Search Results (8)

This case report presents the clinical evaluation of an 11-year-old boy with a unilateral polypoid nasal mass causing nasal obstruction, facial asymmetry, and intermittent epistaxis. His clinical picture raised concerns of a juvenile nasopharyngeal angiofibroma; however, further imaging and histopathological evaluation ultimately confirmed the diagnosis of allergic fungal rhinosinusitis (AFRS). Although this patient was younger in age than those traditionally associated with AFRS, classical features present on both computed tomography (CT) and magnetic resonance imaging (MRI) aided in his diagnosis and management. This case underscores the importance of a comprehensive diagnostic approach when evaluating unilateral sinonasal masses in paediatric patients, specifically in atypical presentations where the diagnosis of AFRS may not initially be considered. It highlights the critical role of imaging as a diagnostic tool, specifically CT and MRI, which were pivotal in the work-up and management of this case. Additionally, the need for caution during biopsies of sinonasal masses in children is emphasised, as there is potential for catastrophic bleeding in vascularised masses such as juvenile nasopharyngeal angiofibroma. This case demonstrates that AFRS can occur in younger children, highlighting the need to include this in the differential diagnosis, even in patients outside of the traditionally described age group. Full article

Introduction: Tuberous sclerosis complex (TSC) is a rare multisystemic genetic disorder characterized by the formation of benign tumors in various organs, including the central nervous system, skin, kidneys, and heart. The diagnosis is based on well-defined clinical criteria, such as those from Schwartz (2007) updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group. The study aims to investigate the clinical, imaging, and molecular characteristics of patients diagnosed with tuberous sclerosis and to explore the correlation between specific genetic mutations (TSC1 and TSC2 genes) and the severity of clinical manifestations. Material and Methods: This is a retrospective longitudinal study of 13 patients diagnosed with tuberous sclerosis, identified in the records of the Bihor Regional Center for Medical Genetics (BRCMG) within the Bihor County Emergency Clinical Hospital from 1984 to 2024. Clinical, imaging, and molecular features were assessed. Patients were evaluated by a multidisciplinary team, including a geneticist, pediatrician, neurologist, psychiatrist, and psychologist. Clinical and imaging data were retrospectively collected from the congenital malformations and genetic disease records of BRCMG Bihor and statistically analyzed. Results: All patients showed clinical and imaging signs consistent with the diagnosis of tuberous sclerosis. Neurological manifestations were present in 83% of patients, including epilepsy and cognitive delays. Renal lesions were detected in 46% of cases, and dermatological lesions, such as facial angiofibromas, were observed in 69% of patients. Mutational variants identified in the TSC2 gene correlated with a more severe clinical presentation, including severe intellectual disability and treatment-resistant seizures, compared to variants in the TSC1 gene. Conclusions: Our study, although involving a small number of patients, highlights the clinical heterogeneity of tuberous sclerosis and the importance of a multidisciplinary approach in patient management. Early diagnosis and ongoing monitoring are essential to improving the quality of life for patients. Further studies are needed to assess the impact of therapeutic interventions and genetic correlations within the studied population. Full article

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD). mTOR inhibitors, notably everolimus, have become central to TSC management, with documented efficacy in reducing the sizes of SEGAs and AMLs and showing promise in addressing additional TSC-related symptoms. Case Presentation: We report the case of an 11-year-old male diagnosed with TSC, presenting with hallmark features including hypopigmented macules, early-onset infantile spasms, SEGA, and AMLs. Initial interventions included adrenocorticotropic hormone (ACTH) therapy and sodium valproate for seizure management and a minimally invasive keyhole craniotomy for SEGA reduction. At age 12, oral everolimus therapy was introduced to address both SEGA recurrence risk and ASD-related social deficits. Over the course of 24 weeks, a reduction in the size and erythema of the patient’s FAs was observed, alongside improvements in social engagement, suggesting potential added benefits of systemic mTOR inhibition beyond tumor control. Results: Treatment with everolimus over a 24-month period led to significant reductions in both FA and AML size, as well as measurable improvements in ASD-associated behaviors. Therapeutic drug monitoring maintained serum levels within the effective range, minimizing adverse effects and underscoring the tolerability and feasibility of long-term everolimus administration. Conclusions: This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care. Full article

Introduction. Juvenile nasopharyngeal angiofibroma is a rare type of benign vascular tumour that affects only young males, especially those between the ages of 9 and 19. Therapeutic management depends on the extent of the lesion, being conditioned by the complexity of the anatomy of the skull base and the risk of massive bleeding due to the abundant vascular supply. The purpose of this article is to describe the modern approach to juvenile nasopharyngeal angiofibroma, starting from the general knowledge on this topic and presenting the experience of our clinic. Materials and Methods. A retrospective study was conducted on 10 male patients with juvenile angiofibroma, with clinical and imaging diagnoses, confirmed by post-ablative histopathological examination. From the 10 juvenile angiofibroma case treated in our clinic, 4 of them were less extensive, 2 with invasion to the pterygopalatine fossa, 3 involving the infratemporal fossa and 1 with minimal intracranial extension. Results. Combined approach (endoscopic trans-nasal approach and Caldwell Luc approach) was necessary in the treatment of a IIC case. Follow-up after surgery was done using MRI scans every 6 months. Recurrence was encountered in one case (9 months from the first surgery), and needed reintervention to remove the residual tumour. Conclusions. Even if it is a rare condition, the development of specific materials and techniques (endoscopic, embolization) has been considerable, allowing the reduction of intraoperative bleeding and residual tumour tissue, in conditions of minimal interference with the facial anatomy of such young patients. Full article

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome. It is manifested mainly in cutaneous lesions, epilepsy and the emergence of hamartomas in several tissues and organs. The disease sets in due to mutations in two tumor suppressor genes: TSC1 and TSC2. The authors present the case of a 33-year-old female patient registered with the Bihor County Regional Center of Medical Genetics (RCMG) since 2021 with a TSC diagnosis. She was diagnosed with epilepsy at eight months old. At 18 years old she was diagnosed with tuberous sclerosis and was referred to the neurology department. Since 2013 she has been registered with the department for diabetes and nutritional diseases with a type 2 diabetes mellitus (T2DM) diagnosis. The clinical examination revealed: growth delay, obesity, facial angiofibromas, sebaceous adenomas, depigmented macules, papillomatous tumorlets in the thorax (bilateral) and neck, periungual fibroma in both lower limbs, frequent convulsive seizures; on a biological level, high glycemia and glycated hemoglobin levels. Brain MRI displayed a distinctive TS aspect with five bilateral hamartomatous subependymal nodules associating cortical/subcortical tubers with the frontal, temporal and occipital distribution. Molecular diagnosis showed a pathogenic variant in the TSC1 gene, exon 13, c.1270A>T (p. Arg424*). Current treatment targets diabetes (Metformin, Gliclazide and the GLP-1 analog semaglutide) and epilepsy (Carbamazepine and Clonazepam). This case report presents a rare association between type 2 diabetes mellitus and Tuberous Sclerosis Complex. We suggest that the diabetes medication Metformin may have positive effects on both the progression of the tumor associated with TSC and the seizures specific to TSC and we assume that the association of TSC and T2DM in the presented cases is accidental, as there are no similar cases reported in the literature. Full article

Previous studies have suggested that the topical mechanistic target of rapamycin (mTOR) inhibitors may be effective in treating facial angiofibromas in patients with tuberous sclerosis complex (TSC). Various concentrations of topical sirolimus for TSC have been tested, but their comparative efficacy and safety remained unclear. To assess the effects of topical mTOR inhibitors in treating facial angiofibromas, we conducted a systematic review and network meta-analysis (NMA) and searched MEDLINE, Embase, and Cochrane Library for relevant randomized controlled trials on 14 February 2022. The Cochrane Collaboration tool was used to assess the risk of bias of included trials. Our outcomes were clinical improvement and severe adverse events leading to withdrawal. We included three trials on 261 TSC patients with facial angiofibromas. The NMA found when compared with placebo, facial angiofibromas significantly improved following the application of various concentrations of topical sirolimus (risk ratio being 3.87, 2.70, 4.43, and 3.34 for 0.05%, 0.1%, 0.2%, and 1%, respectively). When compared with placebo, all concentrations of topical sirolimus did not differ in severe adverse events leading to withdrawal. The ranking analysis suggested topical sirolimus 0.2% as the most effective drug. In conclusion, topical sirolimus 0.05–1% are effective and safe in treating facial angiofibromas in patients with TSC, with topical sirolimus 0.2% being the most effective. Full article

Facial angiofibromas (FA) are one of the most obvious cutaneous manifestations of tuberous sclerosis complex. Topical rapamycin for angiofibromas has been reported as a promising treatment. Several types of vehicles have been used hitherto, but polymeric micelles and especially those made of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) seem to have shown better skin bioavailability of rapamycin than the so far commonly used ointments. To better understand the influence of polymeric micelles on the behavior of rapamycin, we explored it through mixed polymeric micelles combining TPGS and poloxamer, evaluating stability and skin bioavailability to define an optimized formulation to effectively treat FA. Our studies have shown that TPGS improves the physicochemical behavior of rapamycin, i.e., its solubility and stability, due to a strong inclusion in micelles, while poloxamer P123 has a more significant influence on skin bioavailability. Accordingly, we formulated mixed-micelle hydrogels containing 0.1% rapamycin, and the optimized formulation was found to be stable for up to 3 months at 2–8 °C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin. Full article

Rapamycin has been used topically to treat facial angiofibromas associated with tuberous sclerosis for more than a decade. In the absence of a commercial form, a large number of formulations have been clinically tested. However, given the great heterogeneity of these studies, particularly with regard to the response criteria, it was difficult to know the impact and thus to compare the relevance of the formulations used. The objective of this work was therefore to evaluate the link between the diffusion of rapamycin and the physico-chemical characteristics of these different formulations on Strat-M^® membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel > cream > lipophilic ointment), the soluble state of rapamycin and its concentration close to saturation to ensure maximum thermodynamic activity. Thus, this is the first time that a comparative study of the different rapamycin formulations identified in the literature for the management of facial angiofibromas has been carried out using a pharmaceutical and biopharmaceutical approach. It highlights the important parameters to be considered in the development and optimization of topical rapamycin formulations with regard to cutaneous absorption for clinical efficacy. Full article