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.

Healthcare transition from childhood to adulthood in pseudoxanthoma elasticum: Patient experience and recommendations for health practitioners.

PURPOSE: Health-care transition (HCT) is a necessary part of the care process for allsick adolescents, to allow their empowerment while limiting disruption to follow-up care. Pseudoxanthoma elasticum (PXE) runs the risk of losing patients to follow-up because young patients are predominantly asymptomatic. This can be detrimental as it can prevent primary prevention measures from being properly implemented. The purpose of this study was to assess satisfaction of PXE patients with their health-care transition and to identify the factors associated with its success, in order to improve care management in young PXE patients. METHODS: Patients aged 22 to 40 years diagnosed with PXE before the age of 16 years were included from the cohort of patients followed at Angers University Hospital. They were sent a questionnaire for the purposes of collecting data on medical management during adolescence, transition and adulthood. RESULTS: Eleven responses were obtained from the 21 patients surveyed. The median satisfaction score of PXE patients regarding their transition was 5/10. Three patients reported having discontinued follow-up after transition. In adulthood, the majority of the participants were followed up by 4 specialists as recommended. It was incumbent on 50% of the patients who changed doctors to provide details of their own medical history to the new practitioner. CONCLUSION: Better intra-practitioner communication and a chart summarizing the principles of primary prevention, optimal follow-up care and its frequency are simple to implement and in all likelihood result in better health-care transition for young PXE patients.

[Non-tuberculous mycobacterial cervical adenitis in children: 2 cases]. / Deux cas d'adénite cervicale à mycobactéries non tuberculeuses chez l'enfant.

BACKGROUND: Cervical lymphadenitis is the most common manifestation of infection with nontuberculous mycobacteria (NTM) in immunocompetent children. Nevertheless, it is poorly known by dermatologists. Its incidence, which is currently increasing since the cessation of BCG vaccination in 2007, raises several issues regarding its pathophysiology, diagnosis and management. PATIENTS AND METHODS: We report two cases of NTM adenitis: one in a 2-year-old girl vaccinated with BCG and one in an unvaccinated 22-month-old boy, in whom a misleading presentation led to delayed diagnosis. The condition progressed to fistula formation and the diagnosis was finally made on systematic cultures of lymph node samples. The time to diagnosis was 2 and 4months, respectively. The girl was treated with erythromycin for 3 weeks and with clarithromycin for 3 weeks; the boy received clarithromycin for 7 weeks and underwent complete surgical excision. DISCUSSION: NTM adenitis preferentially affects girls under 4 years and occurs more frequently in winter and spring. First, the other differential diagnoses, including tuberculosis, must be ruled out by chest radiography. The diagnosis is oriented by the clinical picture, a positive TST and resistance to conventional antibiotics. However, it is only certified by systematic culture or PCR of lymph node biopsies, with screening for atypical mycobacteria being specified. The decrease in child protection by BCG vaccination coincides with the current increase in NTM infections, of which the most frequent is Mycobacterium avium complex (MAC) for cervical adenitis. The reference treatment is surgery. However, alternative treatments (incomplete excision, antibiotics, watchful waiting, etc.) should be considered where surgery fails or there is excessive risk of injury to a branch of the facial nerve. CONCLUSION: Atypical mycobacterial adenitis in immunocompetent children has become an increasingly common infection since the abandonment of BCG vaccination. Improved knowledge of this disease would result in complete surgical excision at an early stage with a lower rate of aesthetic sequelae.