Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation.

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

What is the association of depression with clinical response to therapy in patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs?

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. METHODS: A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. RESULTS: A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). CONCLUSION: Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

An anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols diet improved patient reported outcomes in fibromyalgia: A randomized controlled trial.

Background: Fibromyalgia (FM) has been associated with dysbiosis and low-grade inflammation. Studies have reported that diet influences clinical features in FM. Objective: To evaluate the effect of an anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols (FODMAP) diet on clinical outcomes of patients with FM. Methods: This two arms Randomized Controlled Trial (NCT04007705) included 46 female patients with FM. The intervention group (n = 22) adopted an anti-inflammatory diet for 3 months, excluding gluten, dairy, added sugar, and ultra-processed foods, along with a low FODMAPs diet in the first month. The control group (n = 24) followed general healthy eating recommendations. Both diets were applied by a certified dietitian. Before and after the intervention, participants were assessed regarding pain, fatigue, gastrointestinal symptoms, quality of sleep, and quality of life, through the Revised Fibromyalgia Impact Questionnaire (FIQR), Visual Analogue Pain Scale (VAS), Visual Analog Scale from gastrointestinal symptoms (VAS GI), Brief Pain Inventory (BPI), Pittsburg Sleep Quality Index (PSQI), Fatigue Severity Survey (FSS), and The Short Form Health Survey (SF-36). A blood sample was collected and high-sensitive C-Reactive Protein and Erythrocyte Sedimentation Rate were quantified. Paired Samples t-test/Wilcoxon and independent samples t-test/Mann-Whitney were used to compare variables between groups. Results: After intervention, there was an improvement in intervention group scores of FIQR (p = 0.001), VAS (p = 0.002), BPI (p = 0.011), FSS (p = 0.042), VAS_GI (p = 0.002), PSQI (p = 0.048), and SF36 (p = 0.045) compared to control group. Inflammatory biomarkers (hs-CRP, ESR) did not change in both groups. The intervention was beneficial in the intervention group, regardless of age, disease duration, body mass index variation, and body fat change between baseline and post-intervention. Conclusion: An anti-inflammatory and low-FODMAP diet improved clinical features in patients with FM and may be useful as a complement to pharmacological therapy. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04007705], identifier [NCT04007705].

Pseudotumoral calcinosis of the spine in systemic sclerosis - an atypical location.

Pseudotumoral calcinosis, particularly around the spine, is a rare complication of systemic sclerosis (SSc). The authors report a case of a 60-year-old woman with a limited cutaneous SSc observed for a 4-month history of back pain. Physical examination revealed a left paravertebral mass measuring around 7cm in the longest axis. The computed tomography (CT) showed the presence of calcified mass in the left paravertebral muscle, extending from the 12th dorsal to the 3rd lumbar vertebra. A diagnosis of pseudotumoral calcinosis secondary to SSc was made. Symptomatic treatment with analgesics allowed a significant improvement of clinical symptoms. Subcutaneous calcinosis is a common complication of SSc, however the pseudotumoral form remains extremely rare, particularly around the dorsolumbar spine. Treatment is limited to analgesic therapy or, in more severe cases, to surgical excision. Follow-up should be conducted to rule out complications.

A study protocol for a randomized controlled trial of an anti-inflammatory nutritional intervention in patients with fibromyalgia.

BACKGROUND: This study aims to analyze the effects of a potentially anti-inflammatory nutritional intervention in disease assessment parameters, inflammatory markers, and quality of life of fibromyalgia (FM) patients. METHODS: A sample of 100 female patients diagnosed with FM, followed up at Portuguese Institute of Rheumatology (IPR) in Lisbon, is being randomly allocated in two groups. Patients in the intervention group are adopting an anti-inflammatory diet, characterized by the exemption of the intake of foods containing gluten, dairy, sugar, and ultra-processed foods, during 3 months. During the first month, a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet is implemented, along with the anti-inflammatory diet, followed by the reintroduction of all fruits and vegetables over a consecutive period of 2 months. Patients in the control group are adopting a diet based on general recommendations for healthy eating. The outcomes are pain, fatigue, quality of sleep, quality of life, gastrointestinal symptoms, and inflammation. Before and after the 3 months intervention, and also 1 month after beginning the intervention, the following questionnaires are applied: Revised Fibromyalgia Impact Questionnaire, visual analog pain scale, Brief Pain Inventory,visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM, Short Form 36, Fatigue Severity Survey, and Pittsburg Sleep Quality Index. Ultra-sensitive serum C-reactive protein, eritrocyte sedimentation rate, and interleukin-8 are determined. Age, physical activity, anthropometric parameters, and body composition are being collected. Student's t test will assess the association between the disease evaluation parameters, the inflammatory markers, and the dietary interventions. DISCUSSION: The results of this study are expected to determine whether a change in patient nutrition helps to alleviate symptoms, which would optimize medical intervention. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT04007705 . Registered on July 5, 2019.

Quantitative analysis of air pollution and mortality in Portugal: Current trends and links following proposed biological pathways.

A wealth of studies focusing on the relationships between negative health outcomes and short-term and long-term exposures to environmental risk factors have produced estimates of the burden of disease attributable to air pollution, which have led to the implementation of air pollution control strategies. However, the call to expand those studies, in terms of geographical units of analysis to produce more accurate estimates of the burden of disease in the different countries has been made. Studies of the specific environment-health relationship concerning air pollution in Portugal are scarce and rather descriptive. Therefore, this work assesses the trends both in atmospheric levels of pollutants including particulate matter (PM10), ozone (O3), nitrogen dioxide (NO2) and sulphur dioxide (SO2), and in mortality rates for diabetes, malignant neoplasms and diseases of the respiratory, digestive and circulatory systems, and explores the links between exposure to air pollutants and mortality, following proposed biological pathways and using inferential statistics methods, for the period 2010 to 2017 in Portugal. The following major conclusions were drawn: (i) despite a somewhat initial downward trend in PM10 and a peak in O3 levels, fairly constant air pollution levels were mostly observed; (ii) concomitantly, increases in age-adjusted mortality rates were significant for all diseases except diabetes; (iii) lower atmospheric levels of pollutants were observed in rural areas, when compared to urban areas, except for ozone; (iv) age-adjusted mortality rates were higher in rural regions, for diabetes, and in urban regions, for malignant neoplasms; (v) for a 10 µg/m3 increase in atmospheric levels of PM10, regression analysis estimated an increase of 0.30% in the mortality rate for diseases of the respiratory, digestive and circulatory systems, and malignant neoplasms combined.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Dietary interventions in fibromyalgia: a systematic review.

Fibromyalgia (FM) is a chronic non-degenerative disease, whose nutritional therapy seems controversial. This systematic review aimed to synthesize the knowledge about the effect of dietary interventions on patient-reported outcomes (PRO) and inflammation in patients with FM. Six electronic databases - PubMed, BioMed Central, Cochrane library, EMBASE, LILACS and ISI - were searched for clinical trials, in which a dietary intervention in patients with FM diagnosed was conducted. Quality of evidence assessment was measured in accordance with GRADE methodology. Seven clinical trials - 3 randomized controlled trials, 1 unrandomized clinical trial and 3 uncontrolled clinical trials were identified. Dietary approaches included gluten-free diet (n = 1), raw vegetarian diet (n = 2), low Fermentable oligo-, di- and monossacharides, alcohols and polyols (FODMAPs) diet (n = 1), hypocaloric diet (n = 2) and monosodium glutamate- and aspartame-free diet interventions (n = 1). The major PRO were pain and functional repercussion, with 5 out of 7 studies reporting an improvement. The progress in secondary outcomes was reported for fatigue (2/5 studies), sleep quality (2/3 studies), depression and anxiety (3/6 studies), quality of life (4/5 studies), gastrointestinal symptoms (1/2 studies) and inflammatory biomarkers (1/1 study). However, according to Cochrane Risk of Bias, these studies had poor statistical quality. Well-designed studies should be performed to investigate the dietary interventions effect on FM. Key messages Fibromyalgia (FM) is a chronic non-degenerative disease, whose nutritional therapy seems controversial but promising. Pain and functional repercussion in FM patients seem to improve with a hypocaloric diet, a raw vegetarian diet or a low FODMAPs diet, as much as quality of life, quality of sleep, anxiety and depression and inflammatory biomarkers. Existing studies in this subject are scarce and low quality, which does not allow conclusions to be drawn.

Intra-articular epithelioid sarcoma of the knee: a diagnostic challenge.

Epithelioid sarcoma is a rare mesenchymal neoplasm characterized by aggregates of epithelioid cells. Intra-articular occurrence is exceedingly rare with only few reports described in the literature. A 22 year-old man presented a progressive mechanical knee pain. Initially, the investigation revealed a non-infectious unspecific synovitis. The patient gradually presented increasing knee enlargement and functional impairment. Intra-articular nodular proliferation with bone invasion was later observed on magnetic resonance imaging reevaluation. Pigmented villonodular synovitis hypothesis was considered. The biopsy ultimately revealed nodules of epithelioid cells with an immunoprofile compatible with epithelioid sarcoma diagnosis. The patient underwent neoadjuvant chemotherapy and radiotherapy and an above-knee amputation was performed.

Determinants of non-nociceptive pain in Rheumatoid Arthritis.

INTRODUCTION: Features suggestive of neuropathic pain (NP) have been described in RA in addition to nociceptive pain. We aimed to determine the clinical predictors of NP in RA patients and study its association with radiographic structural damage. METHODS: Cross-sectional study was performed with RA patients followed at our Rheumatology department. Patients with diagnosed neuropathy of other origin, non-RA related risk factors for NP (e.g. diabetes mellitus) or fibromyalgia according to expert opinion were excluded. Demographic and clinical data were collected and disease activity/functional measures were evaluated. Two questionnaires were applied to assess NP: the Leeds Assessment of Neuropathic Symptoms (LANSS) and the painDETECT questionnaire (PDQ). Radiographs performed in up to 12 months before/after the evaluation were classified according to the modified van der Heijde Sharp´s method. Univariate and multivariate logistic regression were performed to identify the predictors of NP. RESULTS: 112 patients were included. 86 (77%) were women, with a mean (SD) age of 55.1 (10.8) years and median disease duration of 13 [2-41] years. 45 (40%) patients had NP by the LANSS (≥12) and 28% had a possible/likely NP in the PDQ (≥13). Female sex was predictive of NP by both tests and disease duration was inversely associated with LANSS NP. After adjusting for those two variables, pain VAS and TJC were positive predictors of NP by both tests. The same was not true for SJC, ESR or CRP levels. DAS28-CRP was significantly associated with PDQ NP, losing its statistical significance after adjustment for TJC and pain VAS. The HAQ score increased the odds of NP for both tests, independently of DAS 28-CRP. Positivity for ACPA and previous/current hydroxychloroquine treatment had lower odds of NP. 90 patients performed radiographic evaluation. Joint narrowing score was a significant negative predictor of LANSS NP. After adjusting for global radiographic score, current methotrexate treatment had lower odds of LANSS NP and previous/current leflunomide was a positive predictor of NP by both tests. CONCLUSION: NP was associated with disease activity/functional scores but not with objective inflammatory measures. Greater structural damage, increased disease duration and ACPA positivity did not seem to increase the odds of NP. Possible association of NP and underlying csDMARD treatment was uncovered.

PORTUGUESE RECOMMENDATIONS FOR THE USE OF BIOLOGICAL THERAPIES IN PATIENTS WITH PSORIATIC ARTHRITIS--2015 UPDATE.

OBJECTIVE: To update recommendations for the treatment of psoriatic arthritis with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 16 recommendations included in this document were discussed and updated. The level of agreement among Portuguese Rheumatologists was assessed using an online survey. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with psoriatic arthritis (PsA). Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Therapy of calcinosis universalis complicating adult dermatomyositis.

Although frequent in juvenile dermatomyositis, calcinosis is a rare finding in adult dermatomyositis. It has been associated with disease activity and delayed treatment. It is more common in later phases of the disease, in sites under chronic stress and trauma. Calcinosis has been associated with inflammation but information about its pathogeny continues to evolve as we learn more about the underlying processes. Being uncommon, there is no standard therapy and management is guided by case studies and series. Different treatments have been used in an attempt to clear calcinosis lesions and prevent its recurrence but none has been clearly effective. The authors present the case of a 25 year-old female diagnosed with dermatomyositis who developed calcinosis universalis after stopping therapy. Immunossupressive therapy was reinitiated and therapy aiming at reduction of calcinosis was sequentially tried using: colchicine, hydroxide magnesium, diltiazem, alendronate, probenecid and pamidronate. After receiving intravenous pamidronate, calcinosis lesions decreased and the patient regained full range of movement and quality of life. No recurrence has occurred after eight years of follow-up.

Nutritional status assessment in colorectal cancer patients.

The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery procedure. The sample was divided between convention and fast-track procedures. Most of the individuals were overweight or obese but had lost weight on the past six months. Despite mild, there were signs of malnutrition in this sample with high losses of fat free mass, weight and also fat mass during the hospitalization period. These results reinforce the importance of malnutrition assessment in colorectal patients as well as consider weight loss on the past months and body composition in order to complement nutritional status evaluation.

El presente estudio pretende evaluar el estado nutricional de enfermos de cáncer colorectal portugueses teniendo en cuenta el tipo de cirugía y indicativos de calidad de vida. La malnutrición suele afectar hasta 85% de los enfermos de cáncer y 30-60% entre los de cáncer colorectal y puede afectar significativamente las mejorías de salud. Se ha completado una evaluación antropométrica de 50 individuos admitidos en un hospital portugués para cirugía incluido también ingestión alimentaria, historia clínica, complicaciones antes y después de la cirugía. La muestra ha sido dividida entre el procedimento quirúrgico convencional y el fast-track. La mayoría de los individuos era obesa ó tenía sobrepeso pero había perdido peso en los últimos 6 meses antes de entrar en el hospital. Aunque poco severas, tenían señales de malnutrición con grandes pérdidas de masa magra, peso y también grasa corporal durante el período en el hospital. Estés resultados han reenfocado la importancia de una evaluación nutrición en enfermos de cáncer, sobretodo colorectal teniendo en cuenta el peso perdido pero también la composición corporal para que se complete el protocolo de evaluación nutricional.

Tuberculosis in anti-TNF-α treated patients remains a problem in countries with an intermediate incidence: analysis of 25 patients matched with a control population.

BACKGROUND AND AIMS: An increased incidence of tuberculosis (TB) in patients under anti-TNF-α therapy has been reported, but outcome compared with TB in the general population are unknown. METHODS: Patients who had active tuberculosis while taking anti-TNF-α drugs were studied and compared with a control group of community-acquired TB matched for sex, age and data of TB. RESULTS: Twenty-five cases of TB were reported from a cohort of 765 patients under anti-TNF-α from 2001 to 2012. The incidence of TB per 100,000 patient-years was estimated to be 1337, 792 and 405 respectively for those on infliximab, adalimumab and etanercept. Twelve patients had inflammatory bowel disease, ten had rheumatologic diseases and three had psoriasis. From the 17 patients screened for latent TB before anti-TNF-α, three were treated with isoniazid. TB was diagnosed 1-108 months after starting anti-TNF-α, being the median time six, seven and 89 months respectively for those on infliximab, adalimumab and etanercept. Sixty per cent of the cases had extra-pulmonary TB. No deaths occurred in the case groups, while two died in control TB patients. Patients on anti-TNF-α drugs had more frequent extra-pulmonary TB, fever on presentation, higher mean C-reactive protein and lower positive rate of acid-fast bacilli. CONCLUSIONS: TB may still occur in those with negative testing, some of them probably representing new infections instead of reactivations. Three out of 25 patients had TB in spite of previously treated LTB, although, the outcome of TB was not worse than in the general population.

The relationship between duration of initial alcohol exposure and persistence of molecular tolerance is markedly nonlinear.

The neuronal calcium- and voltage-activated BK potassium channel is modulated by ethanol, and plays a role in behavioral tolerance in vertebrates and invertebrates. We examine the influence of temporal parameters of alcohol exposure on the characteristics of BK molecular tolerance in the ventral striatum, an important component of brain reward circuitry. BK channels in striatal neurons of C57BL/6J mice exhibited molecular tolerance whose duration was a function of exposure time. After 6 h exposure to 20 mm (0.09 mg%) ethanol, alcohol sensitivity was suppressed beyond 24 h after withdrawal, while after a 1 or 3 h exposure, sensitivity had significantly recovered after 4 h. This temporally controlled transition to persistent molecular tolerance parallels changes in BK channel isoform profile. After withdrawal from 6 h, but not 3 h alcohol exposure, mRNA levels of the alcohol-insensitive STREX (stress axis-regulated exon) splice variant were increased. Moreover, the biophysical properties of BK channels during withdrawal from 6 h exposure were altered, and match the properties of STREX channels exogenously expressed in HEK 293 cells. Our results suggest a temporally triggered shift in BK isoform identity. Once activated, the transition does not require the continued presence of alcohol. We next determined whether the results obtained using cultured striatal neurons could be observed in acutely dissociated striatal neurons, after alcohol administration in the living mouse. The results were in remarkable agreement with the striatal culture data, showing persistent molecular tolerance after injections producing 6 h of intoxication, but not after injections producing only 3 h of intoxication.

Amyloidosis secondary to rheumatic diseases - 16 cases.

INTRODUCTION: Secondary amyloidosis (SA) results of tissue deposition of an acute phase reactant protein produced by chronic inflammation. Its incidence appears to be declining, following the improvement of medical care to primary diseases. Our aim is to assess a group of Portuguese patients with amyloidosis secondary to inflammatory rheumatic diseases, and their evolution over the past 10 years. METHODS: The study comprised 16 patients with SA confirmed by tissue biopsy, hospitalized in the Rheumatology Department of Hospital São João in Oporto in the last 10 years. We made a protocol on epidemiological, clinical and analytical data focusing the rheumatic disease and SA, and possible elements of connection between them. RESULTS: Of the 16 patients, mainly women (81,2%), with mean age at entry of 56 years, 68,8% had rheumatoid arthritis. Amyloidosis was diagnosed in average at 13,5 years of primary rheumatic disease, and its main manifestation was kidney involvement, which together with infection and orthopaedic surgery or its complications, were the leading causes of hospitalization. In this time interval, 6 patients died. They were older, with longer duration and lower rate of treatment of the primary rheumatic disease, and had SA diagnosed 1,5 years before death (different of the 5 years of those that still alive). They had higher rate of gastrointestinal, neurological and serious kidney involvement, and hospitalizations. CONCLUSIONS: Improving medical care in rheumatic inflammatory diseases has reduced the incidence of SA. Also, biotherapy appears to be achieving positive results in established amyloidosis, whatever the mechanisms involved. Our data, on Portuguese patients, seems to follow this trend.

[Tuberculosis in rheumatic patients treated with tumour necrosis factor alpha antagonists: the Portuguese experience]. / Tubereulose em doentes reumáticos tratados com antagonistas do factor de necrose tumoral alfa: a experiência Portuguesa.

In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.

[Synovial lipoma arborescens]. / Lipoma arborescente da sinovial.

Lipoma arborescens is a rare intraarticular lesion of unknown etiology. The disorder usually presents as painless swelling and recurrent joint effusion. It is typically located in the knee (especially the suprapatellar bursa), though it has also been described in other joints. Laboratory test results are normal, as well as aspirated synovial fluid. Synovectomy is curative in most cases. The authors report a review of the literature, highlighting the importance of magnetic resonance imaging in the diagnosis of this pathology. Although it is a rare lesion, synovial lipoma arborescens should be included in the differential diagnosis of patients with a chronic swollen joint or recurrent joint effusions.