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Tuberous sclerosis complex is a type of genetic multisystem disease that causes hamartomas in various organs. Facial angiofibromas commonly occur in 80% of patients and are prominently distributed over the cheek, chin, and nasolabial folds with severe disfigurement and emotional distress. Recently, photoelectric devices have been identified for the treatment of angiofibromas with great efficacy and fewer side effects. We report a case of a 42-year-old man with facial angiofibromas, who was treated with a combination of high-frequency electrocauterization, Ultrapulse CO2 laser, and microneedle fractional radiofrequency with 7 sessions and a 6-month follow-up. The patient showed great improvement in relation to the elevated lesions and nodules. A low recurrence rate was observed. This is the first study to investigate the efficacy of high-frequency electrocauterization and microneedle fractional radiofrequency in angiofibromas. It may provide an optimal approach for clinicians wherein a combined treatment of various lasers and electric devices is effective for complicated, protuberant, and firm angiofibromas of specific patients.

Introduccion: el complejo esclerosis tuberosa (CET) es un sindrome neurocutaneo de herencia autosomica dominante (AD), caracterizado por la formacion de multiples hamartomas debido a la mutacion de los genes TSC1 y TSC2 encargados de codificar proteinas supresoras de tumores. El CET es una enfermedad multisistemica, sin embargo, el diagnostico se fundamenta en el compromiso neurologico, lesiones en piel y los hallazgos imagenologicos. Caso clinico: adolescente procedente de Cartagena quien a los cuatro meses se le diagnostico Sindrome de West, manejado con Vigabatrin, posteriormente presento epilepsia focal motora. En el examen fisico se encontraron maculas hipocromicas multiples y angiofibromas faciales. La tomografia axial de craneo (TAC) mostro tuberculo en region frontotemporal izquierda y nodulos subependimarios. Basado en estos criterios se hace diagnostico de CET. Conclusion: el diagnostico de CET es un reto para el medico, depende de una excelente historia clinica y un examen fisico completo que incluye la busqueda de lesiones caracteristicas en la piel, estas pueden detectarse desde el nacimiento, al igual que los hallazgos imagenologicos detectables incluso in utero. Las pruebas geneticas, aunque son confirmatorias, no descartan la enfermedad. Rev.cienc.biomed. 2015;6(2):369-375 PALABRAS CLAVE Epilepsia; Esclerosis tuberosa; Tuberomas; Lesiones en piel. SUMMARY Introduction: tuberous sclerosis complex (TSC) is a neurocutaneous syndrome autosomal dominant (AD), characterized by multiple hamartomas formation due to mutation of the TSC1 and TSC2 genes responsible for encoding tumor suppressor proteins. TSC is a multisystem disease; however, the diagnosis is based on the neurological involvement, skin lesions and imaging findings. Clinical case: a male teenager from Cartagena who at four months of age was diagnosed with West syndrome, managed with Vigabatrin, subsequently, he presented focal motor epilepsy. Macules and facial angiofibromas were found in physical examination. Cranial tomography scan (TAC) showed left frontotemporal region tuber and subependymal nodules. Based on these criteria TSC diagnosis was carried out. Conclusion: the TSC is a diagnostic challenge for the physician, it depends on excellent medical history and a complete physical examination even the search of characteristic lesions in the skin, they can be detected from the time of birth, just as detectable imaging findings even in uterus. Genetic tests do not rule the disease, although, they are confirmatory. Rev.cienc.biomed. 2015;6(2):369-375 KEYWORDS Epilepsy; Tuberous sclerosis; Tuberous; Skin lesions.

Although the efficacy of topical sirolimus for facial angiofibromas of tuberosclerosis is now appreciated, drug-induced irrritation complicates the use of the concentration recommended in the literature as 1%. Adjuvant vascular or ablative laser applications may be preferred in adult patients for a variety of purposes, such as treatment of large lesions that tend to be resistant to topical treatment, reduction of topical product concentration and rapid response generation. Herein, we aimed to share the 2-year follow up result of a tuberoussclerosis case where angiofibromas were observed on the chin, malar regions and nose. We combined the full-field erbium-yttrium aluminium garnet laser application with topical sirolimus 0.25% cream on the second month of treatment.

espanolSe presenta el caso de un paciente de 25 anos con multiples papulas y placas de aspecto fibroso, distribuidas principalmente en cara, ademas de cuero cabelludo, torax y region periungueal pedia, asintomatico. Se realizo el diagnostico clinico e histopatologico de esclerosis tuberosa, enfermedad genetica poco frecuente. Se utilizo laser CO2 modo ablativo en 2 ciclos de dos sesiones cada una, en lesiones cutaneas faciales (angiofibroma facial), con el objetivo de mejorar la apariencia y promover calidad de vida. Como resultado se evidencio mejoria de la apariencia y ausencia de recidiva con un metodo terapeutico moderno y aun inaccesible a todas las personas en nuestro pais. EnglishWe present the case of a 25-year-old patient with multiple fibrous papules and plaques, mainly distributed on the face, as well as asymptomatic scalp, thorax and peduncle periungueal region. The clinical and histopathological diagnosis of tuberous sclerosis was performed, a rare genetic disease. CO2 laser was used ablative mode in 2 cycles of two sessions each, in facial skin lesions (facial angiofibroma), with the aim of improving the appearance and promoting quality of life. As a result, improvement in the appearance and absence of recurrence was evidenced by a modern therapeutic method that is still inaccessible to all people in our country

Abstract: Facial angiofibroma is the characteristic symptom and also a major diagnostic criterion for Bourneville–Pringle disease. The centrofacially localized hamartomatous tumours start to appear in early childhood, and progress over time. Facial angiofibromas represent a significant cosmetological problem for the patients and a therapeutic challenge for the physician. Beside the traditional invasive treating methods, topical sirolimus is a new, promising and well-tolerated treatment modality. Several studies and case reports have been published on this new therapeutic approach, but recommendation for the optimal sirolimus concentration still does not exist. We report here two cases when children were successfully treated with topical sirolimus. Orv Hetil. 2019; 160(13): 516–520.

facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition.to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis.a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies.thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA.Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Introduction facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. Purpose to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. Methods a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. Results thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. Conclusions Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol. KEY MESSAGE Updated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder that causes the formation of hamartomatous tumors such as facial angiofibromas (FAs). We present a combination of surgical debulking via shave biopsy, curettage, and electrocautery followed by application of sirolimus ointment 1% to the nose to treat FAs in the setting of TSC. This novel approach achieved an optimal therapeutic response in our patient with minimal recurrence of FAs after 1 year of follow-up.

Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder forming hamartomas throughout the body. Facial angiofibromas (FAs) occur in 75% of TSC patients, which are often enlarged, impairing the appearance of the face, and reducing the patient’s quality of life (QOL). The aim of this study was to characterize the impact of topical sirolimus treatment on the health-related QOL in patients with FA associated with TSC. Methods We investigated a total of 33 patients who received sirolimus gel treatment for FA associated with TSC and assessed the changes in the health-related QOL using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey. SF-36 surveys were performed before and after 3 months of treatment. The conditions of the patients after using the sirolimus gel were categorized into the following three categories: “improved,” “unchanged,” and “aggravated.” Adverse events were investigated using the CTCAE v5.0-JCOG. Results The median age of the patients was 25 (range 14–55) years. After 3 months of sirolimus gel treatment, three scale scores of the SF-36, vitality (VT), social function (SF), and mental health (MH), were significantly improved compared to before the treatment. The VT and SF in patients who had improved FA were significantly better than those in the other patients. There were no significant differences in any scale scores between patients with and without adverse events at 3 months after the initiation of sirolimus gel treatment. Conclusions This is the first report regarding improved health-related quality of life in patients treated with sirolimus gel for FA associated with TSC by using the SF-36. The three scale scores associated with mental health were significantly improved compared to before the treatment. The health-related QOL in patients receiving sirolimus gel treatment is more strongly affected by the treatment efficacy than adverse events. Mini-abstract Sirolimus gel treatment improves the health-related QOL in patients with FA associated with TSC.

The facial angiofbromas due to tuberous sclerosis complex produced significant social and emotional distress for affected individuals, but there is no specific therapeutic strategy up to now. Herein, we report a case of facial angiofibromas successfully treated by 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) with no recurrence for 6 years, thus providing a promising therapeutic option.

Tuberous sclerosis (Morbus Bourneville-Pringle) is a rare, multisystemic,autosomal dominant disease, associated with a mutation of either of two genes TSC1 and TSC2, responsible for synthesis of proteins hamartin and tuberin - tumor growth suppressing factors, involved in cell proliferation and differentiation processes. Perhaps the most common findings of TS are angiophibromas - cutaneous manifestations of the disease, serving as clinical pointers to the diagnosis. Different methods are being used to treat facial angiofibromas with little or no success. Treatment with CO2 laser ablation can provide fruitful results in removing facial angiofibromas. Presented is a case of a 40 year-old female patient, diagnosed with tuberous sclerosis with multiple facial angiofibromas, subjected to CO2 laser ablation.

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement that frequently occurs in early childhood. Dermatologic manifestations include facial angiofibromas, hypomelanotic macules, fibrous cephalic plaques, shagreen patches, and ungual fibromas. The International TSC Consensus Conference in 2012 provided guidelines for standardized baseline evaluation and follow-up. Detailed clinical dermatological evaluation at the time of diagnosis and annual skin examination is recommended for both pediatric and adult populations. The onset of dermatological manifestations is clearly age-related. However, dermatologists also have to assess for clinical manifestations beyond their own specialty. With advances in genetics and the advent of mTORC1 inhibitors, new specific therapeutic options have become available for TSC patients with skin manifestations. Early intervention is commonly recommended for symptomatic, rapidly evolving, disfiguring, or debilitating lesions. The consensus guidelines recommend "treatment as appropriate for the lesion and clinical context" and suggest the use of surgical excision, laser therapy, or topical mTORC1 inhibitors. Topical mTORC1 inhibitors present a useful option for TSC-associated skin lesions, particularly in medically complex patients. They may prevent or reduce the risks of subsequent surgeries and permanent scarring.

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement including facial angiofibromas that often appear in early childhood. Here we report the case of a 12-year-old girl with widespread disfiguring facial angiofibromas that were successfully treated with topical rapamycin, a mTOR inhibitor. A sustained remission of skin lesions was documented in detail over a 3-year follow-up. This case highlights the fact that topical rapamycin is a useful option in treating TSC-associated skin lesions. Especially in medically complex patients topical treatment may lessen the need for surgical interventions, reducing the risks of surgery, its adverse effects and permanent scarring. However, there is no standard dose or formulation at present. Topical rapamycin appears safe, but long-term maintenance therapy is necessary to prevent facial lesions from regrowth.

Facial angiofibromas are benign tumors presenting as firm, dome-shaped flesh-colored to pink papules, typically on the nose and adjoining central face. Clinically and dermoscopically they can mimic melanocytic nevi or basal cell carcinomas (BCC). Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that is useful in diagnosing melanocytic and non-melanocytic facial lesions. To date no studies have described the RCM features of facial angiofibromas. Herein, we present two cases of facial angiofibromas that were imaged with RCM and revealed tumor island-like structures that mimicked BCC, leading to skin biopsy.

We represent a case of 11-year-male child with multiple facial angiofibromas who showed moderate improvement after application of 0.1 and 1% sirolimus. We evaluated the results clinically and dermoscopically.

Introduction: Tuberous sclerosis complex (TSC) is a rare, genetic disease which leads to neurological, cardiological, nephrological, ophthalmic, pulmonary and skin disorders. Case Presentation: Here, we describe a case of a 64-year-old man with the presence of giant angiofibromas located on his chin and nasolabial folds which caused inconvenience and unaesthetic appearance. All angiofibromas were removed with the use of a CO2 laser. The patient was extremely satisfied with the obtained result. No side effects were observed after a 6-month follow-up. Conclusion: Despite the fact that giant facial angiofibromas may be troublesome not only for patients but also for medical doctors, adequate CO2 laser usage with local anesthesia and control of massive bleeding is a promising treatment option for patients with TSC.

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&reg, membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel &gt, cream &gt, 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.

Tuberous Sclerosis Complex (TSC) are clinically associated with the development of non-malignant tumors throughout the body. The clinical presentation of TSC is highly variable among individual in which make the diagnosis is challenging too. Based on the 2012 International TSC Consensus Group guidelines, diagnosis is made either by genetic diagnosis or clinical diagnosis. Managing Tuberous Sclerosis Complex (TSC) is as challenging as diagnosis. Multiple organs are affected, it requires multidisciplinary approach to deal with. An 8-year-old girl consulted from Dermato-venerology department with chronic facial angiofibroma with suspicion of TSC. The symptoms at the time of examination were face lump and decreased ability to concentrate at class subjectively reported by parents. Investigation were carried and revealed that patient had a history of seizure during infancy, had finished anti epilepsy medication and has been remaining symptoms free up to this case were investigated. Diagnosis were made by matching investigation result to clinical diagnosis of the 2012 International TSC Consensus Group guidelines. Several supporting examinations had been done, with result: subependymal nodule from head CT Scan; Rhabdomyoma from echocardiograph; multiple mass on kidney from USG; and EEG abnormality. Management were emphasized on treating the rose symptoms and prioritization of the most potential result that might possess significant burden. TSC possess potential challenge starts from case presentation to management. Thorough investigation and multidisciplinary approached are required to successfully manage the case and eventually reduce the burden of the disease.

PURPOSE To examine the prevalence and spectrum of mosaic variant allele frequency (MVAF) in tuberous sclerosis complex (TSC) patients with low-level mosaicism and correlate genetic findings with clinical features and transmission risk. METHODS Massively parallel sequencing was performed on 39 mosaic TSC patients with 170 different tissue samples. RESULTS TSC mosaic patients (MVAF: 0-10%, median 1.7% in blood DNA) had a milder and distinct clinical phenotype in comparison with other TSC series, with similar facial angiofibromas (92%) and kidney angiomyolipomas (83%), and fewer seizures, cortical tubers, and multiple other manifestations (p

Objectives In recent years, various formulations containing rapamycin, mainly petrolatum-based, have been tested on facial angiofibromas in tuberous sclerosis. They are often poorly tolerated due to irritation and bleeding. In addition, their effectiveness was insufficient in young adults. The objective of this study was to develop and characterise a hydro-alcoholic gel containing solubilised rapamycin. The stability of the product stored at 4°C was evaluated over 1 year. Methods Two different 0.1% rapamycin gels were formulated with or without α-tocopherol and urea. Different methods were used to characterise the gels: HPLC, gas chromatography, pH, visual observation and optical microscopy. A physico-chemical and microbiological stability study was also conducted for 1 year at 4°C. Results Gels were physically and microbiologically stable after 1 year at 4°C: organoleptic characteristics and pH unchanged, no significant decrease in rapamycin was observed, tocopherol droplet size was constant and rheological behaviour was not altered. Conclusions This study describes a new gel formulation to improve skin penetration using various excipients to promote skin tolerance. This study provides, for the first time, detailed stability data for a hydro-alcoholic rapamycin gel.

International audience

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder associated with an enormous range of physical and neuropsychiatric manifestations. Over the last few decades' significant progress has been made in understanding the molecular biology of the disorder, and TSC is now one of the first genetic conditions with molecularly targeted treatment options. Given the significant advances in the scientific study of TSC, revised diagnostic criteria and evidence-based consensus guidelines for the assessment, surveillance and treatment of TSC were published. Here we present an update of TSC for paediatricians and other clinicians who work with individuals and families living with the disorder.

Background Tuberous sclerosis is an autosomal dominant genodermatosis characterized by nonmalignant hamartomas in multiple organs. Facial angiofibromas are most commonly located on the face and have the potential to cause disfigurement. Facial disfigurement negatively affects the quality of life of patients and their families, often leading to negative psychosocial outcomes. Nowadays there are no treatment guidelines for facial angiofibromas but due to the progressive nature of facial angiofibromas a safe technique offering good results is needed. Objective and results We report the case of a 40-year-old female affected by tuberous sclerosis, whose facial angiofibromas were satisfactorily treated by rapamycin 0.05% ointment, and a combined laser therapy.

Facial angiofibromas are a common cutaneous manifestation of tuberous sclerosis complex. Although angiofibromas are usually asymptomatic, they can be highly disfiguring and can have a significant impact on patient quality of life. Treatment for facial angiofibromas is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas. Herein is reported a case of a 27-year-old woman whose facial angiofibromas were successfully treated with topical rapamycin without relevant side effects.

Facial angiofibromas are hamartomatous growths that are closely associated with tuberous sclerosis complex and, in fact, they constitute one of the main diagnostic criteria for that disease. These lesions composed of blood vessels and fibrous tissue appear on the face at an early age. Since they have important physical and psychological repercussions for patients, several treatment options have been used to remove them or improve their appearance. However, the lack of treatment guidelines prevents us from developing a common protocol for patients with this condition. The present article aims to review the treatments for facial angiofibromas used to date and to propose a new evidence-based treatment protocol.