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Abstract This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis. Clinical trials confirm the efficacy of JAKis in combination with MTX in terms of treatment outcomes in RA. However, the number of major adverse cardiovascular events (MACEs) reported is too low to draw conclusions on adverse CV outcomes. Indirect evidence does, however, suggest potential protective effects of MTX on CV outcomes, as several mechanisms may contribute to MTX’s cardioprotective effects, including reduced inflammation, adenosine monophosphate-activated protein kinase (AMPK) activation, increased cholesterol efflux, and adenosine accumulation. These mechanisms and the available data may support the case for CV benefits of concomitant MTX when JAKis are used in the treatment of patients with RA, although further research is needed. In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA.

During the last decade, spondyloarthritis (SpA) has increasingly been considered a disease at the crossroads between autoimmunity and autoinflammation. Some patients may even present with autoinflammatory-related manifestations, including fever, hidradenitis suppurativa, other neutrophilic dermatoses, and an unusually high increase in inflammatory markers. Therefore, a subgroup of SpA patients may be identified, and specific details about this cluster need to be investigated. In this regard, the AutoInflammatory Disease Alliance (AIDA) Network has developed a registry primarily aimed at better understanding the autoinflammatory aspects of SpA. The development of this Registry favors the systematic assessment of SpA through the lens of autoinflammation, giving a voice to patients with atypical presentations, and favoring a personalized treatment approach. By supporting research and facilitating the transfer of new evidence to clinical practice, this specific registry has the potential to significantly advance the field of rheumatology and enhance the lives of patients suffering from this complex and multifaceted disease.

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Polymyositis is a rare disease that belongs to the idiopathic inflammatory myopathies (IIMs) group, characterized by chronic muscle inflammation, and in rare cases a life-threatening condition due to extra-muscular involvement. Even though steroids constitute the building block of treatment of this disease, in severe cases, escalation treatment should be considered in order to obtain good clinical outcomes. We report a clinical case of a 22-year-old female who developed progressive severe systemic muscular weakness, dysphagia and dysphonia, accompanied by elevated serum muscle enzymes, positive myositis-specific antibodies, and muscle biopsy suggestive of inflammatory myopathy. The clinical features and laboratory results led us to the diagnosis of polymyositis. On additional laboratory tests the patient tested positive for Borrelia burgdorferi (Borrelia b) specific antibodies. Due to life-threatening organ involvement the immunosuppressive treatment, immunoglobulin intravenous infusion and pulse therapy with methylprednisolone were initiated and she needed nasogastric tube in order to be fed. Furthermore antibiotic treatment was administrated. The patient improved almost completely after 3 months of treatment.

Cutaneous disease is one of the most frequent manifestations of systemic lupus erythematosus (SLE), being classified as LE-specific and LE-nonspecific. LE-specific skin lesions are divided into acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). The association with systemic involvement varies between each clinical subtype, with non-specific lesions being more frequent associated with active SLE than cutaneous specific lesions. The treatment consists of topical agents (glucocorticoids, topical calcineurin inhibitors) as well as systemic therapies (glucocorticoids, hydroxychloroquine, quinacrine, methotrexate, retinoids, dapsone, mycophenolate mofetil or even biologics). In the presence of strictly cutaneous involvement, periodic patient follow-up and monitoring for the progression to systemic disease remains an important mission for the dermatologist and the rheumatologist.

Sjogren’s syndrome (SSj) is a chronic autoimmune disease mainly targeting the exocrine glands, but sometimes associating extra-glandular manifestations. Xerosis, purpura, Raynaud’s phenomenon, cutaneous vasculitis, annular erythema are the main forms of skin involvement. A 26-year-old female patient was admitted for diffuse erythematous rash and angioedema, xerophthalmia and symmetrical arthralgia of hand joints. Anti-nuclear antibodies, anti-SSA and anti-Ro52 antibodies were identified, Schirmer’s test was positive, thus the diagnoses of primary SSj and associated urticarial vasculitis were established. Treatment with oral methylprednisolone, azathioprine and hydroxychloroquine was initiated, with favourable response over the next week. Patients with primary SSj that develop cutaneous vasculitis, lymphadenopathies or lymphopenia may be at risk for additional extra-glandular manifestations, including non-Hodgkin lymphoma.

Osteomyelitis pubis (OP) is a rare type of infection involving the pubic bones that often poses diagnostic and consecutive therapeutic problems. The infection can be mono or polymicrobial, bacterial, mycotic or bacillary with Staphylococcus aureus being the most common infectious agent involved. OP is generally seen in immune-suppressed patients of oncologic and diabetic population or in pediatric and geriatric subjects. The main symptom is represented by local pain with radiation to thighs which in later stages is accompanied by general non-specific symptoms such as malaise, fever and loss of appetite. The specificity-lacking initial presentation often leads to diagnostic delays which furthermore decrease the effectiveness of drug therapy, leading to higher chances of bone and joint destruction. Initial therapy consists of empirical antibiotherapy that should cover Staph. aureus; depending on culture results, the scheme should be changed accordingly. Moreover, symptomatic treatment of pain and inflammation consisting of NSAIDs, small dose glucocorticoids and minor opioids should be considered. Selected cases may benefit from surgical intervention when improvement or remission is considered improbable under drug therapy or when severe bony destructions are present.

Relapsing polychondritis (RP) is an auto-immune disease which affects the cartilaginous parts of sites like the ear, nose or upper respiratory tract. The condition can also involve other cartilage-containing structures such as the eyes, joints, the heart, kidneys and central nervous system. Early diagnosis of RPis essential for preventing significant damage to vital organs that can lead to increased morbi-mortality rates. First-line therapy in RP is systemic glucocorticoids, while in refractory cases monoclonal antibodies can be used despite scarcity of efficacy data available in published literature. The link between RP and neoplasia, especially hematological malignancy, should not be omitted when screening patients with suspicion of RP diagnosis. The onset of COVID-19 pandemic has generated a new source of immune mediated pathologies, such as small vessel vasculitis, immune thrombocytopenic purpura or Guillain-Barre syndrome and other auto-inflammatory syndromes triggered by COVID-19 seem to unveil. The present case depicts a female patient who presented with erythematous and painful areas of her right ear after priorly experiencing similar episodes in both ears and nose bridge shortly after having the COVID-19 vaccine booster dose.

Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a ‘non-lethal’ manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.

Systemic Lupus Erythematosus is the hallmark of autoimmune diseases, being characterized by multiple organ involvements and immune abnormalities, amongst which the presence of antiphospholipid antibodies with or without specific clinical manifestations (vascular thromboses and pregnancy morbidities) has a significant impact on the disease course, both short and long term, causing the accumulation of irreversible damage. This study evaluates the aforementioned impact, highlighting the importance of very early screening for these antibodies.

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p

Nutrition has been identified as playing a significant role in inflammatory rheumatic conditions. Available recommendations for managing these diseases have recently included lifestyle changes as well as dietary advice as complementary to pharmacological treatments. This is a summary of the first dietary recommendations for patients suffering from rheumatic diseases, postulated by the French Society for Rheumatology. The work was performed by a group of multidisciplinary experts and it was based on a systematic literature review of available published data, also considering the quality of studies. The eight principles and nine recommendations issued target both joint and extra-articular effects of nutritional intervention. The recommendations state following a Mediterranean diet, supplementation of omega-3 polyunsaturated fatty acids. Restrictive-type diets like gluten-free, dairy-free, fasting or vitamins and trace elements supplementation are not recommended because of lack of scientifically proven benefit. The use of probiotics or spices have insufficient rationale to be recommended.

Objective. The spondyloarthritis group comprises chronic inflammatory conditions that share clinical, genetic and radiographic features. The impact of comorbidities on disease activity is not entirely known. The aim of this study is to identify the frequency and management of comorbidities in SpA patients. Materials and methods. A six-month retrospective study included 235 SpA patients for whom demographic, disease data and associated comorbidities were collected, according to EULAR’s designated categories. Statistical analysis was performed using Microsoft Excel. Results. 71% were males, with a mean age of 42.3, suffering from SpA for more than 15 years. 60% patients were overweight or obese, 25% had been diagnosed with hypertension, 28% were smokers. 18% suffered from dyslipidemia and 9% had type II diabetes. 16% had hepatitis B while 2% had C viral infection, 14% had previous mild to moderate urinary or pulmonary infections. Osteoporosis was confirmed in 6% and malignancies in 2.5% cases. Conclusions. The most frequently encountered comorbidities were cardio-vascular events, followed by gastro-intestinal disorders. SpA patients require early comorbidity detection with the aid of their rheumatologist and a multidisciplinary care to avoid additional disease burden.

Impaired fertility is an important public health concern, especially in patients with immune-mediated rheumatic conditions. Frequency of infertility /subfertility vary among rheumatic diseases – higher in systemic lupus erythematosus or rheumatoid arthritis, than in other autoimmune diseases. Risk factors like age, nulliparity, disease activity or medication such as NSAIDs, corticosteroids, cyclophosphamide are mostly encountered. Treating a pregnant woman is a challenge: the well-being of mother and child has to be considered, as tight disease control before, during pregnancy and postpartum is mandatory to minimize adverse outcome risk. Safety of biological therapies during preconception, pregnancy, and postpartum is crucial, anti-TNFs being safe in early pregnancy, second, but not third trimester. Etanercept and certolizumab may be considered for use throughout pregnancy due to low rate of transplacental passage. Concerning the child, live-attenuated vaccines are to be avoided for the first 6 months of life due to persistence of biologics.

Dermatomyositis (DM) is a rare autoimmune disorder defined by weakness of the striated muscles and a distinctive skin rash. Dysphagia is a serious symptom that can be difficult to manage, severely impacting quality of life and long-term survival. The aim of this report is to highlight a case of an anti-NXP-2 positive DM with severe dysphagia refractory to multiple therapies, including steroids, cyclophosphamide and intravenous immunoglobulins. Anti-NXP-2 autoantibodies indicate a specific disease phenotype adding severe muscle weakness, dysphagia, peripheral edema and underlying malignancy.

Although perceived as an adaptative immune disorder, mainly related to Lymphocyte B and T, last years focus on Systemic Lupus Erythematosus (SLE) pathogeny emphasised the important role of innate immunity. This should not take us by surprise since the lupus cell described by Hargraves and colleagues in 1948 was a neutrophil or macrophage with specific aspect after coloration with haematoxylin related to cell detritus engulfment (Hargraves et al., 1948) [1] (Presentation of two bone marrow elements; the tart. Hargraves M, Ricmond H, Morton R. 1948, Proc Staff Meet Mayo Clinic, pp. 23:25–28). Normal immune system maintains homeostasis through innate and adaptative response that are working together to prevent both infection and autoimmunity. Failure of the immune mechanisms to preserve the balance between these two will initiate and propagate autoinflammation and/or autoimmunity. It is well known now that autoinflammation and autoimmunity are the two extremes of different pathologic conditions marked with multiple overlaps in many diseases. Recent findings in SLE demonstrated that innate immune system initiates the abnormal autoimmunity and starts the continuous inflammatory reaction after that, interferon being one of the key cytokines in innate immunity and SLE. Understanding this mechanism might offer a better clue for an efficient treatment in SLE patients. The purpose of this review is to highlight the enormous impact of innate immunity and mostly interferons in SLE.

Systemic sclerosis is a chronic autoimmune disorder characterized by multiorgan involvement, most notably of the skin through fibrosis and vasculopathy. One of its most feared complications requiring rapid intervention is scleroderma renal crisis, as it can be fatal in the absence of prompt treatment. A 34-year old woman presents with a history of acute renal failure and malignant hypertension occurring one month postpartum and no other scleroderma feature in the following 5 years. Eventually, skin, heart and lung involvement is observed, positive anti-ARN III polymerase antibodies and suggestive capillaroscopic findings. Immunosuppressive therapy with mycophenolate mofetil is initiated and later switched to off-label Rituximab, with significant improvement of disease manifestations. Regular patient monitoring for novel symptom occurrence and appropriate treatment adjustment is essential for optimal management of scleroderma.

Introduction. The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Material and method. We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096 . We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 173 patients with SSc were available for the baseline analyses. In the longitudinal analysis after a mean follow-up of 3.5(±0.65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p = 0.004), digital contractures (OR:8.2 (3.1 to 21.9); p < 0.001), arrhythmias (OR: 3.37 (1.36 to 8.34); p = 0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p = 0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7.59); p = 0.016), severe vascular involvement (OR:2.86, (1.22 to 6.73); p = 0.013) and low ventricular ejection fraction (OR: 2.84, (1.2 to 6.73); p = 0.014). Males had significantly reduced survival time after diagnosis (p = 0.004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process.

ObjectiveThe present manuscript aims to describe an international, electronic-based, user-friendly and interoperable patient registry for monogenic autoinflammatory diseases (mAIDs), developed in the contest of the Autoinflammatory Diseases Alliance (AIDA) Network.MethodsThis is an electronic platform, based on the Research Electronic Data Capture (REDCap) tool, used for real-world data collection of demographics, clinical, laboratory, instrumental and socioeconomic data of mAIDs patients. The instrument has flexibility, may change over time based on new scientific acquisitions, and communicate potentially with other similar registries; security, data quality and data governance are corner stones of the platform.ResultsAIDA project will share knowledge and expertise on mAIDs. Since its start, 118 centers from 24 countries and 4 continents have joined the AIDA project. Fifty-nine centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 337 users (122 Principal Investigators, 210 Site Investigators, 2 Lead Investigators, and 3 data managers). The Registry collects baseline and follow-up data using 3,748 fields organized into 21 instruments, which include demographics, patient history, symptoms, trigger/risk factors, therapies, and healthcare information for mAIDs patients.ConclusionsThe AIDA mAIDs Registry, acts both as a research tool for future collaborative real-life studies on mAIDs and as a service to connect all the figures called to participate. On this basis, the registry is expected to play a pivotal role in generating new scientific evidence on this group of rare diseases, substantially improving the management of patients, and optimizing the impact on the healthcare system. NCT 05200715 available at https://clinicaltrials.gov.

ObjectiveThe present paper describes the design, development, and implementation of the AutoInflammatory Disease Alliance (AIDA) International Registry specifically dedicated to patients with Schnitzler's syndrome.MethodsThis is a clinical physician-driven, population- and electronic-based registry implemented for the retrospective and prospective collection of real-life data from patients with Schnitzler's syndrome; the registry is based on the Research Electronic Data Capture (REDCap) tool, which is designed to collect standardized information for clinical research, and has been realized to change over time according to future scientific acquisitions and potentially communicate with other existing or future similar registries.ResultsSince its launch, 113 centers from 23 countries in 4 continents have been involved. Fifty-seven have already obtained the approval from their local Ethics Committees. The platform counts 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) at current (April 28th, 2022). The registry collects baseline and follow-up data using 3,924 fields organized into 25 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, laboratory, instrumental exams, therapies, socioeconomic information, and healthcare access.ConclusionsThis International Registry for patients with Schnitzler's syndrome facilitates standardized data collection, enabling international collaborative projects through data sharing and dissemination of knowledge; in turn, it will shed light into many blind spots characterizing this complex autoinflammatory disorder.

ObjectiveThe aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management. The Registry may potentially communicate with other on-line tools dedicated to VEXAS syndrome, thus enhancing international collaboration and data sharing for research purposes. The Registry is practical enough to be easily modified to meet future needs regarding VEXAS syndrome.ResultsTo date (April 22nd, 2022), 113 Centers from 23 Countries in 4 continents have been involved; 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) are currently able to access the registry for data entry (or data sharing) and collection. The Registry includes 4,952 fields organized into 18 instruments designed to fully describe patient's details about demographics, clinical manifestations, symptoms, histologic details about skin and bone marrow biopsies and aspirate, laboratory features, complications, comorbidities, therapies, and healthcare access.ConclusionThis international Registry for patients with VEXAS syndrome will allow the achievement of a comprehensive knowledge about this new disease, with the final goal to obtain real-world evidence for daily clinical practice, especially in relation to the comprehension of this disease about the natural history and the possible therapeutic approaches. This Project can be found on https://clinicaltrials.gov NCT05200715.

Objective. To evaluate sexual function in a cohort of men with rheumatic disease compared to healthy controls. Patients and methods. The study included 60 patients (ankylosing spondylitis, rheumatoid arthritis, systemic sclerosis, gout, psoriatic arthritis) and 60 healthy age-matched controls. Sexual function of patients and controls was evaluated by the Sexual Health Inventory for Men and a detailed questionnaire. Results. The mean age of study group was 45,26 (7.8) years. In 90% of the cases sexual life changed after diagnosis: only 1.67% described their sexual life as being very satisfying, while 21.67% as being satisfying, 68.33% as not satisfying and 8.33% as absent. 40% of the patients had diminished libido, significantly lower compared to the study group (p = 0.043). Most patients presented with mild erectile dysfunction (60%), while most of the systemic sclerosis patients presented with mild to moderate erectile dysfunction. Erectile dysfunction scores were significantly lower compared to controls (0.009). 55% of the patients reported no influence of the treatment on their sexual life, 38% of the patients reported that specific treatment improved their sexual life.There was no statistical difference between SHIM scores of patients using biological therapies and other drugs. Conclusions. This work suggests that men with rheumatic conditions have a worse sexual function in comparison with healthy control. However, specific disease parameters or treatments were not linked to sexual dysfunction.

Availability of biosimilar medicines is rapidly increasing, potentially leading to a wider prescription and a support for healthcare system costs. Despite efforts of patient and physician educational initiatives there still remains a reluctance in prescribing or administering this type of products. A multi-centric survey was conducted on 336 patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) or lupus (SLE) on biologic treatment. Half of the patients stated never hearing of biosimilars and one third feared adverse events (infections, cancer). Another 20% felt insecure on drug tolerability or efficacy. However, the majority declared relying on their rheumatologist if prescribing a biosimilar. Lack of patient information should be accurately addressed by health organizations so that the choice of treatment is done knowingly.

Introduction: Ankylosing spondylitis is a chronic inflammatory disorder which primarily affects the axial skeleton, the major characteristic of the disease being the early involvement of the sacroiliac joints. The condition manifests by chronic inflammatory back pain and, as the disease progresses, patients will develop extreme impairment of spinal mobility because of spinal fusion. Case presentation: A 66-year-old man, diagnosed with HLA-B27-positive ankylosing spondylitis, permanent atrial fibrillation, ischemic cardiac disease, arterial hypertension, type 2 diabetes mellitus and stage 3A chronic kidney disease, was admitted for cervicalgia radiated to both shoulders and bilateral mechanical gonalgia. His son was also diagnosed with ankylosing spondylitis at the age of 29 years. Regarding the history of ankylosing spondylitis treatment, initially, the patient was prescribed nonsteroidal antiinflammatory drugs (NSAIDs); because of the inadequate response to NSAIDs, biological therapy with an anti-TNF agent was initiated (Infliximab). Fifteen months after the initiation of Infliximab, the patient presented with worsening symptoms; anti-Infliximab antibodies were detected, therefore he was switched to another anti-TNF agent, Adalimumab. Upon current admission, the clinical examination revealed thoracic kyphosis and marked limitation of cervical and lumbar spine mobility. Blood tests revealed mild anemia, inflammatory syndrome and azotate retention. The pelvic X-ray showed grade 3-4 bilateral sacroiliitis. The continuation of treatment with Adalimumab and Sulfasalazine was decided, with close monitoring of the patient. Conclusions: Ankylosing spondylitis is a multisystem inflammatory disorder, whose natural course includes periods of flares and remission. The peculiarity of this case consists in the early development of anti-Infliximab antibodies (secondary non-responder).

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease, with a very complex genetic component, being the most common rheumatic inflammatory disease. Family aggregation and the presence of autoantibodies in patients with RA suggest that the disease has autoimmune pathogenesis, despite the fact that the etiology is not fully known. The family members of patients with rheumatoid arthritis are at increased risk of developing RA and are potential candidates for predictive testing. Identifying relatives at risk of RA may allow targeted interventions to reduce the risk and catastrophic consequence of future disease.

Behçet’s disease is a systemic vasculitis with several well-defined organ manifestations, including various mucocutaneous features. Among them, the urinary tract involvement is rarely cited, most data focusing on bladder dysfunction due to neuroBehçet. This article presents a rare case of a young female patient with urological complaints that was diagnosed with right ureteral ulceration, later confirmed as vasculitis at the histopathological examination. Urological intervention together with adequate immunosuppression let to the healing of the ulcerative lesion. The unusual vasculitic lesion site indicates the complexity of Behçet’s disease that requires careful investigation and treatment.

Pregnancy is one of the most challenging processes the human body is exposed to: the healthy mother can carry to term a genetically different new-born, while her immune system adapts to tolerate this new status and avoids rejection. In autoimmune disorders, motherhood is even more challenging, with additional medical counselling, mother care, and foetus development checks being necessary. While the aspects of supplementary mother care and pregnancy progress tracking are associated with well-established medical procedures and protocols, counselling, be it pre- or post-conception, is still underestimated and scarcely applied. Indeed, over the past decades, medical counselling for this particular population has changed significantly, but from a healthcare’s provider point of view, more is required to ensure a smooth, controllable pregnancy evolution. One of the most frequent autoimmune diseases affecting young females during their fertile years is Systemic Lupus Erythematosus (SLE). Like other heterogenous diseases, it exposes the mother to severe, organ-threatening complications and unpredictable evolution. Both the disease and its treatment can significantly affect the mother’s willingness to engage in a potentially risky pregnancy, as well as the likeliness to carry it to term without any impairments. A good collaboration between the patient’s rheumatologist and obstetrician is therefore mandatory in order to: (a) allow the mother to make an informed decision on pursuing with the pregnancy; (b) ensure a perfect synchronization between pregnancy terms and treatment; and (c) avoid or minimize potential complications. The best approach to achieve these outcomes is pregnancy planning. Moreover, knowing one desired prerequisite for a successful pregnancy evolution in SLE mothers is a stable, inactive, quiescent disease for at least six months prior to conception, planning becomes more than a recommended procedure. One particular aspect that requires attention before conception is the treatment scheme applied before delivery as autoantibodies can influence significantly the course of pregnancy. In this view, future SLE mothers should ideally benefit from preconception counselling within their agreed care pathway. A multidisciplinary team including at least the rheumatologist and obstetrician should be employed throughout the pregnancy, to decide on the appropriate timing of conception and compatible medication with respect to disease activity, as well as to monitor organ involvement and foetus development progress.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which deposit within tissues and fix complement leading to systemic inflammation (1). Is a heterogeneous disease with a continuum of disease activity. Some patients can have predominant skin and joint involvement, whereas others can present with organ-threatening diseases such as nephritis, cardiac involvement or even neurologic manifestations. Relatives of patients with SLE appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable (2,3). The purpose of ANA (antinuclear antibody) determination is generally to screen patients suspected from generalised autoimmune diseases, that is, systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren’ s syndrome, scleroderma, polymyositis, or mixed connective tissue disease. Clinical and paraclinical studies are needed to reach a definitive diagnosis.

Background: Patients with ankylosing spondylitis (AS) are substantial users of healthcare resources due to chronic and potentially disabling disease. This study assessed the impact of adalimumab on clinical outcomes, healthcare resource utilization, and sick leave in patients with AS in five Central and Eastern Europe (CEE) countries. Methods: This was an observational study in the routine clinical setting. Patients diagnosed with AS and starting treatment with originator adalimumab were followed for 12 months by assessing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]) and physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]). Data on healthcare resource utilization and sick leave were collected prospectively and compared with historical data before adalimumab initiation, as well as between treatment responders and non-responders defined by BASDAI-50. Results: The total effectiveness population comprised 450 patients with on average long-standing AS, high disease activity, and functional impairment. At 12 months of adalimumab therapy, mean ASDAS and BASFI scores were in the range of low disease activity and normal physical function, respectively. The mean number of hospital admissions, hospital inpatient days, and healthcare provider visits were decreased by 67.9, 83.0, and 46.3%, respectively. The number and length of sick leaves were decreased by 65.6 and 81.4%, respectively. Reductions were higher in treatment responders than non-responders. Conclusion: Originator adalimumab in routine clinical practice in five CEE countries produced clinically meaningful improvements in disease activity and physical function, and it was associated with reductions in healthcare resource utilization and sick leave.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which deposit within tissues and fix complement leading to systemic inflammation (1). Is a heterogeneous disease with a continuum of disease activity. Some patients can have predominant skin and joint involvement, whereas others can present with organ-threatening diseases such as nephritis, cardiac involvement or even neurologic manifestations. Relatives of patients with SLE appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable (2,3).

B cell hyper-reactivity implied in the pathogenesis of Sjö gren’s syndrome (SS) justifies the therapy that involves B cell depletion. Ultrasound of salivary glands demonstrated alterations during disease progression. Objective. To evaluate changes in salivary gland parenchyma with ultrasound after rituximab treatment in patients’ with secondary SS (sSS). Methods. 7 patients evaluated at baseline (under treatment with rituximab) and after 6 months, underwent ultrasonography of major salivary gland (submandibular and parotid). Clinical data as dryness, pain and diseases activity evaluated with ESSDAI were registered. Salivary gland ultrasound (SGUS) was performed to asses echogenity (using a semiquantitative score from 0-4, with improvement defined as an at least 1 point decrease), size of gland and glandular borders. Results. Of 7 patients, 14% had clinically detectable bilateral parotid tumefaction at baseline. 6 patients (85.71%) showed ultrasonographic alterations at baseline. Parotid parenchyma echostructure improved in 42.85% of patients versus 14.28% in control group (p=0.05). At the submandibular glands, both submandibular glands showed changes in 28.57% of patients, while control group showed no changes. 42.85% patients showed parotid tumefaction which changed in 66.6% of patients at 6 months. Conclusion. Ultrasonography showed improvement in salivary gland echostructure in secondary Sjogren Syndrome with rituximab.

Autoimmune rheumatic disorders have a multifactorial determinism, caused by various environmental factors acting on the individual’s genetic susceptibility, destabilizing the systems which regulate the immune response. Epidemiological and genetic investigations are very important to demonstrate the contribution of genetic factors to the development of these autoimmune diseases. The contribution of genetic factors in causing autoimmune diseases has been demonstrated by familial aggregation. Moreover, it was also quantified by determining heritability, expressing the proportion of genetic factors in the etiology. It is now clear that common genes underlie multiple autoimmune disorders.

The major treatment issues in Antiphospholipid Syndrome (APS) include the the prevention of first thrombosis, the treatment of acute thromboembolic manifestations, the choice of anticoagulation, the duration of anticoagulation and secondary thrombosis prevention. Anticoagulation should individualized to the patient and clinical setting. Clasical anti vitamin K antagonists, warfarin and acenocumoral, carry some risks and disadvantages. Direct thrombin inhibitor and direct anti-Xa inhibitors are currently available and were approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation, for the treatment of deep vein thrombosis (DVT) and for the prevention of recurrent DVT and pulmonary embolism. Besides many case series reports, there are ongoing clinical trials testing their efficiency and safety in patients with APS. In this paper we reviewed the advantages, risks and disadvantages for the use of direct oral anticoagulants in this category of patients.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting 1% of the world population. It has major impact on patients through disability and associated comorbidities. Current treatment strategies have considerably improved the prognosis, but recent innovations (especially biologic drugs and the new class of so-called “JAK/STAT inhibitors”) have important safety issues and are very costly. Glucocorticoids (GCs) are highly effective in RA, and could reduce the need for expensive treatment with biologic agents. However, despite more than 65 years of clinical experience, there is a lack of studies large enough to adequately document the benefit/harm balance. The result is inappropriate treatment strategies, i.e. both under-use and over-use of GCs, and consequently suboptimal treatment of RA. Methods The GLORIA study is a pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess the safety and effectiveness of a daily dose of 5 mg prednisolone or matching placebo added to standard of care in elderly patients with RA. Eligible participants are diagnosed with RA, have inadequate disease control (disease activity score, DAS28 ≥ 2.6), and are ≥ 65 years. The primary outcome measures are the time-averaged mean value of the DAS28 and the occurrence of serious adverse events or adverse events of special interest. During the trial, change in antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost-effectiveness and cost-utility are secondary outcomes. The main challenge is the interpretation of the trial result with two primary endpoints and the pragmatic trial design that allows co-interventions. Another challenge is the definition of safety and the relative lack of power to detect differences between treatment groups. We have chosen to define safety as the number of patients experiencing at least one serious adverse event. We also specify a decision tree to guide our conclusion on the balance of benefit and harm, and our methodology to combat potential confounding caused by co-interventions. Discussion Pragmatic trials minimise impact on daily practice and maximise clinical relevance of the results, but analysis and interpretation of the results is challenging. We expect that the results of this trial are of importance for all rheumatologists who treat elderly patients with RA. Trial registration ClinicalTrials.gov, NCT02585258 . Registered on 20 October 2015.

Hyperuricemia is frequent in psoriatic arthritis (PsA) and it seems to be related to metabolic syndrome rather than extensive psoriatic skin disease. The objectives of this study were to evaluate the prevalence of hyperuricemia in PsA patients and to identify the associ-ated factors. Design: cross-sectional study, including consecutive, unselected, adult PsA patients. Data collection: demographic variables (age, gender, disease duration), clinical variables (affected joints, current moderate/severe psoriasis, nail disease, axial involvement, enthesi-tis, dactylitis), laboratory variables (acute phase reactants), treatment-related variables (non-steroidal anti-inflammatory drugs, corticosteroids, synthetic and biologic disease modifying drugs) and comorbidities. Hyperuricemia was defined as uric acid level above 6.8 mg/dl. Statistical analysis: the factors that were potentially associated with hyperuricemia were assessed by uni- and multivariate logistic regression. In all, 120 PsA patients were included in the study: 69 (57.5%) women, mean age±standard deviation 54±11.8 years, mean disease duration 7±7.4 years; 24 (20%) had moderate/severe psoriasis and 30 (25%) were taking a biologic. Around a quarter of patients had hyperuricemia (33; 27.5%). Hyperuricemia was significantly associated with obesity, diabetes, ischemic heart disease and hypertension, but there was no correlation with current skin psoriasis. In the multivariate analysis, it was best explained by diabetes (odds ratio: 4.95, [95% confidence intervals: 1.47; 16.67]), ischemic heart disease (3.61 [1.00; 12.98]) and obesity (1.86 [1.04; 3.32]). Hyperuricemia in PsA is associated with metabolic syndrome rather than skin dis-ease, but further longitudinal studies are needed to identify causal relationships.

Lupus nephritis is one of the most important organ involvement in patients diagnosed with Systemic Lupus Erythematosus (SLE). It requires aggressive and prolonged immunosuppression in order to induce and maintain remission. There is always a risk of adverse events. It is presented the case of a young woman diagnosed with SLE and active lupus nephritis with acute renal failure, who developed persistent hyponatremia after immunosuppression with Cyclophosphamide was started. The case emphases both the need for synthetic immunosuppression as well as the adverse events that may occur during treatment. Close monitoring of the clinical and biological parameters during immunosuppressive therapy is essential as even one minimally modified parameter may prove important in the evolution of the case. Measures to prevent one side effect do not prevent the developing of other.

Introduction. Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) represent a group of conditions evolving with necrotizing inflammation in small and medium-sized blood vessels. AAV are composed of GPA (granulomatosis with polyangiitis, former Wegener’s granulomatosis), MPA (microscopic polyangiitis) and EGPA (eosinophilic granulomatosis with polyangiitis, former Churg-Strauss syndrome). AAV receive immunosuppressive therapy associated with a high risk of complications. Objective. The aim of this study was to characterize a single center cohort of AAV patients regarding clinical, biological and therapeutic features. Method. We realized a cross-sectional study by consequently enrolling all the patients registered with AAV diagnosis between 2009 and 2017 in Department of Rheumatology of “Sfânta Maria” Hospital. Demographic, diseaserelated and therapeutic-related parameters were collected. The data was extracted from the clinical files. Results. The study sample included 26 cases, 15 females and 11 males: 20 patients GPA, 4 MPA and 2 cases EGPA. Mean age at the time of diagnosis was around 48 but 12 patients presented delays between age at the onset and age at the time of diagnosis (the mean delay was 2 years). The most frequent clinical manifestation identified where pulmonary, musculoskeletal and renal. 15 patients had a diagnostic biopsy performed. ANCA detection revealed 16 cases of c-ANCA and 7 cases of p-ANCA and 11 patients presented other positive serology. A combination of glucocorticoids and cyclophosphamide was used in most of the cases for remission-induction treatment and the same scheme was used for relapse cases. For maintenance phase a combination of glucocorticoids and azathioprine was preferred. 13 patients (50%) developed treatment related complications. Conclusion. Most of the patients were diagnosed with GPA (20) and the least were diagnosed with EGPA (2). Biopsy was performed in 15 cases and it was mostly nasal. For remission-induction prevailed the combination of glucocorticoids and cyclophosphamide. Most treatment related complications were due to glucocorticoids administration. Osteoporosis was predominant.

Familial Mediterranean Fever (FMF) is the most common condition in the group of autoinflammatory diseases. It has a relatively heterogeneous clinical display included in the Tel-Hashomer diagnostic criteria that can be further confirmed by genetic testing showing a mutation in the MEFV gene. AA Amyloidosis is the most sever complication in these patients. Colchicine is the standard treatment and/or alternative biological agents if necessary. This article aims to describe the evolution of a patient with FMF, firstly diagnosed as reactive arthritis, his clinical manifestations and therapeutic options.

Objectives. The objectives of this study were to evaluate the prevalence of disease severity in PsA and to assess the factors that might explain it. Methods. This was a cross-sectional study of unselected PsA patients. Severity was defined according to GRAPPA criteria of severity. Factors potentially associated with severity (demographical, clinical, laboratory variables, treatment related factors and comorbidities) were assessed by uni- and multivariate logistic regressions. Results. A total of 129 PsA patients were analysed: 77 (59.7%) women, mean±standard deviation age 53.5±11.8 years, and mean disease duration 7±7.4 years. Twenty-for patients (18.6%) had severe PsA. In the univariate regression, disease severity was associated with psoriasis duration, PsA duration, current moderate/severe skin disease, nail disease, history of corticotherapy, and total number of previous synthetic and biologic DMARDs. In the multivariate analysis, PsA severity was explained by the presence of current moderate/severe psoriasis – odds ratio 5.88 (95% confidence interval 1.39; 25.00) and history of corticosteroids – 4.65 (1.13; 18.87). Conclusion. PsA severity is best explained by the presence of moderate or severe psoriasis and past treatment with corticosteroids, but further longitudinal studies are needed to identify predictive factors.

Background. Sjögren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs. Ultrasonography (US) demonstrates specificity and sensibility in major salivary glands (SG) evaluation. Recent data confirm US might be used as primary evaluation technique for its ability to show structural alterations of parenchyma (1). Objective. To assess the gray scale (GS) parenchymal inhomogeneity of major SG in patients with established primary and secondary SS and correlate with clinical and biological data. Methods. Consecutive patients with SS were recruited and SG US was performed. Inhomogeneity of glandular parenchyma was quantified binary on each gland. ESSDAI and ESSPRI scores were calculated. Statistics was performed with SPSS. Results. Twenty one (42.85% primary SS, 90.47% female) consecutive patients were included. Mean age was 53.66+/-12.99 years and disease duration 5.33+/-3.74 years. Antibody SSA/SSB presence was found in 85.7% (18/21). ESSDAI mean was 8.67+/-8.9 (0-29), ESSPRI 10.13+/-5.59(0-20). There were no differences regarding ESSDAI and ESSPRI in the two groups (primary and secondary SS). Right parotid gland showed alterations in 71.4% patients (77% with primary SS, 66% with secondary SS). Frequently inhomogeneity was found in all major SG (33%, 22% left and right submandibular, 77%, 44.4% left and right parotid glands) in primary SS. Both submandibular glands were symmetrically involved (p

Both non-radiographic spondyloarthritis (nr-SpA) and ankylosing spondylitis (AS) are medical conditions that belong to the axial spondyloarthritis spectrum; these two terms reveal the extent of sacroiliitis assessed by conventional x-ray or MRI. According to the latest classification criteria (ASAS, 2009), clinicians are able to differentiate patients with nr-SpA from AS and to follow their disease progression. The present study aims to compare the two patient categories undergoing biological therapy with an anti-TNF agent and indicate distinct disease features. We included 94 patients in treatment with IFX, ADL, ETA or GOL and monitored clinical, biological and disease activity parameters. The nr-SpA subgroup included a higher percentage of female patients; AS patients presented higher values of the CRP at follow-up visits; there were no significant differences between the two groups regarding the HLA-B27 presence, uveitis history or smoking status. Patients with an inactive disease status had a lower BMI, shorter disease duration and an early initiation of biological therapy, so that we suggest a close and regular monitoring of these two entities.

Objective. The purpose of the present study was to assess the relevance of therapeutic drug monitoring in spondyloarthritis patients, by determining drug serum levels and anti-drug antibodies and estimating cut-off values for three TNF inhibitors. Methods. Over one year, we enrolled 100 patients with SpA, under consequent treatment with adalimumab (ADL), etanercept (ETA) or infliximab (IFX). Demographic, clinical (BASDAI, ASDAS) and laboratory (ESR, CRP) data was collected together with drug serum level and anti-drug antibodies using the ELISA technique. The statistical analysis was performed using the SPSS software, version 20.0 with the aid of Student t-test, Spearman and Pearson tests. Results. Out of the study cohort, 35% were on ADL, 33% on IFX, and 32% under ETA treatment. Undetectable drug levels correlated to the presence of anti-drug antibodies and to disease activity scores. There were no identified anti-ETA antibodies. For this study lot trough levels are estimated between 2 and 4 μg/mL for an ASDAS-CRP under 2.1. Conclusion. Serum drug level measurement and anti-drug antibody detection can be used as a completion to a clinician’s tools in assessing disease activity, leading to an optimal and personalized manner of patient management.

Spondyloarthritis (SpA) patients do not respond uniformly to TNF inhibitor therapy, some of them losing their beneficial evolution and becoming primary or secondary non-responders. Hence, questions have been raised whether this situation is linked to predictive genetic factors, individual characteristics or to disease activity. Studies have incriminated immunogenicity as being responsible for the loss or lack of response. It appears that the development of anti-drug antibodies leads to a decrease in drug levels with further impact on patients’ clinical state. This brief review aims to clarify some of the processes involved in the immunogenic phenomenon for patients with SpA, based on the current published literature.

Background/Objective. Disease activity in spondyloarthritis (SpA) is evaluated through conventional scores such as BASDAI or ASDAS. The aim of this study was to determine disease activity in SpA patients under biological therapy with further assessment on the quality of each activity indicator and their clinical value together with their impact on NSAID intake. Materials and methods. Over nine months (January–August 2015) we enrolled 100 patients with SpA on anti-TNF therapy (33% IFX; 35% ADL; 32% ETA). We collected demographic, clinical (BASDAI, ASDAS, PtGA) and laboratory data (ESR, CRP). Frequency of NSAID ingestion expressed as days per week was included in a questionnaire. Considering their biologic treatment, patients were divided into disease activity groups and sample characteristics were correlated and compared. Statistical analysis was performed with SPSS 20.0, using specific tests such as Pearson, Spearman or ANOVA. Results. Patients with active disease, stated by both activity scores had an increased NSAID intake. Out of 86% of patients with a BASDAI under 4, only 82.6% had an ASDAS-CRP lower than 1.3. BASDAI correlated to both ASDAS scores (r = 0.65 and 0.71, P

Sjögren syndrome (SS) is a chronic autoimmune condition that mainly targets exocrine glands where it produces lymphocytic infiltrates. The clinical display varies in severity and can include malignancy association such as non-Hodgkin lymphoma. Its incidence ranges from 5 to 8%, while the risk of occurrence is 16 to 44 times higher. This article aims to describe the evolution of a patient with primary SS who developed pulmonary lymphoma for which she received Rituximab as part of the oncological therapeutic scheme. During the course of the disease she developed membranous glomerulonephritis, rarely described in these patients and low complement levels cited as predictive factor for lymphoproliferation.

Background/Objectives: Psoriasis is a chronic inflammatory condition mediated by the immune system with various manifestations. The increased prevalence of subclinical joint involvement has led to the development of early diagnostic methods for psoriatic arthritis, including several instruments that have been validated and used in clinical practice. The aim of this study was to perform the Romanian translation, cultural adaptation, and validation of three assessment tools: the Early Arthritis for Psoriatic Patients (EARP) Questionnaire, Psoriasis Epidemiology Screening Tool (PEST), and Toronto Psoriatic Arthritis Screen 2 (TOPAS 2), which are designed to evaluate early-stage arthritis in patients with psoriasis. Methods: All the activities were carried out in accordance with the internationally recognized methodology recommended by the International Society for Pharmacoeconomics and Outcome Research (ISPOR), the recommendations of the World Health Organization (WHO) regarding the translation process and the validation of instruments, and data from the international literature. These three questionnaires were administered to 29 patients with psoriasis diagnosed by biopsy. A descriptive study was conducted and the data were analyzed with appropriate statistical tests using the PSPP program. A reliability test was assessed using Cronbach’s alpha coefficient. Results: The obtained values were significant for the first two questionnaires, with a value of 0.89 for the EARP and 0.63 for the PEST, but the value was not as significant for ToPAS2, at 0.40. Conclusions: This pilot study revealed that the Romanian and original versions of the three questionnaires are similar.