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ID PMID Title PublicationDate abstract
10510398 Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen- 1999 Oct 15 Rheumatoid arthritis is a chronic inflammatory joint disease, leading to cartilage and bone destruction. In this study, we investigated the effects of local IL-4 application, introduced by a recombinant human type 5 adenovirus vector, in the knee joint of mice with collagen-induced arthritis. One intraarticular injection with an IL-4-expressing virus caused overexpression of IL-4 in the mouse knee joint. Enhanced onset and aggravation of the synovial inflammation were found in the IL-4 group. However, despite ongoing inflammation, histologic analysis showed impressive prevention of chondrocyte death and cartilage erosion. In line with this, chondrocyte proteoglycan synthesis was enhanced in the articular cartilage. This was quantified with ex vivo 35S-sulfate incorporation in patellar cartilage and confirmed by autoradiography on whole knee joint sections. Reduction of cartilage erosion was further substantiated by lack of expression of the stromelysin-dependent cartilage proteoglycan breakdown neoepitope VDIPEN in the Ad5E1 mIL-4-treated knee joint. Reduced metalloproteinase activity was also supported by markedly diminished mRNA expression of stromelysin-3 in the synovial tissue. Histologic analysis revealed marked reduction of polymorphonuclear cells in the synovial joint space in the IL-4-treated joints. This was confirmed by immunolocalization studies on knee joint sections using NIMP-R14 staining and diminished mRNA expression of macrophage-inflammatory protein-2 in the synovium tissue. mRNA levels of TNF-alpha and IL-1beta were suppressed as well, and IL-1beta and nitric oxide production by arthritic synovial tissue were strongly reduced. Our data show an impressive cartilage-protective effect of local IL-4 and underline the feasibility of local gene therapy with this cytokine in arthritis.
10813295 The epidemiology of psoriatic arthritis in Olmsted County, Minnesota, USA, 1982-1991. 2000 May OBJECTIVE: To determine the incidence, prevalence, and outcomes of psoriatic arthritis (PsA) in a geographically defined community. METHODS: Using the Rochester Epidemiology Project computerized medical record system, we screened all records of Olmsted County, Minnesota, residents with any diagnosis consistent with psoriasis and/or PsA made between January 1, 1982 and December 31, 1991. Medical records were reviewed using a pretested data collection form. Only those cases of psoriasis where the diagnosis was confirmed by a dermatologist were included. PsA was defined as inflammatory arthritis associated with a definite diagnosis of psoriasis. All identified cases were followed until death, migration from the county, or January 1, 1992. Cases with seropositive rheumatoid arthritis, systemic lupus erythematosus, crystal induced arthritis, Reiter's syndrome, arthritis associated with inflammatory bowel diseases, and inflammatory osteoarthritis were excluded. Clinical characteristics were described using summary statistics. Age and sex adjusted incidence and prevalence rates were calculated. Survival was estimated using the Kaplan-Meier method. RESULTS: We reviewed the records of 1844 patients with a diagnosis of psoriasis. In 1056 of these, the diagnosis was confirmed by a dermatologist. Among these 1056 psoriasis cases, we identified 66 cases (34 female, 32 male) of PsA first diagnosed between 1982 and 1991. The average age and sex adjusted incidence rate per 100,000 US population was 6.59 (95% confidence interval, CI, 4.99, 8.19) and the prevalence on January 1, 1992, was about one per 1000 (95% CI 0.81, 1.21). The average age at diagnosis was 40.7 years. At diagnosis, 91, 3, and 6% of cases had oligoarthritis, polyarthritis, and spondylitis, respectively. Over the 477.8 person-years of followup, 25 developed extraarticular manifestations (enthesitis, n = 15; ocular inflammation, n = 11; urethritis, n = 9), 10 patients received disease modifying antirheumatic drug treatment (methotrexate, n = 7; sulfasalazine, n = 5; intramuscular gold, n = 1; oral gold, n = 1), 3 received corticosteroids, and 5 had surgical interventions (synovectomy, n = 3; arthroplasty, n = 1; other reconstructive surgery, n = 2). Survival was not significantly different from the general population (p = 0.546). CONCLUSION: Unlike results from previous referral based studies, our findings indicate that PsA is a mild, uncommon inflammatory arthritis, not associated with a significant increase in mortality.
9016334 Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or benzothiazin 1997 Jan 3 Novel methotrexate (MTX) derivatives bearing dihydro-2H-1,4-benzothiazine or dihydro-2H-1,4-benzoxazine were synthesized and tested for in vitro antiproliferative activities against human synovial cells (hSC) and human peripheral blood mononuclear cells (hPBMC) obtained from patients with rheumatoid arthritis and healthy volunteers, respectively. In vivo antiarthritic activities of these derivatives were also evaluated in a rat adjuvant arthritis model. N-[[4-[(2,4-Diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-glutamic acid (3c) exhibited more potent antiproliferative activities in hSC and hPBMC than MTX in vitro. Antiproliferative activities of N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzoxazin-7-yl]carbonyl]-L-homoglutamic acid (3b) and N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1, 4-benzothiazin-7-yl]carbonyl]-L-homoglutamic acid (3d) (MX-68) were comparable to that of MTX in these in vitro assays. Compounds 3b,d (MX-68) significantly suppressed progression of the adjuvant arthritis in a dose-dependent manner ranging from 0.5 to 2.5 mg/kg (po). In addition, 3d (MX-68) completely suppressed this progression at the dose of 2.5 mg/kg (po). Importantly, 3d (MX-68) having benzothiazine and homoglutamate, as expected, did not undergo polyglutamation, a process which may be responsible for the associated side effects of MTX. These results suggest that 3d (MX-68) is a potent and safe candidate antirheumatic agent, absent of the side effects of MTX.
9437544 Enzyme-linked immunosorbent assay using F(ab')2 fragment for the detection of human pulmon 1997 Oct 31 We developed an enzyme-linked immunosorbent assay (ELISA) for detection of SP-D in serum using recombinant SP-D as a standard and horseradish peroxidase conjugated F(ab')2 fragment of mouse monoclonal antibody IgG to avoid the interaction of serum factors including rheumatoid factor. The use of F(ab')2 fragment dramatically decreased the value of serum SP-D concentration in rheumatoid arthritis patients without pulmonary complication to the close level of healthy volunteer. In contrast, the patients with collagen disease having interstitial pulmonary pneumonia exhibited consistently elevated levels of serum SP-D. The use of new ELISA with recombinant SP-D and F(ab')2 fragment of anti-SP-D monoclonal antibody gives a greater advantage for the accurate detection of SP-D in sera from patients with idiopathic pulmonary fibrosis, interstitial pneumonia with collagen disease and pulmonary alveolar proteinosis without interference of rheumatoid factor.
9805178 Sulphasalazine in the treatment of children with chronic arthritis. 1998 The aim of this study was to investigate the efficacy and toxicity of sulphasalazine (SASP) in the treatment of children with chronic arthritis. The medical records of 36 children (25 boys, 11 girls) who received SASP for the treatment of chronic arthritis were reviewed. Twenty-one patients had juvenile spondyloarthropathies (JSA) (eight juvenile ankylosing spondylitis (JAS), 13 undifferentiated JSA (uJSA) and 15 had juvenile rheumatoid arthritis (JRA). The patients received SASP therapy for a mean of 2.5 years (range 3 weeks to 8.1 years). Clinical and laboratory data were reviewed retrospectively to determine the effects of treatment. A clinically significant response occurred in 23 (64%) children: remission in 14 (39%) (JRA 5, JSA 9) and improvement (25% reduction in joint count) in nine (25%) (JRA 4, JSA 5). There was no difference in response rate between JRA and JSA patients (p = 0.11), but the time to remission was shorter in JSA patients (mean 5 months) than in JRA patients (mean 25 months) (p = 0.024). Twelve of the 36 patients discontinued non-steroidal anti-inflammatory drugs, and six of eight patients discontinued prednisolone. A significant fall in erythrocyte sedimentation rate and rise in haemoglobin occurred in SASP-treated patients (p < 0.005) comparing most recent results with pretreatment levels. Side-effects occurred in four of 36 patients (11%); only one patient who had persisting severe diarrhoea required discontinuation of SASP. It was concluded that SASP appears to be effective and safe in the treatment of JRA and JSA patients. As a second-line agent, SASP is the drug of first choice for patients with JSA; for JRA patients SASP may be a useful, possibly less toxic alternative to methotrexate.
9433877 Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential 1998 Jan OBJECTIVE: To compare the expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, in synovial tissue samples between patients with inflammatory arthritis (i.e., rheumatoid arthritis [RA], ankylosing spondylitis [AS], or psoriatic arthritis [PsA]) and patients with osteoarthritis (OA). METHODS: Paraffin-embedded sections of synovial tissue from patients with OA (n = 18), RA (n = 35), AS (n = 9), and PsA (n = 16) were immunostained for COX-1 and COX-2. Staining intensity was quantified videodensitometrically from specific synovial cell areas. In addition, samples of OA and RA synovial tissue were analyzed for levels of COX-1 and COX-2 messenger RNA (mRNA) using reverse transcriptase-polymerase chain reaction. RESULTS: Strong COX-2 immunostaining was observed in synovial blood vessel endothelium, synovial lining cells, chondrocytes, and subsynovial fibroblast-like cells in patients with inflammatory arthritides. In the blood vessels, the mean (+/-SD) optical density (MOD) of staining was elevated, especially in AS samples (2.73 +/- 0.63), but also in PsA (1.99 +/- 0.66) and RA samples (1.54 +/- 0.73), in comparison with OA synovial tissue (0.84 +/- 0.30; P < 0.01 versus other groups). COX-1 staining was almost exclusively localized in synovial lining cells, with no significant differences in the MOD between the diseases. COX-2 mRNA expression was higher in RA than in OA samples (P < 0.05). CONCLUSION: The expression of COX-2, but not the expression of COX-1, was found to be elevated in a disease-related pattern in the synovial tissue from patients with RA, AS, or PsA in comparison with OA samples, and was especially high in AS synovial tissue. These results may improve our understanding of the pathogenesis of different arthritic diseases, and may have implications for the use of selective COX-2 inhibitors in the treatment of inflammatory joint symptoms.
10438962 Direct adenoviral gene transfer of viral IL-10 to rabbit knees with experimental arthritis 1999 Aug 15 IL-10, a cytokine produced primarily by macrophages, B lymphocytes, and Th2 cells, has both immunostimulatory and immunosuppressive properties. A homologue of IL-10 encoded by EBV, known as viral IL-10 (vIL-10), is also able to suppress the immune response, but may lack some of the immunostimulatory properties of IL-10. To evaluate the potential of vIL-10 to block the progression of rheumatoid arthritis, we have utilized a replication-defective adenovirus vector to deliver the gene encoding vIL-10 to the knee joints of rabbits with Ag-induced arthritis. Intraarticular expression of vIL-10 significantly reduced leukocytosis, cartilage matrix degradation, and levels of endogenous rabbit TNF-alpha, as well as the degree of synovitis, while maintaining high levels of cartilage matrix synthesis. Interestingly, an antiarthritic effect was also observed in opposing contralateral control knee joints that received only a marker gene. An adenoviral vector carrying the enhanced green fluorescent protein marker gene was used to demonstrate that a morphologically similar subset of cells infected in the injected knee joint are able to traffic to the uninjected contralateral knee joint. Our results suggest that direct, local intraarticular delivery of the vIL-10 gene may have polyarticular therapeutic effects.
9486403 Mutations of the p53 tumour suppressor gene in erosive rheumatoid synovial tissue. 1998 Feb Erosive rheumatoid arthritis (RA) is accompanied by synovial tissue hyperplasia associated with the proliferation of transformed-appearing synovial lining cells. In the present study we have analysed the expression of the p53 tumour suppressor gene in the synovial pannus tissue from patients at various stages of the disease. We used a combination of polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) on DNA and reverse transcription, PCR and sequencing on cDNAs from synovial tissues or purified synovial cell populations of 24 RA and three osteoarthritis (OA) patients. We also studied p53 expression by immunohistochemical analysis. Mutations suspected after SSCP were identified by systematic sequencing of the p53 exon 6, especially in the fibroblast-like, adherent synovial cell population, associated with an erosive disease. Some accumulation of the protein was detected in immunohistochemical analysis of the p53 tumour suppressor gene in the patients' synovial tissues. However, no sign of malignancy was seen in these patients after a 2-year survey. These results show some abnormalities in the p53 tumour suppressor gene in RA patients, but do not allow this to be related to characteristic proliferative features of the rheumatoid synovium.
10382002 Pediatric case of accidental oral overdose of methotrexate. 1999 Jul Methotrexate is a chemotherapy antimetabolite, folic acid antagonist, that inhibits the enzyme dihydrofolate reductase resulting in decreased levels of tetrahydrofolate in the cells. This in turn blocks synthesis of thymidylate, a nucleotide necessary for DNA synthesis. It is readily absorbed from the gastrointestinal tract. Toxicity from overdose can affect multiple organ systems including bone marrow, liver, intestinal tract, kidneys, lungs, skin, and blood vessels, resulting in death in severe cases. Methotrexate is widely used to treat neoplastic disease, dermatologic disorders (psoriasis), and rheumatologic disorders (severe rheumatoid arthritis). As its indications for use increase, more accidental overdoses can be expected. We present the treatment and clinical course of one such case, that of a 2-year-old who accidentally took her grandmother's arthritis pills. Her initial serum level was 10 times greater than that needed to cause toxicity. She was treated with gastric lavage, activated charcoal, leucovorin rescue, and ICU admission. Her clinical course was unremarkable, and the only evidence of toxicity was a mild elevation in a liver-associated enzyme that resolved without any clinical sequela. Leucovorin at a dose equal to or greater than the possible ingestion should be given as soon as possible in methotrexate overdoses.
11407682 Time to first occurrence of erosions in inflammatory polyarthritis: results from a prospec 2001 Jun OBJECTIVE: To examine the time of occurrence of first radiographic erosions in a cohort of patients with inflammatory polyarthritis. METHODS: Patients were recruited through the Norfolk Arthritis Register, which follows up patients annually. Patients with features of rheumatoid arthritis (other than erosions) sufficient, together with erosions, to meet the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 revised criteria were requested to undergo radiographic examinations of the hands and feet at the first and/or second annual followup visits. All patients were requested to undergo radiographic examinations at the fifth annual followup visit. The most recent erosion-free radiograph was identified for 416 eligible patients, and these data were used to derive the duration of disease since the recalled date of onset of first symptoms. The rate of occurrence of first erosions was then determined (as a cumulative prevalence and as an incidence rate using Poisson regression) from analysis of followup films. Patients were assumed to be free of erosions at symptom onset. RESULTS: The cumulative prevalence of erosions in patients whose first film was obtained 12-24 months after disease onset was 36%, equivalent to an incidence rate of 24.5/1,000 patient-months. We identified 3 analysis groups of patients who were free of erosions based on films obtained 12-24 months, 24-36 months, and 36-60 months since the recalled date of onset of first symptoms. New erosions were observed in all 3 groups, with cumulative prevalences of 23%, 28%, and 47%, respectively. These were equivalent to first-erosion incidence rates/1,000 patient-months of 5.4 (95% confidence interval [95% CI] 3.8-83), 6.8 (95% CI 4.7-10.0), and 13.0 (95% CI 8.9-19.2), respectively. CONCLUSION: Many patients with erosive disease first develop their erosions >2 years from disease onset.
9870869 Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 1998 Dec OBJECTIVE: To identify novel non-major histocompatibility complex (non-MHC) genetic loci controlling the severity of homologous rat type II collagen-induced arthritis (CIA). METHODS: We conducted a genome-wide scan to identify CIA regulatory quantitative trait loci (QTL) in an F2 cross between DA (CIA highly susceptible) and ACI (CIA resistant) inbred rats immunized with homologous rat type II collagen (RII). These strains share the MHC/RT1av1 haplotype required for susceptibility to RII-induced CIA. RESULTS: F2 females had higher median arthritis scores than did males. Relative resistance in the males was determined by inheriting either a DA or an ACI Y chromosome and was independent of the source of the X chromosome. In addition, a major QTL was localized on chromosome 2 (Cia7, logarithm of odds score 4.6). Cia7 is in a region that shows linkage conservation with chromosomal regions that regulate autoimmune diabetes and experimental autoimmune encephalomyelitis in mice and multiple sclerosis in humans. CONCLUSION: Sex chromosomes and Cia7 play an important role in regulating CIA in response to RII. This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis.
9732918 Nonsteroidal antiinflammatory drug use and gallstone disease prevalence: a case-control st 1998 Sep OBJECTIVES: Conflicting results on the relationship between gallstone disease and the use of nonsteroidal antiinflammatory drugs (NSAIDs) have been reported, but studies on the effect of NSAID use in populations not selected on the basis of a high risk for gallstone development are still lacking. METHODS: We conducted a case-control study involving 216 patients, regular NSAID users (43 men and 173 women) consecutively admitted to a rheumatology department, suffering from rheumatoid arthritis (n = 147), osteoarthritis (n = 49), and ankylosing spondylitis (n = 20). Two-hundred sixteen patients who were not NSAID users, matched for gender, age, and body mass index, consecutively admitted to a medical department for various medical pathologies, acted as a control group. All patients underwent upper abdomen ultrasonography. RESULTS: The overall prevalence of gallstones was similar in the two groups: 24.0% in NSAID users (15.7% actual stones and 8.3% previous cholecystectomy) and 21.3% in controls (13.9% gallstones and 7.4% cholecystectomy). The prevalence of gallstone disease was significantly higher in women than in men, and the mean age was higher in gallstone patients than in gallstone-free patients, in both groups. No significant differences in type and duration of arthritis condition, type and dose of NSAID taken, and duration of treatment between gallstone patients and gallstone-free patients were found. On logistic regression analysis only female gender, aging, and family history of gallstone disease were significantly associated with the presence of gallstones, whereas no relationship between NSAID use and gallstone disease was found. CONCLUSIONS: Chronic NSAID ingestion does not seem to prevent gallstones in arthritis patients; in these patients gallstone disease is associated with classic risk factors (female gender and age).
18020548 Intra-articular corticosteroids in arthritic disease: a guide to treatment. 1998 Feb Intra-articular corticosteroid injections are widely used in aseptic arthritis, most often as a supplement to systemic anti-inflammatory therapy. Suppression of local joint inflammation by corticosteroids is rapid and pronounced, and may be achieved with only minor systemic effects; however, this suppression is usually only temporary. The original compound hydrocortisone acetate has been replaced by longer-acting preparations such as methylprednisolone acetate, triamcinolone acetonide and triamcinolone hexacetonide. In controlled studies, triamcinolone hexacetonide has proved most effective, providing clinical effect for a mean period up to several months. However, this compound frequently causes local tissue necrosis when injected outside a synovial cavity, and it should be used only by experienced clinicians. Indications for intra-articular corticosteroids include mono- or oligoarthritis in rheumatoid arthritis and other aseptic inflammatory joint diseases. Intra-articular corticosteroids are also used in osteoarthritis, but in controlled studies the effect is brief and transient. A number of potential adverse effects of intra-articular corticosteroids stress the importance of their judicious use. The risk of cartilage damage and progressive joint destruction is a controversial issue. The results of animal studies are ambiguous. Despite case reports of severe arthropathy, most studies on humans suggest that, when used appropriately, the beneficial effects of intra-articular corticosteroids exceed the harmful effects. Nevertheless, it is recommended that corticosteroid injections into the same joint should be limited, for instance to 1 injection every 6 weeks and no more than 3 to 4 in 1 year. Prior to intra-articular corticosteroid injections the indications and contraindications should always be considered. In particular, infection should be ruled out. Strict aseptic technique is essential to avoid iatrogenic septic arthritis. Correct intra-articular corticosteroid therapy is of great clinical value in the management of aseptic arthritic disease.
9636948 Joint manifestations in Behçet's disease. A review of 340 cases. 1998 May OBJECTIVES: To gain additional knowledge on the joint manifestations of Behçet's disease, with special attention to unusual forms. PATIENTS AND METHODS: Retrospective review of 340 cases with joint manifestations identified among 601 cases of Behçet's disease seen over a 15-year period. All the patients met International Study Group for Behçet's disease criteria. Radiographs of all joints with arthritis were obtained. Starting ten years ago, a radiograph of the sacroiliac joint was taken routinely. RESULTS: Joint manifestations were present in more than half the patients (56.57%) and were inaugural in 18.23% of cases. The knees and ankles were the joints most commonly affected. Monoarthritis and oligoarthritis were seen in 16.17% and 11.76% of cases, respectively and polyarthritis involving the large limb joints and the small joints of the hands and feet in 17.05% of cases. Unusual forms included polyarthritis with deformities and/or destruction (n: 8, including two patients who also met criteria for rheumatoid arthritis), pseudogout (n: 5), popliteal cyst (n: 3, including one case imitating deep vein thrombosis), myositis (n: 1), spondylarthropathy (n: 5), and Sjögren's syndrome (n: 2). Children were more likely than adults to have joint manifestations (73.68%) and polyarthritis (35.7%). CONCLUSION: Joint manifestations are common in Behçet's disease. Their unusual forms deserve to be known since they can raise diagnostic problems when they are inaugural.
9164973 High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. 1997 Jun 1 Collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis, is induced in DBA/1 (H-2q) mice following immunization with type II collagen (CII) in CFA. Since we have previously shown that IFN-gamma exerts a biphasic effect during the evolution of CIA in DBA/1 mice, we analyzed the development of this disease in mice with a disruption of the IFN-gamma receptor gene (IFN-gammaR(0/0)). Mutant mice were interbred with the DBA/1 strain to yield IFN-gammaR(0/0) mice expressing the H-2q haplotype. In three consecutive experiments, IFN-gammaR(0/0) male mice were found to exhibit severe clinical and histologic arthritis with an average incidence of 88.5 vs 94.1% for the wild DBA/1 strain. Notably, onset of clinical symptoms occurred significantly earlier than in DBA/1 mice. Although of a lower magnitude than in males, CIA also developed early in IFN-gammaR(0/0) female mice and with higher clinical severity than in control DBA/1 females. Immunization of knockout mice with CII resulted in the generation of CII-specific T cells belonging to the Th1 phenotype that recognize the same immunodominant peptides as do DBA/1 mice. CIA in IFN-gammaR(0/0) mice was associated with a down-regulation of the CII-specific IgG response, and this impairment was essentially due to a strong reduction of Abs of the IgG2a isotype. Taken together, our findings provide evidence that IFN-gammaR deficiency in DBA/1 mice leads to the occurrence of severe CIA with an accelerated onset compared with that in wild-type mice, indicating that the proinflammatory action of IFN-gamma has been bypassed in the IFN-gammaR(0/0) mice.
9205780 Pharmacological profile of the novel potent antirheumatic 4-(2',4'-difluorobiphenyl-4-yl)- 1997 May On the basis of basic screening for novel, more potent antiarthritics VUFB-16066 (4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid, CAS 112344-S2-2) was chosen as a compound with pronounced anti-inflammatory and immunomodulatory effects, with good gastric tolerance and relatively low toxicity. VUFB-16066 is a dual cyclooxygenase and 5-lipoxygenase inhibitor, and it suppresses alloantigen-driven cellular immune response and phagocytosis of stimulated peritoneal cells. VUFB-16066 exhibits prolonged pharmacological activity connected with its major metabolite having a very long half-life. In the model of adjuvant arthritis VUFB-16066 improves most of disease symptoms including immunopathological disturbances, which indicates possible disease-modifying activity of the drug. The beneficial antiarthritic effect of VUFB-16066 has been also confirmed in patients with rheumatoid arthritis.
10463116 [Sjögren syndrome and bilateral MALT lymphoma of the parotid gland]. 1999 Jul Sjögren's syndrome is an important autoimmune disease in the head and neck. Patients have an increased arrival risk of up to 6% per year for developing B-cell lymphomas, including mucosa-associated lymphoid tissue (MALT) lymphomas. The following case report shows this relation and the difficulty of differentiating clinically recurrent swelling of the parotid gland in Sjögren's syndrome from malignant lymphoma. A 64-year-old woman had a 2-year history of indolent, recurrent swelling of both parotid glands. Blood examination showed elevated ESR and a hypergammaglobulinemia. Immunosuppressive therapy produced no improvement. Two years after the diagnosis of Sjögren's syndrome, swelling of the left parotid gland persisted. Superficial parotidectomy of the left side was performed and histopathological examination revealed a MALT-related lymphoma. Subsequent parotidectomy of the right side also showed infiltration of the gland by a MALT lymphoma. Postoperative radiation therapy was given. During the follow-up period no recurrence or systemic disease was detected. Patients with Sjögren's syndrome should be examined regularly by the otolaryngologist. If a lymphoma cannot be ruled out, open biopsy must be considered for histological diagnosis. Prognostic factors for developing a lymphoma are possibly a high ESR and hypergammaglobulinemia. Further prognostic factors have to be evaluated.
9858428 Clinical characteristics, treatment, and outcome of adult onset Still's disease in souther 1998 Dec OBJECTIVE: To study the clinical characteristics, treatment outcome, and complications of patients with adult onset Still's disease (AOSD) in our local Chinese population. METHODS: Patients with AOSD were identified among others who attended our rheumatology clinics from 1967 to 1997 and were followed. Their clinical and laboratory features at presentation, treatment, and outcome were recorded and compared with other reported series. RESULTS: Sixteen patients with AOSD were identified. Eleven (69%) were female. Nine (56%) had onset of the disease between 16 and 35 years of age. The commonest presenting features were fever (100%), arthritis (94%), rash (85%), weight loss (69%), and sore throat (63%). Fifteen patients presented with pyrexia of unknown origin and the median duration of fever before the establishment of the diagnosis was 6 weeks (range 4-75). The acute phase response was marked in all patients with gross elevation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement levels. Hyperferritinemia (> 5 times normal) was present in 90% of cases. Most patients (81%) required corticosteroid therapy and 85% of those steroid treated patients received additional disease modifying agents. The mean duration of followup of our patients was 93.3 months (range 8-362). Five (33%) had monocyclic systemic disease, 6 (40%) had polycyclic systemic disease, and 4 (27%) had frequent relapses that progressed to a chronic arthropathy. CONCLUSION: AOSD in southern Chinese tends to run a benign course, with few patients evolving into chronic inflammatory arthropathy. A significantly lower incidence of serositis, lung involvement, and enlargement of the reticuloendothelial organs was observed at presentation compared with patients of different ethnic origins.
9638094 [Sicca symptoms and hearing loss in Behçet's syndrome]. 1998 May 22 HISTORY AND ADMISSION FINDINGS: A 39-year-old woman sustained an irreversible hearing loss in the left ear, followed 6 months later by a left facial paresis. Oral aphthous ulcers frequently recurred with fever of up to 39.5 degrees C. Her general condition was noticeably poor. INVESTIGATIONS: An inflammatory disease was suggested by an increased erythrocyte sedimentation rate (70/100 mm), leucocytosis (18,500/microliter), decreased haemoglobin (10.2 g/l) and leftward shift of the neutrophil granulocytes. Diagnostic tests for an infectious, autoimmune or haemato-oncological disease were negative. TREATMENT AND COURSE: Antibiotic and antimycotic treatment failed to bring lasting improvement. Thrombophlebitis and venous thrombosis developed in both upper limbs and acute episcleritis (scleritis) in the left eye. Behçet's disease with oral, ocular, neurological, cutaneous and vascular involvement was diagnosed and treated with chlorambucil (variable dosage around 7 mg/d orally), with rapid regression of symptoms. 3 months later joint pains set in, and another 18 months later she developed sicca symptoms (xerostomia with dry eyes): both responded to symptomatic treatment. CONCLUSION: The combination of loss of hearing, sicca syndrome and Behçet's syndrome has not been previously reported.
9363560 Augmented expression of CD44 splice variants in lymphoproliferative disorder of the lacrim 1997 Sep We explored the involvement of CD44 isoforms in lymphoproliferative disorder (LPD) of the lacrimal gland of a Sjögren's syndrome patient with unilateral LPD. The CD44 variant with the v6 exon was selectively detected from infiltrating lymphocytes in the gland with LPD, but not from infiltrating lymphocytes in the normal lacrimal gland, suggesting that the CD44 v6 variant exon may be closely associated with the development of LPD in Sjögren's syndrome.