Treatment Of Facial Angiofibromas Research Articles

A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium- and long-term efficacy and safety of topical rapamycin

AimsTopical 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. MethodsThe 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. ResultsThis 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. ConclusionThis 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.

Can Radiofrequency Ablation Be Utilized With Equal Effect in Place of Carbon Dioxide Laser in the Treatment of Facial Angiofibromas in Patients of Tuberous Sclerosis?

Can Radiofrequency Ablation Be Utilized With Equal Effect in Place of Carbon Dioxide Laser in the Treatment of Facial Angiofibromas in Patients of Tuberous Sclerosis?

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex-An update.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed in Europe. We conducted a retrospective review with the aim to update the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the optimal concentration and trying to establish which vehicle should be preferred. Thirty-nine reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 483 patients. An improvement of the lesions has been shown in over 90% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%-1%) were proposed, of which a pharmacological analysis has also been performed. Topical rapamycin can be considered an effective and safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has yet to be established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. However, according to this study, the 0.1% concentration represents the first choice. Long-term and comparative studies between topical rapamycin formulations are required in order to establish which treatment has a better outcome and lower recurrence rate.

Evaluating the Long-Term Outcome of the Ablative Lasers in the Treatment of Facial Angiofibromas in Tuberous Sclerosis: A TwoYear Follow-Up Study

Background: Tuberous sclerosis (TS), a genetic multisystem disorder, is characterized by widespread hamartomas in multiple organs. The classic clinical symptoms consist of angiofibromas, epilepsy, and developmental delay. Dermatological change is one of the major features. Bilateral facial angiofibromas (FA), a common form of presentation, cause significant cosmetic, medical, and emotional problems. The emerging treatment for skin lesions is laser therapy. However, there is no report on the long-term outcome of combined use of ultra-pulse carbon dioxide (UPCD) laser and ablative fractional (AF) Er: YAG lasers to treat skin lesions in patients suffering TS. Methods: A retrospective study, conducted from March 2014 to July 2018, investigated 9 patients from the Northwest part of China who had TS treated with a sequential treatment of UPCD laser and AF Er: YAG laser. Results: The sequential use of the UPCD and AF Er: YAG laser is a safe and effective method for the treatment of FA in patients suffering TS with satisfactory long-term outcomes. Conclusions: The sequential use of the UPCD and AF Er: YAG laser is a safe and effective method for the treatment of FA in patients suffering TS with satisfactory long-term outcomes.

Improved health-related quality of life in patients treated with topical sirolimus for facial angiofibroma associated with tuberous sclerosis complex

BackgroundTuberous 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.MethodsWe 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.ResultsThe 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.ConclusionsThis 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-abstractSirolimus gel treatment improves the health-related QOL in patients with FA associated with TSC.

Successful CO2 Laser Treatment of Facial Angiofibromas in a Female Patient with Tuberous Sclerosis: Case Report

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.

Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas.

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. 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. 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. 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.

Topical sirolimus in the treatment of facial angiofibromas

Topical sirolimus in the treatment of facial angiofibromas

Long-term treatment of cutaneous manifestations of tuberous sclerosis complex with topical 1% sirolimus cream: A prospective study of 25 patients

Data on long-term topical sirolimus treatment of the cutaneous manifestations of tuberous sclerosis complex are rare. To evaluate the long-term benefit and tolerance of topical 1% sirolimus in tuberous sclerosis complex. In this 18-month prospective single-center study, 1% sirolimus cream was applied daily to facial angiofibromas (FAs), fibrous cephalic plaques (FCPs), shagreen patches, hypomelanotic macules, and ungual fibromas. After complete clearance (CC) of FAs, we evaluated a maintenance protocol of 3 applications weekly. Twenty-five patients were enrolled. Fifty percent obtained CC of FAs within 9months. Of 7 patients with CC (58%) who were following the maintenance protocol, 6 relapsed within 7months and 1 was still responding at 1year. Of 16 patients with FCPs, 7 (44%) remained stable at 12months and 9 (56%) improved after 3 to 9months of treatment. Only 1 of 5 patients treated for shagreen patches showed improvement at 12months. Treatment was well tolerated with no serious adverse events. The small number of patients was a limitation. Topical 1% sirolimus applied daily produced positive responses in treatment of FAs, FCPs, and facial hypomelanotic macules and was well tolerated. A 3-times-weekly maintenance protocol did not prevent FA relapses.

Efficacy and safety of topical sirolimus in the treatment of facial angiofibromas in children with tuberous sclerosis complex

Objective To investigate the efficacy and safety of sirolimus 0.1% ointment in the treatment of facial angiofibromas in children with tuberous sclerosis complex. Methods Sirolimus 0.1% ointment was prepared. Twenty children with tuberous sclerosis complex who had facial angiofibromas were enrolled in this study. Facial angiofibromas were topically treated with the self-prepared sirolimus 0.1% ointment twice a day for 12 weeks. The facial angiofibroma severity index (FASI)was calculated, the degree of satisfaction with the treatment was evaluated, and adverse reactions were analyzed at weeks 4 and 12. Plasma sirolimus concentrations as well as blood biochemical and immunological parameters were measured, blood coagulation activity was evaluated, and routine blood tests as well as urine tests were performed at baseline and week 12. Results The FASI of patients significantly decreased at weeks 4 (4.400±1.284)and 12 (2.975±1.543)compared with that at baseline (5.750±1.175, both P < 0.000 1), and was significantly lower at week 12 than at week 4 (P < 0.000 1). The efficacy index was 49.87%±22.08% at week 12, significantly higher than that at week 4 (24.43%±10.18%, t = 7.338, P < 0.01). The color, size and number of lesions significantly decreased in all the patients, and facial angiofibromas completely disappeared in 2 patients at week 12. At week 4, 10 parents were satisfied with the improvement of erythema, 3 parents with that of lesion volume, and 3 parents with that of lesion area. The degree of parent satisfaction increased at week 12 in all the cases. The blood concentration of sirolimus was lower than 1.0 μg/L both before and after the treatment. No severe systemic or local adverse reactions were noted in these patients. Conclusion Sirolimus 0.1% ointment is markedly effective and safe for the treatment of facial angiofibromas in patients with tuberous sclerosis complex. Key words: Tuberous sclerosis; Angiofibroma; Sirolimus; Treatment outcome

Use of topical rapamycin in facial angiofibromas in Indian skin type

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.

Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions has historically been challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed. The aim of this review is to analyse the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the risk-benefit profile. A retrospective review of the English-language literature was conducted. Sixteen reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 84 patients. An improvement of the lesions has been shown in 94% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%-1%) were proposed. Only 4 local adverse side-effects were reported after the use of rapamycin solution. Topical rapamycin can be considered a safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has not been established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. Long-term and comparative studies between topical rapamycin and ablative techniques are required to establish which treatment has a better outcome and lower recurrence rate.

Topical Rapamycin Therapy to Alleviate the Cutaneous Manifestations of Tuberous Sclerosis Complex

Facial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas. The study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any form of rapamycin or if they were pregnant. Study subjects applied the study product to their facial angiofibromas nightly for a duration of 6 months. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%). Plasma rapamycin concentrations were measured monthly to test for systemic absorption. Complete blood counts were performed monthly to test for anemia, neutropenia, or thrombocytopenia. Upon completion of the trial, subjects were asked if the formulation had improved the appearance of their facial angiofibromas. Twenty-three subjects completed the study. There was no detectable systemic absorption of rapamycin (all blood concentrations were <1.0 ng/mL). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas. The application of low-dose topical rapamycin (0.003–0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex. ClinicalTrials.gov Identifier: NCT01031901

Topical Rapamycin Therapy to Alleviate the Cutaneous Manifestations of Tuberous Sclerosis Complex

Background and ObjectivesFacial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas.Patients and MethodsThe study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any form of rapamycin or if they were pregnant. Study subjects applied the study product to their facial angiofibromas nightly for a duration of 6 months. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%). Plasma rapamycin concentrations were measured monthly to test for systemic absorption. Complete blood counts were performed monthly to test for anemia, neutropenia, or thrombocytopenia. Upon completion of the trial, subjects were asked if the formulation had improved the appearance of their facial angiofibromas.ResultsTwenty-three subjects completed the study. There was no detectable systemic absorption of rapamycin (all blood concentrations were <1.0 ng/mL). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas.ConclusionThe application of low-dose topical rapamycin (0.003–0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex.Trial RegistrationClinicalTrials.gov Identifier: NCT01031901

CO2, Er:YAG and Pulsed Dye Laser Treatment of Angiofibromas in Patients with Tuberous Sclerosis

Summary Background: Facial angiofibromas in tuberous sclerosis have been treated using various methods, without reproducible efficiency. Laser therapy could be a viable alternative. Objective: The purpose of this study was to evaluate the efficacy and side-effects of pulsed CO2 laser (10600 nm wavelength) or Erbium-YAG laser (2940 nm wavelength), and 595 nm wavelength pulsed dye laser in the treatment of facial angiofibromas. We attempted to make a comparison between these two treatments, and to perform a clinical assessment of pulsed CO2 laser or Erbium-YAG laser and pulsed dye laser treatment of angiofibromas. Methods: We treated 18 patients. We utilised a 595 nm wavelength pulsed dye laser, using a skin cooling system (Spray or Cryo), with a 7 mm spot size, energy density (fluence J/cm2) from 6 to 8 J/cm2, emission modality (repetition rate) at 0.5 Hz to 2, and a short pulse duration of 2 to 0.5 msec or Erbium-YAG laser (1000 mJ, 200 s); KTP 532 nm; Nd:YAG 1064 long pulse (300 J/cm2, 50 ms); and pulsed CO2 laser. Results: Nine patients with fibrous angiofibromas of the entire face were treated using pulsed CO2 laser (ultra or superpulsed). The patients treated showed remarkable cosmetic improvements, without scarring. Mild hyperpigmentation was observed in 2/9 patients, which disappeared within 6 months. Facial erythema persisted for about 2 months in 5/9 patients. The results on fibrous and protuberant angiofibromas were good, with an improvement of 51–75% of the lesions. Seven patients were satisfied after the first pulsed CO2 laser treatment, and only 2 required 1 further treatment at 6-month intervals (mean number of treatments: 1.22). Er:YAG laser was used for 4 patients, with 1 to 2 sessions at 2-month intervals, with good improvement on the fibrous component, and limited adverse effects (1 patient developed hypochromia). Vascular lasers were used for 11 patients. The pulsed Nd:YAG KTP (532 nm) (3 patients) and Nd:YAG-long pulse 1064 nm (1 patient) was used to times and always required the use of another type of laser. With the use of the Nd:YAG KTP (532 nm) a perinasally localised scar occurred. Conclusions: Laser therapy is indicated for angiofibromas in the first instance. Carbon dioxide laser is advocated as the preferable treatment for fibrous or protuberant angiofibromas, while pulsed dye laser is more successful for those with a vascular component. The CO2 laser, however, involves a risk of depigmentation or scarring, so that a combination of lasers may be required to achieve the best results.

Cosmetic Treatment of Shagreen Patches in Selected Patients with Tuberous Sclerosis

Patients with mild forms of tuberous sclerosis may request cosmetic treatment of skin hamartomas. Treatment may consist of planning of an elevated shagreen patch with a Reese dermatome and/or laser treatment of facial angiofibromas. These precise patients, i.e., patients with a forme fruste of tuberous sclerosis, are more likely to have pulmonary involvement than patients with the usual complete disease form. A chest x-ray should be obtained in these patients to rule out pulmonary involvement. Half the patients with pulmonary involvement of tuberous sclerosis die an avoidable death from spontaneous pneumothoraces. Positive-pressure ventilation during anesthesia in these patients should be avoided or monitored closely.