Accelerated silicosis in sandblasters: Pathology, mineralogy, and clinical correlates.

BACKGROUND: With increasing reports of accelerated and acute silicosis, PMF, and autoimmune disease among coal miners and silica-exposed countertop workers, we present previously incompletely-described pulmonary pathology of accelerated silicosis and correlations with mineralogy, radiography, and disease progression in 46 Texas oilfield pipe sandblasters who were biopsied between 1988 and 1995. METHODS: Worker examinations included pulmonary function tests, chest X-ray (CXR), high-resolution computed tomography (HRCT), and Gallium-67 scans. Quantitative mineralogic analysis of pulmonary parenchymal burden of silica, silicates, and metal particles used scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM EDS). RESULTS: Workers had clinical deterioration after <10 years exposure in dusty workplaces. Although initial CXR was normal in 54%, Gallium-67 scans were positive in 68% of those with normal CXR, indicating pulmonary inflammation. The histology of accelerated silicosis is diffuse interstitial infiltration of macrophages filled with weakly birefringent particles with or without silicotic nodules or alveolar proteinosis. Lung silica concentrations were among the highest in our database, showing a dose-response relationship with CXR, HRCT, and pathologic changes (macrophages, fibrosis, and silicotic nodules). Radiographic scores and diffusing capacity worsened during observation. Silica exposure was intensified, patients presented younger, with shorter exposure, more severe clinical abnormalities, higher lung particle burdens, and more rapid progression in a subset of patients exposed to recycled blasting sand. CONCLUSIONS: Accelerated silicosis may present with a normal CXR despite significant histopathology. Multivariable analyses showed silica, and not other particles, is the driver of observed radiologic, physiologic, and histologic outcomes. Eliminating this preventable disease requires higher physician, public health, and societal awareness.

Interstitial pulmonary disease and aluminum trihydrate exposure: A single case report and detailed workplace analysis.

Exposure to aluminum compounds is clearly associated with pulmonary function decrements, and several animal models document possible mechanisms of aluminum- compound-induced pulmonary toxicity. Nevertheless, disagreements remain about the precise mechanism by which exposures lead to damage. We present a strong case for attributing a case of interstitial pulmonary disease to occupational exposure to aluminum trihydrate. This report follows a 2014 publication of another case of interstitial pulmonary disease following a similar exposure. Our patient eventually underwent double lung transplantation nearly 5 years postexposure. Detailed pulmonary particulate elemental analysis suggested that aluminum metal, including aluminum trihydrate, was the most likely cause. A detailed assessment of the worker's relevant occupational exposures accompanies this case report.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

A case of welder's lung with end-stage pulmonary fibrosis.

BACKGROUND: Welding, performed regularly by more than a million workers worldwide, is associated with exposures to irritative, fibrogenic and carcinogenic fumes and gases. METHODS AND RESULTS: We present the case of a welder who had worked under extremely poor hygiene conditions for nearly 20 years and had developed end-stage lung fibrosis, finally requiring lung transplantation. Detailed histopathology and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) analyses of his lungs showed advanced interstitial fibrosis and dust deposits in the lungs and in peribronchial lymph nodes containing welding type bodies, Fe, Si (silica), Ti (titanium), SiAl (aluminum silicates), Fe with Cr (Steel), and Zr (Zirkonium). CONCLUSION: In the absence of a systemic disorder and the failure to meet the criteria for diagnosis of idiopathic pulmonary fibrosis (IPF), these findings suggest welder's lung fibrosis as the most likely diagnosis.

Coal mine dust lung disease in miners killed in the Upper Big Branch disaster: a review of lung pathology and contemporary respirable dust levels in underground US coal mines.

OBJECTIVES: In 2010, 29 coal miners died due to an explosion at the Upper Big Branch (UBB) mine in West Virginia, USA. Autopsy examinations of 24 individuals with evaluable lung tissue identified 17 considered to have coal workers' pneumoconiosis (CWP). The objectives of this study were to characterise histopathological findings of lung tissue from a sample of UBB fatalities and better understand the respirable dust concentrations experienced by these miners at UBB relative to other US coal mines. METHODS: Occupational pulmonary pathologists evaluated lung tissue specimens from UBB fatalities for the presence of features of pneumoconiosis. Respirable dust and quartz samples submitted for regulatory compliance from all US underground coal mines prior to the disaster were analysed. RESULTS: Families of seven UBB fatalities provided consent for the study. Histopathologic evidence of CWP was found in all seven cases. For the USA, central Appalachia and UBB, compliance dust samples showed the geometric mean for respirable dust was 0.468, 0.420 and 0.518 mg/m3, respectively, and respirable quartz concentrations were 0.030, 0.038 and 0.061 mg/m3. After adjusting for quartz concentrations, UBB exceeded the US permissible exposure limit (PEL) for respirable dust in 28% of samples. CONCLUSIONS: Although higher than average respirable dust and quartz levels were observed at UBB, over 200 US underground coal mines had higher dust concentrations than UBB and over 100 exceeded the PEL more frequently. Together with lung histopathological findings among UBB fatalities, these data suggest exposures leading to CWP in the USA are more prevalent than previously understood.

Evidence for Environmental-Human Microbiota Transfer at a Manufacturing Facility with Novel Work-related Respiratory Disease.

Rationale: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease.Objectives: As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers.Methods: Workplace environmental microbiota were evaluated in air and MWF samples. Human microbiota were evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, in lung tissue samples from control subjects, and in skin, nasal, and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B cells were assessed.Measurements and Main Results: An increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared with control subjects. Among workers in different locations within the facility, those that worked in the machine shop area had skin, nasal, and oral microbiota more closely related to the microbiota present in the MWF samples. Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in the pathology of index cases.Conclusions: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Severe lung disease characterized by lymphocytic bronchiolitis, alveolar ductitis, and emphysema (BADE) in industrial machine-manufacturing workers.

BACKGROUND: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures. METHODS: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing. RESULTS: Five previously healthy male never-smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV1 = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B-cell follicles lacking germinal centers, and significant emphysema for never-smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities. CONCLUSION: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never-smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention.

Lanthanum deposition from oral lanthanum carbonate in the upper gastrointestinal tract.

AIMS: Lanthanum carbonate is used as an alternative to calcium-based phosphate binders to manage hyperphosphataemia in patients with renal failure. The deposition of lanthanum within gastroduodenal mucosa of patients treated with the medication has been described, but given the relative novelty of this entity, the histiocytic deposits in the gastroduodenal mucosa can be confused with a variety of other processes, including infections and other drug-induced forms of injury. METHODS AND RESULTS: We describe five cases of lanthanum phosphate deposition in upper gastrointestinal (GI) tract biopsies. Three cases were confirmed with scanning electron microscopy and energy dispersive X-ray analysis, including one unique patient, status post-renal transplant for polycystic kidney disease, who had last taken lanthanum 7 years prior to biopsy. CONCLUSION: Lanthanum deposition in the upper GI tract is a mimic of other drug-related forms of GI injury, including iron pill-related gastropathy. The key to making this diagnosis is a thorough drug history and awareness of the histological features.

Lung Pathology in U.S. Coal Workers with Rapidly Progressive Pneumoconiosis Implicates Silica and Silicates.

RATIONALE: Recent reports of progressive massive fibrosis and rapidly progressive pneumoconiosis in U.S. coal miners have raised concerns about excessive exposures to coal mine dust, despite reports of declining dust levels. OBJECTIVES: To evaluate the histologic abnormalities and retained dust particles in available coal miner lung pathology specimens, and to compare these findings with those derived from corresponding chest radiographs. METHODS: Miners with severe disease and available lung tissue were identified through investigator outreach. Demographic as well as smoking and work history information was obtained. Chest radiographs were interpreted according to the International Labor Organization classification scheme to determine if criteria for rapidly progressive pneumoconiosis were confirmed. Pathology slides were scored by three expert pulmonary pathologists using a standardized nomenclature and scoring system. MEASUREMENTS AND MAIN RESULTS: Thirteen cases were reviewed, many of which had features of accelerated silicosis and mixed dust lesions. Twelve had progressive massive fibrosis, and 11 had silicosis. Only four had classic lesions of simple coal workers' pneumoconiosis. Four had diffuse interstitial fibrosis with chronic inflammation, and two had focal alveolar proteinosis. Polarized light microscopy revealed large amounts of birefringent mineral dust particles consistent with silica and silicates; carbonaceous coal dust was less prominent. On the basis of chest imaging studies, specimens with features of silicosis were significantly associated (P = 0.047) with rounded (type p, q, or r) opacities, whereas grade 3 interstitial fibrosis was associated (P = 0.02) with the presence of irregular (type s, t, or u) opacities. CONCLUSIONS: Our findings suggest that rapidly progressive pneumoconiosis in these miners was associated with exposure to coal mine dust containing high concentrations of respirable silica and silicates.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

Novel Poxvirus Infection in an Immune Suppressed Patient.

BACKGROUND: Human and animal poxvirus infections are being reported with increasing frequency. We describe a challenging case history and treatment of a previously unknown poxvirus rash illness in a renal transplant patient. METHODS: A combination of classical microbiology techniques, including viral culture and electron microscopy, were used to provide initial clinical diagnosis. Subsequent standard polymerase chain reaction assays available in 2001 were noncontributory. Next generation sequencing was used to provide definitive diagnosis. RESULTS: Retrospectively, next generation sequencing methods were used to ultimately provide the definitive diagnosis of a novel poxvirus infection initially identified by electron microscopy. The closest relative of this poxvirus, identified in North America, is a poxvirus collected from a mosquito pool from Central Africa in 1972. CONCLUSIONS: This diagnostic quandary was ultimately solved using next generation DNA sequencing. This article describes the use of classical and next generation diagnostic strategies to identify etiologic agents of emerging infectious diseases and once again demonstrates the susceptibility of immunossupressed patients to novel pathogens. The virus identified is closely related to Yoka virus; these viruses appear to have independently diverged from a common ancestor of all known orthopoxviruses.

An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease.

RATIONALE: Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD). OBJECTIVES: The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD. METHODS: Evidence was identified by a search of MEDLINE. The committee then summarized the evidence, drew conclusions, and described their approach to diagnosis and management. MAIN RESULTS: The beryllium lymphocyte proliferation test is the cornerstone of both medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test without evidence of lung disease is diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in the lung is diagnostic of CBD. The determinants of progression from BeS to CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP ß chain appear to increase the risk. Periodic evaluation of affected individuals can detect disease progression (from BeS to CBD, or from mild CBD to more severe CBD). Corticosteroid therapy is typically administered when a patient with CBD exhibits evidence of significant lung function abnormality or decline. CONCLUSIONS: Medical surveillance in workplaces that use beryllium-containing materials can identify individuals with BeS and at-risk groups of workers, which can help prioritize efforts to reduce inhalational and dermal exposures.

Commentary on pathologic diagnosis of asbestosis and critique of the 2010 Asbestosis Committee of the College of American Pathologists (CAP) and Pulmonary Pathology Society's (PPS) update on the diagnostic criteria for pathologic asbestosis.

We reviewed the 2010 Asbestosis Committee's update on the diagnostic criteria for pathologic asbestosis. We must respectfully disagree with many of the criteria set forth therein, especially for recognizing asbestosis at its earliest stages; with statements focusing on the number of asbestos bodies needed in order to make a pathologic diagnosis of asbestosis; and regarding the benefits and pitfalls of relying on fiber analysis for diagnostic purposes, especially where chrysotile asbestos is concerned, including the methodology used for fiber determination. This critique has become even more relevant with the 2014 Helsinki criteria publication, which adopted the 2010 CAP/PPS criteria. Based on our review of these newer criteria and our experience in this field, we find that the CAP-NIOSH 1982 criteria is still the most acceptable method for the pathologic diagnosis and grading of asbestosis, which can be described as pulmonary fibrosis caused by inhalation of asbestos fibers.

Necrotizing infundibular crystalline folliculitis manifesting as a perforating mucinosis: a case report.

: Necrotizing infundibular crystalline folliculitis (NICF) is a rare entity manifesting as waxy folliculocentric papules comprised of filamentous birefringent crystalline deposits. We report a case of NICF in an 85-year-old man, presenting as gritty, cream-colored, and erythematous papules across the midline back. Biopsy demonstrated a pale plug comprised of copious mucin. The diagnostic crystals were initially overlooked because of softening of the paraffin block with 10% ammonia solution, which dissolved the crystals in the initial sections. X-ray microanalysis confirmed the organic nature of the crystals. This is the first report of NICF from North America. Our case highlights the presence of mucin in some cases of NICF and serves as a cautionary tale on the pitfalls of postprocessing artifacts in the histology laboratory.

Localized cutaneous argyria: two case reports and clinicopathologic review.

We report 2 cases of patients who presented with blue macules clinically suspicious for blue nevi. One patient had no documented history of trauma or silver exposure, and the other reported exposure to silver over 30 years ago. Microscopic examination revealed a dermal population of brown-black globules predominantly adhering to collagen fibers. In both cases, no melanocytic proliferation was identified by immunohistochemistry. Analysis of the skin biopsies with scanning electron microscopy and energy dispersive x-ray spectroscopy demonstrated the presence of silver and selenium. These findings were diagnostic of localized cutaneous argyria. Our case reports highlight the importance of including localized cutaneous argyria in the differential diagnosis of pigmented lesions.

Mining Tenure and Job Duties Differ Among Contemporary and Historic Underground Coal Miners With Progressive Massive Fibrosis.

OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners ( n = 33) had significantly shorter mean total (30.4 years vs 37.1 years, P = 0.0006) and underground (28.8 years vs 35.8 years, P = 0.001) mining tenure compared with historic miners ( n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs 15.8%, P = 0.03) and contemporary miners (58.1% vs 15.2%, P < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention.