Organizing pneumonia after rituximab therapy: Two cases

doi:10.1016/j.jbspin.2007.10.009

Joint Bone Spine

Volume 75, Issue 3, May 2008, Pages 362-365

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Abstract

Rituximab, a chimeric monoclonal antibody against CD20, very rarely causes lung toxicity. Clinical presentations include lung infiltrates, alveolar hemorrhage, and adult respiratory distress syndrome. Three cases of organizing pneumoinia (formerly called bronchiolitis obliterans with organizing pneumonia or BOOP) have been reported. In our experience, organizing pneumonia occurred in 2 of 25 patients treated with rituximab, for RA and Castleman's disease, respectively. Because organizing pneumonia may be asymptomatic, as illustrated by one of our cases, we recommend obtaining a chest radiograph routinely before rituximab re-treatment.

Section snippets

Case report 1

This 64-year-old woman who had seropositive RA with joint erosions diagnosed 4 years earlier, in 2002, was taking 5–10 mg of prednisone per day in combination with methotrexate, then leflunomide, and finally methotrexate plus anakinra. TNFα antagonists were not used, as she had a history of lower-limb paralysis at 25 years of age consistent with a possible demyelinating disease. In October 2006, her disease remained active, as shown by the following variables: visual-analog-scale pain score,

Case report 2

A 55-year-old woman with RA since 1970 had joint destruction despite limited disease activity. She had a history of valve replacement surgery in 2003 to treat aortic incompetence. In 2001, she was evaluated for urticarial vasculitis, high blood eosinophil counts, and marked bilateral lymph-node enlargement at multiple sites (groin, axilla, retroperitoneal space, and pelvis). Lymph-node biopsy findings consisted of atypical lymphoid hyperplasia, immunoblasts, and numerous polyclonal plasma

Discussion

The clinical, lung function test, and imaging findings in organizing pneumonia lack specificity, so that the definitive diagnosis is dependent on obtaining a histological specimen [8]. The diagnosis was confirmed histologically in both of our patients. A gradually worsening dry cough with dyspnea, a fever, and asthenia are the most common clinical manifestations [8], [9]. Chest pain may be a feature, as in our patient #1. The disease may be discovered fortuitously when a chest radiograph is

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Beyond the joints, the extra-articular manifestations in rheumatoid arthritis
2021, Autoimmunity Reviews
Citation Excerpt :
This pattern may be primarily due to RA but also it could be secondary to drug hypersensitivity. In fact, it has been reported following therapies with rituximab, MTX, etanercept, and sulfasalazine [181,182,183]. LIP is a benign lymphoproliferative disorder which is histologically characterized by a diffuse, polyclonal interstitial infiltrate of lymphoid cells [184,185].
Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.
The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.
Effect of rituximab on pulmonary function in patients with rheumatoid arthritis
2016, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
However, side effects were reported to occur preferentially in patients with NHL [4,11,12]. Knowledge on RTX-induced pulmonary toxicity is still scarce and limited to case reports and small case series including up to nine patients [13–27]. Since some of these adverse events are supposedly related to circulating tumor loads of NHL, fewer events are observed in non-oncological diseases [9].
Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking.
Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined as indicative for pulmonary toxicity.
Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a ≥15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone.
Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity.
Pulmonary Complications of Stem Cell and Solid Organ Transplantation
2015, Murray and Nadel's Textbook of Respiratory Medicine: Volume 1,2, Sixth Edition
Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review
2014, Seminars in Arthritis and Rheumatism
Citation Excerpt :
With regard to nbDMARDs, we found 32 articles for MTX (26 for the acute/subacute form [7–32] and 6 for the chronic form [33–38]), 12 for LEF [39–50] (with a total of 34 cases—Table 1), 3 for gold [4,51,52], 1 for AZA [53], and 4 for SSZ [54–57]. Regarding biologics, we identified 27 articles for TNFi (including 24 articles of TNFi-related ILD in RA patients [58–81], and 3 of RA-ILD improved by TNFi [82–84]), 3 for RTX [85–87], 5 for TCZ [88–92], and 1 for ABA [93]. No cases were found for anakinra or for HCQ.
To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice.
We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010–2012 and EULAR 2010–2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes.
The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs.
As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.
Pulmonary Manifestations of Collagen Diseases
2013, Archivos de Bronconeumologia
Citation Excerpt :
In Japan, an incidence of 0.5% of ILD in patients treated with leflunomide has been described.38 Until now, a few cases of ILD associated with tocilizumab have been identified: one case in the series of Smolen et al.39 and one isolated case described by Kawasshiri et al.40 Several cases of ILD associated with ritiximab treatment have also been noted in patients with lymphoma39 and some cases of organizing pneumonia have been reported in patients diagnosed with RA after commencing rituximab treatment.41,42 Pulmonary complications could be responsible for 10%–20% of the mortality in patients with RA.
Collagen diseases are a large group of systemic inflammatory diseases of autoimmune etiology. The etiopathogenesis of collagen diseases is multifactorial. There is genetic susceptibility, as many connective tissue disorders show family history, and environmental factors may trigger the disease. Collagen diseases can affect almost all the organs of the body. The respiratory system is one of the most frequently affected, although the prevalence of pulmonary disease is not precisely known for the different collagen disorders. Any structure of the respiratory tract can be affected, but perhaps the most frequent is pulmonary parenchymal disease in the form of pneumonitis, which can be produced in any of the idiopathic interstitial pneumonitis patterns. The pleura, pulmonary vessels, airways and respiratory muscles may also be affected. The frequency of lung disease associated with collagen diseases is on the rise. This is in due part to the better diagnostic methods that are available to us today (such as high-resolution computed tomography) and also to the appearance of new forms of pneumonitis associated with the new treatments that are currently used. The objective of this article is to offer a global vision of how collagen diseases can affect the lungs according to the latest scientific evidence.
Las enfermedades del colágeno constituyen un gran grupo de enfermedades inflamatorias sistémicas de etiología autoinmune. La etiopatogenia de las enfermedades del colágeno es multifactorial. Existe una susceptibilidad genética, y muchos trastornos del tejido conectivo muestran una agregación familiar, sobre la que actúan factores ambientales que desencadenan la enfermedad. En las enfermedades del colágeno se pueden afectar casi todos los órganos del cuerpo. El sistema respiratorio es uno de los más frecuentemente afectados, aunque no se conoce con exactitud la prevalencia de enfermedad pulmonar en las diferentes enfermedades del colágeno. Cualquier estructura del aparato respiratorio puede estar afectada. Quizá lo más frecuente sea la enfermedad del parénquima pulmonar en forma de neumonitis, que puede manifestarse como cualquiera de los patrones de neumonitis intersticiales idiopáticas. Pero también pueden afectarse la pleura, los vasos pulmonares, la vía aérea y la musculatura respiratoria. La frecuencia de enfermedad pulmonar asociada a las enfermedades del colágeno está aumentando, por una parte gracias a los mejores métodos de diagnóstico de que disponemos hoy en día, como la tomografía computarizada de alta resolución, y también por la aparición de nuevas formas de neumonitis asociadas a los nuevos tratamientos empleados en la actualidad. El objetivo de este artículo es ofrecer una visión en conjunto de cómo las enfermedades del colágeno pueden afectar el pulmón, de acuerdo con las nuevas evidencias científicas.
Clinical Characteristics and Predictors of the Recurrence of Organizing Pneumonia Associated With Rheumatoid Arthritis
2023, Journal of Rheumatology

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Case reportOrganizing pneumonia after rituximab therapy: Two cases

Abstract

Section snippets

Case report 1

Case report 2

Discussion

Cancer Treat Rev

Blood

Respir Med

Semin Arthritis Rheum

Am J Med Sci

Treatment of Castleman's disease

Curr Treat Options Oncol

Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006

Ann Rheum Dis

Case report
Organizing pneumonia after rituximab therapy: Two cases