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Yavordios S, Beltramo G, Freppel R, Beau Salinas F, Le Beller C, Bihan K, Mouillot P, Georges M, Grandvuillemin A, Bonniaud P. Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French Pharmacovigilance Database. Eur Respir J 2025; 65:2400756. [PMID: 39510554 DOI: 10.1183/13993003.00756-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 10/09/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung disease (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through adverse drug reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs. METHODS This retrospective study included cases registered in the FPVD from 1 January 1985 to 1 April 2022 which had ADRs coded in MedDRA with a High-Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged ≥18 years. RESULTS We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and death ensued in 13.3%. Males accounted for 54.4% of the cases. Median (range) age was 69 (18-103) years. The most prevalent ADRs were "Interstitial lung disease" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). Anti-cancer drugs (31.2%) and cardiovascular drugs (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%). CONCLUSION This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify the diseases properly and discontinue the culprit drug urgently.
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Affiliation(s)
- Sophie Yavordios
- Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, Réseau OrphaLung, Filière RespiFil, CHU Dijon-Bourgogne, Dijon, France
| | - Guillaume Beltramo
- Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, Réseau OrphaLung, Filière RespiFil, CHU Dijon-Bourgogne, Dijon, France
- INSERM U1231, Labex LIPSTIC and label of excellence from La Ligue Nationale Contre le Cancer, Dijon, France
- Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France
| | - Romane Freppel
- Regional Pharmacovigilance Centre, François Mitterrand Hospital, University of Burgundy Franche-Comté, Dijon, France
| | - Frédérique Beau Salinas
- Regional Pharmacovigilance Centre of Centre Val de Loire, Department of Pharmacosurveillance, University Hospital of Tours, Tours, France
| | - Christine Le Beller
- Regional Pharmacovigilance Centre, Hôpital Européen Georges Pompidou, AP-HP, Centre - Université Paris Cité, Paris, France
- Paris Cité University, Innovative Therapies in Haemostasis, INSERM, Paris, France
| | - Kevin Bihan
- Pharmacology Department, AP-HP, GHU Sorbonne University, Regional Pharmacovigilance Centre Pitié-Saint Antoine, Paris, France
| | - Pierre Mouillot
- Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, Réseau OrphaLung, Filière RespiFil, CHU Dijon-Bourgogne, Dijon, France
| | - Marjolaine Georges
- Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, Réseau OrphaLung, Filière RespiFil, CHU Dijon-Bourgogne, Dijon, France
- Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France
| | - Aurélie Grandvuillemin
- Regional Pharmacovigilance Centre, François Mitterrand Hospital, University of Burgundy Franche-Comté, Dijon, France
- A. Grandvuillemin and P. Bonniaud contributed equally to this work
| | - Philippe Bonniaud
- Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence Constitutif des Maladies Pulmonaires Rares de l'Adultes de Dijon, Réseau OrphaLung, Filière RespiFil, CHU Dijon-Bourgogne, Dijon, France
- INSERM U1231, Labex LIPSTIC and label of excellence from La Ligue Nationale Contre le Cancer, Dijon, France
- Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France
- A. Grandvuillemin and P. Bonniaud contributed equally to this work
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Atzeni F, Alciati A, Gozza F, Masala IF, Siragusano C, Pipitone N. Interstitial lung disease in rheumatic diseases: an update of the 2018 review. Expert Rev Clin Immunol 2025; 21:209-226. [PMID: 39302018 DOI: 10.1080/1744666x.2024.2407536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 07/25/2024] [Accepted: 09/18/2024] [Indexed: 09/22/2024]
Abstract
INTRODUCTION Interstitial lung disease (ILD) is a potential severe complication of various rheumatic diseases, typically connective tissue diseases (CTD), associated with significant morbidity and mortality. ILD may occur during the course of the disease but may also be its first manifestation. Several cell types are involved in ILD's pathogenesis, and if not controlled, pulmonary inflammation may lead to pulmonary fibrosis. AREAS COVERED We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and February 2017 in the first version, and between 2017 and April 2023 using combinations of words. The most frequent systemic rheumatic diseases associated with ILD are systemic sclerosis (SSc), rheumatoid arthritis (RA), and idiopathic inflammatory myositis. Treatment and monitoring guidelines are still lacking, and current treatment strategies have been extrapolated from the literature on SSc and established treatments for non-pulmonary systemic rheumatic manifestations. EXPERT OPINION Given the complexity of diagnosis and the paucity of treatment trials, managing CTD patients with ILD is challenging. It requires the skills of multidisciplinary CTD-ILD clinics including at least rheumatologists and lung specialists.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Alessandra Alciati
- Department of Clinical Neurosciences, Villa S. Benedetto Menni, Albese, Como, Italy
- Humanitas Clinical and Research Center, Rozzano, Italy
| | - Francesco Gozza
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | | | - Cesare Siragusano
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Nicolò Pipitone
- Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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David M, Dieude P, Debray MP, Le Guen P, Crestani B, Borie R. [Low-dose methotrexate: Indications and side effects, particularly in cases of diffuse interstitial pneumonia]. Rev Mal Respir 2024; 41:605-619. [PMID: 39025770 DOI: 10.1016/j.rmr.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 06/09/2024] [Indexed: 07/20/2024]
Abstract
INTRODUCTION Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use. STATE OF THE ART In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD). PERSPECTIVES AND CONCLUSIONS Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.
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Affiliation(s)
- M David
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France.
| | - P Dieude
- Université Paris Cité, Inserm, PHERE, 75018 Paris, France; Service de rhumatologie A, hôpital Bichat, AP-HP, Paris, France
| | - M P Debray
- Service de radiologie, hôpital Bichat, AP-HP, Paris, France
| | - P Le Guen
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
| | - B Crestani
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
| | - R Borie
- Service de pneumologie A, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France; Université Paris Cité, Inserm, PHERE, 75018 Paris, France
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Jesuthasan A, Baheerathan A, Auger S, Dorsey R, Coker R, Selvapatt N, Viegas S. Methotrexate for the neurologist. Pract Neurol 2024; 24:369-375. [PMID: 38821881 DOI: 10.1136/pn-2024-004156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2024] [Indexed: 06/02/2024]
Abstract
The use of methotrexate in clinical practice has expanded significantly in recent years, as an effective chemotherapeutic agent as well as disease-modifying treatment for conditions such as rheumatoid arthritis, psoriasis and Crohn's disease. It is also used as a steroid-sparing agent for a range of inflammatory diseases of the central and peripheral nervous systems. Clinical neurologists must, therefore, know how to start and uptitrate methotrexate, its monitoring requirements and its potential toxicities. This review aims first to explore the evidence base for using methotrexate in various neurological diseases and second to discuss important practicalities around its use, ensuring its safe application and appropriate monitoring.
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Affiliation(s)
| | | | - Stephen Auger
- Department of Neurology, Charing Cross Hospital, London, UK
| | - Rachel Dorsey
- Department of Neurology, Charing Cross Hospital, London, UK
| | - Robina Coker
- Department of Respiratory Medicine, Hammersmith Hospital, London, UK
| | | | - Stuart Viegas
- Department of Neurology, Charing Cross Hospital, London, UK
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Medhat D, El-Bana MA, El-Tantawy El-Sayed I, Ahmed AAS, El-Naggar ME, Hussein J. Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model. Biol Proced Online 2024; 26:16. [PMID: 38831428 PMCID: PMC11149278 DOI: 10.1186/s12575-024-00240-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 04/30/2024] [Indexed: 06/05/2024] Open
Abstract
BACKGROUND It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1β), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.
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Affiliation(s)
- Dalia Medhat
- Medical Biochemistry Department, Medical Research and Clinical Studies Institute, National Research Centre, 12622, Dokki, Giza, Egypt.
| | - Mona A El-Bana
- Medical Biochemistry Department, Medical Research and Clinical Studies Institute, National Research Centre, 12622, Dokki, Giza, Egypt
| | | | - Abdullah A S Ahmed
- Chemistry Department, Faculty of Science, Menoufia University, 32511, Shebin El Koom, Egypt
| | - Mehrez E El-Naggar
- Institute of Textile Research and Technology, National Research Centre, 12622, Dokki, Giza, Egypt
| | - Jihan Hussein
- Medical Biochemistry Department, Medical Research and Clinical Studies Institute, National Research Centre, 12622, Dokki, Giza, Egypt
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Chan JCK, Boland JM. Granulomatous Lung Diseases: A Practical Approach and Review of Common Entities. Surg Pathol Clin 2024; 17:173-192. [PMID: 38692803 DOI: 10.1016/j.path.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
Abstract
Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes.
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Affiliation(s)
- Jackie Cheuk Ki Chan
- Department of Laboratory Medicine and Pathology, Royal Alexandra and University of Alberta Hospitals, 10240 Kingsway NW, Edmonton, Alberta, Canada, T5H 3V9
| | - Jennifer M Boland
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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Harrison M, Kavanagh G, Corte TJ, Troy LK. Drug-induced interstitial lung disease: a narrative review of a clinical conundrum. Expert Rev Respir Med 2024; 18:23-39. [PMID: 38501199 DOI: 10.1080/17476348.2024.2329612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 03/08/2024] [Indexed: 03/20/2024]
Abstract
INTRODUCTION Drug-induced interstitial lung disease (DI-ILD) is increasing in incidence, due to the use of many new drugs across a broad range of cancers and chronic inflammatory diseases. The presentation and onset of DI-ILD are variable even for the same drug across different individuals. Clinical suspicion is essential for identifying these conditions, with timely drug cessation an important determinant of outcomes. AREAS COVERED This review provides a comprehensive and up-to-date summary of epidemiology, risk factors, pathogenesis, diagnosis, treatment, and prognosis of DI-ILD. Relevant research articles from PubMed and Medline searches up to September 2023 were screened and summarized. Specific drugs including immune checkpoint inhibitors, CAR-T cell therapy, methotrexate, and amiodarone are discussed in detail. The potential role of pharmacogenomic profiling for lung toxicity risk is considered. EXPERT OPINION DI-ILD is likely to be an increasingly important contributor to respiratory disability in the community. These conditions can negatively impact quality of life and patient longevity, due to associated respiratory compromise as well as cessation of evidence-based therapy for the underlying disease. This clinical conundrum is relevant to all areas of medicine, necessitating increased understanding and greater vigilance for drug-related lung toxicity.
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Affiliation(s)
- Megan Harrison
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Grace Kavanagh
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Tamera J Corte
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Lauren K Troy
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
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Kameda H, Yamaoka K, Yamanishi Y, Tada M, Koike R, Nakajima A, Fusama M, Fujii T. Japan College of Rheumatology guidance for the use of methotrexate in patients with rheumatoid arthritis: Secondary publication. Mod Rheumatol 2023; 34:1-10. [PMID: 37819199 DOI: 10.1093/mr/road098] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/17/2023] [Accepted: 09/23/2023] [Indexed: 10/13/2023]
Abstract
Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6-8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5-15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities.
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Affiliation(s)
- Hideto Kameda
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University, Tokyo, Japan
| | - Kunihiro Yamaoka
- Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan
| | | | - Masahiro Tada
- Department of Orthopaedic Surgery, Osaka City General Hospital, Osaka, Japan
| | - Ryuji Koike
- Health Science Research and Development Center of Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Nakajima
- Center for Rheumatic Diseases, Mie University Hospital, Mie, Japan
- Department of Rheumatology, Mie University Graduate School of Medicine, Mie, Japan
| | - Mie Fusama
- School of Nursing, Takarazuka University, Osaka, Japan
| | - Takao Fujii
- Department of Rheumatology and Clinical Immunology, Wakayama Medical University, Wakayama, Japan
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Nishii Y, Okamoto M, Zaizen Y, Kojima T, Nouno T, Naitou-Nishida Y, Matsuo N, Takeoka H, Ishida M, Nakamura M, Masuda T, Tanaka T, Miyamura T, Hoshino T. Successful Treatment of a Patient with Drug-Refractory Rheumatoid Arthritis-Associated Interstitial Lung Disease with Upadacitinib: A Case Report. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1960. [PMID: 38004009 PMCID: PMC10673512 DOI: 10.3390/medicina59111960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/30/2023] [Accepted: 11/03/2023] [Indexed: 11/26/2023]
Abstract
Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that exhibited favorable response to upadacitinib. A 69-year-old man, former smoker, was diagnosed with RA-ILD based on persistent symmetric polyarthritis, elevated C-reactive protein levels and erythrocyte sedimentation rate, reduced diffusing capacity for carbon monoxide/alveolar volume (DLCO 69.9%), and bilateral ground-glass attenuation with traction bronchiectasis, predominantly in the lower lung lobe. Initial treatment with oral prednisolone and methotrexate was started; however, the patient showed worsening dyspnea, chest high-resolution computed tomography abnormalities, and decreased pulmonary function. The dose of prednisolone was increased, and methotrexate was shifted to tacrolimus; however, tacrolimus was eventually discontinued because of renal dysfunction. Subsequent treatment changes included abatacept followed by intravenous cyclophosphamide, but ILD activity continued to worsen and met the criteria of progressive pulmonary fibrosis. Approximately 4.5 years after the RA diagnosis, dyspnea, radiological abnormalities, and DLCO improved following treatment switch to upadacitinib, one of JAKis. JAKi therapy may have potential as a treatment option for refractory RA-ILD.
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Affiliation(s)
- Yuuya Nishii
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Masaki Okamoto
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Yoshiaki Zaizen
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Takashi Kojima
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Takashi Nouno
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Yoshiko Naitou-Nishida
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Norikazu Matsuo
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Hiroaki Takeoka
- Department of Respirology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
| | - Motoko Ishida
- Department of Internal Medicine and Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| | - Masataka Nakamura
- Department of Internal Medicine and Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| | - Toru Masuda
- Department of Internal Medicine and Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| | - Takafumi Tanaka
- Department of Internal Medicine and Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| | - Tomoya Miyamura
- Department of Internal Medicine and Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-0065, Japan
| | - Tomoaki Hoshino
- Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan
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Cavalli CAM, Gabbiadini R, Dal Buono A, Quadarella A, De Marco A, Repici A, Bezzio C, Simonetta E, Aliberti S, Armuzzi A. Lung Involvement in Inflammatory Bowel Diseases: Shared Pathways and Unwanted Connections. J Clin Med 2023; 12:6419. [PMID: 37835065 PMCID: PMC10573999 DOI: 10.3390/jcm12196419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/01/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract, frequently associated with extraintestinal manifestations (EIMs) that can severely affect IBD patients' quality of life, sometimes even becoming life-threatening. Respiratory diseases have always been considered a rare and subsequently neglected extraintestinal manifestations of IBD. However, increasing evidence has demonstrated that respiratory involvement is frequent in IBD patients, even in the absence of respiratory symptoms. Airway inflammation is the most common milieu of IBD-related involvement, with bronchiectasis being the most common manifestation. Furthermore, significant differences in prevalence and types of involvement are present between Crohn's disease and ulcerative colitis. The same embryological origin of respiratory and gastrointestinal tissue, in addition to exposure to common antigens and cytokine networks, may all play a potential role in the respiratory involvement. Furthermore, other causes such as drug-related toxicity and infections must always be considered. This article aims at reviewing the current evidence on the association between IBD and respiratory diseases. The purpose is to raise awareness of respiratory manifestation among IBD specialists and emphasize the need for identifying respiratory diseases in early stages to promptly treat these conditions, avoid worsening morbidity, and prevent lung damage.
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Affiliation(s)
- Carolina Aliai Micol Cavalli
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Roberto Gabbiadini
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
| | - Arianna Dal Buono
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
| | - Alessandro Quadarella
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Alessandro De Marco
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
- Division of Gastroenterology and Digestive Endoscopy, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
| | - Edoardo Simonetta
- Respiratory Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Stefano Aliberti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
- Respiratory Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy;
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (C.A.M.C.); (R.G.); (A.D.B.); (A.Q.); (A.D.M.); (C.B.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy; (A.R.); (S.A.)
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11
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Ren K, Yong C, Wang Y, Wei H, Zhao K, He B, Cui M, Chen Y, Wang J. Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations. Infect Drug Resist 2023; 16:6195-6208. [PMID: 37724090 PMCID: PMC10505384 DOI: 10.2147/idr.s420244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/22/2023] [Indexed: 09/20/2023] Open
Abstract
Aim The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.
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Affiliation(s)
- Keyu Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Chunming Yong
- Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yanting Wang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Hongyun Wei
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Kun Zhao
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Baoguo He
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Mingjuan Cui
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yunqing Chen
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Jin Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
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12
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Shen X, Wang F. The additional treatment value of immunoglobulin for the treatment of rheumatoid arthritis complicated with interstitial lung disease: A propensity score-matched pilot study. Int J Rheum Dis 2023; 26:1745-1750. [PMID: 37507851 DOI: 10.1111/1756-185x.14808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 05/03/2023] [Accepted: 06/19/2023] [Indexed: 07/30/2023]
Abstract
OBJECTIVE To explore the additional treatment value of intravenous immunoglobulin injections for treating interstitial lung disease (ILD) caused by rheumatoid arthritis (RA). METHODS This pilot study included patients with RA-ILD. The RA-ILD patients were grouped by treatment agents: traditional agents (disease-modifying antirheumatic drugs, [D]MARDs] and glucocorticoids) and traditional agents plus immunoglobulin. A propensity matching score (PSM) was performed to balance the bias of baseline characteristics. The treatment efficacy and safety indicators were analyzed and compared between the two groups. RESULTS In total, 134 patients were included in this study. After PSM, 80 patients were finally included, with 40 in each group. The immunoglobulin group consisted of 12 men and 28 women with a mean age of 51.5 ± 8.4 years (22-75 years). The control group included 13 men and 27 women, with a mean age of 50.6 ± 8.2 years (25-74 years). The chronic obstructive pulmonary disease assessment test score in the immunoglobulin group was statistically lower after treatment than in the control group (19.1 ± 3.3 vs. 17.7 ± 3.4, p = .03). The 6-min walking distance (364.4 ± 54.3 vs. 332.3 ± 55.1, p = .04) and forced vital capacity (78.8 ± 12.6 vs. 66.6 ± 11.2, p = .05) were statistically higher in the immunoglobulin group. The high-resolution computed tomography score and erythrocyte sedimentation rate were both statistically lower in the immunoglobulin group (both p < .05). The adverse event rate did not differ between the two groups (p = .61). CONCLUSION The additional use of immunoglobulin intravenous injection is effective for the treatment of RA-ILD with no additional adverse effects.
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Affiliation(s)
- Xiaoxia Shen
- Department of respiratory disease, 72nd Group Army Hospital, Huzhou University, Huzhou, China
| | - Fei Wang
- Department of respiratory disease, 72nd Group Army Hospital, Huzhou University, Huzhou, China
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13
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Tiew HW, Tan JWP, Teo CHY. Delayed organising pneumonia in an immunocompromised host after a mild COVID-19 infection. BMJ Case Rep 2023; 16:16/5/e254737. [PMID: 37192779 DOI: 10.1136/bcr-2023-254737] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2023] Open
Abstract
Organising pneumonia after a mild COVID-19 infection has been increasingly reported and poses a diagnostic challenge to physicians especially in immunocompromised patients. We report a patient with a background of lymphoma in remission on rituximab who presented with prolonged and persistent fever after recovering from a mild COVID-19 infection. The initial workup showed bilateral lower zone lung consolidation; however, the infective and autoimmune workup were unremarkable. Subsequently, a bronchoscopy with transbronchial lung biopsy confirmed the diagnosis of organising pneumonia. A tapering glucocorticoid regimen was commenced with prompt resolution of the patient's clinical symptoms, and subsequent resolution of biochemical markers and radiological lung changes 3 months later. This case highlights the importance of early recognition of the diagnosis of organising pneumonia in immunocompromised populations after a mild COVID-19 infection as it shows promising response to glucocorticoid therapy.
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Affiliation(s)
- Han Wei Tiew
- General Medicine, Tan Tock Seng Hospital, Singapore, Singapore
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14
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Rakez R, Boufrikha W, Cheffaï A, Boukhriss S, Laatiri MA. High-dose methotrexate-related pneumonitis in a child with acute lymphoblastic leukemia. J Oncol Pharm Pract 2023; 29:506-510. [PMID: 35854419 DOI: 10.1177/10781552221112160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Methotrexate is administered through different routes to treat childhood acute lymphoblastic leukemia. Toxicities of low, intermediate, or high doses of methotrexate have been described in the literature. Methotrexate-induced or related pneumonitis is a rare complication that leads, in most cases, to discontinuing this drug. CASE REPORT We report a case of a 17-year-old female patient with newly diagnosed B-acute lymphoblastic leukemia who received a high-dose methotrexate on an induction course. Eight days after methotrexate infusion, she developed fever, dyspnea, hypoxemia, and dry cough. Chest computed tomography showed mosaic attenuation of lung parenchyma and bilateral interstitial infiltrate in favor of hypersensitivity pneumonitis with no evidence of bacterial or fungal infections. MANAGEMENT AND OUTCOME Methotrexate-related pneumonitis was diagnosed and corticosteroids were prescribed. Improvement of the symptomatology was noted within four days. Given the importance of methotrexate in the treatment of acute lymphoblastic leukemia, intrathecal methotrexate was administered without incident and high-dose methotrexate was re-introduced successfully two and a half months after the pneumonitis episode while using corticosteroids. According to Naranjo's algorithm, the reaction to the drug was found to be probable with a score of 6. DISCUSSION Methotrexate is the backbone of acute lymphoblastic leukemia treatment, but numerous adverse reactions have been published of which methotrexate pneumonitis can be fatal in some cases. In this case, we concluded that this drug can be successfully reintroduced after methotrexate-related pneumonitis.
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Affiliation(s)
- Rim Rakez
- Department of Hematology, 314309Fattouma Bourguiba Hospital of Monastir, Monastir, Tunisia
| | - Wiem Boufrikha
- Department of Hematology, 314309Fattouma Bourguiba Hospital of Monastir, Monastir, Tunisia
| | - Areej Cheffaï
- Department of Hematology, 314309Fattouma Bourguiba Hospital of Monastir, Monastir, Tunisia
| | - Sarra Boukhriss
- Department of Hematology, 314309Fattouma Bourguiba Hospital of Monastir, Monastir, Tunisia
| | - Mohamed Adnene Laatiri
- Department of Hematology, 314309Fattouma Bourguiba Hospital of Monastir, Monastir, Tunisia
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Abstract
Drug-induced interstitial lung disease (DI-ILD) is an increasingly common cause of morbidity and mortality as the list of culprit drugs continues to grow. Unfortunately, DI-ILD is difficult to study, diagnose, prove, and manage. This article attempts to raise awareness of the challenges in DI-ILD and discusses the current clinical landscape.
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Affiliation(s)
- Nicole Ng
- Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, PO Box 1232, New York, NY 10029, USA.
| | - Maria L Padilla
- Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, PO Box 1232, New York, NY 10029, USA
| | - Philippe Camus
- Pulmonary and Intensive Care at Universite de Bourgogne, 1 Rue Marion, F21079, Dijon, France
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16
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Huang H, Chen R, Shao C, Xu Z, Wolters PJ. Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective. Chin Med J (Engl) 2023; 136:280-286. [PMID: 36689640 PMCID: PMC10106218 DOI: 10.1097/cm9.0000000000002577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Indexed: 01/25/2023] Open
Abstract
ABSTRACT The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.
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Affiliation(s)
- Hui Huang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Ruxuan Chen
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Chi Shao
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Zuojun Xu
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Paul J. Wolters
- Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA 94117, USA
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17
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Kawai C, Miyao M, Kotani H, Minami H, Abiru H, Hamayasu H, Yamamoto A, Tamaki K. Systemic amyloidosis with amyloid goiter: An autopsy report. Leg Med (Tokyo) 2023; 60:102167. [PMID: 36279710 DOI: 10.1016/j.legalmed.2022.102167] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/07/2022] [Accepted: 10/14/2022] [Indexed: 12/13/2022]
Abstract
Systemic amyloidosis is a rare but potentially lethal disease characterized by amyloid accumulation in all organs. Amyloid goiter is an extremely rare pathological lesion characterized by thyroid gland enlargement with fat deposition due to local or systemic amyloidosis. A 60 s woman with rheumatoid arthritis was found unconscious on her bed and declared dead after failed cardiopulmonary resuscitation. Postmortem computed tomography showed severe enlargement of the heart and thyroid glands, suggestive of cardiac hypertrophy and thyroidism. Histological examination revealed amorphous eosinophilic deposits with parenchymal cell destruction in all organs, including the heart and thyroid gland. Abnormal amorphous deposits in the tissues were positive for amyloid A as noted upon Congo red immunohistochemical staining and birefringence microscopy, confirming systemic amyloidosis with amyloid goiter. Serum biochemical analysis revealed increased levels of C-reactive protein; anti-cyclic citrullinated peptide antibody; creatinine kinase-myoglobin binding and N-terminal pro-brain natriuretic peptide; and thyroglobulin, free triiodothyronine, and free thyroxine, indicating systemic inflammation, active rheumatoid arthritis, heart failure, and destructive hyperthyroidism, respectively. These findings suggested that the cause of death was undiagnosed heart failure due to secondary systemic amyloid A (AA) amyloidosis related to rheumatoid arthritis. In addition, destructive hyperthyroidism caused by systemic AA amyloidosis may have also been one of the causes of death as indicated by cardiac overload. To the best of our knowledge, this is the first forensic autopsy report of cardiac amyloidosis with amyloid goiter. In conclusion, this autopsy report highlights the importance of increased awareness and early intervention for severe but treatable complications of systemic amyloidosis.
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Affiliation(s)
- Chihiro Kawai
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masashi Miyao
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Hirokazu Kotani
- Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Hirozo Minami
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hitoshi Abiru
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hideki Hamayasu
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Akira Yamamoto
- Center for Medical Education, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Keiji Tamaki
- Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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18
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Clinical and Radiological Features of Interstitial Lung Diseases Associated with Polymyositis and Dermatomyositis. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121757. [PMID: 36556960 PMCID: PMC9784142 DOI: 10.3390/medicina58121757] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/17/2022] [Accepted: 11/25/2022] [Indexed: 12/03/2022]
Abstract
Polymyositis and dermatomyositis are autoimmune idiopathic systemic inflammatory diseases, characterized by various degrees of muscle inflammation and typical cutaneous lesions-the latter found in dermatomyositis. The underlying pathogenesis is characterized by a high level of uncertainty, and recent studies suggest diseases may have different immunopathological mechanisms. In polymyositis, components of the cellular immune system are involved, whereas in dermatomyositis, the pathogenesis is mainly mediated by the humoral immune response. The interstitial lung disease occurs in one-third of polymyositis and dermatomyositis patients associated with worse outcomes, showing an estimated excess mortality rate of around 40%. Lung involvement may also appear, such as a complication of muscle weakness, mainly represented by aspiration pneumonia or respiratory insufficiency. The clinical picture is characterized, in most cases, by progressive dyspnea and non-productive cough. In some cases, hemoptysis and chest pain are found. Onset can be acute, sub-acute, or chronic. Pulmonary involvement could be assessed by High Resolution Computed Tomography (HRCT), which may identify early manifestations of diseases. Moreover, Computed Tomography (CT) appearances can be highly variable depending on the positivity of myositis-specific autoantibodies. The most common pathological patterns include fibrotic and cellular nonspecific interstitial pneumonia or organizing pneumonia; major findings observed on HRCT images are represented by consolidations, ground-glass opacities, and reticulations. Other findings include honeycombing, subpleural bands, and traction bronchiectasis. In patients having Anti-ARS Abs, HRCT features may develop with consolidations, ground glass opacities (GGOs), and reticular opacities in the peripheral portions; nonspecific interstitial pneumonia or nonspecific interstitial pneumonia mixed with organizing pneumonia have been reported as the most frequently encountered patterns. In patients with anti-MDA5 Abs, mixed or unclassifiable patterns are frequently observed at imaging. HRCT is a sensitive method that allows one not only to identify disease, but also to monitor the effectiveness of treatment and detect disease progression and/or complications; however, radiological findings are not specific. Therefore, aim of this pictorial essay is to describe clinical and radiological features of interstitial lung diseases associated with polymyositis and dermatomyositis, emphasizing the concept that gold standard for diagnosis and classification-should be based on a multidisciplinary approach.
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Kawami M, Ojima T, Yumoto R, Takano M. Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells. Toxicol Res 2022; 38:449-458. [PMID: 36277370 PMCID: PMC9532481 DOI: 10.1007/s43188-022-00127-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 01/31/2022] [Accepted: 02/23/2022] [Indexed: 11/24/2022] Open
Abstract
Methotrexate (MTX) is widely used to treat various diseases. However, it induces adverse reactions like serious lung injury, including pulmonary fibrosis. Increasing evidence suggests that epithelial-mesenchymal transition (EMT) in injured alveolar epithelium contributes to the development of the pathophysiological state of the lung. We demonstrated that MTX induced EMT in cultured alveolar epithelial cell lines. Integrin-mediated signaling is considered a significant factor in recognizing the EMT process. However, the relationship between MTX-induced EMT and integrin family members is poorly understood. In the present study, we aimed to clarify the role of integrin in MTX-induced EMT in A549 and NCI-H1299 (H1299) cells by focusing on the integrin alpha 2 (ITGA2) subunit, selected based on our microarray analysis. MTX treatment for 72 h significantly increased the mRNA and cell surface expression of ITGA2 in both cell lines. However, this upregulation by MTX was suppressed by co-treatment with SB431542 and folic acid, which are inhibitors of MTX-induced EMT in A549 cells. The mRNA expression levels of EMT-related genes were more affected in the MTX-treated A549 cells with high ITGA2 expression than in those with low ITGA2 expression. Finally, E7820, an ITGA2 inhibitor, suppressed MTX-induced EMT-related phenotypic changes, such as morphology and mRNA and protein expression of α-smooth muscle actin, a representative EMT marker. These findings suggest that ITGA2 may play a key role in MTX-induced EMT in alveolar epithelial cells.
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Affiliation(s)
- Masashi Kawami
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan
| | - Takamichi Ojima
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan
| | - Ryoko Yumoto
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan
| | - Mikihisa Takano
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553 Japan
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20
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Sari E, He C, Margaroli C. Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis. Int J Mol Sci 2022; 23:11443. [PMID: 36232756 PMCID: PMC9570276 DOI: 10.3390/ijms231911443] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/21/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and ultimately fatal diffuse parenchymal lung disease. The molecular mechanisms of fibrosis in IPF patients are not fully understood and there is a lack of effective treatments. For decades, different types of drugs such as immunosuppressants and antioxidants have been tested, usually with unsuccessful results. Although two antifibrotic drugs (Nintedanib and Pirfenidone) are approved and used for the treatment of IPF, side effects are common, and they only slow down disease progression without improving patients' survival. Macrophages are central to lung homeostasis, wound healing, and injury. Depending on the stimulus in the microenvironment, macrophages may contribute to fibrosis, but also, they may play a role in the amelioration of fibrosis. In this review, we explore the role of macrophages in IPF in relation to the fibrotic processes, epithelial-mesenchymal transition (EMT), and their crosstalk with resident and recruited cells and we emphasized the importance of macrophages in finding new treatments.
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Affiliation(s)
- Ezgi Sari
- Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Chao He
- Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Camilla Margaroli
- Department of Pathology, Division of Cellular and Molecular Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia. Afr J Thorac Crit Care Med 2022; 28:10.7196/AJTCCM.2022.v28i3.254. [PMID: 36339108 PMCID: PMC9632629 DOI: 10.7196/ajtccm.2022.v28i3.254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2022] [Indexed: 11/13/2022] Open
Abstract
Methotrexate, an immunomodulatory agent used for a wide variety of indications, can cause pulmonary toxicity in the form of pneumonitis, organising pneumonia, pulmonary fibrosis, pleural effusion, pulmonary infections or lymphoproliferative disease. We report a case of methotrexate pneumonitis in a patient with gestational trophoblastic neoplasia. The diagnosis of methotrexate pneumonitis is challenging, as the signs and symptoms can be caused by intercurrent infection, concomitant medications or an underlying disease condition. A high index of suspicion is required for diagnosis. Management consists of drug discontinuation and steroids in patients with respiratory failure.
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22
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Alhalabi M, Ali Deeb S, Ali F, Abbas A. Ulcerative colitis-associated bronchiectasis: A rare extraintestinal manifestation of inflammatory bowel disease: A case report. Medicine (Baltimore) 2022; 101:e30202. [PMID: 36042661 PMCID: PMC9410614 DOI: 10.1097/md.0000000000030203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Inflammatory bowel disease patients may suffer from extraintestinal manifestations. Although muscles, joints, and skin are the most commonly affected, respiratory involvement is more prevalent than previously believed, and the majority of these patients have no symptoms. Although the large airways are the most frequently affected, the small airways, lung parenchyma, and pulmonary vasculature may also be affected. PATIENT CONCERNS A 24-year-old nonsmoking Syrian female was referred to the pulmonary medicine clinic in December 2020 due to a chronic cough. Her cough had been present for the last year, it was described as scratchy, and produced small amounts of mucoid sputum occasionally. She denied any related wheeze, hemoptysis, weight loss, or night sweats. Multiple courses of antibiotics were prescribed by many doctors, also previous chest radiographs were reported as normal. She was diagnosed with ulcerative colitis in 2012 after presentation with abdominal pain and per rectal bleeding. The diagnosis was confirmed via colonoscopy and colon biopsies, with no prior surgery. Her past medications included prednisone, mesalamine, azathioprine, and infliximab. Tests, including complete blood count, C-reactive protein (CRP), fecal calprotectin, and chest X-ray, were normal. DIAGNOSIS Ulcerative colitis-associated bronchiectasis was established through history and clinical examination beside pulmonary function test, which revealed a mild obstructive pattern, and a chest computed tomography follow-up that revealed bilateral bronchiectasis. INTERVENTIONS Bronchiectasis was treated with inhaled oral steroids and sputum expectoration while she continued mesalamine and azathioprine for ulcerative colitis. OUTCOME Cough improvement and sustained ulcerative colitis remission. CONCLUSIONS Identification of inflammatory bowel disease pulmonary exacerbation is probably poor, as pulmonary symptoms might emerge at any moment during the illness, and are most commonly diagnosed later in life and with the disassociation of inflammatory bowel disease activity. Pulmonologists should be involved in the care of inflammatory bowel disease patients who developed lung symptoms.
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Affiliation(s)
- Marouf Alhalabi
- Gastroenterology department of Damascus hospital, Damascus, Syria
- *Correspondence: Marouf Alhalabi, Damascus, Almujtahed Street, Damascus Hospital (e-mail: )
| | - Sawsan Ali Deeb
- Gastroenterology department of Damascus hospital, Damascus, Syria
| | - Fadwa Ali
- Gastroenterology department of Damascus hospital, Damascus, Syria
| | - Ahmad Abbas
- Gastroenterology department of Damascus hospital, Damascus, Syria
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Kawami M, Honda M, Hara T, Yumoto R, Takano M. Role of Nrf2 in Methotrexate-Induced Epithelial–Mesenchymal Transition in Alveolar A549 Cells. Biol Pharm Bull 2022; 45:1069-1076. [DOI: 10.1248/bpb.b22-00010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Masashi Kawami
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Mikito Honda
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Takuya Hara
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Ryoko Yumoto
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
| | - Mikihisa Takano
- Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University
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24
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Schmid F, Chao CM, Däbritz J. Pathophysiological Concepts and Management of Pulmonary Manifestation of Pediatric Inflammatory Bowel Disease. Int J Mol Sci 2022; 23:7287. [PMID: 35806292 PMCID: PMC9266732 DOI: 10.3390/ijms23137287] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 02/01/2023] Open
Abstract
Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed a systematic Medline search between April 1976 and April 2022. Different pathophysiological concepts were identified, including the shared embryological origin, "miss-homing" of intestinal based neutrophils and T lymphocytes, inflammatory triggering via certain molecules (tripeptide proline-glycine-proline, interleukin 25), genetic factors and alterations in the microbiome. Most pediatric IBD patients with PM are asymptomatic, but can show alterations in pulmonary function tests and breathing tests. In children, the pulmonary parenchyma is more affected than the airways, leading histologically mainly to organizing pneumonia. Medication-associated lung injury has to be considered in pulmonary symptomatic pediatric IBD patients treated with certain agents (i.e., mesalamine, sulfasalazine or infliximab). Furthermore, the risk of pulmonary embolism is generally increased in pediatric IBD patients. The initial treatment of PM is based on corticosteroids, either inhaled for the larger airways or systemic for smaller airways and parenchymal disease. In summary, this review article summarizes the current knowledge about PM in pediatric IBD patients, focusing on pathophysiological and clinical aspects.
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Affiliation(s)
- Florian Schmid
- Catholic Children’s Hospital Wilhelmstift, 22149 Hamburg, Germany;
| | - Cho-Ming Chao
- Department of Pediatrics, University Medical Center Rostock, 18057 Rostock, Germany;
- Cardio-Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), German Center of Lung Research (DZL), Justus-Liebig-University, 35398 Giessen, Germany
| | - Jan Däbritz
- Department of Pediatrics, University Medical Center Greifswald, 17475 Greifswald, Germany
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25
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Serum Biomarkers in a Radiological Pattern of Non-Fibrotic Hypersensitivity Pneumonitis: Implications for Mechanistic Difference and Differential Diagnosis. Diseases 2022; 10:diseases10030036. [PMID: 35892730 PMCID: PMC9326628 DOI: 10.3390/diseases10030036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/15/2022] [Accepted: 06/24/2022] [Indexed: 12/04/2022] Open
Abstract
Hypersensitivity pneumonitis (HP) is a consequence of immune-mediated reactions caused by recurrent exposure to environmental agents. Recently, clinical practice guidelines for the diagnosis of HP were published and increased interest in HP. On the other hand, novel therapies have recently emerged for various diseases, and the management of drug-related pneumonitis (DRP) has become increasingly important. Among DRP, the HP pattern (DRP-HP) shows small, poorly defined centrilobular nodules with or without widespread areas of ground-glass opacity or lobular areas of decreased attenuation and vascularity. A similar radiological pattern of non-fibrotic HP can be induced, irrespective of inhalation (non-fibrotic HP) or intravenous administration (DRP-HP). However, their difference has not been well described, although the distribution of lesions in the lungs was slightly different between these two conditions. In this review, we focus on serum biomarkers of lung epithelial cells in order to investigate the difference between DRP-HP and non-fibrotic HP (common-HP). Serum levels of Krebs von den Lungen 6 (KL-6) might be relatively lower (occasionally normal) in DRP-HP than in common-HP, implying a mechanistic difference. KL-6 could be useful in discriminating between DRP and non-fibrotic HP (common type).
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26
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Chen N, Diao CY, Gao J, Zhao DB. Risk factors for the progression of rheumatoid arthritis-related interstitial lung disease: clinical features, biomarkers, and treatment options. Semin Arthritis Rheum 2022; 55:152004. [DOI: 10.1016/j.semarthrit.2022.152004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/19/2022] [Accepted: 03/28/2022] [Indexed: 11/30/2022]
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27
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Silva MM, Ferreira CC, Garcia MA, Pereira E. Methotrexate Pneumonitis After a Low-Dose Medication Error: A Case Report. Cureus 2022; 14:e23078. [PMID: 35464521 PMCID: PMC9001873 DOI: 10.7759/cureus.23078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2022] [Indexed: 11/13/2022] Open
Abstract
Methotrexate is recommended as the first choice of standard drug therapy following the diagnosis of rheumatoid arthritis. Pneumonitis related to methotrexate is a serious, unpredictable adverse event that may become life-threatening. We reported a case of a 68-year-old woman with rheumatoid arthritis that misunderstood the directions for use and took methotrexate daily, instead of weekly, leading to hepatic, hematological, and pulmonary toxicity.Although the histological evaluation was not performed, patient’s clinical presentation, in addition to subsequent investigational findings, supported a diagnosis of pneumonitis resulting from MTX exposure. Toxic dosing over a long period of time along with the concomitant taking of pantoprazole and hypoalbuminemia could have increased the incidence of some adverse events. Concerning pneumonitis related to methotrexate, the toxic dose may have accelerated the pulmonary manifestations, but we do not know if correct dose had been taken, this adverse event would occur. This case enlightened two important issues in rheumatoid arthritis treatment: the possibility of medication errors and the rare, but potentially life-threatening, methotrexate-induced pneumonitis. Improving education and warnings when prescribing and dispensing low-dose methotrexate is essential.
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28
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Abstract
Pulmonary fibrosis, a kind of terminal pathological changes in the lung, is caused by aberrant wound healing, deposition of extracellular matrix (ECM), and eventually replacement of lung parenchyma by ECM. Pulmonary fibrosis induced by acute lung injury and some diseases is reversible under treatment. While idiopathic pulmonary fibrosis is persistent and irreversible even after treatment. Currently, the pathogenesis of irreversible pulmonary fibrosis is not fully elucidated. The known factors associated with the development of irreversible fibrosis include apoptosis resistance of (myo)fibroblasts, dysfunction of pulmonary vessel, cell mitochondria and autophagy, aberrant epithelia hyperplasia and lipid metabolism disorder. In this review, other than a brief introduction of reversible pulmonary fibrosis, we focus on the underlying pathogenesis of irreversible pulmonary fibrosis from the above aspects as well as preclinical disease models, and also suggest directions for future studies.
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Affiliation(s)
- Qing Yang Yu
- 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiao Xiao Tang
- 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,2Guangzhou Laboratory, Bio-island, Guangzhou, China
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29
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Conway R, Nikiphorou E. Efficacy and safety of conventional synthetic, biologic and targeted synthetic DMARDs in RA-ILD: A narrative review. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_157_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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30
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Chapman MM, Muse VV, Mojica JE, Anahtar MN. Case 35-2021: A 50-Year-Old Woman with Pain in the Left Upper Quadrant and Hypoxemia. N Engl J Med 2021; 385:1995-2001. [PMID: 34788511 DOI: 10.1056/nejmcpc2107356] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Margaret M Chapman
- From the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Massachusetts General Hospital, and the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Harvard Medical School - both in Boston
| | - Victorine V Muse
- From the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Massachusetts General Hospital, and the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Harvard Medical School - both in Boston
| | - James E Mojica
- From the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Massachusetts General Hospital, and the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Harvard Medical School - both in Boston
| | - Melis N Anahtar
- From the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Massachusetts General Hospital, and the Departments of Medicine (M.M.C., J.E.M.), Radiology (V.V.M.), and Pathology (M.N.A.), Harvard Medical School - both in Boston
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31
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Glaubitz S, Zeng R, Rakocevic G, Schmidt J. Update on Myositis Therapy: from Today's Standards to Tomorrow's Possibilities. Curr Pharm Des 2021; 28:863-880. [PMID: 34781868 DOI: 10.2174/1381612827666211115165353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/18/2021] [Indexed: 11/22/2022]
Abstract
Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.
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Affiliation(s)
- Stefanie Glaubitz
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
| | - Rachel Zeng
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
| | - Goran Rakocevic
- Department of Neurology, Neuromuscular Division, University of Virginia, Charlottesville. United States
| | - Jens Schmidt
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
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32
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Liu ZH, Shen H. Methotrexate-Induced Pneumonitis in a Patient With Psoriatic Arthritis and Erythroderma. J Clin Rheumatol 2021; 27:e260-e261. [PMID: 32398511 DOI: 10.1097/rhu.0000000000001401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Ze-Hu Liu
- From the Department of Dermatology, Affiliated Hangzhou Third Hospital, Anhui Medical University, Hangzhou, China
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33
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Jochmann A, Trachsel D, Hammer J. Inflammatory bowel disease and the lung in paediatric patients. Breathe (Sheff) 2021; 17:200269. [PMID: 34295391 PMCID: PMC8291939 DOI: 10.1183/20734735.0269-2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
The prevalence of inflammatory bowel disease (IBD) has increased over the past 20 years. Pulmonary involvement in paediatric IBD is rare but may be missed since the spectrum of symptoms is broad and mimics other diseases. The most important differential diagnoses of pulmonary manifestations of IBD are infections and therapy-related side-effects. There is no gold standard to diagnose respiratory manifestations in children with IBD. Diagnostic tests should be chosen according to history and clinical presentation. Treatment of respiratory manifestations of IBD includes inhaled or oral corticosteroids and initiation or step-up of immunomodulatory IBD therapies. Pulmonary involvement in paediatric IBD is rare but may be underdiagnosed. The spectrum of symptoms is broad and mimics other diseases. The differentiation between IBD-related and drug-induced pulmonary manifestation can be challenging.https://bit.ly/3uZBvpA
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Affiliation(s)
- Anja Jochmann
- Division of Respiratory and Critical Care Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Daniel Trachsel
- Division of Respiratory and Critical Care Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Jürg Hammer
- Division of Respiratory and Critical Care Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
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34
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Cherri S, Noventa S, Fanelli M, Calandra G, Prochilo T, Bnà C, Savelli G, Zaniboni A. Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era. Cancers (Basel) 2021; 13:1052. [PMID: 33801385 PMCID: PMC7958630 DOI: 10.3390/cancers13051052] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 02/24/2021] [Indexed: 12/17/2022] Open
Abstract
Interstitial lung disease is recognized as a group of diseases with a different etiopathogenesis characterized by chronic lung inflammation with the accumulation of inflammatory cells, lymphocytes and macrophages, and the consequent release of proinflammatory cytokines. Various degrees of pulmonary fibrosis can be associated with this inflammatory condition. Interstitial lung disease related to oncological drugs is a relevant problem in clinical practice. The etiopathogenetic mechanisms underlying this adverse event are not completely known but can be partly explained by the mechanism of action of the drug involved. Therefore, knowledge of the relevance of this potentially fatal adverse event supported by the reported safety data of pivotal studies becomes fundamental in the management of patients. The prompt diagnosis of drug-related pneumonia and the consequent differential diagnosis with other forms of pneumonia allow a rapid suspension of treatment and the establishment of an immunosuppressive treatment if necessary. In the context of the health emergency related to SARS CoV2 infection and COVID-19-related interstitial lung disease, such knowledge holds decisive relevance in the conscious choice of cancer treatments. Our intent was to describe the oncological drugs most correlated with this adverse event by reporting, where possible, the percentages of insurgency in pivotal studies to provide an overview and therefore promote greater awareness of this important toxicity related to oncological treatment.
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Affiliation(s)
- Sara Cherri
- Unit of Medical Oncology, Department of Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy; (S.N.); (T.P.); (A.Z.)
| | - Silvia Noventa
- Unit of Medical Oncology, Department of Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy; (S.N.); (T.P.); (A.Z.)
| | - Martina Fanelli
- Medical Oncology Unit, University Hospital of Modena, 41124 Modena, Italy;
| | - Giulio Calandra
- Unit of Radiology, Department of Diagnostic Imaging, Fondazione Poliambulanza, 25124 Brescia, Italy; (G.C.); (C.B.)
| | - Tiziana Prochilo
- Unit of Medical Oncology, Department of Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy; (S.N.); (T.P.); (A.Z.)
| | - Claudio Bnà
- Unit of Radiology, Department of Diagnostic Imaging, Fondazione Poliambulanza, 25124 Brescia, Italy; (G.C.); (C.B.)
| | - Giordano Savelli
- Nuclear Medicine Department, Fondazione Poliambulanza, 25124 Brescia, Italy;
| | - Alberto Zaniboni
- Unit of Medical Oncology, Department of Oncology, Fondazione Poliambulanza, 25124 Brescia, Italy; (S.N.); (T.P.); (A.Z.)
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35
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Liu Y, Liu J, Huang L. A Simple-to-Use Web-Based Calculator for Survival Prediction in Acute Respiratory Distress Syndrome. Front Med (Lausanne) 2021; 8:604694. [PMID: 33665197 PMCID: PMC7921740 DOI: 10.3389/fmed.2021.604694] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 01/29/2021] [Indexed: 11/15/2022] Open
Abstract
Background: The aim of this study was to construct and validate a simple-to-use model to predict the survival of patients with acute respiratory distress syndrome. Methods: A total of 197 patients with acute respiratory distress syndrome were selected from the Dryad Digital Repository. All eligible individuals were randomly stratified into the training set (n=133) and the validation set (n=64) as 2: 1 ratio. LASSO regression analysis was used to select the optimal predictors, and receiver operating characteristic and calibration curves were used to evaluate accuracy and discrimination of the model. Clinical usefulness of the model was also assessed using decision curve analysis and Kaplan-Meier analysis. Results: Age, albumin, platelet count, PaO2/FiO2, lactate dehydrogenase, high-resolution computed tomography score, and etiology were identified as independent prognostic factors based on LASSO regression analysis; these factors were integrated for the construction of the nomogram. Results of calibration plots, decision curve analysis, and receiver operating characteristic analysis showed that this model has good predictive ability of patient survival in acute respiratory distress syndrome. Moreover, a significant difference in the 28-day survival was shown between the patients stratified into different risk groups (P < 0.001). For convenient application, we also established a web-based calculator (https://huangl.shinyapps.io/ARDSprognosis/). Conclusions: We satisfactorily constructed a simple-to-use model based on seven relevant factors to predict survival and prognosis of patients with acute respiratory distress syndrome. This model can aid personalized treatment and clinical decision-making.
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Affiliation(s)
- Yong Liu
- Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jian Liu
- Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Liang Huang
- Department of Emergency, The First Affiliated Hospital of Nanchang University, Nanchang, China
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36
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Juge PA, Lee JS, Lau J, Kawano-Dourado L, Rojas Serrano J, Sebastiani M, Koduri G, Matteson E, Bonfiglioli K, Sawamura M, Kairalla R, Cavagna L, Bozzalla Cassione E, Manfredi A, Mejia M, Rodríguez-Henriquez P, González-Pérez MI, Falfán-Valencia R, Buendia-Roldán I, Pérez-Rubio G, Ebstein E, Gazal S, Borie R, Ottaviani S, Kannengiesser C, Wallaert B, Uzunhan Y, Nunes H, Valeyre D, Saidenberg-Kermanac'h N, Boissier MC, Wemeau-Stervinou L, Flipo RM, Marchand-Adam S, Richette P, Allanore Y, Dromer C, Truchetet ME, Richez C, Schaeverbeke T, Lioté H, Thabut G, Deane KD, Solomon JJ, Doyle T, Ryu JH, Rosas I, Holers VM, Boileau C, Debray MP, Porcher R, Schwartz DA, Vassallo R, Crestani B, Dieudé P. Methotrexate and rheumatoid arthritis associated interstitial lung disease. Eur Respir J 2021; 57:13993003.00337-2020. [PMID: 32646919 PMCID: PMC8212188 DOI: 10.1183/13993003.00337-2020] [Citation(s) in RCA: 125] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 06/13/2020] [Indexed: 01/25/2023]
Abstract
QUESTION ADDRESSED BY THE STUDY Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.
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Affiliation(s)
- Pierre-Antoine Juge
- Dept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.,These authors contributed equally
| | - Joyce S Lee
- Dept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.,These authors contributed equally
| | - Jessica Lau
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.,These authors contributed equally
| | - Leticia Kawano-Dourado
- Pulmonary Division, Heart Institute (InCor) Medical School of the University of São Paulo, São Paulo, Brazil
| | - Jorge Rojas Serrano
- Unidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México
| | - Marco Sebastiani
- Rheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Gouri Koduri
- Rheumatology Dept, Southend University Hospital NHSFT, Southend-on-Sea, UK
| | - Eric Matteson
- Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.,Dept of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Karina Bonfiglioli
- Division of Rheumatology, Medical School of the University of São Paulo, São Paulo, Brazil
| | - Marcio Sawamura
- Division of Radiology, Medical School of the University of São Paulo, São Paulo, Brazil
| | - Ronaldo Kairalla
- Pulmonary Division, Heart Institute (InCor) Medical School of the University of São Paulo, São Paulo, Brazil
| | - Lorenzo Cavagna
- University and IRCCS Policlinico S. Matteo Foundation of Pavia, Pavia, Italy
| | | | - Andreina Manfredi
- Rheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Mayra Mejia
- Unidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México
| | | | - Montserrat I González-Pérez
- Unidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México
| | - Ramcés Falfán-Valencia
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México, México
| | - Ivette Buendia-Roldán
- Research Direction, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Ciudad de México, México
| | - Gloria Pérez-Rubio
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México, México
| | - Esther Ebstein
- Dept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Steven Gazal
- Dept of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Raphaël Borie
- Dept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, INSERM UMR1152, DHU APOLLO, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Sébastien Ottaviani
- Dept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Caroline Kannengiesser
- Dept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Benoît Wallaert
- CHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France
| | - Yurdagul Uzunhan
- Dept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France
| | - Hilario Nunes
- Dept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France
| | - Dominique Valeyre
- Dept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France
| | | | | | - Lidwine Wemeau-Stervinou
- CHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France
| | | | | | - Pascal Richette
- AP-HP, Hôpital Lariboisière, Service de Rhumatologie, DMU Locomotion, Université de Paris, Paris, France.,INSERM, UMR_1132, Paris, France
| | - Yannick Allanore
- APHP, Hôpital Cochin, Service de Rhumatologie A, Université de Paris, Paris, France.,INSERM, U1016, UMR_8104, Paris, France
| | - Claire Dromer
- Service de Pneumologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
| | | | | | | | - Huguette Lioté
- APHP, Hôpital Tenon, Service de Pneumologie, Paris, France
| | - Gabriel Thabut
- APHP, Hôpital Bichat, INSERM 1152, Service de Pneumologie B, DHU FIRE, Université de Paris, Paris, France
| | - Kevin D Deane
- Dept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | | | - Tracy Doyle
- Dept of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Jay H Ryu
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Ivan Rosas
- Dept of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - V Michael Holers
- Dept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Catherine Boileau
- Dept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Marie-Pierre Debray
- Dept of Radiology, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France
| | - Raphaël Porcher
- Université de Paris, CRESS, INSERM, INRA, Paris, France.,Centre d'Epidémiologie Clinique, AP-HP, Hôpital Hôtel-Dieu, Paris, France
| | - David A Schwartz
- Dept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Robert Vassallo
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Bruno Crestani
- Dept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.,These authors contributed equally
| | - Philippe Dieudé
- Dept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.,These authors contributed equally
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Wee J, Sobhi S, De Boer B, Xu D. Liver rheumatoid nodules imitating liver malignancy: a rare occurrence. BMJ Case Rep 2020; 13:13/12/e234366. [PMID: 33328208 DOI: 10.1136/bcr-2020-234366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
We describe a case of a 61-year-old man with a background of rheumatoid arthritis who presented to the emergency department with a single-reported episode of haemoptysis on the background of an upper respiratory tract infection. A CT scan revealed an incidental 40 mm mass in upper right lobe of the liver abutting the diaphragmatic surface. A subsequent positron emission tomography scan confirmed the mass and raised the possibility of another lesion in the liver raising the suspicion of malignancy. The case was complicated by the inability to perform a fine needle aspiration biopsy due to the mass' proximity to the diaphragm. After discussion with the patient, it was decided to resect the affected liver segment. Histological analysis of the mass revealed localised necrotising granulomatous inflammation suggestive of a rheumatoid nodule, which is seldom reported in the literature.
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Affiliation(s)
- Jason Wee
- Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia
| | - Salar Sobhi
- Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia
| | - Bastiaan De Boer
- Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia.,Anatomical Pathology, PathWest Laboratory Medical WA, Murdoch, Western Australia, Australia
| | - Dan Xu
- School of Public Health, Curtin University Bentley Campus, Perth, Western Australia, Australia .,Medical Education, Sun Yan-sen University of Medical Sciences, Guangzhou, China
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38
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Seeliger B, Prasse A. Immunomodulation in Autoimmune Interstitial Lung Disease. Respiration 2020; 99:819-829. [PMID: 33271551 DOI: 10.1159/000511200] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 08/28/2020] [Indexed: 11/19/2022] Open
Abstract
Interstitial lung diseases (ILDs) associated with autoimmune or systemic disease are increasingly recognized and our pathophysiological understanding rapidly expanding. Treatment modalities, however, are still mainly driven by established disease-modifying antirheumatic drugs (DMARDs) where, despite decades of experience of their use in the underlying diseases such as rheumatoid arthritis, mostly ret-rospective data exist informing their effect on the course of interstitial lung disease (ILD). In recent years, randomized trials investigating the effects of biological DMARDs (bDMARDs) have been completed or are currently running, generating new treatment options for often relentlessly progressive diseases. Herein, we summarize the evidence and current use of both synthetic DMARDs and bDMARDs in the context of ILDs associated with autoimmune/systemic disease.
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Affiliation(s)
- Benjamin Seeliger
- Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany,
| | - Antje Prasse
- Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany.,Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
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Abstract
Patients with connective tissue diseases may have pulmonary involvement, including interstitial lung disease. Various patterns of interstitial lung disease have been classically described in certain connective tissue diseases. It is now recognized that there is significant overlap between patterns of interstitial lung disease observed in the various connective tissue diseases. Differentiating idiopathic from connective tissue disease-related interstitial lung disease is challenging but of clinical importance. New concepts in the diagnosis of connective tissue disease related interstitial lung disease may prove useful in making the diagnosis.
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40
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Bernier B, Gallois JC, Cadelis G. [Acute interstitial pneumonia in a patient treated with methotrexate: Late-onset with neutrophilia and eosinophilia in bronchoalveolar lavage fluid]. Rev Mal Respir 2020; 37:829-832. [PMID: 33069501 DOI: 10.1016/j.rmr.2020.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 08/05/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Methotrexate-induced pneumonitis is a rare but potentially fatal side effect. It is a diagnosis of exclusion. There are early and late forms and different cell patterns in the bronchoalveolar lavage (BAL). CASE REPORT We present a case of acute interstitial lung disease in a 54-year-old patient who had been taking methotrexate for a year and a half for rheumatoid arthritis. After excluding other causes and based on the diagnostic criteria of Searles and McKendry, we could reasonably identify methotrexate as the cause of the lung disease. It was of late onset and the BAL showed neutrophilia and eosinophilia. CONCLUSION Methotrexate-induced pneumonitis is a diagnosis of exclusion. A late onset combined with the predominance of neutrophils and eosinophils in BAL is rare in the literature, demonstrating the wide heterogeneity of methotrexate-related interstitial lung disease.
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Affiliation(s)
- B Bernier
- Service de pneumologie, centre hospitalier universitaire de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe.
| | - J-C Gallois
- Service de pneumologie, centre hospitalier universitaire de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe
| | - G Cadelis
- Service de pneumologie, centre hospitalier universitaire de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe
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41
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Robles-Pérez A, Luburich P, Bolivar S, Dorca J, Nolla JM, Molina-Molina M, Narváez J. A prospective study of lung disease in a cohort of early rheumatoid arthritis patients. Sci Rep 2020; 10:15640. [PMID: 32973236 PMCID: PMC7515904 DOI: 10.1038/s41598-020-72768-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 09/02/2020] [Indexed: 01/26/2023] Open
Abstract
Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease.
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Affiliation(s)
- A Robles-Pérez
- ILD Unit, Department of Pneumology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Feixa Llarga S/N, 08907, Barcelona, Spain
| | - P Luburich
- Servei de Diagnòstic Per La Imatge El Prat (SDPI El Prat), Department of Radiology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain
| | - S Bolivar
- Servei de Diagnòstic Per La Imatge El Prat (SDPI El Prat), Department of Radiology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain
| | - J Dorca
- ILD Unit, Department of Pneumology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Feixa Llarga S/N, 08907, Barcelona, Spain
| | - J M Nolla
- Department of Rheumatology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain
| | - M Molina-Molina
- ILD Unit, Department of Pneumology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Feixa Llarga S/N, 08907, Barcelona, Spain.
| | - J Narváez
- Department of Rheumatology, Hospital Universitari de Bellvitge, Universitat de Barcelona, Barcelona, Spain
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Chopra A, Avadhani V, Tiwari A, Riemer EC, Sica G, Judson MA. Granulomatous lung disease: clinical aspects. Expert Rev Respir Med 2020; 14:1045-1063. [PMID: 32662705 DOI: 10.1080/17476348.2020.1794827] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Granulomatous lung diseases (GLD) are heterogeneous group of diseases that can be broadly categorized as infectious or noninfectious. This distinction is extremely important, as the misdiagnosis of a GLD can have serious consequences. In this manuscript, we describe the clinical manifestations, histopathology, and diagnostic approach to GLD. We propose an algorithm to distinguish infectious from noninfectious GLD. AREAS COVERED We have searched PubMed and Medline database from 1950 to December 2019, using multiple keywords as described below. Major GLDs covered include those caused by mycobacteria and fungi, sarcoidosis, hypersensitivity pneumonitis, and vasculidities. EXPERT OPINION The cause of infectious GLD is usually identified through microbiological culture and molecular techniques. Most noninfectious GLD are diagnosed by clinical and laboratory criteria, often with exclusion of infectious pathogens. Further understanding of the immunopathogenesis of the granulomatous response may allow improved diagnosis and treatment of GLD.
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Affiliation(s)
- Amit Chopra
- Department of Medicine, Pulmonary and Critical Care Medicine, Albany Medical Center , NY, USA
| | - Vaidehi Avadhani
- Department of Pathology and Laboratory Medicine, Emory University , Atlanta, USA
| | - Anupama Tiwari
- Department of Medicine, Pulmonary and Critical Care Medicine, Albany Medical Center , NY, USA
| | - Ellen C Riemer
- Department of Pathology, Medical University of South Carolina , SC, USA
| | - Gabriel Sica
- Department of Pathology and Laboratory Medicine, Emory University , Atlanta, USA
| | - Marc A Judson
- Department of Medicine, Pulmonary and Critical Care Medicine, Albany Medical Center , NY, USA
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Eliadou E, Moleiro J, Ribaldone DG, Astegiano M, Rothfuss K, Taxonera C, Ghalim F, Carbonnel F, Verstockt B, Festa S, Maia L, Berrozpe A, Zagorowicz E, Savarino E, Ellul P, Vavricka SR, Calvo M, Koutroubakis I, Hoentjen F, Salazar LF, Callela F, Cañete Pizarro F, Soufleris K, Sonnenberg E, Cavicchi M, Wypych J, Hommel C, Ghiani A, Fiorino G. Interstitial and Granulomatous Lung Disease in Inflammatory Bowel Disease Patients. J Crohns Colitis 2020; 14:480-489. [PMID: 31602473 DOI: 10.1093/ecco-jcc/jjz165] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear. METHODS This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician. RESULTS We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients. CONCLUSIONS ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases.
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Affiliation(s)
- Elena Eliadou
- Gastroenterology Department, Manchester Royal Infirmary, Manchester UK
| | - Joana Moleiro
- Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | | | - Marco Astegiano
- Gastroenterologia-U, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Katja Rothfuss
- Robert-Bosch Hospital, Department of Gastroenterology, Hepatology and Endocrinology, Stuttgart, Germany
| | - Carlos Taxonera
- Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain
| | - Fahd Ghalim
- Gastroenterology Department, Kremlin Bicêtre Hospital, University Paris Sud, Paris, France
| | - Franck Carbonnel
- Gastroenterology Department, Kremlin Bicêtre Hospital, University Paris Sud, Paris, France
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, and Department of CHROMETA, KU Leuven, Leuven, Belgium
| | - Stefano Festa
- Ospedale San Filippo Neri, UOS Malattie Infiammatorie Croniche Intestinali Porto, Portugal
| | - Luís Maia
- Gastroenterology Department, Centro Hospitalar do Porto, Porto, Portugal
| | - Ana Berrozpe
- IBD Unit, Bellvitge's Hospital, Barcelona, SpainWarsaw, Poland
| | - Edyta Zagorowicz
- Maria Sklodowska Curie Memorial Cancer Centre and Institute of Oncology, Department of Gastroenterology,Warsaw, Poland
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology,University of Padua, Padua, Italy
| | - Pierre Ellul
- Division of Gastroenterology, Mater Dei Hospital, Valleta, Malta
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, Center for Gastroenterology and Hepatology, Zurich, Switzerland
| | - Marta Calvo
- Gastroenterology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | | | - Frank Hoentjen
- Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Francesca Callela
- UOC Gastroenterologia, Ospedale San Giuseppe, Empoli, Firenze, Italy
| | | | - Konstantinos Soufleris
- Department of Gastroenterology, Theagenion Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | | | - Maryan Cavicchi
- Department of Gatroenterology, Clinique de Bercy, Creteil, France
| | - Joanna Wypych
- Surgery & Gastroenterology Department, Copernicus Hospital, Gdansk, Poland
| | - Christophe Hommel
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Yvoir, Belgium,Catholic University of Louvain, Brussels, Belgium
| | - Alessandro Ghiani
- Schillerhoehe Lung Clinic [Robert-Bosch-Hospital], Department of Pneumology and Respiratory Medicine, Gerlingen, Germany
| | - Gionata Fiorino
- Humanitas Clinical and Research Center, Gastroenterology Department, Rozzano, Milan, Italy.,Humanitas University, Department of Biomedical Sciences, Rozzano, Milan, Italy
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Matsumoto K, Nakao S, Hasegawa S, Matsui T, Shimada K, Mukai R, Tanaka M, Uranishi H, Nakamura M. Analysis of drug-induced interstitial lung disease using the Japanese Adverse Drug Event Report database. SAGE Open Med 2020; 8:2050312120918264. [PMID: 32528682 PMCID: PMC7262990 DOI: 10.1177/2050312120918264] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 02/20/2020] [Indexed: 12/15/2022] Open
Abstract
Objectives: Drug-induced interstitial lung disease occurs when exposure to a drug causes
inflammation and, eventually, fibrosis of the lung interstitium.
Drug-induced interstitial lung disease is associated with substantial
morbidity and mortality. The aim of this retrospective study was to obtain
new information on the time-to-onset profiles of drug-induced interstitial
lung disease by consideration of other associated clinical factors using the
Japanese Adverse Drug Event Report database. Methods: We identified and analyzed reports of drug-induced interstitial lung disease
between 2004 and 2018 from the Japanese Adverse Drug Event Report database.
The reporting odds ratio and 95% confidence interval was used to detect the
signal for each drug-induced interstitial lung disease incidence. We
evaluated the time-to-onset profile of drug-induced interstitial lung
disease and used the applied association rule mining technique to uncover
undetected relationships, such as possible risk factors. Results: The reporting odds ratios (95% confidence intervals) of drug-induced
interstitial lung disease due to temsirolimus, gefitinib, sho-saiko-to,
sai-rei-to, osimertinib, amiodarone, alectinib, erlotinib, everolimus, and
bicalutamide were 18.3 (15.6–21.3), 17.8 (16.5–19.2), 16.3 (11.8–22.4), 14.5
(11.7–18.2), 12.5 (10.7–14.7), 10.9 (9.9–11.9), 10.6 (8.1–13.9), 9.6
(8.8–10.4), 9.4 (8.7–10.0), and 9.2 (7.9–10.6), respectively. The median
durations (day (interquartile range)) for drug-induced interstitial lung
disease were as follows: amiodarone (123.0 (27.0–400.5)), methotrexate
(145.5 (67.8–475.8)), fluorouracil (86.0 (35.5–181.3)), gemcitabine (53.0
(20.0–83.0)), paclitaxel (52.0 (28.5–77.5)), docetaxel (47.0 (18.8–78.3)),
bleomycin (92.0 (38.0–130.5)), oxaliplatin (45.0 (11.0–180.0)), nivolumab
(56.0 (21.0–135.0)), gefitinib (24.0 (11.0–55.0)), erlotinib (21.0
(9.0–49.0)), temsirolimus (38.0 (14.0–68.5)), everolimus (56.0 (35.0–90.0)),
osimertinib (51.5 (21.0–84.8)), alectinib (78.5 (44.3–145.8)), bicalutamide
(50.0 (28.0–147.0)), pegylated interferon-2α (140.0 (75.8–233.0)),
sai-rei-to (35.0 (20.0–54.5)), and sho-saiko-to (33.0 (13.5–74.0)) days.
Association rule mining suggested that the risk of drug-induced interstitial
lung disease was increased by a combination of amiodarone or sho-saiko-to
and aging. Conclusion: Our results showed that patients who receive gefitinib or erlotinib should be
closely monitored for the development of drug-induced interstitial lung
disease within a short duration (4 weeks). In addition, elderly people who
receive amiodarone or sho-saiko-to should be carefully monitored for the
development of drug-induced interstitial lung disease.
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Affiliation(s)
- Kiyoka Matsumoto
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Satoshi Nakao
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Shiori Hasegawa
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.,Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Toshinobu Matsui
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.,Department of Pharmacy, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | - Kazuyo Shimada
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Ririka Mukai
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Mizuki Tanaka
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
| | - Hiroaki Uranishi
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.,Department of Pharmacy, Nara Medical University Hospital, Kashihara, Japan
| | - Mitsuhiro Nakamura
- Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan
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45
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Anaev EK. [Drug-induced interstitial lung disease: approaches to diagnostics and treatment]. TERAPEVT ARKH 2020; 92:84-91. [PMID: 32598798 DOI: 10.26442/00403660.2020.03.000399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Indexed: 01/15/2023]
Abstract
Drug-induced interstitial lung disease (D-ILD) can be caused by various drugs, including antibiotics, amiodarone, antitumor, rheumatological and non-steroidal anti-inflammatory drugs. D-ILD includes hypersensitivity reactions, organizing and non-specific interstitial pneumonia, eosinophilic lung diseases, diffuse alveolar damage and alveolar hypoventilation. To exclude other causes of pulmonary diseases, an assessment of the medical history, physical data and examination results, which may include chest X-ray/multispiral computed tomography (MSCT), lung function tests, and bronchoscopy with bronchoalveolar lavage, are necessary. Diagnosis of D-ILD is difficult due to the heterogeneity of clinical, radiological and histological data. The X-ray pathological phenotype of D-ILD is different; a specific MSCT pattern has not been identified. Treatment includes drug withdrawal and, in some cases, glucocorticoid therapy, although there are no prospective studies on their effect on the outcome of the disease. This article provides various drugs that cause ILD, approaches to their diagnosis and treatment.
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Affiliation(s)
- E K Anaev
- Pirogov Russian National Research Medical University
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46
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Solomon DH, Glynn RJ, Karlson EW, Lu F, Corrigan C, Colls J, Xu C, MacFadyen J, Barbhaiya M, Berliner N, Dellaripa PF, Everett BM, Pradhan AD, Hammond SP, Murray M, Rao DA, Ritter SY, Rutherford A, Sparks JA, Stratton J, Suh DH, Tedeschi SK, Vanni KMM, Paynter NP, Ridker PM. Adverse Effects of Low-Dose Methotrexate: A Randomized Trial. Ann Intern Med 2020; 172:369-380. [PMID: 32066146 PMCID: PMC7229518 DOI: 10.7326/m19-3369] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred. OBJECTIVE To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo. DESIGN Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333). SETTING North America. PARTICIPANTS Adults with known cardiovascular disease and diabetes or metabolic syndrome. INTERVENTION Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week. MEASUREMENTS Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication. RESULTS After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93]). LIMITATION The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period. CONCLUSION Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Daniel H Solomon
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Robert J Glynn
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Elizabeth W Karlson
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Fengxin Lu
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Cassandra Corrigan
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Josh Colls
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Chang Xu
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Jean MacFadyen
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | | | - Nancy Berliner
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Paul F Dellaripa
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Brendan M Everett
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Aruna D Pradhan
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Sarah P Hammond
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Meredith Murray
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Deepak A Rao
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Susan Y Ritter
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Anna Rutherford
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Jeffrey A Sparks
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Jackie Stratton
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Dong H Suh
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Sara K Tedeschi
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Kathleen M M Vanni
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Nina P Paynter
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
| | - Paul M Ridker
- Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.)
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Fujita T, Kuroki T, Hayama N, Shiraishi Y, Amano H, Nakamura M, Hirano S, Tabeta H, Nakamura S. Pemetrexed Plus Platinum for Patients With Advanced Non-small Cell Lung Cancer and Interstitial Lung Disease. In Vivo 2020; 33:2059-2064. [PMID: 31662538 DOI: 10.21873/invivo.11704] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 08/02/2019] [Accepted: 08/07/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIM Pemetrexed plus platinum followed by pemetrexed maintenance has been one of the standard first-line treatments in advanced nonsquamous non-small cell lung cancer (NSCLC), but little is known regarding its safety and efficacy for patients with interstitial lung disease (ILD). PATIENTS AND METHODS The medical records of 24 patients with advanced nonsquamous NSCLC and preexisting ILD who received pemetrexed and platinum doublet therapy with and without pemetrexed maintenance in the first-line setting between December 2009 and June 2016, were retrospectively reviewed. RESULTS The median progression-free survival time was 4.7 months, and the median overall survival time was 9.5 months. Of the 24 patients analyzed, six received pemetrexed maintenance. Acute exacerbation of ILD (AE-ILD) occurred in five (20.8 %) of 24 patients, including two fatal cases. CONCLUSION The treatment with pemetrexed plus platinum has a high risk of AE-ILD in patients with advanced nonsquamous NSCLC and preexisting ILD.
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Affiliation(s)
- Tetsuo Fujita
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Tsuguko Kuroki
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Nami Hayama
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Yuka Shiraishi
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Hiroyuki Amano
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Makoto Nakamura
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Satoshi Hirano
- Department of Medical Oncology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Hiroshi Tabeta
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
| | - Sukeyuki Nakamura
- Department of Respirology, Funabashi Municipal Medical Center, Kanasugi, Japan
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Ichikawa S, Fukuhara N, Saito K, Onodera K, Shirai T, Onishi Y, Yokoyama H, Fujii H, Ichinohasama R, Harigae H. Successful treatment of methotrexate-associated classical Hodgkin lymphoma with brentuximab vedotin-combined chemotherapy: a case series. Int J Hematol 2020; 111:667-672. [PMID: 31955346 DOI: 10.1007/s12185-020-02822-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 12/28/2019] [Accepted: 01/07/2020] [Indexed: 12/01/2022]
Abstract
Methotrexate (MTX)-associated classical Hodgkin lymphoma (CHL) is unlikely to regress following discontinuation of MTX, and its treatment usually requires chemotherapy. Standard chemotherapy for CHL is the ABVD regimen, which contains pneumotoxic bleomycin. This can be problematic in MTX-CHL patients suffering from an autoimmune disease (AID), such as rheumatoid arthritis (RA), as they frequently have pulmonary complications. However, brentuximab vedotin (BV)-containing chemotherapy without bleomycin (A + AVD regimen) was recently reported to show favorable efficacy for CHL, and could therefore be beneficial in MTX-CHL. We treated three cases of MTX-CHL using the A + AVD regimen. All were female and had received MTX for more than 15 years. Underlying AIDs in these patients were RA in two patients, and overlap syndrome with systemic lupus erythematosus and dermatomyositis in one patient. The A + AVD regimen resulted in a complete response in all patients. Peripheral neuropathy developed in two patients, necessitating reduction of the BV dose. All three patients experienced hematological toxicity necessitating dose reduction; however, no severe adverse effects, including infection or pulmonary complication, were documented. RA was well-controlled without additional immunosuppressants. The A + AVD regimen is a promising chemotherapy for MTX-CHL with favorable efficacy and tolerable toxicity profiles.
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Affiliation(s)
- Satoshi Ichikawa
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan.
| | - Noriko Fukuhara
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Kei Saito
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Koichi Onodera
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Tsuyoshi Shirai
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Yasushi Onishi
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Hisayuki Yokoyama
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Hiroshi Fujii
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Ryo Ichinohasama
- Department of Hematopathology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
| | - Hideo Harigae
- Department of Hematology and Rheumatology, Tohoku University Hospital, 1-1 Seiryo-cho, Sendai, 980-8574, Japan
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Glaubitz S, Zeng R, Schmidt J. New insights into the treatment of myositis. Ther Adv Musculoskelet Dis 2020; 12:1759720X19886494. [PMID: 31949477 PMCID: PMC6950531 DOI: 10.1177/1759720x19886494] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 10/10/2019] [Indexed: 12/17/2022] Open
Abstract
The myositis syndromes include polymyositis, dermatomyositis (DM), necrotizing myopathy, inclusion body myositis (IBM), antisynthetase syndrome and overlap syndromes with myositis. These syndromes mostly occur in middle-aged patients, while juvenile DM occurs in children and adolescents. Patients mostly show a subacute weakness and myalgia in the upper and lower limbs, the diagnosis is based upon these clinical findings in combination with muscle biopsy results and specific serum autoantibodies. In recent years, research achieved a better understanding about the molecular mechanism underlying the myositis syndromes, as well as disease progress and extramuscular organ manifestations, such as interstitial lung disease and association with neoplasias. Treatment mainly consists of glucocorticosteroids and immunosuppressants. IBM is usually refractory to treatments. This review provides an overview of the current standards of treatment and new treatment options like monoclonal antibodies and new molecular therapies and their first results from clinical trials.
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Affiliation(s)
- Stefanie Glaubitz
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Rachel Zeng
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Jens Schmidt
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Robert-Koch-Sr. 40, 37075 Göttingen, Germany
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Abstract
Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.
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