Signs Of Interstitial Lung Disease Research Articles

The Value of Ultrasound for Detecting and Following Subclinical Interstitial Lung Disease in Systemic Sclerosis.

Interstitial lung disease (ILD) is a complication in patients with systemic sclerosis (SSc). Accurate strategies to identify its presence in early phases are essential. We conducted the study aiming to determine the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to ascertain its potential in determining the disease progression. 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), auscultation, chest radiographs, and respiratory function tests (RFT) were performed. A rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. The patients were followed every 12 weeks for 48 weeks. A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p = 0.0001). Anti-centromere antibodies (p = 0.005) and RSS (p = 0.004) showed an association with ILD. A positive correlation was demonstrated between the US and HRCT findings (p = 0.001). The sensitivity and specificity of US in detecting ILD were 91.2% and 88.6%, respectively. In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. US showed a high prevalence of subclinical ILD in SSc patients. It proved to be a valid, reliable, and feasible tool to detect ILD in SSc and to monitor disease progression.

Interstitial lung disease in patients with systemic scleroderma: approaches to predicting lesion volume

Aim. To determine the factors that contribute to the prediction of the volume of pulmonary lesion in patients with systemic scleroderma (SSc).Materials and methods. The analysis included patients with SSc observed in the Registry of Myositis, systemic sclerosis and mixed connective tissue disease (REMISSIS), who underwent high-resolution computed tomography (HRCT) of the lungs. For the immunological characteristic, all patients were tested for anti-topoisomerase (anti-Scl-70), and anti-centromeric (anti-CENP-B) antibodies, and anticentromere antibodies (anti-Pm-Scl).Results. The study included 79 patients with SSc. There was 94.9 % women. Average age – 64.4 ± 11.5 years. Signs of interstitial lung disease (ILD), according to HRCT were detected in 50 patients. The largest extent of lung injury was noted in patients with SSc sine scleroderma (32.7 ± 29.3 %), a smaller extent in patients with diffuse form SSc (16.9 ± 17.1 %) and the lowest in patients with limited SSc (8.5 ± 14.2 %). In addition to the type of disease, the extent of lung injury in patients with SSc-ILD was statistically significantly higher in patients with arthralgia, dyspnea and the presence of antibodies to topoisomerase I and combined autoantibodies. Also, a statistically significant feedback was established with all indicators of the test with a 6-minute walk and forced vital capacity and a direct relationship with indicators of pulmonary artery systolic pressure. When evaluating the correlation between the extent of lung injury and the degree of dyspnea according to Borg, it was found that in patients who assessed dyspnea less than 3 points, the extent of lung injury was less than 25 %. Due to the high degree of correlation, a regression formula was created for the dependence of the extent of lung injury on the distance in the test with a 6-minute walk: extent of lung injury = (52.7–0.1) × distance 6MWT. A multivariate model was also obtained for predicting the extent of lung injury in SSc, in which the patient’s immunotype, distance in the 6-minute walk test, saturation after the 6-minute walk test, and the presence of dyspnea became the most effective.

Abstract B128: Preclinical characterization of ETx-22, a next-generation antibody drug conjugate (ADC) targeting nectin-4

Abstract Nectin-4 is overexpressed in a variety of cancers including urothelial, breast, cervix, lung and ovarian, with low level of expression in normal tissues. Enfortumab vedotin (EV), an anti-Nectin-4 ADC with a monomethyl auristatin (MMAE) payload, has been a significant advancement in the treatment of urothelial cancer. Yet, it is associated with important skin toxicity owing to the expression of nectin-4 in the skin, and peripheral neuropathy secondary to its toxin. We have developed a next-generation anti-nectin-4 ADC, ETx-22, which consists of a humanized IgG1, Fcg-silent antibody that is bound via maleimide-ß-glucuronide poly-sarcosine linkers to 8 molecules of the topoisomerase-I inhibitor, exatecan. Here, we describe the key pharmacological experiments, in-vivo efficacy and results from the good laboratory practice (GLP) toxicology studies. In-vitro studies have shown that the ETx-22 antibody exhibits a high affinity for tumor-expressed Nectin-4, but 10-fold lower affinity for nectin-4 expressed on skin, with significantly higher internalization in tumor cells. In-vivo efficacy was evaluated in various patient-derived xenograft models. ETx-22 was shown to be consistently superior to EV as well as chemotherapy, in a broad array of tumors, including urothelial, ovarian, cervical and triple negative breast cancer irrespective of the degree of nectin-4 expression. Antitumor activity was also observed in MMAE-resistant models. GLP studies evaluated repeated doses of ETx-22 in cynomolgus monkeys at two doses, 10 and 20 mg/kg. The treatment was administered as 30-minute intravenous infusions once every 2 weeks for a total of three cycles. The ETx-22 antibody alone was also evaluated at 20 mg/kg. Both ETx-22 doses were well tolerated and all animals survived up to scheduled euthanasia. The common observation at both doses was mild multifocal skin hyperpigmentation, which was reversible. No skin rash or pruritus was reported. Mild transient decrease in red blood cells was observed in between cycles. No gastrointestinal toxicities were observed. No signs of interstitial lung disease or eye toxicity were detected. Based on these findings, the highly non- severely toxic dose (HNSTD) is at least 20 mg/kg. The half-life of ETx-22 ranged from 3.36 – 3.6 days. In conclusion, preclinical and pharmacological shows that ETx-22 has better tolerance, longer half-life, and higher efficacy to EV. No skin rash was reported in toxicology studies. A first in human study (EXCEED) is planned to start in 2023. Citation Format: Hatem Azim, Florence Lhospice, Xavier Preville, Joanna Fares, Marc Lopez, Emerence Crompot, Emmanuelle Josselin, Remy Castellano, Maria Wehbeh, Yves Collette, Jack Elands, Daniel Olive. Preclinical characterization of ETx-22, a next-generation antibody drug conjugate (ADC) targeting nectin-4 [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B128.

The use of “Acellbia” – a biosimilar of rituximab in systemic sclerosis

Introduction. The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a diseasemodifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B cell therapy, in particular rituximab (RTX). Until now RTX do not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological preparations have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The “biosimilar” versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis).The aim of this study was to investigate the efficacy and safety of Acellbia in patients with systemic sclerosis.Material and methods. Our prospective uncontrolled study included 20 patients (14 women) aged 50±14 years, with a disease duration of 3.5±2.7 years. Indications for the prescribing of ACB were high disease activity and the presence of risk factors for progression. All patients had radiological signs of interstitial lung disease, 13 (65%) were positive for antibodies to topoisomerase 1. None of the patients had previously been treated with biological therapy. All patients received glucocorticoids in low doses and 15 (75%) patients were not on concomitant immunosuppressants during the study. ACB was administered in doses of 2 g (two doses of 1 g with a weekly interval) at inclusion of the study and after 6–8 months according to the same scheme, cumulative dose – 4 g. An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7.2±1.7 mo, Point 1) and at the end of follow-up (13.4±1.6 mo, Point 2). The results are presented in the form of mean values and standard deviations.Results. There was a positive effect on the main manifestations of the disease, which accompanied by stable depletion of CD19+ B lymphocytes in the peripheral blood. At the intermediate assessment (between points 0–1), no significant changes were observed, with the exception of the skin score. At the end of the study, most of the parameters showed a significant improvement between points 0–2. The activity of the disease (EScSG-AI) decreased, and the skin score decreased from 12.8±11 to 6.2±5.6 (p=0.002). The forced vital capacity (% of predicted) increased from 89±18.2 to 98.26±16.13% (p=0.0002), and the diffusion capacity of the lungs (% of predicted) increased from 56.8±15.7 to 61.9±17.2% (p<0.019). A significant decrease in CRP, antitopoisomerase-1 antibodies, as well as IgG (from 12.6±2.6 to 10.2±2.2 g/l) was noted. Repopulation to normal level of B lymphocytes did not occur in any case, and complete depletion of B lymphocytes at the end of the study was maintained in 83% of patients (15 of 18). The quality of life questionnaire SHAQ improved (p=0.0001), and the average dose of prednisolone was reduced from 11.0±2.7 to 9.4±2.3 mg/day (p=0.03). Positive changes according to HRCT was evident in 9 (45%) patients due to a decrease in ground glass opacity. The frequency and spectrum of adverse events (AEs) corresponded to those already known for RTX. Of the 20 patients who received 2 courses of ACB, two withdrew from the evaluation at Point 2 due to pregnancy (1) and lung cancer (1). A total of 11 (55%) AEs were reported in 9 (45%) patients, most of them were classified as mild. Infectious complications developed in 7 (35%) patients: respiratory infections of the upper respiratory tract (4), positivity in the TB skin test (2), otitis (1), cystitis (1) and cholecystitis (1). One patient developed calf vein thrombosis and lung cancer was diagnosed in one case.Conclusion. Our data suggest that Acellbia could be used for the treatment of SSc. A short-term, prospective, uncontrolled study showed good efficacy and acceptable safety of the ACB biosimilar in SSc. A significant decrease of skin fibrosis and improvement of lung functions have been proven. The clinical effect of ACB manifested by the 6th month from the start of therapy and reached its maximum one year after its initiation. Due to the positive efficacy of ACB, it can be prescribed for the patients with SSc with ineffectiveness and/or intolerance to immunosuppressants, and could be considered as a first-line therapy. Our data should be confirmed by the results of controlled clinical trials.

Ways to predict interstitial lung disease in patients with systemic sclerosis: results of an observational study

In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.

Генетические дисфункции системы сурфактанта у детей: результаты многоцентрового исследования

Aim: Genetic, clinical, laboratory-instrumental and morphological characteristics of genetic dysfunctions of the surfactant system in children, therapy and outcomes of the disease. Design: Multicentre, ambispective, open-label, descriptive pilot longitudinal study. Materials and methods. We observed 17 children from 16 families with identified mutations in the SFTPC, ABCA3, NKX2-1 genes. Methods used: genealogical, Sanger sequencing, clinical exome sequencing, computed tomography and histological examination of the lungs. Results. The study included 8 children with congenital deficiency of surfactant protein C, 8 children with brain-lung-thyroid syndrome and 1 patient with congenital deficiency of protein ABSA3. Based on the results of a genetic examination of patients, nucleotide variants c.218T>C were identified in 2 out of 8 patients with a mutation in the SFTPC gene, which is the most common according to the literature. In 5 children, the mutations were hereditary. Congenital deficiency of surfactant protein C, ABCA3 protein and brain-lung-thyroid syndrome were characterized by clinical, computed tomography, and morphological signs of interstitial lung disease. Despite complex respiratory, anti-inflammatory therapy, the frequency of deaths in congenital deficiency of surfactant protein C was 37.5%. Conclusion. Children with severe respiratory distress syndrome of newborns, interstitial lung disease with the development of severe chronic respiratory failure, burdened with a family history should undergo genetic testing to detect mutations in the genes SFTPB, SFTPC, ABCA3. The patient's combination of respiratory symptoms with congenital hypothyroidism and neurological pathology is the basis for genetic examination for NKX2-1 gene mutations to exclude the brain-lung-thyroid syndrome. Keywords: genetic dysfunctions of the surfactant system, congenital deficiency of surfactant protein C, congenital deficiency of ABCA3 protein, brain-lung-thyroid syndrome, NKX2-1 gene, children.

STING-associated vasculopathy with onset in infancy: the first case in Bulgaria and review of the literature

We report a clinical case of a 4-year-and-10-month-old boy whose first symptoms (fever and tachypnoea) were noticed at the age of 6 months. In the upcoming months, skin acral violaceous plaques developed. Failure to thrive and growth impairment were detected. In the journey to find the correct diagnosis, a lot of diseases were suspected. The final diagnosis was suggested after more than 2 years since the first symptoms had appeared. A multi-detector computed tomography of the chest with low radiation dose protocol showed signs of interstitial lung disease (ILD). Next-Generation Sequencing was done, and it revealed a pathogenic heterozygous N154S mutation (NM_198282.4 (Stimulator of IFN genes STING1):c.461A > G (p.Asn154Ser)) in STING1 gene. Treatment with JAK-inhibitor baricitinib was started at the age of 3 years and 10 months. The presence of cutaneous vasculopathy, lung involvement, laboratory signs of inflammation, recurrent fevers and failure to thrive should indicate STING1 gene analysis. STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified type I interferonopathies. SAVI is characterized by systemic inflammation via the overproduction of type I IFN due to heterozygous gain-of-function mutations in STING1. The onset of the symptoms of SAVI is usually early in infancy with recurrent fevers accompanied by increased acute phase reactants and ulcerating skin lesions.

Quantitative assessment of regional pulmonary perfusion using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: pilot study results in 10 patients

Background. Currently there is a high demand in reliable noninvasive diagnostic technique assessing the physiological parameters of the lungs. We are exploring the three-dimensional ultrafast MRI sequence as a novel diagnostic modality allowing the assessment of regional quantitative perfusion parameters in pulmonary tissue.
 Aim. To assess regional differences in quantitative pulmonary perfusion parameters in 10 volunteers with no evidence of interstitial lung disease by computed tomography, clinical, and laboratory data.
 Materials and methods. 10 volunteers with no signs of interstitial lung disease were examined by three-dimensional ultrafast dynamic contrast-enhanced MR imaging using 3D T1-weighted images. The values of pulmonary blood flow (PBF), mean transit time (MTT), and pulmonary blood volume (PBV) for the targeted regions of interest were calculated based on the dynamic image series. For calculations, arterial input function (AIF) was used, as well as the time-intensity curves.
 Results. The values of PBF, MTT, and PBV showed statistically significant differences between central and peripheral sections of lungs. Provided model can be implemented for quantitative assessment of regional pulmonary perfusion allows it to be used to determine the reliability of PBF, MTT and PBV values.
 Conclusions. Three-dimensional ultrafast MRI sequence is a novel diagnostic modality allowing the assessment of regional quantitative pulmonary perfusion parameters in pulmonary tissue, regardless of physiological features of blood supply mechanisms in different lung regions.

Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung disease screening.

Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard. Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings. B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P < 0.0001). A total of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis. LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach.

Novel genetic and molecular pathways in pulmonary arterial hypertension associated with connective tissue disease

Abstract Introduction PAH is a severe complication of CTD, with remarkable morbidity and mortality. SSc is most commonly associated with PAH, but it can be present in other CTD. Despite major advances in PAH therapy, survival in CTD-PAH remains poor. Furthermore, the molecular and genetic basis of PAH in CTD are not well established. Purpose This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH. Methods Since November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of PAH, and PVOD included in a national registry of PAH. A PAH-specific panel of 35 genes was designed. Results During enrolling, 79 patients were recruited: 59 SSc, 11 SLE and 9 other. 69 female, mean age 55,6±1,9 years, mean PVR 8,6±0,5 WU and mean DLCO 47,5±2%. Disease-associated variants were observed in 9 patients: 4 pathogenic/likely pathogenic in 4 different genes (TBX4, ABCC8, KCNA5 and GDF2/BMP9) and 5 VUS in 4 genes (ABCC8, NOTCH3, TOPBP1 and CTCFL). Clinical characteristics of patients with pathogenic/likely pathogenic variants and variant analyses are shown in Tables 1 and 2. Patient 1 is a Caucasian female with mixed CTD, diagnosed with PAH at 58 years of age. She has a frameshift pathogenic variant in TBX4. Pulmonary function test (PFT) ruled out interstitial lung disease (ILD), but a reduction in DLCO was observed (61% of predicted). Two patients carry variants in ABCC8. Patient 2 is a Caucasian female with SSc, diagnosed with PAH at 27 years of age. She carries a splicing variant in ABCC8, classified as likely pathogenic. Her mother was diagnosed with PAH associated with a repaired ASD at 61 years of age. In the genetic testing, no variants were observed in PAH genes. DLCO was 71% of predicted, without signs of ILD. Patient 3 is a Caucasian male, with clinical suspicion of PVOD associated with SSc and HIV infection. PAH was diagnosed at 57 years of age. He presented a missense variant in ABCC8, located in a gating regulatory region, and classified as VUS. Her sister was also diagnosed with PVOD associated with SSc at 48 years of age. No blood or tissue samples are available. In patient 3, DLCO was 22% of predicted value. CT scan showed the typical triad of PVOD. Patient 4 is a Latin American female with SLE, diagnosed with PAH at 25 years of age. She presented a pathogenic nonsense variant in GDF2/BMP9. Patient 5 is a Caucasian female with SSc, diagnosed with PAH at 70 years of age. She presented a pathogenic variant in KCNA5. Patients 6–9 have SSc-PAH and carry VUS in NOTCH1, CTCFL, CTCFL and TOPBP1, respectively. Conclusions We demonstrate the practical diagnostic utility of genetic testing with a panel in CTD-PAH. The discovery of rare variants in these patients forces us to take a comprehensive approach and accurate genetic counseling. Further research is still necessary to confirm these findings and help to provide a personalized medicine approach to these patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project was founded by project “Bases Genético Moleculares de la Medicina de Precisiόn en la Hipertensiόn Arterial Pulmonar”. Funder: Instituto Carlos III. Ministerio de Economía y Competitividad.

Lung magnetic resonance imaging in systemic sclerosis: a new promising approach to evaluate pulmonary involvement and progression.

Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung, due to poorer spatial resolution compared to high-resolution computed tomography (HRCT). We aimed to compare lung MRI signal with HRCT and evaluate the role of MRI in predicting ILD progression. Thirty SSc patients underwent lung MRI and HRCT. STIR and T1 mapping sequences were acquired before and after gadolinium injection. Patients were classified as normal (group 1 with normal HRCT and MRI), discordant (group 2 without ILD signs on HRCT but areas of hyperintensity on MRI), and abnormal (group 3 with ILD signs on HRCT and areas of hyperintensity on MRI). Patients were followed up for ILD progression. Mean STIR and T1 values were different between the three groups (p < 0.0001). STIR values correlated with HRCT score (R = 0.79, p < 0.0001), lung ultrasound B-lines (R = 0.73, p < 0.0001), and %DLco (R = - 0.63, p = 0.0001). Nine events were recorded during a follow-up of 25 ± 20months. Continuous STIR values were independently associated with events (HR 1.018; CI 1.005-1.031, p = 0.005). A STIR value >90ms discriminated patients at a higher risk of worsening pulmonary involvement (HR 8.80; CI 1.81-42.74; p < 0.007). Lung MRI can detect SSc-related ILD, with good correlations with other ILD markers. STIR values, independently of HRCT appearance, may predict worsening lung involvement. Lung MRI, although very preliminary, is a promising tool that in a near future could help selecting patients for an early treatment of SSc-related ILD and a more appropriate use of HRCT. Key points • Lung MRI has the potential to differentiate inflammation-predominant versus fibrosis-predominant lesions, but it is not currently used in routine clinical practice to assess SSc-related ILD. • Lung MRI STIR and T1 values are significantly different between patients with and without SSc-related ILD. STIR values, independently of HRCT appearance, are also able to predict worsening lung involvement over time. • These preliminary data suggest that, in a near future, MRI could support the choice for an early treatment of SSc-related ILD, as well as a more appropriate use of HRCT.

Predictive Features and Clinical Presentation of Interstitial Lung Disease in Inflammatory Myositis

Interstitial lung disease (ILD) represents one of the most severe extra-muscular features of idiopathic inflammatory myositis (IIM). We aimed to identify any clinical and serological predictors of ILD in a monocentric cohort of 165 IIM patients.ILD+ patients were defined as having restrictive impairment in lung function tests and signs of ILD at chest high-resolution computed tomography (HRCT). Available HRCT images were centralized and classified in different ILD patterns: non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), usual interstitial pneumonia-like (UIP), indeterminate for UIP, and interstitial lung abnormalities (ILA). Lung function test data were recorded at onset, at 1 and 5 years after ILD diagnosis.ILD was found in 52 IIM patients (31.5%): 46.2% was affected by anti-synthetase syndrome (ARS), 21% by polymyositis (PM), 19% by dermatomyositis (DM), and 13.5% by overlap myositis. Most of ILD+ showed NSIP (31.9%), OP (19%), indeterminate for UIP (19%), and UIP (12.8%) patterns. At multivariate analysis, ILD was predicted by anti-Ro52 (p: 0.0026) and dyspnea (p: 0.015) at IIM onset. Most of ILD onset within is 12 months after IIM. In five cases, ILD occurs after 12 months since IIM diagnosis: these patients more frequently show dry cough and anti-Ku antibodies. Anti-Ro52 + ILD patients showed a significant increase of DLCO at 1 and 5 years of follow-up, compared with anti-Ro52 negative cases.ILD occurs in about one third of IIM and was predicted by dyspnea at onset and anti-Ro52 antibodies. Anti-Ro52 defines a subgroup of ILD showing a significant improvement of DLCO during follow-up. This retrospective study has been approved by local ethic committee (ASST-Spedali Civili of Brescia, Italy); protocol number: NP3511

Anti-SAE1 Antibodies and Dermatomyositis: A Case Series of Three Patients

To date, few patients with anti-SAE1 dermatomyositis (DM) have been described, and usually in large descriptive cohort studies including all DM subtypes. Thus, it is increasingly important to further describe this rare subtype to solidify cutaneous findings, associated symptoms, and potential therapeutic options. Herein, this case series describes three patients with anti-SAE1 DM with respect to their clinical and laboratory findings, and also their response to treatment. All three patients eventually presented with classic cutaneous manifestations of dermatomyositis, however, Case 2 presented initially with cutaneous manifestations not described in the literature. Furthermore, two patients presented with dysphagia, with Case 2 experiencing a life-threatening dysphagia not typically described in the literature. Two of three patients also presented with early signs of interstitial lung disease. Lastly, cutaneous disease was only responsive to immunosuppressants in one patient. Unfortunately, this observational case-series consisted of only three patients, limiting the generalizability of our results. However, this study provides further support of the recalcitrant nature of this DM subtype, and commonly affected extracutaneous systems including the gastrointestinal and pulmonary systems. Larger studies of this patient population are needed to further confirm our associated findings.

THE CASE OF THE DEBUT OF SYSTEMIC SCLERODERMA IN A PATIENT AGED 10

Aim. To show the diversity and severity of clinical symptoms, a large range of diagnostic search, as well as difficulties in therapy in a 10-year-old patient with systemic manifestations of juvenile scleroderma.Materials and methods. A retrospective analysis of the anamnetic data, the course of the disease, laboratory and instrumental data, as well as the ongoing therapy of a 10-year-old patient with juvenile systemic scleroderma was carried out.Results. The patient was diagnosed with multiple typical sclerodermic foci of irregular shape, with different stages of lesion (edema, induration and atrophy). Joint damage was noted in the form of pseudoarthritis interphalangeal joints of hands with the formation of sclerodactily and right ankle joint. As a result of computed tomography of chest, signs of interstitial lung disease by the type of fibrous alveolitis have been revealed. After verification of the diagnosis, the patient was prescribed basic therapy: methylprednisolone and cyclophosphane.Conclusion. A clinical case of the debut of juvenile systemic scleroderma with rapidly progressive, widespread skin lesions, involvement of the musculoskeletal system and the development of fibrous alveolitis is presented. Due to intensive and long-term pathogenetic therapy (glucocorticoids, cyclophosphamide), the patient's condition was stabilized and the progression of interstitial lung disease was stopped.

Impact of FDG-PET on the Detection of Patients with Lung Cancer at High Risk for ILD.

Idiopathic pulmonary fibrosis IPF is a type of interstitial lung disease (ILD) with poor prognosis. Lung cancer (LC) is a frequent complication in IPF, where all therapeutic options are potential triggers for acute exacerbation of IPF. Patients with 2-deoxy-2-fluoro-D-glucose-positron emission tomography/computer tomography (FDG-PET/CT) results before lobectomy for LC with and without (n=10 each) signs of ILD in initial imaging and after-care CT were retrospectively analyzed. FDG uptake was calculated as the maximum standardized uptake value (SUVmax) in the lung periphery divided by the SUVmax of the mediastinal blood pool (rSUVmax). Regional increase of fibrosis and ground-glass features in lobe-based CT analysis was used as standard reference. Patients with LC with ILD presented a significantly higher rSUVmax of 0.57 compared to patients without ILD with rSUVmax 0.47 (p<0.001). rSUVmax seems to be a valuable imaging surrogate in predicting patients with LC with increased risk for progressive ILD associated with thoracic surgery.

Impact of anti-tumor necrosis factor-α agents on serum levels of KL-6 and surfactant protein-D in patients with psoriasis.

We longitudinally examined the influence of anti-tumor necrosis factor (TNF)-α treatment on serum levels of KL-6 and surfactant protein-D (SP-D). The study group comprised 22 patients with psoriasis treated with infliximab or adalimumab and with no history of interstitial lung disease (ILD). KL-6 and SP-D levels were measured in serum samples. Twelve of the 22 patients (55%) showed at least a 20% increase in KL-6 levels compared with baseline. Of these 12 patients, none exhibited any signs of ILD on chest computed tomography and nine who showed an increase in KL-6 levels (75%) showed at least a 20% increase in SP-D levels. Some patients showed simultaneous increases in KL-6 and SP-D levels after treatment with anti-TNF-α agents. Although these patients may have undetectable or subtle alveolar damage, careful observation is needed.

Isolated decrease of the lung diffusing capacity in patients with systemic sclerosis without pulmonary arterial hypertension: a long-term prospective study

The objective of this 5year prospective study was to investigate a clinical role of isolated decrease of DLCO in patients with systemic sclerosis (SS) without pulmonary arterial hypertension (PAH).Methods. We selected 48 out of 142 patients with SS: 35 (73%) with limited SS and 13 (27%) with diffuse SS. The average length of the disease was 12.9 ± 7.9 years. Inclusion criteria were DLCO &lt; 80% pred., forced vital capacity (FVC) ≥ 80% pred. and systolic pulmonary artery pressure (PAP) ≤ 35 mm Hg according to echocardiographic examination (echoCG). High resolution computed tomography (HRCT), spirometry, DLCO measurement, and echoCG were obtained at baseline and after 4.7 ± 1 year of follow up. All patients were treated with standard therapy.Results. CT signs of interstitial lung disease (ILD) were found in 43 (89.6%) patients at baseline and newly developed in 3 other patients during the followup. During the followup, lung CT improved in 5 (10.4%) patients and progressed in 15 (31.3%) patients. Over 5 years, FVC did not change significantly (97.6 ± 10.7% and 100.8 ± 18.9%; р = 0.15), while DLCO significantly decreased both in limited and diffuse SS groups (59.8 ± 13.5% and 56.3 ± 12%; р = 0.006). Mean PAP values remained within normal range in majority of patients. Clinically significant FVC reduction (≥ 10%) was found in 5 patients; of them, CT signs of ILD at baseline were seen in 3 patients and newly developed during the followup in 2 others. Clinically significant DLCO reduction (≥ 10%) was documented in 11 (23%) patients, all had CT signs of ILD at baseline, although CT progression during the followup was noted only in six of them. Contemporary deterioration in FVC, DLCO and CT was found in 3 patients.Conclusion. Clinical course of ILD in SS patients with isolated DLCO reduction and without PAH was relatively benign, with respiratory volumes being preserved within normal range for long time. Comparison of radiological and functional changes in a prospective study has suggested that DLCO is a more sensitive tool to determine ILD progression compared to HRCT. Regular DLCO measurements could be used as a reliable tool for monitoring of ILD associated with SS.

Erasmus syndrome in a marble worker

Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynaud's phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT) detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage) excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient.

SAT0299 Rituximab Treatment of the Antisynthetase Syndrome

BackgroundAntisynthetase syndrome (ASS) is a severe variant of idiopathic inflammatory myopathies. Unfavorable prognosis of this disease is associated with interstitial lung disease (ILD). Conventional treatment with glucocorticoids (GC) and cytotoxic...

Interstitial lung disease in a female patient with rheumatoid arthritis

Rheumatoid arthritis (RA) is a progressive disease, resulting in joint deformation and development of severe functional disorders. Meanwhile, RA patients frequently have systemic inflammatory disorders of internal organs, which may significantly worsen quality of life, labor capacity, and be a factor determining the prognosis. Idiopathic interstitial pneumonia is of particular interest. This disease is characterized by unfavorable prognosis due to progressive fibrous rearrangement of the lung. We report a clinical case of RA with signs of interstitial lung disease.