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Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA:DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response.
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DNA Polimerase I/metabolismo , DNA/biossíntese , Interferon Tipo I/metabolismo , RNA/biossíntese , Sequência de Bases , Células Cultivadas , Citosol/metabolismo , DNA/genética , DNA Polimerase I/genética , Saúde da Família , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Células HEK293 , Células HeLa , Humanos , Immunoblotting , Masculino , Microscopia Confocal , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Transtornos da Pigmentação/genética , Transtornos da Pigmentação/metabolismo , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To develop consensus on diagnostic criteria for LUMBAR syndrome, the association of segmental infantile hemangiomas that affect the Lower body with Urogenital anomalies, Ulceration, spinal cord Malformations, Bony defects, Anorectal malformations, Arterial anomalies and/or Renal anomalies. STUDY DESIGN: These diagnostic criteria were developed by an expert multidisciplinary and multi-institutional team based on analysis of peer-reviewed data, followed by electronic-Delphi consensus of a panel of 61 international pediatric specialists. RESULTS: After 2 Delphi rounds, a 92% or higher level of agreement was reached for each Delphi statement. 98% of panelists agreed with the diagnostic criteria, and 100% agreed the criteria would be useful in clinical practice. The diagnosis of LUMBAR requires the presence of a segmental, or patterned, infantile hemangioma of the lumbosacral, sacrococcygeal, or pelvic cutaneous regions plus one additional criterion of the urogenital, spinal, bony, anorectal, arterial, or renal organ systems. CONCLUSIONS: These diagnostic criteria will enhance clinical care by improving screening, detection, and overall awareness of this poorly understood neurocutaneous disorder. The criteria can be utilized by a wide variety of pediatric subspecialists. In addition, formal criteria will improve phenotypic uniformity among LUMBAR syndrome cohorts and a patient registry, allowing investigators to assess clinical features, long-term outcomes, and results of genetic sequencing in a standardized manner. Finally, these criteria will serve as a starting point for prospective studies to establish formal screening and management guidelines.
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OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.
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Coartação Aórtica , Anormalidades do Olho , Síndromes Neurocutâneas , Humanos , Lactente , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Síndromes Neurocutâneas/complicações , Anormalidades do Olho/complicações , Coartação Aórtica/complicações , Qualidade de Vida , Estudos Transversais , CefaleiaRESUMO
Capillary malformations (CMs) are the most common type of vascular anomalies, affecting around 0.3% of newborns. They are usually caused by somatic pathogenic variants in GNAQ or GNA11. PIK3CA and PIK3R1, part of the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin pathway, are mutated in fainter CMs such as diffuse CM with overgrowth and megalencephaly CM. In this study, we present two young patients with a CM-like phenotype associated with cerebral anomalies and severe epilepsy. Pathogenic variants in PIK3CA and PIK3R1, as well as GNAQ and GNA11, were absent in affected cutaneous tissue biopsies. Instead, we identified two somatic pathogenic variants in the AKT3 gene. Subsequent analysis of the DNA obtained from surgically resected brain tissue of one of the two patients confirmed the presence of the AKT3 variant. Focal cortical dysplasia was also detected in this patient. Genetic analysis thus facilitated workup to reach a precise diagnosis for these patients, associating the vascular anomaly with the neurological symptoms. This study underscores the importance of searching for additional signs and symptoms to guide the diagnostic workup, especially in cases with atypical vascular malformations. In addition, it strongly emphasizes the significance of genotype-phenotype correlation studies in guiding clinicians' informed decision-making regarding patient care.
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Capilares , Epilepsia , Proteínas Proto-Oncogênicas c-akt , Telangiectasia , Malformações Vasculares , Feminino , Humanos , Recém-Nascido , Masculino , Capilares/anormalidades , Capilares/patologia , Epilepsia/genética , Epilepsia/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Mosaicismo , Mutação/genética , Fenótipo , Proteínas Proto-Oncogênicas c-akt/genética , Telangiectasia/genética , Telangiectasia/patologia , Telangiectasia/diagnóstico , Malformações Vasculares/genética , Malformações Vasculares/patologia , Malformações Vasculares/diagnóstico , Malformações Vasculares/complicações , AdolescenteRESUMO
BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.
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INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.
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Dermatose Linear Bolhosa por IgA , Humanos , Dermatose Linear Bolhosa por IgA/diagnóstico , Dermatose Linear Bolhosa por IgA/tratamento farmacológico , Europa (Continente) , Dermatologia/normasRESUMO
Oral-facial-digital syndrome type 1 (OFD1) is an X-linked dominant development disorder due to mutations in the OFD1 gene. It is characterized by facial, oral, and digital malformations, although expression is variable. Skin manifestations are frequent (20%-30% of patients) and characterized by evanescent milia and patchy alopecia. Trichoscopic findings (broken hairs, black dots, pili torti) can resemble tinea capitis, although such findings have not been well characterized. High clinical suspicion of ectodermal dysplasia-like syndromes due to trichoscopy findings, absence of response to long-term antifungal therapy, and the presence of midline anomalies can raise suspicion for OFD1, which can be confirmed by genetic testing and enable diagnosis.
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Phacomatosis pigmentokeratotica (PPK) is a RASopathy characterized by the presence of a sebaceous nevus and a papular speckled lentiginous nevus. This case report highlights the associated extracutaneous comorbidities, including life-threatening arrhythmia, and introduces topical rapamycin as a potential therapeutic avenue for sebaceous nevus in PPK patients.
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We report two cases with localized vascular malformations clinically resembling the "dominant lesion" seen in capillary malformation-arteriovenous malformation (CM-AVM) syndrome, however, lacking germline RASA1 variants but presenting double somatic RASA1 variants in affected tissue. Both patients presented with localized and superficial high-flow vascular malformations were treated with surgery and laser therapy and showed partial resolution. The study underscores the rarity of somatic RASA1 variants, contributes to understanding the "second-hit" pathophysiology in vascular lesions, and emphasizes the significance of clinical distinctions and genotyping for accurate diagnoses, offering implications for diagnosis, prognosis, and genetic counseling.
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BACKGROUND/OBJECTIVES: Cutis marmorata telangiectatica congenita (CMTC) is a capillary malformation characterized by congenital, reticulated, well-demarcated dark blue, red-purple, or violaceous macules or plaques, with a coarse fixed livedo pattern. Nearly always, contiguous areas of skin atrophy and/or ulceration are present. CMTC is usually localized but may rarely be generalized. Such generalized cases may be a feature of Adams-Oliver syndrome (AOS). The nosologic confusion surrounding the term CMTC and uncertainty about the risk of associated abnormalities hinders the appropriate workup of patients and prognostic counseling for families. We hypothesized that the risk of associated anomalies in children with localized CMTC is very low. METHODS: We performed a literature review and retrospective review of patients with CMTC to propose a more precise clinical definition and ascertain the risk of associated anomalies. RESULTS: We included 78 patients determined to have a diagnosis of CMTC based on consensus. The majority of patients had localized CMTC. Most patients with generalized CMTC met the criteria for the diagnosis of AOS. The associations found in patients with localized CMTC were mostly dermatological, with atrophy, ulcerations, or erosions present in 71%. Extracutaneous findings were present in 34.4% of patients and consisted mainly of extremity asymmetry (24.5%) that improved over time. CONCLUSION: Our study showed a very low frequency of extracutaneous anomalies among patients with localized CTMC, ipsilateral limb discrepancy being the most common. We did not find a strong association with any other visceral anomalies that would justify routine evaluation in patients with localized CMTC.
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A 7-year-old girl presented with proximal muscle weakness and skin lesions. Physical examination revealed violaceous papules on the right forearm in a blaschkoid distribution. Her symptoms and test results were consistent with juvenile dermatomyositis. An unusual superimposed segmental manifestation of this disease is discussed.
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Dermatomiosite , Feminino , Humanos , Criança , Dermatomiosite/diagnóstico , Dermatomiosite/patologiaRESUMO
Tricho-dento-osseous syndrome (TDOS) is a rare ectodermal dysplasia caused by mutations in the DLX3 gene and it is not usually included as a cause of syndromic woolly hair. We present a new case of TDOS with a novel DLX3 variant and woolly hair.
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Doenças do Cabelo , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genética , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/genética , CabeloRESUMO
This study aims to examine transition of care (TOC) practices of multidisciplinary vascular anomalies centers (VACs). Thirty-seven of 71 VAC leaders to whom the survey was sent completed the questionnaire. TOC and transfer practices varied with only 16% of VACs having TOC programs. The most frequently cited barriers to developing a TOC program were lack of resources and difficulty finding expert adult providers.
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Transferência de Pacientes , Malformações Vasculares , Adulto , Humanos , Inquéritos e Questionários , Malformações Vasculares/diagnóstico , Malformações Vasculares/terapiaRESUMO
BACKGROUND/OBJECTIVES: We sought to describe the experience among members of the Hemangioma Investigator Group with pulsed dye laser (PDL) in the treatment of nonulcerated infantile hemangioma (IH) in pediatric patients in the pre- and post-beta-blocker era. METHODS: A multicenter retrospective cohort study was conducted in patients with nonulcerated IH treated with laser therapy. Patient demographics, IH characteristics, indications for/timing of laser therapy, as well as laser parameters were collected. Responses to laser therapy were evaluated using a visual analog scale (VAS). RESULTS: One hundred and seventeen patients with IH were treated with PDL. 18/117 (15.4%) had early intervention (defined as <12 months of life), and 99/117 (84.6%) had late intervention (≥12 months of life). In the late intervention group, 73.7% (73/99) had additional medical management of their IH. The mean age at PDL initiation for the late intervention group was 46.7 ± 35.3 months of life (range 12-172 months) with total number of treatments to maximal clearing of 4.2 ± 2.8 (range 1-17). Those who received propranolol prior to PDL received fewer sessions (1.1 fewer sessions, approaching significance [p = .056]). On the VAS, there was a mean 85% overall improvement compared to baseline (range 18%-100%), with most improvement noted in erythema and/or telangiectasias. The incidence of adverse effects was 6/99 (6.1%). CONCLUSIONS: PDL is a useful tool in the treatment of IH, with notable improvement of telangiectasia and erythema and low risk of complications. PDL is often introduced after the maximal proliferative phase.
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Hemangioma Capilar , Hemangioma , Lasers de Corante , Humanos , Criança , Estudos Retrospectivos , Lasers de Corante/uso terapêutico , Hemangioma Capilar/radioterapia , Hemangioma Capilar/cirurgia , Hemangioma/radioterapia , Hemangioma/cirurgia , Hemangioma/etiologia , Antagonistas Adrenérgicos beta , Resultado do TratamentoRESUMO
Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous entities have been grouped as PIK3CA-Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low-level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient-specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi-system and often complex medical issues seen with PROS. In March 2019, macrocephaly-capillary malformation (M-CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M-CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge.
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Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Padrão de Cuidado , Conferências de Consenso como Assunto , Diagnóstico Diferencial , Gerenciamento Clínico , Estudos de Associação Genética/métodos , Testes Genéticos , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Transtornos do Crescimento/terapia , Humanos , Fenótipo , Diagnóstico Pré-NatalRESUMO
Penttinen type of premature aging syndrome is an autosomal-dominant disorder that can be caused by the c.1994T>A pVal665Ala pathogenic variant in platelet-derived growth factor receptor-B (PDGFRB). Imatinib, a receptor tyrosine kinase (RTK) inhibitor, has been used in Penttinen syndrome (PS) patients with good results. A 21-year-old male presented shortly after birth with a prematurely aged appearance with distinctive facial features and cutaneous atrophy with hypertrophic scar-like lesions. Generalized brachydactyly with acro-osteolysis was observed. Flexion contractures limited his daily activities. Cognitive impairment was not present. Genetic testing found a heterozygous variant c.1994T>A pVal665Ala in exon 14 of PDGFRB. A diagnosis of PS was made and imatinib treatment was started with partial response. After lack of further improvement, in vitro molecular studies with imatinib and dasatinib showed that the Val665Ala variant had greater sensitivity to dasatinib than imatinib. This was seen examining levels of P-PDGFRB directly and on downstream ligands P-AKT and P-STAT. Improved clinical response was observed after treatment with dasatinib. We report a new case of PS with clinical and molecular response to dasatinib after incomplete response to imatinib. Our work provides further molecular and clinical evidence of RTK inhibitors' efficacy in this rare disorder.
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Acro-Osteólise , Anormalidades da Pele , Acro-Osteólise/genética , Dasatinibe/uso terapêutico , Humanos , Mesilato de Imatinib/uso terapêutico , Deformidades Congênitas dos Membros , Masculino , Progéria , Inibidores de Proteínas Quinases/uso terapêutico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Adulto JovemRESUMO
This post hoc analysis examined SCORing Atopic Dermatitis (SCORAD) outcomes in 471 paediatric patients (children age 6-<12 years, n = 304; adolescents age 12-<18 years, n = 167) with atopic dermatitis treated with dupilumab, ± topical corticosteroids, in two 16-week phase 3 randomized controlled trials and a 1-year interim data cut of a subsequent open-label extension study. Paediatric patients treated with dupilumab (± topical corticosteroids) had significantly lower SCORAD, objective SCORAD (o-SCORAD), and individual SCORAD components from week 3 to 16 compared with placebo (± topical corticosteroids) in the randomized controlled trials. The results were sustained or continuously improved over 1 year of open-label treatment with dupilumab ± topical corticosteroids. SCORAD-50 was achieved in almost all patients (91.3-91.8%) by week 52 with continued dupilumab treatment across age groups. Almost all (> 86%) patients achieved mild or absent pruritus and sleep loss at week 52. In conclusion, dupilumab ± topical corticosteroids resulted in rapid and significant improvements in all aspects of SCORAD analysed, and the results were sustained over 1 year.
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Dermatite Atópica , Fármacos Dermatológicos , Adolescente , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Glucocorticoides , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVES: The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS: Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS: The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS: Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.
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COVID-19 , Hemangioma Capilar , Hemangioma , Telemedicina , COVID-19/epidemiologia , Estudos Transversais , Hemangioma/diagnóstico , Hemangioma/terapia , Humanos , PandemiasRESUMO
OBJECTIVES: Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during "off-label use" for vascular anomalies. METHODS: We performed a retrospective, multicenter chart review for SAEs during "off-label" sirolimus therapy for vascular anomalies and analyzed these cases by a predesigned workflow. RESULTS: We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n = 4), Gorham-Stout disease (n = 2), central conducting lymphatic anomaly (n = 1), lymphatic malformation (n = 4), tufted angioma (n = 1), kaposiform hemangioendothelioma (n = 1), and venous malformation in a patient with CLOVES syndrome (n = 1). Three patients presented two SAEs each. The age at initiation of sirolimus therapy was under 2 years (n = 5), 2-6 years (n = 5), and older than 12 years (n = 4). SAEs occurred during the first 3 months of sirolimus therapy (n = 7), between 3 and 12 months (n = 7) and after 1 year of therapy (n = 3). The most frequent SAE was viral pneumonia (n = 8) resulting in one death due to a metapneumovirus infection in a 3 months old and a generalized adenovirus infection in a 28-month-old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis. CONCLUSIONS: Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence of other risk factors, that is, underlying vascular anomaly or immune status, may contribute to the risk of SAEs. Sirolimus is an important therapeutic option for vascular anomalies, but patients and physicians need to be aware that adequate monitoring is necessary, especially in patients with complex lymphatic anomalies that are overrepresented in our cohort of SAEs.
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Malformações Vasculares , Pré-Escolar , Hemangioendotelioma , Humanos , Lactente , Síndrome de Kasabach-Merritt/tratamento farmacológico , Anormalidades Linfáticas/tratamento farmacológico , Uso Off-Label , Estudos Retrospectivos , Sirolimo/efeitos adversos , Malformações Vasculares/tratamento farmacológicoRESUMO
BACKGROUND: High-flow vascular stains (HFVS) are lesions that have the appearance of capillary malformations/port wine stains but are associated with increased arterial flow. OBJECTIVE: To identify features of HFVS that differentiate them from typical "slow-flow" port wine stains. METHODS: Retrospective multicenter cohort study of HFVS evaluated across 7 centers was conducted. HFVS were characterized by clinical features (warmth, thrill, rapid capillary refill), radiologic findings (fast flow), or mutations associated with capillary malformation-arteriovenous malformation syndrome. Investigators reviewed photographs. RESULTS: The study reviewed 70 patients with HFVS (47 multifocal and 23 solitary). Most were flat (77%), warm to the touch (60%), and red or pink-red in color (35%), with heterogeneous color saturation (73%) and well-defined borders (71%). Regional soft tissue swelling/overgrowth was common (47%). Head and neck location was most common (38%). Among 34 HFVS with photographic review over time, all demonstrated changes in appearance. LIMITATIONS: Retrospective design, recall bias, lack of standardized time points or visual analog scale, and image variability. CONCLUSION: Heterogeneity of stain color saturation, warmth to touch, peripheral pallor, and overgrowth/soft tissue swelling help distinguish HFVS from port wine stains. Darkening of color and increased border demarcation may develop over time. These findings raise suspicion for HFVS and provide an indication to assess for extracutaneous involvement.