A PROBABLE CASE OF IGG4-RELATED LUNG DISEASE MIMICKING PNEUMOCONIOSIS

SESSION TITLE: Autoimmune Diseases Gone Wild: Rare Cases of Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a complex entity related to autoimmune dysfunction and inflammation that can cause mass-like lesions and fibrosis of a variety of organs, including pancreas and/or lungs. IgG4-RD in the lung can have diverse clinical and radiographic presentations. We present a case of suspected IgG4-RD that manifested as idiopathic pancreatitis and interstitial lung disease that mimicked coal workers' pneumoconiosis. CASE PRESENTATION: A 72 year-old male with a decades-long coal mining history and a presumptive diagnosis of coal-worker's pneumoconiosis was admitted to the hospital for necrotizing pancreatitis. There was no evidence of gallstones, elevated triglycerides, history of alcohol use or medication known to precipitate pancreatitis. Two years prior, a presumptive diagnosis of coal-worker's pneumoconiosis had been reached largely on the basis of history and chest imaging (Figure 1) showing a progressive massive pulmonary fibrosis pattern. His hospital course was protracted and complicated by nosocomial COVID-19 treated with remdesivir and a 10-day course of dexamethasone. He then had persistent hypoxemia that worsened after dexamethasone was discontinued. Empiric high-dose methylprednisolone was given and the hypoxemia improved dramatically. However, the hypoxemia and pancreatitis repeatedly worsened with significant dose decrease. Inpatient CT chest showed worsening interstitial reticulation and ground-glass opacities superimposed on prior fibrosis (Figure 2). Serum IgG subclass levels were checked;IgG4 and IgG4:IgG ratio were mildly elevated at 93mg/dL and 0.09, respectively. In the setting of idiopathic pancreatitis, pulmonary fibrosis, and steroid-sensitive hypoxemia, he was diagnosed with probable IgG4-RD involving pancreas and lungs. An association between inhaled occupational exposures and development of IgG4-RD has been observed. To confirm the diagnosis of pulmonary IgG4-RD, a tissue biopsy will be necessary. He is now discharged from hospital on a long steroid taper. DISCUSSION: A serum IgG4 level >125mg/dL or an IgG4:total IgG ratio >0.08 support the diagnosis, as does clinical response to steroids. However, these criteria are nonspecific and will be in the normal range in a substantial minority of cases. Lymphocytes and a predominance of IgG4-positive plasma cells infiltrating fibrotic tissue in involved organs are pathologic hallmarks of IgG4-RD. Lung involvement in patients with pancreatitis due to IgG4-RD is common and likely under recognized. CONCLUSIONS: Pulmonary involvement in IgG4-RD can show a wide array of radiographic patterns, but that seen in this case with pseudotumor and fibrosis is among the most commonly reported. Given the overlap in risk factors and radiographic appearance between IgG4-RD and pneumoconiosis, vigilance for IgG4-RD is warranted. Reference #1: Hirano K., Kawabe T., Komatsu Y., et al. High-rate pulmonary involvement in autoimmune pancreatitis. Internal Medicine Journal. 2006;36(1):58–61. doi: 10.1111/j.1445-5994.2006.01009.x Reference #2: Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015 Apr 11;385(9976):1460-71. doi: 10.1016/S0140-6736(14)60720-0. Epub 2014 Dec 4. PMID: 25481618. Reference #3: de Buy Wenniger, L. J., Culver, E. L., & Beuers, U. (2014). Exposure to occupational antigens might predispose to IgG4-related disease. Hepatology (Baltimore, Md.), 60(4), 1453–1454. https://doi.org/10.1002/hep.26999 DISCLOSURES: No relevant relationships by Jordan Minish, source=Web Response No relevant relationships by Robert Ousley, source=Web Response No relevant relationships by Meagan Reif, source=Web Response No relevant relationships by Derek Russell, source=Web Response

Lung Function and Radiographic Disease Worse Among Former Miners in Central Appalachia Than Other Regions of the United States

RATIONALE The COVID-19 pandemic has disrupted national spirometric surveillance of active and former U.S. coal miners since March 2020. Consequently data collected by the Health Resources and Services Administration (HRSA)-funded Black Lung Clinics Program (BLCP) represents the only major source of recent health data on U.S. former coal miners. Using the first available year of national BLCP data we examined associations between mining region and radiographic disease and lung function impairment. METHODS We analyzed pre-bronchodilator spirometry and International Labour Office chest radiograph classifications from miners seen across 15 BLCP grantees from July 1 2020 to June 30 2021. We calculated percent predicted (PP) and lower limits of normal (LLN) for forced expiratory volume in one second (FEV1) forced vital capacity (FVC) and FEV1/FVC ratio. We determined prevalence of patterns of spirometric abnormality (restrictive obstructive/mixed) and moderate to severe impairment (FEV1<70PP). We classified miners who worked the majority of their coal mining career in Kentucky Virginia or West Virginia as Central Appalachian miners. We examined associations between region worked and lung function impairment using logistic regression. RESULTS The 2,891 miners were predominantly non- Hispanic white (98.1%) and male (99.4%) with mean age 66 years (SD9.3). Mean coal mining tenure was 26 years (SD10.7) and 66% (n=1,900) were Central Appalachian miners. Thirty-seven percent had never smoked. Among those with chest radiographs (n=2,464 85%) Central Appalachian miners had a significant three-fold increase in progressive massive fibrosis (PMF) prevalence compared to miners who worked elsewhere in the U.S. (9% vs 3% p<.0001). Smoking history and spirometry were available in 66% (n=1,918). Of these 40% of never-smokers had abnormal spirometry (obstruction/mixed 10%;restriction 30%);among ever-smokers, 54% had abnormal spirometry (obstruction/mixed 27%;restriction 27%). Abnormal FEV1 was present in 30% of never smokers and 42% of ever-smokers. Mean FEV1PP was significantly lower among Central Appalachian miners compared to miners from other regions. Controlling for age, tenure, and pack-years, Central Appalachian miners had significantly elevated odds of having FEV1 impairment compared to non-Central Appalachian miners (OR 1.31, 95%CI 1.06,1.62). A subanalysis controlling for category of radiographic disease showed that odds of impairment remained elevated among Central Appalachian miners (OR 1.24, 95%CI 0.97,1.60). CONCLUSIONS Controlling for smoking, age, and tenure, former miners who worked most of their career in Central Appalachia have significantly increased odds of disabling impairment. These findings highlight the important role of HRSA-funded black lung clinics in understanding work-related lung disease among U.S. coal miners.

Histopathologic survey on lung necropsy specimens of 15 patients who died from COVID-19: A large study from Iran with a high rate of anthracosis.

Background: In the pandemic era of Coronavirus disease 19 (COVID-19), one of the most important issues is the nature of real pathological events that occur during disease course in different parts of the body. There are several ways to know more about COVID-related histopathological events,such as tissue sampling which means biopsy from the tissues of either livepeople or necropsy/autopsy of people who died from COVID-19. Methods: We conducted an original study for assessing histopathological findings of lung necropsy samples collected from 15 Iranian patients.The continuous variables were presented as mean and standard deviation, and for the qualitative data on histopathological findings, the percentage or qualitative scores (0 to +3) were used. Results: We found similar presentations of COVID-related histopathologic events regarding percentage and severity in pulmonary tissue, includinglymphocytic infiltrations, inflammatory infiltrations of septal and perivascular areas, desquamated type2 pneumocytes, hyaline membrane changes, fibrin material depositions, abnormal changes of alveolar capillaries, presence of megakaryocytes, PMN infiltrations, septal necrosis, microabscess formation and bacterial colony formation. Also, we found few interesting features which were not completely compatible with previous similar studies or newly reported by ours asa high percentage of anthracosis (86%: 13 patients) that was not clearly reported in other previous studies, also a lower percentage of microthrombotic vascular lung injuries (20%: 3 patients), and a higher percentage of viral cytopathic effects (27%: 4 patients). Conclusion: This article suggests a greater need for evaluatingthe autopsy samples of COVID-19 patients to provide better management strategies and propose the question of whether anthracosismay be a mortality risk factor in COVID-19 patients.