Long-term survival of patients with idiopathic inflammatory myopathies: anatomy of a single-centre cohort.

OBJECTIVES: We aimed to characterise clinical manifestations, disease course, treatment, and mortality of IIM patients. We have also attempted to identify predictors of mortality in IIM. METHODS: This was a retrospective single-centre study including IIM patients fulfilling the Bohan and Peter criteria. Patients were divided in 6 groups: adult-onset polymyositis (APM), adult-onset dermatomyositis (ADM), juvenile-onset dermatomyositis, 'overlap' myositis (OM), cancer-associated myositis, and antisynthetase syndrome. Sociodemographic, clinical and immunological features, treatment, and causes of death were recorded. Survival analysis and predictors of mortality was performed using Kaplan-Meier and Cox proportional hazards regression. RESULTS: A total of 158 patients were included with a mean age at diagnosis of 40.8±15.6 years. Most patients were female (77.2%) and Caucasian (63.9%). The most frequent diagnoses were ADM (35.4%), OM (20.9%) and APM (24.7%), respectively. Most patients (74.1%) were treated with a combination of steroids and one-to-three immunosuppressive drugs. Interstitial lung disease, gastrointestinal and cardiac involvement affected 38.5%, 36.5% and 23.4% of the patients, respectively. The survival rates at 5, 10, 15, 20 and 25 years of follow-up were 89%, 74%, 67%, 62% and 43%, respectively. During a median follow-up of 13.6±10.2 years, 29.1% have died, infection being the most common cause (28.3%). Older age at diagnosis (HR1.053, 95% CI 1.027-1.080), cardiac involvement (HR 2.381, 95% CI 1.237-4.584), and infections (HR 2.360, 95% CI 1.194-4.661) were independent predictors of mortality. CONCLUSIONS: IIM is a rare disease with important systemic complications. Early diagnosis and aggressive treatment of cardiac involvement and infections could improve survival of these patients.

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

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

Preconception counseling impact in pregnancy outcomes in patients with spondyloarthritis.

INTRODUCTION: Spondyloarthritis (SpA) is a group of chronic inflammatory diseases, often affecting women in reproductive age. These diseases can have a significant impact on the reproductive health of women. Preconception counseling and medication adjustments have shown to reduce flares and improve pregnancy outcomes in women with rheumatoid arthritis. However, in women with SpA data of the impact of preconception counselling on pregnancy outcomes is scarce. The aim of this study is to evaluate that. METHODS: In this retrospective multicentric study, data was collected from medical records of women who gave birth from 2020 to 2022. The study included 45 pregnancies, which were divided into two categories whether they received preconception consultation or not. Data was collected on patient characteristics, disease duration, medications used, and preconception counselling. Outcomes were divided into two groups: maternal and fetal outcomes. RESULTS: 30 out of 45 pregnancies (66.67%) had received preconception counselling, having a significantly lower percentage of flares occurring postpartum compared to the non-counselling group (36.6% vs 6.4%, p=0.031) and lower percentage of contraindicated medication during pregnancy (20.0 vs 0.0%, p=0.011). CONCLUSION: Preconception counselling in women with SpA can increase the likelihood of medication adjustments before pregnancy and decrease the occurrence of flares postpartum. These findings suggest that preconception counselling should be implemented in the management of pregnant women with SpA to improve pregnancy outcomes. Further studies are needed to confirm the effectiveness of preconception counselling and to determine the optimal approach.

Touraine-Solente-Gole syndrome: pathogenic variant in SLCO2A1 presented with polyarthralgia and digital clubbing.

BACKGROUND: Primary Hypertrophic Osteoarthropathy (PHO), also known as Touraine-Solente-Gole Syndrome, is a rare, multisystemic autosomal recessive disorder caused by pathogenic variants in the 15-hydroxyprostaglandin dehydrogenase (HPGD) or Solute Carrier Organic Anion Transporter Family Member 2A1 (SLCO2A1) genes. However, autosomal dominant transmission has also been described in some families with incomplete penetrance. PHO usually starts in childhood or adolescence, presenting with digital clubbing, osteoarthropathy, and pachydermia. We described a complete form of the syndrome in a male patient with a homozygous variant in the SLCO2A1 gene (c.1259G > T). CASE PRESENTATION: A 20-year-old male was referred to our Pediatric Rheumatology Clinic with a five-year history of painful and swollen hands, knees, ankles and feet, prolonged morning stiffness and relief with non-steroidal antiinflammatory drugs. He also reported late onset facial acne and palmoplantar hyperhidrosis. Family history was irrelevant and parents were non-consanguineous. On clinical examination, he presented clubbing of the fingers and toes, moderate acne and marked facial skin thickening with prominent scalp folds. He had hand, knee, ankles and feet swelling. Laboratory investigations showed elevated inflammatory markers. Complete blood count, renal and hepatic function, bone biochemistry were normal, as well as immunological panel. Plain radiographs revealed soft tissue swelling, periosteal ossification and cortical thickening of the skull, phalanges, femur and toe acroosteolysis. Due to the absence of other clinical signs suggesting a secondary cause, we suspected PHO. A genetic study revealed a likely pathogenic variant, c.1259G > T(p.Cys420Phe), in homozygosity in the SLCO2A1 gene, thus confirming the diagnosis. The patient started oral naproxen with significant clinical improvement. CONCLUSIONS: PHO should be kept in the differential diagnosis of inflammatory arthritis affecting children, often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). To the best of our knowledge, this is the second genetically confirmed case of PHO in a Portuguese patient (first variant c.644 C > T), both made at our department.

Predictive factors of fragility fractures and associated mortality: assessment of patients observed at emergency department.

AIM: To assess the predictive factors for a subsequent fragility fracture (FF) and mortality. METHODS: Retrospective monocentric study including patients observed at the emergency department (ED) of a referral hospital with a FF, between 1st January 2017 and 31st December 2018. Fractures events were identified through discharge codes using the 9th International Classification of Diseases codes and FF were adjudicated after revision of the clinical files. We identified 1673 patients with FF. After calculating a representative sample (95% confidence interval), 172 hip, 173 wrist and 112 vertebral fractures were included in the analysis. Their clinical files were reviewed until 31st December 2020. A multivariate analysis was performed in order to identify predictive factors for FF. RESULTS: Overall, during the follow-up period 76 patients (16.6%) had a new FF and 120 patients (26.3%) died. Multivariate analysis showed that previous visits to the ED due to falls (p=0.002) and malignancy (p=0.026) were independent risk factors for a new FF. The main predictors of mortality were age, hip fracture, oral corticosteroid treatment, normal or low BMI and cardiac, neurologic or chronic kidney disease. CONCLUSIONS: FF are a very prevalent public health problem that can lead to significant morbidity and death. Certain comorbidities seem to be associated with new FF and increased mortality. There might be a substantial missed opportunity for intervention in these patients, namely in ED visits.

Barriers and alternatives to pediatric rheumatology referrals: a survey of family doctors and pediatricians in Portugal.

BACKGROUND: Access to pediatric rheumatology (PR) is not well described in Portugal. The main goal of this study was to ascertain barriers to PR referrals and subsequent alternative referral patterns among family doctors and pediatricians. METHODS: A web-based survey was e-mailed to family doctors and pediatricians practicing in Portugal, in order to investigate access to PR care issues. Descriptive and comparative analysis was performed. RESULTS: Two hundred and ninety-two responses were obtained, 24.7% from pediatricians and 75.3% from family doctors. Only 12% claimed to have had specific education on PR. Nearly 70% worked less than one hour away from a PR center. Twenty eight percent had referred a patient to PR at least once, and 9.3% experienced a situation in which they considered referring to PR but ultimately did not. Many referred to other specialties, primarily pediatrics, adult rheumatology, and pediatric orthopedics. Pediatricians encountered more diversified rheumatic diseases. Fifty five percent had no opinion on PR centers' support, while 24% found it sufficient. Having specific training on PR, being a pediatrician and a specialist were associated with greater referrals to PR. The most rated measure for PR referrals' improvement was promoting education. Regional access to PR's discrepancies were documented. CONCLUSION: Mainly lack of education on PR, but also uneven national coverage and greater distances to some PR centers were the main barriers to PR referrals, in Portugal. Pediatricians seem to have better education, greater experience and more referrals to PR. The current alternatives for referral are pediatrics, adult rheumatology and pediatric orthopedics. Educational consolidation was the biggest and most rewarding inconsistency to battle against.

Predictors of Interstitial Lung Disease in Mixed Connective Tissue Disease.

Interstitial lung disease (ILD) frequently complicates mixed connective tissue disease (MCTD) and contributes to increased mortality. We aimed to identify predictors of ILD in MCTD patients. This is a nationwide, multicentre, retrospective study including patients with an adult-onset MCTD clinical diagnosis who met Sharp's, Kasukawa, Alarcón-Segovia, or Kahn's diagnostic criteria and had available chest high-resolution computed tomography (HRCT) data. Univariate and multivariate analyses were conducted. We included 57 MCTD patients, with 27 (47.4%) having ILD. Among ILD patients, 48.1% were asymptomatic, 80.0% exhibited a restrictive pattern on pulmonary function tests, and 81.5% had nonspecific interstitial pneumonia on chest HRCT. Gastroesophageal involvement (40.7% vs. 16.7%, p = 0.043) and lymphadenopathy at disease onset (22.2% vs. 3.3%, p = 0.045) were associated with ILD. Binary logistic regression identified lymphadenopathy at disease onset (OR 19.65, 95% CI: 1.91-201.75, p = 0.012) and older age at diagnosis (OR 1.06/year, 95% CI: 1.00-1.12, p = 0.046) as independent ILD predictors, regardless of gender and gastroesophageal involvement. This study is the first to assess a Portuguese MCTD cohort. As previously reported, it confirmed the link between gastroesophageal involvement and ILD in MCTD patients. Additionally, it established that lymphadenopathy at disease onset and older age at diagnosis independently predict ILD in MCTD patients.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Clinical features and outcome of 1054 patients with Systemic Sclerosis: analysis of Reuma.pt/SSc registry.

BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disorder with heterogeneous manifestations and outcomes. Besides differences in disease characteristics among distinct ethnic groups and geographical regions, several questions regarding the impact of the disease and the effectiveness of treatments remain unanswered. To address these questions, the Rheumatic Diseases Portuguese Register (Reuma.pt) launched a specific protocol for the prospective follow-up of SSc patients. OBJECTIVES: To describe the baseline characteristics, disease subsets, treatments used and survival of SSc patients registered in Reuma.pt/SSc. METHODS: Data from adult patients with SSc included in Reuma.pt up to November 2020 were analysed. Demographic features, SSc subsets, fulfilment of classification criteria, main clinical and immunological features, comorbidities, treatments used and survival data were described and compared between diffuse cutaneous (dc) and limited cutaneous (lc) disease subsets. Survival was calculated for patients included in Reuma.pt within the first two years of diagnosis. RESULTS: In total, 1054 patients were included, 87.5% female, with a mean age at diagnosis of 52.7 +/- 14.8 years. The most common subset was lcSSc (56.3%), followed by dcSSc (17.5%), preclinical SSc (13%), overlap syndrome (9.8%) and SSc sine scleroderma (3.3%). Raynaud's phenomenon (93.4%) and skin thickening (76.9%) were the most frequently observed clinical manifestations. Gastrointestinal (62.8% versus 47.8%), pulmonary (59.5% versus 23%) and cardiac (12.8% versus 6.9%) involvements were significantly more prevalent in dcSSc than lcSSc. Ninety per-cent of patients were Antinuclear antibody positive, 52.5% were Anti-centromere antibody positive and 21% anti-topoisomerase positive, with significant differences between lcSSc and dcSSc. One-third of patients were treated with immunomodulators, 53.6% with vasodilators, 23% with glucocorticoids and 2.3% with biologics. During follow-up, 83 deaths (7.9%) were reported. The overall 1-, 2- and 5-year survivals were 98.0%, 96.8% and 92.6%, respectively, without significant differences between lcSSc and dcSSc. CONCLUSION: Reuma.pt/SSc data highlights the importance of registries in improving knowledge about rare and complex diseases, such as SSc. Clinical features of Portuguese SSc patients are similar to those of other populations. In recently diagnosed patients, 5-year survival is over 92%. To the best of our knowledge, this is the first study showing that clinical features of Portuguese SSc are similar to those of other cohorts.

Gender differences in clinical features and outcomes of a Portuguese systemic sclerosis cohort.

Evidence for the role of sex in the clinical manifestations of systemic sclerosis (SSc) patients is emerging. Some multicenter cohorts have shown that male SSc patients have more severe disease and worse survival. To assess the differences in clinical manifestations and survival in Portuguese SSc patients according to gender. Data from male and female adult SSc patients included in the Rheumatic Diseases Portuguese Register (Reuma.pt) were analysed and compared. Survival was calculated for patients included in Reuma.pt. within the first two years of diagnosis (inception cohort). In total, 1054 adult patients with SSc were included, 12.5% males. No differences in demographic features and comorbidities were found between the sexes, except for a higher rate of cigarette smokers among men. Diffuse cutaneous SSc and anti-topoisomerase antibodies were more prevalent in males than females. Additionally, male patients presented significantly more myositis, interstitial lung disease and gastric involvement. There were no differences in the patterns of drug use between the sexes. During follow-up, more deaths were reported in men than women (12.1% vs 7.3%, p = 0.04). The overall 1-, 3-, and 5-year survivals from diagnosis of the inception cohort (N = 469) for men vs women were 96.4% vs 98.2%, 93% vs 95.9%, and 75.8% vs 93.2%, respectively, with statistically significant differences (p < 0.01). This study confirms the existence of gender differences in clinical and immunological SSc features. Although SSc is less common in men than women, men have a more severe expression of skin and internal organ involvement and worse survival. Key Points • There are differences in SSc disease manifestations between sexes. • Males more commonly have diffuse cutaneous SSc, anti-topoisomerase antibodies, pulmonary and musculoskeletal involvement. • In the inception cohort, men had worse survival rates than women.

Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Uncommon causes of nerve compression in the distal forearm.

INTRODUCTION: Nerve compression by anomalous masses located at the wrist and distal forearm is an infrequent condition. They may compress underlying structures in the carpal tunnel region, causing pain and paresthesias, which leads to the wrong diagnosis of carpal tunnel syndrome. CLINICAL CASES: We present three cases of patients with symptomatology and clinical tests compatible with compression of the median nerve in the carpal tunnel but whose physical examination showed a soft mass in the distal region of the forearm which was compressing the median nerve, as demonstrated by ultrasound evaluation. DISCUSSION: The reported cases of accessory muscles or lipomas described in the literature as causes of median nerve compression clinic are mainly described only after the surgical decompression of the carpal tunnel, due to the maintenance of residual symptoms. CONCLUSION: Careful examination with an ultrasound evaluation prior to surgery may help to identify these cases and help planning surgical treatment.

ANCA-associated vasculitis in a patient with enteropathic spondylarthritis: a case report and literature review.

Coexistence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and inflammatory bowel disease (IBD) is rare (Sy et al. in Semin Arthritis Rheum 45:475-482, 2016). Nevertheless, we present a case of an AAV in a 53-year-old female with enteropathic spondylarthritis previously treated with tumor necrosis factor α inhibitors (TNFi). Management of vasculitis in a patient with IBD may be problematic due to the difficulty in distinguishing if the vasculitis is an extraintestinal manifestation of the IBD or a new coexistent entity. Moreover, in our report, the previous treatment with TNFi is a possible confounding factor due to the paradoxical effects induced by TNFi, including vasculitis (Ramos-Casals et al. in Curr Rheumatol Rep 10:442-448, 2008). The reported case alerts to the complexity in the management of patients with enteropathic spondylarthritis and vasculitis, as well as discusses the diversity of differential diagnosis in this particular clinical scenario.

Strategies for the withdrawal of classic and biological DMARD in clinically inactive patients with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate and describe the strategies of Portuguese rheumatologists and paediatricians, regarding either the maintenance or the withdrawal of classic and biologic disease-modifying anti-rheumatic drugs (cDMARDs and bDMARDs, respectively), when patients with Juvenile Idiopathic Arthritis (JIA) achieved clinical inactive disease (CID). METHODS: We performed a 30-question questionnaire, which was sent to all the 35 clinicians enrolled in the Portuguese group of paediatric rheumatology. RESULTS: Twenty-three complete responses were obtained. The factors with the greatest impact on the decision to withdraw cDMARDs were: the duration of the CID, the therapy-induced toxicity, the presence of erosive disease and joint damage, the subtype of JIA, the time to reach inactive disease and the low adherence to therapy. These factors were classified as "very important" in this decision by more than 50% of the clinicians. The same factors, except for low adherence, had the greatest impact, when considering the withdrawal of bDMARDs. Withdrawal was more likely in patients with persistent oligoarticular JIA and less likely in rheumatoid factor positive polyarticular JIA. Sulfasalazine was more susceptible to be discontinued than methotrexate. Contrariwise, there were no differences concerning bDMARDs. Most participants reported that they started the drug withdrawal only after 12 months of sustained remission, by progressively tapering the dose of the cDMARD and spacing the intake of the bDMARD. Also, they reported that the decision to suspend the DMARD was based on imaging methods, preferably ultrasound, and in patient-reported outcomes. For patients on combination therapy, bDMARDs are reported to be the first to be withdrawn. CONCLUSIONS: Literature is scarce on this matter and there are no well-defined guidelines on how to withdrawal cDMARDs or bDMARDs on JIA. Notwithstanding, most Portuguese physicians were in agreement on the factors that needed to be taken into account with respect to the withdraw decision.

Early retirement attributed to rheumatoid arthritis and its predictors.

OBJECTIVE: To evaluate the rate of early retirement due to rheumatoid arthritis (RA) in Portugal. METHODS: Prospective cohort study involving 11 Portuguese centers, including patients with a clinical diagnosis of RA, based on Reuma.pt registry, enrolled between 2008 and 2019. RESULTS: 3231 patients were included (81.5% female, aged 60.8 ± 13.0 years, mean disease duration 18.0 ± 10.3 years). Until the present time, 37.6% of these patients retired, 59.6% due to RA. Early retirement due to RA translated into losing 7 years of active work when compared to patients retired to other causes. Compared to professionally active patients, retired patients due to RA were diagnosed later in the disease process (p=0.003), had longer disease duration (p < 0.001), were more frequently positive for rheumatoid factor (p=0.043), had more frequently erosive disease (p < 0.001), had a blue-collar occupation (p < 0.001) and had a lower educational level (p < 0.001). Independent predictors for early retirement due to RA were: delayed diagnosis (OR: 2.23; 95% CI 1.18-4.21/year, p=0.013), erosive disease (OR: 2.21 95% CI 1.54-3.16, p < 0.001), need for biologic therapy (OR: 1.32; 95%CI 1.01-1.73, p=0.045) and lower educational level (OR: 0.83; 95%CI 0.79-0.86/year, p < 0.001). CONCLUSION: RA is, itself, the leading cause of early retirement in RA patients, accounting for the loss of an average of 7 years of active work. Delayed diagnosis, erosive disease and lower educational level are the main predictors of early retirement associated with RA in this population.