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To analyze the efficacy and safety of nintedanib in patients with fibrosing autoimmune disease-related interstitial lung diseases (ILDs) with a progressive phenotype.The INBUILD trial enrolled patients with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of10% extent on high-resolution computed tomography, forced vital capacity percent predicted (FVC%) ≥45%, and diffusing capacity of the lungs for carbon monoxide percent predicted ≥30% to80%. Patients fulfilled protocol-defined criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Subjects were randomized to receive nintedanib or placebo. We assessed the rate of decline in FVC (ml/year) and adverse events (AEs) over 52 weeks in the subgroup with autoimmune disease-related ILDs.Among 170 patients with autoimmune disease-related ILDs, the rate of decline in FVC over 52 weeks was -75.9 ml/year with nintedanib versus -178.6 ml/year with placebo (difference 102.7 ml/year [95% confidence interval 23.2, 182.2]; nominal P = 0.012). No heterogeneity was detected in the effect of nintedanib versus placebo across subgroups based on ILD diagnosis (P = 0.91). The most frequent AE was diarrhea, reported in 63.4% and 27.3% of subjects in the nintedanib and placebo groups, respectively. AEs led to permanent discontinuation of trial drug in 17.1% and 10.2% of subjects in the nintedanib and placebo groups, respectively.In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing autoimmune disease-related ILDs, with AEs that were manageable for most patients.

Purpose HRCT is the preferred imaging technique to evaluate Interstitial-Lung-Disease. Optimal Low-Dose-Computed-Tomography protocol for monitoring ILD with lowest radiation dose and optimal diagnostic accuracy and image quality unknown. Methods 28 Patients underwent HRCT. Image reconstructions with varying combinations of tube current (50mA, 20mA, 15 mA, 10mA) and image-thickness/increment (1/1mm, 2/2mm, 3/2.4mm, 5/4mm) were simulated from raw data. 448 CTs evaluated by 2 readers on image quality and ILD-specific features (ground glass opacification (ggo), honeycombing (hc), reticulation (ret)). Results Reduced dose settings with 20 mA did not show any significant difference to standard dose settings for all parameters in reader 1, while results were significantly altered in reader 2. Slice thickness did not significantly influence rating of typical ILD features like ggo, hc, ret or total disease extent. The correct differentiation between UIP and NSIP could be made on all dose settings and with all slice thickness. It was even found, that an increased slice thickness can compensate for the noise associated image quality degradation. Overall, for ggo detection a combination of 20 mA and 3 or 5 mm slice thickness was not different to the original evaluation. Conclusions Assessment of ILD specific CT features down to 20 mA and a slice thickness of 3 or 5 mm is feasible.

Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871.From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths.Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials.Genentech.

Objective: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.Methods: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating whiteboard videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set.Results: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1-Knowledge of options, their potential benefits and harms; 2-Chosen option aligned with each patient's values and preferences; 3-Confidence in the chosen option; 4-Satisfaction with the decision-making process; 5-Adherence to the chosen option and 6-Potential negative consequences of the SDM intervention.Conclusion: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set.Clinical significance: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.(c) 2021 Elsevier Inc. All rights reserved.

Objective.The Outcome Measures in Rheumatology (OMERACT) Shared Decision Making (SDM) Working Group aims to determine the core outcome domain set for measuring the effectiveness of SDM interventions in rheumatology trials.Methods.A white paper was developed to clarify the draft core domain set. It was then used to prepare for interviews to investigate reasons for lack of consensus on it and to suggest further improvements.Results.OMERACT scientists/clinicians (n = 13) and patients (n = 10) suggested limiting the core domain set to outcome domains, removing process domains, and clarifying remaining domains.Conclusion.A revised core domain set will undergo further consensus-building.

International guidelines recommend screening for connective tissue disease (CTD) with autoantibodies when evaluating patients with idiopathic interstitial lung disease (ILD). Idiopathic inflammatory myositis comprises of a subgroup of CTD diagnosed with myositis antibodies (MA), often presenting with ILD. Our aim was to evaluate the utility of MA screening in patients with idiopathic ILD. A retrospective analysis was conducted on patients referred with idiopathic ILD to a tertiary centre ILD clinic who were screened for MA. Patients with known or suspected CTD were excluded. Descriptive statistics, univariate analysis and multivariable logistic regression were used to detect associations between MA and patient characteristics. Of 360 patients, 165 met inclusion criteria and 44 (26.7%) were identified to have MA. Fourteen patients (8.5%) had a change in diagnosis as a result of MA screening. Multivariable logistic regression identified the presence of MA to be associated with current smoking [OR 6.87 (1.65–28.64), p = 0.008] and a diffusing capacity of

Background: Interstitial lung disease (ILD) is an established manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Autoimmune serologic screening is recommended by international consensus guidelines during the evaluation of idiopathic ILD, but ANCA testing only on a case-by-case basis. Objective: We aimed to evaluate the role of ANCA screening in patients with idiopathic ILD. Methods: We performed a retrospective review of patients seen between September 2015 and April 2017 in the ILD clinic at Toronto General Hospital. Patients referred with confirmed or suspected connective tissue disease were excluded. Patient demographics, symptoms, chest imaging, and pulmonary function testing was collected. We performed descriptive statistics based on the presence of ANCAs and estimated operating characteristics for ANCA screening. Results: In total, 360 patients with idiopathic ILD were reviewed, 159 met study inclusion criteria and 4 (2.5%) tested positive for ANCAs. Two patients (1.2%) had elevated myeloperoxidase-ANCAs (MPO-ANCA) and 2 (1.2%) had elevated proteinase-3-ANCAs (PR3-ANCA). There were no significant associations between patient demographics and ANCAs. One patient (0.6%) with PR3-ANCAs was diagnosed with vasculitis following rheumatologic evaluation. Despite negative ANCA testing, 1 patient (0.6%) was diagnosed with vasculitis following rheumatologic evaluation. The sensitivity and specificity of ANCA screening for vasculitis in patients with ILD was calculated as 50% (95% CI, 1.3%-98.7%) and 98% (95%CI, 4.4-155.5) respectively. Negative and positive likelihood ratios were 0.5 (95%CI 0.1-2.0) and 26.2 (95%CI 4.4-155.5) respectively. Conclusion: ANCA screening in patients with idiopathic ILD rarely yields positive results. These results support an individualized approach to ANCA testing as opposed to widespread screening.

Introduction Dans l’etude INBUILD sur 52 semaines de traitement, le nintedanib versus placebo a ralenti le taux de declin de la capacite vitale forcee (CVF) sur la population totale atteinte de PID fibrosantes progressives autres qu’une fibrose pulmonaire idiopathique [n = 663] incluant le sous-groupe des patients avec une PID fibrosante progressive (PID-FP) associee a une maladie auto-immune [n = 170]. Nous avons evalue dans ce sous-groupe le delai de survenue : – du deces ; – de la premiere exacerbation aigue de la PID ou du deces ; – jusqu’a progression de la maladie (declin absolu de la CVF≥ 10 % de la valeur predite) ou deces sur l’ensemble de l’etude. Patients et methodes Les patients ont ete randomises pour recevoir le nintedanib 150 mg bid ou le placebo et ont poursuivi le traitement randomise en aveugle jusqu’a la fin de l’etude. Les taux d’incidence des evenements indesirables pour 100 patient–annees ont ete calcules sur la base des evenements survenus entre la premiere prise du medicament a l’etude et la derniere prise plus 28 jours. Les analyses etaient descriptives. Resultats 89 PID-PR, 39 PID-ScS, 19 PID-CM, 23 autres PID auto-immunes dont PID associee a un syndrome de Gougerot-Sjogren [n = 7], PID avec manifestations auto-immunes [n = 5] et PID associee a une connectivite indifferenciee [n = 3]. Respectivement dans les groupes nintedanib et placebo, 9,8 % et 12,5 % des patients sont decedes, 12,2 % et 20,5 % ont developpe ≥ 1 exacerbation aigue de PID ou sont decedes et 40,2 % et 53,4 % une progression de la maladie ou sont decedes. La diarrhee a ete l’evenement indesirable le plus frequent, avec des taux d’incidence de 139,2 et 26,3 evenements pour 100 patient–annees dans les groupes respectivement nintedanib et placebo. Les evenements indesirables ont entraine l’arret du traitement chez 20,7 % des patients (nintedanib) et 13,6 % des patients (placebo). Conclusion Les donnees de l’etude INBUILD suggerent que le nintedanib a un effet cliniquement significatif sur le ralentissement de la progression de la PID chez les patients atteints d’une PID associee a une maladie auto-immune fibrosante progressive, avec des evenements indesirables pouvant etre toleres par la majorite des patients.

The evaluation of a patient with fibrotic interstitial lung disease (ILD) includes assessment of clinical, radiological, and often histopathological data. There are currently no specific recommenda...

Interstitial lung disease (ILD) is commonly present in patients with an underlying connective tissue disease (CTD), particularly those with systemic sclerosis, rheumatoid arthritis, and inflammatory myositis. The clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. Distinguishing features in the clinical, radiographic, and histopathologic characteristics of CTD-ILD subsets can predict prognosis and treatment response. Treatment often consists of combinations of immunosuppressive medications, but there is a paucity of guidance in the literature to help clinicians determine appropriate screening and management of CTD-ILD. As such, there is a critical need for studies that can elucidate the natural history of the CTD-ILD, as well as clarify optimal therapies for CTD patients with ILD.

Background:In the INBUILD trial in patients with progressive fibrosing ILDs, nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo over 52 weeks both in the overall population and in the subgroup with autoimmune disease-related ILDs. Patients continued blinded randomised treatment until the end of the trial.Objectives:Assess the effects of nintedanib on the risks of death, acute exacerbation of ILD or death, and disease progression or death over the whole INBUILD trial in patients with autoimmune disease-related ILDs and a progressive phenotype.Methods:Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib 150 mg bid or placebo. Time to i) death, ii) first acute exacerbation of ILD or death, and iii) disease progression (absolute decline in FVC ≥10% predicted) or death, over the whole trial were analysed in patients with autoimmune disease-related ILDs. Incidence rates of adverse events per 100 patient–years were calculated based on events with onset between the first trial drug intake and the last intake plus 28 days. Analyses were descriptive.Results:Of 663 patients, 170 (82 nintedanib, 88 placebo) had autoimmune disease-related ILDs (89 RA-ILD, 39 SSc-ILD, 19 MCTD-ILD, 23 other autoimmune ILDs including Sjogren’s disease-related ILD [n=7], interstitial pneumonia with autoimmune features [n=5] and undifferentiated CTD-ILD [n=3]). Over the whole trial, in the nintedanib and placebo groups, respectively, mean (SD) exposure to drug was 15.4 (7.4) and 16.9 (6.1) months and maximum exposure was 26.0 and 25.2 months; 62 (75.6%) and 68 (77.3%) patients in these groups, respectively, completed the planned observation time. Over the whole trial, in the nintedanib and placebo groups, respectively, 9.8% and 12.5% of patients died, 12.2% and 20.5% of patients had ≥1 acute exacerbation of ILD or died, and 40.2% and 53.4% of patients had disease progression or died (Table). Diarrhoea was the most common adverse event, with incidence rates of 139.2 and 26.3 events per 100 patient–years in the nintedanib and placebo groups, respectively. Adverse events led to treatment discontinuation in 20.7% of patients in the nintedanib group and 13.6% of patients in the placebo group.Conclusion:Data from the INBUILD trial suggest that nintedanib has a clinically meaningful effect on slowing the progression of ILD in patients with progressive fibrosing autoimmune disease-related ILDs, with adverse events that can be tolerated by most patients.Table.Nintedanib (n=82)Placebo (n=88)HR (95% CI)*Death8 (9.8)11 (12.5)0.80 (0.32, 1.98)≥1 acute exacerbation of ILD or death10 (12.2)18 (20.5)0.58 (0.27, 1.27)Disease progression (absolute decline in FVC ≥10% predicted) or death33 (40.2)47 (53.4)0.72 (0.46, 1.13)n (%) with event over the whole trial (mean [SD] exposure: 15.4 [7.4] and 16.9 [6.1] months in nintedanib and placebo groups, respectively). *Based on time to first event.Disclosure of Interests:Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Clive Kelly Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, James Seibold Shareholder of: BriaCell, Pacific Therapeutics, Consultant of: Atlantic, Blade Therapeutics, Eicos Sciences, Eiger Biopharmaceuticals, Indalo Therapeutics, Mitsubishi Tanabe Pharma, Bayer, Xenikos, Boehringer Ingelheim, Camurus, Corbus Pharmaceuticals, EMD Serono, Speakers bureau: Boehringer Ingelheim, Shikha Mittoo Grant/research support from: Pfizer, Consultant of: Novartis, Abbvie, Pfizer, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Paul F. Dellaripa Grant/research support from: Paul Dellaripa has received institutional grants from Genentech, Consultant of: Paul Dellaripa participated in advisory boards for Boehringer Ingelheim, Alexandra James Employee of: Employee of Boehringer Ingelheim, Rozsa Schlenker-Herceg Employee of: Employee of Boehringer Ingelheim, Susanne Stowasser Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Kevin R. Flaherty Grant/research support from: Kevin Flaherty has received grants from Boehringer Ingelheim, Consultant of: Kevin Flaherty has acted as a consultant for Boehringer Ingelheim, Bellerophon, Blade Therapeutics, Roche/Genentech, and VeracyteHe was a member of the INBUILD trial Steering Committee

Objective.Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research.Methods.The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants.Results.OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO.Conclusion.There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.

Objective.To describe the dorsal 4-finger technique (DFFT) in examining metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) and compare it to the traditional 2-finger technique (TFT) using ultrasound (US) as a gold standard.Methods.Four rheumatologists evaluated 180 MCP joints of 18 patients with RA. All patients underwent US for greyscale (GSUS) and power Doppler US (PDUS). Agreements between rheumatologists, the 2 techniques, and US were evaluated using Cohen κ and the first-order agreement coefficient (AC1) κ methods.Results.The population comprised 17 females (94.4%) with a mean (SD) age and disease duration of 56.8 (14.4) and 21.8 (12.9) years, respectively. Eight patients (44.4%) were taking methotrexate monotherapy, while 10 patients (55.6%) were receiving biologics. US evaluation revealed 69 (38.3%) and 30 (16.7%) joints exhibited synovitis grade 2–3 by GSUS and PDUS, respectively. Effusion was documented in 30 joints (16.7%). The mean intraobserver agreement using the DFFT and TFT were 80.5% and 86%, respectively. The mean interobserver agreements using the DFFT and TFT were 84% and 74%, respectively. κ agreement with US findings was similar for both techniques in tender joints but was higher for the DFFT in nontender joints (0.33 vs 0.07, p = 0.015 for GSUS) and (0.48 vs 0.11, p = 0.002 for PDUS). The DFFT had a higher sensitivity in detecting ballottement by GSUS (0.47 vs 0.2, p < 0.001) and PDUS (0.60 vs 0.27, p < 0.001).Conclusion.The DFFT is a novel, reproducible, and reliable method to examine MCP joints, and it has a better correlation with US than the traditional TFT.

Background Patients with rheumatoid arthritis – associated interstitial lung disease (RA-ILD) have increased mortality with limited treatment options. We set out to examine post-transplant survival in RA-ILD patients compared with patients with idiopathic pulmonary fibrosis (IPF) and scleroderma-associated ILD (SSc-ILD). We also describe post-transplant quality of life (QoL) outcomes in RA-ILD. Methods A retrospective review was performed on lung transplantation (1989 to 2011) among patients with RA-ILD, IPF (group-matched for age and transplant year) and SSc-ILD. Cumulative survival after transplantation was estimated by the Kaplan – Meier method and compared between groups using the log-rank test. The 36-item Medical Outcomes Survey Short Form (SF-36) and the St. George's Respiratory Questionnaire (SGRQ) scores, before and after lung transplantation, were analyzed. Results Overall, 10 patients with RA-ILD, 53 with IPF and 17 with SSc-ILD underwent lung transplantation with ages (mean ± SD) of 59.4 ± 5.6, 61.0 ± 4.0 and 45.4 ± 12.7 years, respectively. Cumulative survival rates at 1-year post-transplant for the RA-ILD, IPF and SSc-ILD groups were 67%, 69% and 82%, respectively, and there was no significant difference among groups in age- and gender-adjusted analyses. Among the RA-ILD patients, mean SF-36 physical component summary scores improved from 22.4 ± 8.1 to 32.2 ± 12.9 ( p = 0.1), SF-36 mental component summary scores improved from 44.7 ± 15.3 to 54.9 ± 4.8 ( p = 0.19) and SGRQ total scores improved from 70.4 ± 16.1 to 36.0 ± 18.5 ( p = 0.03). Conclusions After lung transplantation, RA-ILD and IPF patients have similar survival rates. Further, in RA-ILD patients, lung transplantation appears to result in a significant improvement in QoL with regard to respiratory symptoms. These data suggest that lung transplantation should be considered in patients with end-stage RA-ILD.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized serologically by an autoantibody response to nucleic antigens, and clinically by injury and/or malfunction in any organ system. During their disease course, up to 50% of SLE patients will develop lung disease. Pulmonary manifestations of SLE include pleuritis (with or without effusion), inflammatory and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, pulmonary hypertension, airways disease, and thromboembolic disease. Two major themes inform our understanding of SLE-associated pulmonary manifestations: first, the presence of specific autoantibodies correlates with the presence of certain pulmonary manifestations and second, vascular injury marks a common pathophysiologic thread among the various SLE-related lung diseases. This review will focus on the clinical presentation, pathogenesis, pathology, management, and prognosis of these SLE-associated lung conditions.

Introduction: Predictors of lung function decline in systemic sclerosis (SSc) are unknown. Serum pneumoprotein levels, surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6), correlate with pulmonary damage. We aimed to test whether levels can predict rapid lung function decline in SSc. Methods: SSc patients who had serial pulmonary function tests (PFT) were analyzed for SP-D and KL-6 levels by enzyme linked immunosorbent assay. Levels were correlated with an annual rate of decline in % predicted forced vital capacity (FVC) of >﹣2% (out-come); controls did not experience this FVC decline. Uni- and multi-variate analysis, adjusting for age, disease duration, gender, baseline % predicted FVC, SP-D, and KL-6, was performed. Results are reported as mean ± SD. Results: Thirty three cases and 25 controls had a disease duration of 8.8 ± 7.3 and 8.3 ± 6.1 years, respectively. In adjusted analyses, lung function decline correlated with greater baseline FVC OR = 1.03 [95% CI of 1.00-1.07]; a trend towards significance was observed for greater levels of SP-D with FVC decline, OR = 1.37 [95% CI of 0.96-2.12]. Conclusion: Our data provide evidence that SSc patients with long-standing disease are still at risk for lung function decline and SP-D levels may predict lung function decline.

We thank Moran-Mendoza et al. for their thoughtful comments regarding the recent Canadian Thoracic Society position statement on the evaluation of patients with fibrotic interstitial lung disease (...

Objective To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). Methods We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. Results In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. Conclusion Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Objective.Certain North American Native (NAN) populations are known to have higher rates of systemic sclerosis (SSc) compared to non-NAN; however, little is known of the specific disease characteristics in this population in Canada. This study compares the clinical and serological manifestations of SSc in NAN and white patients.Methods.This cross-sectional, multicenter study included subjects enrolled in the Canadian Scleroderma Research Group registry between September 2004 and June 2012. Subjects were evaluated with complete medical histories, physical examinations, and self-questionnaires. Ethnicity was defined by self-report. Disease characteristics were compared between NAN and white patients and multivariate analyses were performed to determine the independent association between ethnicity and various clinical manifestations.Results.Of 1278 patients, 1038 (81%) were white, 71 (6%) were NAN, and 169 (13%) were classified as non-white/non-NAN. There were important differences between NAN and white subjects with SSc. In multivariate analysis adjusting for socioeconomic differences and smoking status, NAN ethnicity was an independent risk factor for the severity of Raynaud phenomenon and more gastrointestinal symptoms, and was associated with a nonsignificant increase in the presence of digital ulcers.Conclusion.NAN patients with SSc have a distinct clinical phenotype. Our study provides a strong rationale to pursue further research into genetic and environmental determinants of SSc.

Background. The relative rarity and diversity of fibrotic interstitial lung disease (ILD) have made it challenging to study these diseases in single-centre cohorts. Here we describe formation of a multicentre Canadian registry that is needed to describe the outcomes of fibrotic ILD and to enable detailed healthcare utilization analyses that will be the cornerstone for future healthcare planning.Methods. The Canadian Registry for Pulmonary Fibrosis (CARE-PF) is a prospective cohort anticipated to consist of at least 2,800 patients with fibrotic ILD. CARE-PF will be used to (1) describe the natural history of fibrotic ILD, specifically determining the incidence and outcomes of acute exacerbations of ILD subtypes and (2) determine the impact of ILD and acute exacerbations of ILD on health services use and healthcare costs in the Canadian population. Consecutive patients with fibrotic ILD will be recruited from five Canadian ILD centres over a period of five years. Patients will be followed up as clinically indicated and will complete standardized questionnaires at each clinic visit. Prespecified outcomes and health services use will be measured based on self-report and linkage to provincial health administrative databases.Conclusion. CARE-PF will be among the largest prospective multicentre ILD registries in the world, providing detailed data on the natural history of fibrotic ILD and the healthcare resources used by these patients. As the largest and most comprehensive cohort of Canadian ILD patients, CARE-PF establishes a network for future clinical research and early phase clinical trials and provides a platform for translational and basic science research.

Background: Scleroderma (SSc) patients with active interstitial lung disease (ILD) experience a decline in lung function and increased mortality; cyclophosphamide (CYC) therapy may stabilize lung function at one and two years follow-up. Long-term lung function and survival outcomes of SSc patients with ILD following CYC treatment remain largely unknown. Methodology: We reviewed records of SSc patients with active ILD who had received at least six months of CYC treatment and had pulmonary function tests (PFTs) performed at least two years from the onset of treatment. Principal Findings: Thirty eight patients meeting eligibility criteria had a mean follow-up period from start of CYC to the last follow-up PFT of 5.1 years (range 2.3 -10.8 years). At a median of 4.1 years (range 9 months - 8.4 years), 12/38 (32%) patients had a significant decline in % predicted Forced Vital Capacity from their baseline PFT. At a median of 3.9 years (range 7 months - 8.4 years); 12/36 (33%) patients experienced a significant decline in their % predicted carbon monoxide diffusing capacity. Three patients died at a follow-up between 4.5-6 years and two received bilateral lung transplants because of severe restrictive lung disease. Conclusions: While the majority of SSc patients treated with CYC for active ILD experience long-term lung function stability and survive, greater than 1/3 of patients will experience either lung function decline, death, or require a lung transplant. This suggests that despite aggressive immune suppressing therapy, a subset of patients will have continued lung function decline, highlighting the need for ongoing monitoring and better therapeutic options.

Systemic lupus erythematosus (SLE) is a systemic, inflammatory disorder with a predilection for young women. A wide array of pulmonary manifestations can occur in patients with SLE, including interstitial lung disease. In this review, we will discuss the scope, pathogenesis, management, and prognosis, along with the clinical and pathologic features of SLE-associated ILD (SLE-ILD).

Objective.Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort.Methods.We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression.Results.In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (± SD) was 46.8 ± 13.5 years, and disease duration at study entry was 12.1 ± 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p ≤ 0.0001), age at SLE diagnosis (p = 0.009), and anti-Sm (p = 0.002) and anti-RNP (p = 0.002) seropositivity were significantly associated with pleuritis. In multivariate analysis with adjustment for disease duration, age at diagnosis, and SDI score, concomitant seropositivity for RNP and Sm were related to a nearly 2-fold greater prevalence of pleuritis (OR 1.98, 95% CI 1.31–2.82).Conclusion.Pleuritis occurred in one-third of this Canadian cohort. Concomitant Sm and RNP seropositivity, greater cumulative damage, longer disease duration, and younger age at SLE disease onset were related to a higher rate of SLE pleural disease.

Objective Bronchoalveolar lavage (BAL) is a procedure for sampling the terminal airspace cell population to diagnose alveolitis, a condition that predicts changes in lung function in scleroderma patients. Cyclophosphamide (CYC) stabilizes the progression of lung disease in some, but not all, patients with active alveolitis. However, it is unknown whether the BAL fluid cell count obtained after CYC treatment of alveolitis predicts long-term lung function outcomes and can therefore be used to assist in therapeutic decision-making. The purpose of this study was to determine whether CYC therapy for active lung disease alters BAL fluid neutrophil and eosinophil counts and whether the persistence of abnormal BAL findings after CYC therapy predicts a decline in lung function in patients with scleroderma and interstitial lung disease (ILD). Methods We systematically reviewed the records of scleroderma patients who had active ILD, as evidenced by neutrophilia or eosinophilia on BAL fluid analysis before CYC therapy and on repeat analysis after completion of CYC. Pulmonary function tests (PFTs) were performed before initiation of therapy, at completion of therapy, and during long-term followup (mean ± SD 3.6 ± 1.94 years). Results Of the 25 study patients, in only 6 did the BAL fluid cell counts normalize after CYC therapy. No significant differences were observed between the proportions of patients who had a ≥10% decline in the % predicted DLCO or FVC on the second set of PFTs and had abnormal findings on followup BAL fluid analysis. During long-term followup, patients with persistent alveolitis had a decline in lung function (mean ± SD change in % predicted FVC −0.6 ± 10.8 liters and mean ± SD change in % predicted DLCO −4.7 ± 21.43 ml/minute/mm Hg), but their lung function did not significantly differ from that in patients whose BAL fluid cell counts had normalized (P = 0.70 and P = 0.62, respectively). Conclusion Persistently abnormal results on BAL fluid analysis following CYC treatment is a common finding and does not predict a subsequent decline in lung function.

The impact and natural history of connective tissue disease related interstitial lung disease (CTD-ILD) are poorly understood; and have not been previously described from the patient's perspective. This investigation sought insight into CTD-ILD from the patients' perspective to add to our knowledge of CTD-ILD, identify disease-specific areas of unmet need and gather potentially meaningful information towards development of disease-specific patient-reported outcome measures (PROMs).A mixed methods design incorporating patient focus groups (FGs) querying disease progression and life impact followed by questionnaires with items of importance generated by >250 ILD specialists were implemented among CTD-ILD patients with rheumatoid arthritis, idiopathic inflammatory myopathies, systemic sclerosis, and other CTD subtypes. FG data were analyzed through inductive analysis with five independent analysts, including a patient research partner. Questionnaires were analyzed through Fisher's Exact tests and hierarchal cluster analysis.Six multicenter FGs included 45 patients. Biophysiologic themes were cough and dyspnea, both pervasively impacting health related quality of life (HRQoL). Language indicating dyspnea was unexpected, unique and contextual. Psycho-social themes were Living with Uncertainty, Struggle over Self-Identity, and Self-Efficacy - with education and clinician communication strongly emphasised. All questionnaire items were rated 'moderately' to 'extremely' important with 10 items of highest importance identified by cluster analysis.Patients with CTD-ILD informed our understanding of symptoms and impact on HRQoL. Cough and dyspnea are central to the CTD-ILD experience. Initial FGs have provided disease-specific content, context and language essential for reliable PROM development with questionnaires adding value in recognition of patients' concerns.

Objectives This study examines the effect of pulmonary disease on patient-reported outcomes (PROs) and patient-performed outcome (PPO) in systemic lupus erythematosus (SLE) patients at a single tertiary referral center. Methods Pulmonary function tests (PFTs), chest imaging, SLE-related damage, and disease activity were examined in 110 SLE patients. Presence was noted of abnormal PFTs, pleural disease, pulmonary hypertension (PH), pulmonary infarction, interstitial lung disease (ILD), and shrinking lung syndrome (SLS). PROs included the Medical Outcome Short Form-36 Health Survey, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, Borg Dyspnea Scale, patient dyspnea and cough. The PPO of interest was the six-minute walk test (6MWT). Relationships amongst PROs, 6MWT, and pulmonary disease were studied. Results Pulmonary disease was present in 62 (56%) of 110 subjects: 54 (49%) abnormal PFT, 13 (12%) pleural disease, 12 (11%) ILD, 11 (10%) SLS and five (5%) PH. Dyspnea was the only PRO found to be significantly associated with pulmonary disease ( P = 0.0004). Participants with pulmonary disease compared to those without had significantly reduced distance ( P = 0.00015, 95% CI for mean 39–125 m) and predicted distance ( P = 0.00001, 10%–26%) on 6MWT. Conclusions Pulmonary disease is common in SLE and adversely impacts 6MWT distance and dyspnea without apparent influence on other PROs. The 6MWT may be a promising tool in the assessment of pulmonary disease in SLE.

BACKGROUND: A revised guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) was formulated by the American Thoracic Society (ATS) in 2011 to improve disease diagnosis and provide a simplified algorithm for clinicians. The impact of these revisions on patient classification, however, remain unclear.OBJECTIVE: To examine the concordance between diagnostic guidelines to understand how revisions impact patient classification.METHODS: A cohort of 54 patients with either suspected IPF or a working diagnosis of IPF was evaluated in a retrospective chart review, in which patient data were examined according to previous and revised ATS guidelines. Patient characteristics influencing the fulfillment of diagnostic criteria were compared using one-way ANOVA and χ2tests.RESULTS: Revised and previous guideline criteria for IPF were met in 78% and 83% of patients, respectively. Revised guidelines modified a classification based on previous guidelines in 28% of cases. Fifteen percent of patients meeting previous ATS guidelines failed to meet revised criteria due to a lack of honeycombing on high-resolution computed tomography and the absence of a surgical lung biopsy. Patients failing to meet previous and revised diagnostic criteria for IPF were younger.CONCLUSION: The revised guidelines for the diagnosis of IPF classify a substantial proportion of patients differently than the previous guidelines.

Nearly half of patients with systemic sclerosis (SSc) experience a digital ulcer, and many of these ulcers may progress to digital gangrene. Gangrene can stem from inadequate healing of digital ulcers or complications of comorbidities along with elevated C-reactive protein (CRP) levels. A 49-year-old woman diagnosed with systemic lupus erythematosus (SLE) and an overlap with SSc since 2006 presented in December 2010 with a 1-day history of acute pain and discoloration of all her digits (Figure 1). Figure 1. Dorsal and palmar views showing acute gangrene of all 5 digits on the right hand and chronic ulcers affecting the palmar aspect on the left hand (A, B). Panels (C) and (D) show both hands after 6 months of followup. Note the extensive skin desquamation on both hands. Her connective tissue disease course was characterized by sclerodactyly, gastrointestinal reflux, inflammatory arthritis, serositis, oral ulcers, Raynaud’s phenomenon (RP), positive antinuclear antibody with titer 1:640 in a speckled pattern, rheumatoid factor, anti-Sm, and anti-RNP antibodies. She was treated since 2008 with stable doses of methotrexate and leflunomide. She was not known to have any risk factors for atherosclerosis such as diabetes mellitus, hypertension, or dyslipidemia, and she did …

We present, for the first time to our knowledge, a patient with Systemic Lupus Erythematosus (SLE) with pulmonary Bronchial-Associated Lymphoid Tissue (BALT) lymphoma, refractory to chemotherapy but after a single four-week course of rituximab experienced significant regression of pulmonary lesions and remained progressionfree six months post- treatment. This case report demonstrates the promising role for rituximab in refractory BALT lymphoma.

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized serologically by an autoantibody response to nucleic antigens and clinically by injury and/or malfunction in any organ system. During their disease course, up to 50 % of SLE patients will develop lung disease. Pulmonary manifestations of SLE include pleuritis (with or without effusion), inflammatory and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, pulmonary hypertension, airways disease, and thromboembolic disease. This chapter will focus on the clinical presentation, pathogenesis, pathology, management, and prognosis of these SLE-associated lung conditions.

Background The pulmonary function test (PFT) is an integral part of the assessment of patients prior to hematopoietic cell transplantation (HCT). The HCT comorbidity index (HCT-CI) is a routinely used scoring system using PFTs to determine patient outcomes post HCT. FEV1 and DLCO are used as determinants distinguishing between moderate (DLCO or FEV1 66-80%) and severe dysfunction (DLCO or FEV1 ≤ 65%). While there is a supportive evidence of its use in HCT, there is a debate on stratification of the current threshold of PFTs. Our study attempted to analyze the prognostic impact of each parameter of PFT on outcomes including overall survival (OS), relapse and non-relapse mortality (NRM) including FEV1, FVC, DLCO, FEF50%/75%, FRC, RV as well as TLC. Methods A retrospective review was conducted to analyze pre-transplant PFT values with respect to transplant outcomes in 605 patients receiving allogeneic HCT at Princess Margaret Cancer Centre from 2004 to 2013. PFT results were collected within 30 days prior to HCT. PFT parameters include % predicted FEV1, DLCO, TLC, RV, RV/TLC, FRC, FVC, FEV1/FVC, FEF50% and FEF75%. The main outcomes include OS, cumulative incidence of relapse (CIR) and NRM. The cut-off values in each PFT parameters with respect to OS were calculated using binary recursive partitioning (rpart) method provided by rpart package using R. Each PFT parameter was analyzed for correlation with other PFT parameters using Pearson's correlation test. All the statistical tests were done using EZR and SPSS. OS analysis was done using Kaplan-Meier method, and OS was compared according to the new cutoff derived from rpart and according to the cutoff used in the HCT-CI score. Then prognostic stratification power was compared between these two cutoffs. For the multivariable analysis, all variables were included in the model with the exception of those already included in the HCT-CI score. For the outcome of OS, Cox prop ortional hazard regression model was adopted. Six clinical variables were included in the multivariate analysis including: pre-transplant FEV1 Results Out of 605 patients, OS rate was 46% at 3 years. NRM was 35.6% and relapse rate was 21.0% at 3 years. For correlation among PFT parameters, FEV1 was significantly associated with TLC (r=0.51), FVC (r=0.79), FEF75 (r=0.58) and FEF50 (r=0.68), and was chosen as a surrogate of OS for further analysis. Univariate analysis for the PFT parameters expressed as continuous variables revealed that OS was associated with FEV1, FVC and TLC, while not with other parameters (i.e. DLCO, FEF50%, FEF70%, FRC or RV). Using recursive partitioning, the optimal value for the best stratification of OS was found: FEV1 at 81%, FEV1/FVC at 92%, and TLC as 88%. The OS rate at 3 years in the group with FEV1 ≥81% was 49.9%, versus FEV1 Conclusions 1. FEV1 at 81% is a significant and reliable parameter amongst all the PFT parameters affecting HCT outcomes. 2. DLCO does not predict long-term HCT outcomes in our cohort. 3. Compared to FEV1 cutoff per HCT-CI scoring system, the new cutoff of 81% FEV1 provides better risk stratification power for long-term outcomes after allogeneic HCT. Disclosures No relevant conflicts of interest to declare.

HIV-1 infection results in a dementing illness affecting 20% of patients with AIDS. Several HIV-1 genes have been implicated in the pathogenesis of HIV-induced neurological disease. To search for distinct HIV-1 sequences associated with the development of dementia, brain-derived tat, env, and pol sequences were examined from AIDS patients defined pre-mortem as demented (HIV-D)[n=5] or non-demented (HIV-ND)[n=5]. Estimations of evolutionary distances and frequency of non-synonymous mutation rates revealed significant differences between brain-derived tat, env, and pol-encoded reverse transcriptase sequences. However, established zidovudine-associated resistance mutations in reverse transcriptase sequences were identified in only one HIV-D and one HIV-ND patient despite prolonged treatment of some patients. Non-synonymous/synonymous substitution rates among the tat sequences derived from patients with HIV-D were significantly higher compared to the HIV-ND group (P0.001). The ratios of transversions to transitions were also significantly higher among the HIV-D tat sequences (P0.01). Phylogenetic analyses showed clustering of sequences from each clinical group among the brain-derived tat and env sequences. These studies indicated that differing selective forces act on individual HIV-1 genes in the brain which may influence the development of dementia.

Biologic agents have become a powerful armament in the treatment of immune-mediated diseases, although long-term data are still being collected. It seems biologics may have favorably altered outcomes in mortality and disability in recalcitrant and life-threatening diseases. At the same time, these “miraculous” agents come with important and potentially life-threatening concerns related to immune suppression that can give rise to serious infection, heart failure, demyelinating neural disease, and malignancy.Therefore, continued assessment of efficacy and adverse effects are central to the management of patients treated with biologics. The following chapter outlines important considerations in the clinical assessment during and after a biologic clinical trial. This chapter will cover structural aspects of clinical trial design, surveillance for adverse effects, provide an overview of endpoints in clinical trials design, and discuss the basis for generic (not disease-specific) and disease-specific instruments (aka outcome measures and endpoints) used in trials. This chapter will also provide information on novel forms of developing clinical endpoints from the patient's perspective. Keywords: immune-mediated diseases; clinical trial design; clinical endpoints; pharmacogenetics

Introduction: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS. Methods: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan. SLS was defined as dyspnea with restrictive lung physiology (defined as a forced vital capacity (FVC)

To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE).We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data.In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials.Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Desquamative interstitial pneumonia (DIP) is a rare form of interstitial lung disease (ILD) commonly found among healthy smokers. ILD is a rare manifestation of systemic lupus erythematosus (SLE), and typically associated with a histopathological pattern of nonspecific interstitial pneumonia (NSIP). The present article describes an unusual case of DIP in a non-smoking patient with SLE presenting as NSIP. DIP can occur in the context of SLE in patients with a negative smoking history, and clinicians should consider lung biopsy to correctly classify ILD with unusual presentation on computed tomography scan.

Rheumatoid arthritis (RA) is a systemic, autoimmune, inflammatory disorder affecting 0.51% of the North American population (Gabriel, 2001). It has a predilection for young women with an incidence rate of up to 130 per 100,000 compared with 70 per 100,000 in men [Minaur et al, 2004]. It is associated with a median survival decrease of up to 11 years compared to the general population (Minaur et al., 2004). The disease course may be complicated by extra-articular manifestations that confer an added burden of morbidity and mortality. RA-associated cardiovascular and infectious complications are commonly highlighted as major causes of morbidity and mortality in these patients (Maradit-Kremers et al., 2005). However, pulmonary involvement, the third leading extra-articular manifestation of RA, is now also recognized as a major cause of morbidity and mortality in RA patients. This was demonstrated in an autopsy study of 81 RA patients where the cause of death was determined to be infectious in 23.5%, cardiovascular in 17.3% and respiratory in 9.9% of patients (Suzuki et al., 1994). Pulmonary complications are the presenting manifestation of RA in up to 20% of patients (Brown, 2007). These complications include airway disease, pleural effusion, pulmonary nodules, and interstitial lung disease (ILD). This chapter will discuss the epidemiology, clinical features, management of RA-associated ILD (RA-ILD) and highlight the links between pulmonary involvement and autoimmunity.

A 35-year-old woman with a history of breast cancer, treated 3 years ago with surgery, radiation, and chemotherapy presented with a rapid onset of severe Raynaud’s phenomenon. On physical examination, she had digital ulcers and splinter hemorrhages; there were no signs of an underlying rheumatic condition. Laboratory evaluation revealed anemia, the presence of antinuclear antibody and slight depression in her serum complement C3 level. The remainder of her serologic evaluation, including extractable nuclear antigens, anti-double-stranded DNA antibody, antiphospholipid antibodies, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, cryoglobulins, and cold agglutins, were negative. Within weeks of her presentation, she developed acute renal failure and bilateral lower extremity edema. A computed tomography scan of her abdomen and pelvis showed bulky lymphadenopathy and hydronephrosis; a pelvic lymph node biopsy revealed metastatic breast cancer. She was initially managed with passive rewarming strategies, topical antibiotics, vasodilator and anti-platelet therapy, but had a negligible response. However, once she was started on chemotherapy for her recurrent malignancy, there was a significant improvement in her Raynaud’s symptoms and resolution of her digital ulcers.