Idiopathic Interstitial Lung Disease Research Articles

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies; other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

Phosphodiesterase-5 inhibitors: Raynaud's and beyond

Phosphodiesterases (PDE) are a group of ubiquitously present enzymes involved in regulation of various cellular pathways. PDE5 acts to metabolize cyclic guanosine monophosphate (GMP). The various PDE5 inhibitors available are sildenafil, tadalafil, vardenafil, and mirodenafil. We shall discuss the roles of various PDE5 inhibitors in rheumatic diseases. PDE5 inhibitors prevent degradation of cyclic GMP; hence, they have vasodilatory properties which render them useful in the management of secondary Raynaud's phenomenon. They have also demonstrated efficacy in the healing of digital ulcers in systemic sclerosis and potentially prevent the formation of new digital ulcers. Their vasodilatory property has also been utilized in the management of pulmonary arterial hypertension, wherein their ability to favorably affect hemodynamics of a pressure-overloaded right heart is beneficial. Recent evidences have suggested a potential antifibrotic role of these agents, and studies in idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease hold promise for future exploration of these agents for these indications.

Idiopathic Lymphoid Interstitial Pneumonia: A Case Report

Idiopathic Lymphoid Interstitial Pneumonia (LIP) is considered to be a rare interstitial lung disease. The initial American Thoracic Society/European Respiratory Society (ATS/ERS) International multidisciplinary consensus paper on Idiopathic Interstitial Pneumonia of 2002, LIP was classified as one of the seven major idiopathic interstitial lung diseases. Since the first description of LIP in 1969, so far only 14 biopsy proven cases of idiopathic LIP have been described in the literature. The clinical course is reported to be highly variable in this rare form of interstitial pneumonia.

INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC SCLEROSIS

The basis for the pathogenesis of systemic sclerosis (SS) is immune disorders that initiate inflammation, as well as vasculopathy with obvious microcirculatory disturbances, and generalized fibrosis. In SS, lung injury is due to an arterial lesion and/or a fibrotic process in the lung parenchyma and occurs as two major syndromes that are rarely concurrent in one patient; these are pulmonary arterial hypertension and interstitial lung disease (ILD). In SS, lung injury negatively affects the prognosis and ranks first among the causes of death. The review focuses on ILD, the most common injury of the respiratory tract in SS, which is detectable in 80% of patients, as evidenced by multislice spiral computed tomography (MSCT) of the chest. The histological manifestations are similar to those of idiopathic ILDs, but the histological type does not determine the prognosis. The course of ILD in SS is relatively benign, often subclinical. A severe progressive lesion develops only in 10–15% of cases. Clinically significant changes in the lung parenchyma develop early, within the first 3–5 years of the disease. Pulmonary functional tests show that relatively preserved and stable forced vital capacity is long recorded in the majority of patients, but the diffusing capacity of the lung is reduced in 70–80% of the patients. The values of pulmonary tests during the first examination are of prognostic value; the lower than normal they are, the worse the prognosis. Chest MSCT should be carried out in all patients with newly diagnosed SS, as the quantitative (prevalence) and qualitative (frosted glass, honeycomb lung) indicators affect the determination of therapy policy. ILD treatment is performed only in patients with obvious signs of progression, which are determined from the time course of changes in the decrease of values of pulmonary functional tests. Immunosuppressants, cyclophosphamide being the drug of choice, are used to treat ILD; biological agents, tocilizumab in particular, are currently being tested.

Idiopathic pulmonary fibrosis: The current state of the problem

Idiopathic pulmonary fibrosis (IPF) is a severe lung disease, with death occurring within 2-5 years after its onset. IPF affects people in the second half of life. Its causes are unknown. Before 1999, IPF was out from the group of idiopathic interstitial lung diseases as a separate nosological entity. Practitioners very often (80%) make diagnostic errors in IPF and prescribe antibiotics, anti-inflammatory drugs, which worsen the course of this disease. The distinctive feature of the pathogenesis of IPF is the absence of inflammation, which is clinically manifested by the inefficacy of glucocorticosteroids and other anti-inflammatory drugs. Pharmacological agents for the treatment of IPF have been designed since 2000. One of them has been registered and permitted for use in the Russian Federation. This paper is a review of an update on the problem of IPF, which should facilitate the appropriate orientation of physicians in diagnosing and treating this severe disease.

Plasma Surfactant Protein-D, Matrix Metalloproteinase-7, and Osteopontin Index Distinguishes Idiopathic Pulmonary Fibrosis from Other Idiopathic Interstitial Pneumonias.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) characterized by abnormal extracellular matrix (ECM) remodeling. We hypothesized that ECM remodeling might result in a plasma profile of proteins specific for IPF that could distinguish patients with IPF from other idiopathic ILDs. To identify biomarkers that might assist in distinguishing IPF from non-IPF ILD. We developed a panel of 35 ECM, ECM-related, and lung-specific analytes measured in plasma from 86 patients with IPF (derivation cohort) and in 63 patients with IPF (validation cohort). Comparison groups included patients with rheumatoid arthritis-associated ILD (RA-ILD; n = 33), patients with alternative idiopathic ILDs (a-ILD; n = 41), and healthy control subjects (n = 127). Univariable and multivariable logistic regression models identified biomarkers that differentiated patients with IPF from those with a-ILD. Both continuous and diagnostic threshold versions of biomarkers were considered; thresholds were chosen to maximize summed diagnostic sensitivity and specificity in univariate receiver-operating characteristic curve analysis. A diagnostic score was created from the most promising analytes. Plasma surfactant protein (SP)-D > 31 ng/ml, matrix metalloproteinase (MMP)-7 > 1.75 ng/ml, and osteopontin > 6 ng/ml each significantly distinguished patients with IPF from patients with a-ILD, both individually and in a combined index. The odds ratio for IPF when at least one analyte in the index exceeded the threshold was 4.4 (95% confidence interval, 2.0-9.7; P = 0.0003). When at least two analytes were elevated, the odds ratio for IPF increased to 5.0 (95% confidence interval, 2.2-11.5; P = 0.0002). A biomarker index of SP-D, MMP-7, and osteopontin enhanced diagnostic accuracy in patients with IPF compared with those with non-IPF ILD. Our data suggest that this biomarker index may improve diagnostic confidence in IPF.

Brief Report: Anti-Eukaryotic Initiation Factor 2B Autoantibodies Are Associated With Interstitial Lung Disease in Patients With Systemic Sclerosis.

To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations. Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls. A novel autoantigen with a molecular weight of ∼30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B). We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (∼1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD.

The utility of comprehensive autoantibody testing to differentiate connective tissue disease associated and idiopathic interstitial lung disease subgroup cases.

Interstitial lung disease (ILD) comprises many heterogeneous disease groups, the largest being CTD-associated and those labelled as idiopathic out of necessity. The mechanisms causing ILD are poorly understood, but most CTD- and idiopathic-ILD cases can respond to immunosuppression, clearly suggesting a pathological role for inflammation. By contrast, corticosteroid immunosuppression causes harm without benefit in the feared idiopathic pulmonary fibrosis, suggesting that inflammation plays little pathological role, and where ILD progresses rapidly to lethal outcome even with anti-fibrotic drug use. Given the treatment response differences apparent between ILD subgroups, and the dangers and costs of corticosteroid and anti-fibrotic drug use, respectively, it has become vital in every ILD patient to make an accurate subgroup diagnosis, to optimize treatment selections. This review discusses why differentiating CTD- and idiopathic-ILD subgroup cases remains so problematic, and why existing comprehensive CTD-specific serology would, if generally available, represent an ideal biomarker tool to enhance ILD subgroup diagnostic accuracy.

Interstitial Pneumonia With Autoimmune Features: Clinical, Morphological, and Serological Features

SESSION TITLE: Connective Tissue-Associated Interstitial Lung Disease SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: To determine the frequency and characteristics of interstitial pneumonia with autoimmune features (IPAF) in a group of patients evaluated in two different centres specialized in interstitial lung diseases (ILD). As secondary objective we compared the clinical, morphological and laboratory features of patients with IPAF, idiopathic pulmonary fibrosis (IPF) and ILD associated with connective tissue diseases (CT-ILD). METHODS: Analytic retrospective study. Data were collected from the medical records of all patients diagnosed with ILD in two specialized centers. For the statistical analysis we used Kruskal-Wallis test RESULTS: 199 patients with ILD were evaluated, 121 (60.8%) of who were female. Of them 116 presented some of the tree categories like IPAF (n=28: 14.07%), IPF (n=43: 21.60%) and CTD-ILD (n=45: 22.61%), so they were included in the analysis. The mean age in the group of IPAF was 63.28±11.09, versus 70.32±6.62 in IPF and 62.35±13.95 in CTD (p=0.006). Unlike IPF, where 58.14% were males, there was a predominance in females both in IPAF and CTD (82.14% and 77.77% respectively). Mean forced vital capacity (FVC) expressed in percentage of predicted value in IPAF was 69.21±15.21, 64.17±16.67 in IPF and 77.14±18.79 in CT-ILD (p=0.011). Remarkably, 100% of the patients with IPF, 82.14% of IPAF and 21% of CT-ILD patients presented “velcro” at auscultation (p<0.001), and the clubbing was more frequent in IPF (62.79%), followed by CT-ILD (26.66%) and IPAF (14.28%) (p<0.001). The frequency of gastro-esophageal reflux symptoms was 57.77% in CT-ILD, 44.18% in IPF and 42.58% in IPAF (p=0.335). Within the extra-articular symptoms, arthralgia and gastro-esophageal reflux were the more frequent features in IPAF (67.85% and 42.85% respectively). In the case of CT-ILD, were arthralgia and arthritis (88.88% and 71.11% respectively). Regarding auto-antibodies, the most frequently found in IPF patients was the antinuclear (ANA), which was positive in 64.28%. Only 2 patients with IPAF had antibodies negatives. In the group of IPF 27.90% had some autoantibody positive. In reference to computed tomography, the pattern most frequently found in both the IPAF as in the CT-ILD group was nonspecific pneumonia (NSIP) unlike what happened in the IPF group were 83.72% had UIP pattern. What concerns to prognosis, the mean %FVC at six months of the diagnosis in patients with IPAF were lower than baseline. The same was seen in IPF and CT-ILD. Moreover, in the group of IPAF, fewer exacerbations were observed (7.14% versus 15.55% in CT-ILD and 23.25% in IPF; p=0.332) CONCLUSIONS: In our serie of 199 patients with ILD we found a frequency of IPAF of 14.07%. Of them, the most frequent tomographic and histological pattern was NSIP. The vast majority of patients had a positive autoantibodies. IPAF patients showed lower values of FVC than CT-ILD, but higher than those with IPF. CLINICAL IMPLICATIONS: The term IPAF describes a group of ILD with specific clinical, morphological and laboratory features that suggest an autoimmune condition but are not enough to full fit the established criteria of a specific CTD. Early referral to rheumatology and interdisciplinary discussion is key to the best approach to this group of patients. DISCLOSURE: The following authors have nothing to disclose: Gabriela Tabaj, Brenda Varela, Maria Victoria Gallardo, Cecilia Gonzalez Ginestet, Georgina Gramblicka, Mariana Salomon, Carlos Nigro, Patricia Malamud No Product/Research Disclosure Information

Ameliorative Effects of Atorvastatin on Bleomycin-Induced Pulmonary Fibrosis in Rats

Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease, with a negligible response to available medical therapies and potentially fatal prognosis. Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG CoA] reductase inhibitors) have broad pleiotropic properties and are used to treat multiple diseases. Objectives: The purpose of this study was to investigate the effect of different doses of atorvastatin (10, 20, and 40 mg/kg) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods: Thirty female 8-wk-old Sprague Dawley rats, weighing 200 ± 20 g, were randomly divided into five experimental groups. Group 1 (control) received saline intratracheally (IT), group 2 received a single dose of BLM (7.5 UI/kg/mL, IT) on day 7 and no treatment, and groups 3 - 5 received atorvastatin orally at doses of 10, 20, and 40 mg/kg, respectively, one week before and again three weeks after BLM administration. The rats were sacrificed 21 days after the administration of BLM. Blood and lungs were collected for plasma malondialdehyde (MDA), lung hydroxyproline, and histopathological examination. Results: The results showed that lung hydroxyproline and plasma MDA levels were significantly reduced in the atorvastatin-treated groups, especially the 40 mg/kg group, compared to the BLM untreated group (P < 0.05). Furthermore, atorvastatin prevented infiltration of inflammatory cells, proliferation of fibroblasts, and alveolar thickening due to BLM. Conclusions: Atorvastatin may play a protective role in pulmonary fibrosis, with its effects mediated via the station’s antioxidant and anti-inflammatory properties. Atorvastatin may be a potential agent for the treatment of lung injury and fibrosis.

Comparison of Hibiscus sabdariffa L. Extract and Enalapril with Regard to Their Effect on Lung Fibrosis in a Bleomycin-induced Rat Model of Lung Fibrosis

Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease that responds only weakly to available medical therapies and has a potentially fatal prognosis. Hibiscus sabdariffa L. contains several antioxidants, such as protocatechuic acid (PCA) and anthocyanins, which may be beneficial for the treatment of fibrosis. Objectives: The purpose of this study was to investigate the inhibitory effect of the H. sabdariffa L. extract (HSE) on angiotensin-converting enzyme (ACE) and compare it with that of enalapril in a rat model of bleomycin-induced pulmonary fibrosis. Methods: Female Wistar rats (weighing 180 g- 235 g) were randomly divided into seven groups (n = 8). The negative and positive control groups were intratracheally administered a single dose of saline (1 mL/kg) and bleomycin (7.5 UI/kg/mL) respectively. The treatment groups were orally administered enalapril (20 mg/kg), PCA (100 mg/kg) and HSE (100, 200, and 400 mg/kg) daily for one week before and three weeks after bleomycin administration. The animals were sacrificed 24 hours after the last administration of the therapeutic agent. The transforming growth factor-β1, platelet-derived growth factor, tumor necrosis factor-α and angiotensin II (ANG II) levels in the bronchoalveolar lavage fluid (BALF) and also the malondialdehyde (MDA) and hydroxyproline (HP) levels in lung tissue were measured. The presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in the lung was microscopically evaluated using Masson’s trichrome staining. Results: The results showed a significant increase in the lung index and the levels of MDA, HP, ANG II and pro-inflammatory cytokines after bleomycin administration. Pre-treatment with enalapril, PCA and HSE resulted in a reduction in the levels of the above factors. Enalapril and HSE (400 mg/kg) treatment could mitigate the progression of fibrosis clearly via ACE blocking and a decrease in the level of oxidative stress. Enalapril, PCA and HSE could prevent the infiltration of fibroblasts, inflammatory cells and alveolar thickening caused by bleomycin. Conclusions: Our results indicate that HSE, which has demonstrated anti-hypertensive effects in herbal medicine, can be useful for the treatment of inflammatory and fibrotic disorders.

Risk Factors for De Novo Malignancy Following Lung Transplantation.

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).

Formes frustes de connectivites : atteinte respiratoire et intérêt pour le pneumologue

The diagnosis of interstitial lung disease (ILD) associated with connective tissue disease is often difficult and is based on a set of arguments. There is a probable overlap between ILD related connective tissue disease and idiopathic ILD corresponding to undifferentiated connective tissue, the predictors of which are known (age less than 50, female gender, pattern of nonspecific interstitial pneumonia), but the diagnostic criteria were undetermined. It was necessary to define a uniform set of criteria, due to the impact on management and prognosis. IPAF (Interstitial pneumonia with auto-immune features), as proposed by an ERJ / ATS taskforce, represents uniform criteria that will facilitate an international clinical research effort.

Prélèvements des pneumopathies interstitielles diffuses : du LBA à la cryobiopsie

The gold standard for interstitial lung disease diagnosis is the anatomopathological examination of a surgical biopsy. However this invasive test is not always achievable and there are less invasive alternative tests. Broncho alveolar lavage is not pathognomonic in most interstitial lung diseases yet it will bring arguments in favor of a diagnosis. In idiopathic pulmonary fibrosis, it will show a mixed pattern, while in nonspecific interstital pneumonias and hypersensitivity pneumonias the pattern will be more lymphocytic. However, this pattern, non-specific, could vary depending on the fibrosis level and could not be discriminating for patients with a high level fibrosis. Transbronchial biopsies have a low diagnostic performance for the idiopathic pulmonary fibrosis and non-specific interstitial lung diseases. Cryobiopsy is a promising technique with a good diagnostic performance, still lower than surgical biopsy yet with lower morbidity-mortality

Hypersensitivity pneumonitis: the importance of the radiologist in the multidisciplinary approach to its diagnosis.

Radiol Bras. 2016 Mar/Abr;49(2):VII–VIII Hypersensitivity pneumonitis encompasses a set of diseases with pulmonary involvement and a predominance of histopathologic findings—lymphocytic inflammatory infiltrate, noncaseating granulomas, and foci of bronchiolitis obliterans, as well as fibrosis in the more chronic stages—predominantly distributed around the small airways, as shown in the excellent correlation study conducted by Torres et al., published in this issue of Radiologia Brasileira. That distribution of findings reflects a response to repeated inhalation of various antigenic substances, typically organic substances, such as fungi, thermophilic bacteria, and bird feathers. Farmer’s lung and bird fancier’s lung are well-established forms of hypersensitivity pneumonitis. However, new and curious forms are described every day, such as “saxophonist’s lung”, which is caused by exposure to molds that grow in the mouthpieces of saxophones. Clinically, hypersensitivity pneumonitis can present in acute, subacute, or chronic forms. The acute and subacute forms have systemic symptoms, mimicking those of flu or asthma. The chronic form occurs in individuals with greater re-exposure to antigens, evolving to more pronounced interstitial fibrosis, dyspnea, hypoxemia, digital clubbing, and impaired lung function. The chronic form is also usually associated with failure to identify the causative antigen, and the differential diagnosis includes other idiopathic interstitial lung diseases, although making that distinction is often impossible even with the histopathological findings. There is considerable variation across epidemiological studies of hypersensitivity pneumonitis. It is estimated that hypersensitivity pneumonitis accounts for 3–13% of all cases of interstitial lung disease in Brazil. A study conducted in the city of Sao Paulo, SP, Brazil, involving 99 cases of lung biopsy-confirmed hypersensitivity pneumonitis, indicated that the most frequent causative agents are household mold and bird droppings. In our experience in the Brazilian state of Santa Catarina, we have also found that the disease occurs most frequently in individuals exposed to mold in the home and in individuals who are bird breeders.

(858) - Risk Factors for De Novo Malignancy Following Lung Transplantation

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).

A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy.

Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15-25% of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1-5% or lower. Patients with any anti-ARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of these new antibodies to clinical practice in the future will help in making earlier and more accurate diagnoses and better management for patients.

Comparison of Idiopathic Interstitial Pneumonias with Their Connective Tissue Disease-Associated Counterparts

Interstitial lung disease (ILD) has been described as a potential clinical finding in essentially all of the connective tissue diseases (CTD). Patients with Rheumatoid Arthritis most commonly develop a fibrotic pattern consistent with Usual Interstitial Pneumonia while Non-Specific Interstitial Pneumonia is more commonly seen in the remainder of the collagen vascular diseases, in particular in patients with Scleroderma-spectrum disease. The etiology of ILD in the CTDs is poorly understood and the progression of lung disease may not correlate with the more typical autoimmune manifestations. Therapy of CTD-associated ILD remains unsatisfactory and the clinical picture may be clouded by the probability that some patients with apparently idiopathic ILD will, eventually, evolve into a more clearly-defined CTD and by the possibility that in some patients with lung-dominant disease subtle evidence of underlying CTD may be missed. In this review we will examine the etiologic, histologic, radiographic, and epidemiologic features of the Idiopathic Intersitial Pneumonias in comparison with their CTD-associated counterparts as well as address some of the difficulties in assessing whether ILD is truly idiopathic or instead part of an underlying autoimmune process. Keywords: Idiopathic interstitial pneumonia, non-specific interstitial pneumonia, organizing pneumonia, rheumatoid arthritis, systemic sclerosis, usual interstitial pneumonia.

Difficulties in diagnosis of systemic sclerosis‐related interstitial lung disease

We discuss a case that demonstrates the difficulties in making a confident diagnosis of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). Atypical symptoms can be present, suggesting the diagnosis of an underlying connective tissue disease (CTD), but it can take several years before a definite diagnosis can be made because there are insufficient features to fulfill the preset classification criteria (American College of Rheumatology criteria) for a definite underlying CTD. Close follow-up of these patients is necessary because patients with SSc-ILD have a poorer prognosis than those with SSc without pulmonary involvement. Treatment choice also differs between idiopathic ILD and SSc-related ILD.

Les connectivites

The lung is often the target of collagen vascular diseases (CVD), usually with interstitial pneumonia. The type of interstitial lung disease may be a clue to the diagnosis of CVD, and is sometimes very specific (UIP and rheumatoid arthritis, COP and dermatoymyositis, LIP and Sjogren's syndrome). The development of interstitial lung disease affects the prognosis of CVD (Pulmonary hypertension and systemic sclerosis, UIP and Rheumatoid arthritis). Interstitial lung disease associated with CVD usually has a better prognosis than idiopathic interstitial lung disease. Currently, there is no effective specific treatment for interstitial pneumonia associated with CVD except cyclophosphamide in systemic sclerosis.