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Abstract Background Angiofibroma is a rare, histologically benign but locally aggressive vascular tumour that typically arises within the nasopharynx. Angiofibroma in sites other than the nasopharynx is extremely uncommon. Despite the histological similarities, the clinical features of this tumour are very much different from the typical nasopharyngeal angiofibroma and pose a diagnostic challenge, hence emphasizing the importance of a thorough evaluation and high index of suspicion in establishing the correct diagnosis. Case presentation A 25-year-old gentleman presented with progressive right nasal blockage and intermittent nasal discharge for 3 years duration. He was clinically and radiologically diagnosed as a mucocele. Surgical excision was done via endoscopic medial maxillectomy with complete relief of all the symptoms. Conclusion Although uncommon, angiofibroma can occur outside the nasopharynx. Therefore, thorough evaluation and a high index of suspicion are crucial in establishing the correct diagnosis.

Background: Angiofibroma is a rare, histologically benign but locally aggressive vascular tumour that typically arises within the nasopharynx. Angiofibroma in sites other than the nasopharynx is extremely uncommon. Despite the histological similarities, the clinical features of this tumour are very much different from the typical nasopharyngeal angiofibroma and pose a diagnostic challenge, hence emphasizing the importance of a thorough evaluation and high index of suspicion in establishing the correct diagnosis. Case presentation: A 25-year-old gentleman presented with progressive right nasal blockage and intermittent nasal discharge for 3 years duration. He was clinically and radiologically diagnosed as a mucocele. Surgical excision was done via endoscopic medial maxillectomy with complete relief of all the symptoms. Conclusion: Although uncommon, angiofibroma can occur outside the nasopharynx. Therefore, thorough evaluation and a high index of suspicion are crucial in establishing the correct diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Galicia Clínica is the property of Sociedad Gallega de Medicina Interna and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that can involve multiple organ systems. Diagnosis is based on independent clinical diagnostic criteria and genetic diagnostic criteria (pathogenic variants on TSC1 and TSC2 genes). To make a definitive diagnosis can be especially difficult in oligosymptomatic or asymptomatic patients and in those patients with genetic variants of uncertain significance (VUS). Early diagnosis and lifelong surveillance are paramount to avoid morbidity and potentially life-threatening complications. To increase diagnostic sensibility, less known manifestations of TSC can be helpful. Herein we show a case in which SBLs were used as a diagnostic clue to help diagnose three generations of oligosymptomatic TSC carrying a VUS in TSC1. SBLs are commonly detected in imaging studies of patients with TSC and have been recently included as a minor clinical diagnostic criterion. Clinicians and radiologists should be aware of their significance as they can be mistaken with osteoblastic metastases. [ABSTRACT FROM AUTHOR]

ABSTRACT: 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.

La Esclerosis Tuberosa (ET) ó Complejo Esclerosis Tuberosa es un trastor- no genético autosómico dominante que afecta a niños y adultos. Se debe a la ausencia parcial o total de la expresión de los genes TSC1 (hamartina) o TSC2 (tuberina), lo que genera disfunción orgánica por crecimiento de hamartomas en sistema nervioso central, riñón, corazón, pulmón y piel. Un seguimiento protocolizado nos ayuda a confirmar el diagnóstico así como a identificar precozmente complicaciones clínicamente significati- vas. Nos permite además identificar portadores de mutaciones entre los familiares y realizar eficazmente labores de consejo genético

Abstract Introduction Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results Among 94 enrolled patients (mean age, 21 years; range 3–53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (≥ 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0–86.3%], 66.7% (95% CI 51.1–80.0%), and 72.2% (95% CI 46.5–90.3%), respectively. Conclusions The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective. Trial Registration ClinicalTrials.gov identifier: NCT02634931.

Encephalotrigeminal Angiomatosis, also known as Sturge Weber Syndrome (SWS), Dimitri disease, Sturge Kalischer Weber Syndrome is specifically non familial, congenital rare disorder consisting of hamartomatous malformations that may affect eye, skin, and CNS. Failure of proper vascular development is believed to be the most likely cause of the condition. The malformed blood vessels may lead to port wine stains, epilepsy, and glaucoma depending on its location. We are presenting here a triad of case reports on Sturge Weber Syndrome representing individuals belonging to varied age groups.

Background: Angiofibromas are common benign skin lesions that are diagnosed clinically and histopathologically. Fibrous papule (FP) is one of the clinical types of angiofibromas located primarily on the nose. Methods: The cases with the confirmed diagnosis of angiofibroma were enrolled. Demographic features of the patients and clinical characteristics of the lesions were extracted. Moreover, histopathological features of the available slides were microscopically reviewed. Results: From 83 cases of cutaneous angiofibromas, 57 (69%) had lesions consistent with FP. The mean age at diagnosis was 37.7 ± 16.3 years and the most common site of involvement was the nose (53% of cases). Regarding the histopathological evaluation of 71 slides, most cases represented vascular changes (97%) and dermal fibroplasia (87%). Melanin incontinence (41%), acanthosis (31%), and lichenoid features (25%) were other common histopathological findings. Moreover, a sparse inflammatory cell infiltrate was present in 68% of cases. The most prevalent inflammatory cells were lymphocytes (61%) and histiocytes (34%). Conclusion: This study presented the histopathological findings of a series of cutaneous angiofibromas. Dermatopathologists should be aware of these features, especially those that are less common, to better diagnose and differentiate them from malignant neoplasms. [ABSTRACT FROM AUTHOR]

Non-endocrine findings in patients with MEN1 (multiple endocrine neoplasia) syndrome also include skin lesions, especially tumor-type lesions. This is a narrative review of the English-language medical literature including original studies concerning MEN1 and dermatological issues (apart from dermatologic features of each endocrine tumor/neuroendocrine neoplasia), identified through a PubMed-based search (based on clinical relevance, with no timeline restriction or concern regarding the level of statistical significance). We identified 27 original studies involving clinical presentation of patients with MEN1 and cutaneous tumors; eight other original studies that also included the genetic background; and four additional original studies were included. The largest cohorts were from studies in Italy (N = 145 individuals), Spain (N = 90), the United States (N = 48 and N = 32), and Japan (N = 28). The age of patients varied from 18 to 76 years, with the majority of individuals in their forties. The most common cutaneous tumors are angiofibromas (AF), collagenomas (CG), and lipomas (L). Other lesions are atypical nevi, basocellular carcinoma, squamous cell carcinoma, acrochordons, papillomatosis confluens et reticularis, gingival papules, and cutaneous T-cell lymphoma of the eyelid. Non-tumor aspects are confetti-like hypopigmentation, café-au-lait macules, and gingival papules. MEN1 gene, respective menin involvement has also been found in melanomas, but the association with MEN1 remains debatable. Typically, cutaneous tumors (AF, CG, and L) are benign and are surgically treated only for cosmetic reasons. Some of them are reported as first presentation. Even though skin lesions are not pathognomonic, recognizing them plays an important role in early identification of MEN1 patients. Whether a subgroup of MEN1 subjects is prone to developing these types of cutaneous lesions and how they influence MEN1 evolution is still an open issue.

Importance: We believe this to be the first documented report of multiple endocrine neoplasia type-1 (MEN-1) in which the diagnosis was suspected based purely on cutaneous findings. The patient was initially referred to the dermatology department for cosmetic concerns and had no overt symptoms, laboratory abnormalities, or known family history of MEN-1.Observations: The patient is a 28-year-old man who was referred to the dermatology department for evaluation and removal of skins lesions, later confirmed by biopsy to be facial angiofibromas and a truncal collagenoma. This combination of cutaneous findings was suspicious for a genodermatosis and genetic testing subsequently confirmed the diagnosis of MEN-1. The patient was referred for appropriate follow up and surveillance.Conclusions and Relevance: This case highlights the importance of vigilance on the part of dermatologists to be aware of subtle skin findings that may be characteristic of rare disorders and may have gone unrecognized by other providers and the patients themselves. In this respect, dermatologists are in a unique position given their specialized training in the recognition of inherited skin disorders. An early diagnosis of an inherited disorder, especially one with increased risk of malignancy, can allow for appropriate surveillance and potentially alter the course of the disease.

Copyright of Galicia Clínica is the property of Sociedad Gallega de Medicina Interna and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dermatologists encounter a wide range of cutaneous vascular lesions, including infantile hemangiomas, port-wine stain birthmarks, arteriovenous malformations, venous malformations, Kaposi sarcomas, angiosarcomas, and angiofibromas. Current treatment modalities to reduce these lesions include topical and/or intralesional steroids, laser therapy, surgical resection, and endovascular therapy. However, each method has limitations owing to recurrence, comorbidities, toxicity, or lesion location. Photodynamic therapy, antiangiogenic therapy, and evolving methods of sclerotherapy are promising areas of development that may mitigate limitations of current treatments and offer exciting options for patients and their physicians.

A 35-year-old Indian lady, born out of non-consanguineous parentage, presented with multiple asymptomatic bumps over face and fingers. The facial lesions had started appearing since 2 years of age and finger lesions were first noticed during her adolescence. She had been on anti-epileptic medication for recurrent episodes of seizures since last 15 years. Her family history was insignificant. Examination revealed multiple non-tender, discrete, yellowish-brown to skin-coloured, soft-to-firm papules (1 to 3 mm) distributed symmetrically over centrofacial region. Multiple firm, non-tender, skin-coloured nodules over proximal nail fold along with longitudinal nail grooving were noted (Panel a, red arrow). A small firm skin-coloured plaque (Panel b, red arrow) and a leaf-shaped hypopigmented macule (Panel b, black arrow) were observed over thigh. Oral examination revealed a non-tender soft-to-firm papule over upper gingival (Panel a, black arrow). Systemic examination was insignificant. Routine blood investigations, echocardiography, ultrasonography of abdomen and fundoscopy of eyes failed to reveal any abnormality. Magnetic resonance imaging of the brain revealed cortical tubers and calcified subependymal nodules.

ABSTRACT Tuberous sclerosis complex (TSC) is a rare genetic multisystem disease that involves brain, skin, kidneys, eyes and lungs. It typically presents during childhood with facial adenomas, seizures and mental retardation and its diagnosis is mainly clinical. We report a case of 68-year-old man that sought medical care due to a transient ischemic stroke. The past clinical history and physical observation showed symptoms and signs of TSC. An extend imagiological study allowed for a complete assessment of organ involvement. A delayed diagnosis places adults at increased risk for morbidity and mortality and therefore, clinicians must be familiar with the full spectrum of TSC-associated diagnostic features.

Introduction: Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods: We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results: Among 94 enrolled patients (mean age, 21 years; range 3–53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (≥ 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0–86.3%], 66.7% (95% CI 51.1–80.0%), and 72.2% (95% CI 46.5–90.3%), respectively. Conclusions: The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective. Trial Registration: ClinicalTrials.gov identifier: NCT02634931. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a rare autosomal disorder that typically affects children. The manifestations of TSC include development of benign lesions in various organs, primarily in the brain, skin, kidneys, heart, and lungs. TSC management often involves multidisciplinary specialties. Herein, we present a case of a 5-year-old male patient who presented with a headache, vomiting and fever. Radiological assessment demonstrated a lobulated enhancing tumor in the right lateral ventricle near the foramen of Monro for which he underwent craniotomy (total tumor resection), which turned out to be subependymal giant cell astrocytomas upon histopathological examination. A follow-up MRI after 10 months showed cortical dysplasias, with tiny subependymal nodules. Dermatology examination revealed hypomelanotic macules, angiofibromas and shagreen patch. At his one-year follow-up, the patient exhibited normal mental and physical growth. Therefore, calling attention to TSC diagnosis and management depending upon the particular presentation may improve the quality of life of TSC patients.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. Methods: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Results: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Conclusions: Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disease, with an estimated incidence of 1 in 6000–1 in 10,000. TSC is an autosomal dominant syndrome involving heart, kidneys, lungs, and skin. The classic triad of TSC is seizures, mental retardation, and angiofibromas; this triad occurs in only 29% of patients. The clinical diagnostic guidelines on TSC are prepared based on clinical features, radiographic findings. The most common oral manifestations of TSC are fibroma, gingival hyperplasia, and enamel hypoplasia. Odontogenic myxofibroma represents a rare slow-growing benign neoplasm found rarely in children below 10 years or adults over 50 years of age. The prevalence of myxoma is between 0.04% and 3.7%. Here, we are reporting a rare case of myxofibroma of gingiva in an 8-year-old female TSC patient.

The tuberous sclerosis complex (TSC) is highly variable as far as its clinical presentation is concerned. For the implementation of appropriate medical surveillance and treatment, an accurate diagnosis is compulsory. TSC may affect the heart, skin, kidneys, central nervous system (epileptic seizures and nodular intracranial tumors—tubers), bones, eyes, lungs, blood vessels and the gastrointestinal tract. The aim of this paper is to report renal manifestations as first clinical signs suggestive of TSC diagnosis. A 20-year-old patient was initially investigated for hematuria, dysuria and colicky pain in the left lumbar region. The ultrasound examination of the kidney showed bilateral hyperechogenic kidney structures and pyelocalyceal dilatation, both suggestive of bilateral obstructive lithiasis, complicated by uretero-hydronephrosis. The computer tomography (CT) scan of the kidney showed irregular kidney margins layout, undifferentiated images between cortical and medullar structures, with non-homogenous round components, suggestive of kidney angiomyolipomas, bilateral renal cortical retention cysts, images of a calculous component in the right middle calyceal branches and a smaller one on the left side. The clinical manifestations and imaging findings (skull and abdominal and pelvis CT scans) sustained the diagnosis.

An 11-year-old girl, from a consanguineous family. With history of suspected akinetic seizures and normal intelligence. Physical examination revealed several small-scattered facial angiofibromas that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches on her back. Periungual fibromas were not seen. CT brain showed multiple calcified sub ependymal nodules and cortical tubers. Cardiological consult and ECG were normal. Neurological consult shows: normal status of conscience, without meningeal signs of irritation, cranial nerves without deficit, and no ataxia. No hamartomas or retinal achromic patches was noticed by ophthalmologic evaluation. Radiography of the chest, truncal CT was without abnormality. So with the above clinical findings, a diagnosis of Tuberous sclerosis was made, and the patient is under regular monitoring. Tuberous Sclerosis, also known as Bourneville's disease, is an autosomal dominant syndrome with variable clinical expression. The dermatologist plays an essential role in the history of the disease, since skin manifestations represent the most prevalent clinical features, enabling early diagnosis and intervention in its natural course.

Facial angiofibromas are the most visible and unsightly of all the cutaneous manifestations of tuberous sclerosis (TSC). A 17-year-old female, a known case of TSC, presented for the treatment of cosmetically disfiguring facial angiofibromas. She was started on twice daily application of 0.1% sirolimus ointment prepared from crushed tablets of sirolimus compounded in white soft paraffin. After 3 months of use, there was visible decrease in the erythema and the size of the angiofibromas. In an attempt to accelerate the response, the concentration was further increased to 1% sirolimus which was used for a month, resulting in a decrease not only in the size and redness but also in the number of the angiofibromas. The patient did not experience any cutaneous or systemic complications related to therapy. Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus has been used as a targeted therapy for the renal and neurological manifestations of TSC. Topical preparation of sirolimus is not commercially available till date and hence preparations from crushed tablets or oral solution of sirolimus have been used with beneficial effects in treatment of angiofibromas especially in younger patients with flatter lesions. Randomized controlled trials are necessary to enable us to confirm the efficacy, long-term safety, the optimal dosage and possibility of reappearance once the drug is withdrawn. This is possibly the first case report of the use of topical sirolimus in India.

Aims: Topical rapamycin is used to reduce facial angiofibromas in patients with tuberous sclerosis (TSC). In the absence of a commercially available preparation, numerous formulations have been tested clinically, although only in the short term., Methods: The pharmacy at Angers University Hospital (France) produced a cream formulation that was administered to people presenting this genetic disease. We conducted a questionnaire-based survey among 79 patients with TSC about their perceptions regarding the short-, medium- and long-term efficacy and safety of a topical rapamycin preparation in relation to facial angiofibromas., Results: This formulation was very well tolerated and its efficacy was sustained over the long term with a mean treatment duration of 33 months (extremes 1-60). Efficacy was rated ≥ 8/10 by 67.1% of patients while safety was rated ≥ 8/10 by 84.8% of patients., Conclusion: This survey supports the safety and efficacy of topical rapamycin in the short-, medium- and long-term in the treatment of facial angiofibromas in a cohort of 79 patients with TSC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Tuberous sclerosis complex (TSC) is known to cause severe intractable epilepsy and mental retardation; however, diagnosis can be delayed in milder cases. We report a 26-year-old right-handed female patient who started having convulsions at age 7 days. She had several focal seizures per year that were intractable to treatment with carbamazepine or phenytoin. Her two sisters had several episodes of suspected epileptic seizures but had no symptoms related to TSC. Seizure semiology of the patient comprised of visual hallucination, loss of consciousness, and convulsive movements predominantly on the right. Physical examination revealed several small scattered angiofibromas over the nose that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches, or periungual fibromas were not seen. Neurological examination showed mental retardation (MMSE: 23/30, WAIS-III: VIQ63, PIQ59, FIQ58) and decreased vibration sensation in both legs. Interictal EEG showed slow waves and epileptiform discharges broadly over the anterior quadrants bilaterally. Brain imaging showed multiple cortical tubers and malformation of cortical development but no subependymal nodules. Interictal IMP-SPECT showed hypoperfusion in the left frontal lobe. Cardiac rhabdomyoma was not noticed by cardiac echography. Truncal CT showed sclerosis of the bilateral lumbosacral joints. There was no abnormality in the lung, major arteries, liver, or kidneys. No hamartomas or retinal achromic patches were noticed by ophthalmologic evaluation. Administration of lamotrigine was effective for her seizures. This patient fulfilled two major features of diagnostic criteria for TSC and was diagnosed as definite TSC. Patients with mental retardation and epilepsy should be carefully evaluated for the possible diagnosis of TSC.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. Methods: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Results: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Conclusions: Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients. [ABSTRACT FROM AUTHOR]

Background: The skin is one of the most affected organs in tuberous sclerosis complex and angiofibromas are seen in almost 80% of such patients. These benign tumors impose a great psycho-social burden on patients.Objective: The aim of the study was to evaluate the effectiveness and tolerability of topical sirolimus for facial angiofibromas in patients with tuberous sclerosis complex.Methods: This was a prospective, single-blinded, cross-over study which involved twelve patients. We investigated the effect and safety of topical 0.1% sirolimus, which was obtained by crushing sirolimus tablets and mixing it with petrolatum. The patients were asked to apply the cream to one side of their face, and vaseline to the other side. The effect of topical sirolimus was evaluated using the "facial angiofibroma severity index."Results: There was a significant improvement in the redness and extension of the tumors on the sides to which the active ingredient was applied. Some side effects such as itching and irritation occurred in three patients, which were treated with topical hydrocortisone cream.Conclusion: Topical sirolimus appears to be a promising, fairly well tolerated treatment for facial angiofibromas in patients with tuberous sclerosis complex. Although its efficacy diminishes with time, repetitive usage is effective. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a rare genetic multisystem disease that involves brain, skin, kidneys, eyes and lungs. It typically presents during childhood with facial adenomas, seizures and mental retardation and its diagnosis is mainly clinical. We report a case of 68-year-old man that sought medical care due to a transient ischemic stroke. The past clinical history and physical observation showed symptoms and signs of TSC. An extend imagiological study allowed for a complete assessment of organ involvement. A delayed diagnosis places adults at increased risk for morbidity and mortality and therefore, clinicians must be familiar with the full spectrum of TSC-associated diagnostic features. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis or tuberous sclerosis complex is a dominantly inherited neurocutaneous disorder that variably affects the brain, skin, kidneys, heart, and other organs. Diagnosis of tuberous sclerosis becomes difficult in the young individuals with subtle changes. At this point, a careful inquiry and examination of the accessible signs and symptoms can errand a possible diagnosis. We hereby report such a rare case of tuberous sclerosis in 14-year-old boy, which was diagnosed in a novel approach.

Background: Pulsed dye laser (PDL) has revolutionized treatment of vascular dermatoses. It has been successfully employed to treat several non-vascular conditions in fair skinned individuals without producing significant pigmentary and textural complications. Aim: A preliminary study was undertaken to assess its efficacy in cosmetically distressing facial, vascular and non-vascular dermatoses in Indian patients with skin types IV and V. Materials and Methods: Nine patients of ages 7 to 55 years, with facial verruca plana (VP- 4 cases), angiofibromas (AF- 4 cases) and multiple pyogenic granulomas (PG- one case) were recruited. They had no systemic complaints. Laser parameters used were (spot size/fluence/wavelength/pulse duration):VP- 5mm/5.5-7.5J/585nm/0.45ms; AF-5mm/6-8.5J/585nm/0.45ms;PG- 5mm/7J/585 and 595nm alternately/1.5ms. Response was assessed clinically and photographically. Results and Conclusions: All VP lesions completely resolved after 2-4 sessions (mean 3.25 sessions), AF showed 50% regression in all cases after 2-3 sessions (mean 2.5 sessions) and ≥75% subsidence after 3-7 sessions (mean 5.5 sessions) and in PG, after 3 sessions, there was complete subsidence of small satellite lesions with moderate shrinkage of larger papules and complete resolution after 5 sessions. Complications included transient hyperpigmentation/hypopigmentation only. There was no recurrence during next 6 months. PDL offers significant cosmetic improvement in facial dermatoses in Indian patients.

Tuberous sclerosis complex (TSC) is a rare multisystem genetic disease, with an estimated incidence of 1 in 6000-1 in 10,000. TSC is an autosomal dominant syndrome involving heart, kidneys, lungs, and skin. The classic triad of TSC is seizures, mental retardation, and angiofibromas; this triad occurs in only 29% of patients. The clinical diagnostic guidelines on TSC are prepared based on clinical features, radiographic findings. The most common oral manifestations of TSC are fibroma, gingival hyperplasia, and enamel hypoplasia. Odontogenic myxofibroma represents a rare slow-growing benign neoplasm found rarely in children below 10 years or adults over 50 years of age. The prevalence of myxoma is between 0.04% and 3.7%. Here, we are reporting a rare case of myxofibroma of gingiva in an 8-year-old female TSC patient. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) represents a genetic disorder of hamartoma formation in many organs; particularly the skin, brain, eye, kidney, and heart. We are reporting a case of TSC in a patient and his daughter. The interesting feature is the appearance of the facial angiofibromas in this patient. In this patient, there was a sudden spurt in growth of these lesions in the last 7 months at the age of 50 years giving an appearance of nodular growth, misleading the diagnosis. The lesion was biopsied to know any secondary changes had occurred. There is no mention in the literature regarding such a rapid growth or any secondary changes occurring in angiofibromas. Neither the biopsy revealed any secondary changes. Hence, this interesting phenomenon has been reported. Is it apt to call it as "ANGIOFIBROMA PROLIFERANZA" or "ANGIOFIBROMA VIPULA"? (The word VIPULA in local South Indian Kannada language is prolific growth). [ABSTRACT FROM AUTHOR]

Introduction: Facial angiofibromas (FA) are the most visible cutaneous manifestations in patients with tuberous sclerosis (TS), often resulting in stigmatization of the affected individuals. Recent studies have suggested that topical rapamycin may be an effective treatment for angiofibromas. Aim: To study the safety and efficacy of topical rapamycin in treatment of FA in Type IV-VI skin type. Materials and Methods: Five female patients with FA were included in the study, four of whom had TS, whereas one had isolated angiofibromas without systemic involvement. The age of the patients varied from 6 to 44 years. After baseline evaluation, they were advised to apply topical rapamycin (0.1-1%) in white soft paraffin base twice daily. Follow-up varied from 1 month to 6 months and is ongoing. Results: A sustained improvement was observed with respect to erythema, size as well as extent of the lesions as early as within 2 weeks of starting treatment. No side effects were observed. A correlation between duration of angiofibromas and effectiveness of treatment was noted. Conclusion: Topical rapamycin appears to be a safe and effective alternative to surgical or laser-based treatments in patients with FA. This treatment shows potential to be a first-line management for FA and appears safe to start in early childhood. [ABSTRACT FROM AUTHOR]

Background: Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC).Objective: We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects.Methods: A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment.Results: Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment).Limitations: This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis.Conclusion: Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated. [ABSTRACT FROM AUTHOR]

Facial angiofibromas are the most visible and unsightly of all the cutaneous manifestations of tuberous sclerosis (TSC). A 17-year-old female, a known case of TSC, presented for the treatment of cosmetically disfiguring facial angiofibromas. She was started on twice daily application of 0.1% sirolimus ointment prepared from crushed tablets of sirolimus compounded in white soft paraffin. After 3 months of use, there was visible decrease in the erythema and the size of the angiofibromas. In an attempt to accelerate the response, the concentration was further increased to 1% sirolimus which was used for a month, resulting in a decrease not only in the size and redness but also in the number of the angiofibromas. The patient did not experience any cutaneous or systemic complications related to therapy. Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus has been used as a targeted therapy for the renal and neurological manifestations of TSC. Topical preparation of sirolimus is not commercially available till date and hence preparations from crushed tablets or oral solution of sirolimus have been used with beneficial effects in treatment of angiofibromas especially in younger patients with flatter lesions. Randomized controlled trials are necessary to enable us to confirm the efficacy, long-term safety, the optimal dosage and possibility of reappearance once the drug is withdrawn. This is possibly the first case report of the use of topical sirolimus in India. [ABSTRACT FROM AUTHOR]

Introduction: Facial angiofibromas (FA) are the most visible cutaneous manifestations in patients with tuberous sclerosis (TS), often resulting in stigmatization of the affected individuals. Recent studies have suggested that topical rapamycin may be an effective treatment for angiofibromas. Aim: To study the safety and efficacy of topical rapamycin in treatment of FA in Type IV-VI skin type. Materials and Methods: Five female patients with FA were included in the study, four of whom had TS, whereas one had isolated angiofibromas without systemic involvement. The age of the patients varied from 6 to 44 years. After baseline evaluation, they were advised to apply topical rapamycin (0.1-1%) in white soft paraffin base twice daily. Follow-up varied from 1 month to 6 months and is ongoing. Results: A sustained improvement was observed with respect to erythema, size as well as extent of the lesions as early as within 2 weeks of starting treatment. No side effects were observed. A correlation between duration of angiofibromas and effectiveness of treatment was noted. Conclusion: Topical rapamycin appears to be a safe and effective alternative to surgical or laser-based treatments in patients with FA. This treatment shows potential to be a first-line management for FA and appears safe to start in early childhood.

The objective of this study was to evaluate the efficacy and outcome using the maxillary swing approach for the management of extensive nasopharyngeal angiofibromas. A retrospective analysis in a tertiary care center revealed five cases with extensive nasal angiofibromas operated using the maxillary swing approach between 2010 and 2012. All patients had tumor extension to the lateral-most portions of the infratemporal fossa with complete occupation and destruction of the lateral wall of the sphenoid sinus causing abutment to the cavernous sinus and complete involvement of the pterygopalatine fossa and pterygoid base. One patient displayed full occupancy of the maxillary sinus as a consequence of erosion of the posterior and medial walls of the maxillary sinus, while another had severe temporal lobe compression through the roof of the infratemporal fossa. All patients underwent tumor excision using the maxillary swing approach. Patients were followed up for a minimum period of 1 year after surgery. The maxillary swing approach gave optimal exposure of the entire central skull base including the infratemporal fossa and its extreme lateral and superior aspects. Adequate tumor exposure and vascular control could be achieved in all cases resulting in complete tumor excision. The mean operative time was 4.5 h. Post-operative healing was satisfactory with palatal fistula formation in two cases and all patients remaining disease-free up to the present time. One had minimal misalignment of the halves of the upper jaw and two had epiphora, of which one required dacryocystorhinostomy. The maxillary swing is an effective approach in the management of extensive nasopharyngeal angiofibromas and leads to optimal anatomical exposure with minimal morbidity. [ABSTRACT FROM AUTHOR]

Background: Tuberous sclerosis, an autosomal dominant neurocutaneous syndrome seen in approximately 1 in 6,000 people worldwide, is characterized by the appearance of hamartomas in multiple organs. The classic clinical triad consists of angiofibromas, epilepsy, and developmental delay. Dermatologic disorder is one of the main characteristics. Angiofibromas, a common form of presentation, causes significant cosmetic and medical problems. The current treatment for skin lesions is laser therapy. The carbon dioxide (CO) laser has been used satisfactorily in treating these lesions, but several studies have demonstrated a high percentage of recurrences. Erbium:yttrium-aluminum-garnet (YAG) laser treatment has been used to resurface skin abnormalities in patients with dermatologic conditions. The dye laser as an alternative uses the principles of selective photothermolysis and is very effective in treating the vascular component of tuberous sclerosis. The use of all these lasers to treat skin lesions in patients affected by tuberous sclerosis has never been described in the literature. Methods: A retrospective study, conducted from 2007 to May 2013, investigated 13 patients who had tuberous sclerosis treated with an erbium:YAG/CO/dye laser combination. Results: All the patients showed great improvement of their skin lesions. The results were evident immediately after the first treatment. No patient experienced complications or recurrence. Conclusions: The combined use of the erbium:YAG/Dye/CO laser is a safe and effective treatment for skin lesions in patients affected by tuberous sclerosis. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors . [ABSTRACT FROM AUTHOR]

Non-endocrine findings in patients with MEN1 (multiple endocrine neoplasia) syndrome also include skin lesions, especially tumor-type lesions. This is a narrative review of the English-language medical literature including original studies concerning MEN1 and dermatological issues (apart from dermatologic features of each endocrine tumor/neuroendocrine neoplasia), identified through a PubMed-based search (based on clinical relevance, with no timeline restriction or concern regarding the level of statistical significance). We identified 27 original studies involving clinical presentation of patients with MEN1 and cutaneous tumors; eight other original studies that also included the genetic background; and four additional original studies were included. The largest cohorts were from studies in Italy (N = 145 individuals), Spain (N = 90), the United States (N = 48 and N = 32), and Japan (N = 28). The age of patients varied from 18 to 76 years, with the majority of individuals in their forties. The most common cutaneous tumors are angiofibromas (AF), collagenomas (CG), and lipomas (L). Other lesions are atypical nevi, basocellular carcinoma, squamous cell carcinoma, acrochordons, papillomatosis confluens et reticularis, gingival papules, and cutaneous T-cell lymphoma of the eyelid. Non-tumor aspects are confetti-like hypopigmentation, café-au-lait macules, and gingival papules. MEN1 gene, respective menin involvement has also been found in melanomas, but the association with MEN1 remains debatable. Typically, cutaneous tumors (AF, CG, and L) are benign and are surgically treated only for cosmetic reasons. Some of them are reported as first presentation. Even though skin lesions are not pathognomonic, recognizing them plays an important role in early identification of MEN1 patients. Whether a subgroup of MEN1 subjects is prone to developing these types of cutaneous lesions and how they influence MEN1 evolution is still an open issue.

Objective To document clinical features in patients of tuberous sclerosis. Patients and methods Twenty clinically diagnosed cases of tuberous sclerosis were assessed clinically for features of tuberous sclerosis. Results Males outnumbered females and male: female ratio was 2.3:1. Adenoma sebaceum was the commonest (95%) cutaneous feature of tuberous sclerosis followed by ash leaf macule and shagreen patch each seen in 90% patients followed by Koenen's tumour seen in 75% patients. Positive family history was seen in 25% patients. Regarding the clinical spectrum of tuberous sclerosis it was seen that epileptic fits and cardiac complications were seen in 50% patients each, eye abnormalities including retinal astrocytomas were seen in 40% patients, mental retardation was seen in 25% patients followed by astrocytomas and pulmonary disease seen in 20% patients each. Conclusion Tuberous sclerosis can present with diverse cutaneous and systemic manifestations. Dermatologist may assist in early diagnosis of this multisystem genodermatosis. [ABSTRACT FROM AUTHOR]

Patients with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2, resulting in mammalian target of rapamycin (mTOR) activation. Hamartomas overgrow epithelial and mesenchymal cells in TSC skin. The pathogenetic mechanisms for these changes had not been investigated, and the existence or location of cells with biallelic mutations ("two-hit" cells) was unclear. We compared TSC skin hamartomas (angiofibromas and periungual fibromas) with normal-appearing skin of the same patient, and we observed more proliferation and mTOR activation in hamartoma epidermis. Two-hit cells were not detected in the epidermis. Fibroblast-like cells in the dermis, however, exhibited allelic deletion of TSC2, in both touch preparations of fresh tumor samples and cells grown from TSC skin tumors, suggesting that increased epidermal proliferation and mTOR activation were not caused by second-hit mutations in the keratinocytes but by mesenchymal-epithelial interactions. Gene expression arrays, used to identify potential paracrine factors released by mesenchymal cells, revealed more epiregulin mRNA in fibroblast-like angiofibroma and periungual fibroma cells than in fibroblasts from normal-appearing skin of the same patient. Elevation of epiregulin mRNA was confirmed with real-time PCR, and increased amounts of epiregulin protein were demonstrated with immunoprecipitation. Epiregulin stimulated keratinocyte proliferation and phosphorylation of ribosomal protein S6 in vitro. These results suggest that hamartomatous TSC skin tumors are induced by paracrine factors released by two-hit cells in the dermis and that proliferation with mTOR activation of the overlying epidermis is an effect of epiregulin. [ABSTRACT FROM AUTHOR]

Summary Background Data on the benefits, adverse effects and appropriate types of laser treatment for angiofibromas (AF) in patients with tuberous sclerosis (TS) are limited. Objectives To evaluate the efficacy and side-effect profile of carbon dioxide (CO2 ) 10 600 nm wavelength and flashlamp-pumped pulsed dye (FLPDL) 585 nm wavelength lasers in a retrospective study of 29 patients with TS aged 9–48 years. Methods Long-term results, based on clinical improvement of the vascular, fibrous or protuberant types of AF and the presence or absence of side-effects on follow-up visits, were classified as excellent, moderate or poor. Results Results were excellent in most patients with vascular-type AF treated with one or two sessions of FLPDL, but some required up to six treatment sessions. CO2 lasers produced excellent results with considerable long-term improvement in 10 of 13 (77%) patients with fibrous or protuberant AF, specifically in all (three of three) protuberant and 70% (seven of 10) of fibrous AF. Persistent hypertrophic scarring was seen in three of 13 (23%) patients with either fibrous or protuberant AF treated with the continuous wavelength CO2 laser. Treatment with both lasers used in four patients with combined vascular and non-vascular AF components was excellent in three of four (75%) patients. Significant relapse was seen in one patient treated with the CO2 laser. Conclusions CO2 or FLPDL laser treatment should be considered as an effective treatment for patients with disfiguring TS. A combination of lasers may be required to achieve optimal results. [ABSTRACT FROM AUTHOR]

The objective of this article is to demonstrate a clinical case with a good outcome by using a maxillary swing approach during the surgical treatment of extensive locally advanced form of the juvenile nasopharyngeal angiofibroma (JNA) stage Fisch-Andrews IIIb (Radkowski IIIb). Thus the maxillary swing approach has given an adequate exposure of the skull base and is an effective approach in the surgical treatment of extensive JNA with a good overview of anatomical structures and has a minimal risk of complications and to evaluate an efficacy of the results.

Tuberous sclerosis (TSC) is an autosomal dominant hereditary condition with many varied forms of clinical presentation. The most frequent cutaneous findings in TSC include multiple angiofibromas, hypopigmented macules, periungual fibromas, and shagreen patch. Rarely, unilateral multiple facial angiofibromas have been reported. We report a case of unilateral multiple facial angiofibromas without any other manifestations of TSC. Although rare, unilateral multiple facial angiofibromas may be a mosaic form of TSC.

Abstract: Tuberous sclerosis is a multisystem disorder characterised by the formation of hamartomas in various parts of the body. We present a patient who presented with facial angiofibromas (adenoma sebaceum), shagreen patches, and epileptic seizures. Oral papules showed histological features of angiofibroma, which was peculiar to this case. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

A 50-year-old woman was admitted due to a long-standing history of cutaneous lesions, which were gradually increasing in number and size, located on the trunk and extremities. Histological studies confirmed the initial clinical diagnosis of histiocytomas. Moreover, the patient had numerous smooth erythematous papules on her chin and around her nose, which were diagnosed histologically as angiofibromas. The patient had congenital phocomelia. Analytical and imaging studies revealed the presence of bilateral phocomelia due to absent radii and thrombocytopenia (TAR syndrome). Multiple histiocytomas in a normolipaemic patient bring up several differential diagnoses. Slow progressive evolution without spontaneous resolution and a scattered distribution on the trunk and extremities suggest the diagnosis of progressive nodular histiocytoma. To our knowledge progressive nodular histiocytoma has not been reported previously associated either with TAR syndrome or with angiofibromas. These entities are uncommon, thus their association may not be due to chance. [ABSTRACT FROM AUTHOR]