sirolimus and Port-Wine-Stain

Topics: Angiopoietin-2; Axitinib; Ephrin-B2; Humans; Imiquimod; Phosphatidylinositol 3-Kinases; Photosensitizing Agents; Port-Wine Stain; Proto-Oncogene Proteins c-akt; Receptor, EphA1; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2

Systemic mammalian target of rapamycin (mTOR) inhibitors are currently used in many dermatologic indications. Their topical use is recent and poorly codified.. To provide an overview of the topical use of mTOR inhibitors in dermatologic conditions and evaluate their efficacy and safety.. A literature search was performed in January 2017. Reports of all studies investigating the use of topical mTOR inhibitors in any dermatology diseases were included. The exclusion criteria were systemic use and mucosal administration.. We included 40 studies with a total of 262 patients. In all, 11 dermatologic conditions were found, the most frequent being angiofibromas linked to tuberous sclerosis complex (157 patients). Topical mTOR inhibitors were significantly more efficient than placebo for angiofibromas (relative risk, 2.52; 95% confidence interval, 1.27-5.00; I. High heterogeneity in most studies.. This systematic review supports the efficacy of topical sirolimus for angiofibromas linked to tuberous sclerosis complex, with only local side effects reported. Other indications require further research.

Topics: Administration, Cutaneous; Angiofibroma; Antibiotics, Antineoplastic; Humans; Port-Wine Stain; Psoriasis; Sirolimus; Skin Neoplasms; TOR Serine-Threonine Kinases; Tuberous Sclerosis

Sturge-Weber syndrome (SWS) is characterized by facial capillary malformation, leptomeningeal capillary malformations, and choroidal and episcleral vascular malformations. These malformations produce neurologic and ophthalmological symptoms including seizures and glaucoma. A premature male newborn without prenatal diagnosis presented with severe bilateral SWS and was started on systemic sirolimus and aspirin. The patient has remained seizure-free for 23 months and demonstrated an excellent response to pulsed dye laser treatment.

Topics: Administration, Oral; Aspirin; Drug Therapy, Combination; Electroencephalography; Humans; Infant, Newborn; Infant, Premature; Lasers, Dye; Magnetic Resonance Imaging; Male; Port-Wine Stain; Primary Prevention; Prognosis; Risk Assessment; Seizures; Severity of Illness Index; Sirolimus; Sturge-Weber Syndrome; Treatment Outcome

Port wine stains (PWS) pose a therapeutic challenge. Pulsed dye laser (PDL) is the treatment of choice; however, treatment is often ineffective and recurrences are common.. This article provides a review of topical therapies that have been investigated to improve efficacy of PDL for the treatment of PWS.. A literature search was performed through PubMed, EMBASE, Web of Science, and CINAHL, using the search terms "port wine stain," "pulsed dye laser," and "topical.". Clinical trials have investigated the topical agents, timolol, imiquimod, and rapamycin (RPM) in combination with PDL for the treatment of PWS. Topical timolol with PDL failed to show improved efficacy compared with PDL alone. Two clinical trials using imiquimod and PDL showed enhanced blanching of PWS compared with controls. Rapamycin and PDL were more effective than controls for facial PWS, but not for nonfacial PWS.. Topical imiquimod and RPM have shown some efficacy in treating PWS with PDL, but to date there is no topical adjuvant to PDL that reliably improves results for PWS.

Topics: Administration, Cutaneous; Aminoquinolines; Clinical Trials as Topic; Combined Modality Therapy; Dermatologic Agents; Humans; Imiquimod; Lasers, Dye; Port-Wine Stain; Randomized Controlled Trials as Topic; Sirolimus; Timolol; Treatment Outcome

Port-wine stains (PWSs) are capillary vascular malformations that are commonly resistant to treatment. Currently, the pulsed dye laser (PDL) is the treatment of choice. Multiple treatments are required and complete blanching after laser irradiation is rarely achieved. We review current therapeutic modalities for PWSs and recent developments for enhanced clearance.. Relevant literature was reviewed including PDL modifications for improved efficacy, alternative laser devices for treatment-resistant PWSs, and the addition of agents to modulate the wound-healing response after laser irradiation.. Although PDL is the treatment of choice for PWSs, increased understanding of interactions between PWSs and PDL has led to improvements in therapeutic outcome in terms of lesion blanching.. Preliminary evidence of combination therapy using antiangiogenic agents after laser irradiation appears promising and could lead to the development of a new standard of care for PWSs.

Topics: Angiogenesis Inhibitors; Combined Modality Therapy; Cryotherapy; Humans; Infant; Laser Therapy; Lasers, Dye; Lasers, Solid-State; Low-Level Light Therapy; Photochemotherapy; Port-Wine Stain; Sirolimus; Wound Healing

Port Wine Stain (PWS) is a congenital capillary malformation. Although multiple treatments are required, the gold standard treatment for PWS is Pulsed Dye Laser (PDL). Given its anti-angiogenic effects, sirolimus can be considered as an adjuvant to PDL in PWS.. To evaluate the efficacy and safety of topical sirolimus (Rapamycin) 0.2% cream as adjuvant therapy for PDL for PWS.. In this randomized double-blind placebo-controlled trial, 15 patients with PWS were enrolled. Each lesion was divided into upper and lower parts, and each part was assigned randomly to receive PDL (4 sessions, 2 months apart) plus sirolimus vs PDL and placebo. The response was evaluated using colorimetry, investigator global assessment (IGA), and patient global assessment (PGA) every two months for eight continuous months.. According to the colorimetric analysis, medial and lateral sides of the treatment and placebo parts did not differ significantly (both P-value > .05). However, according to PGA and IGA, there was a significant difference in favor of sirolimus (P-values = .041 and .039, respectively). Itching and dryness (86.7%), contact dermatitis (20%) were the most common adverse effects in the sirolimus group, while none of them were observed in placebo.. Although the improvement was significant subjectively, topical sirolimus 0.2% as an adjuvant to PDL does not appear to improve PWS erythema using calorimetric assessment.

Topics: Humans; Immunosuppressive Agents; Laser Therapy; Lasers, Dye; Port-Wine Stain; Sirolimus; Treatment Outcome

Pulsed Dye Laser (PDL) is currently the gold standard treatment for port wine stains (PWS), although the degree of lesion blanching is variable and often unpredictable. This appears to be due to reformation and reperfusion of blood vessels. Rapamycin has shown potential as an antiangiogenic agent and may prevent the revascularization after PDL treatment. The objective of this study was to evaluate the efficacy of adjuvant use of (commercially available) topical rapamycin after PDL treatment in patients with PWS.. We conducted a prospective, intra-patient, randomized controlled trial. Four treatment areas of 1 cm. Fourteen patients completed the treatment protocol. The highest percentage clearance was achieved with PDL-only treatment (mean [SD] 16% [34]), but there were no statistically significant differences between treatments. The best photographic evaluation and highest patient satisfaction were also achieved with PDL-only treatment, but only the difference between PDL-only and rapamycin monotherapy was statistically significant. The treatment related pain was well tolerated. Application-site pruritus was a frequent occurring adverse event. Allergic contact dermatitis to rapamycin occurred in one patient. There were no serious adverse events.. Topical application of the commercially available solution of rapamycin (Rapamune

Topics: Academic Medical Centers; Administration, Topical; Adolescent; Adult; Biopsy, Needle; Esthetics; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lasers, Dye; Lasers, Solid-State; Low-Level Light Therapy; Male; Middle Aged; Netherlands; Port-Wine Stain; Prospective Studies; Sirolimus; Statistics, Nonparametric; Treatment Outcome; Young Adult

The regeneration or revascularization of blood vessels after pulsed dye laser (PDL) treatment is one of the causes of treatment failures of cutaneous capillary malformations (CM). Recently, topical administration of rapamycin was introduced as a possible adjunctive therapeutic option to minimize postlaser revascularization in facial CM.. We evaluated the effect of combined use of 1% topical rapamycin with PDL compared to PDL alone in cutaneous CM of trunk or extremities and tried to identify the optimal duration of topical rapamycin application.. Three adjacent areas of cutaneous CM that had never been treated before were selected in each patient and underwent the following regimens: (A) PDL + vehicle for 8 weeks post-PDL; (B) PDL + topical rapamycin for 1-week post-PDL and (C) PDL + topical rapamycin for 8 weeks post-PDL. Each test site was treated by PDL for two sessions with 8 weeks interval.. Only one of six patients showed clinical improvement with combined rapamycin treatment. Overall, there was no statistically significant difference in erythema and blanching rate among PDL alone and combined rapamycin regimens.. One percent topical rapamycin does not seem to be effective as a treatment modality for cutaneous CM of trunk or extremities.

Topics: Administration, Topical; Adult; Combined Modality Therapy; Erythema; Female; Humans; Immunosuppressive Agents; Lasers, Dye; Low-Level Light Therapy; Male; Middle Aged; Pilot Projects; Port-Wine Stain; Prospective Studies; Sirolimus; Treatment Outcome; Young Adult

Sturge-Weber syndrome (SWS) is characterized by port-wine stains (PWS) affecting the face, eyes, and central nervous system. Pulsed dye laser (PDL) is the standard treatment for PWS. Unfortunately, recurrence is frequent because of reformation and reperfusion of blood vessels.. We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS.. We conducted a phase II, randomized, double-blind, intraindividual placebo-controlled, clinical trial. We recruited 23 patients with SWS and facial PWS (12 women; median age 33 years, age range 17-65 years) from the University Clinic of Navarra, Spain. Four interventions were evaluated: placebo, PDL + placebo, rapamycin, and PDL + rapamycin. Clinical and histologic responses were evaluated using a chromatographic computerized system, spectrometry, and histologic analyses at 6, 12, and 18 weeks after the intervention.. PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis, and showed a statistically significant improvement compared with the other interventions. The treatment was generally well tolerated.. PDL was only applied to the lateral parts of the PWS area.. Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS.

Topics: Administration, Topical; Adolescent; Adult; Aged; Capillaries; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Lasers, Dye; Male; Middle Aged; Port-Wine Stain; Sirolimus; Sturge-Weber Syndrome; Vascular Malformations; Young Adult

Port-wine stains (PWS) represent a group of vascular malformations that are usually accompanied by psychological distress for affected patients, often reflected in high treatment demand. Although the pulsed-dye laser (PDL) was established as standard therapy for PWS more than a decade ago, therapeutic outcome may be unsatisfactory. One of the main drawbacks to successful PDL therapy is PWS revascularization shortly after laser exposure. Therefore, inhibition of revascularization should improve therapeutic outcome of PDL therapy. In this study, we first evaluated the effects of various light energies on normal cutaneous vessels over a period of 14 days, particularly the proliferation and stem cell marker expression of dermal endothelial cells, which were found to be highest 8 days following laser exposure. We found that PDL exposure induced dose-dependent damage of dermal vessels up to energy densities of 6 J/cm(2), above which no increase in PDL-induced effects were observed with the energies employed in this study. In dermal endothelial cells of PDL-exposed skin, we found strong expression of the proliferation marker Ki-67 as well as the stem cell marker nestin but not other stem cell markers such as CD133 and CD166. The influence of rapamycin (RPM), used as an adjuvant to PDL exposure, was also investigated. RPM administration reduced Ki-67 and nestin expression in dermal endothelial cells and increased PDL-induced destruction of dermal vessels, indicating that the use of RPM after PDL exposure may be an interesting new approach for prolonging and improving PWS laser therapeutic outcome.

Topics: AC133 Antigen; Administration, Topical; Antibiotics, Antineoplastic; Antigens, CD; Biopsy; Cell Adhesion Molecules, Neuronal; Cell Division; Combined Modality Therapy; Dose-Response Relationship, Radiation; Endothelial Cells; Fetal Proteins; Glycoproteins; Humans; Intermediate Filament Proteins; Ki-67 Antigen; Laser Therapy; Lasers, Dye; Nerve Tissue Proteins; Nestin; Peptides; Port-Wine Stain; Recurrence; Sirolimus; Skin; Stem Cells; Up-Regulation

Pulsed dye laser (PDL) is the first-line treatment for port-wine stain (PWS). However, only a small portion of the lesions could be completely cleared by PDL treatment, which might be related to the regeneration and revascularization of the vascular structures after laser irradiation. Recently, it is believed that the suppression of regeneration and revascularization of photocoagulated blood vessels can achieve a better therapeutic outcome. We use rabbit ear and SD rat as the animal models to investigate whether PDL-induced angiogenesis can be suppressed by topical metformin. Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.

Topics: Administration, Cutaneous; Animals; Lasers, Dye; Metformin; Models, Animal; Neovascularization, Pathologic; Port-Wine Stain; Rabbits; Rats; Rats, Sprague-Dawley; Sirolimus; Treatment Outcome

In the last few years, the use of oral sirolimus has shown promising results in the treatment of some complex vascular anomalies, and recently, it has been used in patients with Sturge-Weber syndrome (SWS). We present the case of an 11-year-old girl with the diagnosis of SWS and hemifacial overgrowth treated with oral sirolimus. Throughout the eight months of follow-up, improvement of the port-wine birthmark, intraocular pressure, and neurocognitive development was noted. The mTOR inhibitors may be useful in the treatment of some patients with SWS.

Topics: Child; Face; Facial Asymmetry; Female; Humans; Hyperplasia; Port-Wine Stain; Sirolimus; Sturge-Weber Syndrome

Although pulsed dye laser (PDL) is considered the gold standard treatment for port wine stains (PWS), post PDL revascularization is one of the main causes of incomplete regression and recurrence. Recently, topical sirolimus have been shown to improve treatment outcome probably through minimizing post-laser revascularization. We sought to evaluate the added value of the Tixel drug delivery system (DDS) to the PDL and topical rapamycin treatment for PWS. This case series includes three teenager patients with previously treated PWS with PDL. Upon enrollment, every stain was divided into A and B halves for treatment assignments to the following regimens: (A) PDL + DDS + rapamycin; (B) PDL + rapamycin. Subjects were instructed to apply rapamycin topically over the PWS twice daily for the entire treatment period. Assessment of the treatment and adverse reactions as well as photographs was performed at baseline and before every PDL treatment. There were clinically significant differences in blanching responses favoring PWS receiving PDL + DDS + rapamycin as compared to PDL + rapamycin alone. Transient hyperpigmentation was noted in one patient. Two patients developed mild transient irritation and dermatitis following the treatment on both halves. The use of drug delivery system combined with topical rapamycin has no remarkable adverse effects, improves the results of PDL treatment for port wine stains, and can reduce the total number of required PDL sessions.

Topics: Administration, Cutaneous; Adolescent; Child; Combined Modality Therapy; Drug Delivery Systems; Female; Humans; Lasers, Dye; Male; Port-Wine Stain; Retrospective Studies; Sirolimus; Treatment Outcome

A port wine stain (PWS) is a type of capillary vascular malformation composed of malformed, dilated blood vessels within the papillary and reticular dermis. Currently, pulsed dye laser (PDL) is considered the therapeutic gold standard, although greater than 90% of lesions may be refractory to treatment. Studies have shown that a delay in treatment results in a higher proportion of patients who develop hypertrophy and nodularity within lesions that become more resistant to therapy. Therapeutic resistance is multifactorial, but is believed to be largely due to revascularization after laser treatment. Oral sirolimus and topical imiquimod have shown promise as adjunctive therapies to minimize post-laser revascularization, but both have significant side effects. We wish to demonstrate the utility of adjunct topical sirolimus to reduce revascularization after PDL treatment.. This is a single patient case report of a 56-year-old male patient with an extensive PWS. After seeing initial improvement with PDL alone, he began to experience thickening and nodularity of his PWS necessitating surgical debulking. Since this procedure, topical sirolimus 0.5% ointment has been added to his treatment regimen as an adjunct to PDL. The patient is being treated with PDL (Vbeam Perfecta, Candela/Syneron, Wayland, MA) every 4-6 weeks at varied settings with the following laser parameters: fluence 9-11 J/cm(2), pulse duration 0.45-1.5 ms, focal spot size 7 mm, cooling 30/20. Sirolimus 0.5% ointment is applied to the area twice daily.. The patient showed significant improvement in color and texture of his PWS. Compared to the initial therapy of PDL alone, topical sirolimus ointment in conjunction with PDL demonstrated greater improvement and maintenance of therapeutic results with fewer overall laser treatments.. Topical sirolimus 0.5% ointment is a safe and effective adjunct to PDL in the treatment of PWS.

Topics: Administration, Cutaneous; Angiogenesis Inhibitors; Combined Modality Therapy; Humans; Lasers, Dye; Male; Middle Aged; Port-Wine Stain; Sirolimus

Topics: Administration, Cutaneous; Adult; Chemotherapy, Adjuvant; Dermatitis, Allergic Contact; Female; Humans; Immunosuppressive Agents; Laser Therapy; Port-Wine Stain; Sirolimus

Topics: Adult; Angiogenesis Inhibitors; Combined Modality Therapy; Humans; Lasers, Dye; Male; Port-Wine Stain; Sirolimus; Treatment Outcome

Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.. For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.. In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.. With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.

Topics: Administration, Cutaneous; Animals; Blood Vessels; Combined Modality Therapy; Cricetinae; Disease Models, Animal; Laser Therapy; Lasers, Dye; Male; Port-Wine Stain; Random Allocation; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Combined Modality Therapy; Humans; Immunosuppressive Agents; Laser Therapy; Photomicrography; Port-Wine Stain; Sirolimus; Skin; Treatment Outcome; Wound Healing