Extraglandular Disease Research Articles

Clinical and Cost Burden of Primary Sjögren's Syndrome: Descriptive Analysis Using a US Administrative Claims Database.

Background: Current knowledge of the disease burden of primary Sjögren’s syndrome (pSS) is limited.Objectives: The primary objective of this study was to describe the demographic and clinical characteristics of patients with pSS. The secondary objective was to describe the treatment patterns and healthcare resource utilization of patients with pSS. Furthermore, clinical characteristics of interest were described and the proportions of patients with glandular versus extra-glandular disease were reported.Methods: This was a retrospective cohort study (HO-15-16077) conducted in the US Truven MarketScan Commercial database. We report descriptive data from employees and their families, as covered by employer-sponsored medical insurance. The primary cohort comprised patients with pSS (with ≥1 diagnosis of sicca syndrome prior to January 1, 2013), with continuous enrollment for ≥24 months (January 1, 2012–December 31, 2013). Patients with conditions mimicking sicca symptoms not due to SS were excluded, as were those with connective tissue disease that may have suggested secondary SS. To compare the healthcare burden of patients with and without sicca symptoms, a 1:1 matched comparator population comprising subjects without a previous diagnosis of sicca syndrome (sicca-free) was also identified.Results: There were 12 717 eligible patients in the primary cohort. The majority (86%) was female and the mean age was 51 years. Overall, 60.7% of patients had claims associated with pSS extra glandular disease manifestations. These patients experienced a higher disease burden, and more commonly reported pain, fatigue or insomnia and any combination of pain, fatigue or insomnia (41.3%) compared with patients with glandular disease only (12.4%). Patients in the primary cohort incurred greater annual healthcare service costs (1.6 times greater, all causes) and healthcare resource utilization compared with the sicca-free comparator cohort. Patients with extra glandular disease also incurred greater average annual costs (2.9 times) contributing to ≥2 times/year more resource use for outpatient services than patients with glandular disease only.Conclusion: Patients with pSS experience a high disease burden despite treatment. This study provides novel insights in to the extent of the burden on healthcare resources among patients with pSS, in particular for patients with extra-glandular disease manifestations, when compared with sicca-free subjects.

Systemic manifestations of primary Sjögren's syndrome in the NOD.B10Sn-H2b/J mouse model

Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2b/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD.B10 female mice at early and late disease time points. To this end, sera, exocrine tissue, lung, and kidney were analyzed. NOD.B10 mice have robust lymphocytic infiltration of salivary and lacrimal tissue. In addition, they exhibit significant renal and pulmonary inflammation. We identified numerous autoantibodies, including those directed against salivary proteins. In conclusion, the NOD.B10 model recapitulates both local and systemic pSS disease and represents an excellent model for translational studies.

SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome

ObjectivesTo evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS).Methods31 patients fulfilling the American-European...

Thyroid Carcinoma Pattern Presentation According to Age.

Introduction Patients with thyroid cancer in different age groups present with different prognosis. Objective The objective of this study is to analyze the clinicopathological pattern of thyroid carcinoma presentation according to age groups. Methods This is a retrospective study. From 2000 to 2010, 623 patients underwent thyroidectomy for cancer in our institution, with 596 enrolled. Patients were divided into groups of 10 years and then in four age subgroups (≤ 24, 25–44, 45–64, and ≥65 years) for statistical analysis. We compared age, gender, and histopathological characteristics between groups. Results Individuals belonging to the earlier age group presented with a highest prevalence of neuro-vascular invasion, capsular invasion and lymph node metastasis. Together with individuals of advanced age, that group also had larger tumor diameter and higher prevalence of extra-glandular disease. Even when analyzed only cases with well-differentiated carcinoma, younger individuals remain with a highest prevalence of lymph node metastasis, neuro-vascular invasion and larger tumor diameter. Conclusion We observed a distinct pattern of clinicopathological manifestation of thyroid cancer according to age. Individuals belonging to age extremes resemble in several pathological features, and young people usually present with more aggressive disease characteristics.

Salvage prostate cryoablation for recurrent localized prostate cancer after radiotherapy

Salvage prostate cryoablation (SCA) for recurrent localized prostate cancer after radiotherapy has been studied in Western countries for more than a decade. We present our experience of SCA in a Taiwanese medical center. We performed four cases of SCA for recurrent localized prostate cancer after radiotherapy. The data recorded included age, cancer stage, prostate-specific antigen (PSA) level, Gleason score, prostate volume and patient outcome. The median follow-up period was 17 months. All cases were biopsy-proven to have residual cancer before cryoablation. After SCA, 25% of the patients reached undetectable PSA levels, 50% showed response but did not reach undetectable levels, and 25% showed no decrease in PSA. The median recurrence-free duration after SCA was 18 months in the patients who experienced a decrease in PSA. ADT was initiated after SCA for the patient who did not show any response, and bone metastasis was later diagnosed in that patient. Most patients experienced obstructive voiding problems after SCA, which improved over time. SCA is a safe salvage option for prostate cancer patients with local recurrence after RT. The preliminary results are encouraging. More extensive imagery to exclude extra-glandular disease is warranted before SCA. A longer follow-up period and larger sample size are necessary to delineate the benefits more conclusively.

English

Sjogren syndrome is an autoimmune exocrinopathy with various extra glandular manifestations. Cryoglobulinemia, small vessel vasculitis has been reported in 5-10% of patients with primary Sjogren syndrome. It may be associated with a higher prevalence of extra glandular disease in Sjogren patients. Thrombotic microangiopathy (TMA), a potentially lethal condition characterized by microvascular thrombosis due to endothelial injury, is rare in SS. Its most characteristic histological finding is intravascular and intraglomerular fibrin thrombi. The association of Sjogren syndrome, cryoglobulinemia and thrombotic microangiopathy has not been previously reported. We report the first case of Sjogren syndrome with these three manifestations, occurring in combination.

Primary Sjögren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients

The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization. Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression. The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions. This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is ∼15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.

Childhood Sjögren syndrome

Sjögren syndrome is a chronic autoimmune disease affecting lacrimal and salivary glands that often is accompanied by extraglandular disease manifestations. Although common in adults, the prevalence and prognosis of childhood Sjögren syndrome are unknown, in part due to lack of child-specific diagnostic and classification criteria. This review discusses difficulties in diagnosing childhood Sjögren syndrome and highlights recent findings in Sjögren syndrome treatment and pathogenesis from studies in adults and animal models over the past 18 months. Studies of rituximab show some therapeutic potential in adult Sjögren syndrome, whereas newer modalities including gene therapy and mesenchymal stem cell transfer are promising. The pathogenesis of Sjögren syndrome is emerging, including roles of T and B lymphocytes, autoantibodies, interferons, and glandular epithelial cells. Specific recent notable findings in Sjögren syndrome pathogenesis include identification of a type II interferon signature in salivary glands of Sjögren syndrome patients, characterization of salivary gland-infiltrating T-cell subsets, and characterization of antimuscarinic acetylcholine receptor type 3 autoantibodies. Childhood Sjögren syndrome is a poorly defined and underdiagnosed autoimmune disease that requires child-specific criteria in order to study disease burden and prognosis. Studies in adults and animal models continue to elucidate new potential diagnostic and therapeutic targets, which may be relevant for childhood Sjögren syndrome. http://links.lww.com/COR/A3.

AB0394 Free light chains in sjögren’s syndrome: correlations with eular scores, depression, and quality of life: a prospective cross-sectional study

BackgroundPrimary Sjögren’s syndrome (pSS), a chronic and slowly progressive autoimmune disease, is characterised by lymphocytic infiltration of the exocrine glands characteristically leading to xerostomia and keratoconjunctivitis sicca[1]. Furthermore, the disease...

Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjögren’s syndrome

Background/purposePrimary Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by extraglandular disease and increased prevalence of lymphoma. Environmental and hormonal factors, such as vitamin-D may play a role in the pathogenic process and disease expression. Thus, we aimed to evaluate levels of vitamin-D and their association with manifestations of SS. MethodsVitamin-D levels were determined in 176 primary SS patients and 163 matched healthy volunteers utilizing the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). A correlation between vitamin-D levels and clinical and serological manifestations of SS was performed. ResultsMean vitamin-D levels were comparable between SS patients and control 21.2 ± 9.4 ng/ml and 22.4 ± 10 ng/ml, respectively. Peripheral neuropathy was diagnosed in 23% of SS patients and associated with lower vitamin-D levels (18.6 ± 5.5 ng/ml vs. 22.6±8 ng/ml (p = 0.04)). Lymphoma was diagnosed in 4.3% of SS patients, who had lower levels of vitamin-D (13.2 ± 6.25 ng/ml), compared to SS patients without lymphoma (22 ± 8 ng/ml), (p = 0.03). Other clinical and serological manifestations did not correlate with vitamin-D status. ConclusionsIn this study, low levels of vitamin-D correlated with the presence of peripheral neuropathy and lymphoma among SS patients. The link between vitamin-D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin-D in the pathogenesis of these processes. Plausible beneficial effect for vitamin-D supplementation may thus be suggested.

Aspectos actuales del síndrome de Sjögren: etiopatogenia, manifestaciones clínicas, diagnóstico y tratamiento

Sjögren's Syndrome (SS) is a chronic autoimmune disorder of the exbaocrine glands with associated lymphocytic infiltrates of the affected glands. SS occurs in a primary form not associated with other diseases and in a secondary form that complicates other rheumatic conditions. In both primary and secondary SS, decreased exocrine gland function leads to the “sicca complex”, a combination of dry eyes (xerophthalmia) and dry mouth (xerostomia). The clinical manifestations also include extraglandular disease features (skin, joints and muscles, lungs, kidneys, gastrointestinal tract). A variety of classification schemes have been proposed and discussed in the literature since the 1980s. The latest criteria, known as the American-European classification criteria for SS, were proposed in 2002. These criteria suggest that diagnosis of primary SS requires 4 of 6 criteria, including a positive minor-salivary biopsy sample and/or SS-A/SS-B antibodies. Therapy can be grouped into two separate aspects: treatment of dry eyes and dry mouth (replacement tears, muscarinic agonist agents…) and treatment of extraglandular manifestations (steroidal and non-steroidal anti-inflammatory agents, disease modifying agents, cytotoxic agents and biological therapies).

Postoperative External Beam Radiotherapy for Differentiated Thyroid Cancer: Outcomes and Morbidity With Conformal Treatment

To review institutional outcomes for patients treated for differentiated thyroid cancer with postoperative conformal external beam radiotherapy (EBRT). This is a single-institution retrospective review of 131 consecutive patients with differentiated thyroid cancer who underwent EBRT between January 1996 and December 2005. Histologic diagnoses included 104 papillary, 21 follicular, and six mixed papillary-follicular types. American Joint Committee on Cancer stage distribution was Stage III in 2 patients, Stage IVa-IVc in 128, and not assessable in 1. Thirty-four patients (26%) had high-risk histologic types and 76 (58%) had recurrent disease. Extraglandular disease spread was seen in 126 patients (96%), microscopically positive surgical margins were seen in 62 patients (47%), and gross residual disease was seen in 15 patients (11%). Median EBRT dose was 60 Gy (range, 38-72 Gy). Fifty-seven patients (44%) were treated with intensity-modulated radiotherapy (IMRT) to a median dose of 60 Gy (range, 56-66 Gy). Median follow-up was 38 months (range, 0-134 months). Kaplan-Meier estimates of locoregional relapse-free survival, disease-specific survival, and overall survival at 4 years were 79%, 76%, and 73%, respectively. On multivariate analysis, high-risk histologic features and gross residual disease predicted for inferior locoregional relapse-free survival, whereas high-risk histologic features, M1 disease, and gross residual disease predicted for inferior disease-specific and overall survival. The IMRT did not impact on survival outcomes, but was associated with less frequent severe late morbidity (12% vs. 2%). Postoperative conformal EBRT provides durable locoregional disease control for patients with high-risk differentiated thyroid cancer if disease is reduced to microscopic burden. Patients with gross disease face significantly worse outcomes. The IMRT may significantly reduce chronic radiation morbidity, but requires additional study.

Inhibition of experimental Sjögren's syndrome through immunization with HSP60 and its peptide amino acids 437–460

To investigate a potential immunomodulatory effect of the 60-kd heat-shock protein (Hsp60) on experimental spontaneous Sjögren's syndrome (SS). Seven-week-old nonobese diabetic (NOD) mice were immunized with eukaryotic Hsp60 or an Hsp60-derived peptide (amino acid residue [aa] 437-460). At 21 weeks of age, nondiabetic mice were investigated for salivary gland inflammation, exocrine function, and extraglandular disease manifestations. In addition, biomarker profiles comprising 87 analytes in serum and 75 in saliva were analyzed. In mice immunized with Hsp60 and aa 437-460, SS-related histopathologic features were significantly reduced compared with NOD controls. In addition, 50% of Hsp60-injected mice and 33% of aa 437-460-injected mice retained normal exocrine function. Both treatments induced similar changes in biomarker profiles. Notably, levels of circulating interferon-gamma-inducible 10-kd protein (IP-10) and eotaxin were decreased significantly after treatment. Anti-type 3 muscarinic acetylcholine receptor (anti-M3R) IgG1, interleukin-10, and leptin discriminated best between the different treatment groups. Successful prevention of hyposalivation was accompanied by quantitative alterations in 36 biomarkers, of which 19 mediators of inflammation declined to levels comparable with those found in BALB/c mice. Low secreted vascular endothelial growth factor A was the most accurate predictor of successful prevention of hyposalivation. Low salivary granulocyte chemotactic protein 2 was identified as the best predictor of normal secretory function across the strains. Immunization with Hsp60 and its peptide aa 437-460 led to inhibition of SS in NOD mice. Comprehensive analyses revealed specific biomarker signatures capable of predicting treatment group and treatment outcome. Molecules involved in inflammatory chemotaxis, neovascularization, and regulatory pathways caused the differences displayed by the biomarker profiles.

Primary Sjogren’s Syndrome: Current and Prospective Therapies

To summarize data on existing and experimental therapies for primary Sjogren's syndrome (pSS), referring both to sicca syndrome and to other systemic disease manifestations. Relevant English and non-English articles acquired through Medline were reviewed. pSS usually has a benign clinical course, centered on sicca features and general musculoskeletal manifestations, and is managed symptomatically. However, a subset of patients develops more severe extraglandular disease that warrants close monitoring and aggressive treatment. For dry eyes and mouth, nonpharmacologic measures to preserve secretions, and tear and saliva substitutes, offer some symptomatic relief. Muscarinic agonists and topical cyclosporine yield well-documented improvement in ocular sicca features. Although traditional antirheumatic drugs are used empirically for polyarthritis and other Sjogren's symptoms, their efficacy in pSS overall and as disease-modifying agents is limited. For the potential severe, nonexocrine manifestations complicating pSS, standard high-dose immunosuppression is used. Among the biologic agents already examined in pSS, those targeting tumor necrosis factor (TNF)-alpha failed to demonstrate significant benefit. Nonetheless, rituximab and other B-cell-depleting therapies appear promising. Treatment of pSS patients with severe extraglandular disease should differ from that of patients with predominantly sicca features and/or general muscoloskeletal manifestations. pSS treatment is mainly symptomatic, primarily directed against sicca complaints. The traditional anti-rheumatic agents show limited efficacy in the systemic process and use of systemic TNF-alpha inhibitors has been very disappointing. B cell depleting treatments and other newer biologic therapies appear more promising.

Management of patients presenting with Sjogren's syndrome

Sjogren's syndrome is an autoimmune exocrinopathy that predominantly affects salivary and lachrymal glands, leading to dry eyes and mouth. The most common clinical problems faced by the rheumatologist are those of dry eyes and mouth, parotid swelling, fatigue and extraglandular manifestations. The first stage in management is to make an accurate diagnosis based on the American/European consensus criteria. The most frequent differential diagnoses are dry eyes and mouth symptoms, a variant of chronic fatigue syndrome and fibromyalgia, and sialosis, which causes a non-inflammatory enlargement of the parotid glands. The mainstay of treatment for the sicca symptoms is local therapy, and that for the milder systemic symptoms is hydroxychloroquine. Steroids and immunosuppressive drugs are reserved for more severe extraglandular disease. In spite of intensive research in other systemic treatments including biologic therapies, there is limited evidence to support their use in routine clinical practice.

Autonomic neuropathy associated with sicca complex

We retrospectively studied 52 patients with sicca complex who presented primarily with peripheral neuropathic symptoms to assess the degree of autonomic involvement and its relationship to somatic neuropathy, serological tests and extraglandular disease. One patient presented with severe panautonomic dysfunction, with another six patients reporting prominent autonomic symptoms, and a further 40 patients having mild or asymptomatic disease. Eighty-seven percent of patients showed abnormalities on an autonomic reflex screen (ARS). Fifty-eight percent of patients showed a mixed pattern of autonomic dysfunction with abnormalities in two or more ARS subgroups of sudomotor, cardiovagal and adrenergic function. Three patients had a cholinergic autonomic neuropathy with sparing of adrenergic function. Tonic pupils were present in 13 patients. Autonomic neuropathy occurred in patients with a variety of somatic neuropathy subtypes, without a clear relationship between the type of autonomic neuropathy and the type of somatic peripheral neuropathy. Extraglandular disease was uncommon, occurring in only four patients. Serological abnormalities (extractable nuclear antigen [ENA], SS-A, SS-B) occurred in 20% of patients. We conclude that: (1) A wide spectrum of autonomic dysfunction is seen in sicca complex. (2) Severe autonomic involvement is uncommon, with most patients showing mildly symptomatic or asymptomatic disease. (3) Overall, characteristic patterns of autonomic dysfunction did not predominate, and there were no clear relationships with the different types of somatic peripheral neuropathy. (4) Clinical and serological evidence of non-neurological extraglandular disease is uncommon in this group of patients.

Peripheral neuropathy associated with sicca complex.

Peripheral neuropathy occurs in Sjögren's syndrome, a disorder in which systemic immunologic phenomena, including vasculitis, are common. Neuropathy also occurs with isolated sicca complex (keratoconjunctivits sicca and xerostomia); whether this represents a distinct syndrome is unclear. We retrospectively studied 54 patients with sicca complex and peripheral neuropathy to determine mode of presentation, neuropathic patterns, frequency and pattern of serologic abnormalities, and frequency of systemic disease, including necrotizing vasculitis. Peripheral neuropathy was the presenting problem in 87%. Although sicca symptoms occurred in 93%, they were a presenting complaint in only 11% and were usually mild, reported only after specific inquiry. Minor salivary gland biopsy was positive in 73%. Sensory neuropathies strongly predominated; 61% of patients manifested either sensory polyneuropathy or polyganglionopathy. Less common patterns included sensorimotor polyneuropathy (17%) and polyradiculoneuropathy (11%). Vasculitic neuropathy was demonstrated in only two patients, but nonspecific epineurial inflammation was present in 70% of nerve biopsies. Clinical evidence of systemic disease was uncommon, particularly in the sensory polyganglionopathy group, in whom extraglandular features other than weight loss occurred in only 1 of 12 patients. Antibodies to extractable nuclear antigens, the most specific serologic marker of Sjögren's syndrome, were present in 10.4%. We conclude that peripheral neuropathy and isolated sicca complex form a distinctive syndrome in which neuropathy is the presenting feature and sicca is easily overlooked; sensory polyneuropathy and polyganglionopathy predominate; serology is confirmatory but very insensitive; and extraglandular disease, including vasculitis, is uncommon compared with typical Sjögren's syndrome. Tests of ocular or salivary involvement are needed for diagnosis, and demonstration of inflammation in biopsied nerve is supportive. Improved definition of this disorder should permit further studies of natural history and efficacy of immunotherapy.

Postoperative radiotherapy for malignant tumors of the parotid gland

Purpose : To update our experience using postoperative irradiation in selected patients with carcinomas of the parotid gland. Outcomes of treatment with a focus on the effectiveness of the two primary techniques of radiation used for treating these tumors were evaluated. Methods and Materials : A retrospective analysis of 166 patients with parotid gland malignancies treated in the Department of Radiotherapy at the University of Texas M. D. Anderson Cancer Center between 1965–1989 was performed. All patients were treated following surgery and did not have macroscopic disease at the time of their radiation. The most common histologies were mucoepidermoid carcinoma (28%) and adenocarcinoma (27%). Pathologic features constituting indications for postoperative radiotherapy included: inadequate margins, 104 (63%) cases; extraglandular disease extension, 82 (49%); perineural invasion 57 (34%); and nodal disease 43 (26%). Radiation was delivered through an ipsilateral field of predominantly high energy electrons in 142 patients (86%). Wedged paired 60Co fields were used to treat 19 patients. The median dose was 60 Gy, typically delivered at 2 Gy per fraction. The median follow-up time for surviving patients was 155 months. Results : Forty-seven (29%) patients had disease recurrence, of whom 15 (9%) had disease recur locally and 10 (6%) regionally (neck). There was no association between the dose of radiation and local failure, except for a trend for patients with positive margins and/or named nerve involvement to have improved local control if they received doses >60 Gy. There was no difference in failure rates in patients treated with wedged pair techniques or ipsilateral fields, but there was a higher complication rate in the former. Overall, 37 patients (22%) developed chronic sequelae attributed to radiation. Twelve patients developed decreased hearing, and 15 patients developed soft tissue or bone necrosis or exposure. Conclusions : Local and regional control rates for high risk patients with parotid gland carcinomas treated with radiation following surgery were excellent. The technique of using an ipsilateral field encompassing the parotid bed and treated with high energy electrons often mixed with photons was effective minimal severe late toxicity. The moderate complication rate experienced in this series can be further reduced using modern techniques as described.

Serological and immunogenetic markers of extraglandular primary Sjögren's syndrome.

The clinical course of 48 patients with primary Sjögren's syndrome (primary SS) was reviewed. Forty-three north European patients were typed for HLA class I and class II alloantigens. In this population with primary SS HLA B8, DR3 and DRw52 all occurred more frequently than in the control population (P < 0.009, P < 0.0035, P < 0.02 respectively). The subgroup of primary SS patients with antibodies to Ro and/or La antigen had the greatest prevalence of DR3 (relative risk 33.4). The primary SS patients fall into two distinct groups: those with extraglandular disease in whom lymphopaenia, hypergammaglobulinaemia, antibodies to Ro and/or La and HLA DR3 were all more frequent and those patients with either glandular disease alone or only one extraglandular feature. There was no difference in disease duration between the two groups, although on average the latter group were 10 years older.

Clinical differences between ANA/anti-ENA positive or negative primary Sjögren's syndrome.

Fifty female patients with primary Sjögren's syndrome diagnosed according to the Copenhagen criteria were evaluated for both glandular and extraglandular involvement. They were divided into two groups based on the presence or absence of antinuclear and anti-ENA antibodies (ANA/anti-ENA). ANA/anti-ENA negative patients presented with milder and later glandular and extraglandular disease and required less frequent corticosteroid treatment. No significant differences were noted in extraglandular manifestations with the exception of leukopenia which was noted only in ANA/anti-ENA positive cases.