White matter water diffusion changes in primary Sjögren syndrome.

BACKGROUND AND PURPOSE: Histopathologic studies have demonstrated WM damage in primary Sjögren syndrome. The purpose of this study was to evaluate WM microstructural changes by use of DTI-derived parameters in patients with primary Sjögren syndrome. MATERIALS AND METHODS: DTI was performed in 19 patients with primary Sjögren syndrome (age, 64.73 ± 9.1 years; disease duration, 11.5 ± 7.56 years) and 16 age-matched control subjects. Exclusion criteria were a history of major metabolic, neurologic, or psychiatric disorder and high risk for cardiovascular disease. Data were analyzed by use of tract-based spatial statistics, for which the WM skeleton was created, and a permutation-based inference with 5000 permutations was used with a threshold of P < .01, corrected for multiple comparisons to enable identification of abnormalities in fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. RESULTS: Tract-based spatial statistics showed decreased fractional anisotropy in multiple areas in patients with primary Sjögren syndrome compared with control subjects, located mainly in the corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. Increased mean diffusivity and radial diffusivity and decreased axial diffusivity were observed in most of the fiber tracts of the brain in patients with primary Sjögren syndrome, compared with control subjects. CONCLUSIONS: Patients with primary Sjögren syndrome show loss of WM microstructural integrity, probably related to both Wallerian degeneration and demyelination.

The psychological defensive profile of primary Sjögren's syndrome patients and its relationship to health-related quality of life.

OBJECTIVES: We aimed to assess the defensive profile of primary Sjögren's syndrome (SS) patients and to investigate the independent associations of psychological distress and personality variables with health-related quality of life (HRQOL). METHODS: In 40 primary SS patients we assessed psychological distress (SCL-90-R), ego defense mechanisms (Defense Style Questionnaire), hostility features (HDHQ) and HRQOL (WHOQOL-BREF). Fifty-six patients with Systemic Lupus Erythematosous (SLE) and 80 healthy participants matched for age and sex served as controls. RESULTS: Primary SS patients presented higher rates of general psychological distress compared to SLE and healthy participants. Symptoms of somatisation were more prominent in SS than SLE or healthy controls. SS patients presented less use of humour defense and more help-rejecting complains and delusional guilt hostility, compared to controls. Primary SS patients' HRQOL was more impaired than healthy participants and comparable to SLE. Psychological distress was a constant independent correlate of SS patients' HRQOL, while less use of humour (p<0.001) and higher rates of delusional guilt (p=0.032) were also significantly associated with Physical HRQOL independently of psychological distress; more use of schizoid fantasy was also independently associated with impaired Environment HRQOL (p=0.005). CONCLUSIONS: Primary SS patients exhibit several specific psychological difficulties in adaptation to life stressors, and clinicians and consultation-liaison psychiatrists, apart from the early assessment and treatment of psychological distress and somatisation symptoms, should consider the patients' underlying defensive profile and coping capacities, since such personality traits, although usually underestimated, are also independently associated with the disease outcome.

Coping with health-stressors and defence styles associated with health-related quality of life in patients with systemic lupus erythematosus.

This study aimed to assess the association of coping with health-stressors and defence styles with health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE). In 56 SLE patients we assessed disease activity (SLEDAI), functional limitations (HAQ), psychological distress (SCL-90-R), defence styles (Defence Style Questionnaire), hostility (HDHQ), coping with health-stressors (Sense of Coherence scale) and HRQOL (WHOQOL-BREF). Two hundred and eight rheumatologic patients (168 with rheumatoid arthritis [RA] and 40 with primary Sjögren's syndrome [SS]) served as disease controls. SLE patients' HRQOL was similar to that of patients with RA and primary SS after adjusting for demographic and disease variables. Psychological distress was significantly associated with most aspects of HRQOL, but sense of coherence mediated the relationship of psychological distress with Physical HRQOL; this mediation effect was unique to SLE, as mediation analyses showed. Maladaptive action defence style was also significantly associated with Environment HRQOL independently of psychological distress (p < 0.024). These findings indicate that, apart from the early assessment and treatment of psychological distress, clinicians and consultation-liaison psychiatrists should bear in mind the SLE patients' psychological resources and coping capacities to deal with the stress of the disease, since such traits, although usually underestimated, are strongly independently associated with HRQOL.

Subclinical atherosclerosis in scleroderma patients.

OBJECTIVE: To investigate subclinical atherosclerosis in patients with systemic sclerosis (SSc). METHODS: Sixty-six patients with SSc who met the American College of Rheumatology criteria for the disease were included. The serum levels of total cholesterol (TC), triglycerides, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were determined in all patients. Carotid artery intima-media thickness (IMT) and carotid plaques were measured. Patients with a history of atherosclerosis, hypertension, smokers, or patients suffering from conditions that affect the lipid profile, such as diabetes mellitus, hypothyroidism, liver or kidney diseases, Cushing's syndrome, obesity, and a history of familial dyslipidaemia, were excluded. Patients receiving medication affecting lipid metabolism were also excluded from the study. Fifty-one age- and sex-matched non-smoking volunteers were used as controls. RESULTS: Sixty patients were investigated. Six were excluded. Of these, two were smokers, two had diabetes mellitus, one hypothyroidism, and one had hypertension treated with diuretics. Patients with SSc exhibited mild dyslipidaemia expressed mainly by low serum levels of HDL-C and high TC (p < 0.001 and p < 0.021, respectively) compared to controls. In addition, the atherogenic ratio LDL-C/HDL-C was significantly higher among SSc patients (p < 0.0001). Common carotid artery IMTs were higher in SSc compared to controls (0.77 +/- 0.2 vs. 0.59 +/- 0.14, p < 0.0001). No correlation between IMTs and any SSc features were found. Logistic regression analysis showed an independent association of scleroderma with IMTs and TC. CONCLUSION: The scleroderma patients exhibited an atherogenic lipid profile and subclinical atherosclerosis and have an increased risk for cardiovascular events.

The role of psychological distress and personality variables in the disablement process in rheumatoid arthritis.

OBJECTIVE: To test whether psychological distress and personality variables mediate or moderate physical health-related quality of life (HRQOL) in rheumatoid arthritis (RA) patients. METHODS: In 168 RA patients the following self-report instruments were administered: the Health Assessment Questionnaire (HAQ), the General Health Questionnaire (GHQ), the Defence Style Questionnaire (DSQ), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Sense of Coherence (SOC) scale. A total of 152 patients with several rheumatological disorders [56 with systemic sclerosis (SSc), 56 with systemic lupus erythematosus (SLE) and 40 with Sjögren's syndrome (SS)] served as disease controls. The outcome measure was the physical scale of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF). We used hierarchical regression to determine whether our data were consistent with the disablement process model. RESULTS: In RA patients, sense of coherence was associated with physical HRQOL but the relationship was mediated by psychological distress. Self-sacrificing defence style moderated the relationship between pain and physical HRQOL: pain was associated with impaired physical HRQOL only in patients with predominant self-sacrificing defence style. Although psychological distress and personality variables were also associated with physical HRQOL in the disease control group, the moderating effects of personality on physical HRQOL were unique to RA. Thus, in RA, psychological distress, functional disability, and the interaction term between pain and self-sacrificing defence style were independently associated with physical HRQOL. CONCLUSIONS: In RA patients, psychological distress mediated the association of personality variables with physical HRQOL but personality moderated the effects of pain on physical HRQOL and this could be relevant to psychological interventions.

Epidemiology of primary Sjögren's syndrome in north-west Greece, 1982-2003.

OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality and survival rates, of primary Sjögren's syndrome (pSS) in a defined area of north-west Greece with a population of about 500 000 inhabitants. METHODS: Cases were recorded from the following sources: (i) in- and out-patients referred to the rheumatology clinics of the Ioannina University Hospital and the Ioannina General Hospital; and (ii) patients referred to private rheumatologists practising in the study area. All patients diagnosed between 1 January 1982 and 31 December 2003 who were resident in the study area were included as incident cases. Diagnosis was based on the American-European consensus criteria for SS. Incidence and prevalence rates were calculated as numbers of cases per 10(5) inhabitants. Population data were based on the National Censuses of 1981, 1991 and 2001. RESULTS: A total of 422 incident cases were identified for the study period 1982-2003. Age-adjusted mean annual incidence rate for this period was 5.3 (95% confidence interval [CI] 4.5-6.1) cases per 10(5) adult inhabitants. The female/male ratio of incident cases was about 20/1. The age-adjusted prevalence rate for the adult population was 92.8 (95% CI 83.7-101.9) cases per 10(5) inhabitants on 31 December 2003. The 5-yr survival rate in the incidence cohort was 96.6% and the 10-yr survival rate 92.8%. The standardized mortality ratio in comparison with the general population of the study area was 1.02 (95% CI 0.4-2.0). The main causes of death were cardiovascular diseases and cancer. The occurrence of the disease shows a slightly decreasing, but not statistically significant, trend with time. CONCLUSIONS: The estimated incidence and prevalence of pSS in this study were slightly higher in comparison with data from other studies based on physician-diagnosed cases. The prevalence was significantly lower when compared with the findings of studies based on the examination of a sample of the general population. Mortality rates did not differ significantly between pSS patients and the general population.

Magnetic resonance imaging findings of the cervical spine in patients with rheumatoid arthritis. A cross-sectional study.

OBJECTIVES: To investigate by magnetic resonance (MR) imaging the occurrence of cervical spine (CS) involvement in rheumatoid arthritis (RA) patients. METHODS: Fifty-one consecutive unselected patients, who fulfilled the revised American College of Rheumatology criteria for RA, were investigated. All patients had a complete physical and laboratory evaluation. Radiological evaluation included hand and wrist x-rays, as well as CS radiographs in anteroposterior, lateral and lateral in full flexion views. In addition, MR (Spin Echo T2-weighted sagittal scans [neutral and flexion position], plain and contrast enhanced T1-weighted sagittal and axial scans) was performed in all patients. Hand x-rays were evaluated according to the Larsen's criteria, while CS radiographs were evaluated according to Winfield classification. Disease activity was assessed by disease activity score for 28 joint indices (DAS-28). RESULTS: There were 42 females and 9 males with a mean age of 56.5 +/- 10.4 years and mean disease duration 12.4 +/- 8.5 years. Thirty-three patients (64.7%) had positive IgM rheumatoid factor (RF). Thirty patients presented clinical findings, mainly cervical pain and stiffness of CS (25 with positive and 5 with negative MR), while, radiological findings of CS involvement were found in 40 patients. Forty-four patients (86.2%) presented MR findings of CS involvement (peridental pannus 88%; dens erosion 23.5%; atlantoaxial subluxation 13.7%; subaxial subluxations 10%; brainstem compression 5.9%). Peridental pannus correlated with high DAS-28, positive IgM RF and advanced erosive changes of the wrist and hand (p < 0.05) in the univariate analysis. However, multivariate logistic regression analysis did not confirm such correlation. CONCLUSIONS: We conclude that the frequency of CS involvement in Greek RA patients is high but the destructive changes are mild. However, in patients with active erosive peripheral disease it is very probable to also have some changes in CS. These may be clinically important and in such cases, MR may offer valuable information.

A single pulmonary rheumatoid nodule masquerading as malignancy.

We present a 54-year-old man, a heavy smoker, with clinical and laboratory evidence of familial hypercholesterolemia and an asymptomatic solitary pulmonary nodule (SPN) increasing in size on follow-up chest X-ray. Laboratory work-up revealed high titers of rheumatoid factor and the presence of acute phase reactants. Because of the patient's age and history of smoking, open lung biopsy was performed to rule out malignancy. The biopsy showed histological features compatible with a rheumatoid nodule. Identical features were noted in the histological examination of the subcutaneous nodule. Usually, rheumatoid nodules occur in patients with active, long-standing rheumatoid arthritis (RA) with other extra-articular manifestations. The presence of a single pulmonary rheumatoid nodule as the first manifestation of RA is extremely rare. Histologic proof is often required since pulmonary carcinoma can present an identical clinical and radiological pattern. The diagnostic work-up and the differential diagnosis of an SPN, particularly in a heavy smoker, is a common clinical request and remains a diagnostic challenge.

Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients?

OBJECTIVE: To investigate the association of cigarette smoking with clinical expression, disease activity and severity in a cohort of Greek patients with early rheumatoid arthritis (RA). METHODS: From January 1993 until December 2002, 293 patients with early RA were diagnosed and followed up in our rheumatology clinic. All patients fulfilled the American College of Rheumatology criteria for RA, had disease duration of less than one year, without prior treatment of disease modifying anti-rheumatic drugs (DMARDs) or steroids. The patients were treated with at least one DMARD, and 287 of them had a last follow up during the year 2004. The demographic, personal, clinical, laboratory, radiological and therapeutic features were compared at entry and at the last follow-up, according to their smoking habits at entry. RESULTS: Among the 293 patients, 6 were lost to follow-up, thus 287 patients were evaluated. There were 200 females (67.7%) and 87 males (30.3%). Eighty-two (28.6%) were current smokers, 21 (7.3%) ex-smokers and 184 (64.1%) non-smokers at presentation. RA smoker patients displayed the disease at a younger age than the non-smokers. Additionally, the smokers presented at disease onset more prominent features of articular involvement as was evaluated by the higher number of total joint count with tenderness and swelling and by the higher disease activity for 28 joint indices score (DAS-28). Smokers also presented a higher Larsen's score and higher frequency of IgM and IgA rheumatoid factors as compared to non-smokers. At the end of the study, the smoker patients presented more active and severe disease as evaluated by the higher total number of tender and swelling joint count, the higher DAS-28, and higher Larsen's score as compared to non-smokers. Furthermore, the smokers more frequently had rheumatoid nodules than the ex-smokers and non-smokers. The association of smoking with disease activity and severity was independent of sex, age, educational level, alcohol consumption, and follow-up duration. Finally, no significant differences were observed concerning the therapeutic procedure among the three groups. CONCLUSIONS: In our early RA patients, cigarette smoking was associated with increased disease activity, and severity, independently of several other possible confounders and despite the early disease treatment.

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study.

OBJECTIVE: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). RESULTS: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. CONCLUSION: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated.

Sicca syndrome in patients with sarcoidosis.

Out of 134, 12 sarcoidosis patients with symptoms of mucosal dryness as the first clinical manifestation were identified and compared with 30 consecutive unselected Sjögren's syndrome (SS) patients. Sicca manifestations were similar among the two groups, while parotid gland enlargement (PGE) was more frequently found in sarcoidosis patients (P < 0.05). Patients with sarcoidosis had mainly pulmonary (P < 0.001) and skin involvement (P < 0.05), while SS patients presented more frequently with Raynaud's phenomenon (P < 0.05). Autoantibody profile was more often found in SS patients compared to sarcoidosis (P < 0.0025). The histopathological findings of minor salivary gland biopsy (MSGB) revealed noncaseating granulomas (NCG) in 58% of patients with sarcoidosis, while in SS, MSGB showed focal sialadenitis in the majority of the patients. Transbronchial lung biopsy (TBLB), which was performed in 10 sarcoidosis patients, revealed the presence of NCG in all patients. In patients with sarcoidosis and sicca symptoms as the presenting syndrome, PGE is a useful clinical finding. Searching for pulmonary involvement is a determining factor to differentiate sarcoidosis from SS. The absence of autoantibodies is another useful tool for the diagnosis of sarcoidosis. Finally, MSGB is very helpful to discriminate between sarcoidosis and SS and when MSGB is not specific, then TBLB is valuable to confirm the diagnosis.

Subgroups of primary Sjögren's syndrome. Sjögren's syndrome in male and paediatric Greek patients.

OBJECTIVES: To describe the clinical and serological findings in male and paediatric Sjögren's syndrome (SS) patients. PATIENTS AND METHODS: Using the European criteria for the diagnosis of SS 12 male and 13 paediatric patients were identified and compared with those of 30 consecutive unselected adult female SS patients. RESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years, ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial clinical manifestation in the majority of the children with a statistical significance compared with male (p < 0.01) and with female patients (p < 0.0001). Sicca manifestations were the most common clinical symptoms in male and female patients at disease onset. The systemic manifestations were similar among the three groups except that men showed lower frequency of arthritis (p < 0.05) and Raynaud's phenomenon (p < 0.05) compared with women. No differences were found among the immunological profile of children and female patients, while male patients had a lower frequency of antinuclear antibodies (p < 0.025) and antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women. CONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid gland enlargement is the most common clinical finding at disease onset in children. Male patients seem to have less systemic manifestations and lower frequency of autoantibodies.

Influence of methotrexate on radiographic progression in rheumatoid arthritis: a sixty-month prospective study.

OBJECTIVE: To evaluate if methotrexate (MTX) can slow disease progression, as determined radiographically, in comparison to other disease modifying drugs in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: Pairs of hand and wrist radiographs from 30 patients treated with MTX and 30 treated with D-penicillamine (DP) were evaluated blindly and separately by two radiologists (A and B) using reference radiographs for scoring. A scale scoring similar to Larsen's standard radiographs with minor modifications was used. The radiographs studied were obtained at the beginning and 5 years after therapy in both groups. RESULTS: A significantly greater worsening was found in the DP-treated patients (p = 0.025), as compared to MTX patients. Methotrexate showed a slower rate of disease progression than DP. Furthermore, in the MTX group 15 patients remained radiographically stable, 9 worsened and 6 were healed. In contrast, in the DP group 22 patients remained radiographically stable, 8 worsened and none improved. CONCLUSIONS: The rate of radiographic progression in RA patients was lower in MTX-treated patients compared to those treated with DP. Six patients showed radiological improvement after MTX treatment. Therefore, it seems that MTX could be considered a disease modifying drug.

Safety and efficacy of recombinant gamma interferon in the treatment of systemic sclerosis.

OBJECTIVE: To evaluate the safety and efficacy of recombinant gamma interferon (rIFN gamma) in the treatment of patients with systemic sclerosis. METHODS: Sixteen patients with systemic sclerosis were treated with r-IFN gamma, 60 micrograms m-2 (low dose, n = 10) and 150 micrograms m-2 (high dose, n = 6), three times weekly in an open phase I/II trial of eight months duration. The patients were stratified in low and high dose according to the severity and the extent of scleroderma; the two groups were comparable. RESULTS: The treatment was well tolerated. The most common side effects, almost certainly related to r-IFN gamma, were fever, chills, dizziness, headache, and severe flu-like syndrome with decreasing intensity with the time of treatment. Severe aphthous stomatitis (n = 1), ventricular tachycardia (n = 1), severe oesophageal ulcers due to gastro-oesophageal reflux (n = 1), disease exacerbation alone with frank arthritis and slight pericardial effusion (n = 1), and inability to conform to the requirements of the study (n = 1) were the reasons for discontinuing treatment. Side effects and degree of response were evident during the first five months of treatment. A significant decrease in mean skin thickness score was observed and was higher in the high dose group. Reactive oxygen species of peripheral neutrophils and soluble interleukin-2 receptor serum concentrations were higher than those of normal individuals at study entry and decreased in parallel with clinical improvement. CONCLUSIONS: Treatment of systemic sclerosis patients with r-IFN gamma was relatively safe and well tolerated for doses as high as 150 micrograms m-2 three times weekly. Side effects and the degree of response can be seen during the first months of therapy and can be used as predictors of ultimate toxicity or response. The drug seems to be effective in treating cutaneous scleroderma.

Methotrexate in primary Sjögren's syndrome.

OBJECTIVE: To determine the safety and efficacy of methotrexate (MTX) in the treatment of primary Sjögren's syndrome (SS). METHODS: An open, one-year pilot study of MTX (0.2 mg/kg body weight taken weekly) for the treatment of SS was performed. Seventeen patients with primary SS according to EEC criteria were enrolled in the study. Outcome was determined on the basis of clinical and laboratory parameters. RESULTS: Weekly administration of MTX resulted in improvement of the main subjective symptoms (dry mouth and eyes) as well as in the frequency of parotid gland enlargement, dry cough and purpura. However, no improvement in the objective parameters of dry eyes and dry mouth were observed. Persistent asymptomatic elevation of the hepatic transaminase levels led to a dosage reduction in 7 patients (41%). CONCLUSIONS: Weekly MTX may be an acceptable form of therapy for SS patients. Double-blind trials are needed to substantiate the efficacy of this therapeutic modality.

Anti-5S RNA/protein (RNP) antibody levels correlate with disease activity in a patient with systemic lupus erythematosus (SLE) nephritis.

A patient with systemic lupus erythematosus (SLE) and nephritis without antibodies to dsDNA but with antibodies to a 5S RNA/protein (RNP) complex is presented. Combined RNA precipitation and Western blotting experiments strongly suggested that these newly identified autoantibodies recognized a distinct epitope on the L5 ribosomal protein of the L5/5S RNP complex first described by Steitz et al. [1]. Quantification of the anti-5S RNP antibody levels was done by hybridizing Northern blots of immunoprecipitated RNA from serial serum samples with a 32P-labelled oligoprobe specific for the 5S ribosomal RNA. These studies revealed a strong association between anti-5S RNP autoantibody titre and severity of SLE nephritis over a 3-year prospective study. Our results indicate that the L5/5S RNP can be a target of autoimmune response, and and may serve, in some cases, as marker of SLE severity and response to therapy.