Spontaneous subcapsular and perirenal hemorrhage, known as Wunderlich syndrome (WS), is a rare clinical manifestation of polyarteritis nodosa (PAN). We report a case of a 48-year-old male with a history of recurrent episodes of leg muscle tenderness and dysesthesia, bilateral flank pain, painful nodular skin lesions in the lower limbs, weight loss, and difficult-to-control arterial hypertension. The abdominopelvic computed tomography angiography showed a large left perirenal hematoma, leading to the patient’s admission to the intensive care unit. After the exclusion of infectious or neoplastic foci, the patient was diagnosed with PAN and started intravenous methylprednisolone pulses with a good response. Since WS is a rare initial clinical manifestation of PAN, an early diagnosis and aggressive treatment will significantly improve clinical outcomes.

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. Juvenile dermatomyositis (JDM) is a rare chronic systemic inflammatory disorder with a highly variable clinical course. It is important to identify the patients at risk of developing more severe disease. However, based on the existing literature, there is a lack of data regarding predictors of poor outcomes. Obtaining knowledge about clinical and laboratory risk factors for disease progression and severity at an earlier stage of the disease could potentially lead to a better long-term prognosis for patients with JDM. Methods. A narrative review with the aim of identifying risk factors for poor outcomes in patients with JDM, such as death, severe disease, refractory disease, and functional impairment, was conducted. A total of 27 articles was included. Results. Certain clinical manifestations and immunology features appear to worsen the prognosis in children with JDM. The recognition of these risk factors is essential for all pediatric rheumatologists as it allows the earlier identification of patients with potentially worse outcomes. These patients should receive closer follow-up and aggressive and individualized therapy in order to reduce their morbimortality. Conclusions. Additional research is needed not only to identify more predictors of worse outcomes but also to identify more effective treatment approaches targeted toward these patients.

Introduction 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. Objectives To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. Materials and methods An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. Results A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n=315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p=0.030), with a history of depression (p=0.003) and positive for RF at baseline (p=0.014) in the switch group.In the multivariate analysis, anti-TNF-α agents use (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 need to switch in the first year of treatment due to ineffectiveness. Discussion and conclusion In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients.

( Acta Obstet Gynecol Scand . 2023;102:635–643) Both placental growth factor (PlGF) and tyrosine kinase 1 (sFlt1) are predicted to be factors in impaired placentation, which is known to lead to diseases such as pre-eclampsia and fetal growth restriction (FGR). Previous studies have shown fluctuations in the levels of PlGF and sFlt1 in patients with these diseases. This study aimed to determine the effects that high levels of PlGF and sFlt1 have on the deterioration of FGR in neonates.

Carpal tunnel syndrome (CTS) is the most common type of entrapment neuropathy and affects approximately 1% to 5% of the general population, mostly patients older than 50 years. CTS is present in various conditions and diseases and could also be an early sign of systemic transthyretin amyloidosis (ATTR), associated with amyloid cardiomyopathy and subsequent heart failure. With advances in the treatment of cardiac amyloidosis, patient prognosis could be significantly improved with an early diagnosis. Amyloidosis represents a group of disorders characterized by the extracellular deposition of destabilized protein fragments, aggregating as amyloid fibrils, thereby leading to organ dysfunction. Among these, ATTR is a significant subgroup. This study protocol aims to explore the potential association between CTS and systemic and cardiac ATTR. The study design involves a case-control approach, with assessments including physical examination, laboratory tests, electromyography, electrocardiogram, wrist ultrasound, and scintigraphy with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD). Histopathological analysis and genetic testing will be performed when appropriate. Statistical analysis will be conducted to evaluate the relationship between CTS and ATTR. The study seeks to contribute to a better understanding of the diagnostic and therapeutic implications of identifying ATTR in patients with idiopathic CTS (ClinicalTrials.gov identifier: NCT05409833).

OBJECTIVES:This study aimed to estimate the prevalence of anxiety and depression symptoms and explore the association between these symptoms and clinical and pain characteristics in patients with chronic pain (CP) due to hip and knee osteoarthritis (OA). METHODS:In this cross-sectional study, adult patients with CP and knee and/or hip OA were included. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Visual analogue scale, Western Ontario and McMaster Universities Arthritis Index (WOMAC) and PainDetect Questionnaire assessed pain characteristics and Health Assessment Questionnaire (HAQ) evaluated functional disability. Correlation coefficients were used to explore the associations between anxiety and depression symptoms and clinical and pain characteristics. RESULTS:A total of 61 patients (age 66.2±9.4 years, 67.2% female) were included. Most patients (70.5%) had clinically significant anxiety and/or depression symptoms. Patients with anxiety and/or depression symptoms had higher pain severity (p=0.032) and disability (p=0.014). Depression symptoms had a moderate positive correlation with WOMAC physical function subscale (r=0.520), WOMAC total (r=0.511) and HAQ (r=0.405). CONCLUSIONS:Anxiety and depression symptoms are prevalent in knee or hip OA patients with CP and were associated with higher pain severity and functional disability. These findings support the screening of anxiety and depression symptoms in OA patients, in order to develop more effective multidisciplinary treatments.

Introduction: Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). Materials and methods: A retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. Results: A total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r = 0.55, p < 0.001), the severity of peripheral vascular involvement (r = 0.43, p < 0.001) and the severity of skin involvement (r = 0.34, p = 0.001). The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52-23.86, p = 0.01), muscular involvement (OR 13.09, 95% CI 1.09-156.78, p = 0.04), calcinosis (OR 27.22, 95% CI 5.56-133.33, p < 0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17-2.38, p = 0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53-332.85, p < 0.001). Discussion and conclusion: In this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

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.

Background: Anti-tumor necrosis factor-α (anti-TNF) therapy is often part of the treatment strategy for rheumatic diseases (RD) and inflammatory bowel disease (IBD). An association between anti-TNF agents and the development of lupus erythematosus (LE)-like syndrome has been established and some patients may have a definitive diagnosis of systemic lupus erythematosus (SLE), requiring appropriate treatment. To date, no studies have been conducted to analyze follow-up between rheumatic and IBD patients who have developed LE-like syndrome induced by anti-TNF agents. Objectives: To assess clinical and serological markers of LE-like syndrome induced by anti-TNF therapy, and to characterize its development, in patients with RD and IBD receiving treatment with anti-TNF. Methods: In this monocentric descriptive study, with a minimum 6-month follow-up and conducted at a tertiary university hospital (Rheumatology Department), we reviewed the clinical and serological parameters of 8 patients with RD and 11 patients with IBD, all diagnosed with LE-like syndrome induced by anti-TNF therapy. Statistical analysis, using student's t test, was performed to compare differences in anti-double-stranded DNA (anti-dsDNA) levels between patients with positive and negative anti-histone antibodies (anti-H). Results: Nineteen patients were included, mostly female (n=14). The mean age at the diagnosis of LE-like syndrome was 45.42 (±16.77) years. Ten IBD and 2 RD patients received infliximab. At the time of symptoms onset, anti-TNF agent was discontinued. Fifteen (78.9%) patients developed polyarthritis and 3 (15.8%) polyarthralgias. Three (15.8%) patients had constitutional symptoms (such as fatigue or fever), 2 (10.5%) patients developed skin rash, 2 (10.5%) patients had cytopenia (1 with anemia and 1 with anemia and leukopenia; both in RD group), 2 (10.5%) patients developed serositis (pleural effusion) and 1 (5.3%) patient had vasculitis-like skin lesions in the hands; 1 (5.3%) patient developed venous thrombosis associated with antiphospholipid antibodies positivity. At the time of LE-like syndrome diagnosis, all patients (n=100, 19%) tested positive for antinuclear antibodies (ANA), and almost all patients (n=14, 73.7%) tested positive (≥100 international units/L) for anti-dsDNA. Except for 4 (21.1%) patients (3 in IBD group and 1 in RD group) who had low complement (C3c/C4), complement levels were mostly normal. The relevant data are detailed in Table 1. Of note, positive anti-H were accompanied by low serum levels of anti-dsDNA antibodies, p<0.001 (Table 2). Seven (36.8%), all IBD patients, needed immunosuppressive therapy (methotrexate, azathioprine or hydroxychloroquine) to resolve their LE-like syndrome symptoms (in 3 patients, anti-dsDNA were negative only after at least 1 year of treatment) and continued to receive immunosuppressants during follow-up. In 11 (57.9%) cases, including all RD patients, discontinuation of anti-TNF therapy (and sometimes using low dose of glucocorticoids) was sufficient for symptoms resolution and antibody negativity. Five patients (26.3%) switched to another anti-TNF without experiencing relapse of symptoms. Conclusion: Studies show that SLE-like syndrome frequency has been increasing and recognition of the condition is very important as anti-TNF therapy is commonly used. This study, although limited by its descriptive nature and small sample size, revealed differences between the RD and IBD groups regarding the specific anti-TNF agents used and the necessity of immunosuppressive therapy, more prevalent in the IBD group. On the other hand, most patients improved after discontinuing therapy and those who tolerated the switch to another anti-TNF-α agent had no SLE recurrence. Of interest, positive anti-H was associated with absence or low levels of anti-dsDNA, suggesting that this clinical entity is an independent disease and different from classical drug-induced lupus with positive anti-histone antibodies. Further studies are required to establish definite differences between IBD and RD groups and determine the impact of definitive SLE diagnosis secondary to anti-TNF therapy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.

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

Background The advent of disease-modifying antirheumatic drugs (DMARDs), in the past two decades has been revolutionary in the treatment and prognostic outcomes of patients with Juvenile Idiopathic Arthritis (JIA). Since some patients have inadequate responses to conventional DMARDs, biologic DMARDs (bDMARDs) must be prescribed to guarantee the achievement of complete remission. Early and appropriate treatment can prevent joint destruction, loss of joint function and extraarticular manifestations, with subsequent less morbidity and mortality. Objectives To identify the JIA patients with a higher probability of requiring treatment with bDMARDs and to investigate the predictive factors. Methods A retrospective single-center study of patients with JIA followed in a tertiary Hospital was conducted. Sociodemographic, clinical, laboratory and treatment characteristics were collected from Portuguese Rheumatic Diseases Register and medical records. Statistic was performed with independent samples t-test, Mann-Whitney U test, chi-square test and Fisher’s exact test. Statistical significance was set up at a p-value <0.05. A multivariate logistic regression analysis was performed to identify possible predictive factors for bDMARD use. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results A total of 165 patients with JIA (107 females, 64.8%) were included. Seventy-five patients had oligoarthritis (45.6%, 62 had persistent oligoarthritis and 13 had extended oligoarthritis), 17 psoriatic arthritis (10.3%), 30 rheumatoid factor (RF)-negative polyarthritis (18.1%), 6 RF-positive polyarthritis (3.6%), 14 systemic arthritis (8.5%) and 23 enthesitis related arthritis-juvenile spondyloarthritis (13.9%). Fourty-five patients were treated with bDMARD (27.3%). Males were treated more frequently with bDMARDs than females (p=0.058). Regarding JIA subtype, more RF-positive polyarthritis patients needed bDMARDs to achieve remission (p=0.027). Likewise, concerning disease activity, JIA patients with higher C-reactive protein (CRP) values were more frequent treated with bDMARDs (p=0.032), which was not verified for erythrocyte sedimentation rate (ESR). Uveitis was significantly more frequent in the bDMARD group (p=0.006). Moreover, more patients with bilateral involvement were treated with bDMARDs, compared with patients with unilateral uveitis (n=0.032). Nevertheless, no differences were found concerning age and number of joints involved at onset, disease duration and ANA positivity. In a multivariate regression model adjusted for gender, the presence of uveitis (OR 4.42, 95% CI 1.43 to 13.60, p=0.010) and polyarticular involvement (OR 6.62, 95% CI 2.05-21.43, p=0.002) remained statistically significant predictive factors for bDMARD use in patients with JIA. Conclusion Male patients, polyarticular involvement (with negative or positive RF) and bilateral uveitis were more frequently treated with bDMARDs. In addition, CRP values at onset of JIA were higher in the bDMARD group. Thereby, the presence of uveitis and polyarticular involvement seem to predict the need of bDMARD treatment in JIA patients. Prompt treatment with these agents, early in the disease course, especially in JIA patients with more articular involvement and extraarticular manifestations like uveitis, refractory to conventional DMARDs, should be strongly recommended, in order to avoid irreversible damage and to achieve complete and long-term remission. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

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.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in pediatric patients. It is clinically characterized by fever flares lasting 3-7 days, reappearing every 2-8 weeks with a distinctive clockwork regularity. PFAPA generally begins before 5 years of age and usually ceases 3-5 years after onset. Recurrences may be observed in adolescence and adulthood in up to 20% of cases. The authors aim to describe a case of PFAPA recurrence in adolescence temporally associated with allergen-specific immunotherapy (ASIT). A 16-year-old female patient was referred to the rheumatology unit due to recurrent episodes of fever one month after initiating ASIT for allergic rhinitis. These episodes occurred every 4 weeks and lasted 3 days. During these episodes, she also presented with a sore throat, tonsillar exudates, and cervical lymphadenopathy. Abortive treatment with oral prednisolone was attempted in these episodes, with complete resolution of fever after a single dose. After reviewing her medical background, she had previously experienced febrile episodes accompanied by aphthous ulcers and tonsillar exudates occurring every 7-8 weeks from age 2-7. The etiopathogenesis of PFAPA remains uncertain. Environmental triggers, particularly those with immunomodulator effects, may interfere with the immune responses responsible for PFAPA occurrence, but the mechanisms are still unclear. The authors describe the first report of the reappearance of PFAPA flares, possibly due to ASIT. Further studies are needed to fully clarify if ASIT constitutes a true environmental trigger of PFAPA.

Introduction:Cranial nerve involvement in polyarteritis nodosa(PAN) is underrecognized and rarely reported. The aim of this article is to review the available literature and present an example of oculomotor nerve palsy in the course of PAN.Material and methods:Evaluation of texts describing the analyzed problem using the terms "polyarteritis nodosa", "nerve", "oculomotor", "cranial nerve" and "cranial neuropathy" for searching the PubMed database was done. Only full-text articles in English language with titles and abstracts were included in the analysis. As a guideline for the analysis of articles, the methodology described in the Principles of Individual Patient Data systematic reviews (PRISMA-IPD) was used.Results:After screening articles only 16 reported cases of PAN with cranial neuropathy were included in the analysis. In 10 the cranial neuropathy was reported as the initial manifestation of PAN with optic nerve involvement as the most frequent (62.5%); among these cases the oculomotor nerve was involved in 3 cases. Treatment with glucocorticosteroids and cyclophosphamide was the most common.Conclusions:Although cranial neuropathy, especially oculomotor nerve palsy is a rare first neurological manifestation of PAN, this clinical problem should be considered in the differential diagnosis.Especially patients with peripheral neuropathy, general symptoms, skin lesions and hepatitis B virus infection should be evaluated for cranial nerve involvement in the course of vasculitis.In the case of unclear involvement of the cranial nerves, PAN should also be considered in the differential diagnosis as the cause of symptoms and the first manifestation of the disease.

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.

Background In addition to the impact of Psoriatic Arthritis (PsA) on risk of death and increased morbidity, other factors, such as comorbidity burden (CB), have also an important role[1]. Identifying comorbidities and estimating their impact on the disease course are critical to safely and effectively treating a patient with PsA, as these comorbidities have often implications on therapy selection. Objectives To measure the impact of CB on PsA patients treated with a first-line Biologic Disease Modifying AntiRheumatic Drug (bDMARD) using the Rheumatic Disease Comorbidity Index (RDCI). Methods Retrospective observational cohort-study of patients with diagnosis of PsA, fulfilling the CASPAR criteria and treated with a first bDMARD, using data from the Reuma.pt database. Patients were divided in 2 groups according the RDCI (RDCI=0 and RDCI≥1) for evaluating its role in clinical response and disease activity at baseline and follow up (6 and 12 months). An univariate analysis was performed followed by a multivariate analysis. Results A total of 115 patients were included. 53% (n=61) were females, mean age was 47(±10.7) years old and the median disease duration 10.5 years [1.4-44.1]. At baseline, most of patients exhibited a very high or high disease activity (median DAS284V 4.44, ASDAS-CRP 3.98, BASDAI 6.69) and 68% were concomitantly treated with other DMARD and/or corticosteroids. 43% of patients had at least one comorbidity and the median RDCI score was 1.1 [0.0-6.0]. The most frequently reported comorbidities were cardiovascular disorders (37.7%), depression (13.2%) and pulmonary disease (6.1%). When comparing baseline demographic and clinical characteristics of the 2 subgroups, stratified according RDCI score, we found statistically significant differences in age, age at diagnosis, disease duration, BMI and smoking status. RDCI was poorly correlated with CRP (r=0.162, p<0.01), DAS284V (r=0.263, p=0.008), ASDAS CRP (r=0.284, p<0.001) at 12 months. We also found moderate correlations in RDCI with BASFI (r=0.370, p<0.001) and HAQ-DI (r=0.351, p<0.01). Patients with higher RDCI had lower chance to obtain low disease activity (OR 0.69 (95%CI, 0.61–0.79); p < 0.001). EULAR response rate at 12 months was lower in PsA patients with comorbidities (69.7%vs90.5%, p=0.02). Conclusion To conclude, our study demonstrates that baseline CB is an independent predictor for insufficient 12 months response to the first bDMARD. This confirmed the hypothesis that comorbidity should be treated to improve the long-term prognosis in PsA patients. Reference [1]Cañete,J.D.,Tasende,J.A.P.,Laserna,F.J.R. et al. The Impact of Comorbidity on Patient-Reported Outcomes in Psoriatic Arthritis: A Systematic Literature Review.2020; Rheumatol Ther 7,237–257 Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1RDCI=0 (n=70)RDCI≥1 (n=45)pCurrent age,years48.7±9.858.8±7.7<0.001Sex (M/F)34/7020/450.665Age of diagnosis,years*37.8±7.958.7±6.5<0.001Disease duration,years*6.6±4.110.1±4.40.02Smoking status,n(%)26(10.7)41(13.6)0.013Psoriasis,n(%)55(78.5)33(73.3)0.706Nail involvement,n(%)29(41.4)12(26.6)0.107Axial involvement,n(%)37(53)27(0.6)0.452Dactylitis,n(%)27(38.5)15(33)<0.001Enthesitis,n(%)27(38.5)7(15.5)0.873BMI(*)25.4±4.731.2±4.9<0.001DAS28 4VCRP baseline*3.6±1.43.6±1.10.736ASDAS CRP baseline*3.9±1.14.0±0.90.295BASDAI baseline*6.8±2.17.1±1.50.978BASFI baseline*5.8±2.76.2±1.90.378ESR baseline*29.1±23.539.1±22.80.02CRP baseline*2.1±3.52.3±2.60.275HAQ baseline*0.6±0.70.7±0.60.006DAS28 4VCRP 12M*2.0±0.72.9±1.10.022ASDAS CRP 12M*2.0±0.92.8±1.90.04BASDAI 12M*3.2 ±2.64.4±2.10.106BASFI 12M*2.6 ±2.75.3±2.7<0.001HAQ 12M*0.6±0.71.1±0.60.006EULAR response 12M,n(%)57/63(90.5)30/43(69.7)0.02ASDAS response 12M,n(%)47/70(67.1)24/45(53.3)0.137PSARC response 12M,n(%)45/60(75)23/37(62)0.180Therapeutic,n(%)cDMARDs48(68.5)29(64.4)0.862Glucocorticoids40(57.1)23(51.1)0.526Antidepressants4(5.8)9(20)0.01*(mean±SD)