Search Results (146)

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Background: This systematic review aimed to comprehensively evaluate the clinical, diagnostic, and therapeutic features of synchronous acute cholecystitis (AC) and acute appendicitis (AAP). Methods: The review protocol was prospectively registered in PROSPERO (CRD420251086131) and conducted in accordance with PRISMA 2020 guidelines. A systematic search was performed across PubMed, MEDLINE, Web of Science, Scopus, Google Scholar, and Google databases for studies published from January 1975 to May 2025. Search terms included variations of “synchronous,” “simultaneous,” “concurrent,” and “coexistence” combined with “appendicitis,” “appendectomy,” “cholecystitis,” and “cholecystectomy.” Reference lists of included studies were screened. Studies reporting human cases with sufficient patient-level clinical data were included. Data extraction and quality assessment were performed independently by pairs of reviewers, with discrepancies resolved through consensus. No meta-analysis was conducted due to the descriptive nature of the data. Results: A total of 44 articles were included in this review. Of these, thirty-four were available in full text, one was accessible only as an abstract, and one was a literature review, while eight articles were inaccessible. Clinical data from forty patients, including two from our own cases, were evaluated, with a median age of 41 years. The gender distribution was equal, with a median age of 50 years among male patients and 36 years among female patients. Leukocytosis was observed in 25 of 33 patients with available laboratory data. Among 37 patients with documented diagnostic methods, ultrasonography and computed tomography were the most frequently utilized modalities, followed by physical examination. Twenty-seven patients underwent laparoscopic cholecystectomy and appendectomy. The remaining patients were managed with open surgery or conservative treatment. Postoperative complications occurred in five patients, including sepsis, perforation, leakage, diarrhea, and wound infections. Histopathological analysis revealed AAP in 25 cases and AC in 14. Additional findings included gangrenous inflammation and neoplastic lesions. Conclusions: Synchronous AC and AAP are rare and diagnostically challenging conditions. Early recognition via imaging and clinical evaluation is critical. Laparoscopic management remains the preferred approach. Histopathological examination of surgical specimens is essential for identifying unexpected pathology, thereby guiding appropriate patient management. Full article

Background: The coexistence of extracranial arterial stenoses and intracranial aneurysms presents a unique clinical dilemma. While staged interventions are traditionally preferred to reduce procedural risks, recent advances have enabled single-stage endovascular treatment. This study evaluates the clinical outcomes, procedural strategies, and predictive factors associated with such combined interventions. Methods: This retrospective study included 47 patients treated with single-stage endovascular procedures for concurrent extracranial stenosis and intracranial aneurysm between 2016 and 2024. Clinical, angiographic, and procedural data were collected. Outcomes were assessed using the mmodified Rankin Scale (mRS), and statistical analyses were performed to identify associations between clinical variables and functional outcomes. Results: Of the 47 patients, 85.1% achieved favorable outcomes (mRS 0–2) at ≥6-month follow-up. The most commonly treated arteries were the internal carotid artery (70.2%) and the middle cerebral artery (34%). Stent-assisted coiling or flow diversion was performed in 93.6% of aneurysm cases, while 91.5% underwent carotid or vertebral stenting. Lesion laterality (left-sided aneurysms, p = 0.019) and stenosis length (p = 0.0469) were significantly associated with outcomes. Smoking was linked to multiple stenoses (p = 0.0191). Two patients experienced major complications: one aneurysmal rebleed after stenting, and one intraoperative rupture. Conclusions: Single-stage endovascular treatment for patients with concurrent extracranial stenosis and intracranial aneurysm is technically feasible and clinically effective in selected cases. Lesion configuration, anatomical considerations, and individualized planning are critical in optimizing outcomes. Full article

Canine leishmaniosis (CanL), caused by Leishmania infantum, is a major zoonotic disease primarily transmitted by sand flies. Unlike in adult dogs, the clinical course of CanL in puppies remains poorly characterized, regardless of the transmission pathway (i.e., vertical transmission or vector exposure). This study presents the first systematic literature review (SLR) focused on juvenile CanL, alongside an atypical clinical case report. A PRISMA-compliant search across four databases identified three eligible studies describing CanL in puppies (≤9 months, according to the current canine life stage guidelines). The case involves a 4.5-month-old puppy adopted from southern Italy with papulo-nodular skin lesions and generalized lymphadenomegaly as well as a mild normocytic normochromic anemia and increased C-reactive protein. L. infantum infection was confirmed by serology, polymerase chain reaction (PCR), and cytology. The SLR suggests that dermatological lesions and/or lymphadenomegaly, whether associated with laboratory abnormalities, represent the most common clinical manifestations of CanL in puppies. In the presented case, the coexistence of systemic dissemination signs and papulo-nodular skin lesions, typically associated with vector-borne transmission, suggests the possibility of a dual route of infection by L. infantum. Juvenile CanL should be considered in differential diagnoses and supported by thorough diagnostic evaluation and appropriate follow-up protocols. Full article

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article

Background: There is limited data on somatostatin receptor (SSTR) expression of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using modern imaging techniques and stratifying by primary site and tumor grade (G). Understanding patterns of SSTR expression and tumor heterogeneity is essential when determining the relevance of cold and radiolabeled somatostatin analog treatments. Methods: A single-institutional retrospective analysis of metastatic well-differentiated G1-3 GEP-NET patients who underwent Gallium-68 ([⁶⁸Ga])-DOTATATE or Copper-64 ([⁶⁴Cu])-DOTATATE positron emission tomography (PET) imaging from September 2016 to June 2024 was performed. Results: A total of 1192 patients were considered eligible for this study. Among them, 26 (2.2%) were completely negative on SSTR PET/computed tomography (CT), and 27 (2.3%) had weak uptake (less or equal to the normal liver). Up to 40 (3.4%) had heterogeneous SSTR expression on PET/CT: 26 (2.2%) displayed the coexistence of strongly avid lesions with the absence or near absence of SSTR uptake in measurable tumors (heterogeneous strong), while 14 (1.2%) had a combination of absent and weakly expressing SSTR tumors (heterogeneous low). An additional nine cases with prior homogeneous expression (0.8%) developed new SSTR-negative tumors along with disease progression, potentially indicating dedifferentiation. The absent or heterogeneous SSTR expression rates were greater in NET G3 than G1/G2 and in tumors originating outside the small bowel (midgut). Most NETs with absent or heterogeneous SSTR expression were fluorodeoxyglucose-F-18 ([¹⁸F]FDG)-avid. Conclusions: The large majority of metastatic GEP-NETs demonstrate strong and relatively uniform SSTR expression, but approximately 8% are SSTR-negative, weak or heterogeneous on PET/CT. Higher than average rates of absent/heterogeneous/weak SSTR expression occur in G3 NETs and lower rates among small intestine primaries. Full article

Coronary artery disease (CAD) remains a major cause of cardiovascular morbidity and mortality, with growing evidence linking immune dysregulation to its pathogenesis. Aortic stenosis often coexists with CAD (ASCAD), representing an advanced disease form. This study investigates immune pathways in isolated CAD (iCAD) and ASCAD. For this purpose, peripheral blood from 72 individuals (healthy donors, iCAD, and ASCAD patients) was analysed via flow cytometry to assess immune populations. Circulating cytokine levels were measured, and machine learning models identified predictive immune biomarkers. Our data showed that both iCAD and ASCAD patients exhibited immune dysregulation, with reduced dendritic cells, basophils, NK cells, B cells, and T cells, alongside lower frequencies of DCs, lymphocytes, CD8+CD28+ T cells, and CD57+ T cells. Elevated IL-15 and fractalkine, but reduced IL-8 and MCP-1, suggest impaired monocyte and neutrophil mobilisation due to immune cell sequestration in vascular lesions. Distinct immune features emerged between iCAD and ASCAD. iCAD patients showed heightened immune activation, with increased inflammatory CD14+CD16+ monocytes, higher Treg frequencies, and greater CD4+ T cell differentiation into TEM and TEMRA phenotypes. In contrast, ASCAD patients exhibited pronounced immunosenescence, with higher neutrophil counts, lymphopenia, and increased NK and T cell cytotoxicity. Our predictive model distinguished iCAD from ASCAD with high accuracy, identifying CD4+ T cell memory subsets and CD57 expression as key discriminators. This study reveals iCAD as being driven by immune activation and ASCAD by immunosenescence and cytotoxicity. These insights advance CAD immunopathology understanding and support immune-based classification, particularly for ASCAD, where treatment remains limited to surgical intervention. Full article

Moyamoya angiopathy (MMA) is a cerebrovascular disease determining chronic progressive steno-occlusion of the supraclinoid internal carotid arteries and their main branches. The pathogenesis of MMA remains largely unknown. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system characterized by the progressive accumulation of focal demyelinating lesions, whose pathophysiology has been theorized but still incompletely understood. Beyond misdiagnoses due to mimicking features among the two disorders, MS coexisting with MMA have been previously, rarely, reported. Herein, we present two other cases of patients with MMA with a concomitant, previously missed, diagnosis of MS and discuss their overlapping features as a hint for a potentially shared pathophysiology. The finding of typical angiographic features enables MMA diagnosis, yet it does not allow us to rule out other potentially concomitant disorders affecting the CNS. The association may be easily missed if the clinical/neuroradiological picture is not carefully assessed. Cerebral spinal fluid analysis and spine neuroimaging should be suggested in all MMA patients with atypical MRI lesions. Full article

Background and Clinical Significance: The coexistence of spinal hemangiomas and dural arteriovenous fistula (SDAVF) is uncommon. Unclear imaging and progressive neurological impairment require early surgical management. Case Presentation: A 76-year-old woman presented with progressive thoracolumbar pain and worsening bladder dysfunction. Magnetic resonance imaging (MRI) of the thoracic spine revealed a round-shape expansive lesion at T11 with spinal cord edema and homogeneous contrast enhancement. Despite a chronic presentation, the subacute progression of bladder dysfunction and spinal cord edema warranted timely intervention. Intraoperatively, a vascular malformation resembling a dural arteriovenous fistula (SDAVF), unrecognized at pre-operative imaging, was found in association, and histological examination confirmed the diagnosis of hemangioma. The mechanism of coexistence remains unclear, although venous hypertension due to fistula could induce vascular malformations. Conclusions: This case emphasizes the importance of thorough imaging, timely intervention and intraoperative assessment in patients presenting with a suspicion of spinal hemangioma; it may also provide awareness of potentially associated concurrent lesions such as SDAVFs, unrecognized at pre-operative imaging, and technical insights during surgery. Full article

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults but is rare in Asia. Extramedullary and extranodal manifestations in CLL are generally uncommon, and muscle involvement is extremely rare. A 70-year-old male with CLL presented with bilateral plantar pain, predominantly on the left side. Anemia and reduced platelet count prompted ibrutinib treatment. MRI revealed high-signal areas in the muscles, suggesting inflammation. Anemia and thrombocytopenia improved, but the pain persisted for 8 months. Histopathological findings confirmed CLL infiltration of the muscles. Radiotherapy alleviated the pain, and the patient remains under observation. Careful caution was needed because (1) MRI findings suggested an inflammatory lesion, broadening differential diagnosis, and (2) CLL may coexist with inflammatory diseases. Histopathological examination is essential for correct diagnosis and treatment. Full article

Introduction: About one in four people show an immunological reaction to an infection with Mycobacterium tuberculosis, which can remain latent or lead to active forms of the disease. Psoriasis is a chronic, immune-mediated skin disease that can be associated with numerous comorbidities. Biologic therapies have revolutionized psoriasis treatment but carry the risk of reactivating latent tuberculosis infection. However, the link between tuberculosis as a triggering factor for the onset of psoriasis remains unknown. Clinical Case: We present the case of a patient initially diagnosed with secondary pulmonary tuberculosis, who, two months after the diagnosis, showed a remarkable clinical evolution by developing lesions consistent with vulgar psoriasis, necessitating a multidisciplinary treatment approach. Discussions: This unique case highlights the shared immune mechanism of these diseases, particularly involving TNF-α, IL-17, and CD4+ T cells. Conclusions: The coexistence of these conditions raises critical questions about the interplay between infectious and autoimmune diseases and the impact of genetic susceptibility. Full article

The Wolf isotopic response (WIR) refers to the development of cutaneous lesions in areas of previously healed but unrelated skin disease. While most are observed in healed herpes zoster, WIR has been reported in various other contexts. Affected areas are believed to exhibit immune dysregulation, lymphatic dysfunction, and altered neuromediator activity, increasing susceptibility to inflammatory, neoplastic, and infectious conditions. This phenomenon aligns with the broader concept of the “immunocompromised district”, which also encompasses the Koebner phenomenon and its reverse. Herein, we present the case of a 96-year-old woman who developed multiple cysts and comedones at the site of a resolved herpes zoster. Due to persistent and refractory inflammation, curettage was performed, and histopathological examination revealed angiosarcoma with a pseudolymphomatous reaction interspersed among the cysts. The coexistence of multiple types of WIR is rare but not unprecedented, highlighting the importance of recognizing the diverse pathologic conditions that can arise in such settings. In this review, we explore the historical evolution of terminology used to describe lesions in vulnerable skin areas and related phenomena. We also provide an updated overview of current pathogenic theories and present a comprehensive compilation of postherpetic reactions reported to date. Full article

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension and diabetes mellitus presented with fever and chills following an episode of severe dysmenorrhea and menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema of the perineum and whitish vaginal discharge, with no cervical lesions. Imaging revealed a 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) and CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. A pelvic ultrasound revealed a retroverted uterus and a large ovarian mass suggestive of malignancy. The patient underwent a right salpingo-oophorectomy, during which a 15 cm ovarian tumor adherent to the right pelvic sidewall was excised. Histopathological examination revealed an endometriotic cyst with endometrial glandular epithelium positive for estrogen receptor and focal mucinous metaplasia. CD10-positive endometrial stromal cells and paratubal cysts were also observed. Additionally, a small Leydig cell tumor originated from the ovarian hilum was identified and confirmed by positive staining for inhibin, calretinin, and androgen receptors, as well as negative estrogen receptor staining. The postoperative recovery was uneventful, and at the five-week follow-up, the patient’s hormonal levels were normal, and there were no complications. Conclusions: This case highlights the importance of thorough histopathological evaluation in managing ovarian masses and the potential coexistence of benign and rare pathological entities, such as Leydig cell tumors. Full article

Endometriosis, a prevalent gynecological condition affecting 10–15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases to severe pelvic pain, dysmenorrhea, and dyspareunia. Accurate diagnosis remains challenging, often requiring a combination of patient history, clinical examination, and imaging studies. This paper will discuss the clinical approach to endometriosis during a first-line gynecological appointment, focusing on patient history, including detailed assessment of menstrual, pelvic, and bowel symptoms, and clinical examination; thorough gynecological examination, including abdominal and pelvic palpation, speculum examination, and bimanual examination; imaging evaluation (particularly of the role of ultrasound in identifying and characterizing endometriotic lesions, including the use of the #ENZIAN classification for deep infiltrating endometriosis and evaluation of fertility impact); and discussion of the Endometriosis Fertility Index (EFI) as a tool for assessing fertility potential. This comprehensive approach aims to guide clinicians in identifying and managing endometriosis effectively, improving patient outcomes and optimizing fertility management strategies. Methods: A literature search for suitable articles published from January 1974 to 2024 in the English language was performed using PubMed. Results: Endometriosis is associated with infertility rates ranging from 20% to 68%, with mechanisms including pelvic adhesions, chronic inflammation, and immune dysregulation. The revised American Society for Reproductive Medicine (rASRM) classification and #ENZIAN classification were identified as essential tools for staging and characterizing the disease. Transvaginal ultrasound (TVS) demonstrated high diagnostic accuracy for deep infiltrating endometriosis, with a sensitivity of up to 96% and specificity of 99%. EFI emerged as a valuable predictor of natural conception post-surgery. Additionally, the review underscores the frequent co-occurrence of adenomyosis in women with endometriosis, which may further compromise fertility. Despite advancements in imaging techniques and classification systems, the variability in symptom presentation and disease progression continues to challenge early diagnosis and effective management. Conclusions: Endometriosis is a prevalent gynecological condition affecting women of reproductive age and is associated with infertility. This paper describes the diagnostic approach to endometriosis during a first-line gynecological appointment, focusing on clinical history, physical examination, and the role of imaging, particularly ultrasound, in identifying and characterizing endometriosis lesions. The adoption of standardized classification systems such as #ENZIAN and EFI enhances disease staging and fertility prognosis, allowing for tailored treatment strategies. Despite improvements in non-invasive diagnostic methods, challenges persist in correlating symptom severity with disease extent, necessitating continued research into biomarkers and novel imaging techniques. Additionally, the frequent coexistence of adenomyosis further complicates fertility outcomes, underscoring the need for comprehensive management strategies. Further research is needed to enhance early detection strategies and optimize fertility preservation techniques for affected women. Full article

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance. Full article