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

ID PMID Title PublicationDate abstract
12365721 Intra-articular tissue factor/factor VII complex induces chronic arthritis. 2002 Sep OBJECTIVE: Fibrin accumulation in the joint cavity is a common feature of chronic arthritides, such as rheumatoid arthritis (RA). Complex formation between tissue factor (TF) and factor VII (FVII) is the initial step in such a fibrin formation. METHODS: To assess the role of the TF/FVII complex in the pathogenesis of joint inflammation, 1) the levels of TF/FVII complex were measured in synovial fluid of RA patients; 2) the complex was injected to healthy mice intra-articularly. RESULTS: Morphological analysis of the joints 4 days after TF/FVII injection revealed influx of CD4-Mac1+ mononuclear leukocytes into synovial tissue followed by cartilage and bone destruction. Inflammation induced by TF/FVII complex was more profound than that caused by each of the proteins separately, both with respect to frequency, severity and duration of arthritis. Interaction between macrophages and lymphocytes in sustaining joint inflammation was proved by the requirement of the combined lymphocyte/ monocyte depletion to abolish TF/FVII induced arthritis. Induction of monocyte attracting chemokines (MIP-1 alpha and RANTES) was shown to be one of the potential mechanisms for TF/FVII complex triggered inflammatory cell influx. Interestingly, TF/FVII complexes were detected in synovial fluid of 20/40 patients with RA. CONCLUSIONS: Altogether these findings indicate that TF/FVII complexes, frequently found intra-articularly in joints of RA patients, may be an important component in both induction and progression of chronic destructive arthritis.
15383610 A transient post-translationally modified form of cartilage type II collagen is ignored by 2004 Oct 1 Lysine residues in type II collagen (CII) are normally hydroxylated and subsequently glycosylated in the chondrocyte. The immunodominant T cell epitope of CII involves such post-translationally modified lysine at position 264 that has been shown to be critical in the pathogenesis of murine collagen-induced arthritis and also in human rheumatoid arthritis. In this study we identified a line of transgenic mice expressing a TCR specific for hydroxylated rat CII epitope. They were crossed with transgenic mice expressing the rat CII epitope, either specifically in cartilage (MMC mice) or systemically (TSC mice), to analyze T cell tolerance to a post-translationally modified form of self-CII. The mechanism of T cell tolerance to the hydroxylated CII epitope in TSC mice was found to involve intrathymic deletion and induction of peripheral tolerance. In contrast, we did not observe T cell tolerance in the MMC mice. Analysis of CII prepared from rat or human joint cartilage revealed that most of the lysine 264 is glycosylated rather than remaining hydroxylated. Therefore, we conclude that the transient post-translationally modified form of cartilage CII does not induce T cell tolerance. This lack of T cell tolerance could increase the risk of developing autoimmune arthritis.
12784405 Determinants of synoviocyte clearance of arthritogenic bacteria. 2003 Jun OBJECTIVE: Persistence of intracellular organisms may play a critical role in the initiation and perpetuation of synovitis in reactive arthritis (ReA). We investigated factors that may influence local clearance of arthritogenic pathogens in ReA. METHODS: We studied 11 HLA-B27 positive patients with spondyloarthropathies and contrasted these patients with 6 HLA-B27 negative control patients with rheumatoid arthritis or osteoarthritis. We employed an ex vivo system in which human synoviocytes derived from patients with ReA are cocultured with arthritogenic pathogens, and intracellular clearance is measured by quantitating colony-forming units over time. RESULTS: The clearance kinetics of the organisms bore no relationship to the HLA-B27 status of the patient. Clearance of S. typhimurium over a 10 day period was accompanied by a progressive rise in nitric oxide (NO) production, but this appeared not to be rate-limiting, since (1) clearance kinetics were comparable between high versus low NO-producing synoviocytes; and (2) L-NMMA inhibition of NO production did not alter clearance kinetics of S. typhimurium. Interferon-g (IFN-g) was observed to have a small but measurable effect on bacterial clearance. In certain patients with ReA there was a paradoxical stimulatory response to IFN-g, in which the addition of IFN-g was accompanied by an increase in intracellular bacteria. This effect was found to be attributable to IFN-g mediated suppression of NO production in these cells. This pattern was not observed in B27 negative synoviocytes. CONCLUSION: Intracellular persistence of arthritogenic organisms may contribute to the cellular basis of ReA, but the molecular basis of the bacteriocidal pathways in synoviocytes has not been fully resolved. Our findings indicate that a direct effect of HLA-B27 on these events is unlikely, but that alterations in cytokine response profiles may play a contributory role. Characterizing these mechanisms holds the promise of more specific therapeutic interventions in this disease.
15359107 Resistance to development of collagen-induced arthritis in C57BL/6 mice is due to a defect 2004 Sep Collagen-induced arthritis (CIA) is a rodent model of human rheumatoid arthritis. Mice of the H-2(q) (DBA/1J) background are highly susceptible to disease whereas mice of the H-2(b) (C57BL/6, B6) background are resistant. To determine why B6 mice are resistant to disease induction, we systematically analyzed T and B cell immune responses in B6 mice, compared to DBA/1J mice, following immunization with bovine type II collagen (CII). We found that both strains showed similar T cell proliferation and cytokine responses and similar levels of anti-CII antibodies (Abs) at day 12 or day 14 of initial immunization (primary immune response), however, those B6 mice that did not develop arthritis showed a significant defect in T cell responses and significantly lower levels of anti-CII Abs following secondary boosting immunization (day 35 of initial immunization, secondary immune response) compared to DBA/1J mice. Our results define for the first time that a defective secondary immune responses in B6 mice leads to the resistance of CIA.
12797545 Streptococcal cell wall induced arthritis: leukocyte activation in extra-articular lymphoi 2003 Apr Rheumatoid arthritis (RA) is a common systemic inflammatory disease thought to be T-helper-1 cell driven, though current controversy involves the relative role of T cells versus other leukocytes. Thus, there is a need for better understanding of the role of various leukocytes and their subsets in RA. Using the streptococcal cell wall (SCW) induced arthritis model, we examined leukocytes isolated from peripheral blood, spleen, and lymph nodes using monoclonal antibodies directed against lineage specific cell surface markers. Activation status of these cells was assessed using CD44 and CD71 as markers. T cells in general, and CD4+ T cells in particular were found to be activated in spleen and lymph nodes. B cells and monocytes in spleen demonstrated increased activation as well. The activation of cells in the myeloid and lymphoid lineages in the chronic phase of arthritis indicates ongoing involvement of innate and cognate immunity. This study quantitates specific changes in B and T lymphocytes, and myeloid cells and is consistent with findings in human RA in which specific antibodies, T cells, and myeloid cells are all implicated in the pathogenesis of RA.
12867296 Salivary and serum beta2-microglobulin and gamma-glutamyl-transferase in patients with pri 2003 Aug BACKGROUND: Sialochemistry has been proposed as a simple and useful tool for the diagnosis of Sjögren syndrome (SS). Although many changes have been detected in several constituents of saliva from patients with SS, none are individually sensitive or specific enough for diagnosing SS. The aim of this study was to assess the value of the combined determination of beta2-microglobulin (beta2m) and gamma-glutamyl-transferase (GGT) activity in serum and saliva as a diagnostic instrument for differentiating primary and secondary [to systemic lupus erythematosus (SLE)] SS patients from normal subjects. METHODS: Nineteen primary SS (pSS) patients, 15 patients with SS secondary to SLE, and 25 SLE patients without SS were studied. Thirty healthy subjects were included in the study as control group. RESULTS: By means of a mathematical model, (a) 84.1%, (b) 85.7%, and (c) 87.0% of patients were correctly classified as SS or normal when (a) salivary beta2m and GGT values, (b) serum beta2m and salivary GGT values, and (c) salivary beta2m and GGT along with serum beta2m values, respectively, were considered. To differentiate between pSS and sSS by means of the mathematical model, the combination of serum beta2m and salivary GGT values achieved that 81.8% of the patients were correctly classified. CONCLUSION: Since sialochemistry is an easy, safe and reliable test, the combined determination of beta2m and GGT in saliva and serum was useful for differentiating SS patients from normal subjects, but not excessively good for differentiating pSS from sSS patients.
12695164 Primary Sjögren's syndrome associated agranulocytosis: a benign disorder? 2003 May OBJECTIVE: To report on an uncommon association of agranulocytosis in primary Sjögren's syndrome (SS). METHODS: The clinical, haematological, and immunological features of seven patients with primary SS associated with a chronic (>6 months) agranulocytosis, and the outcome of the patients, were analysed. RESULTS: Patients were white women with an unexplained agranulocytosis. They all had non-erosive arthritis and three had a thrombocytopenia or Evan's syndrome. In three patients, transient or durable expansion of T lymphocytes was present in the peripheral blood or in the bone marrow, but evolved independently from neutrophil counts. There was no paroxysmal nocturnal haemoglobinuria clone or antibodies to neutrophil surface antigens. In vitro bone marrow culture was normal (four patients) or showed a decrease in colony forming unit-granulocyte monocyte (CFU-GM) and colony forming unit-erythroblast (CFU-E) (one patient). Serum levels of soluble Fas ligand (sFasL) were normal, and granulocyte-colony stimulating factor (G-CSF) concentrations were either normal or raised. One patient was treated with steroids associated with intravenous immunoglobulins and achieved a lasting response. Two other patients were treated with steroids and methotrexate, with poor efficacy. Short courses of subcutaneous G-CSF produced a transient and mild response in all three patients. Complete recovery of the neutrophils occurred temporarily during pregnancy in two patients. After a mean follow up of 34.8 months (range 6-139) all patients were alive and none developed serious infections. CONCLUSION: A subset of patients with primary SS and non-destructive arthritis may develop a chronic but well tolerated agranulocytosis that is usually poorly responsive to steroids and oral methotrexate.
12114289 Fatigue in daily life in patients with primary Sjögren's syndrome and systemic lupus eryt 2002 Jun Fatigue is a well-recognized complaint with major impact on daily life in primary Sjögren's syndrome (PSS) and systemic lupus erythematosus (SLE). Previous research has not taken into account several crucial aspects of fatigue. This study examined various aspects of fatigue in the daily life of patients with PSS and SLE and in healthy controls. We compared age-adjusted, repeated measurements of fatigue across the day of female patients with SLE (n = 20, mean age 43.4 +/- 11.3), with PSS (n = 28, mean age 53.7 +/- 13.9) and healthy participants (n = 30, mean age 50.5 +/- 13.4). General and physical fatigue was significantly higher in patients than in healthy participants. Groups did not differ with respect to average levels of reduced motivation or mental fatigue. Both general and physical fatigue and reduced activity varied significantly during the day. Adjusting for depressive symptoms, groups showed significantly different time courses during the day. In healthy participants and patients with SLE, fatigue first decreased and then increased, whereas a rather opposite course-at least for the first part of the day-was observed in patients with PSS. Using an ecologically valid assessment method, we demonstrated substantially higher levels of daily fatigue in SLE and PSS patients as compared to healthy participants, thereby jeopardizing these patients' quality of life. The effect of disease on variations in fatigue over the day should be the subject of further inquiry, especially as it might clarify underlying mechanisms.
11838847 Clinical and immunological factors associated with low lacrimal and salivary flow rate in 2002 Feb OBJECTIVE: To study which clinical and immunological factors may be associated with low salivary and lacrimal flow in patients with primary Sjögren's syndrome (SS). Are the lacrimal and salivary flows influenced by age of the patient, age at diagnosis, disease duration, or findings in the biopsies of the minor salivary glands, or are immunological factors of importance for reduced flow rates? METHODS: In total 72 patients (mean age 57 yrs and disease duration 13.5 yrs) with primary SS diagnosed according to the European classification criteria were evaluated objectively by serological testing and by measures of exocrine gland function, such as unstimulated whole saliva collection (UWSC) and by Schirmer I test. RESULTS: Salivary flow (UWSC) in 72 patients with primary SS correlated to the presence of antinuclear antibodies (ANA) (r = -0.32, p = 0.006) and to anti-SSA/SSB (r = -0.31, p = 0.010). No such correlation was seen for the lacrimal flow, and there was no mutual correlation between lacrimal and salivary flow. UWSC was significantly lower in patients with anti-SSA versus those without anti-SSA (1.63 ml vs 2.63 ml; p < 0.007), while such a significant difference was not observed in the presence versus absence of anti-SSB. The salivary and lacrimal flow was not significantly affected by age of the patient, and did not correlate to age at diagnosis, sex, disease duration, rheumatoid factor finding, or findings in minor salivary gland biopsies. CONCLUSION: Salivary flow in patients with primary SS was negatively correlated with immunological factors such as ANA and anti-SSA/SSB, in contrast to low lacrimal flow, where no such correlation was seen. There was no association of lacrimal and salivary flow with age of patient, age at diagnosis, disease duration, and findings in minor salivary gland biopsies. The results indicate that reduced salivary flow is closely associated with immunological factors, and is not associated with the age of the patient or infiltration of lymphocytes in salivary glands.
12833246 Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic s 2003 Jun OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.
15529344 Identification of new quantitative trait loci in mice with collagen-induced arthritis. 2004 Nov OBJECTIVE: Collagen-induced arthritis (CIA) in the mouse is one of the most widely used autoimmune experimental models, with many features similar to rheumatoid arthritis. This study sought to identify potential genetic regulatory mechanisms of CIA in major histocompatibility complex-matched (H2-q) F(2) hybrid mice. METHODS: We used 126 polymorphic markers to perform simple sequence-length polymorphism analysis on 290 F(2) hybrids of arthritis-susceptible (DBA/1J) and arthritis-resistant (FVB/N) inbred mouse strains. The major clinical traits (disease severity and onset) were assessed, and serum antibodies specific to type II collagen (CII) were determined by enzyme-linked immunosorbent assay in 270 F(2) mice. Lymph nodes from 94 F(2) mice were used to test the ratio of CD4 to CD8 by fluorescence-activated cell sorter analysis, and cell proliferation was determined by XTT test. RESULTS: Two quantitative trait loci (QTLs) identified in previous studies were confirmed; these were severity-controlling Cia2 and onset-controlling Cia4 on chromosome 2. Moreover, we identified 5 new QTLs, 1 for CII-specific IgG2a antibodies on chromosome 5, 2 controlling the CII-specific IgG1 antibody response on chromosomes 10 and 13, 1 for the CD4:CD8 ratio on chromosome 2, and 1 for cell proliferation (measured by XTT test) on chromosome 16. Complement component C5 was identified as the probable main candidate gene for the QTLs Cia2 and Cia4. F(2) mice carrying a 2-basepair deletion of C5, the FVB/N allele, had low incidence and less severe disease as compared with those carrying the DBA/1J allele. CONCLUSION: This genome scan provides additional evidence confirming the role of C5 as a probable candidate gene for Cia2 and Cia4 loci, and identifies new QTLs controlling new traits in autoimmune arthritis.
12124880 Folate-targeted imaging of activated macrophages in rats with adjuvant-induced arthritis. 2002 Jul OBJECTIVE: To determine whether overexpression of the high-affinity folate receptor (FR) on activated macrophages can be exploited to selectively target imaging agents to sites of inflammation in rats with adjuvant-induced arthritis (AIA). METHODS: Folic acid was conjugated to a (99m)Tc chelator (the complex termed EC20), and its distribution was visualized using gamma scintigraphy in healthy rats, rats with AIA, and arthritic rats that had been depleted of macrophages. To confirm that uptake was mediated by the FR, excess folic acid competition studies were conducted, and tissue FR levels were quantitated using a radioligand binding assay. Flow cytometry was also used to investigate uptake of folate conjugates into macrophages of both arthritic and healthy rats. RESULTS: EC20 concentrated in the arthritic extremities of diseased rats but not in the extremities of healthy rats. The intensity of images of affected tissues was greatly reduced in the presence of excess competing folic acid. The livers and spleens of arthritic animals also showed enhanced uptake of EC20 and increased levels of FR. Depletion of macrophages from arthritic animals reduced tissue FR content and concomitantly abolished uptake of EC20. In addition, macrophages isolated from livers of rats with AIA exhibited a significantly higher binding capacity for folate conjugates than did macrophages obtained from healthy rats. CONCLUSION: Although EC20 is currently undergoing clinical evaluation for use in the imaging of ovarian carcinomas, the present results suggest that it may also be useful for assaying the participation of activated macrophages in inflammatory processes such as rheumatoid arthritis.
12528115 Jaccoud's arthropathy in systemic lupus erythematosus: differentiation of deforming and er 2003 Jan OBJECTIVE: To evaluate alterations of the soft tissues, tendons, and bones as detected by magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus (SLE)-associated arthritis of the finger joints. METHODS: Both hands of 14 patients with SLE of various activities and durations and with arthritis and/or deformities of the finger joints were examined by MRI and conventional radiography. Coronal T1-weighted spin-echo (with and without gadolinium contrast), axial T2-weighted turbo spin-echo, coronal fat-suppressed short tau inversion recovery, and 3-dimensional double-echo steady-state sequences were acquired and analyzed, and the findings were compared with those from conventional radiographs. RESULTS: MRI detected periarticular capsular swelling in all 14 patients, joint effusion in 7, edematous tenosynovitis in 6, proliferative tenosynovitis (flexor and/or extensor tendons) in 4, and intraarticular signs of synovial membrane hypertrophy in 10 patients, 9 of whom showed enhancement after administration of contrast medium. Bony erosions were identified in 8 patients by MRI; conventional radiography missed these erosions in 2 of the 8 patients. Four of the 14 patients were designated as Jaccoud's arthropathy index-positive, and all 4 showed severe edematous tenosynovitis and capsular swelling, but no signs of bony erosions despite longstanding disease (mean 21.5 years). Four of the 10 patients with mild deformity exhibited prominent soft tissue pathology, with minimal destruction of bone; the other 6 patients had bony alterations that resembled rheumatoid arthritis. CONCLUSION: In SLE patients with arthritis of the finger joints, MRI detects characteristic signs of soft tissue pathology (e.g., capsular swelling, edematous and proliferative tenosynovitis, synovial hypertrophy) and bony alterations (e.g., erosions, some of which are missed by conventional radiography). MRI thus helps to distinguish different types of lupus arthritis/Jaccoud's arthropathy, which allows more differentiated treatment strategies and monitoring.
15059728 Vogt-Koyanagi-Harada syndrome and keratoconjunctivitis sicca. 2004 Apr PURPOSE: To discover a relationship between Vogt-Koyanagi-Harada (VKH) syndrome and Sjögren syndrome. DESIGN: Observational case-control study. METHODS: Sixteen Italian patients with VKH syndrome and 16 controls with diffuse uveitis underwent tear analysis and rheumatologic evaluation. Biopsy specimens of the minor salivary glands were obtained or salivary gland scintigraphy was performed in patients with xerostomia. RESULTS: The Schirmer test (P <.0001), break-up time (P <.0001), the Ferning test (P <.001), and fluorescein and rose bengal staining (P <.0001) resulted in changes in VKH. Biopsy was positive in two patients and scintigraphy in four. Human leukocyte antigen DR4 was found in 68.75% of VKH cases and in 83.3% of the cases with Schirmer test less than 3 mm. CONCLUSIONS: The incidence of keratoconjunctivitis sicca was higher in VKH syndrome patients than in controls. Two patients satisfied the criteria for Sjögren syndrome, and two others had scintigraphy indicative of salivary gland involvement. The association of these two autoimmune disorders is suggested by the low incidence of VKH syndrome in Italy and might be related to HLA DR4.
14705226 Etanercept in the treatment of patients with primary Sjögren's syndrome: a pilot study. 2004 Jan OBJECTIVE: This pilot study evaluated the effect of anti-tumor necrosis factor-a antiinflammatory treatment with etanercept (Enbrel(R)) on sicca, systemic, and histological signs in patients with primary Sjögren's syndrome (SS). METHODS: Fifteen patients with well defined primary SS were treated with 25 mg etanercept subcutaneously twice per week during 12 weeks, with followup visits at Weeks 18 and 24. Evaluation measures included a Multidimensional Fatigue Inventory (MFI) questionnaire, serological monitoring, salivary flow tests, Schirmer test, rose bengal cornea staining, and tear film breakup time. A sublabial minor salivary gland biopsy was performed at baseline and at Week 12 and lymphocytic focus score and percentage IgA-containing plasma cells (IgA%) were assessed. RESULTS: No increase of salivary or lachrymal gland function was observed in any participant. In 4 patients a decrease of fatigue complaints was noted, which was also reflected by decreased scores in the MFI questionnaire. Reduced erythrocyte sedimentation rate was observed in 3 of 4 patients with reduced fatigue. No significant change of lymphocyte focus score or IgA% was observed. A repeated treatment up to 26 weeks showed the same results. CONCLUSION: A 12-week or prolonged treatment of etanercept 25 mg twice weekly did not appear to reduce sicca symptoms and signs in SS. However, etanercept treatment may be beneficial in a small subgroup of SS patients with severe fatigue. Etanercept 25 mg twice weekly did not affect minor salivary gland biopsy results.
14576992 Inclusion body myositis in connective tissue disorders: case report and review of the lite 2003 Oct We report a patient with systemic lupus erythematosus (SLE) and secondary Sjögren's syndrome (SS) who developed inclusion body myositis (IBM) which, contrary to the typical presentation of this disorder, was symmetrical in nature although the diagnosis was only made after electron microscopy was performed. Therapy with increased doses of methotrexate proved to be beneficial, with the patient having full recovery after 8 months of therapy. It appears that a subset of IBM may be related to autoimmune disorders, an issue that was disputed in the past, and these patients may have a better prognosis than typical IBM patients. This is the first case report of IBM in a patient who had the dual diagnosis of SLE and SS.
12673565 Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease: case report 2003 Mar A 46-year-old female patient with Sjögren's syndrome, hypertension, and stable chronic renal insufficiency (creatinine [CR], 1.9 to 2.1 mg/dL) had a progressive worsening of renal function (CR, 5.0 mg/dL) after 11 months of chloroquine therapy (155 mg/day; cumulative dose of approximately 51 g). Light microscopy revealed nonspecific angionephrosclerosis. Electron microscopy showed accumulations of lamellated myelinoid material and occasionally also of curvilinear bodies, especially in the glomerular podocytes and to a lesser extent in vascular myothelial and endothelial cells. In the tubular system, mainly protein droplets were stored. Activity of alpha-galactosidase A was normal in isolated leukocytes (56 nmol/mg; range, 33.2 to 109 nmol/mg), ruling out Fabry's disease. Clinical, morphological, and biochemical findings were consistent with chloroquine-associated deterioration of renal function that improved considerably after discontinuation of chloroquine treatment. Adverse effects of chloroquine may aggravate preexisting renal disease. Electron microscopy is a worthwhile tool for establishing the correct diagnosis.
12494271 A case of Sjögren's syndrome or multiple sclerosis? A diagnostic and therapeutic dilemma. 2002 Nov BACKGROUND: Primary Sjögren's syndrome (SS) with central nervous system involvement and antiphospholipid syndrome have been reported to mimic multiple sclerosis (MS). SS has also been found in patients diagnosed with definite MS. PATIENTS AND METHODS: A Chinese lady developed multiple relapsing neurological events involving the brain and spinal cord from the age of 40 years. Magnetic resonance imaging of the brain and spinal cord during acute relapses showed increased T2 signals and spinal cord edema. She later developed positive anti-nuclear antibody and anti-Ro autoantibody followed by sicca symptoms, confirming the diagnosis of SS. She died from aspiration pneumonia following pseudobulbar palsy shortly after SS was diagnosed. CONCLUSIONS: Patients with MS-like disease and autoantibodies should be carefully evaluated for other systemic autoimmune diseases as the treatment and prognosis differ from MS. In particular, sicca symptoms should be sought as they often go unnoticed by patients. This is especially important in Orientals in whom MS is relatively uncommon.
12048294 Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjögren's syndrom 2002 Jun OBJECTIVES: To examine salivary function in patients with primary Sjögren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS: We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF
11868599 Two cases of Sjögren's syndrome with multiple bullae. 2002 Feb Here, we report two rare female cases of Sjögren's syndrome with multiple bullae, involving a 66- and a 51-year-old. Neither had any obvious pulmonary complaint. Chest radiographs and high-resolution CT (HRCT) scans showed interstitial linear and nodular opacities and multiple bullae. In the first case spirometry indicated an obstructive change judged by FEV1.0 and V50/V25. In both cases, histologic examination of the lung revealed thickening of alveolar septa and interstitial mononuclear cell infiltration. In the first case the bullae decreased in size with corticosteroid treatment. Airway narrowing due to peribronchiolar mononuclear cell infiltration causes a check-valve mechanism, which may lead to bullae formation. Although a rare occurrence, it is important to recognize that cystic or bullous lung disease can accompany Sjögren's syndrome.