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.

Intramuscular midazolam versus intravenous diazepam for treatment of seizures in the pediatric emergency department: a randomized clinical trial.

AIM: To compare the therapeutic efficacy of intramuscular midazolam (MDZ-IM) with that of intravenous diazepam (DZP-IV) for seizures in children. DESIGN: Randomized clinical trial. SETTING: Pediatric emergency department. PATIENTS: Children aged 2 months to 14 years admitted to the study facility with seizures. INTERVENTION: Patients were randomized to receive DZP-IV or MDZ-IM. MAIN MEASUREMENTS: Groups were compared with respect to time to treatment start (min), time from drug administration to seizure cessation (min), time to seizure cessation (min), and rate of treatment failure. Treatment was considered successful when seizure cessation was achieved within 5min of drug administration. RESULTS: Overall, 32 children (16 per group) completed the study. Intravenous access could not be obtained within 5min in four patients (25%) in the DZP-IV group. Time from admission to active treatment and time to seizure cessation was shorter in the MDZ-IM group (2.8 versus 7.4min; p<0.001 and 7.3 versus 10.6min; p=0.006, respectively). In two children per group (12.5%), seizures continued after 10min of treatment, and additional medications were required. There were no between-group differences in physiological parameters or adverse events (p=0.171); one child (6.3%) developed hypotension in the MDZ-IM group and five (31%) developed hyperactivity or vomiting in the DZP-IV group. CONCLUSION: Given its efficacy and ease and speed of administration, intramuscular midazolam is an excellent option for treatment of childhood seizures, enabling earlier treatment and shortening overall seizure duration. There were no differences in complications when applying MDZ-IM or DZP-IV.

HLA alleles and HLA-B27 haplotypes associated with susceptibility and severity of ankylosing spondylitis in a Portuguese population.

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity.

Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population.

OBJECTIVE: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score. METHODS: The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect Statistical tools, by fixed and random effects models. RESULTS: A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAP1, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS. CONCLUSION: These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.

Portuguese recommendations for the prevention, diagnosis and management of primary osteoporosis - 2018 update.

BACKGROUND: Advances in osteoporosis (OP)case definition, treatment options, optimal therapy duration and pharmacoeconomic evidence in the national context motivated the Portuguese Society of Rheumatology (SPR) to update the Portuguese recommendations for the diagnosis and management of osteoporosis published in 2007. METHODS: SPR bone diseases' working group organized meetings involving 55 participants (rheumatologists, rheumatology fellows and one OP specialist nurse) to debate and develop the document. First, the working group selected 11 pertinent clinical questions for the diagnosis and management of osteoporosis in standard clinical practice. Then, each question was investigated through literature review and draft recommendations were built through consensus. When insufficient evidence was available, recommendations were based on experts' opinion and on good clinical practice. At two national meetings, the recommendations were discussed and updated. A draft of the recommendations full text was submitted to critical review among the working group and suggestions were incorporated. A final version was circulated among all Portuguese rheumatologists before publication and the level of agreement was anonymously assessed using an online survey. RESULTS: The 2018 SPR recommendations provide comprehensive guidance on osteoporosis prevention, diagnosis, fracture risk assessment, pharmacological treatment initiation, therapy options and duration of treatment, based on the best available evidence. They attained desirable agreement among Portuguese rheumatologists. As more evidence becomes available, periodic revisions will be performed. Target audience and patient population: The target audience for these guidelines includes all clinicians. The target patient population includes adult Portuguese people. Intended use: These recommendations provide general guidance for typical cases. They may not be appropriate in all situations - clinicians are encouraged to consider this information together with updated evidence and their best clinical judgment in individual cases.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Tophaceous Gout: a tragic course for a preventable disease.

A 66-year-old man, with a history of chronic tophaceous gout since the age of 30, presented with multiple tophi and significant deformity of all fingers that caused substantial function loss. Due to osteomyelitis refractory to antimicrobial therapy, he underwent disarticulation of several fingers. Finally, both his hands were amputated.

Baastrup's Disease: a poorly recognised cause of back pain.

A 56-year-old male complained about progressive mechanical back pain for more than 10 years, which worsened with prolonged orthostatism and spine extension and improved in fetal position. His lumbar spine radiography revealed enlargement and sclerosis of the spinous processes which was confirmed by computed tomography, suggesting Baastrup's disease. This condition is characterized by enlargement, close approximation and impingement of one spinous process on another ("kissing spines"). There are few studies on Baastrup´s disease epidemiology and their results are inconsistent. Patients often complain of back pain, typically increased with extension and relieved by flexion. Radiographically, spinous process impingement leads to reactive sclerosis, enlargement, flattening, and remodeling of the involved vertebral spines. Physicians frequently miss it on radiographs due to lack of knowledge and overexposure of spinous processes in most X rays. Both conservative and surgical options are available for treatment. Baastrup's disease should be considered in differential diagnosis of back pain, although one must be aware the typical radiographic changes appear to be common with aging and may not be the cause of patient's symptoms.

Outcome after treatment of high-grade squamous intraepithelial lesions: relation between colposcopically directed biopsy, conization and cervical loop excision.

PURPOSE OF INVESTIGATION: The hypothesis that cold-knife conization performed in women with high-grade squamous intraepithelial lesions (HSIL) and unsatisfactory colposcopy is a better procedure than the loop electrosurgical procedure (LEEP) is tested. METHODS: A retrospective study was conducted in conization specimens of women submitted to LEEP (n = 102) or conization (n = 245) due to HSIL. Age, biopsy, compromised surgical margins in conization, and recurrence were analysed. RESULTS: The frequency of invasion, non-compromised margins, and recurrence in conization and LEEP were, respectively, 7.7% versus 2.9%, 64.1% versus 48% (p = 0.008), and 33.8% versus 24.1%. Eight (42.1%) and five (26.3%) of 19 women submitted to conization where invasion was found in surgical specimens were, respectively, menopausal or had unsatisfactory colposcopy. Twenty-five (96.2%) of 26 and 23 (95.8%) of 24, respectively, undergoing conization and LEEP had recurrence in the first five years. CONCLUSION: We recommend the use of cold-knife conization in cases where the lesion is located deep in the cervical canal.

[Psoriatic Arthritis concomitant with Paget's Disease - a case report]. / Artrite Psoriática concomitante com Doença de Paget - a propósito de um caso clínico.

Paget disease of bone is a focal disorder of bone metabolism; it is characterized by an accelerated rate of bone remodeling, with profound changes in the bone structure, making it fragile. This condition affects approximately 2% to 5% of the population older than 40. The main clinical manifestations of Paget's disease are pain and bone deformity, although the majority of patients are asymptomatic. Psoriatic Arthritis is a spondyloarthritis with a prevalence of about 0,1%. It is characterized by the presence of arthritis, enthesitis and/or dactylitis associated with a familiar or personal history of psoriasis. Several clinical patterns of joint involvement in psoriatic arthritis have been identified, namely, the polyarticular pattern, similar to rheumatoid arthritis. Arthritis precedes skin disease in approximately 13 to 17 % of the cases. The authors report a clinical case of a 60 years old patient with polyarthritis and dactylitis who was diagnosed with psoriatic arthritis and Paget's disease of bone. The concomitance of the two entities, in the same individual, with so different pathogenesis and clinical features, have never been described on literature. Because of the complexity on the clinical and imaging evaluation as the result of the coexistence of both pathologies, the authors consider relevant to publish this singular case.

Ocular and parotid sarcoidosis - panda sign.

Sarcoidosis is a multisystem disease with ocular involvement in 25-50% of patients, parotid and other salivary glands involvement in 6%, resulting in this characteristic panda sign in Gallium-67 scan, present in a 16 year old male with a history of bilateral recurrent uveitis.

Mantle cell lymphoma and systemic sclerosis.

Systemic sclerosis (SSc) is a rare disease with an increased incidence of cancer, but the ocorrence of Non-Hodgkin lymphoma (NHL) is a very uncommon event. We report a case of a 76-year-old female addmited to the hematology clinic with long-term adenopathies and ocasional gastro-intestinal symptomatology. Progressive symmetrical swelling of hands was also noticed. Colonoscopy revealed multiple polyps and histopathology was consistent with Mantle-Cell Lymphoma (MCL)-NHL. R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) regimen was promptly iniated with complete response. Persistent swelling of both hands was observed, with thickening of the skin of both hands with proximal extension until the forearm. Biopsy confirmed the diagnosis of scleroderma. Symptomatic and rehabilitation treatment was initiated with mild improvement of symptoms. To our knowledge this is the first case of MCL associated with SSc.

Sexuality in spondyloarthritis--the impact of the disease.

INTRODUCTION: The impact of rheumatic diseases on patients' sexual life has been gathering the attention of the scientific community over the last decade. The existing studies are scarce, especially related to spondyloarthritis, and particularly to psoriatic arthritis. Several factors associated with the disease may condition sexual function: pain, stiffness, decreased range of motion, joint swelling and extraarticular features such as fatigue, enthesopathy and cutaneous lesions in psoriatic arthritis. OBJECTIVES: To assess sexual satisfaction and limitations in sexual activity in a cohort of patients with spondyloarthritis. METHODS: An anonymous questionnaire was performed, consisting in two parts. One part consisted in a questionnaire filled by the doctor with data on the disease; the other part was filled by the patient, with demographic data, multiple choice questions and questions to be answered through a visual analogic scale, including items approached in some validated indexes of sexual function and satisfaction assessment. Statistical treatment was performed using SPPS system, version 17.0. RESULTS: 76 patients with the diagnosis of spondyloarthritis were enrolled; 31 had psoriatic arthritis, 30 had ankylosing spondylitis, 9 had undifferentiated spondyloarthritis and 6 had inflammatory bowel disease spondyloarthritis. In a visual analogic scale, the perception of conditioning in the conjugal relationship was 33.68±31.56 mm; limitation on sexual activity was 32.72±31.06 mm; limitation imposed by pain, joint swelling, fatigue, stiffness, decreased range of motion, decreased libido and cutaneous lesions ranged from 29.17±28.51 mm (swelling) to 46.94±32.31 mm (fatigue); there was no significant difference between sexes, diagnose and type of involvement. A strong correlation was identified between some analysed factors and ASQoL and HAQ values, but only moderate between them and disease function and activity indexes. Most of patients did not talk about their sexual limitations with their partners or with health professionals. CONCLUSION: This work highlights the impact of spondyloarthritis on patients' sexual function. The type of disease and joint involvement didn't imply statistically significant differences on the analyzed parameters in this cohort. This work also emphasizes the unawareness of health professionals towards this subject, whose approach is equally difficult to the patients, and might deserve greater attention.

SARCOSPA - Sarcopenia in spondyloarthritis patients.

INTRODUCTION: The loss of muscle mass (MM) is a serious problem which has been demonstrated in patients with rheumatoid arthritis. There are few studies about the loss of MM in patients with spondyloarthritis (Spa). OBJECTIVE: To assess muscle mass index (MMI) in a cohort of patients with Spa and compare it with a control group of healthy individuals; to verify if a higher risk of sarcopenia is related with disease activity, functional impairment, duration of the illness and radiological damage. METHODS: Case control study. Muscle mass index (MMI) was determined, from the value of MM, using Lee's equation, in a cohort of patients with spondyloarthritis and in a control group. Bath Ankylosing Spondylitis Disease Activity and Function Indexes (BASDAI and BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) and Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were assessed in a cohort of patients with axial Spa, as well as Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 (DAS28) in patients with peripheral disease. Data were treated using SPSS version 17.0. Values of p<0,05 were considered with statistical significance. RESULTS: 60 patients were enrolled; 48.2% were males, mean age 45.5±13.4 years, mean disease duration 10.9±11.6 years; 36 had ankylosing spondylitis and 24 had psoriatic arthritis. 62% of patients had sarcopenia and there was a significant difference in mean MMI between patients and controls (7.65±0.98 vs 8.25±0.92; p=0.001, OR =5.23. In male patients, there was a statistically significant moderate negative correlation between MMI and BASDAI and BASFI (p=-0.536 and p=-0.445). No other significant correlations were identified. CONCLUSION: Our study supports the hypothesis of a greater prevalence of sarcopenia in patients with Spa compared to healthy controls. Some limitations included the sample size, potential confounding factor such the bias of measurement and the use of a non-validated equation to Portuguese population to calculate MM.

Portuguese version of the bath indexes for ankylosing spondylitis patients: a cross-cultural adaptation and validation.

The Bath Ankylosing Spondylitis Activity Index (BASDAI), Functional Index (BASFI), Metrology Index (BASMI), and Global Score (BASG) are commonly used to assess patients with ankylosing spondylitis (AS). The aim of this study was to cross-culturally adapt and validate these indexes into the Portuguese language. Seventy-eight patients were included in the study. After forward and backward translations, the questionnaires were administered and tested for internal consistency, test-retest reliability, face validity, content validity, and construct validity. The outcome measures HAQ, EQ-5D, and SF-36 were also implemented. Metrological parameters (BASMI components) and chest expansion were evaluated. Correlation coefficients for test-retest were 0.875, 0.937, 0.831, and 0.961 for BASDAI, BASFI, BASMI, and BASG, respectively. Internal consistency coefficients were between 0.747 and 0.953. The adapted and translated questionnaires demonstrated an acceptable comprehensibility by a panel of patients, and face validity was assured by the cognitive debriefing performed. Content validity was assured by comparing the scores obtained by the questionnaires when age and gender, age of symptoms onset, and disease duration were considered. Construct validity was assured by significant correlations established between the Bath scores and generic health status HAQ, EQ-5D and SF-36, morning stiffness duration, chest expansion, and physician disease activity assessment. The Portuguese version of the BASDAI, BASFI, BASG, and BASMI showed adequate reliability and validity in patients with AS. The measurement properties were comparable to versions in other languages, indicating that the indexes can be used for evaluation of Portuguese-speaking AS patients.

Intramuscular midazolam versus intravenous diazepam for treatment of seizures in the pediatric emergency department: A randomized clinical trial

AIM: To compare the therapeutic efficacy of intramuscular midazolam (MDZ-IM) with that of intravenous diazepam (DZP-IV) for seizures in children. DESIGN: Randomized clinical trial. Setting Pediatric emergency department. PATIENTS: Children aged 2 months to 14 years admitted to the study facility with seizures. Intervention Patients were randomized to receive DZP-IV or MDZ-IM. Main measurements Groups were compared with respect to time to treatment start (min), time from drug administration to seizure cessation (min), time to seizure cessation (min), and rate of treatment failure. Treatment was considered successful when seizure cessation was achieved within 5min of drug administration. RESULTS: Overall, 32 children (16 per group) completed the study. Intravenous access could not be obtained within 5min in four patients (25%) in the DZP-IV group. Time from admission to active treatment and time to seizure cessation was shorter in the MDZ-IM group (2.8 versus 7.4 min; p < 0.001 and 7.3 versus 10.6 min; p = 0.006, respectively). In two children per group (12.5%), seizures continued after 10min of treatment, and additional medications were required. There were no between-group differences in physiological parameters or adverse events (p = 0.171); one child (6.3%) developed hypotension in the MDZ-IM group and five (31%) developed hyperactivity or vomiting in the DZP-IV group. CONCLUSION: Given its efficacy and ease and speed of administration, intramuscular midazolam is an excellent option for treatment of childhood seizures, enabling earlier treatment and shortening overall seizure duration. There were no differences in complications when applying MDZ-IM or DZP-IV

OBJETIVO: Comparar la eficacia de midazolam intramuscular (MDZ-IM) con la de diazepam intravenoso (DZP-IV) para convulsiones en niños. DISEÑO: Ensayo clínico aleatorizado. ÁMBITO: Servicio de Urgencias Pediátricas. PACIENTES: Niños de entre 2 meses y 14 años internados con convulsiones .Intervención Los pacientes fueron aleatorizados para recibir DZP-IV o MDZ-IM. MEDICIONES PRINCIPALES: tiempo hasta el inicio del tratamiento (minutos), tiempo entre la administración del medicamento y el cese de la convulsión (minutos), tiempo hasta el cese de la convulsión (minutos), y tasa de fallo del tratamiento. El tratamiento fue considerado exitoso cuando las convulsiones cesaron en los 5 min tras la administración del medicamento. RESULTADOS: Completaron el estudio 32 niños (16 por grupo). No fue posible obtener acceso intravenoso en 4 pacientes (25%) del grupo DZP-IV. El tiempo entre la internación y el tratamiento fue menor en el grupo MDZ-IM (2,8 vs. 7,4 min; p < 0,001), así como el tiempo hasta el cese de la convulsión (7,3 vs. 10,6 min; p = 0,006). En 2 niños de cada grupo (12,5%), las convulsiones continuaron después de 10min de tratamiento. No hubo diferencias entre los grupos en los parámetros fisiológicos o eventos adversos (p = 0,171); un niño (6,3%) del grupo MDZ-IM presentó hipotensión, y 5 del grupo DZP-IV (31%) presentaron hiperactividad o vómitos. CONCLUSIÓN: Dada su eficacia, facilidad y velocidad de administración, MDZ-IM es una excelente opción para el tratamiento de convulsiones infantiles, posibilitando un tratamiento precoz y reduciendo la duración de la convulsión. No hubo diferencias en las complicaciones al aplicar MDZ-IM o DZP-IV