Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients.

OBJECTIVE: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. METHODS: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ΔPGA ≥ 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. RESULTS: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho = 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ≥ 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. CONCLUSIONS: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research.

Overactive bladder symptom bother and health-related quality of life in patients with systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). METHODS: We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. RESULTS: We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient -3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. CONCLUSIONS: Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

Psoriatic Arthritis Quality of Life questionnaire: translation, cultural adaptation and validation into Portuguese language.

Psoriatic arthritis (PsA) has a strong negative impact on the quality of life of patients. The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire is a disease-specific instrument developed to measure the quality of life in patients with PsA. The aims of this study were to culturally adapt the questionnaire for Portugal and evaluate its reliability and validity in patients with PsA. The original UK English version of the PsAQoL was translated into Portuguese by a bilingual and lay panel. Structured cognitive debriefing interviews were conducted with ten PsA patients. The Portuguese PsAQoL was subsequently applied to PsA patients followed at the Rheumatology Department of Centro Hospitalar do Baixo Vouga, E.P.E. To assess reproducibility, 30 patients with PsA completed the Portuguese PsAQoL on two occasions, 2 weeks apart. A larger sample was recruited to determine internal consistency and construct validity. The Nottingham Health Profile (NHP) was used as a comparator instrument. Translation and adaptation were successful. Cronbach´s alpha for the Portuguese version of the PsAQoL was 0.91 and the test-retest reliability was 0.93. The PsAQoL could distinguish between groups of patients defined by self-reported general health status, self-reported severity of PsA and flare of arthritis. There was a positive correlation between the total score of the PsAQoL and each of the sections of the NHP. The Portuguese version of the PsAQoL was found to be relevant, understandable and easy to complete, reliable and valid.

Encephalopathy with upper body hypertonia and myoclonus in patient with systemic lupus erythematosus and anti-CASPR2.

Systemic lupus erythematosus (SLE) may involve the nervous system but there are no specific biomarkers of neuroSLE. Limbic encephalitis has been rarely associated with SLE. We present a case of a 22-year-old black woman where typical SLE psychosis evolved to an encephalopathy with atypical features, normal MRI, electroencephalogram slowing and frontal and occipito-temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG PET).Memory deficits, bizarre behaviour, psychosis, neuromyotonia and movement disorders have been described in autoimmune central nervous system disorders and associated with specific antibodies. Brain MRI may be normal and cortical brain hypometabolism on FDG PET scans has been reported. We have not found any report of limbic encephalitis or other SLE neurological manifestation associated to positive titres of anti-CASPR2 antibodies and this may warrant systematic investigation. In the rare cases of limbic encephalitis associated with SLE no specific antibodies were documented. Anti-CASPR2 antibodies have been associated not only with limbic encephalitis but also with neuromyotonia and Morvan syndrome. Although our patient had a specific pattern of tone abnormalities with an impressive cervical and upper limb hypertonicity and flaccid lower limbs, no myotonic discharges were found. We did not find any association between myoclonus and anti-CASPR2 antibodies. We cannot exclude that a non determined autoantibody could have played a role; however, clinical and FDG PET improvement supports an antibody-mediated injury, in this case of neuroSLE.

The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG.

Psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) - a contribution to the Portuguese validation of the scale.

BACKGROUND: Fibromyalgia (FM) remains a relatively misunderstood and clinically challenging condition that impact significantly in the individual´s life, impairing global functioning and diminishing quality of life. Management is complex and frequently unsatisfactory, requiring personal tailoring and adaptation of interventions according to the fluctuations of the disease manifestations and their response to therapy. The use of comprehensive and quantified assessment tools constitutes, therefore, an essential component of the management of patients with FM. The Revised Fibromyalgia Impact Questionnaire (FIQR) is currently one of the most used and well validated instruments to assess functional (in)capacity and global impact of FM and associated symptoms. OBJECTIVES: To translate to Portuguese the FIQR and to study its psychometric properties. MATERIAL AND METHODS: The total sample comprised 103 women with fibromyalgia, defined according to the established criteria for FM. A self-report battery composed by the Revised Fibromyalgia Impact Questionnaire (FIQR), the Portuguese version of Beck Depression Inventory-II (BDI-II) and the Profile of Mood States (PoMS) was administered. The FIQR was re-administered to twenty-four participants, six weeks after the first evaluation. Internal reliability was assessed through Cronbach's alpha, corrected item-total score correlations and alpha if item deleted. Spearman and Pearson correlations along with repeated measures tests were computed to assess the temporal stability of the scale. Convergent and divergent validity were assessed via Spearman and Pearson correlations. RESULTS: The FIQR demonstrated a good to very good internal consistency (from α = 0.87 to α = 0.94). All items correlated to a good degree (above 0.30) to the total score and contributed significantly to the overall reliability. Moreover, FIQR presented a good temporal stability (from r = .617 to r = .886, p ≤ .001) and favorable convergent and discriminant validity with depressive symptoms (r > .289, p ≤ .01) and positive (r > -.186, p > .05) and negative affect (r > .206, p ≤ .05). CONCLUSIONS: The Portuguese version of the FIQR demonstrated good psychometric properties, which renders it a proper and valuable tool to be used in different settings.

[Dermatomyositis-like syndrome in x-linked agammaglobulinemia]. / SÍNDROMA DERMATOMIOSITE-LIKE EM DOENTE COM AGAMAGLOBULINÉMIA LIGADA AO CROMOSSOMA X.

Primary immunodeficiencies (PIDs) encompass more than 250 different pathological conditions. X-linked agammaglobulinemia (XLA) has been occasionally associated with cutaneous and muscular manifestations resembling dermatomyositis, often termed dermatomyositis-like syndrome (DLS). This syndrome has been associated with cutaneous, muscular and central nervous system manifestations, accompanying a persistent infection by an Echovirus. According to sixteen previously reported cases, this syndrome has a poor prognosis. We report the case of a 27-years old male, with XLA and DLS, successfully treated with 6 cycles of human immunoglobulin and methotrexate. Clinical symptoms improved dramatically with a complete resolution of the musculoskeletal manifestations. Despite this clinical response, prognosis should remain reserved. The evolution of this syndrome remains unpredictable and therapeutic options are limited. To the best of our knowledge, there are only a few reports of similar cases which have survived so many months after the diagnosis.

Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid arthritis.

Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and are widely use in the management of rheumatoid arthritis in combination with other synthetic and with biological disease-modifying anti-rheumatic drugs. Concerns about the risk of adverse effects of glucocorticoids, especially if they are given at higher dosages and for a longer time, hamper their use despite the clear symptomatic and disease modifying benefits. However, the evidence base for these concerns for low dose glucocorticoid therapy is quite limited due to the scarcity of quality literature on its safety in rheumatoid arthritis. This review discusses the current understanding about their disease-modifying effects, toxicity data from recent trials and observational studies, recommendations for their management and the current efforts to improve the therapeutic ratio of glucocorticoid through the development of new formulations, such as modified-release prednisone.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.

Septic arthritis: patients with or without isolated infectious agents have similar characteristics.

PURPOSE: Septic arthritis can be disabling and life-threatening, requiring prompt diagnosis and treatment. The infectious agent is not always identified in these patients. We revaluate septic arthritis cases discharged from our department, describing the affected population, causative microorganisms and antibiotic therapy used, and characterised differences between patients with and without isolated pathogenic agents. METHODS: Sixty-eight septic arthritis patients were included in this study. Diagnosis was based on clinical findings, and/or the presence of joint purulent material, and/or bacterial pathogen isolation from joint fluid/synovial membrane/blood cultures and response to antibiotics. Data analysis was performed using SPSS 20. RESULTS: Patients had a mean age of 61.1 ± 18.8 years, without sex predominance. 26.5 % had an infection ≤ 15 days before septic arthritis diagnosis. Besides previous infection, 57.4 % had ≥ 1 risk factors for septic arthritis, most commonly pharmacological immunosuppression (20.6 %), diabetes mellitus type 2 (19.1 %) and rheumatoid arthritis (17.6 %). The knee was the most often affected (54.3 %). Only 39.7 % presented fever from clinical onset until hospital admission (mean 13.4 ± 18.9 days). Leucocytosis was present in 45.6 % of patients, elevated erythrocyte sedimentation rate (ESR) in 75 % and elevated C-reactive protein (CRP) in 97.1 %. 5.9 % had articular damage attributable to septic arthritis. An infectious agent was isolated in 41.2 % of patients, with Staphylococcus aureus being the most frequent. 38.7 % of synovial fluid and 23.5 % of synovial membrane cultures were positive. Patients with an identified infectious agent have no significant differences other than more days of hospitalisation (p = 0.003) and in-hospital antibiotic treatment (p = 0.017). CONCLUSION: Synovial fluid and synovial membrane cultures more often identified pathogens compared to blood or urine cultures. Patients with and without an identified infectious agent have similar demographic, clinical, laboratory and radiographic characteristics.

[Osteoarticular brucellosis: an analysis of the past decade]. / Brucelose osteo-articular: um retrato dos últimos 10 anos.

OBJECTIVES: Characterize Osteoarticular Brucellosis in the University Hospital of Coimbra (HUC) in the past decade. MATERIAL AND METHODS: A retrospective study of the cases diagnosed between January/2000 and December/2009 in the HUC. RESULTS: Ninety patients were admitted with the dia-gnosis of brucellosis in our hospital, of whom 44 (49%; 18 men; 26 women, mean 49.5 years) had osteoarticular complications. Twenty-five (45%) patients had a positive epidemiological context. The most frequent clinical manifestation was local pain (73%) followed by polyarthralgias and constitutional symptoms. The C-reactive protein was the inflammatory marker most often increased (82%). The Rose Bengala test was positive in 42 patients, and a Wright's sero-aglutination above than 1/160 was detected in 28 patients. An etiologic agent was isolated in 28 (64%) patients, with 70% of positive blood cultures. The imaging procedure of choice was magnetic resonance imaging (MRI) (46%). The osteo-articular manifestation most frequent was spondylodiscitis (57%) with a lumbosacral involvement in 40%. All patients completed antibiotic therapy. One patient underwent surgery to drain the abscess. Patients had an average length of admission of 28.3 days, with a good outcome in 60%, and a reasonable outcome in 20%, despite 20% of the patients lost follow-up. CONCLUSIONS: Brucellosis is a disease of obligatory declaration not eradicated in Portugal, with a great impact on socio-economic and public health. So, this epidemiological knowledge of brucellosis cases, allows an early intervention and therapy.

BioRePortAP, an electronic clinical record coupled with a database: an example of its use in a single centre.

AIMS: To evaluate the efficacy and safety of the treatment of psoriatic arthritis (PsA) patients with tumor necrosis factor (TNF) antagonists in the Rheumatology Department of Hospital de Santa Maria using the BioRePortAP. METHODS: The Portuguese Society of Rheumatology (SPR) developed an electronic medical chart coupled with a database for the follow up of PsA patients, the BioRePortAP, which was launched in May 2009. This evaluation was based on all the PsA patients that were on active treatment with TNF antagonists in September 2009 and were registered in the BioRePortAP. All the previous data on these patients were introduced in BioRePortAP using the prospective paper based follow up protocol that this Department was using since 1999. Only patients with more than 9 months of treatment were analyzed. RESULTS: Forty-two patients with PsA, actively treated with anti-TNF agents in September 2009, for at least 9 months, were analyzed in BioRePortAP. Twenty-three patients were male (55%) and nineteen were female (45%). The average age of these patients was 49.8+/-10.9 years old, the average disease duration was of 10.7+/-5.6 years and the mean duration of biological therapy was of 37.8+/-27.8 months. For the 81% of patients with peripheral joint disease there was a mean reduction of more than 80% in the swollen and tender joint counts, and almost 50% in the health assessment questionnaire (HAQ) value. In the 19% of the patients with axial involvement the reduction of BASDAI and BASFI was not statistically significative. On top of that, PASI score suffered a reduction of 64%. Fourteen patients (33.3%) had to switch their TNF antagonist treatment. 58.8% of the switches were due to adverse effects and 41.2% due to therapy failure. Regarding the 56 adverse reactions registered, only one was a severe reaction. The remaining adverse reactions were not severe and 67% of them were due to infections. DISCUSSION: The results of this first report of the use of the BioRePortAP in clinical practice confirm the efficacy and safety of TNF antagonist treatment in PsA. The results shown here elucidate the potential applications of BioRePortAP as a tool for efficacy and safety assessment of PsA patients treated with biotechnological drugs.

Global functional status in rheumatoid arthritis: disease duration and patient age.

With the aim of clarifying whether patient age could be an additional explanation for the differences in the clinical expression of rheumatoid arthritis (RA) found in different populations, we evaluated the possibility of patient age being a significant factor associated with global functional status, independent from disease duration. Our present results suggest that both disease duration and patient age are major factors in the global functional status of patients with RA, and that patient age is particularly important when a subgroup of patients with more than 60 years of age and more than 20 years of disease duration is considered. These data are relevant when comparing two different RA groups: not only should we have a similar mean age and mean disease duration, but also the subgroups of patients more than 60 years of age and with more than 20 years of disease duration should correspond to equivalent proportions in the populations studied.

Effects of the neuropeptide, substance P, on lymphocyte proliferation in rheumatoid arthritis.

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10(-10) M to 10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

Peptide containing nerves in human synovium: immunohistochemical evidence for decreased innervation in rheumatoid arthritis.

The innervation of normal and rheumatoid human synovium was studied by immunofluorescence microscopy. Antibodies against the general neuronal marker protein gene product (PGP) 9.5 and specific neuropeptides were used. We observed sensory nerves containing substance P (SP) and calcitonin gene related peptide (CGRP) as well as autonomic sympathetic fibers immunoreactive for neuropeptide tyrosine (NPY), its C terminal peptide (C-PON) and the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). Three subpopulations of nerve fibers labelled with SP and CGRP were identified: some stained for SP or CGRP only and others contained both peptides. NPY/C-PON and TH labelled predominantly perivascular nerves. Quantification of immunostained nerves revealed a significantly decreased innervation of rheumatoid synovia. The densities of both PGP 9.5 and neuropeptide containing nerves were lower in all rheumatoid samples. Our results are compatible with a local release of neuropeptides into joint fluid and point to a disturbed neuronal control of rheumatoid synovial tissue.