Search

Primary Sgögren's syndrome (SSP) is one of the most common connective tissue disorder with an estimated prevalence between 0.6 and 1.7% of the general population. Lymphocytic infiltration of salivary gland is easily accessible favoring the diagnosis, and clinical and fundamental research. However, while many advances have been obtained in the recent decades, the pathophysiology of SSP remains unclear combining environmental factors with genetic predisposition. A central role tends to be attributed to salivary gland epithelial cells, originally designated as "innocent bystanders" and to B cells through the intervention of survey factors like BAFF. New T cells subsets are also carefully studied, particularly natural T regulatory and Th17 cells. They could indeed represent new therapeutic targets., (Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: Up to 68% of patients with primary Sjögren's syndrome (pSS) undergo neurological complications, and evidence for distinct immunological subgroups is emerging. We sought to determine systemic and immunological profiles associated with neurological manifestations., Methods: 420 patients fulfilling the 2002 American-European pSS criteria were retrospectively analyzed. Neurological manifestations were diagnosed through clinical, biological, electrophysiological, and imaging findings. Biographical, clinical, and laboratory data were compared., Results: Within 93 (22%) patients with neurological manifestations, peripheral and central nervous systems were involved in 66% and 44%, respectively. Raynaud's phenomenon, cutaneous vasculitis, renal involvement, and cryoglobulinemia were associated with sensorimotor neuropathy and mononeuritis multiplex (p<0.05). Conversely, pure sensory neuropathy occurred without extraglandular manifestation, and without anti-Ro/SSA antibodies (p<0.05). All neurological manifestations were associated with increased use of corticosteroids and immunosuppressive drugs (p<0.05)., Conclusions: In pSS, patients with sensorimotor neuropathies and pure sensory neuropathies have distinct extraglandular and immunological profiles., (© 2013.)

Primary Sjögren's syndrome (pSS) is an autoimmune inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands leading to a chronic sicca syndrome. However, extraglandular organ systems may frequently be involved, including both central and peripheral nervous systems. Clinically significant neurologic manifestations affect approximately 20% of patients and may be the first manifestation of the disease in at least 25% of the cases. The spectrum of pSS-related neuropathies is wide including sensory neuropathies, neuronopathies, sensory-motor neuropathies, mononeuritis multiplex related to vasculitis… Central nervous system involvement is composed by multiple sclerosis-like manifestations including acute and chronic myelopathies and by more diffuse manifestations (cognitive dysfunction, subacute aseptic meningitis, encephalopathy, psychiatric symptoms, chorea, seizures…). The diagnosis and treatment of such pSS-related manifestations must be optimized in order to avoid severe disability., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Primary Sjogrën's syndrome (pSS) could be restricted in 50% of the cases to glandular involvement with a chronic sicca syndrome, with a considerable alteration of quality of life. It could be complicated by systemic involvements, which are responsible of the visceral severity. Thus systemic complications could appear many years after initial pSS diagnosis and justify long-term surveillance. Initial parotid gland enlargement, Raynaud phenomenon, cutaneous vasculitis and immunological abnormalities (anti-SSA and/or SSB positivity, hypergammaglobulinemia, and cryoglobulinemia) are also implicated in systemic complications.

Sjögren's syndrome is defined as an autoimmune disease characterized by a progressive sicca syndrome associated with anti-SSA or SSA positivity and/or significant infiltrate at minor salivary gland biopsy. This autoimmune disease is relatively frequent, with a clinical diagnosis among women after the 5 decade. Its physiopathology, complex, associates the intervention of both environmental and genetic factors. Salivary epithelial cell is at the center of the pathological immune response of primary Sjögren's syndrome, characterized by a chronic B cell polyclonal activation potentially leading to the development of B cell lymphoma.

Background: The aim of this paper was to study the evolution of primary Sjögren's syndrome (pSS) immunological profile, its impact on pSS activity and long-term evolution in a bicentric cohort of French patients with pSS (n = 445, mean age 53.6 ± 14 years, mean follow-up 76.1 ± 51 months)., Methods: This is a retrospective cohort study., Results: Two hundred twelve patients were Sjögren's syndrome A (SSA) positive, and 131 were both SSA and Sjögren's syndrome B (SSB) positive. Sixty-eight patients (15%) had cryoglobulinemia. Active systemic profile (i.e., hypergammaglobulinemia, rheumatoid factor (RF), and anti-Sjögren's syndrome A (anti-SSA), anti-Sjögren's syndrome B (anti-SSB) positivity), associated with multisystemic involvement, leads to an increased utilization of corticosteroid and hydroxychloroquine. Multivariate analysis pointed out independent statistical association between hypergammaglobulinemia, anti-SSA, anti-SSB, and RF. Cryoglobulinemia is associated with multi-systemic involvement, lymphoma, and pSS-related death., Conclusion: The subset of patients with active immunological profile is characterized by systemic complications leading to immunosuppressive drug utilization and polyclonal B-cell activation profile.

Purpose: About forty percent of the patients with primary Sjögren's syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy., Methods: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN., Results: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n=14), prickling (n=4), dysesthesia (n=8)] with paroxystic exacerbations (n=10) and allodynia (n=13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n=13), with a distal (n=9) and leg (n=4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n=14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n=12), mean 3.5±1.7 fibers/mm (N>6.9)] and proximal site of biopsy [(n=9), mean 7.04±2.63 fibers/mm (N>9.3)]., Conclusion: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objective: To study evolution of pSS immunological profile, impact on pSS activity and the long-term evolution of patients with atypical auto-antibodies in a bicentric cohort of patients with pSS (n=445, mean age 53.6+/-14years, mean follow-up 76.1+/-51months)., Results: 212 patients were SSA positive and 131 were both SSA and SSB positive. During follow-up, SSA antibodies disappear in 8 patients; 2 of them exhibit new systemic complications of pSS. 68 patients had cryoglobulinemia. 52 patients had other anti-nuclear antibodies (ANA) specificities: anti-RNP (n=12), anti-centromere (n=14), anti-DNA native (n=19), anti-Scl70 (n=3), anti-JO1 (n=3), anti-Sm (n=3) and anti-histone (n=1). Fourteen patients developed ANA-associated auto-immune disease during the follow-up: 5 polymyositis (mean apparition delay 78months), 6 systemic lupus erythematosus (mean occurrence delay 77months) and 2 systemic sclerosis (mean occurrence delay 133+/-64months). Among these 14 patients, only three presented atypical-ANA at pSS diagnosis. Cryoglobulinemia and anti-SSA and SSB antibodies at diagnosis were associated with new systemic involvements., In Conclusion: Cryoglobulinemia and SSA/SSB positivity are associated with systemic activity after diagnosis in pSS. Although atypical ANA are found in 12% of the cases, long-term evolution to ANA associated auto-immune diseases concerned patients with active immunological profile and extra-glandular manifestations.

Objectives: Articular manifestations (AMs) occurred in approximately 30-60% of patients with primary SS (pSS). We conducted the current study to describe clinical presentation, specific treatment and to report clinical outcome of pSS patients with AM in a large bicentric French cohort., Methods: Clinical, biological and immunological features of 419 consecutive patients with pSS were recorded in order to describe the clinical and immunological course of pSS AM and to point out the impact of those rheumatological features on pSS evolution., Results: A total of 188 patients with pSS (172 women, 16 men) exhibited AM. They preceded sicca symptoms in 32, were simultaneous to pSS diagnosis in 98 and followed diagnosis in 59 patients. Clinical presentation was polyarticular and concerned mostly peripheral joints (synovitis, n = 66). Symptoms responded readily to symptomatic treatment in 45 cases (24%). DMARDs or immunosuppressive treatments were introduced in 133 patients: HCQ (n = 111), corticosteroid (n = 53), MTX (n = 12), SSZ (n = 6), AZA (n = 3), LEF (n = 1), etanercept (n = 1) and allochrysine (n = 1). Only one case of RA was diagnosed during the evolution. Statistical analysis identified clinical and biological factors associated with AM (P < or = 0.05): RP, muscular manifestations, renal involvement, peripheral neuropathy, cutaneous vasculitis, and positivity of RF, anti-SSB antibodies and cryoglobulinaemia. Patients with AM at diagnosis were characterized by a multisystemic involvement at the end of the follow-up period (P < 0.001)., Conclusion: Although AMs are frequent and usually mild in pSS, these manifestations are associated with a pluri-systemic involvement of pSS.

Objectives: Identification of factors associated with disease activity and B and T cell activation is a challenge in primary Sjogren's syndrome (pSS). Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell activation factors seem to be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)., Methods: Samples from 18 pSS patients and 12 control subjects were studied to determine serum levels of nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their relationships with T- and B-cell activation and disease activity. Peripheral blood mononuclear cells (PBMCs) from patients with pSS and controls were examined by flow cytometry for HLA-DR expression by activated T cells. B cell activation was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme-linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain (FLC) levels., Results: Mean serum levels of BDNF in pSS patients were significantly higher than in healthy controls and correlated directly with disease activity. NGF levels were associated with the subgroup of patients with hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and CD8+ T cell activation that correlated positively with BDNF and NGF levels, respectively., Conclusion: NT levels are potential biomarkers for lymphocyte activation in pSS patients.

Objective: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient., Methods: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study., Results: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04)., Conclusion: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.

Unlabelled: Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study., Methods: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C., Results: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment., Conclusion: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.

Objective: To describe the prevalence and clinical and laboratory characteristics of sicca syndrome and Sjögren's syndrome (SS) in chronic hepatitis C virus (HCV) infection., Methods: Forty-five consecutive HCV infected patients referred for liver biopsy were enrolled in a prospective study. Subjective and objective criteria of xerophthalmia or xerostomia were systematically investigated and the patients classified according to 3 sets of criteria (European, Manthorpe, and Fox criteria) for the diagnosis of SS., Results: Sicca syndrome was present in 28 (62%) patients; all had oral dryness and 14 had both oral and ocular dryness. Twenty-four (53%) patients had SS by the European criteria, 25 (56%) by Manthorpe criteria, and 4 (8%) by Fox criteria. Salivary gland biopsy was positive for SS (grade III or IV by Chishom classification) in 21 samples (47%); 9 samples (21%) were classified grade 0, and 15 (32%) grade I or II. No patient had anti-SSA or anti-SSB antibodies. The presence of SS or sicca syndrome was associated with older age and liver disease activity according to the METAVIR scoring system, but not with the presence of other extrahepatic manifestations or with HCV genotype. A high METAVIR activity score was only statistically associated with primary SS., Conclusion: HCV infection appears to account for a subgroup of patients with sicca syndrome in which half the cases meet the definition for SS according to European and Manthorpe criteria. This subgroup is characterized by the constant finding of xerostomia, the absence of classical systemic manifestations observed in primary SS, and the absence of anti-SSA or anti-SSB antibodies. Such characteristics delineate a distinctive, virus associated entity that differs from primary SS.

Purpose: The aim of our study was to investigate the frequency of auto-immune diseases in patients suffering from autoimmune thyroid diseases., Method: We realised a retrospective study from 1981 to 1993 including 218 patients suffering from thyroiditis who were followed in the same hospital service. There were 202 women and 16 men with a mean age 49 at the moment their thyroid pathology was discovered., Results: Thirty patients had one or more autoimmune disease associated to their thyroid disorders, representing 13.7% of total patients. The two most frequent autoimmune diseases were lupus and Sjögren's syndrome. In 17 cases the diagnosis of the associated autoimmune disease was made simultaneously. The systemic disease preceded with an 8-year delay the thyroid disease in five cases, and the thyroid disease was annunciatory in eight cases with a delay of 5 years. The frequency of autoimmune diseases seems to be higher in patients suffering from thyroid disorders than in the general population. They are probably common physiopathological mechanisms., Conclusion: The frequency of these associations suggests the need for a long-lasting survey of those patients having thyroid disorders. Initial evaluation and a regular checking in patients suffering from an autoimmune disease is recommenced.

Seventy-two cases of primary Sjögren's syndrome, according to the European classification criteria, were studied looking for a correlation between anatomic criteria and clinico-biological signs in this disease. Labial salivary gland biopsy was performed in all patients and anatomic criteria were evaluated according to both Chisholm and Chomette scales. Work-up included recording of functional and clinical signs. Our study shows no clinico-histological correlation in Sjögren's syndrome. Moreover, we did not find any correlation between the two histological scales. We think, therefore, that labial salivary gland biopsy appears to be an important step in Sjögren's syndrome diagnosis according to European criteria. However, it does not present any benefit in patient treatment.

The aim of this study was to evaluate the role of human herpesvirus-6 (HHV-6) in the development of primary Sjögren's syndrome (PSS). Serum HHV-6 antibody levels, as measured by immunofluorescence assay (IFA) and the prevalence of HHV-6 DNA in peripheral blood mononuclear cells (PBMCs) determined by polymerase chain reaction (PCR), were studied in 49 PSS patients and 50 control subjects, all in-patients in the University Hospital Internal Medicine ward, Limoges, France. In addition, portions of labial salivary gland were obtained from 34 patients and 15 controls, the presence of viral DNA being detected by the same PCR technique. The results were then compared with clinical observations of systemic disease manifestations in patients and a histological study of salivary gland involvement. No significant difference in HHV-6 seroprevalence was found between control subjects (50.0%) and patients (63.3%) nor was there any statistically significant difference between patient and control groups for total viral DNA in PBMCs (22.4%, 12.0%) and salivary glands (8.8%, 6.6%). Analysis of clinical and histological data revealed no detectable correlation between disease severity and viral involvement. Tests for HHV-6A and HHV-6B proved positive in patient and control groups, HHV-6B being the most frequently encountered type in both groups. In conclusion, the results of this large-scale trial does not confirm the suspected direct role of HHV-6 in the etiology of PSS.

Forty-eight patients with primary Sjögren syndrome are documented together with the results of their baseline investigations. The majority of patients were female (44 out of 48) and mean age was 63.2 years. Common clinical features included 20 parenchymal lung disease, among which 4 had interstitial pulmonary fibrosis and 2 lymphocytic interstitial pneumonitis, 12 neurologic manifestations, 16 Raynaud's phenomenon, 12 arthritis, and 3 gastrointestinal involvement. Haematological features occurred in 15 patients and another autoimmune disease was encountered in 13 cases. These extraglandular manifestations were the dominating reasons for hospital referral in 43.5% of cases, the sicca syndrome were most often only mentioned by the patients after special questioning which explain considerable delay before the diagnosis.

Abstract: Purpose: About forty percent of the patients with primary Sjögren''s syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy. Methods: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN. Résults: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n =14), prickling (n =4), dysesthesia (n =8)] with paroxystic exacerbations (n =10) and allodynia (n =13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n =13), with a distal (n =9) and leg (n =4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n =14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n =12), mean 3.5±1.7 fibers/mm (N >6.9)] and proximal site of biopsy [(n =9), mean 7.04±2.63 fibers/mm (N >9.3)]. Conclusion: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown. [Copyright &y& Elsevier]