Search Results (172)

Recent advances in the structural characterization of the phagocyte NADPH oxidase coupled with the description of its chaperone EROS for Essential for Reactive Oxygen Species have led to a better understanding of its function and activation in phagocytic cells. This review examines the role of EROS chaperone in flavocytochrome b₅₅₈ biosynthesis and function and in physiological and pathological conditions. Based on experimental data and structural insights, we synthesize knowledge from former work on flavocytochrome b₅₅₈ synthesis and structure combined with recent advances on the specific role of EROS chaperone on the potential control of Reactive Oxygen Species (ROS) production by c flavocytochrome b₅₅₈. We particularly emphasize its role in the pathological context of Chronic Granulomatous Disease (CGD), with already described EROS mutations (known as CGD5), as well as rare X91^minus-CGD (or X91⁻-CGD) cases characterized by low flavocytochrome b₅₅₈ expression in phagocytes that could be due to a lack of interaction with EROS. Future works should address in more detail how EROS binding and release from flavocytochrome b₅₅₈ is regulated, and whether the inhibitory effect on ROS production that was observed in EROS overexpression studies is relevant in a more physiological context. Full article

Nocardia spp. and Mycobacterium spp. are known etiological agents of granulomatous pulmonary infections in humans and animals; however, co-infections involving these pathogens have not previously been reported in veterinary medicine. This paper describes the first documented case of co-infection with Mycobacterium bovis and Nocardia spp. in a captive roan antelope (Hippotragus equinus). The animal was a 9-year-old female roan antelope from a safari park in northern Italy that died suddenly with a one-month history of weight loss. Post-mortem examination revealed severe, diffuse, chronic granulomatous pneumonia associated with fibrino-granulomatous pleuritis and granulomatous pericarditis. Histologically, multifocal to coalescing necrotizing granulomas were observed, with intralesional acid-fast bacteria. Microbiological culture and biomolecular analyses allowed the identification of M. bovis and Nocardia spp. in lung tissue samples. The Nocardia genome sequence was 98.5% similar to N. tengchongensis, a recently discovered species. The findings emphasize the importance of comprehensive diagnostic approaches in animal granulomatous lung disease. Mixed infections in captive wildlife represent a One Health concern, as the potential for zoonotic adaptation and transmission to humans cannot be excluded. Therefore, pathogen surveillance is of particular importance within zoological collections. Full article

Background/Objectives: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory disease of the breast that may present with recurrent and treatment-resistant courses and can clinically and radiologically mimic breast cancer. Despite its benign nature, IGM may significantly impair quality of life, and its underlying pathophysiology remains unclear. This study aimed to evaluate oxidative stress and DNA damage in patients with IGM. Methods: In this prospective case–control study, 28 patients with clinically and histopathologically confirmed idiopathic granulomatous mastitis who had not received corticosteroid or immunosuppressive therapy within the previous six months were enrolled. An age-matched control group of 27 healthy women was included. Venous blood and urine samples were collected for the assessment of total oxidant status (TOS), total antioxidant status (TAS), and calculation of the oxidative stress index (OSI). Mononuclear leukocyte DNA damage was evaluated using the alkaline Comet assay, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured by ELISA. Sociodemographic data, laboratory and imaging results of the patients were also evaluated. Results: The mean ages of the patient and control groups were 37.3 ± 5.3 and 35.4 ± 8.6 years, respectively, with no significant difference (p = 0.081). Patients exhibited significantly higher inflammatory markers and oxidative stress parameters, including TOS, OSI, and urinary 8-OHdG (p < 0.05), whereas TAS did not differ between groups (p = 0.534). Comet assay analysis demonstrated significantly increased tail intensity (%) and tail moment in the patient group (p = 0.029 and p = 0.016). Conclusions: IGM is associated with increased oxidative stress and mononuclear leukocyte DNA damage. These findings suggest that oxidative stress-induced DNA damage may play a role in the pathophysiology of IGM and highlight the potential value of antioxidant-based therapeutic strategies as adjunctive treatment options. Full article

Phaeohyphomycosis is an opportunistic fungal infection caused by dematiaceous fungi and is considered uncommon in dogs, particularly when associated with visceral or systemic involvement. Pulmonary disease as a primary site of infection is rarely reported in veterinary medicine and is often associated with an unfavorable outcome. This report describes a fatal case of pulmonary phaeohyphomycosis in a dog, characterized by severe granulomatous pneumonia, vascular invasion by pigmented fungal hyphae, and the development of large vessel thrombosis. Histopathological examination revealed septate, pigmented hyphae consistent with dematiaceous fungi associated with an intense granulomatous inflammatory response. Although molecular analysis by polymerase chain reaction was unsuccessful due to the absence of amplifiable DNA in archived FFPE tissue, the clinicopathological correlation and histopathological findings were sufficient to support a diagnosis consistent with phaeohyphomycosis. Severe pulmonary inflammation likely contributed to vascular endothelial injury, resulting in pulmonary hypertension and thrombosis of major veins. This case highlights the diagnostic and clinical challenges associated with phaeohyphomycosis in dogs and emphasizes the importance of considering this infection in the differential diagnosis of chronic or progressive respiratory diseases accompanied by systemic complications. Furthermore, it reinforces the relevance of histopathology and comprehensive clinicopathological evaluation when molecular confirmation of the etiological agent is not achievable. Full article

In this report, we describe systemic granulomatous mycobacteriosis in an orbiculate batfish from an aquarium in South Korea. Gross examination of the deceased fish showed multifocal nodular lesions in multiple internal organs including the gills, spleen, and kidney. Histopathological analysis demonstrated severe chronic systemic granulomatous inflammation, and Ziehl–Neelsen staining highlighted abundant intralesional acid-fast bacilli. Molecular analysis based on partial sequencing of the 16S ribosomal RNA (rRNA) and heat shock protein 65 (hsp65) genes showed that the detected organism was most closely related to Mycobacterium marinum. Because the molecular analysis was performed using partial sequences obtained from formalin-fixed, paraffin-embedded tissues, definitive species-level identification was not possible. This case represents systemic granulomatous mycobacteriosis associated with a Mycobacterium marinum-like organism in orbiculate batfish in an aquarium in South Korea and emphasizes the need for continuous disease surveillance and improved diagnostic awareness of non-tuberculous mycobacterial infections in ornamental and public aquarium fish. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and to outline a context-adapted multimodal screening strategy for CEE settings. Methods: A structured review of PubMed-, Scopus-, and Web of Science-indexed literature published from 2010 through 27 December 2025 was performed, focusing on lung cancer epidemiology, screening, implementation barriers, risk stratification, and adjunctive diagnostic approaches in the four selected CEE countries. A total of 297 articles were included. Results: The evidence confirms a persistently high burden of late-stage lung cancer across CEE, driven by tobacco exposure, air pollution, radon, comorbidities, diagnostic delays, fragmented registries, workforce shortages, and marked socioeconomic and geographic inequalities. In addition, tuberculosis-related granulomatous lesions and chronic inflammatory lung disease complicate nodule interpretation and reduce screening specificity in parts of the region. Screening experience from Poland and Hungary supports the feasibility of low-dose computed tomography (LDCT) when paired with volumetric assessment and structured follow-up. Risk-prediction models may improve participant selection, while biological triage may help reduce unnecessary invasive procedures, although prospective validation remains limited. Conclusions: In CEE, lung cancer screening should be implemented as a multimodal, context-adapted program combining risk-based enrollment, volumetric LDCT, selective biological triage, smoking-cessation support, and centralized multidisciplinary delivery. Full article

Recently, a strain of Streptococcus agalactiae serotype Ia sequence type 7 clonal complex 1 (SaIa ST7 CC1) has emerged in Latin American tilapia aquaculture as an international threat. This study evaluated outbreaks of acute streptococcosis occurring between 2021 and 2025 on commercial Nile tilapia (Oreochromis niloticus) farms in six Latin American countries, aiming to integrate molecular, clinical, pathological, and environmental data. In total, 360 moribund or recently dead fish at various production stages (larvae/fry, pre-grow-out, and grow-out) were examined, and 25 S. agalactiae isolates were serotyped and subjected to real-time PCR analysis, multilocus sequence typing (MLST), virulence and antimicrobial resistance gene profiling, and antimicrobial susceptibility testing. All isolates belonged to SaIa and shared the same ST7 CC1 MLST profile, forming a highly homogeneous cluster with reference SaIa ST7 CC1 strains previously isolated from tilapia farms in Asia. These results are consistent with the regional spread of a single clonal line. At the larval and fry stages, SaIa ST7 CC1 was associated with hyperacute septicemia, gastrointestinal hemorrhage, and frequent intestinal intussusception, whereas in pre-grow-out and grow-out fish, neurological signs were more prominent, followed by ocular signs, systemic hemorrhages, and coelomic lesions. Histopathological examination showed profuse colonization of the brain, spleen, liver, and intestine by Gram-positive cocci, accompanied by marked acute circulatory and inflammatory lesions and few chronic granulomatous responses, consistent with a rapidly progressing, highly aggressive infectious process. All outbreaks occurred during extended periods of warm water (>32 °C), with large day–night thermal gradients and reduced dissolved oxygen, suggesting that thermal stress may exacerbate disease expression in affected systems. All SaIa ST7 CC1 strains exhibited phenotypic susceptibility to florfenicol and amoxicillin, whereas 84% (21/25) and 100% (25/25) exhibited intermediate susceptibility to oxytetracycline and enrofloxacin, respectively. In total, 5 of the 21 isolates (23.8%) with intermediate susceptibility to oxytetracycline carried tetracycline resistance genes (tetM, tetO). These findings identify SaIa ST7 CC1 as a clinically significant emerging threat associated with thermally facilitated and geographically expanding streptococcosis in tilapia production in Latin America. Immediate priorities include screening imported broodstock using MLST or whole-genome sequencing (WGS), harmonized regional molecular surveillance, climate-adaptive farm management practices, prudent antimicrobial use, and serotype-matched vaccination and breeding strategies that improve both disease and heat resilience. Full article

Schistosomiasis (bilharzia) is a parasitic infection caused by trematodes of the Schistosoma genus and remains a significant health burden in endemic regions. Granulomatous host responses to deposited Schistosoma eggs in small veins and tissues result in progressive changes and characteristic imaging findings. This diagnostic radiological review synthesizes the published literature and highlights key and robust imaging findings that facilitate the diagnosis of Schistosoma mansoni and Schistosoma haematobium, with emphasis on modality-specific patterns and disease staging. Schistosoma mansoni primarily affects the liver, causing periportal fibrosis visible as “pipe-stem” echogenic thickening upon ultrasonography, which may progress to portal hypertension and chronic liver disease. Liver cirrhosis is the end-stage disease manifested as an irregular liver contour with surface nodularity and lobar redistribution as right lobe atrophy with left and/or caudate lobe hypertrophy. Schistosoma haematobium predominantly affects the genitourinary system, causing urinary bladder wall thickening and calcification. Early disease, within three months of infection, may present with fine calcification, firstly in the bladder base and then extending to the whole bladder and even to the ureters. Calcification appears as a line or two parallel lines on radiography and as a circle in axial computed tomography (CT) images, which is pathognomonic for early-stage Schistosomiasis. In contrast studies, including conventional urography and CT urography, Schistosoma eggs appear as bubble-like filling defects in the ureter, kidney, and bladder, manifested as ureteritis, pyelitis, and cystitis cystica. Late stages appear as coarse calcification, fibrosis, strictures, and reduced bladder capacity and are associated with an increased risk of bladder squamous cell carcinoma. Moreover, Schistosomiasis calcification can present in genital organs, especially in the seminal vesicles; in the prostate in males; and in the vulva, cervix, and perineum in females. Ultimately, Schistosoma mansoni and haematobium eggs can reach the spinal cord, leading to acute myelopathy with paraparesis, urinary retention, or paraplegia. Recognition of characteristic imaging patterns of Schistosomiasis is essential for early diagnosis, accurate staging, and prevention of long-term complications. Full article

Vogt–Koyanagi–Harada syndrome (VKH) is a rare granulomatous autoimmune disease characterised by a systemic immune response directed against melanocytes. This multisystem condition primarily affects organs that are rich in melanocytes, such as the eyes, inner ear, meninges and skin. VKH might be responsible for the development of chronic uveitis and permanent visual impairment, particularly in cases where a diagnosis is delayed and treatment is not administered in a timely manner. A key factor in its pathogenesis is the loss of immune tolerance to melanocytes, driven by a T-cell–mediated immune response and genetic susceptibility, including the presence of HLA-DRB1*04 antigens. In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment in oncology, including non-small cell lung cancer and unresectable melanoma. However, it should be noted that their utilisation carries with it the potential for immune-related adverse events, including rare cases of VKH-like uveitis. The objective of this review is to outline the clinical features of VKH syndrome, examine current diagnostic and treatment approaches, and emphasise the immunopathological mechanisms associated with drug-induced forms of VKH, with a particular focus on programmed cell death protein 1 (PD-1) inhibitors. The article also includes an analysis of the genetic, epigenetic, and environmental factors that predispose individuals to the disease. This analysis facilitates a deeper understanding of the pathogenesis of the disease and assists in the identification of patients at increased risk of drug-induced VKH manifestations. Full article

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

Background: Cervicofacial actinomycosis is an uncommon chronic bacterial infection that can mimic neoplasia or granulomatous disease because of its infiltrative presentation. Diagnosis is often delayed, particularly in pregnant patients in whom imaging and invasive procedures may be limited. Case report: A 25-year-old woman at 14 weeks of gestation presented with a multiple-fistulized cervical mass. The lesion was initially diagnosed as a cutaneous furuncle in a private dermatology practice and treated with topical therapy, resulting in only transient improvement. Two weeks later, multiple fistulizations developed, prompting consultation in the emergency department. ENT assessment and ultrasound raised suspicion of cervical actinomycosis versus fistulized tuberculous lymphadenitis. Considering the pregnancy, drainage of the collection was performed under local anesthesia and empiric antibiotic therapy with amoxicilin-clavulanic acid was started. Microbiological confirmation of Actinomyces (Schaalia) georgiae led to infectious disease evaluation that established a long-term antibiotic therapy while monitoring fetal safety. Progressive clinical improvement was observed, with complete resolution after three months. The pregnancy progressed without complications and fetal morphology remained normal under therapy. Conclusions: This case illustrates the diagnostic complexity of cervicofacial actinomycosis caused by A. georgiae during pregnancy, representing the first such report in the current literature, and emphasizes the need for a multidisciplinary approach. Full article

Blastomycosis-like pyoderma (BLP) is a rare chronic inflammatory dermatosis characterized by exuberant vegetative and verrucous plaques, most frequently associated with bacterial colonization, particularly Staphylococcus aureus. Owing to its striking clinical and histopathological resemblance to squamous cell carcinoma (SCC) and other granulomatous or hyperplastic dermatoses, BLP represents a well-recognized diagnostic pitfall, often leading to delayed diagnosis or unnecessary surgical management. We report an unusual case of bilateral auricular BLP in a 58-year-old apparently immunocompetent woman, initially misdiagnosed as SCC. Comprehensive clinicopathological reassessment revealed pseudoepitheliomatous hyperplasia, intraepidermal neutrophilic microabscesses, and a dense mixed inflammatory infiltrate, findings consistent with a reactive rather than neoplastic process. Microbiological cultures confirmed Staphylococcus aureus, supporting the final diagnosis of BLP and guiding effective antimicrobial therapy. To better contextualize this rare presentation, we reviewed all previously reported cases of BLP, summarizing available clinical, histopathological, microbiological, and therapeutic data. This case further raises the possibility of an association between BLP and systemic inflammatory conditions, as the patient subsequently developed severe colitis, highlighting the potential role of immune dysregulation and the gut–skin axis in disease pathogenesis or a possible temporal association, without allowing causal inference. Beyond inflammatory bowel disease, blastomycosis-like pyoderma has been reported in association with a variety of systemic and immune-mediated conditions, including diabetes mellitus, hematologic malignancies, HIV infection, chronic renal failure, autoimmune disorders, and prolonged immunosuppressive therapies. These associations support the concept that BLP represents a hyperinflammatory reaction pattern occurring in the setting of altered immune surveillance rather than a purely infectious disease. Accurate recognition and management of BLP require careful integration of clinical features, histological findings, and microbiological results. Increased awareness of its diverse presentations is essential to avoid misdiagnosis and to ensure appropriate, conservative treatment. Full article

Cardiac sarcoidosis (CS) is a critical and frequently underdiagnosed phenotype of sarcoidosis, characterized by non-caseating granulomatous infiltration of the myocardium. This review synthesizes current knowledge regarding the pathogenesis, diagnosis, and management of CS. The disease manifests with a heterogeneous clinical spectrum ranging from asymptomatic conduction abnormalities to life-threatening ventricular arrhythmias and heart failure. Diagnosis remains challenging due to the patchy distribution of granulomas, which limits the sensitivity of endomyocardial biopsy. Consequently, a multimodal diagnostic approach is essential, integrating advanced imaging modalities such as cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). These tools not only facilitate detection but also enable the differentiation of active inflammation from chronic fibrosis. Histopathological assessment, supported by specific immunophenotyping and electron microscopy, remains the gold standard for confirming diagnosis and excluding mimics like giant cell myocarditis or infectious granulomatous diseases. Management requires a multidisciplinary strategy combining immunosuppressive therapy, primarily corticosteroids and steroid-sparing agents, with guideline-directed cardiac care, including implantable cardioverter-defibrillators for arrhythmia risk stratification. Emerging biomarkers and artificial intelligence-driven imaging analysis promise to further refine risk stratification and therapeutic monitoring, advancing precision medicine in this complex disorder. Full article

Chromoblastomycosis is a chronic mycosis of the skin and subcutaneous tissue typically caused by traumatic inoculation of dematiaceous fungi of the Herpotrichiellaceae. A 59-year-old male presented with a 12-month history of an asymmetrical, scaly plaque on the left forearm that has been slowly increasing in size. Past medical history included atrial fibrillation on apixaban, hypertension and a cardiac stent. A 4 mm punch biopsy of the left forearm revealed superficial dermal fibrosis with mild pseudoepitheliomatous hyperplasia and granulomatous inflammation with scattered multinucleate histiocytes. There were giant cells with dark brown, somewhat round, yeast-like structures, some with internal septation exhibiting moderate staining for PAS, compatible with Medlar bodies suggestive of chromoblastomycosis. The patient was on rosuvastatin, rendering itraconazole not a possible treatment option, and instead the patient underwent curettage and cautery with two bouts of cryotherapy freeze and thaw cycles. A twelve-month follow-up noted a crusted area on the distal aspect of the scar. A shave biopsy of this area revealed pigmented organisms suggesting a recurrence of chromoblastomycosis. A further excisional biopsy was performed, with no evidence of chromoblastomycosis. This case highlights multiple surgical options for the management of chromoblastomycosis in patients where medical management is contraindicated. It highlights the therapeutic challenge of this disease due to frequent recurrence of lesions and that repeat biopsy may be efficacious in monitoring for recurrence. Full article

Vitamin D, a fat-soluble vitamin functioning as a hormone via the vitamin D receptor (VDR), is critical for calcium homeostasis and bone health. Vitamin D deficiency is linked to nutritional rickets, osteomalacia, and increased risk of non-communicable diseases such as cancer and diabetes. While serum 25(OH)D₃ is used to assess vitamin D status, its active form, 1α,25(OH)₂D₃, exerts context-dependent effects on calcium metabolism. Nonetheless, the therapeutic utility of native vitamin D is limited in certain pathologies. In chronic kidney disease (CKD), the renal conversion of 25(OH)D₃ to active 1α,25(OH)₂D₃ is compromised, necessitating the use of active synthetic analogs to bypass this metabolic defect. Furthermore, for dermatological and oncological disorders requiring supraphysiological dosing, synthetic analogs have been designed to dissociate beneficial anti-proliferative effects from the severe hypercalcemia induced by high-dose 1α,25(OH)₂D₃. VDR mediates transcriptional responses, modulated by co-regulators and chromatin remodeling complexes. Recent discoveries include non-genomic VDR pathways and SCAP (SREBP cleavage-activating protein)-dependent signaling that modulate lipid metabolism. Despite promising preclinical results, most synthetic VDR agonists fail to show efficacy in cancer therapy due to calcemic toxicity. However, compounds like eldecalcitol are effective in osteoporosis, especially in low-calcium-intake populations. Selective VDR modulators, akin to SERMs, exhibit tissue-specific effects. Moreover, novel VDR antagonists such as ZK168281 demonstrate potential to suppress hypercalcemia and vitamin D toxicity by inhibiting transcriptional activity and altering VDR localization. These agents may enable anti-inflammatory or anti-proliferative actions without calcemic risks. Understanding the nuanced biology of vitamin D and its analogs offers new avenues for therapeutic intervention beyond bone metabolism, including managing hyperparathyroidism, granulomatous diseases, and inflammation-associated disorders. Full article