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Necrobiotic Pulmonary Nodules of Rheumatoid Arthritis
Author’s Accepted Manuscript Necrobiotic Pulmonary Nodules of Rheumatoid Arthritis Satoru Yanagisawa, Chihiro Inoue, Masakazu Ichinose www.elsevier.com
PII: DOI: Reference:
S0002-9629(17)30118-0 http://dx.doi.org/10.1016/j.amjms.2017.02.007 AMJMS394
To appear in: The American Journal of the Medical Sciences Accepted date: 22 Cite this article as: Satoru Yanagisawa, Chihiro Inoue and Masakazu Ichinose, Necrobiotic Pulmonary Nodules of Rheumatoid Arthritis, The American Journal of the Medical Sciences, http://dx.doi.org/10.1016/j.amjms.2017.02.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Yanagisawa, page.1
Necrobiotic pulmonary nodules of rheumatoid arthritis
SATORU YANAGISAWA, PhD,1, CHIHIRO INOUE, MD,2, and MASAKAZU ICHINOSE, PhD.1
1
Department of Respiratory Medicine, 2Department of Anatomic Pathology,
Tohoku University Graduate School of Medicine, Sendai, Japan.
Correspondence: Satoru Yanagisawa, M.D., Ph.D. Assistant Professor, Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan TEL: +81-22-717-8539, FAX: +81-22-717-8549 E-mail: [email protected]
Conflicts of interest (COI): The authors have reported that no potential COI exist with any companies/organizations whose products or services may be discussed in this article.
Funding Sources: No External Funding.
Key terms: rheumatoid arthritis, necrobiotic nodules, pulmonary complication.
- 1 -
Yanagisawa, page.2
CASE PRESENTATION A 66-year-old woman with a heavy smoking history was referred for multiple bilateral lung nodules. Two years ago, she was diagnosed as rheumatoid arthritis (RA), and had been treated with various drugs for RA such a leflunomide or etanercept; all of which had limited effects. Because of her persistent productive cough and progressive dyspnea, the chest radiograph was evaluated, which showed the right pleural effusion with multiple bilateral lung nodules. Physical examination revealed right pleural friction rubs, and slight RA change of bilateral hands. All of the serological or bacteriological study such as blood/ sputum/ urine staining & culture was turned out to be negative. A computed tomographic scan of the chest revealed the bilateral cavitating lung nodules (Figure 1A, arrows). After non-diagnostic bronchoscopy, a left lower lung nodule (Figure 1A, red arrow) was excised by the video-assisted thoracoscopic surgery; which showed the abscess-like, tense lesion just beneath the visceral pleura (Figure 1B, white arrow). Pathologically, the nodule consists of fibrinoid necrotic core (Figure 1C, NC) surrounded by the palisading histiocytes (Figure 1C, PH) and multinucleated giant cells (Figure 1C, blue arrow heads) with peripheral vasculitis; all of which were compatible with the diagnosis of necrobiotic pulmonary nodule (NPN) of RA. The periodic acid-schiff staining and acid-fast staining were both negative, and there was no evidence of malignancy. Pulmonary nodules in the patients with RA are caused by various etiologies, ranging from the infection, malignancy or RA-associated inflammation (1). Among them, the infection is the most likely cause; however the NPNs are well-known but relatively rare complication of RA. The NPNs are known to occur mainly in male with smoking history, and to arise predominantly in upper lung with subpleural distribution. As a - 2 -
Yanagisawa, page.3
contributing factor for the development of NPNs, the long-term hypoxia or smoking has been thought to be important, because they impair the function of alveolar macrophages which usually remove excess rheumatoid factor in the lung parenchyma and prevent the development of NPNs (2). Interestingly, recent reports elucidated that the treatment with leflunomide (2) or with the tumor necrosis factor (TNF) inhibitors (3) might contribute to the occurrence and progression of NPNs; probably because of the dysregulation of macrophages by these drugs. Taken together, it might be possible in our patient that the heavy smoking exposure with the usage of biological drugs simultaneously had impaired the alveolar macrophage, with resultant development of cavitating lung nodules. REFERENCES 1.
Patel R, Naik S, Amchentsev A, et al. A rare cause of multiple cavitary nodules. Chest 2009;136:306–309.
2.
Rozin A, Yigla M, Guralnik L, et al. Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. Clin Rheumatol 2006;25:384–388.
3.
Toussirot E, Berthelot JM, Pertuiset E, et al. Pulmonary nodulosis and aseptic granulomatous lung disease occurring in patients with rheumatoid arthritis receiving tumor necrosis factor-α- blocking agent: A case series. J Rheumatol 2009;36:2421–2427.
- 3 -
Figure 1 Yanagisawa, page.4
B
C NC
PH
- 4 -
PII: DOI: Reference:
S0002-9629(17)30118-0 http://dx.doi.org/10.1016/j.amjms.2017.02.007 AMJMS394
To appear in: The American Journal of the Medical Sciences Accepted date: 22 Cite this article as: Satoru Yanagisawa, Chihiro Inoue and Masakazu Ichinose, Necrobiotic Pulmonary Nodules of Rheumatoid Arthritis, The American Journal of the Medical Sciences, http://dx.doi.org/10.1016/j.amjms.2017.02.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Yanagisawa, page.1
Necrobiotic pulmonary nodules of rheumatoid arthritis
SATORU YANAGISAWA, PhD,1, CHIHIRO INOUE, MD,2, and MASAKAZU ICHINOSE, PhD.1
1
Department of Respiratory Medicine, 2Department of Anatomic Pathology,
Tohoku University Graduate School of Medicine, Sendai, Japan.
Correspondence: Satoru Yanagisawa, M.D., Ph.D. Assistant Professor, Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan TEL: +81-22-717-8539, FAX: +81-22-717-8549 E-mail: [email protected]
Conflicts of interest (COI): The authors have reported that no potential COI exist with any companies/organizations whose products or services may be discussed in this article.
Funding Sources: No External Funding.
Key terms: rheumatoid arthritis, necrobiotic nodules, pulmonary complication.
- 1 -
Yanagisawa, page.2
CASE PRESENTATION A 66-year-old woman with a heavy smoking history was referred for multiple bilateral lung nodules. Two years ago, she was diagnosed as rheumatoid arthritis (RA), and had been treated with various drugs for RA such a leflunomide or etanercept; all of which had limited effects. Because of her persistent productive cough and progressive dyspnea, the chest radiograph was evaluated, which showed the right pleural effusion with multiple bilateral lung nodules. Physical examination revealed right pleural friction rubs, and slight RA change of bilateral hands. All of the serological or bacteriological study such as blood/ sputum/ urine staining & culture was turned out to be negative. A computed tomographic scan of the chest revealed the bilateral cavitating lung nodules (Figure 1A, arrows). After non-diagnostic bronchoscopy, a left lower lung nodule (Figure 1A, red arrow) was excised by the video-assisted thoracoscopic surgery; which showed the abscess-like, tense lesion just beneath the visceral pleura (Figure 1B, white arrow). Pathologically, the nodule consists of fibrinoid necrotic core (Figure 1C, NC) surrounded by the palisading histiocytes (Figure 1C, PH) and multinucleated giant cells (Figure 1C, blue arrow heads) with peripheral vasculitis; all of which were compatible with the diagnosis of necrobiotic pulmonary nodule (NPN) of RA. The periodic acid-schiff staining and acid-fast staining were both negative, and there was no evidence of malignancy. Pulmonary nodules in the patients with RA are caused by various etiologies, ranging from the infection, malignancy or RA-associated inflammation (1). Among them, the infection is the most likely cause; however the NPNs are well-known but relatively rare complication of RA. The NPNs are known to occur mainly in male with smoking history, and to arise predominantly in upper lung with subpleural distribution. As a - 2 -
Yanagisawa, page.3
contributing factor for the development of NPNs, the long-term hypoxia or smoking has been thought to be important, because they impair the function of alveolar macrophages which usually remove excess rheumatoid factor in the lung parenchyma and prevent the development of NPNs (2). Interestingly, recent reports elucidated that the treatment with leflunomide (2) or with the tumor necrosis factor (TNF) inhibitors (3) might contribute to the occurrence and progression of NPNs; probably because of the dysregulation of macrophages by these drugs. Taken together, it might be possible in our patient that the heavy smoking exposure with the usage of biological drugs simultaneously had impaired the alveolar macrophage, with resultant development of cavitating lung nodules. REFERENCES 1.
Patel R, Naik S, Amchentsev A, et al. A rare cause of multiple cavitary nodules. Chest 2009;136:306–309.
2.
Rozin A, Yigla M, Guralnik L, et al. Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. Clin Rheumatol 2006;25:384–388.
3.
Toussirot E, Berthelot JM, Pertuiset E, et al. Pulmonary nodulosis and aseptic granulomatous lung disease occurring in patients with rheumatoid arthritis receiving tumor necrosis factor-α- blocking agent: A case series. J Rheumatol 2009;36:2421–2427.
- 3 -
Figure 1 Yanagisawa, page.4
B
C NC
PH
- 4 -