Pulmonary Granulomatosis Research Articles

Potential Association of Cutibacterium acnes with Sarcoidosis as an Endogenous Hypersensitivity Infection.

The immunohistochemical detection of Cutibacterium acnes in sarcoid granulomas suggests its potential role in granuloma formation. C. acnes is the sole microorganism ever isolated from sarcoid lesions. Histopathologic analysis of some sarcoid lymph nodes reveals latent infection and intracellular proliferation of cell-wall-deficient C. acnes followed by insoluble immune-complex formation. Activation of T helper type 1 (Th1) immune responses by C. acnes is generally higher in sarcoidosis patients than in healthy individuals. Pulmonary granulomatosis caused by an experimental adjuvant-induced allergic immune response to C. acnes is preventable by antimicrobials, suggesting that the allergic reaction targets C. acnes commensal in the lungs. C. acnes is the most common bacterium detected intracellularly in human peripheral lungs and mediastinal lymph nodes. Some sarcoidosis patients have increased amounts of C. acnes-derived circulating immune complexes, which suggests the proliferation of C. acnes in affected organs. In predisposed individuals with hypersensitive Th1 immune responses to C. acnes, granulomas may form to confine the intracellular proliferation of latent C. acnes triggered by certain host-related or drug-induced conditions. Current clinical trials in patients with cardiac sarcoidosis are evaluating combined treatment with steroids and antimicrobials during active disease with continued antimicrobial therapy while tapering off steroids after the disease subsides.

Une sarcoïdose difficile à diagnostiquer

AbstractAbout a case of pulmonary granulomatosis disease first diagnosed as a tuberculosis from thoracic X ray examination; anamnesis, thoracic scanner and biological analyses established diagnosis of sarcoidosis which could be confirmed by pathological analysis of cutaneous lesions found after deep physical examination. Biological analyses showed that intern organs were also injured; corticoid therapy easily cured the disease with normalized biological values. The increase in serum angiotensin converting enzyme activity (ACE) is not specific for sarcoidosis but guides the physician toward diagnosis in this case and can follow efficacy of the therapy. Serum ACE activity is determined by spectrophotometric methods developed on biochemistry automates.

Pulmonary granulomatosis of genetic origin

Granulomatous inflammation of the lung can be a manifestation of different conditions and can be caused by endogenous inflammation or external triggers. A multitude of different genetic mutations can either predispose patients to infections with granuloma-forming pathogens or cause autoinflammatory disorders, both leading to the phenotype of pulmonary granulomatosis. Based on a detailed patient history, physical examination and a diagnostic approach including laboratory workup, pulmonary function tests (PFTs), computed tomography (CT) scans, bronchoscopy with bronchoalveolar lavage (BAL), lung biopsies and specialised microbiological and immunological diagnostics, a correct diagnosis of an underlying cause of pulmonary granulomatosis of genetic origin can be made and appropriate therapy can be initiated. Depending on the underlying disorder, treatment approaches can include antimicrobial therapy, immunosuppression and even haematopoietic stem cell transplantation (HSCT). Patients with immunodeficiencies and autoinflammatory conditions are at the highest risk of developing pulmonary granulomatosis of genetic origin. Here we provide a review on these disorders and discuss pathogenesis, clinical presentation, diagnostic approach and treatment.

Subclinical Pulmonary Granulomatosis With Polyangiitis With Dramatic Response to Treatment.

Subclinical Pulmonary Granulomatosis With Polyangiitis With Dramatic Response to Treatment.

RECURRENT ARDS IN THE SETTING OF POLYSUBSTANCE ABUSE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Drug abuse remains a significant social problem in many countries. Adverse pulmonary complications of substance abuse are well documented, including diffuse alveolar haemorrhage, aspiration pneumonitis, and opportunistic infections related to HIV and hepatitis. Acute lung injury and acute respiratory distress syndrome are well known complications of narcotic overdose, but ARDS from drug use without overdose is a much rarer entity. [1] CASE PRESENTATION: We report a case of a 39 year old female, current 10 pack-year smoker, with a history of polysubstance abuse including heroin, cocaine and alcohol, who was admitted 5 times in 8 months with recurrent episodes of dyspnea, fever, myalgias and fatigue. Each time she presented with hypoxic respiratory failure and bilateral infiltrates on chest imaging, and required high flow oxygen and BIPAP. She was treated with IV antibiotics, steroids and diuresis with good response. An extensive workup was performed including negative cultures, negative connective tissue disease serologies, and negative HIV testing. Echocardiogram showed a normal ejection fraction and negative bubble study. CT scan during the first hospitalization showed diffuse bilateral ground-glass opacities with bilateral lower lobe predominance and subpleural sparing without bronchiectasis or subpleural honeycombing. Outpatient PFTs showed only a moderately decreased diffusing capacity; methacholine challenge test showed mild bronchial hyperresponsiveness. Patient underwent bronchoscopy during one hospitalization that showed grossly normal airways, neutrophil predominant BAL and no eosinophilia; endobronchial biopsy showed atypical bronchial epithelium favoring reactive process. Surgical lung biopsy revealed rare intracapillary granulomas with exogenous polarizable material – microcrystalline cellulose consistent with IV drug injection. DISCUSSION: Pulmonary foreign body granulomatosis is described in patients who inject oral drugs intravenously. [2-3]. This would not account for the fulminant respiratory failure with ARDS in this patient. A case series of 6 patients using narcotics, gabapentin, and other psychoactive drugs, with presentation similar to our patient, with recurrent ARDS and diffuse alveolar damage on lung biopsy, has been reported [4]. DAD was not identified on this patient’s surgical lung biopsy, perhaps because the patient was biopsied in between recurrences. Management of this condition is unclear with some reports indicating a potential benefit from systemic glucocorticoids [5]. Some patients with recurrent ARDS progress to worsening fibrosis and may eventually need lung transplant. Our patient has been managed with recurrent prolonged prednisone taper, but further treatment is complicated by her social issues and medication noncompliance. CONCLUSIONS: DAD is pathologic manifestation of severe acute lung injury, recurrence can be attributed to polysubstance abuse. Reference #1: [1] Benson MK, Bentley AM. Lung disease induced by drug addiction. Thorax. 1995; 50(11): 1125–1127. Reference #2: [2]Bishay A, Amchentsev A, Saleh A, Patel N, Travis W, Raoof S. A hitherto unreported pulmonary complication in an IV heroin user. Chest 2008;133(2)549-51. Reference #3: [3] Radow SK, Nachamkin I, Morrow C, et al. Foreign body granulomatosis. Clinical and immunologic findings. Am Rev Respir Dis 1983;127:575. [4] Savici D, Katzenstein A-LA. Diffuse alveolar damage and recurrent respiratory failure: report of 6 cases. Human Pathology 2001;32(12):1398-402. [5] Chau CH, Yew WW, Lee J. Inhaled budesonide in the treatment of talc-induced pulmonary granulomatosis. Respiration. 2003;70(4):439. DISCLOSURES: No relevant relationships by Moayad Al Sona, source=Web Response No relevant relationships by Sandrine Hanna, source=Web Response No relevant relationships by Margaret Zambon, source=Web Response

Pyothorax and pulmonary lymphomatoid granulomatosis in a cat

Pyothorax and pulmonary lymphomatoid granulomatosis in a cat

Functional state of the autonomic nervous system, adaptation, homeostasis and reactivity of the organism in the clinic of tuberculosis and sarcoidosis

In recent decades, the shift in priority in the treatment of patients with pulmonary granulomatosis in the direction of etiotropic therapy and reduced attention to the state of the macroorganism led to a decrease in the effectiveness of treatment. In modern conditions, when carrying out complex therapy for patients with tuberculosis and sarcoidosis, insufficient attention is paid to the state and dynamics of adaptation, resistance, homeostasis and reactivity of the organism. At the same time, the dynamics of these processes in patients is insignificant, the homeostatic balance of the organism is not restored, and the reactivity of the organism remains at the pathological level, with the predominance of paradoxical, hyporeactive and areactive types. This is due to the continuing influence on the regulatory centers of the vegetative system of not diagnosed, latent, ongoing tuberculosis intoxication. Undetected specific intoxication causes in patients activation of the sympathetic department, suppression of parasympathetic and development of dysfunction of the autonomic nervous system. Its dysfunction leads to a decrease in vascular supply of the organism, a high tension of anabolic processes, and a further change in the functional activity of both parts of this system when pathology develops. In addition, the emergence of vegetative dysfunction leads to a high consumption of plastic materials, energy resources, a decrease in the functional reserves of the body, a decrease and depletion of the body’s defense systems, its anti-inflammatory potential and the reactivity of the organism as a whole. These changes lead to an extension of the main course of treatment and the formation of expressed residual tubercular and sarcoidosis in the respiratory organs. To restore these disorders, it is necessary to carry out complex therapy with the inclusion of a personified appointment of activators of protective systems under the control of monitoring their effectiveness.

Unusual cause of a fatal foreign body pulmonary granulomatosis

Pulmonary foreign body granulomatosis is a rare disease characterized by granuloma as a result of exposure to mineral substances. It has been reported in intravenous drug abusers who inject powdered medications. In the present case a 57-year-old female tourist with a history of cancer died in her hotel room. The autopsy revealed pulmonary fibrosis with granulomatosis containing birefringent particles (mainly talc). The cause of death was an acute right heart failure due to chronic pulmonary hypertension triggered by regular therapeutic use of painkillers after cancer occurring in previous years.

Cosmetic Talc–Related Pulmonary Granulomatosis

Inhalation of cosmetic talc can lead to pulmonary foreign-body granulomatosis, though fewer than 10 cases of inhaled cosmetic talc–related pulmonary granulomatosis have been reported in adults. We report the case of a 64-year-old man with diffuse, bilateral pulmonary nodules and ground glass opacities associated with chronic inhalation of cosmetic talc. Transbronchial biopsy showed peribronchiolar foreign-body granulomas. After cessation of talc exposure, the patient demonstrated clinical and radiographic improvement without the use of corticosteroids. This case demonstrates that a conservative approach with cessation of exposure alone, without the use of corticosteroids, can be an effective therapy in cosmetic talc–related pulmonary granulomatosis.

A Case of Pulmonary Granulomatosis with Polyangiitis Mimicking Septic Pneumonia Resulting from Middle Ear Infection

A Case of Pulmonary Granulomatosis with Polyangiitis Mimicking Septic Pneumonia Resulting from Middle Ear Infection

English

English

Acute Pulmonary Vascular Talcosis: Mimicking Acute Pulmonary Embolism

Intravenous injection of powdered tablets intended to oral use is a common practice among drug abusers, given the greater effectiveness attributed to accelerate delivery of the drug through this route compared to oral intake. This can result in both acute and chronic changes in the pulmonary vessels and parenchyma. Various terms have been used to describe this entity and include self-induced pulmonary granulomatosis, pulmonary antithrombotic granulomatosis, pulmonary mainline granulomatosis, and angiocentric systemic granulomatosis. Acute right ventricular failure is a life threatening complication from intravenous injection of powdered medications and very few such cases have been reported in the literature.

Small Airway-Centered Granulomatosis Caused by Long-term Exposure to Polytetrafluoroethylene

To date, there have been no reports of chronic pulmonary granulomatosis associated with exposure to polytetrafluoroethylene (PTFE). Here, we report three cases of small airway-centered granulomatous lesions in workers employed at facilities that apply coatings to pans and other utensils. The workers were repeatedly exposed to PTFE particles that were probably generated by the drying process when PTFE coatings are dried in a convection oven at high temperatures (380-420 °C). The duration of inhalational PTFE exposure was between 7 and 20 years. We found granulomatous lung lesions around the small airways in lung biopsy specimens obtained from the workers. Scanning electron microscopy/energy-dispersive x-ray spectroscopy analysis was performed focusing on areas where the PTFE particles were suspected to be located in macrophages. The scanning electron microscopy/energy-dispersive x-ray spectroscopy analyses revealed fluorine in the particles. Lung tissue samples from all cases were analyzed using a fully automated Fourier transform infrared spectrometer. Analysis of the spectrum extracted from the position of the foreign particles enabled precise identification of the foreign bodies as PTFE. Fourier transform infrared revealed that all of the lung tissue samples had bands at 1,202 to 1,148 cm(-1) and 1,202 to 1,146 cm(-1), which are characteristic of the asymmetric and symmetric stretching vibrations of the C-F bonds of PTFE. These cases suggest that recurrent inhalational exposure to PTFE particles causes chronic pulmonary granulomatosis.

Wegener's granulomatosis simulates pulmonary adenocarcinoma

Wegener's granulomatosis is a rare systemic granulomatous necrotizing vasculitis that characteristically involves the upper airways, lungs, and kidneys. Pulmonary Wegener's granulomatosis can present with multifocal lung involvement or solitary lung lesions. Diagnosing Wegener's granulomatosis on the basis of cytological material from sputum may be challenging for pathologists. A wrong diagnosis may lead to inappropriate treatment. We report a case of Wegener's granulomatosis in a patient who first presented with hemoptysis, poor appetite, and weight loss. Multifocal pulmonary nodules were seen on a chest radiograph and the features seen on sputum cytology were similar to those of lung adenocarcinoma. A lung biopsy sample proved granulomatous inflammation. Wegener's granulomatosis was diagnosed based on the biopsy sample and a positive cytoplasmic antineutrophil cytoplasmic antibody titer (1:1280). After treatment with prednisone and cyclophosphamide, the lung lesions resolved. We recommend measuring the cytoplasmic antineutrophil cytoplasmic antibody titer in patients with bilateral pulmonary lesions. A lung biopsy sample should always be obtained, even when the cytology findings suggest a malignancy.

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF EOSINOPHILIC PULMONARY GRANULOMATOSIS IN FIVE DOGS

Canine pulmonary eosinophilic granulomatosis is a rare inflammatory pulmonary disease characterized by formation of eosinophilic granulomas that tend to obliterate the normal pulmonary architecture. The purpose of this retrospective study was to describe the CT characteristics of confirmed idiopathic pulmonary eosinophilic granulomatosis in a group of dogs. Five dogs met inclusion criteria. All patients were young adult dogs of variable breeds. No dog had concurrent occult heartworm disease. Computed tomographic characteristics most commonly included pulmonary masses and nodules of variable size, and lesions were most commonly located in the caudal lung lobes. Four dogs had large pulmonary masses with or without additional nodules and one dog had nodular lesions disseminated throughout the entire lung parenchyma. All large eosinophilic granulomas were smoothly margined, heterogeneous pulmonary masses displaying heterogeneous contrast enhancement. A honeycomb-like enhancement pattern was observed in all but one mass and consisted of multiple hyperattenuating rims delineating central hypoattenuating areas, suggestive of bronchiectatic lung with peripheral enhancing airway walls and fluid-filled, necrotic bronchial lumen. One dog had evidence of tracheobronchial lymphadenopathy. Findings indicated that canine eosinophilic pulmonary granulomatosis should be included as a differential diagnosis for dogs with CT characteristics of multiple pulmonary masses and/or nodules in caudal lung lobes, and a honeycomb-like enhancement pattern in masses after intravenous administration of iodinated contrast medium.

Stimulants and the Lung

Illicit stimulants, such as cocaine, amphetamine, and their derivatives (e.g., "ecstasy"), continue to exact heavy toll on health care in both developed and developing countries. The US Department of Health and Human Service reported over one million illicit drug-related emergency department visits in 2010, which was higher than any of the six previous years. Both inhaled and intravenous forms of these substances of abuse can result in a variety of acute and chronic injuries to practically every part of the respiratory tract, leading potentially to permanent morbidities as well as fatal consequences--including but not limited to nasal septum perforation, pulmonary hypertension, pneumothorax, pneumomediastinum, interstitial lung disease, alveolar hemorrhage, reactive airway disease, pulmonary edema, pulmonary granulomatosis, infections, foreign body aspiration, infections, bronchoconstriction, and thermal injuries. Stimulants are all rapidly absorbed substances that can also significantly alter the patient's systemic acid-base balance and central nervous system, thereby leading to further respiratory compromise. Mounting evidence in the past decade has demonstrated that adulterants coinhaled with these substances (e.g., levamisole) and the metabolites of these substances (e.g., cocaethylene) are associated with specific forms of systemic and respiratory complications as well. Recent studies have also demonstrated the effects of stimulants on autoimmune-mediated injuries of the respiratory tract, such as cocaine-induced midline destructive lesions. A persistent challenge to studies involving stimulant-associated respiratory toxidromes is the high prevalence of concomitant usage of various substances by drug abusers, including tobacco smoking. Now more than ever, health care providers must be familiar with the multitude of respiratory toxidromes as well as the diverse pathophysiology related to commonly abused stimulants to provide timely diagnosis and effective treatment.

Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis

Cathepsin K and tartrate-resistant acid phosphatase (TRAP) are two proteins expressed in osteoclastic giant cells. Recently we showed that lesional multinucleated giant cells (MNGs) in pulmonary granulomatosis with polyangiitis expressed these proteins. We aimed to clarify whether the expression of these two proteins has any specificity or is a general feature of MNGs associated with multiple types of granulomatous inflammation. In total, 7 Crohn's disease (CD), 5 GCA, 5 giant cell myocarditis (GCM), 11 sarcoidosis and 6 tuberculosis cases were examined for expression of cathepsin K and TRAP using immunohistochemistry (IHC). Protein expression was semi-quantitatively classified as none, weak, moderate or strong. In addition, tissue TRAP activity was examined using an enzymatic reaction. The expression of cathepsin K was robust in >95% of MNGs of all examined disease groups, whereas TRAP expression varied; CD, GCA and tuberculosis showed strong TRAP expression. TRAP expression in sarcoidosis and GCM was weaker (CD vs GCM, P = 0.04; CD vs sarcoidosis, P = 0.06). Compared with IHC, TRAP detection using an enzymatic colour reaction had limited sensitivity. Expression of TRAP and cathepsin K is a general feature of MNGs and their expression might be related to histopathological pattern.

Eosinophilic pulmonary granulomatosis in a young dog with prolonged remission after treatment

A two-year-old Jack Russell terrier was presented for evaluation of chronic cough and exercise intolerance. Previous treatment with antibiotics and glucocorticoids had only partially ameliorated the clinical signs. During investigation, hypoxaemia, peripheral eosinophilia and an eosinophilic bronchoalveolar lavage fluid were noted. Thoracic radiographs revealed two ovoid clearly delineated soft-tissue opacities, one in the caudal segment of the left cranial lung lobe (diameter 26 mm) and the other in the right cranial lung lobe (diameter 20 mm). These findings were verified by computed tomography, which identified an additional smaller lesion (diameter 16 mm) dorsally in the right caudal lobe. Ultrasound-guided fine-needle aspiration samples confirmed the diagnosis of eosinophilic pulmonary granulomatosis and treatment with prednisolone and azathioprine was initiated. Within 1 month, granulomas were no longer detectable radiographically. All medication was discontinued after 7 months and currently, after 2·5 years, the dog remains free of clinical signs. To the authors' knowledge this is the first case report to describe prolonged remission from idiopathic canine eosinophilic pulmonary granulomatosis.

Hypersensitivity pneumonitis induced by Shiitake mushroom spores

Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

Pulmonary Hypertension in Pulmonary Langerhans Cell Granulomatosis

Introduction. Pulmonary Langerhans cell granulomatosis is a rare disease with a variable course. In pulmonary Langerhans cell granulomatosis pulmonary hypertension is frequent and has an independent prognostic impact. A vasculopathy which ist not related to ventilatory disturbance and fibrosis has been identified. An arteriopathy and even a venulopathy have been described. Due to this possible venulopathy vasodilators carry a significant risk for pulmonary congestion and edema. No drugs have been approved until now. Case Presentation. One female with PLCG developed severe PH four years after primary diagnosis of pulmonary Langerhans cell granulomatosis. Retrospective analysis of lung biopsies revealed an arterial vasculopathy at the time of primary diagnosis without clinical signs of PH at this time. Sildenafil led to a sustained improvement of hemodynamic features and exercise capacity. Conclusion. This paper underlines that patients with PLCG with an arterial vasculopathy-related PH might improve under sildenafil. Further trials addressing treatment of PH and vasculopathy are needed.