Lung Disease Associated with Rheumatoid Arthritis

199 Pages·2018·30.57 MB·English

by  Takahisa Gono

Lung Disease
Associated with
Rheumatoid Arthritis
Takahisa Gono
Hitoshi Tokuda
Fumikazu Sakai
Tamiko Takemura
Editors
123
Lung Disease Associated
with Rheumatoid Arthritis
Takahisa Gono • Hitoshi Tokuda
Fumikazu Sakai • Tamiko Takemura
Editors
Lung Disease Associated
with Rheumatoid Arthritis
Editors
Takahisa Gono Hitoshi Tokuda
Department of Allergy and Rheumatology Department of Respiratory Medicine
Nippon Medical School JCHO Tokyo Yamate Medical Center
Graduate School of Medicine Tokyo
Tokyo Japan
Japan
Tamiko Takemura
Fumikazu Sakai Department of Pathology
Department of Diagnostic Radiology Japanese Red Cross Medical Center
Saitama International Medical Center Tokyo
Saitama Medical University Japan
Hidaka, Saitama
Japan
ISBN 978-981-10-6749-5 ISBN 978-981-10-6750-1 (eBook)
https://doi.org/10.1007/978-981-10-6750-1
Library of Congress Control Number: 2017964232
© Springer Nature Singapore Pte Ltd. 2018
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is
concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction
on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not
imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed
to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty,
express or implied, with respect to the material contained herein or for any errors or omissions that may have been
made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Printed on acid-free paper
This Springer imprint is published by Springer Nature
The registered company is Springer Nature Singapore Pte Ltd.
The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore
Preface
Recent advances in the treatment strategy of rheumatoid arthritis (RA), including novel
biological disease-modifying antirheumatic drugs (bDMARDs) and conventional synthetic
DMARDs (csDMARDs), have revolutionized its management, resulting in the successful con-
trol of joint inflammation in a majority of patients and a significant improvement in their
prognosis.
As a systemic inflammatory disease, RA frequently affects not only synovial joints but also
various extra-articular organs. These extra-articular manifestations (EAMs) are the most seri-
ous predisposing factor for morbidity and mortality of RA patients. According to recent epide-
miological studies, these EAMs are decreasing with the introduction of novel therapeutics,
which would explain the improvement in prognosis. However, pulmonary involvements are an
exception; they are becoming more and more serious and now are the major obstacles to the
successful treatment of RA.
In the prebiologics era, lung diseases caused serious problems in the management of RA as
well. As shown in a large-scale cohort study conducted in Japan, they were the major cause of
death of RA patients, together with malignancy. Lung diseases comprise infection, interstitial
lung disease (ILD), and drug-induced pneumonia.
With the introduction of novel DMARDs in the 2000s, severe pulmonary infections and
drug-induced lung disease, along with exacerbations of preexisting ILD, began to occur with
considerable frequency as adverse events of this therapy.
A Japanese cohort study conducted recently reported that among RA patients undergoing
biologics therapy, nearly 50% of the fatalities were attributable to lung diseases such as respi-
ratory infections and ILD. This means that one of the most vital challenges in the current treat-
ment of RA is the control of lung complications.
The risk factors for such severe lung complications under the novel DMARD treatments
have been enthusiastically screened and surveyed by many investigators. However, treatment
strategies to address such complications have not been established in a sufficient manner.
How should we confront these situations? Should patients with risk factors for such com-
plications be excluded from beneficial treatment in this novel era? What should we do to diag-
nose and treat each lung complication, sometimes in slowly progressive disease and sometimes
in acutely developing illness? Except for tuberculosis, no practical guidelines have been for-
mulated so far. In this book, we aim to answer these questions at the best level possible, on the
basis of knowledge obtained from our recent investigations along with the current best evi-
dence available.
First, we clarify the pathogenesis and clinical implications of the lung diseases directly
associated with RA (pulmonary EAMs), including airway diseases and ILD, from various
aspects: clinical, radiological, and pathological.
We emphasize the importance of airway disease, as one of the major risk factors of infec-
tions in RA patients. Also, we show that it can ultimately progress to respiratory failure due to
obstruction of the peripheral airways. A new pathological classification of obliterative bronchi-
olitis is also presented.
We also introduce a new insight into the pathogenesis of honeycombing seen in RA-ILD,
the so-called UIP (usual interstitial pneumonia) type. We clarify that this cystic structural
v
vi Preface
derangement is caused by persistent inflammatory destruction derived from RA in the periph-
eral airways. From this insight, a possible treatment strategy is proposed against the progres-
sion of RA-ILD.
For ILD itself, clinical, radiological, and pathological problems are discussed, with a few of
our original insights inserted among the established knowledge.
Lastly, we discuss the diagnosis and treatment of lung infections and their cognate disor-
ders, including organizing pneumonia and acute diffuse lung disease along with Pneumocystis
pneumonia and drug-induced pneumonia. Here, we propose specific and practical procedures
to handle these complicated conditions.
We believe that the discussions presented here, which contain many of our new ideas and
concepts, will be useful and beneficial for rheumatologists, pneumologists, and radiologists
confronted with this vital clinical challenge, the diagnosis and treatment of lung diseases asso-
ciated with RA.
Tokyo, Japan Takahisa Gono
Tokyo, Japan Hitoshi Tokuda
Saitama, Japan Fumikazu Sakai
Tokyo, Japan Tamiko Takemura
Contents
Part I Introduction
1 Overview: Clinical Significance of Lung Disease Associated
with Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �3
Takahisa Gono
Part II Airway Disease in Rheumatoid Arthritis
2 Comprehensive Understanding of Airway Disease in Rheumatoid Arthritis � � � � �11
Hitoshi Tokuda
3 Pathology of Airway Disease in Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � � � � � �33
Akira Hebisawa, Masashi Kitani, Hirotoshi Matsui, and Atsuhisa Tamura
4 Imaging of Airway Diseases of Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � � � � � � �43
Fumikazu Sakai
5 Therapeutic Strategy for Airway Disease in Rheumatoid Arthritis � � � � � � � � � � � �59
Hitoshi Tokuda
Part III Interstitial Lung Disease in Rheumatoid Arthritis
6 Comprehensive Understanding of Interstitial Lung Disease
in Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �81
Takahisa Gono
7 Pathology of Interstitial Lung Disease in Patients with Rheumatoid Arthritis � � � � �91
Tamiko Takemura
8 Radiological Characteristics of Interstitial Lung Diseases in Patients
with Connective Tissue Disease: Focus on Rheumatoid Arthritis � � � � � � � � � � � � �117
Kiminori Fujimoto
9 Therapeutic Strategies for Interstitial Lung Diseases in Rheumatoid Arthritis � � � �141
Takafumi Suda
Part IV Diagnosis and Treatment of Acute Lung Disease in Rheumatoid Arthritis
10 Bacterial and Fungal Infections in Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � �151
Yutaka Tsuchiya and Hironori Sagara
11 Mycobacterium Infections in Rheumatoid Arthritis (Tuberculosis
and Nontuberculous Mycobacteriosis) � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �165
Hiroshi Moro and Toshiaki Kikuchi
vii
viii Contents
12 Organizing Pneumonia in Rheumatoid Arthritis � � � � � � � � � � � � � � � � � � � � � � � � � �175
Takahisa Gono
13 Acute Pulmonary Infiltrates in Patients with Rheumatoid Arthritis:
Differential Diagnosis and Management� � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �187
Sadatomo Tasaka
Part I
Introduction
Overview: Clinical Significance of Lung 1
Disease Associated with Rheumatoid
Arthritis
Takahisa Gono
Abstract
Rheumatoid arthritis (RA) is an immune-mediated disease that primarily affects joints. In the
2000s, numerous novel antirheumatic agents, called biological disease-modifying antirheu-
matic drugs (bDMARDs) as well as methotrexate, have becom available worldwide. These
developments in treatment have resulted in RA remission or low disease activity in greater than
50% of RA patients. This recent progress has allowed RA patients attain improved physical
function and prognosis. However, treatment-related events, such as infections, have occurred
and occasionally caused severe or fatal outcomes in RA patients. Thus, clinicians must pay
attention to complications during treatment with corticosteroids and/or DMARDs, especially
bDMARDs. Approximately 50% of the causes of death in RA patients treated with bDMARDs
involve respiratory disease, including pneumonia and interstitial lung disease. Therefore, clini-
cians should manage these pulmonary complications promptly. In this book, we will describe
the current status of knowledge about lung disease in RA and would suggest the best form of
management of lung disease in RA patients for clinicians, including general practitioners, rheu-
matologists, respirologists, radiologists, and pathologists. We hope that this book will prove
helpful to all types of medical staff and clinicians who take care of RA patients.
Keywords
Rheumatoid arthritis • Lung disease • Management • bDMARDs
Table 1.1 List of antirheumatic agents
1.1 Introduction
Conventional synthetic DMARDs
Methotrexate
Rheumatoid arthritis (RA) is an autoimmune disease that
Sulfasalazine
primarily affects joints. Recent advances in therapy for RA
Leflunomide
have been hugely beneficial in providing a better outcome Hydroxychloroquine
in patients with arthritis. In the 2000s, numerous novel Biological DMARDs
antirheumatic agents, called biological disease-modifying TNF inhibitor Adalimumab
antirheumatic drugs (bDMARDs) as well as conventional Certolizumab pegol
Etanercept
synthetic DMARDs (csDMARDs), are now available
Golimumab
worldwide as presented in Table 1.1 [1]. These develop-
Infliximab
ments in treatment have resulted in RA remission or low Anti-B cell Rituximab
disease activity in greater than 50% of RA patients [2, 3]. Anti-T cell co-stimulation Abatacept
Anti-IL-6R Tocilizumab
This condition has allowed RA patients to achieve and
Targeted synthetic DMARDs
Tofacitinib
T. Gono, M.D., Ph.D.
Baricitinib
Department of Allergy and Rheumatology, Nippon Medical School,
Graduate School of Medicine, Tokyo, Japan DMARDs disease-modifying antirheumatic disease, TNF tumor necro-
e-mail: [email protected] sis factor, IL-6R interleukin 6 receptor
© Springer Nature Singapore Pte Ltd. 2018 3
T. Gono et al. (eds.), Lung Disease Associated with Rheumatoid Arthritis, https://doi.org/10.1007/978-981-10-6750-1_1