Use of topical rapamycin in the treatment of superficial lymphatic malformations

García-Montero, P.; Boz, J. del; Baselga-Torres, E.; Azaña-Defez, J.M.; Alcaraz-Vera, Manuel; Sánchez, Jesús Tercedor; Noguera‐Morel, Lucero; Vera-Casaño, Ángel

doi:10.1016/j.jaad.2018.09.050

Cited by 33 publications

(22 citation statements)

References 32 publications

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“…In general, we found topical sirolimus was very effective in reducing blebs, exudate, and bleeding. Eleven other patients treated with topical sirolimus for macro‐ and microcystic LMs have been reported in the literature, all of which document improvement in lymphorrhea and bleeding (in cases where this was an issue) . Over half of our patients with CLVM had a >50% reduction in bleeding and >25% reduction in blebs and exudate.…”

Section: Discussionmentioning

confidence: 66%

“…The degree of improvement may be related to the extent of lymphatic vs capillary and venous involvement although specifics on the individual makeup of each patient's anomaly were not available. A small case series, which included three CLVMs, documented improvement in blebs and exudate in each patient . In response to this study, Cai et al suggested immunohistochemistry and genetic studies before and after to determine which portions of the anomaly respond to treatment.…”

Section: Discussionmentioning

confidence: 89%

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Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

Dodds

Tollefson

Castelo‐Soccio

et al. 2020

Pediatric Dermatology

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Background Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. Objective We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. Methods Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. Results Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. Limitations The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. Conclusion Topical sirolimus appears to be a safe and useful non‐invasive therapy that is well‐tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 89%

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

Dodds

Tollefson

Castelo‐Soccio

et al. 2020

Pediatric Dermatology

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“…Subsequently, its application has been used in an increasing number of complex vascular malformations [14,[21][22][23][24][25][26]. Meanwhile, a growing number of authors have indicated that sirolimus can decrease the size of LMs and alleviate associated symptoms [15,16,18,19,[27][28][29][30][31][32]. Therefore, we explored 56 cases of complex LMs treated with oral sirolimus to investigate the drug's efficacy and safety in our hospital.…”

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confidence: 99%

Effectiveness of sirolimus in the treatment of complex lymphatic malformations: Single center report of 56 cases

Tian

Zhang

et al. 2020

Journal of Pediatric Surgery

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Background: Lymphatic malformations are common congenital vascular lesions. Neither surgical resection nor other surgical treatments have been found to be effective for invasive cases. Recent research has suggested that sirolimus is effective in treating complex lymphatic malformations (LMs). We aimed to evaluate the effectiveness and safety of oral sirolimus for children living with LMs in our hospital. Methods: Fifty-six cases of complex LMs treated with sirolimus were collected from Shanghai Children's Medical Centre between June 2016 and March 2019. All cases were confirmed either by pathology (44) or enhanced MRI (12). Following informed consent, sirolimus 0.8 mg/m 2 bid was administered orally to participants and maintained at a trough concentration of 10-15 ng/ml. Children's ages at diagnosis were neonate to 16 years (mean 44.3 months). All children were followed up for 5 to 30 months, with a mean of 16.8 months. Results: During the follow-up period, blood, liver and kidney function as well as disseminated intravascular coagulation was regularly reviewed in all 56 children. Enhanced MRI was regularly performed to evaluate therapeutic effects. Total effective rate (complete response or partial response) of LMs was 89.3% (50/56). No serious adverse reactions were found. Conclusion: This study suggests that sirolimus is effective and tolerable for decreasing lesions in children with complex LMs, leading to fewer and more tolerable side effects. There is no need to pursue an excision rate to reduce unnecessary operative complications since adjuvant sirolimus therapy modifies the complex LMs clinical appearance and alleviates their symptoms. Type of study: Clinical research.

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“…33 Topical sirolimus was shown to improve superficial (microcystic) lymphatic malformations. 34 A case report showed that selective inhibition of AKT1 with miransertib leads to regression of the cerebriform connective tissue naevus in Proteus syndrome. 35 Alpelisib, a selective inhibitor of PIK3CA, significantly improved hemihypertrophy and secondary complications in patients with PROS or CLOVES [congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal naevi and scoliosis/skeletal/spinal anomalies] syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Children with extensive lymphatic anomalies, venous or combined slow‐flow VMs responded well to oral sirolimus 33 . Topical sirolimus was shown to improve superficial (microcystic) lymphatic malformations 34 . A case report showed that selective inhibition of AKT1 with miransertib leads to regression of the cerebriform connective tissue naevus in Proteus syndrome 35 .…”

Section: Discussionmentioning

confidence: 99%

Genes and phenotypes in vascular malformations

Hoeger

2020

Clin Exp Dermatol

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Vascular malformations (VMs) are caused by localized defects of vascular development. Most VMs are due to sporadic, postzygotic mutations, while some are the result of autosomal dominant germline mutations. Genotype-phenotype correlation is influenced by many factors. Individual genes can induce different phenotypes (pleiotropy), and similar phenotypes can be due to different genes/mutations (redundancy). The phenotypic spectrum of somatic mutations is wide, and depends on variant allele frequency, timing during embryogenesis, cell type(s) involved and type of mutation. The phenotype of germline mutations is determined by penetrance and expressivity, and is influenced by epigenetic factors (DNA methylation, histone modification) or 'second-hit' somatic mutations. Except for disorders with pathognomonic phenotypes such as Proteus syndrome or a characteristic constellation of symptoms such as CLOVES [congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal naevi and scoliosis/ skeletal/spinal anomalies] or PIK3CA-related overgrowth spectrum syndrome, differential diagnosis of VM is therefore difficult. It will be greatly facilitated with increasing analytic sensitivity of sequencing techniques such as next-generation sequencing. High-sensitivity molecular techniques are a prerequisite for targeted pharmacotherapy, i.e. selective therapeutic inhibition of activating mutations underlying VM, which has shown promising results in preliminary studies.

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Use of topical rapamycin in the treatment of superficial lymphatic malformations

Cited by 33 publications

References 32 publications

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series

Effectiveness of sirolimus in the treatment of complex lymphatic malformations: Single center report of 56 cases

Genes and phenotypes in vascular malformations

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