Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis: autopsy findings with a mosaic pattern of acute and organizing diffuse alveolar damage

Abstract Introduction/Objective Acute interstitial pneumonia (AIP) is a rare disease clinically characterized by rapidly progressing respiratory failure in individuals with no history of respiratory illness or other inciting factors. While most often diagnosed in middle-aged adults, it may present in any age group. Initial presentation is described as influenza- like, and respiratory failure requiring ventilatory support often progresses within weeks to months. Prognosis is poor, with an estimated mortality rate approaching 80% without treatment. Methods We present the case of a 44-year-old male nonsmoker with no significant medical history, who presented in 2018 with 1.5 months of dyspnea and headache initially diagnosed as atypical pneumonia. Chest imaging revealed bilateral opacities; however, microbial workup revealed no evidence of infectious etiology. Autoimmune serology studies were likewise unrevealing. Despite aggressive supportive and medical management, he deteriorated to respiratory failure and succumbed. Results At autopsy, the lungs were symmetrically congested and edematous (combined weight 2,340 g) but free of evident consolidation or discrete lesions. Microscopic examination revealed diffuse alveolar damage with extensive hyaline membrane formation, interstitial edema, and fibroblastic proliferation. The vasculature was severely congested, and the alveoli contained hemorrhage and scattered macrophages. No fungal or mycobacterial elements were identified by staining. Based on the histologic features and clinical context, the diagnosis of AIP was made. Conclusion AIP is a rare, aggressive, and diagnostically challenging disease that includes a broad range of both clinical and histologic differentials. Timely recognition and intervention with aggressive respiratory support and high- dose glucocorticoids are the mainstays of clinical management. The diagnostic role of histology is significant, but hinges on early clinical consideration of AIP as disease progression may later preclude the biopsy procedure. We share this case to raise awareness of this rapidly progressive and diagnostically troubling interstitial lung disease while emphasizing the importance of clinicopathologic correlation.

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Video-Assisted Thoracoscopic Lung Biopsy as a Possible Cause of Acute Interstitial Pneumonia in a Patient with Nonspecific Interstitial Pneumonia

Canadian Respiratory Journal ◽

10.1155/2004/805742 ◽

2004 ◽

Vol 11 (6) ◽

pp. 437-440 ◽

Cited By ~ 8

Author(s):

D Jeffrey Moore ◽

Colm P McParland ◽

Martin J Bullock ◽

Yannick Cartier ◽

Paul Hernandez

Keyword(s):

Case Report ◽

Interstitial Pneumonia ◽

Lung Biopsy ◽

Diffuse Alveolar Damage ◽

Usual Interstitial Pneumonia ◽

High Resolution Computed Tomography ◽

Present Case Report ◽

Video Assisted ◽

Acute Interstitial Pneumonia ◽

Nonspecific Interstitial Pneumonia

The present case report describes a 44-year-old woman who presented with dyspnea due to diffuse interstitial lung disease. High-resolution computed tomography showed features of usual interstitial pneumonia, but the lung biopsy obtained by video-assisted thoracoscopy was consistent with a histological pattern of nonspecific interstitial pneumonia. Following the procedure, the patient developed progressive respiratory distress and died on postoperative day 13 with a clinical picture of acute interstitial pneumonia. The autopsy showed evidence of diffuse alveolar damage superimposed on the background pattern of nonspecific interstitial pneumonia. The present case report supports the notion that patients with a variety of subtypes of idiopathic interstitial pneumonias may be at risk of exacerbation of their underlying disease following thoracic procedures, including video-assisted thoracoscopic lung biopsy.

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Leflunomide-induced acute interstitial pneumonia in a patient treated for rheumatoid arthritis

Pneumonologia i Alergologia Polska ◽

10.5603/piap.2015.0007 ◽

2015 ◽

Vol 83 (1) ◽

pp. 50-54 ◽

Cited By ~ 2

Author(s):

Marta Maskey-Warzęchowska ◽

Krzysztof Karwat ◽

Benedykt Szczepankiewicz ◽

Renata Langfort ◽

Małgorzata Szołkowska ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Pneumonia ◽

Acute Interstitial Pneumonia

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BLEOMYCIN-INDUCED REVERSIBLE ACUTE INTERSTITIAL PNEUMONIA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i5.17121 ◽

2017 ◽

Vol 10 (5) ◽

pp. 6 ◽

Cited By ~ 1

Author(s):

Balaji Ommurugan ◽

Amita Priya ◽

Navin Patil ◽

Joseph Thomas

Keyword(s):

Adverse Drug Reaction ◽

Interstitial Pneumonia ◽

Pulmonary Toxicity ◽

Causality Assessment ◽

Chemotherapeutic Agent ◽

Diffuse Alveolar Damage ◽

Germ Cell Tumors ◽

Lymphoma Patient ◽

Drug Induced ◽

Acute Interstitial Pneumonia

As of now, about 380 medications are implicated in causing respiratory reactions and most common among that is drug-induced interstitial disease.Oral, parental as well inhalational drugs are known to cause drug-induced interstitial lung disease. Bleomycin is a chemotherapeutic agent used inthe treatment of lymphomas, germ cell tumors of the testes. Most common pulmonary toxicity is diffuse alveolar damage with nonspecific interstitialpneumonitis being next. We report a case of bleomycin-induced reversible acute interstitial pneumonia in a Hodgkin’s lymphoma patient with adriamycin, bleomycin, vinblastine, dacarbazine regimen. Causality assessment was done using Naranjo scale, and probable causal relationship was established. Adverse drug reaction was found to be moderately severe and not preventable as per Hartwig’s severity and Thornton’s preventability scaling respectively.Keywords: Naranjo scale, Lymphoma, Bleomycin, Pneumonia.

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COVID-19 Autopsies: A Case Series from Poland

Pathobiology ◽

10.1159/000512768 ◽

2020 ◽

pp. 1-10

Author(s):

Ewa Chmielik ◽

Joanna Jazowiecka-Rakus ◽

Grzegorz Dyduch ◽

Anna Nasierowska-Guttmejer ◽

Lukasz Michalowski ◽

...

Keyword(s):

Interstitial Pneumonia ◽

Diffuse Alveolar Damage ◽

Case Series ◽

Acinetobacter Baumanii ◽

Autopsy Findings ◽

Molecular Tests ◽

History Of ◽

Thrombotic Complications ◽

Lung Vessels ◽

Lymphoid Infiltrates

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, <i>Acinetobacter baumanii</i> sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with <i>SARS</i>-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

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Acute Interstitial Pneumonia (AIP): Relationship to Hamman-Rich Syndrome, Diffuse Alveolar Damage (DAD), and Acute Respiratory Distress Syndrome (ARDS)

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0032-1325158 ◽

2012 ◽

Vol 33 (05) ◽

pp. 476-485 ◽

Cited By ~ 38

Author(s):

Joseph Parambil ◽

Sanjay Mukhopadhyay

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Interstitial Pneumonia ◽

Distress Syndrome ◽

Diffuse Alveolar Damage ◽

Acute Interstitial Pneumonia

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Preliminary evidence that hydrostatic edema may contribute to the formation of diffuse alveolar damage in a Holstein calf model

F1000Research ◽

10.12688/f1000research.14153.1 ◽

2018 ◽

Vol 7 ◽

pp. 374

Author(s):

Joseph M. Neary ◽

Dee Church

Keyword(s):

Diastolic Dysfunction ◽

Interstitial Pneumonia ◽

Diffuse Alveolar Damage ◽

Interventricular Septum ◽

Clinical Signs ◽

Preliminary Evidence ◽

Left Ventricular ◽

Feedlot Cattle ◽

Acute Interstitial Pneumonia ◽

Pulmonary Arterial

Background: Two notable findings of clinically healthy feedlot cattle suggest they may have pulmonary hydrostatic edema during the finishing phase of production: increased pulmonary arterial wedge pressures and pulmonary venous hypertrophy. The goal of this study was to determine if increased pulmonary arterial wedge pressure (PAWP) in a Holstein calf could lead to diffuse alveolar damage consistent with the early, exudative phase of acute interstitial pneumonia of feedlot cattle. Methods: Six male Holstein dairy calves were given daily subcutaneous injections of the nonspecific ß-adrenergic agonist isoprenaline (10 mg/kg/d), to induce left ventricular diastolic dysfunction, or sterile water for 14 days. On Day 14, pulmonary arterial pressures and wedge pressures were measured, echocardiography performed, and the ratio of mitral valve flow velocity (E) to septal lengthening velocity (e’) calculated. Calves were euthanized on Day 15 and lung lesions semi-quantitatively scored. Results: Mean PAWP was 12 ± 1 mm Hg in calves that received isoprenaline and 7 ± 1 mm Hg in controls (P = 0.01). Calves that received isoprenaline tended to have greater relative wall thickness than control calves (P = 0.15) and greater E/e’ ratios (P = 0.16), suggestive of concentric hypertrophy and diastolic dysfunction, respectively. Calves that received isoprenaline also tended to have a left ventricle and interventricular septum that was 29 ± 10 g heavier than control calves (P = 0.10) when controlling for body mass. Hyaline membranes, the hallmark feature of diffuse alveolar damage, were evident in lung sections from all calves that received isoprenaline but none of the controls. Conclusions: Consistent with prior pathological and physiological studies of feedlot cattle, this study provides preliminary evidence that cattle presenting with clinical signs and pathology consistent with early stage acute interstitial pneumonia could be attributable to hydrostatic edema associated with left ventricular failure.

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Acute Interstitial Pneumonia Presenting as Diffuse Alveolar Damage With Positive Scl-70 Antibodies: Cart Before the Horse?

CHEST Journal ◽

10.1378/chest.1995013 ◽

2014 ◽

Vol 146 (4) ◽

pp. 383A

Author(s):

Mohammed Moizuddin ◽

Muhammed Imtiaz ◽

Mohammed Nayeem ◽

Ria Gripaldo

Keyword(s):

Interstitial Pneumonia ◽

Diffuse Alveolar Damage ◽

Acute Interstitial Pneumonia

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Diffuse Alveolar Damage of the Lungs in Forensic Autopsies: Assessment of Histopathological Stages and Causes of Death

The Scientific World JOURNAL ◽

10.1100/2012/657316 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6

Author(s):

Halide Nur Urer ◽

Gokhan Ersoy ◽

Emine Dilek Yılmazbayhan

Keyword(s):

Interstitial Pneumonia ◽

Histopathological Examination ◽

Diffuse Alveolar Damage ◽

Lung Damage ◽

European Respiratory Society ◽

Acute Interstitial Pneumonia ◽

Morphological Criteria ◽

Hematoxylin And Eosin ◽

Independent Variable ◽

Lung Biopsies

Introduction. Diffuse alveolar damage (DAD) is a morphological prototype of acute interstitial pneumonia. Hospital autopsies or open-lung biopsies are used to monitor common alveolar damage and hyaline membrane (HM) development histopathologically. The aim of this study was to detect histopathological profiles and frequency of DAD and HM in adult forensic autopsies.Materials and Methods. In total, 6813 reports with histopathological samples in 12,504 cases on which an autopsy was performed between 2006 and 2008 were investigated. Sixty-six individuals >18 years of age who were diagnosed with DAD were included. Hematoxylin- and eosin-stained lung preparations were reexamined in line with the 2002 American Thoracic Society/European Respiratory Society idiopathic interstitial pneumonia consensus criteria.Results. Histopathological examination revealed that 50 cases (75.7%) were in the exudative phase and 16 (24.2%) were in the proliferative phase. Only the rate of alveolar exudate/oedema in exudative phase cases (); those of alveolar histiocytic desquamation (), alveolar fibrosis (), chronic inflammation (), and alveolar fibrin () in proliferative cases were significantly higher. The presence of alveolar fibrin was the only independent variable in favour of proliferative cases ().Conclusion. The detection of all DAD morphological criteria with the same intensity is not always possible in each case. Forensic autopsies may provide a favourable means for expanding our knowledge about acute lung damage, DAD, and interstitial lung disease.

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