Advanced ankylosing spondylitis: a multisite, multimodality densitometric analysis for investigation of bone loss in the axial and appendicular skeleton.

OBJECTIVE: The aim of this study was to investigate if there is a bias in bone mineral density measurements among major densitometric techniques across multiple skeletal sites. METHODS: In 25 advanced ankylosing spondylitis patients, bone mineral density measurements were acquired in the lumbar spine, the hip, and the forearm. RESULTS: In total, 60% of patients had a bone mineral density Z-score of -2 or less at one or more skeletal sites. Dedicated loss of cortical bone was identified at the distal forearm (60% of patients). Differences in bone mineral density measurements across all densitometric techniques were highly significant (p≤0.001). Bone loss was more striking in spinal trabecular bone by three-dimensional quantitative computed tomography [Z-score -2.1] versus dual-energy X-ray absorptiometry [Z-score 0]. A trabecular bone loss quantified by quantitative computed tomography was about twice as much as a cortical bone loss by single-energy X-ray absorptiometry (p=0.001). CONCLUSIONS: Low bone mineral density is prevalent in advanced ankylosing spondylitis patients, predominating in the spine. Bone mineral density measurements have systematic differences when compared to each other. Knowledge of these offsets is useful for improved diagnosis of regional bone loss that allows for targeted treatment of osteoporosis. Three-dimensional quantitative computed tomography is more suitable for evaluating spinal osteoporosis in advanced ankylosing spondylitis than dual-energy X-ray absorptiometry, which rather underestimates bone loss.

Counting Costs under Severe Financial Constraints: A Cost-of-Illness Analysis of Spondyloarthropathies in a Tertiary Hospital in Greece.

OBJECTIVE: To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece. METHODS: Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros. RESULTS: The mean ± SD annual direct cost for the patients with SpA reached €8680 ± 6627. For the patients with PsA and AS, the cost was estimated to be €8097 ± 6802 and €9531 ± 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA. CONCLUSION: SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments.

Sense of coherence and self-sacrificing defense style as predictors of psychological distress and quality of life in rheumatoid arthritis: a 5-year prospective study.

Individual differences in adjustment during a disease's course determine psychological response and outcome. This study aimed to investigate prospectively whether coping with health stressors and self-sacrificing defense style could predict psychological adjustment and health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA). Seventy-four consecutive RA patients attending a rheumatology clinic were assessed for psychological distress (SCL-90-R), sense of coherence (SOC scale), self-sacrificing defense style (Defense Style Questionnaire-88), disease activity (DAS-28), pain, disability (Health Assessment Questionnaire) and HRQoL (World Health Organization Quality of Life Instrument, Short Form) at baseline and 5 years later. Multiple regression and moderator analyses were carried out. The results showed that disease activity (p < .001), pain (p = .005), psychological distress (p = .031), social relations HRQoL (p = .042) and environment HRQoL (p = .020) significantly improved over time. SOC was found an independent predictor of improvement in psychological distress (p = .003), overall general health (p = .002) and social relations HRQoL (p = .004); self-sacrificing independently predicted environment HRQoL (p = .042). The self-sacrificing defense style moderated the relationships between improvement in pain and improvement in overall general health (p = .024) and between improvement in pain and improvement in social relations HRQoL (p = .006). These findings indicate that, in RA, SOC predicts improvement in psychological distress and HRQoL over time, while a self-sacrificing defense style moderates the relationship of pain with HRQoL in the long term. These variables may partly explain inter-individual differences in adaptation to RA. Therefore, the design of psychotherapeutic trials targeting the patients' defensive profiles and coping with health stressors capacities is an important research perspective.

Heart involvement in systemic sclerosis: a combined echocardiographic and scintigraphic study.

The aim of this study is to investigate systemic sclerosis (SSc) patients without clinically evident heart disease for cardiac abnormalities. SSc patients and age- and sex-matched healthy controls from the hospital staff underwent transthoracic echocardiography for the assessment of the left ventricle (LV) morphology and function and estimation of the pulmonary artery systolic pressure (PASP). Patients further underwent stress-rest myocardial perfusion imaging (MPI) scintigraphy by single-photon emission computed tomography (SPECT). Thirty-seven patients were included (33 women, 19 with diffuse, and 18 with limited SSc). LV hypertrophy was more common in SSc patients than controls (24.3 vs 0 %, p = 0.001). Impaired LV relaxation was found in 45.9 % of patients and 40.5 % controls (p = 0.639). Excluding patients with arterial hypertension, LV hypertrophy was still found in 23.1 % and LV relaxation impairment in 38.5 %. PASP over 30 mmHg was found in 13 patients (35.1 %), 11 of whom had no history of pulmonary arterial hypertension (PAH). Of 35 patients who underwent SPECT, 21 patients (60 %) exhibited reversible LV perfusion defects. Their mean age was 51.8 years; four patients were younger than 40 years old and eight patients younger than 50 years. In all cases, ischemia was graded as mild or moderate and in a single case, graded as significant. Subclinical heart involvement is common in SSc patients even in the younger age groups. LV hypertrophy and impaired relaxation, raised PASP, and ischemia on MPI with SPECT are found in a significant proportion of SSc patients. Careful screening of SSc patients for potential heart involvement and consultation by a cardiologist may be of value.

Illness perceptions and psychological distress associated with physical health-related quality of life in primary Sjögren's syndrome compared to systemic lupus erythematosus and rheumatoid arthritis.

Notwithstanding that psychological distress and illness perceptions are important in determining outcomes in rheumatic diseases, few studies investigated these variables in primary Sjögren's syndrome (pSS). We aimed to compare illness perceptions and psychological distress in patients with pSS, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and to test whether their associations with health-related quality of life (HRQoL) are similar in these groups of patients. In 57 patients with pSS, 75 with SLE and 199 with RA, we administered the Patient Health Questionnaire (PHQ-9), the Symptom Check-List and the Brief-Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short-Form to assess HRQoL. Hierarchical regression models determined the associations of psychological variables with HRQoL after adjusting for demographic variables and clinical parameters. The prevalence of clinically significant depressive symptoms (PHQ-9 ≥ 10) was 24.6 % in pSS, 29.3 % in SLE and 25.1 % in RA. Patients with pSS showed little understanding of their disease (comprehensibility) and attributed more symptoms to their illness (identity) compared with the other groups of patients. Illness perceptions and depressive symptoms were independently associated with physical HRQoL in a similar pattern in all three groups. In pSS, however, the patients' worries about the consequences of their illness was a stronger correlate of physical HRQoL than pain. These findings indicate that psychological factors are important correlates of HRQoL in these disease groups and encourage the design of psycho-educational therapies targeting disease-related cognitions in pSS in an attempt to improve patient's physical HRQoL.

The relationship between depressive symptoms, illness perceptions and quality of life in ankylosing spondylitis in comparison to rheumatoid arthritis.

Anxiety and depressive symptoms as well as cognitive variables are important in determining outcome in rheumatic diseases. We aimed to compare psychological distress symptoms and illness perceptions in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and to test whether their associations with health-related quality of life (HRQoL) were similar in these rheumatologic disorders. In 55 AS and 199 RA patients, we administered the Patient Health Questionnaire (PHQ-9), the Symptom Check-List and the Brief-Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQoL. We used hierarchical regression analyses to determine the associations between psychological variables and HRQoL after adjusting for demographic variables and disease parameters. The prevalence of clinically significant depressive symptoms (PHQ-9 ≥ 10) was 14.8 % in AS and 25.1 % in RA patients, but adjustment for demographics rendered these differences in depressive symptoms' severity non-significant. Psychological distress levels and HRQoL were similar in both disorders. Illness concern (b = -0.37) was the only significant independent correlate of physical HRQoL in AS. In RA, depression (b = -0.25), illness concern (b = -0.14) and worries about the consequences of the disease (b = -0.31) were the independent correlates of physical HRQoL. These findings suggest that cognitive variables are important correlates of HRQoL in AS, whereas in RA depressive symptoms and illness perceptions equally contribute to HRQoL. Our data encourage the design of psychotherapeutic trials targeting disease-related cognitions in AS in an attempt to improve patient's physical HRQoL.

Adult-onset Still's disease: clinical, serological and therapeutic considerations.

OBJECTIVES: This paper aims to describe the clinical manifestations, laboratory abnormalities and treatment of adult-onset Still's disease (AOSD) in Greek patients. METHODS: This is a retrospective observational study. Forty-four patients, diagnosed with AOSD, followed since 1985 up to June 2011, were included. The disease course and treatment were recorded and compared to previously published studies. RESULTS: Twenty-one males and 23 females were identified. Mean age at diagnosis was 38.3 years. The most common clinical manifestations were fever (100%), arthralgias (97.7%), arthritis (93.2%), salmon-coloured rash (84%), myalgias (50%) and sore throat (38.6%). Characteristic laboratory abnormalities were leucocytosis with neutrophilia (81.8%), elevated C-reactive protein (100%) and erythrocyte sedimentation rate (100%). Elevated liver enzymes and hyperferritinaemia were found in 50% and in 59% of the patients respectively. Very high ferritin serum levels (>5000 µg/l) were found in 22.7%. Rheumatoid factor and antinuclear antibodies were negative in all patients. Thirty patients (68.2%) received non-steroidal anti-inflammatory drugs or aspirin with or without corticosteroids. Response to corticosteroids was common (58.9%). When this treatment was ineffective, a disease-modifying anti-rheumatic drug (DMARD), usually methotrexate, was added with a response rate of 63.6%. Anakinra was used in cases resistant to conventional immunosuppressive treatment. Ten out of 44 patients (22.7%) were treated with anakinra and response was achieved in all of them. CONCLUSIONS: Our results regarding clinical manifestations and laboratory abnormalities were similar to those of previous reports. High ferritin serum levels were reported in all studies of AOSD and are considered as diagnostically valuable. When treatment with corticosteroids and DMARDS had failed, biologic agents such as anakinra were successfully applied.

Anxiety and depressive symptoms and illness perceptions in psoriatic arthritis and associations with physical health-related quality of life.

OBJECTIVE: Symptoms of psychological distress, including anxiety and depressive symptoms, and illness perceptions are important in determining outcome in patients with rheumatic disease. We aimed to compare psychological distress in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and to test whether the association between psychological variables and health-related quality of life (HRQOL) was similar in the 2 forms of arthritis. METHODS: In 83 PsA patients and 199 RA patients, we used the Patient Health Questionnaire 9 (PHQ-9), the Symptom Checklist-90-Revised, and the Brief Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQOL. We used hierarchical regression analysis to determine the associations between psychological variables and HRQOL after adjusting for demographic variables and disease parameters. RESULTS: The prevalence of moderate to severe levels of depressive symptoms (PHQ-9 score ≥10) was 21.7% in PsA patients, 25.1% in RA patients, and 36.7% in those PsA patients with polyarthritis. After adjustment for severity of disease and pain, anxiety (ß = -0.28) and concern about bodily symptoms attributed to the illness (ß = -0.33) were independent correlates of physical HRQOL in PsA. In RA, depressive symptoms (ß = -0.29) and concern about the consequences of the arthritis (ß = -0.27) were independent correlates of physical HRQOL. CONCLUSION: These findings suggest strongly that psychological factors are important correlates of HRQOL in PsA as well as in RA. Attention to patients' anxiety and their concern about numerous bodily symptoms attributed to the illness may enable rheumatologists to identify and manage treatable aspects of HRQOL in PsA.

CNS involvement in primary Sjogren Syndrome: assessment of gray and white matter changes with MRI and voxel-based morphometry.

OBJECTIVE: The purpose of this study was to evaluate with MRI the involvement of gray matter and white matter structures in patients with primary Sjögren syndrome. SUBJECTS AND METHODS: Fifty-three patients with primary Sjögren syndrome, 18 age- and disease duration-matched patients with systemic sclerosis, and 35 age-matched control subjects were examined for differences in white matter hyperintensities (WMHIs) detected on FLAIR MR images. Differences in brain volume between patients with primary Sjögren syndrome and controls were studied by application of voxel-based morphometry to a 3D T1-weighted sequence. RESULTS: WMHIs were observed in 38 of the 53 patients with primary Sjögren syndrome, six of 18 patients with systemic sclerosis, and 17 of 35 controls. The numbers of WMHIs 2 mm or larger and the number smaller than 2 mm were higher in patients with primary Sjögren syndrome than in controls (≥ 2 mm, p = 0.004; < 2 mm, p < 0.001). No significant difference was observed in the number of WMHIs in primary Sjögren syndrome patients and that in systemic sclerosis patients. After control for age, a positive relation was found between disease duration and total number of WMHIs (p = 0.037) and number of WMHIs 2 mm or larger (p = 0.023) in patients with primary Sjögren syndrome. In comparison with the controls, patients with primary Sjögren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum. Associated loss of white matter volume was observed in areas corresponding to gray matter atrophy and in the corpus callosum (p < 0.05). CONCLUSION: Patients with primary Sjögren syndrome have WMHIs and gray and white matter atrophy, probably related to cerebral vasculitis.

Diagnostic accuracy, internal consistency, and convergent validity of the Greek version of the patient health questionnaire 9 in diagnosing depression in rheumatologic disorders.

OBJECTIVE: The Patient Health Questionnaire 9 (PHQ-9) was developed to screen for depressive disorders in community, primary care, and medical settings. We aimed to estimate its diagnostic accuracy, internal consistency, reliability, and convergent validity in diagnosing major depressive disorder (MDD) in Greek patients with rheumatologic disorders. METHODS: In a 2-phase sampling design study, we recruited 475 patients with established rheumatologic disorders. One of 2 of the high scorers (PHQ-9 score ≥9, n = 85) and 1 of 3 of the low scorers (PHQ-9 score 0-8, n = 128) were interviewed using the Mini International Neuropsychiatric Interview to confirm MDD. A receiver operator characteristic curve analysis was performed to confirm the optimum threshold value. The scale's dimensional structure was tested with factor analysis, and internal consistency reliability was assessed with Cronbach's alpha. Psychological distress (Symptom Check List-90-Revised [SCL-90-R]), disability (Health Assessment Questionnaire disability index), and health-related quality of life (HRQOL; World Health Organization Quality of Life Instrument [WHOQOL-BREF]) were also assessed to test convergent validity with bivariate correlations. RESULTS: At an optimum threshold of 10, the PHQ-9 showed a sensitivity of 81.2% and a specificity of 86.8%. The area under the curve was 0.91. The PHQ-9 presented unidimensional structure with good scale reliability (α = 0.82). The PHQ-9 score presented the greatest correlations with SCL-90-R depression (r = 0.736) and WHOQOL-BREF mental HRQOL scales (r = -0.571), and all other correlations with disability and HRQOL were in the expected direction. CONCLUSION: At a cutoff of 10, the PHQ-9 is an accurate, reliable, and valid measure for screening for MDD among Greek rheumatologic patients.

Comparison of health-related quality of life and associated psychological factors between younger and older patients with established rheumatic disorders.

OBJECTIVES: To compare health-related quality of life (HRQOL) between younger and older patients with established rheumatic disorders and to assess the relative impact of a number of psychosocial parameters on HRQOL. METHODS: In a cross-sectional study of 320 patients (245 < 65 and 75 > or = 65 years old, response rate: 74.9%) with various rheumatic disorders (rheumatoid arthritis, 168; systemic lupus, 56; scleroderma, 56; and Sjogren's syndrome, 40) attending a follow-up clinic, HRQOL was assessed by the WHOQOL-BREF. Functional limitations (Health Assessment Questionnaire), psychological distress (Symptom Distress Checklist-90-R), defense mechanisms (Defense Style Questionnaire and Life Style Index), sense of coherence, and interpersonal difficulties (Inventory of Interpersonal Problems-40) were also assessed. RESULTS: Older patients presented more impaired physical HRQOL (p = 0.018) and social relationships HRQOL (p = 0.041) independent of disease type, education, and pain. Functional limitations were more prominent in the older group (p = 0.030). Pain, functional limitations, and psychological distress were independently associated with physical HRQOL in both groups. Psychological distress was the only common independent correlate of social relationships HRQOL. Personality factors were significant correlates of physical and social relationships HRQOLs only in the younger group, while the impact of pain in physical HRQOL was greater for younger than older patients, as shown by a moderator analysis. CONCLUSION: Older patients with rheumatic diseases experience more impaired HRQOL than the younger ones, and the management and prevention of functional limitations and psychological distress should be a priority, since they are strongly associated with HRQOL. Pain also warrants attention in all age groups, but especially in younger patients. Personality factors impact on HRQOL in younger patients, and this might be relevant to psychological interventions.

Somatization is associated with physical health-related quality of life independent of anxiety and depression in cancer, glaucoma and rheumatological disorders.

PURPOSE: To test the relative importance of anxiety, depression and somatization as correlates of physical health-related quality of life (HRQOL) in several chronic physical disorders. METHODS: In a cross-sectional study of patients with colorectal cancer (N = 162), glaucoma (N = 100), rheumatoid arthritis (N = 168), systemic sclerosis (N = 56) and systemic lupus erythematosus (N = 56), we assessed specific disease severity and used the Symptom Distress Checklist (SCL-90) for psychologic dimensions. Outcome was assessed with the WHO Quality of Life Instrument, Short Form using hierarchical regression to determine independent correlates of HRQOL. RESULTS: After adjustment for demographic features, stage of cancer and pain (final models), the SCL-90 somatization score was the only psychologic distress covariate significantly correlated to physical HRQOL in all diseases (Betas between -0.33 and -0.49) except in systemic sclerosis and scleroderma, where depression was also a correlate. In glaucoma patients, the SCL-90 somatization score was the only significant covariate for physical HRQOL in the final model. CONCLUSIONS: Since reported number of bodily symptoms is both associated with physical HRQOL and treatable in its own right, our findings suggest a possible new avenue to improve the HRQOL in patients with chronic physical disease. Whether this offers greater benefit than treatments for anxiety and depression needs further research.

Sustained clinical response and high infliximab survival in psoriatic arthritis patients: a 3-year long-term study.

OBJECTIVE: To investigate the efficacy, toxicity, and survival of infliximab in patients with psoriatic arthritis (PsA). METHODS: Thirty-two patients with PsA, refractory to at least 2 disease-modifying antirheumatic drugs, were included in this prospective, open-label, uncontrolled study. All had active disease, defined as having a tender or swollen joint count > or =6, Psoriasis Area and Severity Index (PASI) scores > or =10, and erythrocyte sedimentation rate > or =28 mm Hg/h, or C-reactive protein > or =10 mg/L. The primary endpoints were the percentage of patients who achieved the Psoriatic Arthritis Response criteria (PsARC) and the improvement of PASI. Patients were treated with infliximab (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter for a period of 3 years. Data concerning infliximab efficacy, tolerability, concomitant therapy, adverse events, and drug discontinuation were recorded. The clinical response according to the American College of Rheumatology (ACR) criteria as well as the disease activity for 28 joint indices score (DAS-28) were also recorded. RESULTS: After the third year of treatment, PsARC was achieved by 23/32 of patients, PASI 70 by 24/32, and PASI 90 by 23/32. A significant improvement of ACR and DAS-28 was noted. Clinical improvement was associated with a reduction of acute phase reactants. Eight patients withdrew from the study primarily for acute allergic reactions. After the first year, infliximab survival was 84%, while after the second year, it was 75%, which was maintained throughout the third year of treatment. CONCLUSION: Infliximab was effective, safe, and well tolerated in patients with PsA. The clinical response was maintained for a period of 3 years with high infliximab survival.

Neurological manifestations of connective tissue diseases mimicking multiple sclerosis.

The objective of the study was to analyze retrospectively the clinical, laboratory and imaging findings of multiple sclerosis (MS), such as the manifestations in a cohort of 132 patients referred to the neurology in and outpatient clinic. The proposed clinical and laboratory diagnostic criteria for MS and connective tissue disorders were systematically assessed in 132 consecutive patients. Cerebrospinal fluid serology and brain or spinal cord MRI were studied in all cases. In patients suspected for connective tissue disorder, schirmer test, rose bengal staining and biopsy of minor salivary glands were performed. A total of 115 (87%) patients were diagnosed to have definite MS, while 17 (13%) were diagnosed to have connective tissue disorder. Positive neurological and MRI findings were observed in both groups. The majority of patients with connective tissue disorder demonstrated extra-neurological manifestations like Raynaud's phenomenon, arthritis, livedo reticularis, purpura and presence of multiple autoantibodies in their sera. All patients with MS should be screened systematically for connective tissue disorder. In the absence of pathognomonic clinical and laboratory findings, the diagnosis of MS is a diagnosis of exclusion.