RESUMO
ABSTRACT: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 ( Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.
Assuntos
Carcinoma Basocelular , Inibidores de MTOR , Transdução de Sinais , Sirolimo , Neoplasias Cutâneas , Serina-Treonina Quinases TOR , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Carcinoma Basocelular/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Masculino , Feminino , Transdução de Sinais/efeitos dos fármacos , Pessoa de Meia-Idade , Inibidores de MTOR/farmacologia , Inibidores de MTOR/uso terapêutico , Adulto , Idoso , Síndrome do Nevo Basocelular/tratamento farmacológico , Síndrome do Nevo Basocelular/patologia , Síndrome do Nevo Basocelular/metabolismo , Imuno-Histoquímica , Antibióticos Antineoplásicos , Criança , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Uso Off-Label , Resultado do Tratamento , Proteínas de Ciclo Celular , Proteínas Adaptadoras de Transdução de SinalRESUMO
BACKGROUND: In two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics. AIM: This analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes. METHODS: Participants ≥ 9 years with genetically confirmed XLRI or ARCI-LI and ≥ 2 (of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%/TMB-001 0.1%/vehicle, twice daily for 12 weeks. The proportion of participants with ≥ 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored. RESULTS: Among enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4â years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of ≥ 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions. CONCLUSION: Regardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and ≥ 2-grade IGA improvement vs. vehicle.
Assuntos
Eritrodermia Ictiosiforme Congênita , Ictiose Lamelar , Ictiose Ligada ao Cromossomo X , Ictiose , Humanos , Adulto , Ictiose Lamelar/tratamento farmacológico , Ictiose Lamelar/genética , Isotretinoína/uso terapêutico , Imunoglobulina ARESUMO
BACKGROUND: Emollients and keratolytics are frequently used to manage symptoms of congenital ichthyosis (CI). Systemic retinoid treatment is complicated by teratogenicity and dose-limiting adverse effects. OBJECTIVES: This analysis from the randomized Phase IIb CONTROL study investigated the characteristics of participants who responded to treatment with TMB-001, a novel topical isotretinoin ointment formulation. METHODS: Participants ≥ 9â years of age with genetically confirmed CI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%, TMB-001 0.1% or vehicle, twice daily for 12 weeks. Efficacy endpoints included the proportion of participants with ≥ 50% reduction in VIIS-scaling (VIIS-50) compared with baseline and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score compared with baseline. Changes in body surface area (BSA) involvement, Dermatology Life Quality Index (DLQI) scores and Itch-Numeric Rating Scale (I-NRS) scores were assessed. RESULTS: Among the 33 participants (11 randomized to TMB-001 0.05%, 10 to TMB-001 0.1% and 12 to vehicle), median age was 29â years (range 9-80), and most were male (64%) and White (79%). Baseline demographics were generally similar among participants who did or did not achieve TMB-001 treatment success. Participants who had lower mean BSA involvement and higher DLQI and I-NRS scores at baseline were more likely to achieve VIIS-50. Similarly, higher baseline DLQI and I-NRS scores were associated with IGA response; BSA involvement was similar for IGA responders vs. nonresponders. CONCLUSIONS: Higher DLQI and I-NRS scores at baseline were associated with participants achieving treatment success by VIIS-50 and IGA response. Lower BSA involvement was associated with VIIS-50 success.
Assuntos
Ictiose Lamelar , Isotretinoína , Humanos , Masculino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Recém-Nascido , Feminino , Isotretinoína/efeitos adversos , Ictiose Lamelar/tratamento farmacológico , Emolientes , Resultado do Tratamento , Prurido , Imunoglobulina A , Índice de Gravidade de Doença , Método Duplo-CegoRESUMO
BACKGROUND: In epidermolysis bullosa simplex (EBS), epithelial structural fragility results in blisters and erosions. Diacerein 1% ointment has been shown to reduce this blistering. OBJECTIVE: To evaluate the efficacy and safety of diacerein 1% ointment in the treatment of EBS. METHODS: A double-blind study of 54 patients with EBS were randomized to diacerein 1% or vehicle ointment once daily. The primary endpoint ( ≥60% reduction in body surface area of EBS) and the key secondary endpoint ( ≥2-point reduction in the Investigator’s Global Assessment) were evaluated at 8 weeks. RESULTS: There was no difference in the proportion of patients achieving either key efficacy endpoint between the diacerein 1% and vehicle groups (P>0.05). No difference in treatment emergent adverse events were noted between the groups. In post hoc analysis stratified by EBS subtypes, an IGA score of 0 or 1 was reported in 6 of 13 patients with severe EBS in the diacerein group (46.2%), compared with 2 of 13 patients with severe EBS in the vehicle group (15.4%); (relative risk= 3.08, 95% CI = 0.71, 13.4). CONCLUSIONS: Although there was no significant difference in outcomes between the groups, further study may elucidate the effects of diacerein on EBS lesions, especially in patients with severe EBS. Teng J, Paller AS, Bruckner AL, et al. Diacerein 1% ointment for the treatment of epidermolysis bullosa simplex: a randomized, controlled trial. J Drugs Dermatol. 2023;22(6):599-604. doi:10.36849/JDD.7108.
Assuntos
Epidermólise Bolhosa Simples , Humanos , Epidermólise Bolhosa Simples/diagnóstico , Epidermólise Bolhosa Simples/tratamento farmacológico , Epidermólise Bolhosa Simples/patologia , Pomadas , Antraquinonas/efeitos adversos , Método Duplo-Cego , ExcipientesRESUMO
Chanarin-Dorfman syndrome (CDS) is a rare, autosomal recessive disorder of impaired triacylglycerol catabolism leading to cytoplasmic deposition of triglycerides in various cell types. We describe the case of an 8-month-old boy with cataracts, strabismus, motor delays, and an ichthyosiform rash since birth. Genetic testing revealed a pathogenic variant of the ABHD5 gene, suggestive of CDS, and further workup demonstrated hepatic steatosis and myopathy. His ichthyosis improved with initiation of a diet low in very long-chain fatty acids and medium-chain fatty acid supplementation.
Assuntos
Catarata , Eritrodermia Ictiosiforme Congênita , Ictiose Lamelar , Ictiose , Erros Inatos do Metabolismo Lipídico , Doenças Musculares , Masculino , Humanos , Lactente , Eritrodermia Ictiosiforme Congênita/diagnóstico , Eritrodermia Ictiosiforme Congênita/genética , Ictiose Lamelar/diagnóstico , Ictiose Lamelar/genética , Ictiose/diagnóstico , Ictiose/genética , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/patologia , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/patologia , Catarata/diagnóstico , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genéticaRESUMO
Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of (1) an intact epidermal barrier to prevent epicutaneous antigen presentation, (2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and (3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.
Assuntos
Dermatite Atópica , Hipersensibilidade Alimentar , Dermatite Atópica/etiologia , Dermatite Atópica/prevenção & controle , Humanos , Lactente , MucosaRESUMO
ALK rearrangements define a histopathologically distinctive yet diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of gene partners, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13-year-old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next-generation RNA sequencing revealed an in-frame EHBP1-ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5' ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK-rearranged melanocytic tumors.
Assuntos
Quinase do Linfoma Anaplásico/metabolismo , Proteínas de Transporte/metabolismo , Nevo de Células Epitelioides e Fusiformes , Nevo Pigmentado , Neoplasias Cutâneas , Adolescente , Quinase do Linfoma Anaplásico/genética , Feminino , Fusão Gênica , Humanos , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population. METHODS: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes. RESULTS: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites. CONCLUSIONS: T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma.
Assuntos
Clonagem Molecular , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T/genética , Pitiríase Liquenoide/genética , Adolescente , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MasculinoRESUMO
Biallelic mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6, or PMS2 result in one of the most aggressive genetic cancer conditions, constitutional mismatch repair syndrome (CMMRD). We present a case of a 10-year-old boy with biallelic MSH6 mutation and systemic lupus erythematosus with eruptive melanocytic nevi after receiving chemotherapy for mediastinal T-cell lymphoblastic lymphoma.
Assuntos
Neoplasias Encefálicas , Síndromes Neoplásicas Hereditárias , Nevo , Neoplasias Cutâneas , Criança , Neoplasias Colorretais , Humanos , Masculino , Mutação , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genéticaRESUMO
Cutaneous adverse events (cAEs) from targeted antineoplastic agents and immune checkpoint inhibitors are common in children with cancer and may lead to dose reduction or cessation of critical oncologic treatment. Timely diagnosis and proper management of cAEs in pediatric oncology patients is essential to optimize ongoing cancer-directed therapy and improve quality of life. This systematic review of published studies summarizes dermatologic toxicities to targeted anticancer treatments and immune checkpoint inhibitors.
Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/efeitos adversos , Criança , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Qualidade de Vida , PeleRESUMO
BACKGROUND/OBJECTIVES: Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform eruptions after initiation of dupilumab in children. METHODS: Records of patients ≤18 years of age with atopic dermatitis who developed psoriasiform dermatitis during treatment with dupilumab were reviewed retrospectively. RESULTS: Six children, 4-18 years of age, on dupilumab for severe atopic dermatitis developed new-onset psoriasiform dermatitis at a median duration of 8 months (range, 6-12 months) after dupilumab initiation. Typical locations of psoriasis were involved (face, scalp, trunk, and extensor extremities). The majority showed clearance or near clearance with the use of medium-strength to potent topical corticosteroid ointments and 83% continued use of the dupilumab. A 7th patient had psoriasis, in addition to severe atopic dermatitis, and the psoriasis was unmasked by its failure to respond to dupilumab. CONCLUSION: Although unusual, psoriasiform lesions can appear during effective treatment with dupilumab for atopic dermatitis, potentially reflecting a shift toward cutaneous IL-23/TH 17 pathway activation with dupilumab-induced suppression of type 2 immunity.
Assuntos
Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Humanos , Estudos RetrospectivosRESUMO
Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.
Assuntos
Ictiose Lamelar , Ictiose , Adolescente , Criança , Consenso , Humanos , Ictiose/tratamento farmacológico , RetinoidesRESUMO
Arteriovenous malformations are a vascular anomaly typically present at birth, characterized by an abnormal connection between an artery and a vein (bypassing the capillaries). These high flow lesions can vary in size and location. Therapeutic approaches are limited, and AVMs can cause significant morbidity and mortality. Here, we describe our current understanding of the pathogenesis of arteriovenous malformations based on preclinical and clinical findings. We discuss past and present accomplishments and challenges in the field and identify research gaps that need to be filled for the successful development of therapeutic strategies in the future.
Assuntos
Malformações Arteriovenosas/genética , Animais , Artérias/patologia , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/terapia , Modelos Animais de Doenças , Humanos , Terapia de Alvo Molecular , Receptor Cross-Talk , Veias/patologiaRESUMO
Calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam is a topical agent indicated for the treatment of plaque psoriasis. While topical treatments are typically reserved for milder disease, in clinical trials with Cal/BD foam, the vast majority of patients had beyond-mild psoriasis at baseline, and multiple studies (including subgroup analyses from randomized controlled trials and other small-scale studies) have demonstrated favorable outcomes with the use of Cal/BD foam in this population. The objective of this article is to review existing data on the efficacy, safety, and cost-effectiveness of Cal/BD foam used in patients with beyond-mild psoriasis, either alone as topical monotherapy or as adjunctive therapy. Practical recommendations for managing beyond-mild psoriasis with Cal/BD foam are also provided. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5300.
Assuntos
Betametasona/análogos & derivados , Produtos Biológicos/administração & dosagem , Calcitriol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Administração Cutânea , Aerossóis , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Betametasona/economia , Produtos Biológicos/efeitos adversos , Produtos Biológicos/economia , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Calcitriol/economia , Análise Custo-Benefício , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/economia , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Humanos , Psoríase/diagnóstico , Psoríase/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Talidomida/economia , Resultado do TratamentoRESUMO
Eosinophilic fasciitis (EF) is a rare condition in children that is typically treated with systemic corticosteroids. We present the case of a 9-year-old boy with biopsy-proven EF, refractory to systemic corticosteroids and methotrexate. The tyrosine kinase inhibitor imatinib was added as adjuvant therapy, leading to improvement in joint function and skin laxity. Our case is the first to suggest the anti-fibrotic properties of imatinib may benefit EF patients.
Assuntos
Eosinofilia , Fasciite , Corticosteroides , Criança , Eosinofilia/tratamento farmacológico , Fasciite/diagnóstico , Fasciite/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , MasculinoRESUMO
Phacomatosis pigmentovascularis (PPV) comprises a family of rare conditions that feature vascular abnormalities and melanocytic lesions that can be solely cutaneous or multisystem in nature. Recently published work has demonstrated that both vascular and melanocytic abnormalities in PPV of the cesioflammea and cesiomarmorata subtypes can result from identical somatic mosaic activating mutations in the genes GNAQ and GNA11. Here, we present three new cases of PPV with features of the cesioflammea and/or cesiomarmorata subtypes and mosaic mutations in GNAQ or GNA11. To better understand the risk of potentially occult complications faced by such patients we additionally reviewed 176 cases published in the literature. We report the frequency of clinical findings, their patterns of co-occurrence as well as published recommendations for surveillance after diagnosis. Features assessed include: capillary malformation; dermal and ocular melanocytosis; glaucoma; limb asymmetry; venous malformations; and central nervous system (CNS) anomalies, such as ventriculomegaly and calcifications. We found that ocular findings are common in patients with phacomatosis cesioflammea and cesiomarmorata. Facial vascular involvement correlates with a higher risk of seizures (p = .0066). Our genetic results confirm the role of mosaic somatic mutations in GNAQ and GNA11 in phacomatosis cesioflammea and cesiomarmorata. Their clinical and molecular findings place these conditions on a clinical spectrum encompassing other GNAQ and GNA11 related disorders and inform recommendations for their management.
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Síndromes Neurocutâneas/diagnóstico , Fenótipo , Alelos , Criança , Diagnóstico Diferencial , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Genótipo , Humanos , Lactente , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Mutação , Síndromes Neurocutâneas/genética , Pele/patologia , Sequenciamento do ExomaRESUMO
PURPOSE OF REVIEW: Vascular malformations (VaMs) are a consequence of disrupted morphogenesis that may involve arterial, capillary, venous, or lymphatic endothelium alone or in a combination. VaMs can have serious health impacts, leading to life-threatening conditions sometimes. Genetic mutations affecting proliferation, migration, adhesion, differentiation, and survival of endothelial cells, as well as integrity of extracellular matrix are believed to be the pathogenesis of these disorders. Here, we present an updated review of genetic mutations and potential therapeutic targets for VaMs. RECENT FINDINGS: Increased number of genetic mutations have been discovered in vascular anomalies via targeted deep sequencing. When a genetic defect is identified, it often presents in only a small percentage of cells within the malformation. In addition, mutations within the same gene may result in different clinical phenotypes. Management of VaMs can be challenging depending on the severity and functional impairment associated. There are no standard treatment algorithms available to date for VaMs, therefore the disorder has significant unmet clinical needs. Currently, the focus of therapeutic development is to target constitutively activated intracellular signaling pathways resulted from genetic mutations. SUMMARY: Knowledge about the genetic mutations and altered signaling pathways related to VaMs have improved our understanding about the pathogenesis of vascular anomalies and provided insights to the development of new targeted therapies.
Assuntos
Terapia de Alvo Molecular , Mutação/genética , Transdução de Sinais/genética , Doenças Vasculares/genética , Malformações Vasculares/genética , Malformações Vasculares/terapia , Células Endoteliais , Marcadores Genéticos , Humanos , Fenótipo , Malformações Vasculares/patologiaRESUMO
Maffucci syndrome is a rare genetic disease due to somatic mutation of IDH1 gene. Currently there is no medical treatment available for spindle cell hemangioma associated with this disorder. Here we report successful management of these hemangiomas using sirolimus in combination with surgery.
Assuntos
Encondromatose/complicações , Hemangioma/terapia , Adulto , Feminino , Humanos , Sirolimo/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVES: Congenital hemangiomas (CH) are a group of benign vascular tumors that are present at birth and exhibit variable involution during infancy. Congenital hemangiomas that do not involute are typically solitary patch or plaque-type tumors that grow proportionally with somatic growth. We report a case series of 9 patients with persistent CH, which exhibited uncommon features including segmental involvement, recurrent or severe pain, or growth via volumetric increase in size or apparent increased extent of anatomic involvement over time. METHODS: Via retrospective chart review, we included patients with persistent CH and atypical presentations. Available data regarding clinical characteristics, natural history, histopathology, imaging, and genetic tests were collected. RESULTS: Data on 9 patients were collected, including 7 noninvoluting CH and 2 partially involuting CH. Three of the 9 cases had segmental distribution, 6 had apparent growth or clinical evolution, and 4 were symptomatic with pain. One also had marked localized intravascular coagulopathy. CONCLUSIONS: Ongoing or recurrent pain and large extent of anatomic involvement can be features of CH, albeit uncommon ones, and can pose both diagnostic and management challenges. Tissue genomic studies can offer a novel tool for CH diagnosis.
Assuntos
Hemangioma/congênito , Neoplasias Cutâneas/congênito , Neoplasias Vasculares/congênito , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Hemangioma/diagnóstico , Hemangioma/terapia , Humanos , Lactente , Masculino , Medição da Dor , Fenótipo , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/terapiaRESUMO
PURPOSE OF REVIEW: Childhood malnutrition is a major global health issue. It is often thought of as a developing world problem and therefore, underdiagnosed or misdiagnosed in developed countries. The delay in diagnosis and treatment can lead to increased morbidity and mortality. Cutaneous manifestations are often the initial presenting signs of nutritional deficiency. Early recognition is essential in timely initiation of the necessary interventions. This article will review pertinent cutaneous findings and systemic manifestations associated with common nutritional deficiencies. RECENT FINDINGS: Malnutrition has historically been associated with poverty in developing countries. However, recent literatures suggest that the incidence of nutritional deficiencies continuous to rise among infants from developed countries, as a result of dietary restrictions because of perceived food allergies or intolerance. It is also an emerging finding in children with complicated medical problems. SUMMARY: It is very important to raise awareness about cutaneous manifestations of nutritional deficiency as early and appropriate treatment results in excellent prognosis.