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ID PMID Title PublicationDate abstract
16715039 [Prolactin in connective tissue diseases]. 2006 This paper presents interactions between prolactin (PRL) and the immune system. We describe the role of PRL in the pathogenesis of rheumatic diseases, particularly connective tissue diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome, systemic sclerosis, polymyalgia rheumatica, and seronegative arthritis. We present current opinion on the mechanisms responsible for hyperprolactinemia in SLE patients and the association between hyperprolactinemia and SLE activity and organ involvement. The role of dopamine receptor agonists in the treatment of connective tissue diseases is discussed.
16582691 Role of adhesion molecules in synovial inflammation. 2006 May PURPOSE OF REVIEW: The ability of cells to adhere to other cells and extracellular matrix (ECM) through cellular adhesion molecules (CAMs) is central to tissue remodeling and inflammation. This review discusses the potential role of CAMs in development of synovial inflammation through regulating the recruitment of inflammatory cells via endothelial-leukocyte interactions, the organization and activation of leukocytes in the synovial sublining, and the formation and behavior of the hyperplastic synovial lining. RECENT FINDINGS: Over the past several years valuable insight has been gained into the role of cell-cell and cell-ECM adhesive interactions in synovial organization and inflammation. Recently, cadherin-11 was identified on fibroblast-like synoviocytes and has been demonstrated to play a central role in synovial lining organization. Furthermore, studies using animal models of inflammatory arthritis have demonstrated critical roles for E- and P-selectins, CD11a/CD18 [lymphocyte function-associated antigen (LFA)-1], alpha4beta1 integrin, and cadherin-11 in the development of synovial inflammation. SUMMARY: Cell-cell and cell-ECM interactions through CAMs play an important role in synovial inflammation. Future studies of CAMs are needed to define more thoroughly their role in synovial inflammation and their potential as therapeutic targets in the treatment of rheumatoid arthritis and related inflammatory arthritic conditions.
21794232 [Perception of sexuality in women with rheumatic disease: case-control pilot study]. 2005 Jun INTRODUCTION: Rheumatic diseases are characterized by chronic inflammation with systemic involvement and are often accompanied by functional limitation and depression. Their effect on sexual response has been little studied. The objective of the present study was to evaluate perception of sexuality in women with rheumatic disease. PATIENTS AND METHODS: We administered a questionnaire that included general data, socioeconomic aspects, disease characteristics, serum markers of inflammation and measured perception of sexuality, depression traits and self-esteem. RESULTS: Sixteen patients were interviewed, of which nine had rheumatoid arthritis, six had systemic lupus erythematosus and one had psoriatic arthritis. Twentyfive women were selected as controls. All patients were receiving treatment and had a functional class that allowed them to be self-dependent. Patients presented a worse perception of sexuality than controls (p=0.001) with a trend to more depressive traits and lower self-esteem. CONCLUSIONS: Patients with rheumatic disease gain benefits from treatment in terms of quality of life and functionality. Perception of sexuality is affected by chronic inflammatory disease but is independent of the patient's functional class.
16646024 Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthriti 2006 May OBJECTIVE: Intraarticular corticosteroids are frequently used as successful adjuvant therapy for inflammatory arthritides, but little is known about their effects on molecules that regulate bone biology. We undertook this study to investigate the effect of intraarticular corticosteroids on the synovial expression of RANKL and osteoprotegerin (OPG). METHODS: We evaluated RANKL, OPG, and surface marker expression by immunohistochemical methods in synovial knee biopsy samples obtained from 13 patients with inflammatory arthritis before and 2 weeks following intraarticular injection of triamcinolone hexacetonide. We further investigated the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL and OPG expression in osteoblast-like cells, by Western blotting. RESULTS: Intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages, evaluated as both CD68+ and CD163+ cells. This change was paralleled by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL:OPG ratio. DEX down-regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro pretreatment of osteoblast-like cells with tumor necrosis factor favored an antiresorptive effect of DEX treatment through a similar down-regulation of RANKL expression. CONCLUSION: The decrease in inflammation attributed to intraarticular corticosteroids is accompanied by down-modulation of bone destruction markers. These findings offer a rationale for the beneficial effect of corticosteroids on joint erosion in arthritis.
16941192 Enhanced MR imaging of tenosynovitis of hand and wrist in inflammatory arthritis. 2006 Nov OBJECTIVE: The purpose of this study is to describe the appearance of tenosynovitis in various tendon groups in the wrist and hand and to compare MR enhanced and non-enhanced imaging evaluation of tenosynovitis of hand and wrist in inflammatory arthritis. DESIGN AND PATIENTS: We reviewed 72 MRI studies of hands and wrists, including coronal, axial and sagittal images in 30 consecutive patients with inflammatory arthritis and tenosynovitis. We compared the degree of synovitis on T2-weighted vs contrast-enhanced T1-weighted images, using a predetermined scale. We also measured the extent of tenosynovitis in three dimensions. The tendons were assigned to volar, dorsal, ulnar and radial groups in the wrist and to extensor, flexor and thumb groups in the hand. Degree of tenosynovitis (graded 0-3), cross-sectional area and volume of the inflamed synovium in various tendon groups were then compared by statistical analysis. RESULTS: Review of the medical records revealed the following diagnoses in our patient population: rheumatoid arthritis (n=16), unspecified inflammatory polyarthritis (n=9), psoriatic arthritis (n=2), CREST syndrome (n=1), systemic lupus erythematosus (n=1), paraneoplastic syndrome with arthritis (n=1). The average T2 brightness scores and post-gadolinium enhancement scores were 1.0 and 1.7, respectively (P<0.001) in the wrist studies. The average T2 brightness scores and post-gadolinium enhancement scores were 0.7 and 1.4, respectively (P<0.001) in the hand studies. The average sensitivity of T2-weighted imaging for detection of tenosynovitis was 40% in the hand and 67% in the wrist tendons, when contrast-enhanced images were used as a reference. Carpal tunnel flexor tendons were the most frequently affected tendons of the wrist. The most frequently affected tendons of the hand were second and third flexor tendons. The hand flexors demonstrated higher degrees of enhancement and larger volumes of the inflamed tenosynovium than did the hand extensors and tendons of the thumb. CONCLUSION: Enhanced MR imaging of the hand and wrist is a superior technique for detection of tenosynovitis. We observed carpal tunnel flexor tendons to be the most frequently affected tendons of the wrist. The flexor tendons of the second and third digits were the most frequently affected tendons of the hands. Higher contrast-enhancement scores and inflammation were noted in the hand flexor than in the extensor tendons.
16855167 DHEA metabolism in arthritis: a role for the p450 enzyme Cyp7b at the immune-endocrine cro 2006 Jun For dehydroepiandrosterone (DHEA) both immunosuppressive and immuno-stimulating properties have been described. The immunosuppressive effects may be explained by the conversion of DHEA into androgens and/or estrogens. The described immuno-stimulating effects of DHEA may be due to the conversion of DHEA into 7alpha-hydroxy-DHEA (7alpha-OH-DHEA) by the activity of the p450 enzyme, Cyp7b. 7alpha-OH-DHEA is thought to have anti-glucocoticoid activity preventing the anti-inflammatory action of endogenous glucocorticoids. To investigate a putative role of Cyp7b in the arthritic process, tissues from both the murine collagen-induce arthritis (CIA) model and from patients with rheumatoid arthritis (RA) were studied. We determined the Cyp7b expression levels in synovial tissue and the level of 7alpha-OH-DHEA in both serum and arthritic joints of mice with CIA. Our studies showed that the severity of arthritis correlates with increased Cyp7b activity. Next, we investigated Cyp7b expression and activity in RA patients where the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are known to control the disease process. Fibroblast-like synoviocytes (FLS), isolated from RA synovial biopsies were found to express Cyp7b mRNA. In addition, Cyp7b enzymatic activity was detected in these cells. We also investigated whether Cyp7b activity is regulated by cytokines. Proinflammatory (e.g., TNF-alpha and IL-1beta) cytokines were found to stimulate Cyp7b activity and the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta) was found to suppress Cyp7b activity in FLS. Next, we studied which signal transduction pathway is involved in the TNF-alpha-mediated induction of Cyp7b activity in human FLS. The results show a role for nuclear factor kappa B (NFkappaB) and activator protein-1 (AP-1) in the regulation of Cyp7b expression. Finally, we established that the effects of DHEA or 7alpha-OH-DHEA on the immune system can not be explained by glucocorticoid receptor (GR) engagement. The role of the p450 enzyme Cyp7b in DHEA metabolism and its relevance in the arthritic process will be discussed.
16736518 Surface-bound anti-type II collagen-containing immune complexes induce production of tumor 2006 Jun OBJECTIVE: Type II collagen (CII) is a major component of hyaline cartilage, and antibodies against CII are found in a subgroup of patients with rheumatoid arthritis. We undertook this study to investigate whether and how antibodies directed against CII can form solid-phase immune complexes (ICs) with cytokine-inducing properties in a model theoretically resembling the situation in the inflamed joint, in which CII is exposed for interaction with anti-CII antibodies during periods of inflammation. METHODS: Sixty-five arthritis patients with varying levels of anti-native CII antibodies and 10 healthy controls were evaluated concerning anti-CII and cytokines induced in a solid-phase IC model. Monocytes were either depleted or enriched to define responder cells. Antibodies blocking Fc gamma receptors (Fc gammaR) were used to define the responsible T cell surface receptors. RESULTS: ICs containing anti-CII from arthritis patients induced the production of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-8. We found a close correlation between enzyme-linked immunosorbent assay optical density values and induction of TNFalpha (r = 0.862, P < 0.0001), IL-1beta (r = 0.839, P < 0.0001), and IL-8 (r = 0.547, P < 0.0001). The anti-CII-containing IC density threshold needed for cytokine induction differed among peripheral blood mononuclear cell donors. Anti-CII-containing IC-induced cytokine production was almost totally abolished (>99%) after monocyte depletion, and receptor blocking studies showed significant decreases in the production of TNFalpha, IL-1beta, and IL-8 after blocking Fc gammaRIIa, but not after blocking Fc gammaRIII. CONCLUSION: These findings represent a possible mechanism for perpetuation of joint inflammation in the subgroup of arthritis patients with high levels of anti-CII. Blockade of Fc gammaRIIa and suppression of synovial macrophages are conceivable treatment options in such patients.
16762145 Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune 2006 Mar OBJECTIVE: To determine the usefulness of plasma procalcitonin (PCT) measurement to suspect infectious etiology in febrile patients with systemic autoimmune disease. METHODS: PCT, C-Reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) were measured in 44 consecutive inpatients with a diagnosis of systemic autoimmune disease and fever >38 masculine C. After careful microbiologic screening no obvious infection was demonstrated in 24 patients (Group A) while an infectious bacterial complication was diagnosed in 20 cases (Group B). RESULTS: Median PCT levels were significantly higher in the group B (1.11 vs 0.24 ng/ml; p = 0.0007), whereas the differences for CRP, WBC and ESR did not reach statistical significance. PCT also exhibited a good sensitivity and specificity (75%) in differentiating patients with infection from those with disease flare. With respect to positive and negative predictive values (71.4% and 78.2%), PCT markedly exceeded the other variables. By analyzing PCT values by disease we identified a false positive subgroup of patients suffering from adult onset Still's disease (AOSD), showing markedly elevated PCT levels in absence of infection. By excluding these patients, PCT showed a very good sensitivity and specificity (73.6% and 89.4%) and the area under receiver operating characteristics (ROC) curve rose from 0.801 to 0.904. CONCLUSION: Our data indicate that elevated PCT concentrations offer good sensitivity and specificity for the diagnosis of systemic bacterial infection in febrile patients with systemic autoimmune diseases. However, in fever associated with AOSD PCT may be elevated even in the absence of infectious complication.
16522680 Identification of parotid salivary biomarkers in Sjogren's syndrome by surface-enhanced la 2006 Sep OBJECTIVES: To identify the most significant salivary biomarkers in Sjögren's syndrome (SS) using proteomic methods. METHODS: Parotid saliva from 20 non-SS subjects and 41 primary SS patients was analysed. Protein expression profiles for each sample were generated by surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry (SELDI-TOF-MS). Mean peak intensities of SS patients and non-SS subjects were compared by univariate analyses. Samples pooled by diagnosis (SS and non-SS) and labelled with different Cy dyes were compared by two-dimensional difference gel electrophoresis (2D-DIGE). Two protein levels that were most significantly different by SELDI-TOF-MS and 2D-DIGE were validated by enzyme-linked immunosorbent assay in individual samples. RESULTS: SELDI-TOF-MS of 10-200 kDa peaks revealed eight peaks with >2-fold changes in the SS group that differed from non-SS at P < 0.005. Peaks of 11.8, 12.0, 14.3, 80.6 and 83.7 kDa were increased, while 17.3, 25.4, and 35.4 kDa peaks were decreased in SS samples. 2D-DIGE identified significant increases of beta-2-microglobulin, lactoferrin, immunoglobulin (Ig) kappa light chain, polymeric Ig receptor, lysozyme C and cystatin C in all stages of SS. Two presumed proline-rich proteins, amylase and carbonic anhydrase VI, were reduced in the patient group. Three of these ten biomarkers have not been associated previously with SS. CONCLUSIONS: The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS.
16341369 [Viral Tax protein expression in salivary glands of patients infected with human t-cell ly 2005 Oct BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. AIM: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. MATERIAL AND METHODS: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. RESULTS: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. CONCLUSIONS: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.
16251389 Immune-related conditions and immune-modulating medications as risk factors for non-Hodgki 2005 Dec 15 In immunosuppressed or autoimmune disease states, disordered immune responses may lead to non-Hodgkin's lymphoma (NHL). In a US population-based case-control study of NHL (1998-2000), the authors collected personal histories of immune-related conditions and use of immune-modulating therapies as well as family histories of autoimmune conditions. The study included 1,321 NHL cases and 1,057 controls; only half received some questionnaire components. NHL was associated with Sjögren's syndrome (odds ratio (OR) = 13, 95% confidence interval (CI): 1.7, 100) and lupus (OR = 4.2, 95% CI: 1.2, 15). Two specific NHL subtypes were strongly associated with Sjögren's syndrome: salivary gland (OR = 290, 95% CI: 33, 2600) and marginal zone (OR = 75, 95% CI: 9.1, 610). NHL was less convincingly associated with receipt of an organ transplant (OR = 2.0, 95% CI: 0.4, 11). Other autoimmune conditions were too rare to evaluate or not associated with NHL. Corticosteroid use was unrelated to NHL (OR = 1.0, 95% CI: 0.8, 1.2), but methotrexate use was marginally associated (OR = 2.3, 95% CI: 0.7, 7.5). Family history of dermatomyositis was associated with NHL (7 cases vs. 0 controls, OR = infinite; two-sided p = 0.02), but dermatomyositis was absent in cases themselves. Family history of remaining conditions was unrelated to NHL. Results suggest that disordered immunity in some immune-related conditions can lead to NHL.
16234994 A case of cutaneous polyarteritis nodosa manifested by spiking high fever, arthralgia and 2006 May A 24-year-old Japanese woman was admitted for investigation of recurrent spiking high fever associated with a macular eruption of the upper extremities associated with fever and polyarthralgia. These symptoms were self-limiting but recurrent and seemed to be consistent with a diagnosis of adult-onset Still's disease (AOSD). However, livedo reticularis was detected on the lower extremities, suggesting the presence of vasculitic disease rather than AOSD. Investigation did not reveal any evidence of visceral involvement. Skin biopsy of the affected lower extremity demonstrated a necrotizing vasculitis of small muscular artery and confirmed a diagnosis of cutaneous polyarteritis nodosa (PAN) rather than AOSD. Treatment with 30 mg of prednisolone daily improved the skin lesions and the recurrent spiking high fever and the arthralgia were resolved. PAN and AOSD are clinically similar, and discrimination may be sometimes difficult. The presence of livedo reticularis and the finding of a characteristic skin biopsy appearance may be diagnostically useful to distinguish PAN from AOSD. Indeed, the clinical features of cutaneous PAN may be more similar to AOSD than systemic PAN, and a skin biopsy may be necessary to distinguish cutaneous PAN from AOSD in some cases.
13680143 Protein kinase C expression in salivary gland acinar epithelial cells in non-obese diabeti 2005 Jan We planned to investigate the expression of protein kinase C (PKC) isoforms in acinar epithelial cells of salivary glands in the non-obese diabetic (NOD) mouse to find out if they develop changes of the PKC system like those seen in the human counterpart, i.e. in Sjögren's syndrome. Parotid, submandibular, and sublingual glands from NOD and control BALB/c mice were stained with a panel of monoclonal antibodies directed against conventional (alpha, beta, and gamma), novel (delta, epsilon, and theta), and atypical (lambda and iota) PKC isoforms using the streptavidin/HRP method. Similarly to human labial salivary glands, acinar epithelial cells of the healthy control BALB/c mice contained two of the conventional PKC isoforms, alpha and beta. Acinar and ductal epithelial cells also contained the atypical PKC isoforms lambda and iota. PKC isoforms gamma, delta, epsilon, and theta were not found. NOD mice which displayed focal sialadenitis contained the same conventional and atypical PKC isoforms. The acinar cells in NOD mice, in contrast to the Sjögren's syndrome patients, did not lack PKC alpha or beta. On the contrary, PKC alpha and beta staining was stronger than in the control BALB/c mice. The present results demonstrate that both conventional and atypical PKC isoforms participate in the salivary epithelial cell biology and that there are mouse strain-associated and/or disease state-associated changes in their expression. The lack of PKC alpha and beta isoforms found in Sjögren's syndrome was not reproduced in NOD mice, which discloses one more difference between the human disease and its NOD mouse model.
15819815 Sjögren's syndrome. 2005 Apr Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands, primarily the salivary and lacrimal glands. It has been suggested that exogenous agents may trigger SS in genetically predisposed individuals. However, at present, the etiology of SS is far from being understood, and no direct evidence for any of these triggers has been presented. The salivary and lacrimal glands from patients with SS harbor unique and highly selected T- and B-cell populations. Disturbance in glandular cell apoptosis may be one possible explanation for the sicca symptoms in SS. However, discrepancies between glandular destruction and salivary flow give rise to processes causing glandular dysfunction preceding or triggering glandular cell destruction. Recent reports suggested autoantibodies inhibiting neuronal innervation of acinar cells and defective water transport to be implicated in salivary secretion deficiency observed in SS. Several types of autoantibodies have been suggested to contribute to the pathogenesis of SS. However, how the tolerance to these structures is broken down is unknown at present. Studies on B-cell activating factor indicated that diminished apoptosis and disturbed B-cell maturation could be responsible for the occurrence of autoreactive B-cells and B-cell hyperreactivity. B-cell activation may also provide a basis for lymphoma development observed in up to 5% of the patients with SS.
17156671 [Clinical features of undifferentiated connective tissue diseases: analysis of 145 patient 2006 Sep 19 OBJECTIVE: To investigate the clinical features and prognosis of undifferentiated connective tissue disease. (UCTD) METHODS: 1105 connective tissue disease (CTD) patients, including 751 cases of systemic lupus erythrematosus (SLE), 63 cases of systemic sclerosis (SSc), 103 cases of polymyositis/dermatomyositis (PM/DM), 159 cases of primary Sjögren's syndrome (pSS), and 29 cases of overlap syndrome (29), were randomly selected. The clinical data of these patients were analyzed to identify those who displayed the manifestations of UCTD as the onset manifestations so as to summarize the clinical manifestation, immunological parameters, and long term development of UCTD. RESULTS: These 145 patients with UCTD developed SLE, SSc, SS, PM/DM, or overlap syndrome within two to five years. The patients with arthritis and arthralgia often developed into SLE. Raynaud's syndrome was often related to SSc. The patients with rash or face edema were more likely turned out to be PM/DM patients. The patients with dry eyes or dry mouth often developed into pSS patients. CONCLUSION: UCTD can develop into various autoimmune diseases, such as SLE, SSc, pSS or PM/DM. Some clinical features of onset are related with the outcome.
15988601 Polymyalgia rheumatica in primary Sjögren's syndrome. 2006 Mar The aim of the study was to describe the clinical and laboratory aspects of primary Sjögren's syndrome (pSS) associated with polymyalgia rheumatica (PMR). The retrospective study compares the clinical and laboratory aspects of patients with pSS associated with PMR on a relatively large cohort of patients (n=16) and pSS patients without PMR (n=531). The prevalence of PMR among pSS patients was 3%, while in the average population, the prevalence of PMR is only 0.75%. PMR developed 8.7 years after the diagnosis of pSS in the older female pSS population (over 50 years of age), and in those with only glandular features. Interestingly the pSS/PMR patients had hypo gammaglobuline levels, while in the pSS patient group hypergammaglobulinaemia presented. Furthermore, positive ANA serology was more frequent among pSS/PMR patients. Since the clinical management of pSS/PMR is different from pSS, a better understanding of this clinical entity is essential.
15848148 Influence of the time of measurement of unstimulated human whole saliva on the diagnosis o 2005 Jun OBJECTIVE: An unstimulated whole saliva flow rate (UWSFR) of less than 0.1 mL/min is often related to symptoms of dry mouth. It is also used as a diagnostic criterion for Sjogren's syndrome, and for assessment of hyposalivation as a caries risk factor. The main hypothesis was that the circadian rhythm of salivary flow affects this diagnosis if saliva is collected at different morning time-points. DESIGN: UWSFR was tested at 7:30 and 11:30 a.m. in 108 individuals, age 15-46 years (mean 33+/-9). The participants were allocated to one of three groups (very low< or =0. 1/min, low 0.1-0.2 mL/min and normal>0.2 mL/min) based on the UWSFR at 7:30 a.m. Different aspects of the perception of oral dryness were rated using Visual Analog Scales. RESULTS: All three groups displayed a statistically significant increase in UWSFR at 11:30 a.m. compared with 7:30 a.m., all of similar magnitude (0.08-0.09 mL/min). In the group with very low UWSFR, 70% at 11:30 a.m. exceeded the 0.1 mL/min limit. There were significant difference in perception of oral dryness between the normal group and both the low and the very low groups. Only the subjects in the groups with a low or very low UWSFR perceived an increase in oral wetness at 11:30 a.m. CONCLUSIONS: It was concluded that the time of measurement strongly influences the diagnosis of hyposalivation. To control the influence of variations in the time of saliva collection, we suggest that unstimulated whole saliva tests are performed at a fixed time-point or in a limited time interval early in the morning.
16287920 Clinical significance of quantitative immunohistology in labial salivary glands for diagno 2006 Apr OBJECTIVES: Because patients with primary Sjögren's syndrome (pSS) are at risk of developing other autoimmune phenomena and malignant lymphoma, it is important to distinguish pSS from non-Sjögren's (nSS) sicca syndrome. However, this distinction might be difficult because of the lack of a gold standard for pSS. We studied the clinical significance of quantitative immunohistology (QIH) in labial salivary glands for diagnosing pSS. METHODS: In a model mimicking the making of a clinical diagnosis, five experts diagnosed 396 patients as nSS, 'indefinite', pSS or secondary SS (sSS) using 25 clinical parameters. Patients were diagnosed twice, namely without (yielding gold-standard diagnoses) and with knowledge of QIH. The numbers of changes in diagnosis from 'indefinite' to 'definite' (nSS, pSS or sSS) or vice versa were compared. Patient groups with vs without a changed diagnosis in the four gold-standard diagnosis groups were compared regarding objective autoimmune parameters. RESULTS: Sensitivity, specificity, positive and negative predictive value for abnormal QIH in pSS vs nSS were 93, 86, 76 and 96%, respectively. Changes in diagnosis from 'indefinite' to 'definite' (31%) were found more often (P = 0.00) than changes from 'definite' to 'indefinite' (10%). Knowledge of QIH distinguished patient groups within the gold-standard nSS, indefinite and pSS patient group with regard to autoimmune parameters. CONCLUSION: In view of the consequences of distinguishing pSS from nSS, these results point to an additional diagnostic role for QIH in clinical practice.
15818699 Sustained benefits of infliximab therapy for dermatologic and articular manifestations of 2005 Apr OBJECTIVE: To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). METHODS: One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. RESULTS: The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. CONCLUSION: Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.
17006270 Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term me 2006 Sep We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus and the viral DNA was monoclonal. She achieved complete remission after MTX withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis receiving low dose MTX therapy.