Search Results (137)

Scrofuloderma, a cutaneous manifestation of tuberculosis, is a rare but clinically significant form of mycobacterial infection. It typically results from the local spread of Mycobacterium tuberculosis from an infected lymph node or bone area to the overlying skin. This disease is mainly characterized by chronic granulomatous inflammation, leading to skin ulcers and abscesses. Due to its nonspecific clinical presentation, scrofuloderma can mimic various dermatological conditions, making its diagnosis particularly challenging. This case report presents the clinical course of a patient who was positive for the Human Immunodeficiency Virus (HIV) with a diagnosis of scrofuloderma, managed at a tertiary healthcare center, with follow-up before and after treatment. A literature review was also made, highlighting the importance of maintaining a high index of clinical suspicion and utilizing appropriate diagnostic methods to ensure timely diagnosis. Full article

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes. Full article

Cutibacterium acnes (C. acnes) is a commensal bacterium of the skin microbiota that can transform itself into a pathogen depending on the peculiar susceptibility of the host: it is the sole microorganism so far to be found in the specific organ lesions of sarcoidosis, and C. acnes-induced activation of T-helper-type-1 cell responses is generally higher in patients with sarcoidosis than in healthy subjects. This bacterium acts as an opportunistic agent in several inflammatory conditions other than sarcoidosis, such as prostate cancer and prosthetic joint infections. Both innate and adaptive immunity systems are involved in the pathogenesis of C. acnes-mediated sarcoid lesions, and a seminal role is played by host toll-like receptor (TLR)-2, TLR-4, TLR-6, NOD-like receptors, and mononuclear cell cytoplasmic receptors. This review summarizes current knowledge on the potential cause–effect relationship existing between C. acnes and sarcoidosis, addressing issues of future research directions and novel therapeutic strategies in the management of a complex disease such as sarcoidosis. Full article

Although publications have documented the osteo-inductive effects of various bioactive materials on tissue sections, the associated morphologic patterns of tissue remodeling pathways at the cellular level have not been detailed. Therefore, we present a comparative histopathological follow-up evaluation of bone defect repair mediated by silica aerogels and methacrylate hydrogels over a 6-month period, which is the widely accepted time course for complete resolution. Time-dependent microscopic analysis was conducted using the “critical size model”. In untreated rat calvaria bone defects (control), re-ossification exclusively started at the lateral regions from the edges of the remaining bone. At the 6th month, only a few new bones were formed, which were independent of the lateral ossification. The overall ossification resulted in a 57% osseous encroachment of the defect. In contrast, aerogels (AE), hydrogels (H), and their β-tricalcium-phosphate (βTCP)-containing counterparts, which were used to fill the bone defects, characteristically induced rapid early ossification starting from the 1st month. This was accompanied by fibrous granulomatous inflammation with multinucleated giant macrophages, which persisted in decreasing intensity throughout the observational time. In addition to lateral ossification, multiple and intense intralesional osseous foci developed as early as the 1st month, and grew progressively thereafter, reflecting the osteo-inductive effects of all compounds. However, both βTCP-containing bone substituents generated larger amounts and more mature new bones inside the defects. Nevertheless, only 72.8–76.9% of the bone defects treated with AE and H and 80.5–82.9% of those treated with βTCP-containing counterparts were re-ossified by the 6th month. Remarkably, by this time, some intra-osseous hydrogels were found, and traces of silica from AE were still detectable, indicating these as the causative agents for the persistent osseous–fibrous granulomatous inflammation. When silica or methacrylate-based bone substituents are used, chronic ossifying fibrous granulomatous inflammation develops. Although 100% re-ossification takes more than 6 months, by this time, the degree of osteo-fibrous solidification provides functionally well-suited bone repair. Full article

Background and Clinical Significance: Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder, characterized by severe hypogammaglobulinemia and disturbed antibody production. In addition to increased susceptibility to recurrent respiratory and gastrointestinal infections, CVID can lead to a wide array of complications associated with immune dysregulation, which can also affect the liver. Liver involvement occurs in about 10% of patients with CVID, and can result from a range of causes, including infections, autoimmune disorders, lymphoproliferative conditions, granulomatous inflammation, and infiltrative processes. The most common liver manifestations include nodular regenerative hyperplasia, granulomatous or autoimmune hepatitis, and lymphocytic infiltration. The prevalence, pathophysiology, extent, and prognosis of liver involvement in CVID have not been systematically studied. Case Presentation: The object of this article is to present two patients with CVID-related liver disease and to illuminate the most relevant causes of liver involvement in CVID, describe the clinical features of their liver disease, and summarize the diagnostic and therapeutic approaches for its management. Conclusions: Liver involvement is an expected complication in patients with CVID syndrome. The delayed recognition of this pathology significantly worsens the disease prognosis, making the early detection of this potential complication crucial. Full article

Background: Invasive aspergillosis with orbital apex and intracranial involvement is rare and often misdiagnosed due to nonspecific imaging findings. Misinterpretation may lead to inappropriate therapies, such as corticosteroids, which can exacerbate fungal infections. Case Presentation: A 50-year-old immunocompetent woman with diabetes mellitus presented with right ptosis and systemic malaise. Magnetic resonance imaging (MRI) performed three months prior had shown a subtle low-signal lesion in the right orbital apex. The lesion was small and thought to represent a granulomatous process, with minimal systemic inflammation and only mild surrounding changes on imaging. Biopsy was considered too invasive at that stage, and the patient was placed under observation. Over time, her condition progressed, and repeat imaging revealed intracranial extension, including involvement of the cavernous sinus and frontal lobe. Differential diagnoses included granulomatous diseases such as sarcoidosis or tuberculosis, prompting empirical anti-tuberculosis treatment. However, the patient’s condition worsened, and biopsy of the sphenoid sinus revealed septated fungal hyphae consistent with Aspergillus species on Grocott staining. Voriconazole therapy was initiated, resulting in significant clinical and radiological improvement. Discussion: This case highlights the diagnostic challenge of identifying orbital apex aspergillosis with early MRI changes and demonstrates the risk of misdiagnosis as granulomatous disease. Differentiating fungal infections from other inflammatory etiologies based on subtle imaging features is critical, especially when considering immunosuppressive therapy. Conclusion: Clinicians should maintain a high index of suspicion for fungal infections in patients with progressive orbital apex lesions, even in the absence of classic immunosuppression. Early imaging review and biopsy are essential to prevent misdiagnosis and inappropriate treatment. Full article

This article documents the first outbreak of aeromoniasis caused by Aeromonas veronii in farmed European seabass (Dicentrarchus labrax) along the Greek Ionian Sea coast. In late spring 2024, commercially sized fish exhibited anorexia, hemorrhages, and ulcers on the skin, accompanied by elevated morbidity and mortality rates. The outbreak spread rapidly across local farms in Sagiada Bay, reaching its peak in late summer, and extending into the Astakos Gulf, southern in the Ionian Sea. The postmortem examination revealed hemorrhages, organomegaly, abscess formation, and granulomatous inflammation. Aeromonas veronii was isolated from all examined individuals in nutrient media and confirmed by biochemical and molecular methods. Whole genome sequencing and phylogenetic analysis demonstrated genetic homogeneity among two strains from two different areas along the Ionian Sea and a close evolutionary relationship with other Aeromonas veronii strains from the Aegean Sea. Although genetically similar, the isolates exhibited differences in phenotypic and biochemical characteristics, indicating regional variability. The present study provides an overview of the pathology, clinical characteristics and progression of aeromoniasis in Ionian Sea aquaculture, highlighting the need for continued monitoring, in-depth genomic and phenotypic assessment, and the design of region-specific preventive strategies, including autogenous vaccines, for effective disease management. Full article

Background: Granulomatous and amyloidogenic cardiomyopathies are infiltrative conditions that can be fatal if left untreated. Among these, cardiac amyloidosis and cardiac sarcoidosis are significant but often underdiagnosed causes of heart failure, each serving as cardiac manifestations of broader systemic diseases. Advancements in imaging techniques and the emergence of novel therapies—particularly for cardiac amyloidosis—have brought these conditions into sharper focus for both clinicians and researchers. Methods: We conducted a comprehensive review of the literature by searching databases including PubMed and Scopus for studies published since 1990 regarding clinical features, diagnostic techniques, and treatment strategies for cardiac amyloidosis and cardiac sarcoidosis. Studies were selected based on relevance to imaging methods, including echocardiography, cardiac magnetic resonance imaging (CMR), positron emission tomography (PET), and technetium-labeled nuclear scintigraphy, as well as treatment modalities for both conditions. Results: Imaging techniques, particularly CMR, technetium-labeled nuclear scan, and PET, were found to be crucial for the early identification and differentiation of cardiac amyloidosis and cardiac sarcoidosis. Distinct late gadolinium enhancement patterns were observed in CMR along with morphological differences, aiding in diagnosis. Technetium-labeled nuclear scintigraphy can definitively distinguish between subtypes of cardiac amyloidosis in the absence of paraproteinemia. Early diagnosis has been shown to significantly improve patient outcomes. Early treatment can reduce morbidity in both cardiomyopathies. Conclusions: Multimodality imaging can help in the early detection of cardiac amyloidosis and cardiac sarcoidosis. Treatment strategies differ substantially: cardiac amyloidosis is primarily managed with disease-modifying therapies for the transthyretin subtype and chemotherapy/stem cell transplant for the AL subtype, while cardiac sarcoidosis is treated with corticosteroids and immunosuppressive drugs to reduce inflammation. Early and accurate diagnosis through advanced imaging techniques is critical to improving outcomes for patients with these conditions. Full article

Background: A previous published Phase 2 trial using 2–4 doses of neoadjuvant cemiplimab in stage II–IV resectable cutaneous squamous cell carcinoma (CSCC) demonstrated that a complete pathological (pCR) rate of 51% and major pathological response (mPR) rate of 13% could be achieved with durable disease control. Methods: In this open-label, single-institution phase II trial (NCT05878288), patients with stage II–IV resectable CSCC received up to four doses of neoadjuvant cemiplimab prior to surgery. The primary endpoint of the study was to perform comprehensive molecular profiling. The focus of this report are the secondary clinical endpoints of pCR rate, mPR (defined as <10% viable tumour) rate, overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, immune-modified RECIST (imRECIST) and Immune PET Response Criteria in Solid Tumours (iPERCIST), disease-free survival (DFS), overall survival (OS), safety, and to describe changes in planned surgery. Results: Eleven patients were enrolled, with all proceeding with surgery. An ORR and pCR rate of 73% (8/11; 95% CI 0.39–0.93) was achieved, whilst 3/11 patients progressed on treatment. On pre-operative imaging, all 8/11 pCR patients demonstrated a partial response (RECIST 1.1), whilst 6/8 achieved a complete metabolic response and 2/8 a partial metabolic response (iPERCIST). Median follow-up was 10.2 (IQR 6.7–16.4) months. DFS was 91% (95% CI 0.57–1) and OS was 100% (95% CI 0.68–1), with one non-responder patient who developed recurrent locoregional and distant metastatic disease. There were no unexpected safety signals. Pathological features of response to neoadjuvant immunotherapy most commonly were granulomatous inflammation with keratin, fibrosis and inflammation. No cases with a dense inflammatory infiltrate were observed. Neoadjuvant immunotherapy did not impact the intra-operative planning and execution of surgery, but in the eight pCR cases, it reduced the extent of required surgery, whilst in the three non-responder cases, surgery was more extensive than originally planned. Conclusions: The DISCERN trial confirms that an excellent complete response rate can be achieved with four doses of neoadjuvant immunotherapy in stage II–IV CSCC. Proposed refinements to the pathological assessment of response and metabolic response criteria in CSCC for the neoadjuvant context are provided. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

Isolated intrahepatic lymphoid follicles (ILFs), also referred to as reactive lymphoid hyperplasia, are rare benign lymphoid proliferations that can closely mimic hepatocellular carcinoma (HCC) on imaging. This case highlights the diagnostic complexity of hepatic mass lesions in chronic hepatitis B patients, particularly when radiologic and serologic features raise concern for malignancy. A 60-year-old man with chronic hepatitis B presented with a liver mass, elevated alpha-fetoprotein levels, and imaging findings of heterogeneous arterial enhancement, all suggestive of HCC. Despite initial treatment with atezolizumab plus bevacizumab, the lesion progressed, leading to an extended left hepatectomy. Histopathological examination revealed well-formed lymphoid follicles with reactive germinal centers, without evidence of malignancy or granulomatous inflammation. Serum IgG was elevated, and ANA was positive, supporting the possibility of an underlying immune-mediated process. The patient showed clinical and serologic improvement following corticosteroid therapy, with no evidence of recurrence at 10-month follow-up. This case underscores the importance of histopathological confirmation in hepatic masses with atypical features and highlights the need to consider benign immune-related mimickers in the differential diagnosis, particularly in the era of immunotherapy. Full article

Background/Objectives: Granulomatosis with polyangiitis (GPA) is a necrotising vasculitis characterised by granulomatous inflammation involving small vessels. In addition to specific findings for the affected organ, constitutional symptoms and joint and muscle pain can be observed. The prodromal phase, where symptoms last for months before clinical diagnosis, may suggest infection or malignancy. This may cause a delay in GPA diagnosis. The period from the first symptoms to diagnosis may last from one month to three years. In this study, we aimed to demonstrate that, as the time between the onset of symptoms and diagnosis increases, the disease involvement may become more severe, and the possibility of recurrence may increase, indicating the importance of early diagnosis. Methods: For this cross-sectional retrospective study, data from 40 patients with GPA were evaluated. Demographic, clinical, treatment, and follow-up characteristics of the patients were obtained from their medical records. Results: The mean time between the presentation of the first complaints and GPA diagnosis was 7.40 ± 11.84 (0, 60, 3; mean ± standard deviation [minimum, maximum, and median]) months. The time between the first complaints and diagnosis was longer for patients with a history of recurrence (11.44 ± 16.73 [0, 60, 4.5] vs. 4.71 ± 6.04 [0, 24, 2.5], p value = 0.260). Conclusions: GPA is an inflammatory disease with various clinical presentations. In the management of patients with GPA, awareness of its presentation is important for rheumatologists as well as other clinicians during the initial evaluation, demonstrating the importance of interclinical collaboration. Full article

Background: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug (NSAID), but its conventional formulations may have limited efficacy and are associated with adverse effects. This study aimed to evaluate the anti-inflammatory and antioxidant effects of diclofenac encapsulated in chitosan-coated lipid microvesicles (DCF-m) compared to free DCF in a rat model of subacute inflammation. Method: DCF-m was prepared using L-α-phosphatidylcholine and coated with chitosan (CHIT). Subacute inflammation was induced using the cotton pellet granuloma model, and animals were divided into four groups (n = 5): a negative control group without granuloma receiving vehicle (double-distilled water), a control group with granuloma receiving vehicle, a group with granuloma treated with 15 mg/kg of free DCF, and a group with granuloma treated with 15 mg/kg of DCF-m. Results: Both DCF and DCF-m significantly reduced granuloma mass, body weight gain, and serum inflammatory markers compared to the control group with granuloma. Moreover, DCF-m treatment led to a more pronounced reduction in granulomatous inflammation and a greater enhancement of antioxidant enzyme activity than free DCF. Conclusions: These findings suggest that DCF-m exhibits superior anti-inflammatory and antioxidant properties compared to conventional diclofenac in a model of subacute inflammation. Full article

Reighardia sternae is a pentastomid parasitising the respiratory system of larids and skuas, the pathological significance of which is still poorly understood. In this study, pentastomes found in the interclavicular air sac of a deceased and necropsied yellow-legged gull (Larus michahellis) were identified by parasitological and molecular methods and associated gross and histopathological lesions were evaluated. After morphological evaluation and molecular characterisation, the species R. sternae was identified. This is the first report of R. sternae infecting L. michahellis in Italy. Gross pathology showed generalised aerosacculitis, parabronchial edema, and enlargement of the heart, liver, and spleen. The systemic lesions found at histopathological examination were indicative of chronic cardiocirculatory failure, which led to the death of the gull. Moreover, inflammation was present throughout the lungs and air sacs in the form of some granulomas and diffuse small nodular aggregates rich in lymphocytes. The remnants of a parasite were observed within a granulomatous lesion in the lung, suggesting a primary host response to the parasite. These latter findings may suggest that the migration of R. sternae was the cause of the pathological granulomatous pictures in the examined yellow-legged gull. Full article

Background: Tracheobronchial stenosis is a significant complication in granulomatosis with polyangiitis (GPA), a systemic vasculitis that primarily affects the upper respiratory tract, kidneys, and lungs. The involvement of the tracheobronchial tree in GPA leads to airway narrowing, which can result in severe respiratory symptoms and increased morbidity, often requiring prompt diagnosis and management to prevent life-threatening airway obstruction. Method: We present the case of a 28-year-old male with mild exertional dyspnea, stridor, and retropharyngeal sputum. Clinical investigations revealed subglottic and bronchial concentric stenosis with granulomatous inflammation. A diagnosis of granulomatosis with polyangiitis (GPA) with isolated tracheobronchial stenosis (TBS) was confirmed. Results: Given the severity of airway obstruction, multidisciplinary management was initiated, combining rigid bronchoscopy with systemic immunosuppressive therapy. Post-intervention follow-up demonstrated significant airway improvement and maintained remission after two years. Conclusions: This case highlights TBS as a potentially debilitating GPA manifestation requiring a combination of systemic and endoscopic therapies. Further studies are needed to optimize therapeutic approaches and improve outcomes in GPA-associated TBS. Full article