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

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.

Use of mTOR inhibitors (rapalogs) for the treatment of skin changes in tuberous sclerosis complex.

BACKGROUND: Skin manifestations of Tuberous Sclerosis Complex (TSC) are present in more than 90% of patients. Facial angiofibromas (AF) are considered a skin hallmark of TSC. They are responsible for esthetic impact in patients. We aimed at reviewing the data available on the use of rapamycin (sirolimus) and everolimus for the oral or topical treatment of AF and other TSC-related skin changes and reporting our preliminary experience at Angers University Hospital. METHODS: The literature search has been performed in combining the terms "rapamycin", "sirolimus", "everolimus", "tuberous sclerosis complex", "skin" and "trial". We have splited the findings of the literature search into two parts: 1) the value of rapalogs used systemically for extracutaneous purposes and 2) the role of topical rapalogs used specifically for skin lesions. RESULTS: Large clinical trials using rapamycin or everolimus for the treatment of brain, lung or kidney manifestations of TSC unfortunately poorly define the "skin lesion response rate" they report. Conversely, the trials with topical rapamycin demonstrate significant, albeit transient, efficacy on AF size and visibility and acceptable tolerance. Several trials suggest better efficacy in younger patients than in adults. Long-term evaluation (up to 136 weeks) point to sustained response and good local and systemic tolerance. However, maintenance therapy appears to be mandatory to preserve skin response. Other skin changes, especially shagreen fibrotic plaques, hypomelanotic macules and ungual tumors still need far more research. Our experience in 124 patients (children and adults) treated for facial AF at Angers University Hospital showed that about 80% of them had an impressive and sustained response. CONCLUSION: The issues of cost and access to affordable topical rapamycin formulations are critical for the patients even if skin changes do not cause serious harm in the context of TSC. We strongly suggest to improve and standardize the formulation of topical rapamycin, to encourage the pharmaceutical industry for providing commercial products, and the Health systems (social welfare) to reimburse them. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

[Prevalence of the tuberous sclerosis complex at patients taken care for a renal angiomyolipoma]. / Prévalence de la sclérose tubéreuse de Bourneville chez des patients pris en charge pour un angiomyolipome rénal.

INTRODUCTION: Bourneville's tuberous sclerosis or Tuberous Sclerosis Complex (TSC) is an autosomal dominant hereditary phakomatosis associated with angiomyolipomas (AML) of the kidney. The aim of this study was to identify the prevalence of TSC in patients diagnosed and cared for AML in our department of urology. MATERIALS AND METHODS: All the patients with AML were included between March 2009 and June 2016 in a French university hospital. Each patient was reviewed in consultation with a clinical examination and imaging. Specific clinical criteria were used to refer patients to genetic analysis. Patients with a high TSC probability had a genetic analysis to search TSC1 and TSC2 genes mutations. RESULTS: In all, 28 patients were included and 3 (11%) were diagnosed TSC. The median age of the patients was 62 years (36-82 years). The most frequent clinical criteria were facial angiofibromas in 7 patients (25%). Among the 8 patients (29%) with evocative clinical criteria, a mutation of the TSC1 and TSC2 genes was identified in 3 patients (11%) with a diagnosis of TSC made before the AML diagnosis. CONCLUSION: In this study, 8 patients (29%) presented clinical criteria suggestive of TSC, preferentially dermatological. The diagnosis was confirmed by screening TSC1 and TSC2 genes mutations in 3 patients (11%), nevertheless prevalence of TSC is most probably underestimated by the genetic mosaïcisme of this pathology.

[Conchal cartilaginous delta graft in secondary or post-traumatic rhinoplasties]. / Le greffon cartilagineux conchal "delta" dans les rhinoplasties secondaires ou post-traumatiques.

The authors study several cases of surgical revision in post-traumatic or secondary rhinoplasty. Cartilaginous grafts with temporal fascia are recommended. The removal of ear cartilage is performed via a posterior approach for the concha cartilage associated with a septum or an alar cartilage removal. They describe the delta graft associating a concha cartilage supported by a prop (auricular or septal) to repair a defect of the middle or lower third of the pyramid.

["Delta" cartilaginous graft in secondary or post traumatic rhinoplasty]. / Le greffon cartilagineux "Delta" dans la rhinoplastie secondaire ou post-traumatique.

The authors study some cases of surgical revision in post traumatic or secondary rhinoplasty. Cartilaginous grafts with temporal superficialis fascia are recommended. The removal of ear cartilage is used by a posterior approach for the concha cartilage associated with a septum or an alar cartilage removal. They describe the Delta graft associating a concha cartilage supported by a prop (auricular or septal) to repair a loss of substance from the middle or lower third of the nasal pyramid.

[Efficacy and side effects of long-term treatment with amiodarone. Retrospective study. Apropos of 460 cases]. / Efficacité et effets secondaires du traitement au long cours par l'amiodarone. Etude rétrospective. A propos de 460 cas.

A retrospective study was conducted in a group of 460 patients in order to evaluate the effectiveness and frequency of side effects of amiodarone over a mean observation period of 2 years. The effectiveness was considered to be excellent or good in 71.5 p. cent of cases of ischaemic heart disease, in 84.8 p. cent of cases of supraventricular arrhythmia and in 92.3 p. cent of cases of ventricular arrhythmia. Side effects were observed in 32.8 p. cent of patients and treatment had to be suspended in 19.8 p. cent of cases. The most frequent side effects were photosensitisation (11.9%), thyroid disorders (5.6%) and bradycardia or sinus dysfunction (11.9%). Some of these side effects appear to be related to the cumulative dose received.