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The Index for Facial Angiofibromas (IFA), a novel scoring system for angiofibromas, has been validated in patients with tuberous sclerosis complex (TSC). The objective of this analysis was to further validate the IFA using data from a clinical trial of topical sirolimus in patients with TSC. This was an analysis of photographs from a Phase III trial conducted in Japan (NCT02635789). Patients (n = 62) were randomized 1:1 to receive sirolimus or placebo gel for 12 weeks. Changes in angiofibromas were independently assessed using the primary composite endpoint, the Facial Angiofibroma Severity Index (FASI), and the IFA. Thresholds for a clinically meaningful change in IFA score were evaluated using receiver operating characteristic (ROC) analysis. The IFA scores had good-to-excellent inter-assessor reliability, very high intra-assessor reliability, and could be used to evaluate the distribution of disease severity at baseline. High correlations were observed between the categorized change from baseline in IFA scores and the primary composite endpoint (Kendall's coefficient of concordance, W = 0.8655, p < 0.0001), and between the change from baseline in IFA and FASI scores (Kendall's coefficient of concordance, W = 0.745, p < 0.0001). By ROC analysis, an optimal IFA cut-off point of 1.667 was determined to distinguish patients with markedly improved or improved angiofibromas from those with slightly improved or unchanged angiofibromas (area under the curve 0.937) as determined by the primary composite endpoint. The IFA score is potentially clinically useful because of its high validity and reliability. A decrease in score from baseline of ≥1.667 may be considered clinically meaningful., (© 2024 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients., Objective: To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC., Methods: Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented., Results: This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent., Study Limitations: Observational cohort design without a control group for comparison., Conclusions: Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

A 98-year-old woman presented with histologically confirmed locally advanced basal cell carcinoma of the face. A multidisciplinary approach excluded surgery because of the site near sensitive organs, extension, age, and comorbidities. Patient and caregivers declined radiotherapy considering the necessity of multiple hospital appointments. The patient was then placed on therapy with sonidegib, an oral inhibitor of the Hedgehog signaling pathway. There was a very rapid clinical response after only 28 days of treatment. The basal cell carcinoma improved progressively, with no adverse events reported. This case illustrates the efficacy and safety of this treatment in an advanced age patient. This treatment had a remarkably positive impact on quality of life, including that of the caregivers.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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., (© 2022 European Academy of Dermatology and Venereology.)

Competing Interests: Conflicts of interest None disclosed.

Facial angiofibromas are one of the dermatological hallmarks of tuberous sclerosis complex. Facial angiofibromas often lead to disfigurement and cosmetic concerns, which has a serious negative effect on the quality of life of the patients. There are no guidelines or consensus on the management of facial angiofibromas up to now. We report a patient with extensive facial angiofibromas treated with the combination of photodynamic therapy and ultrapulse carbon dioxide laser, achieving satisfying results. We suggest this might be a promising therapeutic option for facial angiofibromas in tuberous sclerosis complex., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Facial angiofibromas may be present since early childhood in individuals with tuberous sclerosis complex (TSC), causing substantial cosmetic disfigurement. Current therapies are partially effective, but they are uncomfortable, produce scarring, and are especially expensive., Objective: The aim of the present study was to evaluate the efficacy of oral everolimus for TSC-associated angiofibromas., Methods: This retrospective study included TSC patients being treated with oral everolimus for subependymal giant cell astrocytomas (SEGAs) and angiomyolipomas (AMLs). We recorded the changes in facial angiofibromas. Changes in the Angiofibroma Grading Scale (AGS) indicators were recorded according to erythema, average lesion size, lesion density, and percent involvement on the forehead, nose, cheeks, and chin. The scores were recorded before and after the administration of oral everolimus., Results: Twenty-one patients being treated with oral everolimus were enrolled in this study. The mean age was 20.5 years (range 11-44 years, 4 males, and 17 females). The mean dose of oral everolimus was 3.6 mg/day. Clinically meaningful and statistically significant improvement was observed in erythema (p = 0.001), average lesion size (p < 0.001), lesion density (p < 0.001), and percent involvement (p < 0.001). Changes in the AGS findings were statistically significant on the forehead (p = 0.001), nose (p < 0.001) cheeks (p < 0.001), and chin (p = 0.004)., Conclusion: Everolimus shows evident improvement and is approved for TSC-associated SEGAs and AMLs. The current study demonstrated the efficacy of oral everolimus in reducing facial angiofibromas, showing the parallel benefits of the treatment protocol for TSC., (© 2020 S. Karger AG, Basel.)

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder that causes the formation of hamartomatous tumors such as facial angiofibromas (FAs). We present a combination of surgical debulking via shave biopsy, curettage, and electrocautery followed by application of sirolimus ointment 1% to the nose to treat FAs in the setting of TSC. This novel approach achieved an optimal therapeutic response in our patient with minimal recurrence of FAs after 1 year of follow-up.

Background: Infantile hemangiomas are the most common vascular tumors in childhood. Although spontaneous regression is common; several infantile hemangioma patients need treatment due to possible morbidities. The aim of this study was to investigate the medical methods used in the treatment of infantile hemangiomas and to evaluate the factors affecting treatment response., Methods: Clinical and demographic characteristics, risk factors, treatment indications, modalities, duration, and responses of 100 patients between January 2007 and January 2017 were evaluated., Results: The most common form of hemangiomas was superficial lesions. Sixty three per cent of the patients were female. Ulceration and hemorrhage were found in 26% of the cases and ocular problems were detected in 3% of the cases. Among the indications for treatment were cosmetic reasons with 56%, ulcer and bleeding with 25% and risk of vision problems with 13%. Propranolol with/without steroid was used as first line treatment and response rates were: 84 patients with more than 50% response, 9 patients with less than 50% response and 7 patients with treatment refractory. The most important factor affecting the treatment response was age at the beginning of the treatment. Duration of treatment, presence of ulceration, location, and size of hemangioma were also found to have significant effects on responses., Conclusions: This study demonstrated the importance of the kind and initiation time of infantile hemangioma treatment. A strong positive effect can be reached by starting treatment before the end of the proliferation phase. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5009.

Background: The efficacy of topical rapamycin is well documented for tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs). Calcitriol has been shown to lessen skin fibrosis and may be therapeutically beneficial to FAs., Objectives: To evaluate whether topical rapamycin-calcitriol combination is an effective and safe treatment for TSC-related FAs., Methods: Fifty-two patients with TSC with FAs were enrolled in this prospective study including three 12-week periods. In period 1, either topical rapamycin 0·1% or calcitriol 0·0003% single-agent therapy vs. their combination was applied in a double-blind, left-right-randomized, split-face comparison. The primary outcome was the reduction of modified Facial Angiofibroma Severity Index (mFASI) at week 12. In period 2, the patients were reassigned to use on both cheeks the ointment that resulted in the better primary outcome in period 1. The treatment was discontinued in period 3 (week 25-36) and a follow-up mFASI was scored to evaluate the degree of recurrence., Results: The mean changes in mFASI at week 12 compared with baseline were -0·92, -0·44 and -1·09 for rapamycin (P ≤ 0·001), calcitriol (P = 0·039) and rapamycin-calcitriol combination (P ≤ 0·001), respectively. Although rapamycin-calcitriol combination and rapamycin had similar statistically significant decreases of mFASI at week 12, rapamycin-calcitriol combination resulted in faster improvement in erythema, greater reduction of papule elevation and longer durability after discontinuing treatment than rapamycin alone. The treatments were well tolerated., Conclusions: This randomized clinical trial demonstrates that topical rapamycin-calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. What is already known about this topic? Facial angiofibromas (FAs) cause substantial psychological distress in individuals with tuberous sclerosis complex (TSC), but invasive procedural treatments are not applicable to all patients. Topical rapamycin has been demonstrated as an effective and safe treatment regimen for TSC-related FAs. What does this study add? Compared with baseline (day 0), both topical rapamycin 0·1% and rapamycin 0·1%-calcitriol 0·0003% combination ointment achieved statistically significant reductions in modified Facial Angiofibroma Severity Index at week 12. Compared with rapamycin alone, extended use of the rapamycin-calcitriol combination regimen until week 24 showed more effectiveness in decreasing papule elevation and could maintain a longer therapeutic effect after treatment discontinuation. Linked Comment: Lee. Br J Dermatol 2020; 183:604-606., (© 2020 British Association of Dermatologists.)

Background: Tuberous 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., Methods: We 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., Results: The 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., Conclusions: This 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. Sirolimus gel treatment improves the health-related QOL in patients with FA associated with TSC.

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Nadolol is a β-adrenergic antagonist that has been shown to be efficacious in the treatment of infantile hemangioma. It has been suggested that this drug may have fewer side effects compared with the gold standard therapy, propranolol, because it does not exhibit membrane-stabilizing effects and has little ability to cross the blood-brain barrier. However, the pharmacokinetics and safety of nadolol in infants are not well understood, potentially making this therapy dangerous. β-adrenergic antagonist toxicity causes bradycardia, hypotension, hypoglycemia, and even death. We report a case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity. Pharmacokinetics studies show a large fraction of oral nadolol either remains in the feces unchanged or is excreted into feces via the biliary system, allowing continued absorption over time in infants who stool infrequently. Propranolol may be a safer therapy overall. Not only does it have a shorter half-life, but propranolol is hepatically metabolized and renally eliminated, allowing for less drug accumulation in healthy infants with variable stooling patterns. We suggest that if nadolol is selected for therapy, pediatricians should instruct parents to monitor their infants' bowel movements closely and encourage early intervention in the event of decreased stooling. This intervention may greatly improve the safety of nadolol in this vulnerable patient population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

The facial angiofbromas due to tuberous sclerosis complex produced significant social and emotional distress for affected individuals, but there is no specific therapeutic strategy up to now. Herein, we report a case of facial angiofibromas successfully treated by 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) with no recurrence for 6 years, thus providing a promising therapeutic option., (Copyright © 2019 Elsevier B.V. All rights reserved.)

PHACE syndrome describes the association of large segmental haemangioma with extracutaneous features (posterior fossa anomalies, arterial, cardiac, eye and endocrine anomalies). We report a case of segmental facial infantile haemangioma with PHACE syndrome treated successfully with oral propranolol without neurological sequelae.

A 68-year-old woman was referred to the unit of dermatology for a large basal cell carcinoma on the chin. She was treated with imiquimod cream 5%, and 4 weeks after she developed isolated and grouped tense serum-filled vesicles and bullae on lips, nose, scalp, ankles and lumbar area, and then expanded to the whole body. Histological examination was consistent with a subepidermal bullous dermatosis. Moreover, direct immunofluorescence showed linear deposition of IgA at the basement membrane zone supporting the diagnosis of linear IgA bullous dermatosis (LABD). Dapsone 50 mg/day was administered, and the lesions gradually improved within some weeks, and no new lesions appeared. The temporal relationship between the application of the drug and the development of the disease indicates a role of this topical agent in triggering LABD., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare haematological malignancy defined by concurrent expression of CD4, CD56, BCL-2 and CD123. The disease has a very poor prognosis and there are no well-established treatment guidelines. We describe a case of BPDCN in a 65-year-old female patient with myeloproliferative disorder (essential thrombocythemia) and chronic lymphocytic leukaemia. She presented with rapidly progressive facial and scalp lesions. Skin biopsy confirmed BPDCN and the imaging revealed widespread disease. Patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) and intrathecal methotrexate. Due to progression on initial treatment, she was treated with decitabine and venetoclax (BCL-2 inhibitor). However, patient continued to deteriorate and died after 4 months from initial diagnosis. We emphasise on the clinical features, emerging treatment modalities and prognosis of BPDCN., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Alveolar soft part sarcoma (ASPS) is an extremely rare neoplasm that tends to occur in the lower limbs of children and adolescents. Metastatic breast tumors constitute 0.5-2.0% of all malignant mammary neoplasms, and cases of ASPS with mammary metastases are very rare., Case Presentation: Three years ago, an 11-year-old girl presented to the hospital with pain in the right jaw after becoming aware of a mass in the right cheek. After detailed examination, the patient was diagnosed with ASPS with the primary tumor in the right cheek and multiple lung metastases, and chemotherapeutic treatment was initiated. One year later, accumulation of fluorodeoxyglucose (FDG) was observed in the right front of the skull (standardized uptake value (SUV)-max 2.8) and left breast (SUV-max 2.4) using FDG-positron emission tomography (PET) / computed tomography (CT). Ultrasonography revealed the mammary tumor as a hypoechoic, internally heterogeneous mass measuring 22.4 × 16.2 × 21.1 mm with a rich blood supply. Using pathological findings of core-needle biopsy, we diagnosed it as ASPS. Based on the above information, we made a diagnosis of ASPS with left mammary and cranial metastases. Due to chemoresistance, surgical excision was selected as the mode of treatment; resection of the metastatic cranial bone was performed first, and partial mastectomy of the left breast was performed in two stages. Postoperative conditions were good, and we are currently performing regular follow-ups (visual palpation every 3 months and semi-annual mammary gland ultrasonography)., Conclusions: We have reported an extremely rare case of ASPS with mammary metastasis with some reference-based discussion. In our case, disease control was obtained by a combination of drug therapy and surgical treatment.

Facial angiofibroma is the characteristic symptom and also a major diagnostic criterion for Bourneville-Pringle disease. The centrofacially localized hamartomatous tumours start to appear in early childhood, and progress over time. Facial angiofibromas represent a significant cosmetological problem for the patients and a therapeutic challenge for the physician. Beside the traditional invasive treating methods, topical sirolimus is a new, promising and well-tolerated treatment modality. Several studies and case reports have been published on this new therapeutic approach, but recommendation for the optimal sirolimus concentration still does not exist. We report here two cases when children were successfully treated with topical sirolimus. Orv Hetil. 2019; 160(13): 516-520.

The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of this transmissible cancer, we combined pharmacological screens with an integrated systems-biology characterization. Sensitivity to inhibitors of ERBB tyrosine kinases correlated with their overexpression. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to the evolutionary conserved oncogenic STAT3. ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB or STAT3 prevented tumor growth in xenograft models and restored MHC class I expression. This link between the hyperactive ERBB-STAT3 axis and major histocompatibility complex class I-mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and puts forward a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD. VIDEO ABSTRACT., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infantile hemangioma (IH) is a common benign vascular tumor in children. In most cases, diagnosis is based entirely on clinical examination. When the diagnosis is uncertain, the first-line complementary examination is Doppler ultrasound. We report 4 cases of atypical infantile hemangiomas with delayed diagnosis and non-contributory imaging., Patients and Methods: One child had congenital purple papules and nodules on the back of the foot, the second had inaugural ulceration of the buttocks, and the last two presented telangiectasia, either isolated or on an erythematous macula. In two cases, ultrasound showed no vascular lesions, and in the other two cases, the absence of hyperemia did not allow a diagnosis of IH to be made. For one patient, diagnosis was made on the basis of cutaneous biopsy, and for the other three, on the basis of clinical course., Discussion: We report 4 rare forms of infantile hemangioma resulting in initial diagnostic error. The atypical nature of some IHs may direct the clinician and the radiologist toward other diagnoses that in some cases have no vascular contingent. It is important for the dermatologist to be aware of these rare forms of IH in order to reduce the time to diagnosis and allow early initiation of appropriate management., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Multiple eccrine hidrocystomas (MEH) are benign cystic lesions of the sweat gland ducts. They are characterized by translucent, skin-colored or bluish dome-shaped papules on the face, causing cosmetic concern. Recently, botulinum toxin-A, because of its antiperspirant properties, has been used to treat facial MEH. However, there are only some case reports in the literature., Objective: Here, we conducted a prospective study to assess the efficacy and safety of intralesional injection of botulinum toxin-A (Dysport) for the treatment of MEH., Material and Methods: Twenty patients (3 men and 17 women), aged from 31 to 75 years old, participated in this study. A 300 unit vial of botulinum toxin-A (Dysport, Ipsenn Biopharm, United Kingdom) was diluted with 4 ml of saline solution without preservative to achieve a concentration of 7.5U/.1 ml. Up to 1.5 unit of botulinum toxin was injected intradermally at the base of each lesion to raise a visible wheal. The patients were evaluated 7 days later, and any clinical changes or adverse effects were recorded., Results: In all patients, more than 75% of eccrine hidrocystoma lesions resolved without any scaring. The result sustained for 2-5 months. In two patients mild smile asymmetry and in one patient lagophthalmos were noted approximately 5-7 days after injection that gradually resolved in 3 weeks., Conclusion: Intralesional botulinum toxin-A for treatment of multiple hidrocystomas is a simple and well-tolerated procedure. It is accompanied by excellent results, a good postoperative course, and no risk of scarring. It can be considered in patients who did not respond to other treatment or even as the first line therapy.

Background: Infantile hemangiomas (IH) are the most common benign vascular tumors in childhood. Approximately 10% to 15% of these tumors require drug or surgical intervention. There are many options for IH treatment, of which propranolol is currently considered the gold standard. This study aims to compare the therapeutic results of 2 distinct drugs (ethanolamine oleate and propranolol), in order to increase the available therapeutic arsenal for the treatment of IH, thereby benefiting a larger group of patients., Methods: A retrospective observational study was conducted to assess 16 patients with facial IH, allocated into 2 groups (n = 8). All patients met the same inclusion and exclusion criteria. The resulting evolution assessment was based on photographic documentation produced in a professional setting, and was performed before, during, and after treatment. Two measurement scales, photographic-based assessment of infantile hemangioma characteristics, and outcomes were used for comparison between the 2 therapeutic methods., Results: Both assessment methods did not present any significant statistical difference (P > 0.05) at 1 year of follow-up., Conclusion: Both therapeutic modalities are able to offer the patient similar and satisfactory final esthetic results.

Importance: Facial angiofibromas occur in approximately 75% of individuals with tuberous sclerosis complex (TSC), causing substantial morbidity and disfigurement. Current therapies are partially effective, uncomfortable, produce scarring, and need repeating to treat recurrence., Objective: To evaluate the efficacy and safety of topical rapamycin for TSC-related facial angiofibromas., Design, Setting, and Participants: This prospective, multicenter, randomized, double-blind, vehicle-controlled trial with 6 monthly clinic visits enrolled 179 patients with TSC-related facial angiofibromas not treated within 6 months from May 2012 to March 2014 in 9 clinical sites in the United States and 1 in Australia., Interventions: Patients were randomized (1:1:1) to topical formulation containing 0.3 g per 30 g (1%) rapamycin, 0.03 g per 30 g (0.1%) rapamycin, or vehicle alone. Participants applied 1.0 mL to designated areas daily at bedtime., Main Outcomes and Measures: Angiofibroma Grading Scale (AGS) change from baseline scored from photographs by independent masked dermatologists. Safety analyses included adverse events (AEs) and serum rapamycin levels., Results: All 179 patients randomized (99 [55.3%] female) comprised the primary analysis population (59 in the 1% rapamycin group, 63 in the 0.1% rapamycin group, and 57 in the vehicle-only group). The mean age was 20.5 years (range 3-61 years). Clinically meaningful and statistically significant improvement in facial angiofibromas was observed for both 1% and 0.1% rapamycin relative to the vehicle-only control group, and for 1% vs 0.1% rapamycin, with most of the improvement realized within the first month. At 6 months, AGS mean improvement for 1% rapamycin was 16.7 points compared with 11.0 for 0.1% rapamycin and 2.1 points for vehicle only (P < .001 for 1% and 0.1% vs vehicle only). Compared with baseline, end-of-treatment photos were rated "better" for 81.8% of patients in the 1% rapamycin group, compared with 65.5% for those in the 0.1% rapamycin group and 25.5% for those in the vehicle-only group (P < .001, all 3 pairwise comparisons). Topical rapamycin was generally well-tolerated, with no measurable systemic absorption. Apparent drug-related adverse effects were limited to 10% or less incidence of application site discomfort and/or pain, pruritus, erythema, and irritation. Nearly all AEs were mild, with no drug-related moderate, severe, or serious events., Conclusions and Relevance: Topical rapamycin appears effective and safe for treatment of TSC-related facial angiofibromas. In this trial, the preferred dose was 1% once daily. Future studies are needed to evaluate prophylactic, early, and long-term use of topical rapamycin, durability of response, and combination therapy with oral mammalian target of rapamycin (mTOR) inhibitors., Trial Registration: ClinicalTrials.gov Identifier: NCT01526356.

Importance: Most patients with tuberous sclerosis complex (TSC), an autosomal-dominant disorder that is caused by the constitutive activation of mammalian target of rapamycin, experience disfigurement caused by skin lesions involving facial angiofibromas. Many have been left untreated because of a lack of therapeutic options that are less invasive than surgery or laser treatment., Objective: To confirm the efficacy and safety of sirolimus gel, 0.2%, for treatment of patients with angiofibromas and/or skin lesions., Design, Setting, and Patients: Multicenter, randomized clinical trial at 9 centers in Japan from December 2015 to October 2016 including 62 children and adults with TSC., Interventions: Patients who developed angiofibromas were randomly assigned, in a 1:1 ratio, to receive sirolimus gel, 0.2%, or placebo, each applied topically twice daily for 12 weeks., Main Outcomes and Measures: The primary end point was composite improvement in the size and color of angiofibromas in photographs at week 12 of treatment. It was assessed by an independent review committee comprising 3 blinded dermatologists who categorized patient results into the following 6 categories: "markedly improved," "improved," "slightly improved," "unchanged," "slightly aggravated," and "aggravated.", Results: Sixty-two patients (27 pediatric and 35 adult; 34 [55%] female; mean [SD] age, 22.5 [11.9] years) were enrolled and randomly assigned to receive sirolimus gel, 0.2% (30 patients), or placebo (32 patients). The response rates of angiofibromas at weeks 4, 8, and 12 of treatment were 0 each in the placebo group in contrast to 20% (95% CI, 8%-39%; P = .01), 43% (95% CI, 26%-63%; P < .001), and 60% (95% CI, 41%-77%; P < .001), respectively, in the sirolimus group. None of the 31 assessable patients in the placebo group were rated improved or better, and 26 of them (84%) were rated unchanged. In contrast, 5 (17%) and 13 (43%) patients in the sirolimus group were rated markedly improved and improved, respectively. Adverse events were mild to moderate and were observed in 27 (90%) and 22 (69%) patients in the sirolimus and placebo groups, respectively; however, none of the trial participants discontinued treatment. Acute pancreatitis developed as a serious adverse event in 1 patient in the sirolimus group, and the patient recovered soon after hospitalization without discontinuing treatment., Conclusions and Relevance: Sirolimus gel, 0.2%, demonstrated a significant clinical benefit for patients with TSC involving angiofibromas, thus providing a promising therapeutic modality., Trial Registration: ClinicalTrials.gov Identifier: NCT02635789.

Infantile hemangioma can be linked to other organ malformations. In 1996, PHACE syndrome was first defined as the association of large and segmental infantile hemangioma, usually on the face, head, or cervical region, with malformations of the posterior fossa of the brain, arterial anomalies of the central nervous system, coarctation of the aorta, cardiac defects, and ocular abnormalities. Over 300 cases of PHACE syndrome have been reported, and it is cconsidered one of the most common neurocutaneous vascular disorders in childhood. Knowledge of the features and locations of lesions that imply a greater risk of systemic involvement is crucial for the diagnosis and proper management of PHACE syndrome patients. This review highlights the diagnostic criteria for PHACE syndrome, the imaging workup for extracutaneous involvement, the treatment of infantile hemangioma, and the importance of a multidisciplinary approach in the management of these patients.

The Tasmanian devil (Sarcophilus harrisii), the largest extant carnivorous marsupial and endemic to Tasmania, is at the verge of extinction due to the emergence of a transmissible cancer known as devil facial tumour disease (DFTD). DFTD has spread over the distribution range of the species and has been responsible for a severe decline in the global devil population. To protect the Tasmanian devil from extinction in the wild, our group has focused on the development of a prophylactic vaccine. Although this work has shown that vaccine preparations using whole DFTD tumour cells supplemented with adjuvants can induce anti-DFTD immune responses, alternative strategies that induce stronger and more specific immune responses are required. In humans, heat shock proteins (HSPs) derived from tumour cells have been used instead of whole-tumour cell preparations as a source of antigens for cancer immunotherapy. As HSPs have not been studied in the Tasmanian devil, this study presents the first characterisation of HSPs in this marsupial and evaluates the suitability of these proteins as antigenic components for the enhancement of a DFTD vaccine. We show that tissues and cancer cells from the Tasmanian devil express constitutive and inducible HSP. Additionally, this study suggests that HSP derived from DFTD cancer cells are immunogenic supporting the future development of a HSP-based vaccine against DFTD.

Background: Recent reports have suggested that the topical formulation of sirolimus is effective in treating facial angiofibromas in tuberous sclerosis complex (TSC). Here, we determined the safety and efficacy of 0.2% topical sirolimus for the treatment of facial angiofibroma and compared its effects based on age., Method: This was a retrospective study which involved 36 TSC patients with facial angiofibromas who were treated with 0.2% sirolimus ointment. Its effect was evaluated using the Facial Angiofibroma Severity Index (FASI). In order to observe its comparative effect based on patient age, a subgroup analysis was performed, between the adult group (> 18 years old) and the pediatric group (≤18 years old)., Results: The total FASI as well as its subcategories (erythema, size, and extent) showed statistically significant improvements after the topical treatment with 0.2% sirolimus ointment (FASI before treatment: 7.2 ± 1.1, FASI after treatment: 4.4± 1.4, p < 0.001). Among the subcategories of FASI, the erythema was most significantly reduced with the fastest response to the treatment. In a subgroup analysis, the pediatric group showed significantly greater improvements in FASI (improvement of FASI in the pediatric group = 49.7 ± 12.2%, adult group = 27.9 ± 15.6%, p < 0.001). The serial improvement analysis also showed that the pediatric group achieved a consistently greater improvement in FASI at all visits. Its 1-year application in 3 patients demonstrated a continuous maintenance effect. No significant adverse effects were observed., Conclusion: 0.2% sirolimus ointment is safe and effective for facial angiofibromas. Considering its higher efficacy in younger patients, an early initiation of the treatment is recommended., (© 2018 S. Karger AG, Basel.)

A 14-month-old Nepalese infant had developed a rapidly growing facial tumor originating from a dark spot on her upper eyelid. A cavernous hemangioma was suspected and treated with high doses of propranolol and prednisolone. Remission was dramatic. Histology confirmed alveolar rhabdomyosarcoma. Chemotherapy was planned but not carried out due to complicated logistics. The girl died at the age of 3. We present this case for discussion as to whether propranolol and prednisolone might be effective in rapidly growing rhabdomyosarcomas.

Pain and anxiety are common symptoms in head and neck cancer patients. The anticonvulsant pregabalin has therapeutic indication for the treatment of pain and anxiety, and may represent a useful drug for both conditions. Thus, the aim of this study was to investigate the relationship between pain and anxiety in rats with facial carcinoma, as the influence of pregabalin treatment in both aspects. Facial carcinoma was induced by subcutaneous inoculation of Walker-256 tumor cells in the vibrissa pad of Wistar rats. On day 6 after inoculation spontaneous facial grooming and conditioned place preference were assessed as non-evoked pain measurements and facial mechanical hyperalgesia were assessed 3 and 6 days after tumor cells inoculation. Moreover, anxiety-like behavior was evaluated on the elevated plus maze and light-dark transition tests at the same time points. The effect of pregabalin treatment (30 mg/kg, p.o.) was evaluated in all tests. Our results demonstrated that pregabalin treatment reduced the spontaneous facial grooming and induced conditioned place preference 6 days post tumor inoculation. Tumor-bearing rats developed mechanical hyperalgesia starting 3 days post tumor induction, which was also significant on day 6, but the anxiety-like behavior was detected only in tumor-bearing rats that developed mechanical hyperalgesia and only six days after tumor cells inoculation. Both, the mechanical hyperalgesia and the anxiety-like behavior related to the tumor were significantly reduced by pregabalin treatment on day 6. Pregabalin treatment resulted in antinociceptive and anxiolytic-like effects on facial tumor-bearing rats and may represent a promising therapeutic option for cancer patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)