The Levels of Serum Serotonin Can Be Related to Skin and Pulmonary Manifestations of Systemic Sclerosis.

Background and Objective: The most prominent feature of systemic sclerosis (SSc), besides vasculopathy and autoimmune disorders, is excessive fibrosis. Serotonin affects hemostasis and can induce vasoconstriction, which is presumed to be one of the pathophysiological patterns in SSc that leads to fibrosis. Our aim was to explore the possible association of serotonin with some of the clinical features of SSc in our cohort of patients. Materials and Methods: We measured serotonin levels in sera of 29 female SSc patients. Patients were 41-79 years old, their average disease duration was 9 years. Serotonin values were analyzed in correlation with clinical and laboratory parameters, such as modified Rodnan skin score (mRSS), digital ulcers (DU), and spirometry parameters-forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and lung diffusion capacity of carbon monoxide (DLCO). Statistical analyses were performed using statistical software Statistica. Results: We found correlation of serotonin level with mRSS (r = 0.388, p = 0.038). The highest values of serotonin were documented in patients with refractory DU, but this was not statistically significant. We also found a negative correlation between serotonin and FVC (r = -0.397), although it did not reach the level of significance (p = 0.114). Conclusions: Our study suggests that levels of serum serotonin could affect the course of skin fibrosis and partially restrictive pulmonary dysfunction in patients with SSc. We assume that serotonin might have influence on several features of SSc, but more studies are needed to reveal those relations.

[Polymyositis and systemic sclerosis overlap - A case report and a review of the literature].

Polymyositis (PM) is an autoimmune disease which affects skeletal muscles. In young age, it usually occurs as an idiopathic disorder associated with specific autoantibodies (anti-Jo), while in older age it is often associated with neoplasms. It can present with symptoms of other autoimmune diseases, such as systemic sclerosis (SSc), a rare progressive disease characterized by collagen deposits in various tissues and organs. A 65-year-old patient, long-time smoker, came to the ER because of painful edema in the distal parts of his limbs and proximal muscle weakness of his arms and legs. Although his muscle enzymes were not increased, PM was confirmed by the characteristic pathohistological finding. The patient had sclerodermal skin lesions on his back, but he did not have other typical SSc symptoms, and the specific autoantibodies were negative. He received glucocorticoid therapy (GC) after we had finished screening for malignant tumors. He felt better, his muscle strength returned, and the limb edema disappeared. Four weeks later, he developed symptoms which are more typical of SSc, such as dysphagia, Raynaud's phenomenon, and skin thickening of the limbs that had been swollen. PM is often associated with SSc. It is not clear if the exacerbation of latent SSc was stimulated by GC, or if it was just a simple overlap of the two diseases with different onsets. There are no therapy guidelines for the treatment of this combination of diseases. Careful use of GC is necessary even if SSc symptoms are discreet, because of the well-known effects of GC in SSc.

[Vasculitides--introduction]. / Sindrom vaskulitisa--uvod.

Vasculitis is clinicopathologic process characterized by inflammation and damage of blood vessels, often resulting in complete or partial occlusion of the involved vessels and ischemic damage to the supplied organ or tissue. The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. It may be a primary or secondary manifestation of a disease process and may affect single or multiple organs. Inflammation affects vessel's walls partly or completely resulting with the loss of vascular integrity. Vasculitides has been classified by whether inflammation predominantly damage small, medium, or large vessels.

[Clinical approach to a patient with rheumatoid arthritis]. / Klinicki pristup bolesniku s reumatoidnim artritisom.

Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practi- tioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease.

[Sex hormones, immune disorders, and inflammatory rheumatic diseases]. / Spolni hormoni, imunoloski poremecaji i upalne reumatske bolesti.

It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.

Relationship between interleukin-6 and cardiac involvement in systemic sclerosis.

OBJECTIVES: To explore the relationship between IL-6 levels and echocardiographic abnormalities, and N-terminal probrain natriuretic peptide (NT-proBNP) levels in SSc patients and to correlate tested parameters with European Scleroderma Activity (EUSTAR) score. METHODS: This case-control study included 31 SSc patients with preserved left ventricular ejection fraction (LVEF) and 32 matched healthy controls. Serum IL-6 and NT-proBNP levels were measured and subjects were evaluated by conventional and pulsed-wave tissue Doppler echocardiography. RESULTS: The level of IL-6 was significantly increased in patients with SSc (3.2 vs 2.2 pg/ml, P < 0.001). SSc patients had significantly lower values of LV systolic (7.7 vs 9.25 cm/s, P < 0.001) and early diastolic (8.7 vs 10.3 cm/s, P = 0.014) myocardial velocities and higher E/e' (9.04 vs 7.37, P = 0.001) ratio, although there was no between-group difference according to LVEF (68% vs 65%, P = 0.248). On evaluating the right ventricle there was no significant between-group difference in systolic tricuspid annular velocity (13 vs 13.9 cm/s, P = 0.105), but the peak early diastolic velocity was significantly lower (11.7 vs 13.6, P = 0.044) and E/e' was significantly higher (4.3 vs 3.38, P = 0.008) in SSc patients. IL-6 level showed correlation with LV mean e' (r = -0.57, P = 0.001), E/e' (r = 0.55, P = 0.001) and NT-proBNP (r = 0.52, P = 0.003). EUSTAR score correlated with LV E/e' (r = 0.48, P = 0.006), mean e' (r = -0.67, P < 0.001), mean s' (r = -0.51, P = 0.004), NT-proBNP (r = 0.60, P < 0.001) and IL-6 (r = 0.79, P < 0.001). CONCLUSION: IL-6 level is increased in patients with SSc and significantly correlates with LV diastolic dysfunction, NT-proBNP and EUSTAR score. These results support the role of IL-6 in the development of cardiac disease in SSc patients.

[Paraneoplastic hypertrophic osteoarthropathy]. / Paraneoplasticna hipertroficna osteoartropatija.

Hypertrophic osteoarthropathy is a syndrome presenting with dclubbing, limbs enlargement, pain and swelling of foot and long bones osteitis. Hypertrophic osteoarthropathy is a rare paraneoplastic syndrome in the patients with primary or metastatic lung cancer. We report 39-year old female patient who presented with arthritis and paraneoplastic hypertrophic osteoarthropathy revealing lung adenocarcinoma.

[The existence of geographical clusters of rheumatiod arhritis according to their origin in a tertiary care based register]. / Postojanje zemljopisnih klastera reumatoidnog artritisa na osnovu podrijetla prema podacima tercijarnog centra.

The objective was to analyse epidemiological tendencies of rheumatoid arthritis (RA) in Dalmatia County in order to identify possible spatial clusters of RA. Patient-interviewers were trained to administer telephone surveys. 197 RA patients controlled at Rheumatology and immunology department of Clinical hospital of Split were mapped to place of residence by telephone survey. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Four clusters were identified; the largest one was in the region of Sinj. The female/male ratio was 5.79:1. Majority of RA patients were among age 50 to 59 (30.45 %). The results show inter-regional variations with the marked clusters in the north of Dalmatia suggesting that clusters with higher incidence of RA have specific genetic and environmental background. Prevalence of RA in female was higher than in current literature, while the age of onset 50-59 years is similar with data from recent studies.

Left Atrial Myxoma and Antiphospholipid Syndrome-A Case Report.

Cardiac myxoma (CM) is the most frequent type of primary cardiac neoplasm and is responsible for 58 to 80% of primary cardiac tumors. The antiphospholipid syndrome (APS) occurs most commonly in the systemic lupus erythematosus but it can be also found in other conditions. The coexistence of CM and APS is rarely described in the literature. We report an unusual case of the left atrial myxoma and concomitant APS in a female patient who presented with right-sided hemiplegia. Although rare, we must think about the CM in patients with a newly diagnosed APS and left atrial mass. Nevertheless, we must make a distinction from other possible cardiac structures, especially atrial thrombus. Transthoracic echocardiography is the most frequently used initial imaging modality to detect CM. The aim of this case report was to emphasize that additional imaging modalities and multidisciplinary approach are mandatory in making a proper diagnosis and to choose a further treatment strategy.

The Croatian Primary Sjögren's Disease Oral Health Study: Oral Status and Oral Health-Related Quality of Life.

To determine salivary flow rate, oral and periodontal status, oral health-related quality of life (OHRQoL), objective and subjective indexes, and serum antibody reactivity in patients with primary Sjögren's disease (pSD). Thirty-one patients with pSD and 31 control subjects participated in this cross-sectional, single-center study. The unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (DMFT = D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, OHRQoL, objective European League Against Rheumatism (EULAR) SS Disease Activity Index (ESSDAI) and subjective (EULAR SS Patient Reported Index (ESSPRI), 6-items-VAS-SS (Visual Analog Scale), Profile of Fatigue) indexes were analyzed. The patients with pSD had a blood sample taken in the morning between 7 and 10 a.m. for comprehensive laboratory analysis. Patients with pSD had statistically significant lower UWSFR (0.20 vs. 0.90 mL/min) and SWSFR (0.56 vs. 1.64 mL/min) values compared with control subjects (p < 0.001, Mann-Withney U test). Salivary pH value of pSD patients was significantly lower compared with control subjects (6.00 vs. 7.00; p < 0.001, Mann-Whitney U test). The mean DMFT index of patients with pSD compared to control subjects was not statistically significant (23.74 ± 7.28 vs. 20.77 ± 5.73; p = 0.08, t-test). Interincisal distance was significantly decreased in the pSD group compared with control subjects (43.80 ± 0.38 vs. 47.60 ± 0.50; p = 0.003, t-test). The prevalence of periodontitis was similar in patients with pSD and control subjects (83.9% vs. 77.4%; p = 0.35, λ2 test). The mean Oral Health Impact Profile (OHIP-49) total score was statistically significantly higher in pSD patients compared with control subjects (32.00 vs. 8.00; p < 0.001, Mann-Whitney U test). Patients with pSD have decreased salivary flow and salivary pH, poor oral health, decreased interincisal distance, high prevalence of periodontitis, and worse OHRQoL. These findings highlight the need for a multidisciplinary approach to the management of patients with pSD that includes physical and psychological aspects of the disease.

Salivary Flow Rate and Oral Status in Patients with Primary Sjögren's Syndrome and Diffuse Cutaneous Systemic Sclerosis: A Cross-Sectional Study.

Determination of salivary flow rate and oral status in patients with primary Sjögren's Syndrome (pSS) and diffuse cutaneous systemic sclerosis (dcSSc) and comparison with control subjects. Thirty-one pSS patients, 28 dcSSc patients, and 28 control subjects participated in this single-center, cross-sectional study. Unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, and OHRQoL (oral health-related quality of life) were analyzed in all three groups of subjects. Primary SS and dcSSc patients had statistically significant lower values of UWSFR (0.20; 0.38 vs. 0.91 mL/min) and SWSFR (0.56; 0.70 vs. 1.64 mL/min) compared with control subjects (p < 0.001, Kruskal-Wallis test). Salivary pH values were statistically significantly lower in pSS and dcSSc patients compared with control subjects (6.00; 6.25 vs. 7.00, respectively) (p < 0.001, Kruskal-Wallis test). The DMFT index of dcSSc patients was higher (28.50) and statistically significant compared to control subjects (20.00) (p = 0.01). The prevalence of periodontitis was the same in pSS and dcSSc patients and control subjects (p = 0.384). Primary SS and dcSSc patients had a statistically significant decreased interincisal distance compared to control subjects (43.80; 38.00 vs. 48.00) (p = 0.003 and p < 0.001, respectively). Primary SS and dcSSc patients show decreased UWSFR and SWSFR, salivary pH values closer to an acidic medium, higher DMFT index, higher prevalence of periodontitis, decreased interincisal distance, and poorer OHRQoL, i.e., poor oral and periodontal health.

Real world experience with nintedanib in connective tissue disease-related interstitial lung disease: a retrospective cohort study.

Various connective tissue diseases tend to affect specific organs, lungs being the organ with the most serious repercussions and consequences. The diagnosis of interstitial lung disease makes the treatment more difficult and worsens long-term prognosis and overall survival. Positive results from the registration studies of nintedanib led to approval of the drug for the treatment of idiopathic pulmonary fibrosis and chronic fibrosing interstitial lung diseases in connective tissue diseases. After registration, real-world data on the use of nintedanib are being collected in everyday clinical practise. The objective of the study was to collect and analyse real world experience gathered after the registration of nintedanib for the treatment of CTD-ILD and to show if the positive results collected from a homogeneous and "representative" study population can be applied to everyday clinical practice. We are presenting a retrospective observational case-series study of patients treated with nintedanib from the three largest Croatian centers specialised in the treatment of connective tissue diseases with interstitial lung diseases. Stabilisation or improved of lung function tests was reported in 68% of patients when changes in predicted FVC were observed and in 72% of patients when changes in DLco were analysed. Almost all of the reported patients (98%) were treated with nintedanib as an add-on drug to immunosuppressants. The most common side-effects were gastrointestinal symptoms and abnormal liver function tests in less extent. Our real-world data confirm the tolerability, efficacy and similar side-effects of nintedanib as reported in pivotal trials. Key Points • Interstitial lung disease is a common manifestation of several connective tissue diseases and its progressive fibrosing phenotype contributes to high mortality rate and many unmet needs regarding the treatment remain. • Registration studies of nintedanib obtained sufficient data and positive results to support approval of the drug. • Real-world evidence from our CTD-ILD centres confirm the clinical trial data regarding efficacy, tolerability and safety of nintedanib.

Prescription Trends of Biologic DMARDs in Treating Rheumatologic Diseases: Changes of Medication Availability in COVID-19.

Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.

[Treatment of systemic lupus erythematosus]. / Lijeccenje sistemskog eritemskog lupusa.

Treatinent of systemic lupus erythematosus is very difficult because of heterogeneous clinical manifestations. Standard therapy includes non-steroidal anti-inflammatory drugs, glucocorticoids, anitimalarials and cytotoxic agents. A numerous biological agents have been investigated for treatment of the systemic lupus erythematosus. They are directed to B and T cell depletion, blockade of co-stimulatory molecules, inhibition of cytokines and complement modulation. Sirolimus, tacrolimus, autologous hematopoietic stem cell transplantation and allogenic mesenchymal stem cells transplantation have been also investigated for treatment of systemic lupus erythematosus.

[Polymyositis, dematomyositis: overlap syndromes with connective tissue diseases and malignancies]. / Polimiozitis, dermatomiozitis: sindromi preklapanja s autoimunim i malignim bolestima.

Polymyositis and Dermatomyositis are often connected with autoimmune diseases and are closely linked with specific autoantibodies. Clinical manifestations are mild in correlation with clinical picture ofmyositis related to malignancy. Pulmonary complications are main cause of mortality in overlap syndromes with autoimmune diseases. Infection, cardiovascular complications and underlying malignancy provide greater mortality risk.

Serum Adropin Levels in Patients with Rheumatoid Arthritis.

Adropin is a secretory protein that mainly modulates metabolic homeostasis and endothelial function. There is growing evidence supporting association of adropin with various inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to compare serum adropin levels between 70 patients with RA and 70 matched healthy controls. Furthermore, we explored adropin correlations with RA disease activity, glucose metabolism parameters and inflammatory biomarkers. Serum adropin levels were determined by a competitive enzyme-linked immunosorbent assay. Serum adropin levels were significantly lower in RA patients than in the control group (2.85 ± 0.91 vs. 4.02 ± 0.99 ng/mL, p < 0.001). In the RA group, serum adropin levels had a significant negative correlation with total cholesterol (r = -0.172, p = 0.043), HbA1c (r = -0.406, p < 0.001), fasting glucose (r = -0.377, p < 0.001) and HOMA-IR (the homeostasis model assessment-estimated insulin resistance; (r = -0.315, p = 0.008)). Multiple linear regression analysis showed that serum adropin levels retained a significant association with levels of fasting glucose (ß ± SE, -0.450 ± 0.140, p = 0.002) and HbA1c (-0.528 ± 0.223, p = 0.021) after model adjustments. These findings imply that adropin could have an impact on metabolic homeostasis in RA, although further well-designed studies are warranted in order to establish this.

Serum catestatin levels in patients with rheumatoid arthritis.

Catestatin (CST) is an important peptide that influences various inflammatory diseases. Our goal was to investigate CST concentrations in patients with RA compared to healthy subjects. This cross-sectional observational study included 80 patients with RA and 80 healthy control subjects. Demographic characteristics and laboratory parameters were recorded. Serum CST levels were determined by an enzyme-linked immunosorbent assay (ELISA). Serum CST levels were significantly higher in RA patients than in the control group (10.53 ± 3.90 vs 5.24 ± 2.37 ng/mL, p < 0.001). In RA patients, there was a statistically significant correlation between CST and patient age (r = 0.418, p < 0.001) and both DAS28 (r = 0.469, p < 0.001) and HAQ scores (r = 0.483, p < 0.001). There was a statistically significant correlation between serum CST levels and RA duration (r = 0.583, p < 0.001). Multiple linear regression analysis showed that serum CST levels retained a significant association with RA duration (ß ± SE, 0.13 ± 0.04, p = 0.002) and DAS28 score (0.94 ± 0.45, p = 0.039) after model adjustment for age, body mass index (BMI) and HAQ score, with serum CST levels as a dependent variable. These findings imply that CST is possibly associated with RA complex pathophysiology and disease activity. However, future larger multicentric longitudinal studies are necessary to define the role of CST in RA.

Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in southern Croatia.

OBJECTIVE: The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity. METHODS: A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C­reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index. RESULTS: The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC. CONCLUSION: The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR.

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study).

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.