Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

Association of Anti-Saccharomyces cerevisiae antibodies with clinical phenotype in spondyloarthritis patients / Asociación de anticuerpos anti-Saccharomyces cerevisiae con fenotipo clínico en pacientes con espondiloartritis

Introduction: The association between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) has been shown in many studies. More recently, with the hypothesis that increased gut inflammation is of etiopathogenic importance in the development of SpA, evaluation of anti-Saccharomyces cerevisiae antibodies (ASCA) has gained increasing relevance. Objective: To study the status and frequency of ASCA in SpA patients and the association of these biomarkers with the clinical profile. Methods: An observational study was performed including 231 SpA patients treated with biologic therapy. ASCA IgA and IgG levels were determined by micro-enzyme-linked immunosorbent assay. Results: Our data showed an increase of ASCA IgA positivity among SpA patients. No relationship was found between ASCA status and the demographic aspects, genetic factors or clinical presentation, except for the association with IBD. Conclusion: Our study confirms that ASCA IgA are elevated in SpA patients. Although there was no evidence of association with a particular disease phenotype, the existence of higher ASCA levels sustains a close relationship between gut and SpA.(AU)

Introducción: La asociación entre la espondiloartritis (SpA) y la enfermedad inflamatoria intestinal (EII) se ha demostrado en muchos estudios. Recientemente, con la hipótesis de que el aumento de la inflamación intestinal es de importancia etiopatogénica en el desarrollo de la SpA, la evaluación de los anticuerpos anti-Saccharomyces cerevisiae (ASCA) ha adquirido una relevancia creciente. Objetivo: Estudiar los niveles de los ASCA en pacientes con SpA, y la asociación de estos biomarcadores con el perfil clínico. Métodos: Se realizó un estudio observacional que incluyó a 231 pacientes con SpA tratados con terapia biológica. Los niveles de ASCA IgA e IgG se determinaron por técnica de ensayo de inmunoabsorción ligado a enzimas. Resultados: Nuestros datos mostraron un aumento de la positividad de ASCA IgA entre los pacientes con SpA. No se encontró ninguna relación entre los ASCA y los aspectos demográficos, factores genéticos o presentación clínica, excepto la asociación con la EII. Conclusión: Nuestro estudio confirma que los niveles de ASCA IgA están elevados en pacientes con SpA. Aunque no hubo evidencia de asociación con un fenotipo de enfermedad en particular, la existencia de niveles más altos de ASCA mantiene una relación estrecha entre el intestino y la SpA.(AU)

Association of Anti-Saccharomyces cerevisiae antibodies with clinical phenotype in spondyloarthritis patients.

INTRODUCTION: The association between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) has been shown in many studies. More recently, with the hypothesis that increased gut inflammation is of etiopathogenic importance in the development of SpA, evaluation of anti-Saccharomyces cerevisiae antibodies (ASCA) has gained increasing relevance. OBJECTIVE: To study the status and frequency of ASCA in SpA patients and the association of these biomarkers with the clinical profile. METHODS: An observational study was performed including 231 SpA patients treated with biologic therapy. ASCA IgA and IgG levels were determined by micro-enzyme-linked immunosorbent assay. RESULTS: Our data showed an increase of ASCA IgA positivity among SpA patients. No relationship was found between ASCA status and the demographic aspects, genetic factors or clinical presentation, except for the association with IBD. CONCLUSION: Our study confirms that ASCA IgA are elevated in SpA patients. Although there was no evidence of association with a particular disease phenotype, the existence of higher ASCA levels sustains a close relationship between gut and SpA.

Happiness, quality of life and their determinants among people with systemic sclerosis: a structural equation modelling approach.

BACKGROUND: Patients' objectives and experiences must be core to the study and management of chronic diseases, such as SSc. Although patient-reported outcomes are attracting increasing attention, evaluation of the impact of disease on the overall subjective well-being, equivalent to 'happiness', is remarkably lacking. OBJECTIVES: To examine the determinants of happiness and quality of life in patients with SSc, with emphasis on disease features and personality traits. METHODS: Observational, cross-sectional multicentre study, including 142 patients, with complete data regarding disease activity, disease impact, personality, health-related quality of life (HR-QoL) and happiness. Structural equation modelling was used to evaluate the association between the variables. RESULTS: The results indicated an acceptable fit of the model to the data. Perceived disease impact had a significant negative direct relation with HR-QoL (ß = -0.79, P < 0.001) and with happiness (ß = -0.52, P < 0.001). Positive personality traits had a positive relation with happiness (ß = 0.36, P = 0.002) and an important indirect association upon QoL (ß = 0.43) and happiness (ß = 0.23). Perceived disease impact is influenced by body image, fatigue and SSc-related disability to a higher degree (ß = 0.6-0.7) than by disease activity (ß = 0.28) or form (ß = 0.17). Impact of disease had a much stronger relation with HR-QoL than with happiness. CONCLUSIONS: The results suggest that treatment strategies targeting not only disease control but also the mitigation of relevant domains of disease impact (body image, fatigue, global disability) may be important to improve patients' experience of the disease. The reinforcement of resilience factors, such as positive psychological traits, may also play a contributory role towards better patient outcomes.

Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant?

BACKGROUND: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to the second TNFi in axial spondyloarthritis (axSpA). METHODS: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started the second TNFi between June 2008 and May 2018, were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA), and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as primary failure (no response ≤ 6 months), secondary failure (response ≤ 6 months but lost thereafter), adverse events, and others. The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models. RESULTS: In total, 193 patients were included. The reason for discontinuation of the first TNFi did not influence the response to the second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g., there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR 7.3 [95%CI 1.9; 27.7]), adverse events (OR 9.1 [2.5; 33.3]), or other reasons (OR 7.7 [1.6; 37.9]) compared to primary failure. CONCLUSION: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have a better response to the second TNFi according to stringent outcomes.

Eligibility criteria for biologic disease-modifying antirheumatic drugs in axial spondyloarthritis: going beyond BASDAI.

OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.

Remission and low disease activity matrix tools: results in real-world rheumatoid arthritis patients under anti-TNF therapy.

BACKGROUND: Remission/ low disease activity (LDA) are the main treatment goals in rheumatoid arthritis (RA) patients. Two tools showing the ability to predict golimumab treatment outcomes in patients with RA were published. OBJECTIVES: To estimate the real-world accuracy of two quantitative tools created to predict RA remission and low disease activity. METHODS: Multicenter, observational study, using data from the Rheumatic Diseases Portuguese Register (Reuma.pt), including biologic naïve RA patients who started an anti-TNF as first-line biologic and with at least 6 months of follow-up. The accuracy of two matrices tools was assessed by likelihood-ratios (LR), sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and area under the ROC curve (AUC). RESULTS: 674 RA patients under first-line anti-TNF (266 etanercept, 186 infliximab, 131 adalimumab, 85 golimumab, 6 certolizumab pegol) were included. The median (IQR) age was 53.4 (44.7-61.1) years and the median disease duration was 7.7 (3.7-14.6) years. The majority were female (72%). Most patients were RF and/or ACPA positive (75.5%) and had erosive disease (54.9%); 58.6% had comorbidities. At 6-months, 157 (23.3%) patients achieved remission (DAS28 ESR < 2.6) and 269 (39.9%) LDA (DAS28 ESR ≤ 3.2). Area under the curve for remission in this real-world sample was 0.756 [IC 95% (0.713-0.799)] and for LDA was 0.724 [IC 95% (0.686 -0.763)]. The highest LR (8.23) for remission state was obtained at a cut-off ≥ 67%, with high specificity (SP) (99.6%) but low sensitivity (SN) (3.2%). A better balance of SN and SP (65.6% and 73.9%, respectively) was observed for a cut-off >30%, with a LR of 2.51, PPV of 43.3% and NPV of 87.6%. CONCLUSION: In this population, the accuracy of the prediction tool was good for remission and LDA. Our results corroborate the idea that these matrix tools could be helpful to select patients for anti-TNF therapy.

Chondrosarcoma as inaugural manifestation of monostotic Paget's disease of Bone.

Sarcomatous degeneration is one of the serious and rare complications of Paget's disease of bone. Osteosarcoma is the most common secondary tumour, while other variants such as chondrosarcoma are extremely uncommon. We describe a unique case of Paget's chondrosarcoma of the pelvis in an elderly female patient, with no previous established diagnosis of osteitis deformans. We emphasize clinical and radiologic aspects that should raise suspicion of malignant transformation, revealing good correlation with the final histopathological diagnosis.

Osteopoikilosis: case series from Portuguese Rheumatology Centers.

Osteopoikilosis (OPK) is a rare, hereditary, usually asymptomatic disease characterized by the presence of multiple, well-defined sclerotic lesions distributed in peri-articular locations, frequently diagnosed as an incidental finding. Differential diagnosis with osteoblastic metastases is fundamental. This article reports six cases of OPK diagnosed in Portuguese Rheumatology Centers.

Silent acute myocarditis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis is a rare multisystemic disorder, characterized by necrotizing vasculitis affecting small to medium-sized vessels, associated with asthma and eosinophilia. Cardiac involvement is the most important predictor of mortality and it seems to be more frequent in anti-neutrophil cytoplasmic antibodies-negative patients. Cardiomyopathy and congestive heart failure can occur but a significant proportion of patients are asymptomatic. We present a case of this condition in a 65-year-old woman with a past medical history of rhinosinusitis and recent episodes of asthma, that developed palpable purpura, sensory deficiency and excruciating pain mainly in the lower limbs. A significant hypereosinophilia and elevated troponin level were found, although she had not cardiac symptomatology. Cardiovascular magnetic resonance revealed late gadolinium enhancement and a severe reduction of the left ventricular ejection fraction. Mononeuritis multiplex was documented and diagnosis was confirmed by biopsy. Complementary cardiac investigation is mandatory in any patient with suspicion of Eosinophilic granulomatosis with polyangiitis. Early detection and the appropriate treatment are crucial due to the possible life-threatening manifestations.

Haemophagocytic syndrome in Systemic Lupus Erythematosus - clues to an early diagnosis.

Macrophage activation syndrome (MAS) is a rare life-threatening condition that involves excessive activation of inflammatory cells and overproduction of different cytokines. It is characterized by persistent fever, hepatosplenomegaly, cytopenias and coagulopathy. Other prominent features are hyperferritinemia and findings of activated macrophages in haemopoietic organs, often associated with multi-organ impairment. Its occurrence has been linked to numerous triggers such as viral agents, malignancy and rheumatic diseases. With overlap of clinical features, distinguishing MAS from autoimmune disease flare or sepsis can represent a major challenge. Therefore, a high degree of suspicion is necessary to prompt diagnosis and treatment. Our purpose is to highlight important clinical aspects for an early and differential recognition of this syndrome.