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.

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.

Pathologic Findings in Severe Coal Workers' Pneumoconiosis in Contemporary US Coal Miners.

CONTEXT.­: The pathology of coal workers' pneumoconiosis (CWP) and its most severe form-progressive massive fibrosis (PMF)-in US coal miners has changed in recent years. Severe disease is occurring in younger miners and has been linked to an increase in silica dust exposure. OBJECTIVE.­: To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. DESIGN.­: This study is a retrospective expert classification of lung tissue from 85 historical and contemporary coal miners with PMF. Significant pathologic features were scored by using a standardized instrument with consensus achieved for major findings, including newly defined categories of PMF as coal-type, mixed-type, and silica-type. RESULTS.­: Pathologic features associated with silica dust exposure, including silica-type PMF, mineral dust alveolar proteinosis (MDAP), and immature (early stage) silicotic nodules were increased in contemporary miners. Detailed descriptions of the pathology of contemporary CWP with illustrative figures are provided. CONCLUSIONS.­: Silica-related pathologies are more common in contemporary miners. Severe forms of CWP can be detected by subtyping PMF lesions (if present) or by identification of mature and immature silicotic nodules, coal mine dust-related alveolar proteinosis, and severe inflammation in coal miners' lungs. Silica-type PMF cases showed significantly higher levels of MDAP than either mixed- or coal-type PMF (P < .001). High profusion of birefringent silica/silicate particles was observed more frequently in cases with immature (early stage) silicotic nodules (P = .04). Severe inflammation was also significantly increased in contemporary miners (P = .03). Our findings underscore the urgent need to revise current exposure limits and monitoring of respirable crystalline silica in US coal mines.

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.

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.

Barium Sulfate Deposition in the Gastrointestinal Tract: Review of the literature.

BACKGROUND: Barium sulfate is utilized for imaging of the gastrointestinal tract and is usually not deposited within the wall of the intestine. It is thought that mucosal injury may allow barium sulfate to traverse the mucosa, and allow deposition to occur uncommonly. Most pathology textbooks describe the typical barium sulfate deposition pattern as small granular accumulation in macrophages, and do not describe the presence of larger rhomboid crystals. This review will summarize the clinical background, radiographic, gross, and microscopic features of barium sulfate deposition in the gastrointestinal tract. A review of the PubMed database was performed to identify all published cases of barium sulfate deposition in the gastrointestinal tract that have been confirmed by pathologic examination. CONCLUSIONS: A review of the literature shows that the most common barium sulfate deposition pattern in the gastrointestinal tract is finely granular deposition (30 previously described cases), and less commonly large rhomboid crystals are seen (19 cases) with or without finely granular deposition. The fine granules are typically located in macrophages, while rhomboid crystals are usually extracellular. There are various methods to support that the foreign material is indeed barium sulfate, however, only a minority of studies perform ancillary testing. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS) can be useful for definitive confirmation. This review emphasizes the importance of recognizing both patterns of barium sulfate deposition, and the histologic differential diagnosis.

Pathology and Mineralogy Demonstrate Respirable Crystalline Silica Is a Major Cause of Severe Pneumoconiosis in U.S. Coal Miners.

Rationale: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States are not yet fully understood. Objectives: To compare the pathologic and mineralogic features of contemporary coal miners with severe pneumoconiosis with those of their historical counterparts. Methods: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) with those in miners born in or after 1930 (contemporary). Results: We found a significantly higher proportion of silica-type PMF (57% vs. 18%; P < 0.001) among contemporary miners compared with their historical counterparts. Mineral dust alveolar proteinosis was also more common in contemporary miners compared with their historical counterparts (70% vs. 37%; P < 0.01). In situ mineralogic analysis showed that the percentage (26.1% vs. 17.8%; P < 0.01) and concentration (47.3 × 108 vs. 25.8 × 108 particles/cm3; P = 0.036) of silica particles were significantly greater in specimens from contemporary miners compared with their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, mineral dust alveolar proteinosis, silicotic nodules, or immature silicotic nodules were present (P < 0.05). Conclusions: Exposure to respirable crystalline silica appears causal in the unexpected surge of severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure to prevent the disabling and untreatable adverse health effects afflicting U.S. coal miners.

Successful treatment with secnidazole for trichomoniasis in the setting of metronidazole hypersensitivity.

Limited effective treatment options currently exist for trichomoniasis management among patients with metronidazole hypersensitivity. We report a patient with a documented history of metronidazole hypersensitivity who initially was treated with nitazoxanide but demonstrated clinical and microbiological failure. Secnidazole was subsequently used for treatment, which resulted in clinical and microbiological cure without observation of cross-reactivity. Secnidazole may represent a potential treatment option for trichomoniasis in patients with metronidazole hypersensitivity after consultation with an infectious disease specialist.

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.

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.

Hydroxyurea-induced hyperpigmentation with iron deposition.

Hydroxyurea is a chemotherapeutic agent that is used in the treatment of various hematological diseases including chronic myelogenous leukemia, polycythemia vera, and sickle cell anemia. Hydroxyurea is also used to treat psoriasis. Drug-induced hyperpigmentation is a known cutaneous side effect of hydroxyurea along with xerosis, dermal ulcers, and dermatomyositis-like eruptions. Hyperpigmentation has been observed in the oral mucosa, nails, and in a generalized or a diffuse pattern. The mechanism of hyperpigmentation related to hydroxyurea is believed to be correlated with increased melanin. Classically, clinical types of diffuse hyperpigmentation owing to iron deposition in the dermis have been associated with minocycline and not with hydroxyurea. We report a novel case in which hydroxyurea hyperpigmentation is associated with iron deposition.

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.

Mixed-dust pneumoconiosis: Review of diagnostic and classification problems with presentation of a work-related case.

Environmental aerosolized particulates pose a potential risk to human health worldwide. Among others, high amounts of contaminants are generated especially in newly industrializing countries in the vicinity of industrial manufacturing, mining operations, but also during agricultural and natural processes. As an example of the needed multi-disciplinary diagnostic and differential diagnostic approach, we report a case of a 59-year old industrial worker who has suffered from chronic bronchitis and progressive dyspnea on exertion for 8years. He showed severe lung function impairment, a cavity in his right upper lung lobe, nodular and irregular opacities, fibrotic pleural changes and emphysema. According to the occupational history and the industrial hygiene report, he had been engaged in the production of various refractory materials and been exposed to very high levels of inorganic dust, especially to silica, silicon carbide and aluminum compounds, but also to carbon and other dusty materials for 28years. Histopathology of the two resected lung segments showed focally infarcted granulomas and chronic inflammation. Stains for organisms were negative. The lung tissue away from the granulomas showed significant dust deposition including dust macules. In spite of the inorganic dust deposits, with adjacent tissue lesions evident from the radiological findings (which were interpreted as atypical for pneumoconiosis) and the presence of granulomas in lung tissue, a diagnosis of necrotizing sarcoid granulomatosis was made, which was later changed to mixed-dust pneumoconiosis on further detailed examination. Scanning Electron Microscopy/Energy-Dispersive X-ray Spectroscopy (SEM/EDS) analysis of individual particles showed predominantly Si (silica or silicon carbide [SiC]) and Al particles (consistent with aluminum metal and/or oxide), as well as numerous Al silicates, Ti, and occasional Zr, Nb, V, steel, including Si fibers (consistent with SiC). We present the controversy about the pathogenesis of the lung disorder and whether it represents an occupational disease - which is more or less representative for many such cases.

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.

Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis--an autopsy-based review.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a systemic disorder of patients with severe renal insufficiency who have received gadolinium (Gd)-based magnetic resonance contrast agents (GBCAs). The causative association with Gd exposure was strengthened by the demonstration of Gd in various tissues of NSF patients, predominantly at the bulk chemical level. The distribution of Gd at the histologic level of organs other than skin has not been reported previously. METHODS: We analysed tissues from an autopsy case with verified advanced NSF by light microscopy and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Furthermore, we reviewed published literature to compare the histological and histochemical findings in NSF patients and chronic renal failure (CRF) patients without NSF. RESULTS: Insoluble Gd-phosphate deposits were detected in the skin, liver, lungs, intestinal wall (ileum), kidney, lymph node, skeletal muscle, dura mater and cerebellum of the NSF autopsy case, primarily in vascular walls. Some, but not all, Gd deposits were seen in fibrotic areas. Literature review highlighted that non-specific tissue fibrosis and calcification are frequent findings in tissues of patients with CRF with and without NSF. CONCLUSIONS: Vascular and extracellular Gd deposits are found in multiple organs of NSF patients, associated with calcification, and often in fibrotic areas. Gd deposits are not seen in patients with CRF unexposed to GBCAs but rarely may be seen in GBCA-exposed patients without clinical signs of NSF. Apart from diagnostic findings in skin, fibrosis of muscle and dura may be more prominent in NSF patients. Our findings should stimulate further investigation of mechanisms of fibrosis and pathologic calcification.

Tissue gadolinium deposition and fibrosis mimicking nephrogenic systemic fibrosis (NSF)-subclinical nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis is a condition with significant and often debilitating cutaneous manifestations. Recent research on this disease has delineated an association between nephrogenic systemic fibrosis and exposure to magnetic resonance imaging studies using gadolinium-based contrast agents in patients with ongoing renal failure. This metal has been detected in cutaneous biopsy specimens taken from lesional skin suggesting that gadolinium provides an impetus for the deposition of circulating fibrocytes in the skin and subsequent fibrosis. We describe a hemodialysis-dependent liver transplant recipient who received a gadolinium-based contrast agent and demonstrated insoluble gadolinium deposition in a fibrotic dermis and subcutaneous septum using scanning electron microscopy/energy dispersive x-ray spectroscopy. He has yet to manifest symptoms and signs of nephrogenic systemic fibrosis 3 years after his magnetic resonance imaging study.

Nephrogenic systemic fibrosis: report of an additional case with granulomatous inflammation.

Nephrogenic systemic fibrosis (NSF) is a novel disease entity described over the past 10 years. NSF is a progressive systemic fibrosing disorder that occurs arguably exclusively in patients with impaired renal function who have been exposed to gadolinium-containing contrast agents. As no single clinical or histopathologic finding is diagnostic of NSF, a careful review of the cumulative characteristics of each case is essential in making a correct diagnosis. The spectrum of histologic variants of NSF continues to expand, including a report of NSF mimicking erythema nodosum and several case reports of NSF with giant cells and calcification. We report an additional case of NSF with the uncommon pathologic features of granulomatous and lymphocytic inflammation in the fibrous septae similar to erythema nodosum.