Granulomatous Research Articles

Leprosy as a cause of nasolacrimal duct obstruction.

Leprosy, also known as Hansen disease, is an airborne spread disease caused by Mycobacterium leprae (M. leprae) which commonly presents with skin lesions, peripheral neuropathy, and ocular involvement. This report describes a patient who presented with epiphora secondary to chronic nasolacrimal duct obstruction four years after completing antimicrobial treatment for tuberculoid leprosy. At the time of endoscopic dacryocystorhinostomy (DCR), the lacrimal sac demonstrated chronic dacryocystitis with granulomatous inflammation and a Fite positive staining bacterial rod-like structure. Pathological examination of the surgical specimen demonstrated numerous non-necrotizing granulomas in a perivascular and neural distribution, compatible with sequelae of previously treated M. leprae infection. The patient has remained symptom free six months after surgery.

Granulomatous cheilitis: a rare case report

Granulomatous cheilitis is a rare granulomatous disorder characterized by a recurrent firm swelling of one or both lips. This is called the cheilitis granulomatosa of Miescher (CGM) when it occurs in isolation. It is called Melkersson-Rosenthal syndrome (MRS) if the classical triad of recurrent or persistent orofacial edema, plicated or fissured tongue (lingua plicata), and relapsing peripheral facial nerve paralysis is present. A 40-year-old female patient came to the Dermatology Department with persistent painless swelling of both lips and perioral area for the last one year. On histopathological examination there was a nodular tuberculoid granulomatous inflammation in patchy pattern present throughout the submucosa. The granuloma consists of lymphocytes, histiocytes and occasional plasma cells. AFB stain and PAS stain were negative. Diagnosis of granulomatous cheilitis was made and patient was put on tab clofazimine and intralesional corticosteroids. The case is being reported due to its rarity and the role of dermatopathologist to make a diagnosis.

Granulomatosis with polyangiitis: clinical characteristics and updates in diagnosis.

Granulomatosis with polyangiitis (GPA) is a rare systemic disease characterized by granulomatous inflammation of the respiratory tract and necrotizing vasculitis of small and medium vessels often associated with the production of anti-neutrophil cytoplasmic antibodies (ANCA) directed mainly against leukocyte proteinase 3 (PR3). Usually, it involves upper airways, lungs, and kidneys, however any organ may be affected. The diagnosis is based on clinical, radiological, and serological findings. Biopsies, although strongly recommended, are not always feasible and often provides non-specific features. ANCA plays a crucial role in the diagnosis of GPA; nevertheless, ANCA detection is not a substitute for biopsy, which plays an important role in suspected cases, particularly when histological confirmation cannot be obtained. Significant advances have been made in classification criteria and phenotyping of the disease, particularly in determining the nuances between PR3-ANCA and myeloperoxidase (MPO)-ANCA vasculitis. This has led to better characterization of patients and the development of targeted treatment in the future. In addition, better identification of cytokine and immunological profiles may result in immuno-phenotyping becoming a new approach to identify patients with ANCA-associated vasculitis (AAV). Due to the chronic relapsing-remitting nature, strict follow-up of GPA is necessary to provide appropriate management. The search for the accurate marker of disease activity and to predict relapse is still ongoing and no predictor has been found to reliably guide therapeutic decision-making.

Iatrogenic allogenesis and autoimmune diseases

Introduction. Iatrogenic allogenesis is currently a public health problem due to the constant increase in cases, especially in underdeveloped countries. Objective. To characterize patients diagnosed with iatrogenic allogenesis. Methods. An observational, descriptive, cross-sectional study was conducted in 23 patients with a confirmed diagnosis of iatrogenic allogenesis. Adverse reactions, the appearance of autoimmune diseases, and their association with the type of substance injected were described. Results. Women aged 30-39 years, single, and with non-university education predominated. 48% of patients received the infiltration by stylists in beauty salons. The most common infiltration area was the face, and 39% of patients did not know the substance that was injected. Granulomatous reactions, generalized pain, and nodule formation predominated, associated with all the molding agents used and with injections in the face. Contour changes and asymmetry were associated with the use of silicones and biopolymers and were more common with injections in the face and buttocks. 47.8% of patients were diagnosed with autoimmune diseases, with vasculitis and systemic lupus erythematosus being the most common. 63.6% of those diagnosed with autoimmune diseases were infiltrated with substances of unknown type. Conclusions. Granulomatous reactions, generalized pain, and nodule formation predominated, along with the diagnosis of vasculitis and systemic lupus erythematosus; these were more frequently associated with the injection of substances of unknown origin and composition

Diagnostic value of soluble Interleukin-2 receptor in patients suffering neurosarcoidosis: A systematic review.

Neurosarcoidosis is an inflammatory granulomatous disease. Up to 25% of occult sarcoidosis affecting the nervous system are only detected by autopsy. In addition, in recent years the suspicion arose that the soluble Interleukin-2 Receptor (sIL-2R) might be useful in differentiating between neurosarcoidosis and neurosarcoidosis-like diseases such as neurotuberculosis, multiple sclerosis, or cerebral lymphoma. Therefore, we aimed to systematically review randomized controlled trials (RCT), observational studies, and case-control studies evaluating sIL-2R levels in neurosarcoidosis patients. For this systematic review, a comprehensive literature search of electronic databases including EMBASE, The Web Of Science, The Cochrane Library, MEDLINE, and Google Scholar was conducted. The search was limited to the English language and publication date up to January 08th, 2024. As part of the search strategy conducted, 6 articles met the inclusion criteria. Two independent reviewers extracted the relevant data from each article. In addition, 2 independent reviewers assessed the quality of each study using the Newcastle-Ottawa Scale (NOS). We included 6 studies comprising 98 patients suffering from neurosarcoidosis, 525 non-sarcoidosis patients, and 118 healthy controls. Included studies were published between 2010 and 2023. Cerebrospinal fluid (CSF) sIL-2R levels differed significantly between neurosarcoidosis patients and multiple sclerosis, vasculitis, and healthy controls whereas serum sIL-2R levels did not reveal sufficient discriminative power. sIL-2R index was able to discriminate neurosarcoidosis from neurotuberculosis, bacterial/viral meningitis, and healthy controls. In this systematic review, we found indications that sIL-2R may be a useful biomarker for the diagnosis of neurosarcoidosis. To determine an additional diagnostic value of sIL-2R, large prospective studies are needed that not only examine absolute sIL-2R levels in serum or CSF but also the dynamic changes as well as the implications of renal function on sIL-2R levels.

Profile of juvenile systemic lupus erythematosus patients with a special reference to monogenic lupus and lupus nephritis: a cross-sectional study.

To study the clinical, laboratory profile and outcome of juvenile Systemic Lupus Erythematosus (jSLE) patients at a tertiary care centre in South India. A retrospective review of the medical records of all jSLE patients visiting the Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, India from February 2017 to December 2023 was performed. The clinical characteristics, treatment and outcomes were recorded and tabulated. Seventy patients diagnosed with jSLE were included in the study. The female-to-male ratio was 4.4:1. Mean age at onset and delay in diagnosis were 120.1 (+/- 56.8) and 11.7 (+/- 22.7) months respectively. The median follow-up period was 13 months (range 4, 29 months). Nine patients presented with early onset SLE (< 5 years). Most common manifestations were constitutional symptoms (n = 56), followed by haematologic (n = 55), and mucocutaneous(n = 50) involvement. Immunological workup showed SLE-specific antibody positivity in 38 patients, hypocomplementemia in 40 patients, and anti-phospholipid antibody positivity in 13 patients. Mortality was observed in five patients with LN while there was no mortality in the non-nephritis group (p 0.004). C1q deficiency was the most common cause of monogenic lupus seen in 5/9 patients; protein kinase C delta (PRKCD) defect and chronic granulomatous disease (CYBB mutation) were seen in one patient each. We describe a large cohort of jSLE from Southern India. Lupus nephritis was noted in 35.7% of our cohort and had a direct correlation with mortality. 10% of patients had monogenic lupus. Serious infections were more frequent in patients with monogenic lupus.

Identification of overlapping molecular mechanisms in tuberculosis and sarcoidosis: A bioinformatics approach

BackgroundTuberculosis (TB) and sarcoidosis are chronic granulomatous diseases sharing similar symptoms, immune responses, and radiological characteristics. Transcriptome analysis offers insights into gene expression, regulation, and cellular processes, facilitating the understanding of shared molecular mechanisms. MethodsMicroarray datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) were analysed to identify differentially expressed genes (DEGs) in TB and sarcoidosis compared to controls. DEGs were identified using the GEO2R tool, and subsequent functional enrichment analysis was conducted using EnrichR. Protein-protein interaction (PPI) networks, as well as gene-miRNA and transcription factor-DEG interaction networks, were constructed. In addition, pathway analysis and molecular docking of target proteins were conducted to further elucidate the biological mechanisms involved in both diseases. ResultsFifteen genes, including ANKRD22, BATF2, DHRS9, EPSTI1, ETV7, FCGR1A, FCGR1B, GBP1, GBP5, SERPING1, NELL2, CCR7, PASK, LRRN3, and SLC16A10, were commonly altered in TB and sarcoidosis as compared to controls. Gene network analysis revealed 48.89% co-expression and 26.10% physical interaction between these overlapping genes. PPI networks showed a total of 15 nodes and 28 edges present between the connected proteins (PPI enrichment p-value:<1.0e−16). MiRNAs and transcription factors that exhibited the highest interaction with DEGs included hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-335-5p, and EPAS1, HIF1A, KLF2, respectively. Pathway analysis indicated enrichment of IFN gamma signaling in both diseases. Molecular docking revealed weighted scores of −884.4, −851.9, and − 637.1 between three key proteins (PASK-GBP1, PASK-GBP5, and GBP1-GBP5). ConclusionThe shared dysregulated genes in TB and sarcoidosis demonstrate notable co-expression and physical interaction, constituting a PPI network enriched in the IFN-gamma signaling pathway.

Granulomatous Folliculotropic Secondary Syphilis: An Unusual Histopathological Clue.

Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti-Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider.

Tumefactive Multiple Sclerosis: The Lethal Chameleon.

Tumefactive multiple sclerosis is an uncommon variant of multiple sclerosis that presents a substantial diagnostic challenge due to its potential to resemble the clinical and radiological characteristics of other central nervous system (CNS) pathologies, including neoplasms, granulomatous diseases, abscesses and vasculitis.Despite the fact that multimodal imaging studies may help narrow the differential diagnosis, a biopsy is often required to reach a definitive diagnosis and should not be delayed.Awareness of this condition among non-neurologists is critical since a timely and accurate diagnosis prompts aggressive immunomodulatory treatments that may delay a second demyelinating event or progression to clinically definite multiple sclerosis.

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis

BackgroundMelkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement.Case presentationThis paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis.ConclusionsThese findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Systemic disseminated nocardiosis in a patient with normal immune function: a case report

Nocardiosis, characterized by poor prognosis and high mortality, is a local or systemic suppurative or granulomatous disease caused by Nocardia that is common in immunosuppressed individuals but rare in populations with normal immune function. This paper described one case of Nocardia gipuzkoensis disseminated infection in a patient with normal immune function by outlining the process of treatment, conducting literature review and by outlining the clinical characteristics, diagnostic criteria and standardized treatments of nocardia disease, in the hope of providing reference for subsequent treatment of rare Nocardia subspecies infections.

Cardiac sarcoidosis presenting as multiple right intra-atrial masses mimicking cardiac tumor

BackgroundCardiac sarcoidosis though in itself, a rare entity, very rarely presents primarily with conduction abnormalities as the primary manifestation in the spectrum of presentations accounted by this chronic granulomatous systemic disease. Sarcoidosis presenting as intra-atrial masses is virtually unheard of.CaseA middle aged female presented with progressive conduction system disease was found to have right atrial masses of unclear etiologic on relevant imaging. Over the course of 3 months she underwent a dual-chamber ICD implant for her eventual complete heart block and a surgical resection following an inconclusive biopsy of the right atrial free wall mass. She was then diagnosed with cardiac sarcoidosis and started on immunosupressants almost instantaneously as a part of her treatment.ConclusionThis is an entirely new and unreported presentation of cardiac sarcoidosis as an intra-atrial mass. Through this case we bring light to cardiac sarcoidosis as a potential differential for intra-cardiac masses and how with available data do we go about treating it.

Evaluation of presentation, treatment and outcome in dogs with granulomatous steatitis associated with hypercalcaemia: six cases (2019-2023).

To report the presentation, treatment and outcome of dogs with granulomatous steatitis associated with total and ionised hypercalcaemia. Six dogs diagnosed with ionised and/or total hypercalcaemia and histologically diagnosed granulomatous steatitis were evaluated to determine the clinical signs, clinical findings, response to treatment and outcome. These cases were seen at different primary care and referral veterinary hospitals in the United Kingdom between 2019 and 2023. No alternative aetiology to explain the total and/or ionised hypercalcaemia or steatitis was identified. The most common presenting signs were lethargy, anorexia or hyporexia, vomiting and polyuria/polydipsia. Other clinical signs included weight loss, discomfort and panting. Five out of the six dogs responded to prednisolone. Four dogs were alive at the time of writing, one dog was lost to follow-up and one dog died 2 weeks post-diagnosis. It is well-established that granulomatous disease can cause hypercalcaemia. In this case series we found granulomatous steatitis associated with total and/or ionised hypercalcaemia. Dogs diagnosed with granulomatous steatitis should have ionised calcium measured, which may prompt further diagnostics and treatment options. Dogs with hypercalcaemia should be evaluated for evidence of steatitis where more common differentials have been excluded.

An immunocompetent lady with invasive aspergillosis presenting as disseminated lesions: a case report

BackgroundInvasive Aspergillosis is a fungal infection caused by Aspergillus species, typically posing life-threatening risks to immunocompromised individuals. While occurrences in immunocompetent hosts are rare, a recent case report documented fulminant pulmonary aspergillosis in an immunocompetent patient during autopsy. Here, we present a case of invasive aspergillosis in an immunocompetent woman, manifesting with disseminated lesions.Case presentationA 29-year-old Asian woman presented to our hospital in March 2022, reporting chest pain and shortness of breath persisting for two months. Upon examination, she appeared thin and unwell, with no notable abnormalities otherwise. Radiographic imaging revealed an ill-defined lesion in her left lung. Subsequent bronchoscopy and lavage were performed, followed by initiation of empirical antibiotic therapy. Lavage results were negative for gram staining, culture, and ZN staining for AFB, but revealed numerous septate hyphae on fungal smear. Histopathological examination indicated chronic granulomatous inflammation with septal fungal hyphae, indicative of aspergillosis. Subsequent culture confirmed Aspergillus species, prompting initiation of voriconazole therapy. Remarkably, the patient exhibited significant improvement, with weight gain and restored appetite observed within a short period. Within 2 months of treatment, her symptoms resolved, and she resumed near-normal daily activities.ConclusionThis case highlights the diagnosis of aspergillosis in an immunocompetent individual presenting with disseminated nodular lesions across the lungs, mediastinum, and abdomen. Clinicians should maintain a high index of suspicion for aspergillosis in cases of non-resolving pneumonia and disseminated nodular lesions, even in patients lacking traditional predisposing factors.

Autoimmune disorders in patients with granulomatosis diseases after COVID-19: T- and B-cells subsets function

Sarcoidosis and tuberculosis are both granulomatous diseases that have many similarities, making the differential diagnosis of sarcoidosis and tuberculosis difficult, as well as leading to inappropriate treatment selection of both diseases. Autoimmune inflammation (AI) is one of the processes identified tuberculosis and sarcoidosis. Current evidences about the risk and clinical outcomes of COVID-19 infection in patient with sarcoidosis and M. tuberculosis co-infection are still not well understood. SARS-CoV-2 has direct damage to the epithelial cells of the respiratory system, and in-directly due to circulatory disorders. Materials and methods. In the study we analyzed characteristics of autoimmune response in patients with granulomatosis diseases (tuberculosis and sarcoidosis) after COVID-19. We have analyzed articles for the period of December 2019 to March 2023, published in international database (“Medline”, “PubMed”, “Scopus”). The keywords we used “COVID-19”, “SARS-CoV-2”, “tuberculosis”, “sarcoidosis”, “granulomatosis diseases”, “T cells”, “B cells”, “Treg”, “follicular Treg” and “Treg subsets”. The narrative review was carried out in accordance with the PRISMA protocol (http://www.prisma-statement.org) used for this type of study (ID-423604). Results. The influence of COVID-19 infection can also make a significant contribution to the violation of the T- and B-cell immune response, the violation of the nature of cellular metabolism, which will affect the course of granulomatous inflammation in various ways. According to the different researches, autoimmune inflammation can be an important protective mechanism in sarcoidosis and, at the same time, exacerbates the course of tuberculosis infection with the disease progression and pathogen drug resistance formation subsequently. The study of immune response features in patients with COVID-19 showed the presence of several similar characteristics in cellular components of the immune response. Conclusion. Evidence of the presence of autoimmune inflammation in patients with these granulomatous lung diseases, the development of patient immunotypes, including the transferred COVID-19, will be a significant contribution to the development of personalized patient management tactics, taking into account the identified violations of the immune response mechanisms.

Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

Spectrum of Haematological Disorders On Bone Marrow Examination In a Tertiary Care Hospital

Background: Hematological disorders are quite common in all age groups. The most common presentation is Anemia. Bone marrow examination is a necessary adjunct to the study of diseases of the blood and how a correct diagnosis can be made. The study aimed to analyze the various causes of haematological disorders. Aim of the study: To study the spectrum of haematological disorders on bone marrow examination, to know the age and sex incidence and to determine the causes of pancytopenia. Materials and Methods: This was a retrospective study carried out in the upgraded department of pathology, Osmania General Hospital, Hyderabad, Telangana from May 2022 to April 2023. Bone Marrow Aspiration of 100 cases of suspected haematological disorders was carried out complete detailed history, examination and complete blood counts were recorded. Results: In this study, out of 100 cases, the age of patients ranged from 11 to 80 years with a mean age of 31.8 years with male preponderance (1.5: 1). Most of the patients clinically presented with fever, easy fatiguability and generalized weakness. The most common cause is Megaloblastic Anemia (45%), followed by normal bone marrow study (22%), hypocellular marrow (12%), acute leukaemia (10%), idiopathic thrombocytopenic purpura (6%), multiple myeloma (4%), granulomatous disease (1%). Conclusion: The current study showed the usefulness of bone marrow aspiration in the evaluation of bone marrow in routine haematological disorders and for understanding disease progression. Keywords : Bone Marrow Aspiration, Haematological disorders, Megaloblastic Anemia.

Abstract We067: A meta-analysis of RNA sequencing data to characterize immune cell activation among patients with cardiac sarcoidosis

Introduction: Cardiac sarcoidosis (CS) is a life-threatening auto-immune disorder that causes the formation of non-caseating granulomas in cardiac tissue. Th17.1 cell have been found to be upregulated in patients with pulmonary sarcoidosis (PS) although data is lacking among CS patients. This meta-analysis integrates all publicly available granuloma single-cell and single-nuclei RNA sequencing data to identify patterns in immune cell activation across different granulomatous diseases while focusing on CD4+T cell activation among CS patients. Methods: Five studies were included, spanning cardiac tissue from healthy controls and DCM (Koenig 2022, PMID:35959412), cardiac tissue from ICM and cardiac sarcoidosis (Liu 2022, PMID:36111531), BAL from beryllium sensitized, chronic berylliosis, and PS (Liao 2021, PMID: 33602861), peripheral blood samples from sarcoidosis (Garman 2020, PMID: 33363531), and lesional and nonlesional skin tissue from sarcoidosis (Krausgruber 2023, PMID: 36750099) for a total of 122 patients. All integrative analysis was performed using the R package Seuratv5 on Stanford’s computing cluster, Sherlock. After quality control filtering, a total of 127,335 cells were integrated using Seurat’s reference-based integration. After labeling the UMAP with general immune cells (figure 1A), we subsetted T cells into CD4+ and CD8+ and examined the landscape of CD4+ T cells (figure 1B). Results: We found significantly more Tregs in CS than PS (P=0.013, figure 1C). Additionally, patients with CS had significantly more Th17.1 cells in CS in comparison to PS (P=0.0041). However, significantly less Th2 cells were found in CS than PS patients (P=0.0152). These differences remained statistically significant across various analyses comparing Tregs and Th17.1 cell as a proportion of CD4+, CD3+, and CD45+ cells. Conclusions: In comparison to patients with PS, pathways which differentiate naive CD4+ cells into TH17.1 and Tregs are upregulated among CS patients while the TH2 differentiation pathway is downregulated. Our findings indicate distinct CD4+ T cell patterns among CS and PS patients. Our ongoing work aims to further evaluate T cell proliferation and expression to elucidate mechanistic pathways as potential drug targets for CS.

Challenges in Managing Newly Diagnosed Granulomatosis With Polyangiitis and Concurrent Respiratory Infections: A Retrospective Case Series.

Granulomatosis with polyangiitis (GPA), formerly termed Wegener's granulomatosis, is an autoimmune disease marked by necrotizing granulomatous inflammation and vasculitis affecting small-sized vessels. It commonly impacts the renal and respiratory systems. This retrospective case series sampling conductedin a tertiary care hospital between May 2023 and April 2024 examined six newly diagnosed GPA patients who wereproteinase 3 cytoplasmic-antinuclear cytoplasmic antibody (PR3 c-ANCA) positive and had concurrent respiratory infections. None of them had any prior immunosuppressive conditions.The age range was 18-47 years with a mean of 35.0 (standard deviation: 11.83). All the patients had pneumonia (N=6, 100%). Out of all, five hadbacterial pneumonia (N=5, 83.3%) and one had tuberculous pneumonia (N=1, 16.7%). A high levelof PR3 c-ANCA (>150 RU/mL) was noted in four patients (N=4, 66.7%).Common symptoms included dry cough (N=5, 83.3%), loss of weight and appetite(N=2, 33.3%), and fever (N=2, 33.3%). Three patients had otitis mediaand/or nasal polyposis (N=3, 50%). Two patients (N=2, 33.3%) with life-threatening organ dysfunction were given concurrent antibiotics and steroids; the antibiotics were later modified based on culture and sensitivity results. One of these patients received antituberculosis therapy as Mycobacterium tuberculosis (MTB) was detected after 27 days of incubation in mycobacterial growth indicator tube broth. The remaining four patients (N=4, 66.7%)receivedantibiotics initially for 5-7 days until clinical resolution of pneumonia. Ultimately, they all showed clinical and radiological resolution (N=6, 100%) within 3-6 months of treatment. The patients exhibited constitutional symptoms such as fever and weight loss; lower airway disease symptoms including dry cough and hemoptysis; nasal and ear disease symptoms like epistaxis, ear pain, and ear discharge; and a renal disease symptom, hematuria.Computed tomography of the thorax revealed bilateral consolidations, most of which were cavitating. Bronchoalveolar lavagecultures grew Escherichia coli, Burkholderia cepacia, Pseudomonas aeruginosa, Klebsiella pneumoniae, and MTB, whereas pus swab cultures from otitis media grew Pseudomonas aeruginosa, Staphylococcus aureus,and coagulase-negative staphylococci. This study highlights the therapeutic challenges of GPA complicated by concurrent infections. Patients exhibited typical GPA signs, confirmed by PR3 c-ANCA levels. Concurrent infections require cautious antibiotic treatment before starting immunosuppressive therapy, except in life-threatening organ dysfunction. A unique case presented with both tuberculosis and GPA. Tailored treatment regimens combining antibiotics and immunosuppressives, including corticosteroids, methotrexate, and rituximab, resulted in clinical and radiological improvement in all the patients within 3-6 months. The addition of co-trimoxazole reduced the incidence of non-severe GPA relapses. Tailored treatment plans addressing both infectious and autoimmune aspects are essential for optimal care in GPA complicated by concurrent infections. This study highlights the need for a multidisciplinary approachinvolving pulmonologist, rheumatologist, microbiologist, and pathologistin the diagnosis and treatment of GPA, emphasizing the importance of individualized treatment plans tailored to the specific clinical scenario.

Permissive lung neutrophils facilitate tuberculosis immunopathogenesis in male phagocyte NADPH oxidase-deficient mice.

NADPH oxidase 2 (NOX2) is an enzyme responsible for generating reactive oxygen species, primarily found in phagocytes. Chronic Granulomatous Disease (CGD), along with bacterial infections such as Mycobacterium tuberculosis (Mtb), is a representative NOX2-deficient X-linked disease characterized by uncontrolled inflammation. However, the precise roles of host-derived factors that induce infection-mediated hyperinflammation in NOX2-deficient condition remain incompletely understood. To address this, we compared Mtb-induced pathogenesis in Nox2-/- and wild type (WT) mice in a sex-dependent manner. Among age- and sex-matched mice subjected to Mtb infection, male Nox2-/- mice exhibited a notable increase in bacterial burden and lung inflammation. This was characterized by significantly elevated pro-inflammatory cytokines such as G-CSF, TNF-α, IL-1α, IL-1β, and IL-6, excessive neutrophil infiltration, and reduced pulmonary lymphocyte levels as tuberculosis (TB) progressed. Notably, lungs of male Nox2-/- mice were predominantly populated with CD11bintLy6GintCXCR2loCD62Llo immature neutrophils which featured mycobacterial permissiveness. By diminishing total lung neutrophils or reducing immature neutrophils, TB immunopathogenesis was notably abrogated in male Nox2-/- mice. Ultimately, we identified G-CSF as the pivotal trigger that exacerbates the generation of immature permissive neutrophils, leading to TB immunopathogenesis in male Nox2-/- mice. In contrast, neutralizing IL-1α and IL-1β, which are previously known factors responsible for TB pathogenesis in Nox2-/- mice, aggravated TB immunopathogenesis. Our study revealed that G-CSF-driven immature and permissive pulmonary neutrophils are the primary cause of TB immunopathogenesis and lung hyperinflammation in male Nox2-/- mice. This highlights the importance of quantitative and qualitative control of pulmonary neutrophils to alleviate TB progression in a phagocyte oxidase-deficient condition.