Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results.

OBJECTIVE: To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls. METHODS: Data on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group. RESULTS: Primary SS patients had a higher prevalence of hypertension (28­50% versus 15.5­25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it. CONCLUSION: Primary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

Dry eyes and mouth syndrome--a subgroup of patients presenting with sicca symptoms.

OBJECTIVE: To evaluate the characteristics of patients presenting with symptoms suggestive of Sjögren's syndrome (SS) but failing to satisfy diagnostic criteria. METHODS: Clinical, serological and histological data were collected on 34 patients presenting with dry eyes and/or mouth who did not satisfy the Vitali criteria for the diagnosis of SS. They were compared with 136 patients with primary SS, 38 patients with secondary SS, and 13 patients without SS. Questionnaires on symptoms from each group were compared with 43 healthy controls. RESULTS: The 34 patients who did not satisfy the diagnostic criteria for SS or any other connective tissue disease were designated dry eyes and mouth syndrome (DEMS). Their demography including age was similar to that of a primary SS group and there was no more atrophy seen on their biopsies compared with SS and non-SS controls. They scored highly on visual analogue scales of symptoms but had few objective signs. All were negative for anti-Ro and anti-La although the prevalence of antinuclear antibodies (19%) was increased compared with a normal population. There was no excess of SS-associated tissue types. CONCLUSION: There was no evidence that age, salivary gland atrophy or subclinical SS accounted for the symptoms in DEMS. Most of the patients fitted into a spectrum of disease which tended more towards fibromyalgia and/or chronic fatigue syndrome.

A double blind placebo controlled trial of azathioprine in the treatment of primary Sjögren's syndrome.

OBJECTIVE: To establish whether there is a place for low dose azathioprine (AZA) as a disease modifying agent in patients with uncomplicated primary Sjögren's syndrome (SS). METHODS: Twenty-five patients with primary SS were entered into a double blind, placebo controlled trial of AZA (1 mg/kg/day) for a period of 6 months. RESULTS: Six patients, all receiving active drug, withdrew because of side effects. There was no significant change in disease activity variables when measured clinically, serologically, or histologically. CONCLUSION: This trial suggests that low dose AZA does not have a role as a disease modifying agent in SS.

T cell clones from a Sjögren's syndrome salivary gland biopsy produce high levels of IL-10.

Sjögren's syndrome (SS) is characterized by a focal periductal salivary gland infiltrate consisting mainly of T and B lymphocytes. Most of the T cells bear the memory CD4+ Th1-like phenotype and express high levels of class II, though CD8+ cells are also present. We have studied 17 labial salivary gland and 15 peripheral blood T cell clones from a patient with primary SS. The tissue clones were 71% CD8+ and 29% CD4+, and the peripheral blood-derived clones were 60% CD8+ and 40% CD4+. The CD4+ T cell clones from both the salivary gland and autologous peripheral blood were of the Th1 phenotype, in that they produced interferon-gamma (IFN-gamma) and IL-2 but very little IL-4 after 24 h stimulation with phorbol myristate acetate and anti-CD3 antibody. The salivary gland-derived CD4+ clones produced 15 times more IL-10 (7.92 ng/ml) than peripheral blood-derived CD4+ clones (0.52 ng/ml, P < or = 0.02). The tissue CD8+ clones produced 1.2 times (P < 0.04) more IFN-gamma and CD4+ clones produced 3.5 times less IL-2 (P < 0.02) than the respective PBM-derived clones. The accumulation of Th1-type cells producing high levels of IL-10 in the salivary gland suggests a specific immunoregulatory function at the site of inflammation in SS.

The etiopathogenesis of Sjögren's syndrome.

With increasing awareness and improved diagnostic tests, Sjögren's syndrome (SS) is becoming recognized as a common autoimmune disease, affecting as many as 3% of women over age 55 years. Apart from keratoconjunctivitis sicca, systemic features are common, leading to considerable morbidity and occasionally mortality. Predisposing factors for SS include HLA determinants that have been linked to DR3 and heterozygosity for DQ-1 and DQ-2. There is accumulating evidence that activated epithelial cells and their interaction with T cells play a central role in pathogenesis. Some restriction of T-cell receptor gene usage to V beta 6.7b and V beta 13.2 and a profile of cytokine production consistent with Th-1-type cells has been observed in affected tissues. Antibodies to Ro (SS-A) and La (SS-B) are found in about 50% of patients and are associated with more severe glandular and extraglandular manifestations. There is evidence that the antibodies are pathogenic, not only in patients, but in their infants born with congenital heart block. Studies of herpesviruses have led to conflicting results, and interest has recently focussed on retroviruses, based on the findings of the expression of retroviral elements in salivary glands of SS patients and antiretrovial antibodies in serum. Mice infected with or transgenic for retroviruses develop SS-like pathology and are currently being studied as animal models of the disease. In the last few years, considerable progress has been made in the understanding of the pathogenesis of SS, and the disease has become the prototype for the investigation of a viral etiology for autoimmune rheumatic disease. Study of its etiopathogenesis may be the key to understanding autoimmune disease in general.

Drug-induced lupus.

Drug-induced lupus is a syndrome resembling mild systemic lupus erythematosus which can complicate treatment with certain apparently unrelated therapies. The most common individual agents are procainamide and hydralazine. Drugs less frequently associated with the disease are chlorpromazine, isoniazid, methyldopa, penicillamine, quinidine and sulfasalazine. Whole drug groups have also been implicated, such as the anticonvulsants, beta-blockers, sulfonamides and some of the newer 'biological' agents. The syndrome is characterised by arthralgia, myalgia, pleurisy, rashes and fever in association with antinuclear antibodies in the serum. More serious features of idiopathic lupus such as nephritis and cerebral disease are rare in drug-induced disease. The pathogenesis is unknown but in some cases is thought to be due to interactions between the drug and DNA or histones, rendering them immunogenic. For the biological agents, including interferons and antibodies to tumour necrosis factor-alpha, it has been suggested that it is due to disruption of the cytokine network. Although extremely rare, recognition of drug-induced lupus is important because it reverts within a few weeks of stopping the drug. It is possible that understanding its pathogenesis may shed light on its more serious relative, systemic lupus erythematosus.

Interferon-gamma and epithelial cell activation in Sjögren's syndrome.

We have examined the hypothesis that interferon-gamma (IFN-gamma) and its interaction with epithelium may play a role in the perpetuation of inflammation in Sjögren's syndrome (SS). Labial salivary gland primary cell cultures from 16 patients with primary SS (pSS) and eight cultures from patients with SS symptoms but histologically normal biopsies were examined for expression of HLA-DR and cytoplasmic La (SS-B). Epithelial HLA-DR expression was found in 80% of cultures from pSS patients and 38% of those from patients not fulfilling diagnostic criteria. Cytoplasmic La was detected in 50 and 38% of cultures, respectively. Treatment of 14 of the cultures with IFN-gamma increased HLA-SR and cytoplasmic La expression above that of untreated cultures. Depletion of IFN-gamma using neutralizing antibody had the reverse effect. These findings suggest that the perpetuation of chronic inflammation of pSS may be due to the induction of HLA-DR and La antigen expression on epithelial cells by IFN-gamma.

Quinine-induced cutaneous vasculitis.

We report a 60-year-old woman who developed severe cutaneous vasculitis three weeks after commencing quinine sulphate (300 mg at night) for nocturnal cramps. The patient died despite immunosuppressive treatment with prednisolone and cyclophosphamide. We review three previous cases and conclude that cutaneous vasculitis is a rare but life-threatening complication of treatment with this widely-prescribed drug. Quinine sulphate is prescribed frequently for nocturnal cramps, although its efficacy is unsupported by stringently controlled clinical trials. Adverse reactions to the drug are unusual. We describe a 60-year-old woman with fatal cutaneous vasculitis related to quinine treatment.