Organisierende Pneumonie als seltene, unerwünschte Wirkung von Tocilizumab bei der Therapie von rheumatoider Arthritis

2020 ◽  
Vol 8 (6) ◽  
pp. 332-333
Author(s):  
Nicolas Carlos Kahn

Interstitial lung disease is a significant extra-articular manifestation of rheumatoid arthritis, due to its prevalence, morbidity and mortality. Biological therapies are widely used for rheumatoid arthritis treatment. However, some biological agents have been related to the induction or exacerbation of interstitial lung disease. We report a 51-year-old woman with knee arthralgia, hand and foot joint deformities. Although there were no respiratory symptoms, rheumatoid arthritis and interstitial lung disease were diagnosed. High-resolution computed tomography (HRCT) detected a radiological pattern of nonspecific interstitial pneumonia. After tocilizumab therapy for nine months, a second HRCT detected a worsening of interstitial lung disease, presenting a pattern of organizing pneumonia. Tocilizumab was discontinued and prednisone (1 mg/kg/day) was introduced. After two months, a further HRCT detected a significant improvement in organizing pneumonia. There are few similar cases in the literature of tocilizumab-induced organizing pneumonia in patients with rheumatoid arthritis. Despite being a rare adverse effect, knowledge of this association is important for monitoring the use of tocilizumab.

2015 ◽  
Vol 47 (2) ◽  
pp. 588-596 ◽  
Author(s):  
Joshua J. Solomon ◽  
Jonathan H. Chung ◽  
Gregory P. Cosgrove ◽  
M. Kristen Demoruelle ◽  
Evans R. Fernandez-Perez ◽  
...  

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a “definite” or “possible” usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.


Cureus ◽  
2020 ◽  
Author(s):  
Mahesh Gautam ◽  
Mah Jabeen Masood ◽  
Sadaf Arooj ◽  
Mufazzal-e-Haque Mahmud ◽  
Muhammad Umer Mukhtar

2017 ◽  
Vol 46 (1) ◽  
pp. 448-456 ◽  
Author(s):  
Daniel Traila ◽  
Cristian Oancea ◽  
Emanuela Tudorache ◽  
Ovidiu Fira Mladinescu ◽  
Bogdan Timar ◽  
...  

Objective Unclassifiable interstitial lung disease (ILD) is a common problem in clinical practice. These patients pose a distinct challenge with regard to appropriate evaluation and management. We investigated the clinical features and prognosis of unclassifiable ILD and compared its clinical profile with that of idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP). Methods Patients with IPF (n = 40), NSIP (n = 14), and unclassifiable ILD (n = 27) were selected from an ongoing database. Baseline clinical features, pulmonary function, and the extent of fibrosis on high-resolution computed tomography (HRCT) were evaluated. Mortality was estimated based on the ILD–Gender, Age, Physiology (ILD-GAP) index and composite physiologic index (CPI). Results IPF was associated with the worst survival (hazard ratio [HR] = 4.361 compared with NSIP), followed by unclassifiable cases (HR = 1.251 compared with NSIP). Increasing mortality was significantly impacted by age (HR = 1.04 per 1-year increase), lower carbon monoxide diffusing capacity of the lung (HR = 0.97), HRCT interstitial score (HR = 1.119 per 1-point increase), ILD-GAP score (HR = 1.570 per 1-point increase), and CPI (HR = 1.039 per 1-point increase). Conclusions Patients with unclassifiable ILD had an intermediate prognosis between that of IPF and NSIP. Patients at high risk of mortality can be identified using baseline clinical, physiological, and radiological features.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 969.1-970
Author(s):  
M. DI Carlo ◽  
M. Tardella ◽  
E. Filippucci ◽  
F. Salaffi

Background:In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. LUS allows the detection of artifacts (B-lines) characteristic of ILD, without the need to use ionizing radiation. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD.Objectives:To determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods:A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS, chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of HRCT using a computer-aided method (CaM). The 10% of fibrosis, measured with this method, was considered as a cut-off for the presence of significant RA-ILD. The LUS was carried out in 14 defined intercostal spaces using a linear multifrequency probe 6-18 MHz (MyLab Class C, Esaote S.p.A., Genoa, Italy) and the number of B-lines present in each intercostal space was counted and summed up (Figure 1). The discriminating validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Figure 1.LUS B-line illustrative.Results:72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years), a mean ACPA titre of 327.6 (SD 633.3) U/ml and a rheumatoid factor of 324.6 (SD 748.7) U/ml. The mean estimate of pulmonary fibrosis using the CaM was 11.2% (SD 7.5) at HRCT, while at LUS the mean number of B-lines was 10.6 (SD 15.1). Pulmonary fibrosis of 10% as measured by the CaM at HRCT was detected in 25 patients (34.72%). Applying this HRCT cut-off point as an estimate of significant fibrosis, the presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant fibrosis with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4 (Figure 2).Figure 2.Area under the ROC curve to determine the number of B-lines at LUS to define a significant RA-ILD, applying the 10% of fibrosis at chest HRCT measured by OsiriX as external criterion.Conclusion:The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.References:[1] Tardella M, et al. Ultrasound B-lines in the evaluation of interstitial lung disease in patients with systemic sclerosis: Cut-off point definition for the presence of significant pulmonary fibrosis. Medicine (Baltimore). 2018;97(18):e0566.[2] Salaffi F, et al. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore). 2019;98(38):e17088.Disclosure of Interests:Marco Di Carlo: None declared, Marika Tardella: None declared, Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work., Fausto Salaffi: None declared


2020 ◽  
Vol 79 (5) ◽  
pp. 587-594 ◽  
Author(s):  
Raul Castellanos-Moreira ◽  
Sebastian Cruz Rodríguez-García ◽  
Maria Jose Gomara ◽  
Virginia Ruiz-Esquide ◽  
Andrea Cuervo ◽  
...  

ObjectiveTo analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.MethodsCross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.ResultsWe enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.ConclusionsAnti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1056.1-1056
Author(s):  
P. Muñoz Reinoso ◽  
F. J. Toyos Sáenz de Miera ◽  
D. Ruiz-Montesinos ◽  
I. García Hernández ◽  
P. Guerrero Zamora ◽  
...  

Background:Diffuse interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA)1,2. The most common pattern is the usual interstitial pneumonia (UIP), conditioning a worse prognosis3.Objectives:To describe epidemiological, clinical, and radiological characteristics and treatment used in a cohort of patients diagnosed with RA and ILD.Methods:Retrospective descriptive study, including patients with a diagnosis of RA and ILD, reviewed in the Rheumatology and Pneumology consultations of the Virgen Macarena University Hospital, from 2010 to 2019. Data obtained from medical records are analyzed. SPSS statistical software is used.Results:26 patients were included, 18 women (69.2%). Median age at diagnosis of ILD was 62 years (53-73). Twelve patients (46.6%) used to smoke. The mean time from RA diagnosis to ILD diagnosis was 79 months (8-264). The RF was positive in 91.3% cases (21) and 87% of them (20) were ACPA positive. Fourteen patients (53.8%) had erosions and 3 (11.5%) had an associated Sjögren’s Syndrome. When ILD was diagnosed, the RA activity by DAS28PCR was moderate (3.28; 2.34-3.28) and 13 patients (54.1%) suffered from dyspnea. The mean value of FVC and DLCO in the first assessment was 84% (63-108) and 71.7% (64-86), respectively. The most frequent radiological pattern of ILD was NINE in 15 patients (57.7%), 6 of them (23.1%) had UIP and 5 (19.3%) presented other patterns. Prior to ILD diagnosis, 24 (92.3%) patients received oral glucocorticoids, 18 (69.2%) cases started treatment with c-DMARD and 11 (42.3%) of them with b-DMARD; the most widely used were methotrexate (MTX) in 17 patients (65.4%) and anti-TNFα in 10 (38.5%). After diagnosis, treatment was changed to 12 patients (46.6%); the most used DMARD was leflunomide, in 11 (42.3%), MTX was maintained in 7 patients (26.9%); the number of anti-TNFα used decreased to 4 cases (15.4%), using instead drugs such as rituximab 5 (19.2%), abatacept 3 (11.5%), baricitinib 2 (7.7%) and anti-IL6 2 (7, 7%). During follow-up, 11 cases (57.9%) remained radiologically stable. A slight deterioration in DLCO was observed (66%; 51-80) and there was one death due to lung disease (UIP).Conclusion:In this study, the most frequent radiological pattern was NINE. Half of the patients used to smoke. At the diagnosis of ILD (at ILD diagnosis), dyspnea was the most relevant clinical symptom, with a slight deterioration in the? respiratory function tests. This represented a change in the therapeutic strategy.References:[1]Olson AL, Swigris JJ, Sprunger DB, et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011;183:372-78.[2]Fragoulis GE, Nikiphorou E, Larsen J, Korsten P and Conway R. Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment. Front. Med. 2019;6:238.[3]Tanaka N, Kim JS, Newell JD, et al. Rheumatoid arthritis-related lung diseases: CT findings. Radiology. 2004;232:81-91.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 600.2-600
Author(s):  
C. Aguilera Cros ◽  
M. Gomez Vargas ◽  
R. J. Gil Velez ◽  
J. A. Rodriguez Portal

Background:Among the risk factors associated with the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) are: male sex, old age, erosive RA, rheumatoid nodules, smoking and high levels of rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA). The factors of poor prognosis include: HRCT (High Resolution Computed Tomography) pattern of usual interstitial pneumonia (NIU) with altered baseline functional tests (forced vital capacity FVC <60%, diffusion capacity of the lung for carbon monoxide DLCO<40%).RA associated UIP (RA-UIP) has an appearance that is identical to idiopathic UIP (idiopathic pulmonary fibrosis [IPF]) on HRCT.Objectives:To analyze different risk factors and poor prognosis in a cohort of patients with ILD-RA.To assess the degree of association between tobacco (smokers, ex-smokers and non-smokers) and altered baseline functional respiratory tests (FRT) (FVC <80% and DLCO <40%) with HRCT patterns.Methods:Descriptive study of 57 patients treated in our Hospital (1/1/2018 until 12/31/2019) with a diagnosis of RA (ACR 2010 criteria) and secondary ILD.The most recent American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines define three HRCT (High Resolution Computed Tomography) patterns of fibrosing lung disease in the setting of idiopathic pulmonary fibrosis (IPF): definite UIP (traction bronchiectasis and honeycombing), possible UIP and inconsistent with UIP. The distinction between definite UIP and possible UIP in these to the presence or absence of honeycombing. Approved by the Ethics Committee.Quantitative variables are expressed as mean (SD) and dichotomous variables as percentages (%). The association between tobacco-UIP and FVC-UIP was studied using two Chi-square tests and the DLCO-UIP relationship with an exact Fisher test. Statistical analysis with SPSS version 21.Results:21 men and 36 women were included, with a mean age of 69 ± 10 years (mean ± SD), history of smoking (smokers 14%, non-smokers 43%, ex-smokers 42%). 83% were positive RF and 70% positive ACPA. Regarding the HRCT findings: 29 (50%) had a inconsistent with UIP pattern and 28 (49%) had an UIP pattern (45% defined, 3% possible). Of the UIP patients, 14 (50%) had a smoking relationship (35% ex-smokers, 25% smokers) and 15 were male (53%). Of the sample analyzed, 8% (5 patients) have died, all ex-smoking men, the UIP pattern being the most frequent found (4 UIP, 1 inconsistent with UIP).No statistical association was observed between patients with exposure to tobacco and the UIP pattern (p = 0.438), nor among patients with baseline FVC <80% and UIP (p = 0.432) and also among patients with baseline DLCO <40% and UIP pattern (p = 0.459).Conclusion:Our results, in general, do not match what is published in the literature. Male sex, smoking exposure and fibrosing pattern (UIP) represent a worse prognosis for patients with ILD-RA. However, more studies are required to determine more precisely how these risk factors affect the disease.Disclosure of Interests:None declared


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