Granulomatous Infection Research Articles

Amoxicillin-clavulanic Acid and Trimethoprim/ Sulphamethoxazole Combination Therapy for Actinomycetoma in an Elderly Farmer: A Case Report

Actinomycetoma is a chronic, localised, progressive granulomatous infection of the skin and subcutaneous tissues, typically affecting the lower extremities. It is caused by Actinomycetes bacteria, which are commonly found in soil and water. The infection usually results from minor trauma, such as walking barefoot or exposure to thorny vegetation. Upon inoculation, the bacteria form grains that help evade the host immune response, facilitating the establishment of infection. It is characterised by discharging sinuses and the presence of granules. This condition predominantly affects individuals in rural, resource-limited areas with limited access to healthcare. Although it affects both men and women, men are more commonly affected due to occupational exposure. The disease progresses slowly, often leading to severe complications, including tissue destruction and sinus tract formation, with amputation being the only option in advanced cases. Authors hereby report a case of Actinomycetoma in an 86-year-old male farmer who presented with painful erythematous nodules and purulent discharge from lesions on his left leg for the past four years. The diagnosis was established through clinical, histopathological and microbiological investigations, including Gram stain, Gomori Methenamine Silver (GMS), and Periodic Acid-Schiff (PAS) stain. Treatment with a combination of amoxicillin-clavulanic acid and trimethoprim/sulphamethoxazole was initiated. This led to a complete resolution of the condition within three weeks, demonstrating the efficacy of this treatment as a safe and cost-effective option. This case highlights the importance of early diagnosis and appropriate treatment for Actinomycetoma, emphasising the value of affordable therapeutic interventions.

Establishment of epidemiological cutoff values for Fonsecaea pedrosoi, the primary etiologic agent of chromoblastomycosis, and eight antifungal medications.

Chromoblastomycosis, a fungal neglected tropical disease, is acquired through traumatic inoculation and is clinically characterized by a chronic granulomatous infection of the skin and subcutaneous tissue. Fonsecaea pedrosoi is the most commonly reported etiologic agent globally. Itraconazole is considered first-line therapy, but successful treatment with terbinafine, voriconazole, and posaconazole has been reported. F. pedrosoi minimum inhibitory concentration (MIC) data are limited, and epidemiological cutoffs (ECVs) are lacking; such data are important to help monitor antifungal resistance trends and guide initial antifungal selection. Thus, we performed antifungal susceptibility testing (AFST) on F. pedrosoi isolates and determined the MIC distributions and ECVs. AFST on Fonsecaea pedrosoi isolates was conducted at six laboratories from October 2023 to June 2024. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (version 2.1) following CLSI M57 guidelines. We analyzed MIC results from 148 Fonsecaea pedrosoi isolates. The calculated ECVs were itraconazole, 0.5 µg/mL; voriconazole, 0.5 µg/mL; posaconazole, 0.5 µg/mL; isavuconazole, 1 µg/mL; ketoconazole, bimodal, no ECV determined; terbinafine, 0.25 µg/mL; flucytosine, rejected; and amphotericin, 8 µg/mL. These Fonsecaea pedrosoi ECVs, obtained through a multicenter international effort, provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. Clinicians and researchers can use these values to detect non-wild-type isolates with reduced susceptibility, reevaluate therapeutic options, and investigate potential clinical resistance if treatment failure occurs.IMPORTANCEChromoblastomycosis is a neglected tropical disease caused by an environmental, dematiaceous fungus. This fungal disease is acquired after a break in the skin that allows the fungus to enter, leading to a chronic infection in the skin and subcutaneous tissue. It is difficult to treat and often requires years of antifungal treatment. Fonsecaea pedrosoi is the most reported causative agent globally. Limited antifungal susceptibility data exist for F. pedrosoi making interpreting minimum inhibitory concentration (MIC) results difficult. We performed antifungal susceptibility testing on 148 F. pedrosoi isolates to establish MIC distributions and epidemiologic cutoff values (ECVs) for eight antifungals, including those commonly used to treat chromoblastomycosis. The calculated ECVs for the commonly used antifungals itraconazole and terbinafine were 0.5 and 0.25 µg/mL, respectively. ECVs can be helpful in choosing potential treatment options for F. pedrosoi and monitoring antifungal resistance epidemiology.

A Longstanding Case of Black Grain Mycetoma in a Somalian Male Patient: A Case Report.

Mycetoma is a chronic granulomatous infection predominantly affecting young individuals, characterized by painless swelling and often misdiagnosed due to its resemblance to other conditions. This case report presents the first documented instance of eumycetoma located in the buttock of a 44-year-old male patient from Somalia, a region with limited literature on this disease. The patient exhibited a 10-year history of indurated swelling, which progressed to the discharge of dark granules, leading to the diagnosis of black grain eumycetoma. Comprehensive diagnostic methods, including imaging and histopathological analysis, were used, confirming the fungal etiology. Surgical excision followed, alongside antifungal therapy, resulting in significant improvement. This case emphasizes the necessity for increased awareness and consideration of mycetoma in clinical practice, especially in atypical presentations and underreported geographical areas.

Neurosarcoidosis: A Diagnostic Challenge.

Neurosarcoidosis when presents with isolated cranial nerve involvement is a significant diagnostic challenge as it can mimic many other conditions like granulomatous infections, vasculitis, IgG4 disease and malignancy. Our patient is a 59 year old lady with symptoms of left sided facial pain, head ache and diplopia. Clinical examination revealed 5th and 6th cranial nerve involvement. MRI revealed enhancing smooth soft tissue lesion in pterygopalatine fossa, pterygomaxillary fissure with extension along V2 and V3. PET-CT revealed hypermetabolic lesion along left mandibular nerve in infratemporal fossa. Vasculitis panel also failed to aid in diagnosis. Biopsy done from the maxillary and mandibular nerve revealed non caseating granuloma which finally led to the diagnosis of Neurosarcoidosis. Presence of non caseasting granuloma in the histopathological examination with absence of infection and malignancy is diagnostic of Neurosarcoidosis. Patient was started on steroids and she improved clinically and symptomatically.

Revisit of Histopathology in Rheumatoid Lung Nodules.

Diagnosing pulmonary rheumatoid nodules (RN) is challenging because they are rare and share clinical, radiologic, and histopathologic features with other necrotizing granulomatous diseases such as infectious granulomas (IG) and granulomatosis with polyangiitis (GPA). Herein, we revisit the histopathologic features of RN and the findings in the adjacent lung tissue, in comparison with IG and GPA, to identify distinguishing features. Twenty-eight cases with surgically resected RN evaluated at our institution (1991 to 2024), 33 IG (10 mycobacterial infection, 10 histoplasmosis, 13 coccidiomycosis), and 10 GPA cases were included in the study. All available slides with H&E and special stains were reviewed for various histologic parameters within the nodules and in surrounding lung tissue. Many histopathologic features of RN overlap with the necrotizing granulomas seen in infections and GPA. However, some findings in the adjacent lung tissue showed significant differences. The lack of airspace granulomas/non-necrotizing granuloma and the absence of necrotizing vasculitis in the setting of RN can help to differentiate between infection cases and GPA, respectively. Given their considerable overlap, correlation with clinical context, serologic and microbiologic studies, as well as careful evaluation of special stains is crucial in the diagnosis of RN.

Granulomatous liver disease in Thailand: a 20-year retrospective clinicoradiopathological analysis

ObjectiveGranulomatous liver disease (GLD) is a rare condition with various aetiologies and is characterised by the formation of hepatic granulomas. A comprehensive evaluation of GLD from a broad perspective is...

Clinical Presentation and Histopathological Characteristics of Sporotrichosis.

Sporotrichosis is the most prevalent deep mycosis worldwide. The differential diagnosis of its clinical symptoms and histopathological features presents considerable complexity. A thorough understanding of the clinical manifestations and pathological characteristics of sporotrichosis is crucial for its accurate clinical diagnosis. This study involved a retrospective analysis of cases diagnosed with sporotrichosis at our hospital between April 2017 and April 2019, summarizing their clinical and histopathological characteristics. Among the 323 patients included in this study, a higher prevalence was observed in females. The disease predominantly affected middle-aged and elderly patients, aged between 41 and 67 years, with a higher incidence noted in winter and spring. Among the 323 patients, 170 patients (52.7%) presented with the fixed pattern, 128 (40%) with the lymphatic type, 24 (7%) with the special type, and one patient with the cutaneous-disseminated type. There were no cases of the systemic type. Histopathological findings included diffuse infectious granulomas and inflammatory infiltration, primarily characterized by diffuse and non-specific mixed inflammatory cell infiltration (without granulomas). The granulomas were primarily tuberculoid and purulent, with a lesser occurrence of granulomas exhibiting a three-zone structure, which is typically uncommon. An increase in lymphocytes, plasmacytes, and neutrophils was noted as one of the pathological features of the disease. In this region, sporotrichosis was more prevalent among female patients compared to male patients, with the fixed pattern being more common than the lymphatic type. Histopathological manifestations included diffuse infectious granulomas, with inflammatory infiltration primarily characterized by diffuse infiltration and non-specific mixed inflammatory cell infiltration (without granulomas).

Imaging features and management of tuberculomas: a review of cases and literature.

Imaging features and management of tuberculomas: a review of cases and literature.

Analysis of the efficacy of Langhans giant cells in controlling cutaneous Mycobacterium marinum infections.

Analysis of the efficacy of Langhans giant cells in controlling cutaneous Mycobacterium marinum infections.

Pulmonary granuloma formation during latent Cryptococcus neoformans infection in C3HeB/FeJ mice involves progression through three immunological phases.

Cryptococcus neoformans is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs. To investigate this, we performed an analysis of pulmonary immune cell populations, cytokine changes, and granuloma formation during infection with a latent disease-causing clinical isolate in C3HeB/FeJ mice over 360 days. We found that latently infected mice progress through three phases of granuloma formation where different immune profiles dominate: an early phase characterized by eosinophilia, high IL-4/IL-13, and C. neoformans proliferation in the lungs; an intermediate phase characterized by multinucleated giant cell formation, high IL-1α/IFNγ, granuloma expansion, and increased blood antigen levels; and a late phase characterized by a significant expansion of T cells, granuloma condensation, and decreases in lung fungal burden and blood antigen levels. These findings highlight a complex series of immune changes that occur during the establishment of granulomas that control C. neoformans in the lungs and lay the foundation for studies to identify critical beneficial immune responses to Cryptococcus infections.IMPORTANCECryptococcus neoformans is a fungal pathogen that disseminates from the lungs to the brain to cause fatal disease. Latent C. neoformans infection in the lungs is controlled by organized collections of immune cells called granulomas. The formation and structure of Cryptococcus granulomas are poorly understood due to inconsistent human pathology results and disagreement between necrotic granuloma-forming rat models and non-necrotic granuloma-forming mouse models. To overcome this, we investigated granuloma formation during latent C. neoformans infection in the C3HeB/FeJ mouse strain which forms necrotic lung granulomas in response to other pathogens. We found that latent C. neoformans granuloma formation progresses through phases that we described as early, intermediate, and late with different immune response profiles and granulomatous characteristics. Ultimately, we show that C3HeB/FeJ mice latently infected with C. neoformans form non-necrotic granulomas and could provide a novel mouse model to investigate host immune response profiles.

Hidden in plain sight: A case of misdiagnosed leprosy mimicking rheumatoid arthritis

<i>Mycobacterium leprae</i> is a causative agent of leprosy, a chronic granulomatous infection that primarily affects the skin and the peripheral nerves.<b> </b>Musculoskeletal involvement, including inflammatory arthritis, is quite common despite being under recognized. Leprosy presents protean manifestations, making it a great mimicker. Herein, we report a case of a 41-year-old Indonesian who resided in Malaysia for the past 20 years and presented with chronic joint pain and swelling of hands for a year, along with gradual facial swelling and numbness in the toes. Retrospectively, the patient noticed an erythematous skin lesion over the trunk and lower limbs 6 months before these symptoms, which did not improve with standard treatment for allergic reactions. These spectral manifestations and the subtle signs of leprosy led to a diagnostic delay of more than a year. In this study, we aim to enhance clinical awareness among primary care providers about recognizing, classifying, and appropriately treating the disease to prevent life-long deformity and disability.

Differences analysis between spinal tuberculosis and brucella spondylitis with preoperative non-invasive differential diagnosis.

Spinal tuberculosis (STB) and Brucella spondylitis (BS) represent two types of granulomatous infections affecting the spine, which exhibit significant similarities that often result in misdiagnosis and overlooked diagnoses during preoperative evaluations. This study aims to identify non-invasive evaluative indicators that facilitate the differentiation between STB and BS. This study conducted a retrospective collection of clinical features, laboratory tests, and imaging characteristics from 89 patients diagnosed with STB and 66 patients diagnosed with BS. Differences were assessed utilizing χ² tests, independent non-parametric tests, Mann-Whitney U tests, or Fisher's exact tests. Binary logistic regression analysis was employed to identify independent predictive factors for differential diagnosis, and receiver operating characteristic (ROC) curves were generated to assess the effectiveness by calculating the area under the curve (AUC). Root symptoms (including limb pain and numbness) and necrosis formation exhibited statistically significant differences, with P values of 0.024 and 0.045, respectively. Furthermore, gender, decreased A/G ratio, involvement of thoracic vertebrae, number of damaged vertebrae, and straightening of spinal curvature were identified as independent predictive factors for differentiating between STB and BS, with P values of 0.009, 0.003, < 0.001, 0.005, and 0.014, respectively. ROC analysis revealed that the AUC and 95% confidence intervals (CIs) for these five evaluative indicators were 0.626 (0.537-0.714), 0.621 (0.533-0.709), 0.694 (0.612-0.777), 0.597 (0.508-0.686), and 0.631 (0.540-0.722), respectively. The predictive model exhibited an AUC and 95% CI of 0.854 (0.796-0.911), indicating strong predictive performance. Statistically significant differences were observed between STB and BS regarding root symptoms and necrosis formation. In cases where the patient is male, presents with a decreased A/G ratio, does not have thoracic vertebra involvement, number of vertebral body destructions < 2.5, and exhibits straightening of spinal curvature, the likelihood of diagnosing BS is significantly greater than that of STB.

Splenic Calcifications in a Patient with Systemic Lupus Erythematosus: A Case Report

Abstract Splenic calcifications are very rarely reported in systemic lupus erythematosus (SLE), a multisystem autoimmune disease. We report a 52-year-old woman having SLE, diagnosed in 1992, with lupus nephritis class IV/V treated with prednisolone, hydroxychloroquine, mycophenolate mofetil, and rituximab. A computed tomography scan of her abdomen and pelvis done in 2019, postdiagnosis of breast carcinoma showed incidental findings of innumerable tiny uniform benign calcifications in the spleen. Follow-up imaging tests of the abdomen and pelvis done until 2024 showed unchanged small scattered calcifications in the spleen. As in our case, splenic calcifications in SLE show a distinctive well-defined pattern of circular dense calcification, which excludes the capsular tissue unlike in other connective tissue diseases, are bigger than the punctate calcifications observed in granulomatous infections and are different in size and imaging appearance from splenic calcified metastases. Our case is one of the few case reports describing the rare feature of characteristic splenic calcifications in SLE.

Immunopathology in human tuberculosis.

Mycobacterium tuberculosis (M.tb) is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells, and innate lymphoid cells, interact via cytokines, cell-cell communication, and eicosanoid signaling to contain or eliminate infection but can alternatively mediate pathological changes required for pathogen transmission. Clinical manifestations include pulmonary and extrapulmonary TB, as well as post-TB lung disease. Risk factors for TB progression, in turn, largely relate to immune status and, apart from traditional chemotherapy, interventions primarily target immune mechanisms, highlighting the critical role of immunopathology in TB. Maintaining a balance between effector mechanisms to achieve protective immunity and avoid detrimental inflammation is central to the immunopathogenesis of TB. Many research gaps remain and deserve prioritization to improve our understanding of human TB immunopathogenesis.

Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures.

The ovary is one of the first organs to exhibit signs of aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed by macrophage fusion, typically occur in chronic immune pathologies, including infectious and non-infectious granulomas and the foreign body response 1 , but are also observed in the aging ovary 2-4 . The function and consequence of ovarian MNGCs remain unknown as their biological activity is highly context-dependent, and their large size has limited their isolation and analysis through technologies such as single-cell RNA sequencing. In this study, we define ovarian MNGCs through a deep analysis of their presence across age and species using advanced imaging technologies as well as their unique transcriptome using laser capture microdissection. MNGCs form complex interconnected networks that increase with age in both mouse and nonhuman primate ovaries. MNGCs are characterized by high Gpnmb expression, a putative marker of ovarian and non-ovarian MNGCs 5,6 . Pathway analysis highlighted functions in apoptotic cell clearance, lipid metabolism, proteolysis, immune processes, and increased oxidative phosphorylation and antioxidant activity. Thus, MNGCs have signatures related to degradative processes, immune function, and high metabolic activity. These processes were enriched in MNGCs compared to primary ovarian macrophages, suggesting discrete functionality. MNGCs express CD4 and colocalize with T-cells, which were enriched in regions of MNGCs, indicative of a close interaction between these immune cell types. These findings implicate MNGCs in modulation of the ovarian immune landscape during aging given their high penetrance and unique molecular signature that supports degradative and immune functions.

Mandibular Actinomyces Osteitis Associated with Florid Cemento-Osseous Dysplasia

Introduction: Actinomycosis is a rare chronic suppurative granulomatous infection caused by actinomyces. The Florid cemento-osseous dysplasia (FCOD) is a benign fibro-osseous lesion. We report a case of simultaneous association of these two entities with the use of PRF for the first time in this context. Case Report: A 59-year-old female with no medical history was received in our clinic for painful swelling on the right mandible. On clinical examination, we noticed a facial asymmetry caused by the swelling and bone exposure with pus on the right mandibular ridge. The panoramic radiography showed right and left posterior mandibular opacities. On the cone beam reconstructions, we noted a hyperdense posterior right mandibular image surrounded by a hypodense border and a hyperdense posterior left mandibular image surrounded by a hypodense border, in contact with the apices of tooth 36. Based on the clinical, radiographic and pathological findings, the present case was diagnosed as mandibular actinomyces osteitis associated with florid cemento-osseous dysplasia. The treatment consisted of surgical excision of the lesion, filling of the defect with PRF and prescription of antibiotics. Conclusion: Despite its rarity, practitioners should be aware of the possibility of the coexistence of these two entities simultaneously. Thus, they can initiate the appropriate treatment.

Infectious brain abscesses and granulomas: analysis of 110 episodes in adults

BackgroundInfectious brain abscesses and granulomas, characterized by localized collections of pus or inflammatory tissue within the brain parenchyma, pose significant clinical challenges due to their potentially life-threatening nature and complex management requirements.MethodsThis cross-sectional study investigated patients diagnosed with infectious brain abscesses and granulomas from March 1, 2012, to October 22, 2021, in Mashhad, Iran. Data were collected from adult patients admitted to the two primary referral centers for community-acquired neuroinfections and neuroinflammations. Demographic information, clinical features, laboratory and neuroimaging characteristics, and clinical outcomes were analyzed.ResultsA total of 110 episodes were identified in 106 patients, with a median age of 45 years (IQR 30-56.3) and 62.7% male. Predisposing conditions included immunocompromised states (27.5%), preceding otitis/mastoiditis (16.2%), sinusitis (13.3%), and pulmonary infections (17.2%). The most common clinical manifestations were headache (57.3%), fever (49.1%), altered consciousness (44.4%), and seizures (31.8%). Neuroimaging revealed that brain lesions were solitary in 51% and multiple in 48% of episodes. Surgical intervention was performed in 46.4% of cases. The in-hospital mortality rate was 24.5%, with significant associations found between mortality and factors such as age, altered consciousness, multiple brain lesions, and cerebellum and brainstem involvement. The median length of hospital stay was 28 days (IQR 16-46.5).ConclusionOur study underscores challenges in diagnosing and treating brain abscesses and granulomas, with high mortality rates (24.5%) despite advanced techniques. Age, altered consciousness, and lesion characteristics predict death. Addressing changing microbial patterns and improving diagnostics are vital for better outcomes, especially in low- and middle-income countries.

Saliva NIR spectroscopy and Aquaphotomics: a novel diagnostic approach to Paratuberculosis in dairy cattle.

Paratuberculosis is a granulomatous intestinal infection that affects ruminant animals worldwide. The disease is often detected when most animals are already infected due to the long incubation period and the high transmissibility of the infectious agent. The lack of a comprehensive method to diagnose Paratuberculosis is a global challenge. Therefore, a non-destructive, fast, and cost-effective diagnostic method for early detection of Paratuberculosis is crucial. Near-infrared spectroscopy (NIRS) and Aquaphotomics have the potential to diagnose the disease by detecting changes in biological fluids. This study aimed to investigate the diagnostic ability of NIRS and Aquaphotomics for Paratuberculosis in dairy cattle by monitoring and data mining of saliva. The diagnostic models were developed according to saliva spectra of dairy cattle in the NIR range and 12 water absorbance bands from 100 to 200 days after calving in two groups: positive and negative, based on the same results of seven ELISA tests of blood plasma, as a reference test. Both NIRS and Aquaphotomics methods had high diagnostic accuracy. Using QDA and SVM models, 99% total accuracy, 98% sensitivity, and 100% specificity were achieved in internal validation. The total accuracy in external validation was 90%. This study presents two novel approaches to diagnosing Paratuberculosis in dairy cattle using saliva. The study found that changes in water absorbance spectral patterns of saliva caused by complex physiological changes, such as the amount of antibody related to Paratuberculosis in dairy cattle as biomarkers, are crucial in detecting Paratuberculosis using NIRS and Aquaphotomics.

Neurosarcoidosis

Sarcoidosis is an autoimmune multisystemic inflammatory disease characterized by non-caseating granulomatous infection, most commonly involving the lung and lymph nodes. About 5–15% of cases involve the central nervous system (CNS), neurologic involvement in sarcoidosis is in the form of peripheral or central nervous system involvement. Recent years have seen substantial advancements in our understanding of neurosarcoidosis, including updated diagnostic standards and improved methods for treatment. We provide an overview of current developments in the identification and management of neurosarcoidosis in this review.

Rhinosporidiosis Presenting as a Large Oral Cavity Mass: A Case Report

Rhinosporidiosis Presenting as a Large Oral Cavity Mass: A Case Report