves local treatment of dry eyes and mouth with replacement and stimulation therapies. Patients with more serious systemic involvement may require immunosuppressive therapy. Medications that are routinely used in the treatment of patients with SS often have limited use in the elderly population because patients in the latter group may have complex co-morbid conditions and be taking multiple medications. Recently, use of newer targeted therapies has been explored in SS. This article provides an update on recent developments in the diagnosis and management of SS, with emphasis on issues that may arise when treating elderly patients with this condition.
17992592 T lymphocytes in Sjögren's syndrome: contributors to and regulators of pathophysiology. 2007 Jun Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjögren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent autoimmune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention.
17634717 Successful treatment of a patient with primary Sjögren's syndrome complicated with perica 2007 A 35-year-old woman with primary Sjögren's syndrome (pSS) developed fever and chest pain during pregnancy. When the dose of prednisolone was reduced, she experienced chest pain with elevated CRP and D-dimer, resulting in admission to our hospital with marked cardiomegaly and pleural effusion. Because there was no evidence of other autoimmune disorders or infection, oral prednisolone was increased to 30 mg daily with heparin, and hypercoagulopathy was carefully monitored. The patient's condition improved rapidly, and she delivered a healthy baby. This is the first case to support the beneficial effect of prednisolone in pericarditis with pSS, and illustrates its safety during pregnancy.
17039737 [Adult-onset Still disease. 11 cases]. 2006 Jul Still's Disease of the adult is a systemic disease that the cause is unknown. If the pediatric forms are frequent, the affection of the adult is rare and its diagnosis is difficult. The purpose of this study is to analyse the features of the clinical evolution of adult Still's disease and to compare our results with the literature. It is a retrospective study about 21 years that permitted to collect 11 cases according the criteria of Yamaguchi. It is a matter of 6 men and 5 women that the mean age is 31 years old (age range: 16 to 48 years old). The fever was constant, the skin rash was noticed in 8 patients (72.7%); a polyarthritis was noticed in all the patients, chronic in 10 cases (90.9%) which 2 erosive forms. Adenopathies were present in 5 patients, a splenomegaly and a hepatomegaly were noticed respectively in 4 and 2 cases. Inflammatory syndrome with hyperleukocytosis was constant, and a hepatic cytolysis was noticed in 80%. The total ferritinemia titrated in 8 patients was constantly high. The hemocultures realized in all the patients were sterile and the complete immunologic examination was negative. The strong dose of corticoid was prescribed with success in all the patients. The immediate evolution was favourable in 10 patients. We deplore one death after a state of deep denutrition. Still's disease of the adult is rare, its diagnosis is difficult, sensitive to corticotherapy and its clinical evolution in our country is comparable to the literature.
17490637 Blockage of the formation of new blood vessels by recombinant human endostatin contributes 2007 Jul 12 The formation of new blood vessels permits a supply of nutrients and oxygen to the proliferating synovial cells and augmented inflammatory cell mass in rheumatoid arthritis (RA). Angiogenesis inhibition is not dependent on a down-regulated immune system. Therefore, angiogenesis is an attractive target in treating rheumatoid arthritis. To confirm the effect of recombinant human endostatin, an angiogenesis inhibitor, on inflammatory angiogenesis and to elucidate the related mechanisms, rat adjuvant arthritis model induced by Freund's complete adjuvant was used. The secondary arthritis was evaluated by using clinical scores and determining the volume of hind paw swelling. The number of new blood vessels was counted under microscope based on HE (hematoxylin and eosin) staining and positive immunoreactivity of factor VIII related antigen. factor VIII related antigen and vascular endothelial growth factor (VEGF) expressions in synovial tissue were determined by using immunohistochemistry. It was found that endostatin attenuated rat secondary paw swelling induced by Freund's complete adjuvant in a dose-dependent manner. Meanwhile, the number of new blood vessels in synovial tissue stained with HE was reduced after treatment with endostatin, which was proved by the positive immunostaining of factor VIII related antigen. Further, endostatin decreased the expression of VEGF in both cartilage and synovial tissue. These suggest that endostatin inhibiting VEGF expression contributes to the regression of rat adjuvant arthritis.
16394006 Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells 2006 Jan 15 Pristane-induced arthritis (PIA) in rats, a model for rheumatoid arthritis (RA), is a T cell-dependent disease. However, pristane itself is a lipid and unable to form a stable complex with a MHC class II molecule. Therefore, the specificity and function of the T cells in PIA are as unclear as in rheumatoid arthritis. In this study, we show that activated CD4+ alphabetaT cells, which target peripheral joints, transfer PIA. The pristane-primed T cells are of oligo or polyclonal origin as determined by their arthritogenicity after stimulation with several mitogenic anti-TCRVbeta and anti-TCRValpha mAbs. Arthritogenic cells secreted IFN-gamma and TNF-alpha (but not IL-4) when stimulated with Con A in vitro, and pretreatments of recipient rats with either anti-IFN-gamma or a recombinant TNF-alpha receptor before transfer ameliorated arthritis development. Most importantly, we show that these T cells are MHC class II restricted, because treatment with Abs against either DQ or DR molecules ameliorates arthritis development. The MHC class II restriction was confirmed by transferring donor T cells to irradiated recipients that were syngenic, semiallogenic, or allogenic to MHC class II molecules, in which only syngenic and semiallogenic recipients developed arthritis. These data suggest that the in vivo administration of a non-antigenic adjuvant, like pristane, activates CD4+ alphabetaT cells that are MHC class II restricted and arthritogenic.
16724638 Recurrent infections and joint pain. 2006 Mar A seven-year-old white male presented with recurrent bouts of paranasal sinusitis, streptococcal pharyngotonsillitis, lower respiratory tract infections, continuous low-grade fever, and conjunctivitis, which required frequent use of antibiotics over a period of two years. A careful review of systems also revealed a six-month history of arthralgia affecting his knees, elbows, and hands, which limited his daily activities. Prominent in the history were recurrent bouts of a generalized salmon-red, nonpruritic rash, which was most pronounced on the face and trunk and which was exacerbated by fever. His past medical history revealed severe bouts of gastroesophageal reflux disease, chronic intermittent bloody mucous diarrhea, and atopic dermatitis. A detailed review of the patient's family pedigree over five generations revealed a strong genetic predisposition for autoimmune diseases of several types. His physical examination revealed a thin, pale, chronically ill-appearing male, bilateral conjunctivitis, and pale nasal mucosae with no lymphadenopathy, organomegaly, arthritis, or rash. All laboratory results were unremarkable except for a positive rheumatoid factor and a suboptimal antibody response to immunization with pneumococcal vaccine. A diagnosis of juvenile rheumatoid arthritis of the systemic onset type was established, and, based upon his humoral immune deficiency, treatment with intravenous immunoglobulin was initiated with remarkable improvement in his symptomatology.
18839267 Multi-organ failure in adult onset Still's disease: a septic disguise. 2009 Jun The diagnosis of adult onset Still's disease is difficult in the absence of definite clinical and laboratory criteria. A delayed diagnosis of adult onset Still's disease was made in a 23-year-old female who developed multi-organ failure and disseminated intravascular coagulation with fingertip auto-amputation during a febrile illness considered septic due to the persistence of elevated serum procalcitonin concentration.
17668215 Adult onset Still's disease flared with pericardial effusion. 2008 Jan Adult onset Still's disease (AOSD) is characterized by spiking fevers, arthritis, rash, and involvement of multiple organs, and can be classified as self-limited, intermittent, and chronic disease groups. Cardiac manifestations include pericarditis and myocarditis. The case of this disease flared only with pericardial effusion is not reported. We describe a patient with adult onset Still's disease who was flared with pericardial effusion without other AOSD-associated symptoms, and propose that pericardial effusion should be included as a feature of flare in the intermittent disease group of adult onset Still's disease.
17031484 Cervical myelopathy caused by periodontoid synovial pannus in a patient with psoriatic art 2007 Aug The atlantoaxial subluxation and the formation of a synovial periodontoid pannus are associated with rheumatoid arthritis causing mechanical compression of the spinal cord and cervical myelopathy. Atlantoaxial subluxation is very rare in psoriatic arthritis (PsA). Even more rare is the formation of a periodontoid synovial pannus associated with PsA and signs of myelopathy. In this report, cervical myelopathy caused by periodontoid synovial pannus in PsA is described.
18976259 Quality of life in patients with Sjögren's syndrome and sicca complex. 2008 Dec To investigate the general and oral quality of life in patients with Sjögren's syndrome (SS) and sicca complex. Forty-four patients with SS were studied consecutively, 33 were primary SS and 11 secondary SS, classified in accordance with the Vitali European criteria. The Spanish version of the Medical Outcome Short Form (36) Health Survey questionnaire (SF-36) was used to evaluate general quality of life and the Oral Health Impact Profile (OHIP-49) Spanish version to study oral quality of life. Regarding general quality of life using the SF-36, when comparing the SS and the control groups, lower scores were obtained in the SS groups in all domains and on comparing primary and secondary SS, lower scores were found for primary SS in all the subscales. With respect to oral quality of life using the OHIP-49 (all items), we found lower scores for the primary SS group with respect to the control group. Patients with primary SS present lower scores for both oral and general quality of life.
17823601 Interstitial cystitis and systemic autoimmune diseases. 2007 Sep The cause of interstitial cystitis, a chronic disease that affects the bladder, is unknown. Autoantibodies, such as those against nuclear and bladder epithelium antigens, have been found in patients with interstitial cystitis, but these are likely to be secondary to the disease. No data support a direct causal role of autoimmune reactivity in the pathogenesis of interstitial cystitis. Indirect evidence, however, does support a possible autoimmune nature of interstitial cystitis, such as the strong female preponderance and the clinical association between interstitial cystitis and other known autoimmune diseases within patients and families. The strongest association occurs between interstitial cystitis and Sjögren's syndrome. Increasing evidence suggests a possible role of autoantibodies to the muscarinic M3 receptor in Sjögren's syndrome. The M3 receptor is also located on the detrusor muscle cells of the bladder and mediates cholinergic contraction of the urinary bladder and other smooth muscle tissues. Autoantibodies to the M3 receptor might be important in both the early noninflammatory and the late inflammatory features of interstitial cystitis.
18466441 A genome-wide ordered-subset linkage analysis for rheumatoid arthritis. 2007 Rheumatoid arthritis (RA) is a chronic, complex autoimmune inflammatory disorder with poorly known etiology. Approximately 1% of the adult population is afflicted with RA. Linkage analysis of RA can be complicated by the presence of phenotypic and genetic heterogeneity. It is shown that the ordered-subset analysis (OSA) technique reduces heterogeneity, increases statistical power for detecting linkage and helps to define the most informative data set for follow-up analysis. We applied OSA to the family data from the North American Rheumatoid Arthritis Consortium study as part of the Genetic Analysis Workshop 15 (GAW15). We have incorporated two continuous covariates, 'age of onset' and 'anti-CCP level' (anti-cyclic citrinullated peptide), into our genome-wide ordered-subset linkage analysis using 809 Illumina SNP markers in 5713 individuals from 606 Caucasian RA families. A statistically significant increase in nonparametric linkage (NPL) scores was observed with covariate 'age of onset' in chromosomes 4 (p = 0.000003) and 9 (p = 0.002). With the covariate 'anti-CCP level', statistically significant increases in NPL scores were observed in chromosomes 2 (p = 0.0001), 18 (p = 0.00007), and 19 (p = 0.0003). Once we identified the linked genomic region, we then attempted to identify the best plausible parametric model at that linked locus. Our results show significant improvement in evidence for linkage and demonstrate that OSA is a useful technique to detect linkage under heterogeneity.
18520119 Upper motor neuron syndrome associated with subclinical Sjögren's syndrome. 2008 We present two patients with primary lateral sclerosis-like upper motor neuron disease accompanying subclinical Sjögren's syndrome. Both patients showed progressive spastic quadriparesis, but neither sensory involvement nor detrusor dysfunction was noted. Lower motor neuron signs were detected only in their late follow-up period. Although sicca symptom was nearly absent, salivary labial gland biopsy revealed marked sialoadenitis in both patients. They also displayed a constellation of findings that suggested an autoimmune etiology closely related to Sjögren's syndrome, including germinal center formation in one patient, and markedly elevated levels of anti-nuclear antibody with abnormal sialography in the other. Both patients showed significant neurological improvement after the initial course of intravenous immunoglobulin therapy. We suggest that the evidence for subclinical Sjögren's syndrome should be sought in patients presenting with selective upper motor neuron involvement.
16978198 Synovitis score: discrimination between chronic low-grade and high-grade synovitis. 2006 Oct AIMS: To standardize the histopathological assessment of synovial membrane specimens in order to contribute to the diagnostics of rheumatic and non-rheumatic joint diseases. METHODS AND RESULTS: Three features of chronic synovitis (enlargement of lining cell layer, cellular density of synovial stroma, leukocytic infiltrate) were semiquantitatively evaluated (from 0, absent to 3, strong) and each feature was graded separately. The sum provided the synovitis score, which was interpreted as follows: 0-1, no synovitis; 2-4, low-grade synovitis; 5-9, high-grade synovitis. Five hundred and fifty-nine synovectomy specimens were graded by two independent observers. Clinical diagnoses were osteoarthrosis (n=212), post-traumatic arthritis (n=21), rheumatoid arthritis (n=246), psoriatic arthritis (n=22), reactive arthritis (n=9), as well as controls (n=49) from autopsies of patients without joint damage. Median synovitis scores when correlated with clinical diagnoses were: controls 1.0, osteoarthritis 2.0, post-traumatic arthritis 2.0, psoriatic arthritis 3.5, reactive arthritis 5.0 and rheumatoid arthritis 5.0. The scores differed significantly between most disease groups, especially between degenerative and rheumatic diseases. A high-grade synovitis was strongly associated with rheumatic joint diseases (P<0.001, sensitivity 61.7%, specificity 96.1%). The correlation between the two observers was high (r=0.941). CONCLUSION: The proposed synovitis score is based on well-defined, reproducible histopathological criteria and may contribute to diagnosis in rheumatic and non-rheumatic joint diseases.
18814432 The effectiveness for prevention of tuberculosis in patients with inflammatory rheumatic d 2008 BACKGROUND: New biologic therapies blocking TNF undoubtly constitute a considerable advancement in the management mentioned diseases, but are also associated with higher risk of activation of tuberculosis. METHODS: An assessment of tuberculosis activation rate in the group of patients with rheumatoid arthritis, juvenile idiopatic arthritis, ankylosing spondylitis and psoriatic arthritis threated by anti-TNF inhibitors since January 1st 2001 to June 30th 2007 in Slovakia and went in for special anti-tuberculosis screening before start of therapy. RESULTS: A total 537 rheumatic patients received the anti-TNF therapy. There were 346 rheumatoid arthritis patients, 68 juvenile idiopatic arthritis patients, 71 patients suffered from ankylosing spondylitis and 52 from psoriatic arthritis. Duration of anti-TNF therapy was 843 of patient-years. Infliximab took 203 patients with duration of therapy 348 patient-years, etanercept 201 patients with duration of therapy 331 patient-years and adalimumab 133 patients with duration of therapy 164 patient-years. The activation of tuberculosis reached the incidence 0.37% (2 cases for 537 patients) representing 0.237 cases for 100 patient-years. Both patients had extrapulmonary forms of tuberculosis which was in one patient disseminated, but they fully recovered after the anti-TNF drugs were stopped and chemotherapy was completed. CONCLUSION: Our results demonstrate a low incidence of tuberculosis activation during anti-TNF treatment in patients with inflammatory rheumatic diseases in the Slovak Republic and confirm the high effectiveness ours specified complex screening measures (Tab. 3, Ref. 13). Full Text (Free, PDF) www.bmj.sk.
17851546 Application of a disease-regulated promoter is a safer mode of local IL-4 gene therapy for 2007 Dec The application of disease-regulated promoters in local gene therapy for rheumatoid arthritis potentiates the development of a sophisticated treatment that relies on a restricted and fine-tuned supply of biologicals. Although several studies have investigated regulated promoters for achieving effective transgene expression during arthritis, none have explored their potential for minimizing deleterious effects arising from constitutive overexpression of transgenes under naive conditions. Using naive and collagen-induced arthritic mice, we examined the applicability of a hybrid interleukin-1 enhancer/interleukin-6 proximal promoter for achieving efficacious murine interleukin-4 gene therapy under arthritic conditions, while minimizing interleukin-4-induced inflammation under naive conditions. We found strong upregulation of transgene expression in virally transduced knee joints under arthritic conditions compared to levels in naive animals. Besides its responsiveness, the promoter strength proved sufficient for generating therapeutically efficacious levels interleukin-4, as demonstrated by the successful protection against cartilage erosion in collagen-induced arthritis. Most importantly, promoter-mediated restriction of the potent chemotactic interleukin-4 in naive animals strongly reduced the amounts of inflammatory cell influx. This study suggests the suitability of the interleukin-1 enhancer/interleukin-6 proximal promoter for the development of a local gene therapy strategy for rheumatoid arthritis that requires fine-tuned and restricted expression of transgenes with a pleiotrophic nature.
19097399 [Still disease in adult: a Senegalese case report]. 2007 INTRODUCTION: The adult Still's disease is a systematic disease rarely reported in the black Africans. We are reporting a case characterized among other difficulties by its diagnostic difficulties. OBSERVATION: It is about a 29 years old black Senegalese woman patient, without particular antecedents, which presented a systematic chronic syndrome composed of a pharyngitis, a polyarthritis and general symptoms (fever, chills, sweats, change of the general state), a cutaneous eruption, a polyadenopathy, a hepatosplenomegaly. The biological analyses showed among others, an inflammatory syndrome (VS at 115 mm in the 1st hour, CRP at 100 mg/L, WBC at 10,400/mm3 with neutrophilia), a hyperferritinemia in 643 ng/l with collapse of the glycosylated ferritin at 13% (N between 60 in 80%). After elimination of any autoimmune or neoplastic suppurative infectious pathology in the decline of a check up as exhaustive as possible, the diagnosis of a Still disease in adult had been retained. Their was improvement under the combination of prednisone and methotrexate. CONCLUSION: Although it is exceptional in black African, this pathology shall be however part of the differential diagnoses of any unexplained systematic sign. The dosage of the ferritinemia and its glycosylated fraction as well as the resort to the criteria of Yamaguchi and Fautrel's classification of Still Disease in Adult shall allow to establish more prematurely the diagnosis of this potentially severe affection.
16651289 A multicenter case-control study on predictive factors distinguishing childhood leukemia f 2006 May OBJECTIVE: Acute lymphocytic leukemia (ALL) often presents with musculoskeletal concerns such as pain or swelling, even before appearance of blasts in the peripheral blood. Such presentation may lead to misdiagnosis of a child with juvenile rheumatoid arthritis (JRA). This study was designed to identify the predictive factors for leukemia using basic clinical and laboratory information. METHODS: A retrospective chart review was performed using a simple questionnaire to compare the clinical and laboratory findings present during the initial visit to a pediatric rheumatology clinic for 277 children who were ultimately diagnosed with either JRA (n = 206) or ALL (n = 71). Sensitivity and specificity analysis of a variety of parameters, both singly and in combination, was performed to identify predictive value for ALL. RESULTS: The majority (75%) of children with ALL did not have blasts in the peripheral blood at the time of evaluation by pediatric rheumatologists. In children presenting with unexplained musculoskeletal complaints, the 3 most important factors that predicted a diagnosis of ALL were low white blood cell count (< 4 x 10(9)/L), low-normal platelet count (150-250 x 10(9)/L), and history of nighttime pain. In the presence of all 3, the sensitivity and specificity for a diagnosis of ALL were 100% and 85%, respectively. Other findings, including antinuclear antibody, rash, and objective signs of arthritis, were not helpful in differentiating between these diagnoses because they occurred at similar rates in both groups. CONCLUSIONS: When a child develops new-onset bone-joint complaints, the presence of subtle complete blood count changes combined with nighttime pain should lead to consideration of leukemia as the underlying cause.
22294231 Animal models of collagen-induced arthritis. 2008 Dec Collagen-induced arthritis in rats is associated with inflammatory polyarthritis, sharing clinical and pathological features with those of human rheumatoid arthritis (RA). Described in this unit is a protocol for consistently inducing arthritis in female Lewis rats by immunizing them with bovine type II collagen (CII) emulsified in complete Freund's adjuvant. This model is of value not only in defining the underlying pathogenesis of RA, but also as a tool for evaluating pharmacological strategies for treating this condition.