The evolving landscape of IL-10, IL-22 and IL-26 in pleurisy especially in tuberculous pleurisy.

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies.

[Treatment of malignant effusion]. / Sravnitel'naya kharakteristika metodov lecheniya metastaticheskogo plevrita (obzor literatury).

Malignant effusion complicates more than 15% of all cancers in delayed stages of progression. The most common causes of metastatic pleuritis are lung cancer, breast cancer, ovarian cancer, lymphoproliferative diseases or dissemination of gastrointestinal tumors. Malignant effusion is associated with negative prognosis for overall survival regardless of etiology of tumor, significantly complicates the course of the underlying disease, impairs life quality and complicates treatment. Despite various methods for pleural cavity obliteration in recurrent metastatic pleuritis, there is still no a uniform approach to choosing the optimal treatment strategy. We analyzed the main methods of conservative and surgical treatment of recurrent metastatic pleuritic regarding efficacy, risk of recurrence and reproducibility.

Rheumatoid pleurisy confirmed by biopsy of a chest wall nodule by thoracoscopy under local anaesthesia.

Rheumatoid pleurisy is common in patients with rheumatoid arthritis, but distinguishing it from other diseases, such as heart failure and tuberculous pleurisy, is often difficult. A man in his 70s with stable rheumatoid arthritis presented with cardiac enlargement and bilateral pleural effusion on chest radiography. Pleural fluid studies showed lymphocytosis, adenosine deaminase level of 51.6 U/L and rheumatoid factor level of 2245.3 IU/mL, suggestive of rheumatoid pleurisy and tuberculous pleurisy. Thoracoscopy under local anaesthesia revealed erythema of the parietal pleura, small papillary projections and fibrin deposits. H&E-stained biopsy specimens showed inflammatory granulomas with strong lymphocytic infiltration and non-caseating granulomas. He was diagnosed with rheumatoid pleurisy. His symptoms improved with 30 mg of prednisolone. This study highlights that biopsy using thoracoscopy under local anaesthesia effectively diagnoses rheumatoid pleurisy, which may be challenging to diagnose.

Idiopathic Lymphocytic Pleuritis Responding to Corticosteroid Therapy.

An 83-year-old man presented with chronic dyspnea, and chest X-ray showed bilateral pleural effusion. Right thoracentesis revealed lymphocyte-predominant exudate with no malignancy; bacterial and mycobacterial cultures were negative. Thoracoscopy via the right chest and a biopsy of the same site were performed; these showed lymphoplasmacytic infiltration and fibrosis, ruling out malignancy or tuberculosis. We decided to start corticosteroid therapy for the diagnosis of idiopathic lymphocytic pleuritis (ILP). The patient was discharged after clinical improvement, and steroids were tapered off. An early diagnosis by thoracoscopy and the exclusion of other diseases are important for initiating steroid therapy in patients with ILP.

Diagnostic flowchart for tuberculous pleurisy, pleural infection, and malignant pleural effusion.

BACKGROUND: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers. METHODS: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers. RESULTS: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/µL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion. CONCLUSION: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.

Is there a common definition for massive pleurisy?

The concept of massive pleurisy (MP) is frequently used to emphasize the significance of the amount of pleural effusion. However, there are significant disagreements about it due to the lack of a universal definition for MP. In our study, we sought to elucidate these distinctions. We employed a questionnaire comprised of visual and true/false sections. In the visual section, participants were shown real-time lung radiographs and schematic drawings and asked which ones were MP. On the other hand, suggestions regarding diagnosis, treatment, and consultations for MP were questionnaired. The study was comprised of 150 physicians from four distinct centers. On true/false and radiograph questions, physicians from the same branch exhibited differences of up to 50% (p < 0.05). On the level question, each branch involved reached a consensus (p = 0.003). In questions 3, 4, and 5, which also contained a true-false section, the branches gave varying responses, with the exception of the opinion that tube thoracostomy is unquestionably indicated in MP (p < 0.05). Establishing a common language for MP is crucial for clinician collaboration and appropriate patient management. Our study elucidates the divergences of opinion between branches and highlights the need for a unified definition.

LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy.

Pleural effusion (PE) is a common medical concern, often requiring thoracentesis for a definitive diagnosis. An elevated pleural fluid adenosine deaminase (ADA) may indicate tuberculosis, but this is not always the case. This study aimed to evaluate the accuracy of biomarkers determined in pleural fluid and propose a new diagnostic strategy for PE in patients with high levels of ADA in pleural fluid. This retrospective analysis studied patients with PE who received thoracentesis for the first time with an ADA level of > 33 U/L in the pleural fluid analysis at two tertiary hospitals from March 2019 to March 2023. Demographic and clinical data, as well as pleural fluid biomarkers and their ratios, were studied and compared between different PE groups, and a decision tree was developed. During the study period, 259 patients were enrolled, with four different types of PE: parapneumonic (PPE) 155, tuberculosis (TPE) 41, malignant (MPE) 50, and miscellaneous 13. Biomarkers and their ratios performed well in the differential diagnosis of PE, with the LDH/ADA ratio distinguishing between PPE and non-PPE with sensitivity and specificity of 98.06% and 98.08%, respectively. The combination of LDH/ADA ratio, ADA, and mononuclear cell percentage was identified as important factors for creating a decision tree with an overall accuracy of 89.96%. The pleural fluid LDH/ADA ratio was a useful diagnostic for distinguishing PPE from non-PPE, and a decision tree with an accuracy of 89.96% was created to differentiate the four forms of PE in clinical situations.

A case of synchronous IgG4-associated pleuritis and type 1 autoimmune pancreatitis.

A 50-year-old man presented to the emergency department with left chest pain, epigastralgia, and low-grade fever for several days. A CT scan showed left pleural effusion, ground-glass opacities in the lower lobes of both lungs, and a capsule-like rim in the pancreas. ERCP showed narrowing of the main pancreatic duct. EUS-FNA was performed, but pathological findings showed no IgG4-positive cells. A thoracoscopic biopsy was performed, and pathological findings showed many IgG4-positive cells. A diagnosis of autoimmune pancreatitis and IgG4-associated pleurisy was made according to international diagnostic criteria. After that, oral steroid therapy was started, and left pleural effusion and pancreatic enlargement improved.

Brucella pleuritis misdiagnosed as tuberculous pleuritis: a case report.

Pleurisy and pleural effusion caused by Brucella infection are rare. However, clinicians lack an understanding of these possibilities, and the underlying disorder is easy to misdiagnose. We report a 52-year-old male farmer who was admitted to hospital with a fever, chest pain, and shortness of breath. Closed chest drainage was performed by thoracocentesis, and the concentration of adenosine deaminase (ADA) in the pleural fluid was >45 U/L. Mononuclear cells in the pleural fluid accounted for 90% of the cells, and pathology indicated a large number of lymphocytes. The clinical diagnosis was tuberculosis with tuberculous pleurisy. However, subsequent pleural fluid culture results did not support tuberculous pleurisy. The results of pleural fluid culture indicated Brucella, and the results of Brucella tiger red plate agglutination indicated a titer of 1:400 (+++). The final diagnosis was brucellosis with pneumonia and pleurisy. After 12 weeks of oral treatment, the patient underwent follow-up chest radiographs. Radiography indicated complete resolution of the hydrothorax and pneumonia, and the patient reported no discomfort. The short-term curative effect was excellent. Pleurisy associated with brucellosis should be considered a differential for pleurisy in regions where brucellosis is endemic, to minimize the risk of misdiagnosis.

[Pulmonary re-expansion in metastatic pleural effusions after thoracentesis: A pilot study]. / Échogénicité des pleurésies : facteur prédictif d'amélioration de la dyspnée ? Étude pilote concernant les pleurésies métastatiques.

INTRODUCTION: Metastatic pleural effusion is a cause of dyspnea. The American thoracic society has strongly suggested that studies evaluating thoracic ultrasonography as potentially predictive of improvment of dyspnea are needed. METHODS: We conducted a prospective monocentric observational study to assess chest ultrasound predictors of response to thoracentesis. Fifteen patients with metastatic pleural effusion were included. RESULTS: The initial mean VAS score was5 ± 2,9 cm. The majority of patients had pleural effusions equal to or greater than 5 intercostal spaces (EIC) in height, while 7 patients had an abnormal curvature of the hemidiaphragm (flattened or inverted). PRIMARY ENDPOINT: The volume removed was greater in the group with anechoic pleurisy compared to the group with sonographic septation, notwithstanding complex pleural effusion (non-septated, relatively hyperechoic, with some spots in the effusion). The patients with complex pleural effusions had an higher score of dyspnea. SECONDARY ENDPOINTS: The 7 patients with abnormal diaphragmatic curvature presented significant dyspnea with a pain score of approximately 7 and profuse pleurisy occupying 8 intercostal spaces in height. The effusions of those who could not normalize their curvature had a complex aspect and the volume removed was lower. CONCLUSIONS: The ultrasound characteristics of pleural effusions seem to be predictors of improvment of dyspnea after thoracentesis. The septated and complex aspects are probably predictors of non improvment of dyspnea.

DNA methylation-based machine learning classification distinguishes pleural mesothelioma from chronic pleuritis, pleural carcinosis, and pleomorphic lung carcinomas.

OBJECTIVES: Our goal was to evaluate the diagnostic value of DNA methylation analysis in combination with machine learning to differentiate pleural mesothelioma (PM) from important histopathological mimics. MATERIAL AND METHODS: DNA methylation data of PM, lung adenocarcinomas, lung squamous cell carcinomas and chronic pleuritis was used to train a random forest as well as a support vector machine. These classifiers were validated using an independent validation cohort including pleural carcinosis and pleomorphic variants of lung adeno- and squamous cell carcinomas. Furthermore, we performed differential methylation analysis and used a deconvolution method to estimate the composition of the tumor microenvironment. RESULTS: T-distributed stochastic neighbor embedding clearly separated PM from lung adenocarcinomas and squamous cell carcinomas, but there was a considerable overlap between chronic pleuritis specimens and PM with low tumor cell content. In a nested cross validation on the training cohort, both machine learning algorithms achieved the same accuracies (94.8%). On the validation cohort, we observed high accuracies for the support vector machine (97.8%) while the random forest performed considerably worse (89.5%), especially in distinguishing PM from chronic pleuritis. Differential methylation analysis revealed promoter hypermethylation in PM specimens, including the tumor suppressor genes BCL11B, EBF1, FOXA1, and WNK2. Deconvolution of the stromal and immune cell composition revealed higher rates of regulatory T-cells and endothelial cells in tumor specimens and a heterogenous inflammation including macrophages, B-cells and natural killer cells in chronic pleuritis. CONCLUSION: DNA methylation in combination with machine learning classifiers is a promising tool to reliably differentiate PM from chronic pleuritis and lung cancer, including pleomorphic carcinomas. Furthermore, our study highlights new candidate genes for PM carcinogenesis and shows that deconvolution of DNA methylation data can provide reasonable insights into the composition of the tumor microenvironment.

Cough and Progressive Pleuritic Chest Pain With an Enlarging Cavity on Imaging.

CASE PRESENTATION: A 49-year-old woman sought treatment at the hospital for evaluation of an enlarging cavitary mass of the right lung associated with worsening ipsilateral pleuritic chest pain and cough. She had recent hospitalizations for complications relating to recurrent lung abscesses, including one in which she underwent wedge resection of the right lung. She had been treated with several courses of antibiotics, which only temporarily relieved her symptoms. She did not report any fevers, chills, skin changes, diarrhea, or changes to her bowel habits. Her long-term medications included albuterol, dapsone, and prednisone 15 mg or 20 mg doses alternating daily. Her only past medical history was asthma and primary cutaneous pyoderma gangrenosum. The patient never smoked and did not report any recent sick contacts.

Epidemiologic evaluation of pleurisy diagnosed by surgical pleural biopsy using data from a nationwide administrative database.

BACKGROUND: Pleural biopsies for investigating the causes of pleurisy are performed through modalities including needle biopsies, local anesthetic thoracoscopic procedures, and surgery (video-assisted thoracoscopic surgery and open thoracotomy). To date, there have been no large-scale nationwide epidemiological studies regarding pleurisy diagnosed via surgical pleural biopsy. This study examined the epidemiology of pleurisy diagnosed via surgical pleural biopsy in a Japanese nationwide administrative database. METHODS: We evaluated Japanese Diagnosis Procedure Combination data of 24 173 patients who underwent video-assisted thoracoscopic surgery or open thoracotomy and received a diagnosis of pleurisy between April 2014 and March 2020. In addition to pleurisy diagnoses, the patients' clinical information, including age, sex, smoking status (pack-years), dyspnea grade, length of in-hospital stay, and comorbidities, were extracted from the dataset. RESULTS: This study included data from 1699 patients. The most frequent causes of pleurisy were neoplastic diseases (55.9%; malignant mesothelioma 22.5%, lung cancer 15.7%, lymphoma 2.5%), followed by infectious diseases (24.0%; tuberculosis 16.2%, parapneumonic pleural effusion 3.6%, empyema 3.5%, nontuberculous mycobacteriosis 0.5%), collagen vascular diseases (2.8%; rheumatoid arthritis 1.3%, immunoglobulin G4-related diseases 0.7%, systemic lupus erythematosus 0.3%), and paragonimiasis (0.1%). CONCLUSIONS: Neoplastic diseases, including malignant mesothelioma and lung cancer, were frequently and accurately diagnosed as pleurisy via surgical pleural biopsy. The next leading cause was infectious diseases such as mycobacterial infections. Physicians should consider performing surgical biopsy in light of the knowledge regarding the etiology of pleurisy when a definitive diagnosis cannot be made via needle pleural biopsy.

Concomitant pleuritis and pericarditis developing during glucocorticoid therapy: a case report on granulomatosis with polyangiitis.

Granulomatosis with polyangiitis is an anti-neutrophil cytoplasmic antibody-associated vasculitis that manifests in various ways by affecting the small-sized vessels in multiple organs. Acute pleuritis and pericarditis are both rare among the different manifestations of granulomatosis with polyangiitis. The symptoms in each of the organs are often apparent at the time of diagnosis and tend to diminish with treatment. Organ damage and progression of the disease during treatment are uncommon. We encountered a patient with granulomatosis with polyangiitis who, after starting intravenous methylprednisolone pulse therapy, concurrently developed acute pleuritis and pericarditis. The patient was a 47-year-old Japanese man with myalgia in whom kidney dysfunction, proteinase 3-anti-neutrophil cytoplasmic antibody positivity, and a lung mass were detected. Granulomatosis with polyangiitis was diagnosed pathologically from a lung and a kidney biopsy. Acute pleuritis and pericarditis, which developed after the first course of intravenous methylprednisolone pulse therapy, both resolved following the second course. The present report indicates that secondary serositis such as pleuritis and pericarditis can develop in patients with granulomatosis with polyangiitis even during glucocorticoid therapy.

Cryptogenic Fibrosing Pleuritis with Rapidly Progressive Restrictive Ventilatory Dysfunction.

Cryptogenic bilateral fibrosing pleuritis is a rare condition, and its pathogenesis and clinical course are poorly understood, with no established therapy available. A 61-year-old man presented with bilateral pleural thickening and lymphocytic exudative effusions. The patient was diagnosed with fibrosing pleuritis with no evidence of a known etiology on a surgical pleural biopsy. Within 16 months from the onset of respiratory symptoms, restrictive ventilatory impairment progressed rapidly, resulting in hypercapnic respiratory failure requiring home oxygen and non-invasive positive pressure ventilation therapies.

UHRF1 Immunohistochemical Staining Separates Benign Reactive Spindle Cell Mesothelial Proliferations From Sarcomatoid Mesotheliomas.

The separation of benign from malignant mesothelial proliferations is often a difficult pathologic problem. UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains-1) is a regulator of DNA methylation and an epigenetic driver of various human cancers. It has recently been reported that UHRF1 is overexpressed in mesotheliomas. We asked whether UHRF1 immunohistochemistry could be used to separate benign from malignant mesothelial proliferations. Initial studies showed that UHRF1 stained mesothelial cells but also endothelial and other non-neoplastic cells, so that accurate counting of positive mesothelial cells was difficult. Therefore, we ran dual UHRF1-AE1/AE3 stains on 2 tissue microarrays containing 40 reactive mesothelial proliferations and 61 mesotheliomas and only counted UHRF1 staining in keratin-positive cells. On average 10.3±8.6% (mean±SD; range: 0% to 36, median: 6.8%) of epithelioid mesothelioma cells stained compared with 5.3±4.8% (range: 0% to 15%, median: 4.1%) of reactive epithelial mesothelial cells. This difference was statistically significant but there was too much overlap to use diagnostically. In contrast, 37±26% (range: 2.5% to 95%, median: 31%) of cells in sarcomatoid mesotheliomas compared with 1.2±1.2% (range: 0% to 3.0%, median: 1.0%) of cells in reactive spindle cell mesothelial proliferations stained. To confirm this difference we stained whole sections of 21 sarcomatoid mesotheliomas and 19 cases of organizing pleuritis. Staining of mesothelial cells was seen in 2.1±2.4% (range: 0% to 6.8%, median: 1.0%) of organizing pleuritis cases and 44±22% (range: 14% to 90%, median: 41%) of sarcomatoid mesotheliomas. We conclude that dual UHRF1-AE1/AE3 immunohistochemistry is very useful for separating benign spindle cell mesothelial proliferations from sarcomatoid mesotheliomas.

Immunoglobulin G4-related Pleuritis Complicated with Minimal Change Disease.

A 70-year-old woman with bilateral pleural effusion and respiratory failure was admitted to our hospital. Nephrotic syndrome due to minimal change disease had been diagnosed four months before admission. Because blood tests and a pleural fluid analysis did not reveal the etiology of her condition, we performed a video-assisted thoracoscopic pleural biopsy. No specific thoracoscopic findings were noted. The pathological findings revealed an increase in immunoglobulin G4 (IgG4)-positive cells; IgG4-related pleuritis was diagnosed. Her pleuritis improved with oral corticosteroid therapy. A further investigation was performed on previous kidney samples; however, the etiology of the nephrotic syndrome was not IgG4-related disease but minimal change disease.

Life-threatening Mycobacterium intracellulare pleuritis in an immunocompetent host: Case reports.

RATIONALE: Nontuberculous mycobacteria (NTM)-associated pleuritis is a very rare disease. Here, we describe 2 cases of life-threatening Mycobacterium intracellulare-associated pleuritis in immunocompetent hosts. PATIENT CONCERNS: A 78-year-old man with sudden onset-onset dyspnea (case 1) and an 80-year-old man with cough, sputum and fever (case 2) presented to our emergency room. DIAGNOSES: Both the patients were diagnosed with Mycobacterium intracellulare-associated pleuritis. INTERVENTION: In case 1, the patient underwent intubation with mechanical ventilation due to hypoxemic respiratory failure. Daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week was administered. In case 2, the patient received daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week. OUTCOMES: In case 1, after receiving NTM treatment for 14 months, NTM-associated pleuritis was cured, with radiologic improvement. In case 2, however, bronchopleural fistula was developed. Despite tube drainage, air leak continued. The patient refused surgical management and eventually died of respiratory failure. LESSONS: Pleural effusion arising from NTM lung disease located in the subpleural area should be considered a possible cause of NTM-associated pleuritis. Drainage and a multidrug regimen are required to treat NTM, and surgical treatment should be considered when complications occur.