This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

Objective.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 ttest 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. Conclusion. 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.

Background Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionized the treatment of chronic inflammatory rheumatic diseases. However, the physician and the patient should be aware of possible adverse reactions. Skin is one of the most frequent organs involved in bDMARD adverse reactions and immune-mediated skin lesions (IMSL) have rarely been described before in cohort studies and their incidence is unknown. Objectives To explore the cumulative incidence, type of lesions, management and outcomes of IMSL related to bDMARD in a large cohort of patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods We conducted a retrospective single-center study including patients with RA, axSpA and PsA followed at a Rheumatology Department from a University Hospital Center between April 2000 and December 2021, treated with at least one bDMARD for at least 6 months. Sociodemographic characteristics, disease duration, age at diagnosis, concomitant immunosuppressive medications, type and duration of the treatment with bDMARD and number of previous bDMARD were collected. For all patients with IMSL, age at onset, disease duration at the time of the IMSL, culprit bDMARD and duration of the treatment, specific management and outcomes were collected. Descriptive statistics for continuous variables were presented with mean and standard deviation and categorical variables were presented with absolute and relative frequencies. Results A total of 441 patients with RA, 386 with axSpA and 162 with PsA were included. The majority were female (63.4%), with a mean age of 54.3 ± 12.8 years. An important proportion of patients (47.6%, n=471) were taking csDMARDs and the most prescribed bDMARD was adalimumab (21.8 %), followed by etanercept (16.5%). Twenty-seven (2.7%) patients presented IMSL potentially related to the bDMARD. Regarding the patients with IMSL, 55.6% were females, mean age at the onset of IMSL was 48.4 ± 12.0 years, mean duration of the treatment with bDMARDs was 4.3 ± 4.5 years and mean duration of the treatment with the culprit bDMARD was 2.3 ± 2.1 years. The majority of patients had SpA (n= 14), followed by RA (n=10) and PsA (n=3). Adalimumab was the culprit agent in half of the patients (n=14), followed by etanercept (n=4), golimumab (n=3), infliximab (n=3), rituximab (n=2) and tocilizumab (n=1). Four patients (14.8%) needed hospitalization with the purpose of performing a clinical, laboratorial and histological investigation. In most patients, skin lesions resolved completely with topical (n=12) or systemic (n=6) treatment. IMSL led to withdrawal of bDMARD in 18 patients (66.7%). More information about the type of IMSL was described in table 1. Conclusion IMSL related to bDMARDs are unusual events with an estimated cumulative incidence of 2.9%, in our sample. The most frequent IMSL were psoriasis and cutaneous manifestations of DILE and the most frequent culprit bDMARD was adalimumab. The majority of patients didn't need hospitalization and presented complete resolution of IMSL. IMSL led to withdrawal of the bDMARD in 2/3 of patients. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Description of number of cases, age at IMSL onset, disease duration and duration of treatment with the culprit bDMARD for each type of IMSL.Type of immune-mediated skin lesionNumber of patients, n(%)Age at skin lesion onset, mean±SD, yearsFemale, n(%)Disease duration, mean±SD, yearsDuration of treatment with culprit bDMARD, mean±SD, yearsPsoriasis1249.3 ± 14.56 (50.0)19.5 ± 15.31.9 ± 1.7Plaque psoriasis5 (41.7)Palmoplantar pustulosis4 (33.3)Guttate psoriasis1 (8.3)Inverse psoriasis1 (8.3)Undefined1 (8.3)Drug-induced lupus erythematosus640.8 ± 2.94 (66.7)15.2 ± 7.82.4 ± 1.4Malar Rash1 (16.7)Alopecia2 (33.3)Chilblains2 (33.3)Subacute cutaneous LE1 (16.7)LE tumidus1 (16.7)Alopecia areata34.4 ± 6.71 (33.3)12.2 ± 6271.2 ± 0.6Leukocytoclastic vasculitis260.9 ± 2.80 (0)31.92.9 ± 3.6Urticaria257.3 ± 15.92 (100)27.8 ± 22.10.9 ± 1.2Rosacea1481 (100)18.59.7Erythema nodosum1601 (100)40.72.9

Background Treatment of inflammatory rheumatic diseases has dramatically changed with the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDs). However, these drugs aren't exempt from risks and skin lesions are the most frequent adverse reactions. Among the possible adverse skin reactions, immune-mediated skin lesions (IMSL) may occur. Risk factors associated with the occurrence of IMSL in rheumatic patients under bDMARDs are poorly known and studied. Objectives To identify predictive factors for IMSL in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) under bDMARD therapy. Methods A retrospective single-center cohort study including patients with RA, axSpA and PsA followed at the Department of Rheumatology of a University Hospital Center between April 2000 and December 2021, treated with at least one bDMARD for at least 6 months was conducted. Data were collected from a national register of rheumatic patients (Reuma.pt) and medical records. Sociodemographic characteristics, disease duration, age at diagnosis, smoking and drinking habits, concomitant immunosuppressive medications, type and duration of the bDMARD treatment and number of previous bDMARD were collected. IMSL development were also collected. Independent samples t-test for normally distributed continuous data and chi-square tests for categorical variables was performed. Also, a multivariate logistic regression analysis was performed to identify possible predictive factors for the occurrence of IMSL. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at a p-value <0.05. Results From a total of 441 patients with RA, 386 with axSpA and 162 with PsA, 27 developed IMSL related to bDMARD (2.7%). Comparing the groups with and without IMSL, no differences were found regarding age, gender, BMI, presence of concomitant csDMARD or type of rheumatic disease. Patients with IMSL have a significant younger age at diagnosis (p=0.038), a longer disease duration (p=0.018) and a longer duration of bDMARD treatment (p=0.008). Patients with IMSL also have a higher number of previous bDMARDs (p<0.001) and adalimumab was the bDMARD with the higher risk of IMSL development (p<0.001). Table 1 described the demographic and clinical features of these two groups.In a multivariate regression model, number of previous bDMARDs (OR 2.13, 95% CI 1.47 to 3.10, p<0.001) and treatment with adalimumab (OR 4.60, 95% CI 1.96 to 10.80, p<0.001) were statistically significant predictive factors for IMSL development. Conclusion In our cohort, we found that a younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development. In the multivariate regression model, number of previous bDMARDs and exposure to adalimumab were statistically significant predictive factors for IMSL development. Further research is required to better understand and recognize the risk factors for IMSL. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Demographic and clinical features in patients with and without IMSL.With IMSL (n=27)Without IMSL (n=962)p-valueAge, mean ± SD, years55.5 ± 14.052.2 ± 12.70.605Female, n (%)15 (55.6)612 (63.6)0.391BMI, mean ± SD25.4 ± 4.827.2 ± 7.50.227Current/Former smoker, n (%)10 (37.0)327 (34.0)0.477Alcohol consumption, n (%)4 (14.8)140 (14.6)0.599Disease duration, mean ± SD, years24.4 ± 12.719.2 ± 11.10.018Duration of bDMARD treatment, mean ± SD, years9.3 ± 4.46.6 ± 5.30.008Age at diagnosis, mean ± SD, years29.4 ± 12.835.0 ± 13.20.038Number of previous bDMARDs, mean ± SD1.6 ± 1.10.74 ± 0.84<0.001Presence of concomitant csDMARD, n (%)10 (37.0)467 (48.5)0.238Adalimumab vs other bDMARD, n (%)14 (51.9)211 (21.9)<0.001

Introduction: Immune-mediated skin lesions (IMSL) can be very disabling leading to treatment discontinuation. Although these lesions have rarely been previously described, the true incidence is unknown. Objective: To explore the cumulative incidence, management and outcomes of IMSL related to bDMARD in a large cohort of patients with chronic inflammatory rheumatic diseases. To explore possible associations and risk factors for IMSL development. Methods: A retrospective single-center study of patients with rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) that had been treated with at least one bDMARD for at least 6 months was conducted. IMSL related to bDMARD characteristics and outcomes were collected. Results: A total of 989 patients with RA, SpA and PsA were included. Twenty-seven patients (2.7%) presented IMSL potentially related to bDMARD, being psoriasis the most common IMSL (n=12, 44.4%), followed by drug-induced lupus erythematosus (n=6), alopecia areata (n=3) and leukocytoclastic vasculitis (n=2). IMSL led to withdrawal of bDMARD in 18 of the 27 patients (66.7%). Patients with IMSL had younger age at diagnosis (p=0.038), longer disease duration (p=0.018), longer duration of bDMARD treatment (p=0.008), and higher number of previous bDMARDs (p<0.001) than patients without IMSL. In the group of patients with IMSL there was a significantly higher percentage of patients treated with adalimumab (p<0.001). In multivariable regression model, the number of previous bDMARDs (OR 2.13, 95%CI 1.47-3.10, p<0.001) and treatment with adalimumab (OR 4.60, 95%CI 1.96-10.80, p<0.001) were statistically significant predictive factors for IMSL development. Conclusion: In our study, IMSL related to bDMARDs had an estimated cumulative incidence of 2.7%. Younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development.

INTRODUCTION:Immune-mediated necrotizing myopathy (IMNM) is characterized by acute or subacute, severe proximal muscle weakness and myofiber necrosis with minimal inflammatory cell infiltrate observed on muscle biopsy. On the other hand, sarcoidosis is characterised by the presence of non-caseating granulomas that can develop in several organs. CASE REPORT:We present the unique case of a 49-year-old woman, with no previous medical history, who had a rare concomitant occurrence of IMNM and pulmonary sarcoidosis. This condition was successfully treated with a combination of corticosteroids and rituximab along with rehabilitation program. DISCUSSION:This association has been reported in only two previous case reports. This highlights the importance of further research on the connection between sarcoidosis and other forms of inflammatory myopathies.

Le syndrome du canal carpien (SCC) est la neuropathie d’enclavement la plus fréquente, affectant 1 à 5 % de la population générale. Plusieurs conditions peuvent causer ou augmenter le risque de SCC. Cependant, la majorité des cas sont qualifiée d’idiopathiques. Selon certaines études, la prévalence des dépôts d’amylose dans la synoviale ou réticulatum des fléchisseurs, de patients âgés, peut atteindre jusqu’à 10 % des cas, en particulier, la forme sporadique de l’amylose à transthyrétine (ATTRwt). La gravité de ATTRwt réside surtout dans l’atteinte cardiaque. À noter que le SCC précède le diagnostic d’amylose cardiaque de plusieurs années, d’où l’importance du diagnostic précoce d’une cardiopathie amyloïde, puisqu’il existe des thérapeutiques qui permettent une amélioration du pronostic. Explorer l’association entre le SCC idiopathique, les dépôts d’amylose dans la synoviale/réticulatum des fléchisseurs et la présence d’amylose cardiaque. Une étude prospective a été menée dans un hôpital tertiaire avec des patients âgés de 60 ans ou plus, qui présentaient un SCC bilatéral et symptomatique avec indication chirurgicale. Tous les patients ont été soumis à un examen physique, un bilan sanguin, un électromyogramme, une échographie des poignets, un électrocardiogramme et une scintigraphie cardiaque au Technétium-99m-DPD, avant la chirurgie. Un prélèvement de la synoviale lors de la chirurgie a été réalisée chaque fois que cela était possible. La coloration au rouge Congo a été effectuée pour identifier les dépôts d’amylose. Le diagnostic de l’amylose cardiaque ATTR reposait sur une captation cardiaque de haut grade (grade 2 ou 3 selon la classification de Perugini) à la scintigraphie cardiaque. Un total de 20 patients (12 femmes, 60,0 %, âge moyen de 72,5 ± 8,8 ans) ont été inclus. L’âge moyen des premiers symptômes du SCC était de 65,9 ± 9,8 ans et la plupart des patients présentaient un SCC bilatéral modéré à sévère (n = 14, 70,0 %), confirmé par l’électromyogramme, et l’échographie des poignets (n = 12, 60,0 %). Des 9 patients ayant subi une biopsie de la synoviale, 3 (33,3 %) présentaient des dépôts d’amylose. Des 20 patients ayant fait une scintigraphie cardiaque, 4 (20,0 %) montraient une captation cardiaque de haut grade (grade 2 de Perugini chez un patient et grade 3 chez trois patients). Parmi ces derniers, deux ont subi une biopsie synoviale et l’un d’entre eux présentait des dépôts d’amyloïde. Dans notre étude, 3 sur 9 patients présentaient des dépôts d’amylose à la biopsie synoviale, et 4 sur 20 patients étaient atteints d’amylose cardiaque. Bien que ces résultats demeurent préliminaires et reposent sur un échantillon réduit, les patients souffrant de SCC idiopathique bilatéral semblent présenter une prévalence élevée de dépôts d’amylose dans la synoviale, ainsi qu’une prévalence élevée d’amylose cardiaque. Cette étude met en évidence l’importance du dépistage de l’amylose cardiaque chez les patients atteints de SCC, notamment chez les patients âgés de 60 ans ou plus souffrant de SCC idiopathique bilatéral. Des études prospectives supplémentaires sont nécessaires.

Background Biological Disease-modifying Antirheumatic Drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD, early in the course of the treatment, and the reasons why this happens aren’t fully understood. Objectives To determine the percentage of RA patients who failed to respond to bDMARD and need to switch in the first year of treatment, describe their characteristics, and identify specific baseline features as possible predictors of bDMARD early failure. Methods An observational monocentric retrospective cohort study was conducted with RA patients (according to 2010 ACR/EULAR criteria), registered in the national database (Reuma.pt) that started their first bDMARD between June 2000 and December 2021 and had a minimum follow-up of 12 months. Demographic data, disease characteristics, laboratory parameters and treatment at baseline were collected. Disease activity scores (CDAI, SDAI and DAS-28-CRP), functional scores (HAQ) and clinical response to treatment (according to EULAR and ACR response criteria) were collected at 3, 6 and 12 months after the start of bDMARD. The proportion of patients who failed to respond (according to treat-to-target strategies) and who switched to another bDMARD was calculated. Patients who discontinued treatment in the first year due to adverse events were excluded. Chi-square test, t-test and Mann-Whitney U test were conducted (categorical, normally and not normally distributed continuous variables, respectively). Also, a multivariate logistic regression analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A p-value <0.05 was considered statistically significant. Results 437 (364 females, 83.3%) patients with RA were included. The mean age was 52.4 ± 11.4 years and the disease duration was 11.8 ± 8.8 years. The majority of these patients started an anti-TNF-α agent as their first bDMARD (n=315, 72.1%). The remaining patients started rituximab (n=66, 15.1%), tocilizumab (n=51, 11.7%) and abatacept (n=5, 1.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment (mean duration of bDMARD treatment was 0.75 ± 0.3 years) and needed to switch to another bDMARD. Demographic characteristics were similar in the group of patients that switch due to ineffectiveness and patients that didn’t switch in the first year. Disease activity scores (DAS-28-CPR, CDAI, SDAI) and HAQ at baseline were also similar in the two groups. There were significantly more current or former smokers in the group of patients that needed to switch in the first year of therapy (p=0.030). Moreover, depression was significantly more frequent in the switch group (p=0.003). Positivity for rheumatoid factor at baseline was also significantly more frequent in the switch group (p=0.014). Regarding the type of bDMARD, patients in the switch group were more frequently treated with anti-TNF-α agents than patients that didn’t switch (p<0.001). In the multivariate analysis, anti-TNF-α agents use (versus non-anti-TNF-α agents) (OR 8.3, 95% CI 2.4-28.8, p=0.001), tobacco exposure (OR 2.3, 95% CI 1.1-4.8, p=0.02) and history of depression (OR 3.1, 95% CI 1.3-7.7) seem to predict the bDMARD early failure and the need to switch in the first year of treatment. Conclusion In our study, anti-TNF-α agents were associated with a higher switch rate due to ineffectiveness in the first year of treatment in RA patients, when comparing to non-anti-TNF-α agents. Moreover, current and former smokers, patients with depression and with positive rheumatoid factor had a higher switch rate due to ineffectiveness. This study reinforces the importance of RA patients quit smoking, as tobacco may interfere with clinical response to bDMARD. Furthermore, routine screening for depression should be included in daily clinical practice and a multidisciplinary treatment approach should be offered to these patients. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

La sclérodermie systémique (SSc) est une maladie auto-immune rare qui se caractérise par l’installation progressive d’une fibrose cutanée et viscérale. Des efforts considérables sont déployés pour étudier des biomarqueurs de sévérité de la maladie. La capillaroscopie péri-unguéale (CPU) est une méthode simple et non invasive qui permet l’observation directe de la microcirculation. Certaines études soutiennent que le degré des lésions de la microcirculation pourrait être associé à la sévérité de l’atteinte viscérale chez ces patients. Analyser s’il existe une association entre la gravité des lésions microvasculaires, l’atteinte viscérale et l’activité globale de la maladie chez les patients atteints de SSc. Une étude de cohorte rétrospective monocentrique a été réalisée sur des patients atteints de SSc (ACR/EULAR 2013) ayant fait une CPU dans les 6 premiers mois du diagnostic. Les données démographiques, l’atteinte viscérale et les résultats de la CPU ont été recueillis à partir du Registre portugais (Reuma.pt) et des dossiers médicaux. La CPU a été évaluée selon la classification standardisée par l’EULAR (Smith et al., 2020). Les lésions microvasculaires ont été classée en 4 stades (0 = non sclérodermie, 1 = précoce, 2 = actif et 3 = tardif). La sévérité de l’atteinte des organes a été évaluée selon l’échelle de gravité de la maladie (DSS) de Medsger. En tant que mesure globale de la gravité de la maladie, la somme du DSS de Medsger a été utilisée. Des corrélations de Pearson et une analyse de régression logistique ont été réalisées. Un total de 86 patients (71 femmes : 82,6 %, âge moyen de 52,6 ± 15,9 ans) atteints de SSc ont été inclus, dont 74 avaient une maladie cutanée limitée, 5 une maladie cutanée diffuse et 7 une SSc sine sclérodermie. Une corrélation modérée a été retrouvée entre la gravité des lésions microvasculaires et la mesure globale de la sévérité de la maladie (r = 0,55, p < 0,001) ainsi qu’entre la gravité des lésions microvasculaires et la sévérité de l’atteinte vasculaire périphérique (r = 0,43, p < 0,001) et de l’atteinte cutanée (r = 0,339, p = 0,001). Les zones avasculaires observées à la CPU semblent prédire la présence d’ulcères digitaux (OR 6,75, IC à 95 % 1,72–26,45, p = 0,006), d’atteinte œsophagienne (OR 3,43, IC à 95 % 1,10–11,57, p = 0,039), d’atteinte musculaire (OR 11,67, IC à 95 % 1,06–138,94, p = 0,04) et de calcinose (OR 22,67, IC à 95 % 4,76–107,90, p < 0,001). Les formes anormales des capillaires semblent prédire la présence d’ulcères digitaux (OR 3,48, IC à 95 % 1,12–10,82, p = 0,025), d’atteinte musculaire (OR 29,82, IC à 95 % 9,14–97,32, p < 0,001), d’atteinte cutanée sévère (OR 5,33, IC à 95 % 1,17–24,31, p = 0,031) et de calcinose (OR 18,85, IC à 95 % 3,68–77,17, p < 0,001). Dans notre étude, la sévérité de la maladie dans la SSc est associée à la gravité des stades observés à la CPU. De plus, la sévérité de l’atteinte vasculaire périphérique et l’étendue de l’atteinte cutanée étaient associées à l’aggravation microvasculaire observés à la CPU. Les zones avasculaires et les formes anormales de la CPU semblent prédire la présence d’ulcères digitaux, d’atteinte musculaire et de calcinose. Cette étude met en évidence l’importance de la CPU en tant qu’outil pronostique, montrant qu’un stade tardif semblent avoir un risque accru de maladie sévère.

INTRODUCTION Immune-mediated skin lesions (IMSL) can be very disabling leading to treatment discontinuation. Although these lesions have rarely been previously described, the true incidence is unknown. OBJECTIVE To explore the cumulative incidence, management and outcomes of IMSL related to bDMARD in a large cohort of patients with chronic inflammatory rheumatic diseases. To explore possible associations and risk factors for IMSL development. METHODS A retrospective single-center study of patients with rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) that had been treated with at least one bDMARD for at least 6 months was conducted. IMSL related to bDMARD characteristics and outcomes were collected. RESULTS A total of 989 patients with RA, SpA and PsA were included. Twenty-seven patients (2.7%) presented IMSL potentially related to bDMARD, being psoriasis the most common IMSL (n=12, 44.4%), followed by drug-induced lupus erythematosus (n=6), alopecia areata (n=3) and leukocytoclastic vasculitis (n=2). IMSL led to withdrawal of bDMARD in 18 of the 27 patients (66.7%). Patients with IMSL had younger age at diagnosis (p=0.038), longer disease duration (p=0.018), longer duration of bDMARD treatment (p=0.008), and higher number of previous bDMARDs (p < 0.001) than patients without IMSL. In the group of patients with IMSL there was a significantly higher percentage of patients treated with adalimumab (p < 0.001). In multivariate regression model, the number of previous bDMARDs (OR 2.13, 95%CI 1.47-3.10, p < 0.001) and treatment with adalimumab (OR 4.60, 95%CI 1.96-10.80 , p < 0.001) were statistically significant predictive factors for IMSL development. CONCLUSION In our study, IMSL related to bDMARDs had an estimated cumulative incidence of 2.7%. Younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development.

INTRODUCTION:Anti-tumor necrosis factor α (anti-TNFα) agents can potentially induce the anti-nuclear antibodies (ANA) development over time. Evidence of the real impact of these autoantibodies on clinical response to treatment in rheumatic patients is still scarce.OBJECTIVES:To explore the impact of ANA seroconversion induced by anti-TNFα therapy on clinical outcomes in biologic-naïve patients with Rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA).METHODS:An observational retrospective cohort study enrolling biologic-naïve patients with RA, axSpA and PsA who started their first anti-TNFα agent was conducted for 24 months(M). Sociodemographic data, laboratory findings, disease activity and physical function scores were collected at baseline, 12M and 24M. To examine the differences between the groups with and without ANA seroconversion, independent samples t-tests, Mann-Whitney U-tests and chi-square tests were performed. Linear and logistic regression models were used to assess the effects of ANA seroconversion on the clinical response to treatment.RESULTS:A total of 432 patients with RA (N=185), axSpA (N=171) and PsA (N=66) were included. ANA seroconversion rate at 24M was 34.6%, 64.3% and 63.6% for RA, axSpA and PsA, respectively. Regarding sociodemographic and clinical data in RA and PsA patients, no statistically significant differences between groups with and without ANA seroconversion were found. In axSpA patients, ANA seroconversion was more frequent in patients with higher body mass index (p=0.017) and significantly less frequent in patients treated with etanercept (p=0.01). Regarding disease activity, DAS28 for RA patients and ASDAS-CRP for axSpA patients were significantly higher in ANA seroconversion group at 12M (p=0.017 and p=0.009, respectively). For PsA patients, CDAI was significantly higher in ANA seroconversion group at 24M (p=0.043). Overall switching rate of biologic disease-modifying antirheumatic drugs (bDMARD) was significantly higher in the ANA seroconversion group over time (p=0.025). For RA patients, ANA seroconversion predicted DAS28 (β=-0.21, 95%CI[-1.86;-0.18], p=0.017) at 12M.CONCLUSIONS:ANA seroconversion induced by anti-TNFα agents could interfere in clinical response of patients with rheumatic diseases. The presence of these autoantibodies can be considered as a potential predictor of poor treatment response and higher need for bDMARD switching over time.

Background Fatigue is a common constitutional feature and has a significant impact on quality of life in patients with chronic inflammatory rheumatic diseases, such as psoriatic arthritis (PsA). It is a complex phenomenon and its pathogenesis remains unclear. Despite being a common symptom, it is largely ignored and rarely assessed in clinical practice. Objectives This study aims to evaluate the incidence and severity of fatigue in PsA patients under biological agents and to assess the influence of several clinical and demographic features on PsA related fatigue. Methods We conducted a cross-sectional study including patients with PsA, according to CASPAR criteria, treated with biological agents, from our University Hospital and registered in the national database (reuma.pt). Fatigue was assessed by a 13-item self-administered questionnaire (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]). Data collected and analyzed included: demographic data, disease activity data, functional status, comorbidities and therapies. Student’s t-test, ANOVA and Pearson’s correlation were performed to compare data, as appropriate. A p-value <0.05 was considered statistically significant. Results 60 PsA patients were included, 61.7% were males, with a mean age at diagnosis of 38.1±10.5 years and a median disease duration of 13.0 (8.75-19.25) years. Most of the included patients had a predominant polyarticular pattern (n=33, 55.0%). The mean FACIT-F score was 34.48±11.61. No differences were found in the FACIT-F score according to gender, pattern of joint involvement , presence or absence of cutaneous involvement, nail dystrophy and/ or dactylitis. Patients with depression and enthesitis exhibited a lower FACIT-F score (p=0.017 and p=0.007, respectively). Patients treated with tofacitinib had a lower FACIT-F score than patients treated with adalimumab (p=0.025). No differences were found among the other biological agents. Patients in remission (according to EULAR response criteria) had a higher FACIT-T score than patients with moderate disease activity (p=0.032). In patients with a predominant axial involvement, inactive disease (according to ASDAS) was associated with a higher FACIT-T score, when compared to very high disease activity (p=0.02). Also, patients with moderate disease activity had a higher FACIT-T score than patients with very high (p=0.003) and high (p=0.008) disease activity. FACIT-F showed a significant correlation with disease activity scores as BASDAI (r=-0.546, p<0.001), DAS 28 CRP (r=-0.506, p<0.001), CDAI (r=-0.672, p<0.001), SDAI (r=-0.641, p<0.001) and ASDAS CRP (r=-0.500, p<0.001). FACIT-F was also correlated with BASFI (r=-0.598, p<0.001), HAQ (r=-0.701, p<0.001), BASMI (r=-0.431, p<0.001) and MASES (r=-0.401, p<0.001). The authors found strong correlations between FACIT-F and HADS domains (Depression and Anxiety domains; r=-0.850, p<0.001 and r=-0.748, p<0.001, respectively). A strong correlation was also found between the FACIT-F and the 8 domains of health of the SF36 (p<0.001). Conclusion Fatigue was a common symptom in our sample of PsA patients and, its magnitude was closely related with disease activity, physical function, depression and anxiety status, indicating its multifactorial nature. We can speculate that achieving disease remission could significantly alleviate the fatigue intensity and vice versa. As recommended by EULAR/ACR task force in 2008, fatigue should be measured in clinical practice and should be part of the multidisciplinary approach, in addition to controlling disease activity. Disclosure of Interests None declared

Background: Induction of autoantibodies is frequently observed in patients treated with a TNF-α blocker. According to other authors, the incidence of induction of antinuclear antibodies (ANA) and anti-double stranded DNA antibodies (anti-dsDNA) varies between 23-57% and 9-33%, respectively. However, it is unknown whether the induction of these autoantibodies affects the pharmacokinetics and bioavailability of biotherapy and, consequently, reduces the efficacy and safety of the drug. Objectives: To analyze if there is an association between autoantibodies induction and therapeutic efficacy in a monocentric cohort of patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) treated with anti-TNF-α agents. Methods: The authors performed a retrospective analysis of patients with axSpA and PsA treated in our University Hospital with a TNF-α blocker as first biologic agent, and analysed the autoantibodies induction rate after 12 (T12) and 24 (T24) months of therapy. Then, they investigated the influence of autoantibodies in therapeutic efficacy at T12 and T24. Clinical evaluation, laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and disease activity and functional scores (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI, AS Disease Activity Score with CPR - ASDAS-CRP, Bath AS Functional Index - BASFI) were collected from reuma.pt and medical records. For PsA patients, Disease Activity Score-28-CRP (DAS28-CRP), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were also collected. Patients with positive ANA (titer > 1/100) prior to anti-TNF-α therapy were excluded. Continuous variables were analyzed using a t-test and categorical variables using a Chi-square test. P-value <0.05 was considered statistically significant. Results: In the axSpA group, 235 patients were included, 44.5% were females, mean age at diagnosis of 42.3 ± 12.4 years and median disease duration of 11.5 (IQR 6.0-21.0) years. Positive ANA were observed in 16.9% at T12 and 26.3% at T24 and positive anti-dsDNA in 3.4% at T12 and 3.8% at T24, with similar conversion rates between different anti-TNF drugs and no significant gender difference. A significant difference in ASDAS-CPR was found in axSpA patients with and without ANA at T12 (p=0.047). ASDAS-CPR was 1.16 times higher in patients with ANA comparing to patients without them. However, no difference was found in the others disease activity and functional scores at T12. Furthermore, no significant difference, including ASDAS-CPR, was found at T24. Also, there was no significant difference found when comparing patients with and without anti-dsDNA. In the PsA group, 94 patients were included, 46.8% were females, mean age at diagnosis of 46.7 ± 11.7 years and median disease duration of 11.5 (IQR 6.5-16.5) years. Positive ANA were found in 14.9% at T12 and 21.3% at T24 and positive anti-dsDNA in 2.1% at T12 and 3.2% at T24. When comparing the groups with and without ANA and with and without anti-dsDNA at T12 and T24, no significant difference in disease activity and functional scores was found. Conclusion: This study revealed high rates of serology conversion, similar to the rates described before. The authors found that ASDAS-CPR was higher in axSpA patients with ANA after 12 months of therapy. However, this difference was no longer evident after 24 months. No other significant difference was found between patients with and without ANA or with and without anti-dsDNA. The authors consider that the induction of autoantibodies may interfere with the response to anti-TNF-α therapy in a short and initial period of time. Long-term follow-up data are lacking to say whether that influence will disappear consistently over the long run, as they observed after 12 months of therapy. However, they can state that, a priori , seroconversion should not lead to treatment suspension because of concerns about loss of efficacy. Disclosure of Interests: None declared

Background: Drug-induced lupus erythematosus (DILE) secondary to anti-TNF-α agents results from an immunogenicity phenomena not yet fully understood and is a rare condition. Withdrawal of anti-TNF- α therapy usually leads to total resolution of symptoms, however sometimes immunosuppression is needed. It is not clear if this condition is drug specific or class related. Therefore, there are doubts about the safety of switching to a second TNF inhibitor: will a further anti-TNF-α agent increase the risk of DILE recurrence? Objectives: To analyze the outcomes in patients with DILE secondary to an anti-TNF-α agent that switch to a second anti-TNF-α agent. Methods: We performed a retrospective analysis of patients with spondyloarthritis, psoriatic arthritis and rheumatoid arthritis from our University Hospital, who developed DILE secondary to an anti-TNF-α agent as a first biologic and switch to a second anti-TNF-α agent. Because specific criteria for the diagnosis of DILE have not been established, DILE diagnosis was considered when a temporal relationship between clinical manifestations and anti-TNF alpha treatment was found and ACR/EULAR 2019 classification criteria for SLE were fulfilled. Clinical and laboratorial features and outcomes were collected from the Portuguese Rheumatic Diseases Register (Reuma.pt) and medical records. Results: Six of 617 patients developed DILE secondary to anti-TNF-α agents (2 secondary to etanercept, 2 to adalimumab and 2 to infliximab). These patients had total resolution of symptoms and autoantibodies (ANA and anti-DNAds), induced by the therapy, disappeared after withdrawal of the anti-TNF-α agent implied. Afterwards, 4 of these 6 patients switched to a second anti-TNF-α agent: 1 to etanercept, 1 to certolizumab, 1 to adalimumab and another to golimumab. The time interval between the two therapies was 2,0 ± 0,8 months. Regarding the outcomes, in all four patients, no DILE recurrence or autoantibodies induction recurrence was observed. These patients have a good response to the new biotherapy, without side effects reported, and a significant clinical improvement was observed. Conclusion: Our study results are in agreement with the literature described before. It seems that exist a low rate of DILE recurrence with an alternative anti-TNF-α agent. Thus, this condition seems to be drug specific rather than class related. Therefore, it seems secure to use a second anti-TNF-α agent, even in a short period of time after DILE development. There is no evidence about the best or securest second TNF inhibitor, so any anti-TNF-α agent can be prescribed. A carefully monitoring of symptoms of relapse should be ensured. In conclusion, DILE secondary to a TNF inhibitor should not be an absolute contraindication to the use of a subsequent anti-TNF-α agent. Disclosure of Interests: None declared.

Background: The minor salivary gland biopsy (MSGB) is considered the “ gold standard ” for the diagnosis of primary Sjögren’s syndrome (pSS). The histological hallmark is focal lymphocytic infiltration with the presence of 50 or more lymphocytes per 4 mm 2 (focus score ≥ 1). Several studies have documented the association between focus score (FS) and extraglandular involvement, suggesting that FS could be used as a histological index of disease severity and a prognostic tool. Objectives: To investigate the association between the FS and clinical, haematological and serological findings in a cohort of patients with pSS. Methods: We performed a retrospective analysis of patients with pSS who fulfilled the ACR/EULAR 2016 classification criteria that were submitted to a minor salivary gland biopsy (MSGB). Demographic data, disease duration, extraglandular involvement and histopathologic data were collected and analyzed. The severity of histologic changes was graded according to the Chisholm and Mason scoring system and the FS was determined. Fisher’s exact test/Chi-square test and Mann-Whitney U test were used to compare the patients with and without positive biopsy (FS <1 versus FS ≥ 1). Futhermore, to investigate the association between the quantitative value of focus score in groups with and without each extraglandular manifestations the authors used the Mann-Whitney U test. P-value < 0.05 was considered statistically significant. Results: A total of 59 pSS patients were included. Regarding the histopathologic pattern, 40 of 59 patients had a FS ≥ 1, while 19 patients had a FS <1. Although described as having FS ≥ 1, the pathologists failed to report the absolute value in 11 of 40 (27,5%) patients. Germinal center-like structures were found in 1 (1,7%) patient. The demographic and clinical features in pSS patients with FS <1 and with FS ≥ 1 are presented in table 1. Anti-SSA was strongly associated with FS <1 (p <0,001). No significant difference in demographic and clinical features were found between the two groups. Table 1. Demographic and clinical features in pSS patients with FS <1 and with FS ≥ 1 (* Fisher’s exact/Chi-square test; † T-test; ‡ Mann-Whitney U test). FS <1 (n=19 ) FS ≥ 1 (n=48 ) p-value Gender (female), n (%) 17 (89,5) 34 (85,0) 0,639 * Current age (years) (mean ± SD) 60,11+-13,39 54,78 (+-13,48) 0.16 † Disease duration (years) (median, P25-P75) 3 (2-7) 4 (3-5) 0,507 ‡ Extraglandular involvement Arthralgias/Arthritis, n (%) 6 (31,7) 22 (55,0) 0,092 * Myositis, n (%) 0 (0) 1 (2,5) - Pulmonary involvement, n (%) 3 (15,8) 5 (12,5) 0,704 * PNS involvement, n (%) 0 (0) 1 (2,5) - CNS involvement, n (%) 0 (0) 1 (2,5) - Cutaneous involvement, n (%) 1 (5,3) 1 (2,5) 0,544 * Lymphoma, n (%) 0 (0) 2 (5,6) - Haematological and serological characteristics Leukocytopenia, n (%) Hypergammaglobulinaemia, n (%) 10 (52,6) 16 (40,0) 0,361 * RF positivity, n (%) 5 (26,3) 10 (25,6) 1 * ANA positivity, n (%) 18 (94,7) 34 (85,0) 0,411* Anti-SSA positivity, n (%) 19 (100) 21 (52,5) < 0,001 * Anti-SSB positivity, n (%) 7 (36,8) 12 (32,5) 0,742 * ESSDAI score (median, P25-P75) 2 (0-8) 2 (0-7,25) 0,816 ‡ When comparing the quantitative value of FS in groups with and without each extraglandular manifestation, the authors found that patients with articular involvement had a significant higher FS value than patients without articular manifestations (p=0.037). No other significant association was found. Conclusion: Regarding the clinical manifestations, we didn’t find a significant difference between patients with a FS < 1 and those with a FS ≥ 1. Anti-SSA was strongly associated with a FS <1, which corroborates the importance of anti-SSA for the pSS diagnosis in patients with a negative biopsy. We found that a higher FS value was associated with articular involvement. However, this study has limitations such as a small sample and a low incidence of extraglandular manifestations. In conclusion, more studies are needed to clarify the associations found in the literature. Disclosure of Interests: None declared

Background: Induction of autoantibodies is frequently observed in patients treated with TNF-α antagonist and the possible development of drug-induced lupus erythematosus (DILE) remains a matter of concern. The prevalence of DILE secondary to anti-TNF-α therapy is estimated around 0.5-1% and clinical features include arthritis/arthralgia, rash, serositis, fever, myalgias, cytopenias, among others. According to the literature, DILE secondary to anti-TNF-α agents differs in several ways from the clinical and laboratory findings typically associated with classic DILE. Objectives: To estimate the incidence of induction of antinuclear antibodies (ANA) and DILE in a monocentric cohort of patients with spondyloarthritis and psoriatic arthritis treated with anti-TNF-α agents. To describe the clinical and laboratorial features and outcomes of patients with DILE. Methods: We performed a retrospective analysis of patients with spondyloarthritis and psoriatic arthritis treated with anti-TNF-α agents, from our University Hospital, who have been registered on the Portuguese Rheumatic Diseases Register (Reuma.pt) between July 2001 and December 2020. Patients with positive ANA (titer > 1/100) before the anti-TNF-α therapy were excluded. Because specific criteria for the diagnosis of DILE have not been established, we considered the diagnosis in case of a temporal relationship between clinical manifestations and anti-TNF-α treatment and fulfillment of ACR/EULAR 2019 classification criteria for SLE. In patients with DILE, clinical features, laboratory findings, systemic therapies and outcome after discontinuation of medication were collected from reuma.pt and medical records. For the clinical and demographic predictors, continuous variables were analyzed using a two-sided t-test and categorical variables using a Fisher’s exact test. P-value <0.05 was considered statistically significant. Results: In the spondyloarthritis group, 290 patients were included (44.8% females, mean age at diagnosis of 33.3 ± 11.5 years and mean disease duration of 15.1 ± 10.4 years) and in the psoriatic arthritis group, 116 patients were included (50.0% females, mean age at diagnosis of 40.1 ± 11.0 years and mean disease duration of 13.1 ± 6.8 years). In our study, we observed high serology conversion rates (positive ANA in 67.9% and 58.6% of patients with Spondyloarthritis and Psoriatic Arthritis, respectively), with similar conversion rates between different anti-TNF drugs. Three patients with spondyloarthritis (1.0%) and 1 patient with psoriatic arthritis (0.9%) developed DILE. Etanercept was the causative agent in 2 cases, infliximab and adalimumab in 1 case, each. Peripheral arthritis (new onset or abrupt worsening) occurred in 2 patients, serositis in 1 patient, constitutional symptoms in 2 patients, subnephrotic proteinuria in 1 patient, lymphopenia in 2 patients and hypocomplementemia in 1 patient. Specific treatment was prescribed to the 4 patients (oral corticosteroids) and they achieved complete recovery. After anti–TNF-α treatment interruption, no patient had recurrent disease. We observed that patients with DILE had a significantly longer disease duration (> 8.4 years; p=0.04) and a significantly longer duration of therapy with anti-TNF (> 4.0 years; p=0.04) when compared to patients without DILE. Conclusion: Despite the frequent induction of autoantibodies, the development of DILE secondary to anti–TNF-α agents is rare. Our study demonstrates an incidence rate similar to other studies reported before. The clinical and laboratorial characteristics of our patients with DILE attributable to anti–TNF-α agents differ significantly from DILE due to more traditional agents, as is described in literature. Overall, patients in this study had mild disease that improved after therapy discontinuation, without recurrence of the disease. It seems that a longer disease duration and a longer period under anti-TNF-α therapy may increase the risk of DILE development. Disclosure of Interests: None declared

Our results confirm the value of this technique especially in the early stages of Dupuytren's disease, with immediate satisfactory results and a low rate of complications.

La enfermedad de Dupuytren es un trastorno fibroproliferativo de la aponeurosis palmar que conduce a contracturas de flexión digital. Esta afección incapacitante se puede tratar con un procedimiento mínimamente invasivo, llamado aponeurotomía percutánea con aguja (APA). Presentar los resultados de 10 años de experiencia en el tratamiento de la contractura de Dupuytren por APA en la Consulta de Mano Reumatológica de nuestro departamento. Se ha realizado un estudio retrospectivo con la descripción del método de ejecución de la APA junto con el análisis de los resultados posteriores al procedimiento. Se han observado un total de 197 pacientes con enfermedad de Dupuytren. Noventa y ocho pacientes (49,7%) fueron tratados con APA, lo que equivale a 117 dedos tratados. Hubo un 84% de buenos resultados inmediatos, con mejores resultados para las etapas menos avanzadas. Se observaron recurrencias en un 12% de los pacientes. Se registró una tasa de complicación del 1,7%. Nuestros resultados confirman el valor de esta técnica especialmente en las primeras etapas de la enfermedad de Dupuytren, con resultados satisfactorios inmediatos asociados a una baja tasa de complicaciones. Dupuytren's disease is a fibroproliferative disorder of the palmar aponeurosis that leads to digital flexion contractures. This disabling condition can be treated with a minimally invasive procedure, called percutaneous needle aponeurotomy (PNA). To report the results of 10 years of experience treating Dupuytren's contracture by PNA in the rheumatology hand unit of our department. We conducted a retrospective study with a description of method to perform PNA and analysis of post-procedure results. There were 197 patients with Dupuytren's disease. Ninety-eight patients (49.7%) underwent PNA, corresponding to 117 treated fingers. Good immediate results were achieved in 84% of the patients, with results being better in those with less advanced stages. Recurrences occurred in 12% of the patients. The complication rate was 1.7%. Our results confirm the value of this technique especially in the early stages of Dupuytren's disease, with immediate satisfactory results and a low rate of complications.

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.