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Colmenero-Sendra M, Del Boz-González J, Baselga Torres E, Bernabéu-Wittel J, Roé-Crespo E, Vicente A, Valdivieso-Ramos M, Martín-Santiago A, Palencia-Pérez SI, Montserrat-García MT, Azón-Masoliver A, Dañino M, Tubau Prims C, Prat C, Giacaman A, Domínguez-Cruz JJ, Bauzá Alonso A, Grau-Pérez M, Descalzo MÁ, García-Doval I. Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort. ACTAS DERMO-SIFILIOGRAFICAS 2025; 116:T327-T336. [PMID: 39643113 DOI: 10.1016/j.ad.2024.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 06/11/2024] [Indexed: 12/09/2024] Open
Abstract
BACKGROUND Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (≥9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS The median follow-up was 3.1years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; P<.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; P>.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.
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Affiliation(s)
- M Colmenero-Sendra
- Departamento de Dermatología, Hospital Costa del Sol, Marbella, Málaga, España; Programa de Doctorado en Medicina Clínica y Salud Pública, Universidad de Granada, Granada, España
| | - J Del Boz-González
- Departamento de Dermatología, Hospital Regional Universitario de Málaga, Málaga, España.
| | - E Baselga Torres
- Departamento de Dermatología, Hospital Sant Joan de Déu, Universitat Autònoma de Barcelona, Barcelona, España
| | - J Bernabéu-Wittel
- Departamento de Dermatología, Hospital Virgen del Rocío, Sevilla, España; Departamento de Dermatología, Hospital Viamed Santa Ángela de la Cruz, Sevilla, España
| | - E Roé-Crespo
- Departamento de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - A Vicente
- Departamento de Dermatología, Hospital Sant Joan de Déu, Barcelona, España
| | | | - A Martín-Santiago
- Departamento de Dermatología, Hospital Son Espases, Palma de Mallorca, España
| | | | - M T Montserrat-García
- Departamento de Dermatología, Hospital Virgen del Rocío, Sevilla, España; Departamento de Dermatología, Hospital Viamed Santa Ángela de la Cruz, Sevilla, España
| | - A Azón-Masoliver
- Departamento de Dermatología, Hospital Sant Joan de Reus, Reus, Tarragona, España
| | - M Dañino
- Departamento de Dermatología, Hospital Virgen del Rocío, Sevilla, España
| | - C Tubau Prims
- Departamento de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - C Prat
- Departamento de Dermatología, Hospital Sant Joan de Déu, Barcelona, España
| | - A Giacaman
- Departamento de Dermatología, Hospital Son Espases, Palma de Mallorca, España
| | - J J Domínguez-Cruz
- Departamento de Dermatología, Hospital Virgen del Rocío, Sevilla, España; Departamento de Dermatología, Hospital Viamed Santa Ángela de la Cruz, Sevilla, España
| | - A Bauzá Alonso
- Departamento de Dermatología, Hospital Son Espases, Palma de Mallorca, España
| | - M Grau-Pérez
- Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, España; Departamento de Dermatología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España
| | - M Á Descalzo
- Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, España
| | - I García-Doval
- Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, España; Departamento de Dermatología, Complejo Hospitalario Universitario de Vigo, Vigo, Pontevedra, España
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Colmenero-Sendra M, Del Boz-González J, Baselga Torres E, Bernabéu-Wittel J, Roé-Crespo E, Vicente A, Valdivieso-Ramos M, Martín-Santiago A, Palencia-Pérez SI, Montserrat-García MT, Azón-Masoliver A, Dañino M, Tubau Prims C, Prat C, Giacaman A, Domínguez-Cruz JJ, Bauzá Alonso A, Grau-Pérez M, Descalzo MÁ, García-Doval I. Parental Assessment of Infantile Hemangioma Cosmetic Clinical Outcomes: Results of the Spanish Hemangioma Nationwide Prospective Cohort. ACTAS DERMO-SIFILIOGRAFICAS 2025; 116:327-336. [PMID: 39032773 DOI: 10.1016/j.ad.2024.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 06/11/2024] [Indexed: 07/23/2024] Open
Abstract
BACKGROUND Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.
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Affiliation(s)
- M Colmenero-Sendra
- Dermatology Department, Hospital Costa del Sol, Marbella, Spain; Programa de Doctorado en Medicina Clínica y Salud Pública, Universidad de Granada, Spain
| | - J Del Boz-González
- Dermatology Department, Hospital Regional Universitario de Málaga, Spain.
| | - E Baselga Torres
- Dermatology Department, Hospital Sant Joan de Déu, Universitat Autònoma de Barcelona, Spain
| | - J Bernabéu-Wittel
- Dermatology Department, Hospital Virgen del Rocío, Sevilla, Spain; Dermatology Department, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain
| | - E Roé-Crespo
- Dermatology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - A Vicente
- Dermatology Department, Hospital Sant Joan de Déu, Barcelona, Spain
| | | | - A Martín-Santiago
- Dermatology Department, Hospital Son Espases, Palma de Mallorca, Spain
| | | | - M T Montserrat-García
- Dermatology Department, Hospital Virgen del Rocío, Sevilla, Spain; Dermatology Department, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain
| | - A Azón-Masoliver
- Dermatology Department, Hospital Sant Joan de Reus, Tarragona, Spain
| | - M Dañino
- Dermatology Department, Hospital Virgen del Rocío, Sevilla, Spain
| | - C Tubau Prims
- Dermatology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - C Prat
- Dermatology Department, Hospital Sant Joan de Déu, Barcelona, Spain
| | - A Giacaman
- Dermatology Department, Hospital Son Espases, Palma de Mallorca, Spain
| | - J J Domínguez-Cruz
- Dermatology Department, Hospital Virgen del Rocío, Sevilla, Spain; Dermatology Department, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain
| | - A Bauzá Alonso
- Dermatology Department, Hospital Son Espases, Palma de Mallorca, Spain
| | - M Grau-Pérez
- Research Unit, Fundación Piel Sana AEDV, Madrid, Spain; Dermatology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - M Á Descalzo
- Research Unit, Fundación Piel Sana AEDV, Madrid, Spain
| | - I García-Doval
- Research Unit, Fundación Piel Sana AEDV, Madrid, Spain; Dermatology Department, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
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Rešić A, Barčot Z, Habek D, Pogorelić Z, Bašković M. The Evaluation, Diagnosis, and Management of Infantile Hemangiomas-A Comprehensive Review. J Clin Med 2025; 14:425. [PMID: 39860430 PMCID: PMC11765582 DOI: 10.3390/jcm14020425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/28/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Infantile hemangioma (IH) is the most common pediatric benign vascular tumor. Its pathogenesis is still poorly understood, and it usually appears during the first few weeks of life and follows a characteristic natural course of proliferation and involution. Most IHs are small, benign, resolve spontaneously, and do not require active treatment but only active observation. A minority of IHs are potentially problematic because they can cause life-threatening complications, permanent disfigurement, and functional impairment. Diagnosis is usually clinical, and propranolol is currently the mainstay of treatment. Other therapeutic modalities may be used alone or in combination, depending on the characteristics of the specific IH. New treatment options are being explored every day, and some are showing promising results. It is undeniable that therapeutic modalities for IHs must be selected based on the child's age, the size and location of the lesion, the presence of complications, the implementation conditions, and the possible outcomes of the treatment. The future of IH management will certainly be reflected in improved advanced imaging modalities, research into the genetic and molecular basis, the development of new pharmacological agents or techniques, and the development of standardized protocols, all to optimize outcomes with minimal side effects.
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Affiliation(s)
- Arnes Rešić
- Department of Pediatrics, Children’s Hospital Zagreb, Ulica Vjekoslava Klaića 16, 10000 Zagreb, Croatia
- University Department of Health Studies, University of Split, Ruđera Boškovića 35, 21000 Split, Croatia
| | - Zoran Barčot
- Department of Pediatric Surgery, Children’s Hospital Zagreb, Ulica Vjekoslava Klaića 16, 10000 Zagreb, Croatia
| | - Dubravko Habek
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Croatian Academy of Medical Sciences, Kaptol 15, 10000 Zagreb, Croatia
- Department of Obstetrics and Gynecology, Clinical Hospital Merkur, Zajčeva ulica 19, 10000 Zagreb, Croatia
- School of Medicine, Catholic University of Croatia, Ilica 242, 10000 Zagreb, Croatia
| | - Zenon Pogorelić
- Department of Pediatric Surgery, University Hospital of Split, Spinčićeva ulica 1, 21000 Split, Croatia
- School of Medicine, University of Split, Šoltanska ulica 2a, 21000 Split, Croatia
| | - Marko Bašković
- Department of Pediatric Surgery, Children’s Hospital Zagreb, Ulica Vjekoslava Klaića 16, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Croatian Academy of Medical Sciences, Kaptol 15, 10000 Zagreb, Croatia
- Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
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Yasuda-Koiwa M, Ogawa T, Ogawa A, Takizawa F, Mukoyama Y, Moriguchi S, Kishi A, Hayashi N, Isojima T. Optimizing Propranolol Therapy for Infantile Hemangiomas: The Role of the Multidisciplinary Team. Cureus 2024; 16:e75806. [PMID: 39822455 PMCID: PMC11735240 DOI: 10.7759/cureus.75806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Oral propranolol therapy is currently the first choice for infants with infantile hemangiomas (IHs) requiring systemic treatment. This study aims to evaluate the safety and effectiveness of oral propranolol therapy for IHs and to assess the role of a multidisciplinary medical team in supporting optimal treatment. MATERIALS AND METHODS Clinical data were retrospectively reviewed from medical records in 150 Japanese infants with IH treated with propranolol orally at Toranomon Hospital. Patients with problematic IH, such as tumor-type IH or IH with ulceration, were eligible for inclusion. Treatment was managed by a medical team consisting of pediatricians, dermatologists, pediatric nurses, pharmacists, and nutritionists. Patients' general conditions and vital signs, such as blood pressure, pulse rate, respiratory rate, and blood sugar, were closely monitored before, one hour, and two hours after drug administration. RESULTS Close collaboration among multidisciplinary medical team members allowed for accurate patient evaluation, contributing to the early detection of side effects, even if asymptomatic. When side effects were suspected, pediatricians and dermatologists discussed the need to reduce or discontinue the medication. Of the 150 patients, no one experienced severe side effects. Although five cases (3.3%) were suspected of having mild side effects (i.e., hypotension, n = 3; hypotension and hypoglycemia, n = 1; inspiratory stridor, n = 1), treatment could be continued by adjusting the dosage. One hundred twenty patients have completed the oral propranolol therapy with successful outcomes. CONCLUSIONS This study provided additional evidence of the safety and effectiveness of oral propranolol therapy in 150 Japanese infants with IH. A well-functioning multidisciplinary medical team is essential for optimal patient treatment.
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Affiliation(s)
| | - Tetsushi Ogawa
- Department of Pediatrics, Toranomon Hospital, Tokyo, JPN
| | - Atsushi Ogawa
- Department of Pediatrics, Toranomon Hospital, Tokyo, JPN
| | | | - Yuri Mukoyama
- Department of Pediatrics, Toranomon Hospital, Tokyo, JPN
| | - Shun Moriguchi
- Department of Pediatrics, Toranomon Hospital, Tokyo, JPN
| | - Akiko Kishi
- Department of Dermatology, Toranomon Hospital, Tokyo, JPN
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López Gutiérrez JC, Pozo Losada J, Gómez Tellado M. Vascular anomalies in childhood. Review and update. An Pediatr (Barc) 2024; 101:278-285. [PMID: 39406619 DOI: 10.1016/j.anpede.2024.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 07/18/2024] [Indexed: 10/25/2024] Open
Abstract
Vascular anomalies are changes in vascularization that usually appear in the foetal stage, at birth or in early childhood. They can cause chronic pain, motor impairment, cosmetic changes or coagulopathy and may be fatal in some cases, but in every case they have a negative impact on the quality of life of the child and the family. Up to 150 different subtypes have been described. They can involve arteries, capillaries, veins, lymphatic vessels or a combination thereof. They may be associated with additional malformations and frequently cause musculoskeletal and soft tissue hypertrophy or hypotrophy. They can develop anywhere in the body, invade any tissue and affect the function of various organs. The prevalence of the different subtypes varies greatly, from 1/20 to 1/1 000 000. Subtypes considered rare diseases (incidence <1/2000) continue to affect more than 500 000 people in the European Union. Differentiating between vascular tumours and vascular malformations is critical, especially in paediatric patients. They are completely different diseases, although they are often grouped under the umbrella term of vascular anomalies. The diagnostic algorithm used in the clinical evaluation of vascular anomalies should be based on a thorough history-taking and detailed physical examination. Future knowledge in this field will be based above all on genetic findings and therapeutic innovations. New molecules and their indications are being explored with the aim of reducing the aggressiveness of previous treatments and increasing the life expectancy and quality of life of patients who do not respond to conventional treatments.
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Affiliation(s)
| | - Jesús Pozo Losada
- Servicio de Dermatología, Hospital Universitario de A Coruña, A Coruña, Spain
| | - Manuel Gómez Tellado
- Servicio de Cirugía Pediátrica, Hospital Universitario de A Coruña, A Coruña, Spain.
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Lu W, Yang Z, Wang M, Zhang Y, Qi Z, Yang X. Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation. Drug Des Devel Ther 2024; 18:4065-4088. [PMID: 39286286 PMCID: PMC11404501 DOI: 10.2147/dddt.s460575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/26/2024] [Indexed: 09/19/2024] Open
Abstract
Introduction Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology. Methods Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD). Results Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value. Conclusion Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.
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Affiliation(s)
- Wei Lu
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
| | - Zhenyu Yang
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
| | - Mengjie Wang
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
| | - Ye Zhang
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
| | - Zuoliang Qi
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
| | - Xiaonan Yang
- Department of Hemangioma and Vascular Malformation, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People's Republic of China
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Yuan W, Wang X. Therapeutic evaluation of electrochemical therapy combined with local injection of pingyangmycin for the treatment of venous malformations in the tongue. Front Neurol 2024; 15:1425395. [PMID: 39233678 PMCID: PMC11371561 DOI: 10.3389/fneur.2024.1425395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/02/2024] [Indexed: 09/06/2024] Open
Abstract
Background Venous malformations are congenital developmental abnormalities that consist of enlarged dysplastic blood vessels. The tongue is a common site of venous malformations in the head and neck region. The aim of the present study was to evaluate the therapeutic effect of using electrochemical therapy (ECT) combined with local injection of pingyangmycin (PYM) for venous malformations in the tongue. Methods 60 patients (20 male and 40 female; age range, 8 to 68 yr) with venous malformations in the tongue were treated with a combination of ECT and PYM injection or with local injection of PYM alone in the department of oral and maxillofacial surgery of the stomatological hospital of China Medical University from January 2013 through June 2019. Among them, 30 patients (group A) were treated with ECT combined with PYM injection for tongue venous malformations and 30 patients (group B) were treated with local injection of PYM alone for tongue venous malformations. The size of the lesions in the two groups varied from 3.5 × 3 × 3 to 8 × 6 × 5 cm. There was no statistical difference in the volume of the lesions between group A and group B (p > 0.05). There was no statistical difference in the age between the two groups (p > 0.05). A repeated treatment of ECT combined with PYM injection or PYM injection alone was administered for venous malformations of tongue in the group A and group B. According to the size of the lesions, the amount of ECT was 5-10 C/cm2. The injection dose of PYM was 3 ~ 5 mL and the injection concentration of PYM was 1.6 mg/mL for adults and 1.0 mg/mL for children. Glucocorticoids were given to prevent postoperative swelling. The therapeutic interval was 3 months for ECT combined with PYM injection and 2 to 4 weeks for PYM injection alone. Hemisphere measurements were used to measure the size of the lesions. 4-scale score and feedback from the patients were used to evaluate the clinical efficacy. Results During the follow-up period from 6 months to 3 years, 60 patients achieved different degree of improvement, with a total effective rate of 85%. 30 patients in the group A received ECT combined with local injection of PYM, with an effective rate of 97%. 30 patients in the group B received local injection of PYM alone, with an effective rate of 73%. The effectiveness of ECT combined with PYM injection in the group A was significantly higher than that of PYM injection alone in the group B (p < 0.05). Postoperative symptoms such as local pain, swelling and fever often occurred in the patients, and the symptoms generally disappeared after 5 to 7 days. No mucosa necrosis or nerve damage was found. Postoperative subjective sensation and function of the tongue were normal. Conclusion Electrochemical therapy combined with local injection of pingyangmycin was a reliable, safe and minimally invasive method for the treatment of venous malformation in the tongue. The treatment modality has fewer complications and is worth of further promotion in clinic.
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Affiliation(s)
- Weili Yuan
- Department of Stomatology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xukai Wang
- Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, China
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Beltrami EJ, Gronbeck C, Jain N, Hargis G, Feng H, Grant-Kels JM, Sloan B. Surface anatomy in dermatology: Part I-Clinical importance, diagnostic utility, and impact on medical management. J Am Acad Dermatol 2024; 91:207-220. [PMID: 37429436 DOI: 10.1016/j.jaad.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/27/2023] [Accepted: 07/02/2023] [Indexed: 07/12/2023]
Abstract
This continuing medical education series reviews updated Delphi consensus surface anatomy terminology through the lens of common medical and procedural dermatology scenarios, helping to underscore high-yield points that can be readily integrated into clinical practice to support patient care. Part I of this series will discuss the current state of surface anatomy terminology in dermatology, outline implications of precise and consistent terminology, provide an illustrative overview of high-yield consensus terminology, highlight prominent landmarks that can aid in critical diagnoses, and relate the importance of precise terminology to medical management. Part II will draw upon consensus terminology to inform the management of cutaneous malignancies and support optimal outcomes in dermatologic procedures.
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Affiliation(s)
- Eric J Beltrami
- University of Connecticut School of Medicine, Farmington, Connecticut
| | - Christian Gronbeck
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut
| | - Neelesh Jain
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut
| | - Geneva Hargis
- University of Connecticut School of Medicine, Farmington, Connecticut
| | - Hao Feng
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut.
| | - Jane M Grant-Kels
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; Department of Dermatology, University of Florida College of Medicine, Gainesville, Florida
| | - Brett Sloan
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut
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Manlove AE, Quintana EN, Cuellar LM, Linnebur AM. Benign Intraoral Soft Tissue Lesions in Children. Oral Maxillofac Surg Clin North Am 2024; 36:265-282. [PMID: 38395668 DOI: 10.1016/j.coms.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2024]
Abstract
Benign intraoral soft tissue pathology in pediatric patients includes developmental, traumatic, inflammatory, and infectious lesions. Common pathology includes gingival cysts, mucoceles, fibromas, and parulis. Less common lesions include peripheral ossifying fibromas, congenital epulis of the newborn, and congenital mandibular duct atresia. Most of these lesions present at painless masses but can have significant effects on children and their caregivers. Although these lesions are generally harmless, evaluation and treatment is necessary for appropriate management and health of the child.
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Affiliation(s)
- Ashley E Manlove
- Carle Illinois College of Medicine, Carle Cleft and Craniofacial Team, Carle Foundation Hospital, Urbana, IL, USA.
| | - Erik N Quintana
- Division of Oral and Maxillofacial Surgery, Carle Foundation Hospital, Urbana, IL, USA
| | - Leticia M Cuellar
- Division of Oral and Maxillofacial Surgery, Carle Foundation Hospital, Urbana, IL, USA
| | - Alexis M Linnebur
- Arnold Palmer Hospital for Children - Orlando Health, 207 W. Gore Street, 3Road Floor, Suite.302, Orlando, FL 32806, USA
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Chen Q, Rong H, Zhang L, Wang Y, Bian Q, Zheng J. KLF2 Orchestrates Pathological Progression of Infantile Hemangioma through Hemangioma Stem Cell Fate Decisions. J Invest Dermatol 2024; 144:1850-1864.e9. [PMID: 38382868 DOI: 10.1016/j.jid.2024.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/23/2024]
Abstract
Infantile hemangioma (IH) is the most prevalent vascular tumor during infancy, characterized by a rapid proliferation phase of disorganized blood vessels and spontaneous involution. IH possibly arises from a special type of multipotent stem cells called hemangioma stem cells (HemSCs), which could differentiate into endothelial cells, pericytes, and adipocytes. However, the underlying mechanisms that regulate the cell fate determination of HemSCs remain elusive. In this study, we unveil KLF2 as a candidate transcription factor involved in the control of HemSCs differentiation. KLF2 exhibits high expression in endothelial cells in proliferating IH but diminishes in adipocytes in involuting IH. Using a combination of in vitro culture of patient-derived HemSCs and HemSCs implantation mouse models, we show that KLF2 governs the proliferation, apoptosis, and cell cycle progression of HemSCs. Importantly, KLF2 acts as a crucial determinant of HemSC fate, directing their differentiation toward endothelial cells while inhibiting adipogenesis. Knockdown of KLF2 induces a proadipogenic transcriptome in HemSCs, leading to impaired blood vessel formation and accelerated adipocyte differentiation. Collectively, our findings highlight KLF2 as a critical regulator controlling the progression and involution of IH by modulating HemSC fate decisions.
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Affiliation(s)
- Qiming Chen
- Department of Oromaxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Hao Rong
- Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ling Zhang
- Department of Oromaxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Yanan Wang
- Department of Oromaxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Qian Bian
- Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jiawei Zheng
- Department of Oromaxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China.
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Neri I, Orioni G, Leuzzi M, Facchini E, Mengozzi E, Chessa MA. Infantile Hemangioma with Minimal or Arrested Growth (IHMAG): A Retrospective Analysis of Clinical and Dermoscopic Diagnostic Clues. Dermatol Pract Concept 2024; 14:dpc.1403a206. [PMID: 39122516 PMCID: PMC11313902 DOI: 10.5826/dpc.1403a206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2024] [Indexed: 08/12/2024] Open
Abstract
INTRODUCTION Infantile hemangioma with minimal or arrested growth (IHMAG) is an unusual subset of infantile hemangioma, difficult to recognize because they are often mistaken for capillary malformation or other entities. Dermoscopic features of IHMAG have been described only in small case series so far. OBJECTIVES The aim of our study was to evaluate epidemiological, clinical, and dermoscopic features in 79 cases of IHMAG with a specific focus on neonates and toddlers with segmental complicated IHMAG and to provide a remarkable dermoscopic criterion to achieve diagnosis. METHODS This case series collected all the cases of IHMAG recorded in our Clinical Registry from January 2012 to March 2022. RESULTS A total of 79 cases of IHMAG were identified in our study; 53 (67.1%) were localized and 26 (32.9 %) were segmental. Patients showed some complications during follow-up such as ulceration and soft tissue anomalies. One PHACE syndrome and two LUMBAR syndromes were included. Our study highlights the main dermoscopic features differentiating IHMAG from infantile hemangiomas and capillary malformations in neonatal patients, highlighting the presence of enlarged unfocused telangiectatic vessels as remarkable clues. CONCLUSIONS This is a large case series described in the literature about this rare entity. We emphasize that segmental IHMAG may be associated with structural abnormalities and may pose a diagnostic challenge especially in its rare facial segmental localization. The use of dermoscopy allowed us to find typical signs for IHMAG, thus avoiding the execution of invasive methods and ensuring the prompt suspicion of a syndrome in segmental neonatal cases.
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Affiliation(s)
- Iria Neri
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola Malpighi, Bologna, Italy
| | - Gionathan Orioni
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola Malpighi, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy
| | - Miriam Leuzzi
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola Malpighi, Bologna, Italy
| | - Elena Facchini
- Pediatric Oncology and Hematology Unit “Lalla Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Elena Mengozzi
- 1st Radiology Department, Maggiore Hospital, Bologna, Italy
| | - Marco Adriano Chessa
- Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola Malpighi, Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Italy
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Jiang Y, Li X, Liu Q, Lei G, Wu C, Chen L, Zhao Y, Hu Y, Xian H, Mao R. Apolipoprotein A-I Binding Protein Inhibits the Formation of Infantile Hemangioma through Cholesterol-Regulated Hypoxia-Inducible Factor 1α Activation. J Invest Dermatol 2024; 144:645-658.e7. [PMID: 37832842 DOI: 10.1016/j.jid.2023.07.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/11/2023] [Accepted: 07/12/2023] [Indexed: 10/15/2023]
Abstract
Infantile hemangioma (IH) is the most frequent vascular tumor of infancy with unclear pathogenesis; disordered angiogenesis is considered to be involved in its formation. Apolipoprotein A-I binding protein (AIBP)-also known as NAXE (NAD [P]HX epimerase)-a regulator of cholesterol metabolism, plays a critical role in the pathological angiogenesis of mammals. In this study, we found that AIBP had much lower expression levels in both tissues from patients with IH and hemangioma endothelial cells (HemECs) than in adjacent normal tissues and human dermal vascular endothelial cells, respectively. Knockout of NAXE by CRISPR-Cas9 in HemECs enhanced tube formation and migration, and NAXE overexpression impaired tube formation and migration of HemECs. Interestingly, AIBP suppressed the proliferation of HemECs in hypoxia. We then found that reduced expression of AIBP correlated with increased hypoxia-inducible factor 1α levels in tissues from patients with IH and HemECs. Further mechanistic investigation demonstrated that AIBP disrupted hypoxia-inducible factor 1α signaling through cholesterol metabolism under hypoxia. Notably, AIBP significantly inhibited the development of IH in immunodeficient mice. Furthermore, using the validated mouse endothelial cell (ie, EOMA cells) and Naxe-/- mouse models, we demonstrated that both endogenous AIBP from tumors and AIBP in the tumor microenvironment limit the formation of hemangioma. These findings suggested that AIBP was a player in the pathogenesis of IH and could be a potential pharmacological target for treating IH.
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Affiliation(s)
- Yongying Jiang
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China
| | - Xingjuan Li
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China
| | - Qin Liu
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China
| | - Gongyun Lei
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China
| | - Changyue Wu
- Department of Dermatology, Affiliated Hospital of Nantong University, Nantong University, Jiangsu, China
| | - Long Chen
- Department of Pediatric Surgery, Affiliated Hospital of Nantong University, Nantong University, Jiangsu, China
| | - Yinshuang Zhao
- Department of Pediatric Surgery, Affiliated Hospital of Nantong University, Nantong University, Jiangsu, China
| | - Yae Hu
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China
| | - Hua Xian
- Department of Pediatric Surgery, Affiliated Hospital of Nantong University, Nantong University, Jiangsu, China
| | - Renfang Mao
- Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu, China.
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13
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Zou Y, Wu Z, Jin P, Fu R, Cheng J, Bai H, Huang M, Huang X, Yuan H. Historical and contemporary management of infantile hemangiomas: a single-center experience. Front Pharmacol 2024; 15:1280948. [PMID: 38370473 PMCID: PMC10869534 DOI: 10.3389/fphar.2024.1280948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 01/22/2024] [Indexed: 02/20/2024] Open
Abstract
Objective: This study explores the 22-year evolution of Infantile Hemangiomas (IHs) treatment strategies at a single-center hospital, aiming to establish an individualized IHs management protocol. Methods: Retrospective review of IHs infants 2000-2022 at the Department of Plastic Surgery, Jiangxi Provincial Children's Hospital. Results: In our study of 27,513 IHs cases, 72.2% were female, with the median age at first hospital visit being 25 days. The majority of cases had localized and superficial lesions primarily on the head, face, and neck (67.5%). Ulceration rates fell from 21.1% to 12.6% with the introduction of propranolol. Management strategies have shifted over time, with the proportion of cases undergoing expectant management dropping from 32.9% to 12.4%. Since 2008, 26.1% of patients were treated with oral propranolol, largely replacing corticosteroids. Topical β-blockers have been used in 12.1% of cases, leading to a reduction in local injection therapy from 20.8% to 13.2%. Laser therapy, introduced in 2016, has been used in 13.8% of cases, while surgical excision has dropped from 25.0% to 8.5% due to alternative treatment options. Combination therapy was used in 8.8% of cases post-2015, indicating a rising trend. Drawing from the evolution of IHs management strategies, an individualized protocol for the management of IHs was successfully established. Conclusion: Treatment for IHs has evolved over recent decades, with less invasive medical interventions increasingly replacing more invasive methods. Furthermore, a personalized treatment protocol established in this study could boost the cure rate of IHs while minimizing potential side effects and complications.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Hua Yuan
- Department of Plastic Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, China
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14
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Hermans MM, Schappin R, de Laat PCJ, Mendels EJ, Breur JMPJ, Langeveld HR, Raphael MF, de Graaf M, Breugem CC, de Wildt SN, Okkerse JME, Pasmans SGMA, Rietman AB. Mental Health of School-Aged Children Treated with Propranolol or Atenolol for Infantile Hemangioma and Their Parents. Dermatology 2024; 240:216-225. [PMID: 38228125 PMCID: PMC10997238 DOI: 10.1159/000536144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 01/03/2024] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. OBJECTIVE This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. METHODS This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children's outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents' outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). RESULTS Data of 105 children (36 propranolol, 69 atenolol; 6.0-11.8 years) were analyzed. Mental health outcomes did not differ between both β-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. CONCLUSION No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant's β-blocker treatment.
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Affiliation(s)
- Mireille M Hermans
- Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands,
| | - Renske Schappin
- Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, Rotterdam, The Netherlands
| | - Peter C J de Laat
- Department of Pediatrics (-Hemato-oncology), Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Utrecht, The Netherlands
| | - Elodie J Mendels
- Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Johannes M P J Breur
- Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Hester R Langeveld
- Department of Intensive Care and Pediatric Surgery, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Martine F Raphael
- Department of Dermatology, UMC Utrecht Center for Vascular Anomalies, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
- Department Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands
| | - Marlies de Graaf
- Department of Dermatology, UMC Utrecht Center for Vascular Anomalies, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Corstiaan C Breugem
- Department of Plastic Surgery, UMC Utrecht Center for Vascular Anomalies, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Plastic, Reconstructive and Hand Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands
| | - Saskia N de Wildt
- Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jolanda M E Okkerse
- Department of Child and Adolescent Psychology/Psychiatry, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Suzanne G M A Pasmans
- Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, Member of the ERN-SKIN-Mosaic Group and ERN-VASCERN-VASCA Group, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - André B Rietman
- Department of Child and Adolescent Psychology/Psychiatry, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
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15
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Labow BI, Alshamekh SA, Carlberg VM, Zacur JL, Uihlein LC, Mulliken JB, Liang MG. Infantile Hemangioma of the Breast: Long-Term Assessment of Outcomes. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2024; 12:e5506. [PMID: 38196847 PMCID: PMC10773794 DOI: 10.1097/gox.0000000000005506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/24/2023] [Indexed: 01/11/2024]
Abstract
Background The literature is meager regarding the natural history and outcomes of infantile hemangiomas (IHs) in the breast. Treatment in childhood may be considered due to psychosocial and physical concerns with breast development. Early surgical intervention may cause iatrogenic breast asymmetry and possibly impair lactation later in life. This study characterizes the clinical presentation, management, and long-term outcomes of IHs arising in the breast. Methods Female patients aged 11 years or older at presentation were included in a retrospective review of the Vascular Anomalies Center database for patients with IHs of the breast seen at our institution between 1980 and 2020. Breast development was ascertained by a structured telephone interview, physical examination, or photographs. Results A total of 10 patients met criteria for inclusion in this study. The median age at enrollment was 14 years (11-36 years). Breast asymmetry was noted in 60% of patients (n = 6). Of the four patients who underwent subtotal excision of breast IH, three developed ipsilateral breast hypoplasia. Breast asymmetry was also noted in three of five patients who did not receive medical treatment: two with hypoplasia and one with hyperplasia. No asymmetry was noted in the single patient who received corticosteroid. Conclusions IHs involving the nipple-areola complex can be associated with breast asymmetry. Hypoplasia was noted in patients not treated with corticosteroid or resection in childhood. These findings suggest that systemic treatment should be considered. Longitudinal follow-up on patients treated with propranolol will elucidate its possible benefits in minimizing breast asymmetry.
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Affiliation(s)
- Brian I. Labow
- From the Harvard Medical School, Boston, Mass
- Department of Plastic and Oral Surgery, Boston Children’s Hospital, Boston, Mass
| | - Shomoukh A. Alshamekh
- From the Harvard Medical School, Boston, Mass
- Dermatology Program, Boston Children’s Hospital, Boston, Mass
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Valerie M. Carlberg
- From the Harvard Medical School, Boston, Mass
- Dermatology Program, Boston Children’s Hospital, Boston, Mass
- Dermatology Program, Children’s Hospital Wisconsin, Milwaukee, Wis
| | - Jennifer L. Zacur
- From the Harvard Medical School, Boston, Mass
- Dermatology Program, Boston Children’s Hospital, Boston, Mass
- St Joseph Mercy Chelsea Hospital, Chelsea, Mich
| | - Lily C. Uihlein
- From the Harvard Medical School, Boston, Mass
- Dermatology Program, Boston Children’s Hospital, Boston, Mass
- Department of Dermatology, Kaiser Permanente, Petaluma, Calif
| | - John B. Mulliken
- From the Harvard Medical School, Boston, Mass
- Department of Plastic and Oral Surgery, Boston Children’s Hospital, Boston, Mass
| | - Marilyn G. Liang
- From the Harvard Medical School, Boston, Mass
- Dermatology Program, Boston Children’s Hospital, Boston, Mass
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16
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Maliqari N, Duka E, Kuneshka L. Cardiac side effects of propranolol in infants treated for infantile haemangiomas. Cardiol Young 2023; 33:2616-2620. [PMID: 37078179 DOI: 10.1017/s1047951123000847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2023]
Abstract
OBJECTIVES This study aims to add proof to the safety profile of propranolol as first-line choice in treating infantile haemangiomas, in particular related to its cardiac side effects the main hindering reason for parents and physicians to start and comply with treatment. METHOD This is a prospective observational and analytic study with a sample of 476 patients diagnosed with infantile haemangioma and treated with systemic propranolol during the time interval January 2011 to December 2021. We studied clinical propranolol adverse events experienced in hospital or outpatient and measured the impact of propranolol on blood pressure and heart rate. RESULTS This study showed that symptomatic adverse events caused by propranolol were mild and severe adverse events were rare. The most common clinical side effects were paleness, sweating, reduced feeding, and agitation. Only in 28 (5.9%) cases these symptoms were severe enough to review treatment, 1.8% had severe respiratory symptoms, 2.7% experienced hypoglycaemia, and 1.2% had heart-related symptoms. Mean blood pressure reduction with treatment was statistically significant only after achieving the maintenance dose 2 mg/kg body weight. Blood pressure under the 5th percentile was registered in 2.9% of cases, but only four patients had symptomatic hypotension. While heart rate reduction was noticed with the first dose, only two experienced symptomatic bradycardia. CONCLUSION We conclude that propranolol is not only an excellent drug in treating infantile haemangioma, but it has also a very safe profile, with mild side effects and very rare severe cardiac adverse events, easily overcome with treatment interruption.
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Affiliation(s)
- Numila Maliqari
- Pediatric Cardiology Department, Mother Theresa University Hospital, Tirana, Albania
| | - Enkeleda Duka
- Pediatric Hemato Oncology Department, Mother Theresa University Hospital, Tirana, Albania
| | - Loreta Kuneshka
- Pediatric Dermatology Department, Mother Theresa University Hospital, Tirana, Albania
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Li L, Yu L, Xu Z, Wei L, Zhang B, Han X, Sun Y, Ma L. Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment. J Cosmet Dermatol 2023; 22:3369-3374. [PMID: 37313653 DOI: 10.1111/jocd.15823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 04/28/2023] [Accepted: 05/04/2023] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. MATERIALS AND METHODS The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. RESULTS Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. CONCLUSIONS The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.
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Affiliation(s)
- Li Li
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Lu Yu
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Zigang Xu
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Li Wei
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Bin Zhang
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Xiaofeng Han
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Yujuan Sun
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
| | - Lin Ma
- Department of Dermatology, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China
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18
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Lin Q, Cai B, Shan X, Ni X, Chen X, Ke R, Wang B. Global research trends of infantile hemangioma: A bibliometric and visualization analysis from 2000 to 2022. Heliyon 2023; 9:e21300. [PMID: 37920523 PMCID: PMC10618776 DOI: 10.1016/j.heliyon.2023.e21300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 10/10/2023] [Accepted: 10/19/2023] [Indexed: 11/04/2023] Open
Abstract
Background Infantile hemangioma (IH) has received global attention, resulting in a significant volume of literature. However, there is a lack of bibliometric analyses specifically focusing on IH publications. This study aims to fill this gap by conducting a comprehensive analysis of IH publications, investigating their characteristics, contribution distribution, and developmental trends. By enhancing our understanding of IH and identifying potential research topics and collaborators, this study will contribute to the advancement of the field. Methods A total of 4333 articles and reviews on IH were collected from the Web of Science (WoS) database, spanning the years 2000-2022. The study encompassed a comprehensive analysis of IH publications, evaluating their quantity and quality. Additionally, we profiled publishing groups based on country, institution, author publication records, and collaboration networks. Lastly, we identified and summarized the prominent research topics. Results Annual publications on IH have increased over the past 20 years. The United States has the highest number of publications and the highest total number of citations. Pediatric Dermatology was the most influential journal in the IH field. The citation analysis indicated that the articles published by Léauté-Labrèze in 2008 had the highest number of citations. The articles published by North PE in 2000 and Boye E in 2001 laid a certain research foundation for this field. Concerning institutions, most of the cooperative relationships were established in the same country/region. The United States has the largest number of scientific research institutions and IH researchers, leading most of the cross-country collaboration. The University of California, San Francisco, Medical College of Wisconsin, Harvard University, and Shanghai Jiaotong University were the research centers that published the most IH-related research. Frieden IJ, Mulliken JB, and Drolet BA were the top three most influential authors. Frieden IJ, Garzon MC, and Mulliken JB were the top three authors with the most cited frequency. In addition, keywords and keyword co-occurrence networks prompted that the pathological mechanism of IH, clinical analysis, and other vascular anomalies are research hotspots. Analysis of trending topics suggests that research on IH has evolved from treatment-focused studies towards investigations of other vascular diseases and a series of clinical case studies. Currently, clinical case studies receive the most attention in the field. Conclusions This comprehensive bibliometric study provides a thorough analysis of post-2000 publications in the field of IH, offering insights into current research trends for the first time. The findings suggest that future investigations will continue to prioritize understanding IH mechanisms, treatment approaches, and treatment evaluation. Furthermore, the exploration of other vascular diseases and the inclusion of clinical case studies are expected to contribute to advancements in IH clinical practice. By identifying potential collaborators, partner institutions, and new research avenues, this study offers valuable guidance for future in-depth research on IH.
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Affiliation(s)
- Qian Lin
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Beichen Cai
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xiuying Shan
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xuejun Ni
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xuanfeng Chen
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Ruonan Ke
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Biao Wang
- Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Plastic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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19
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Saleh JS, Whittington CP, Bresler SC, Patel RM. Cutaneous vascular tumors: an updated review. Hum Pathol 2023; 140:53-65. [PMID: 37059271 DOI: 10.1016/j.humpath.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/30/2023] [Accepted: 04/06/2023] [Indexed: 04/16/2023]
Abstract
Cutaneous vascular tumors constitute a heterogeneous group of entities that share overlapping morphologic and immunohistochemical features, which can be diagnostically challenging for pathologists and dermatopathologists. Our understanding and knowledge of vascular neoplasms have improved over time, resulting in both a refinement of their classification by the International Society for the Study of Vascular Anomalies (ISSVA) and an improvement in the accurate diagnosis and clinical management of vascular neoplasms. This review article aims to summarize the updated clinical, histopathological, and immunohistochemical characteristics of cutaneous vascular tumors, as well as to highlight their associated genetic mutations. Such entities include infantile hemangioma, congenital hemangioma, tufted angioma, spindle cell hemangioma, epithelioid hemangioma, pyogenic granuloma, Kaposiform hemangioendothelioma, retiform hemangioendothelioma, pseudomyogenic hemangioendothelioma, Kaposi sarcoma, angiosarcoma, and epithelioid hemangioendothelioma.
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Affiliation(s)
- Jasmine S Saleh
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
| | | | - Scott C Bresler
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Rajiv M Patel
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA; Cutaneous Pathology, WCP Laboratories, Inc., Maryland Heights, MO 63043, USA.
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20
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Sandru F, Turenschi A, Constantin AT, Dinulescu A, Radu AM, Rosca I. Infantile Hemangioma: A Cross-Sectional Observational Study. Life (Basel) 2023; 13:1868. [PMID: 37763272 PMCID: PMC10532986 DOI: 10.3390/life13091868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/31/2023] [Accepted: 09/02/2023] [Indexed: 09/29/2023] Open
Abstract
(1) Background: With an incidence of 4-10%, infantile hemangiomas (IH) are the most encountered benign tumors in infancy. Low birth weight (LBW), prematurity, female sex, multiple gestations, and family history of IH are some of the statistically proven risk factors for developing IH. The aim of our study was to evaluate the prevalence of IH in our clinic and its connection to maternal and perinatal factors. (2) Methods: We conducted a cross-sectional study, over three years (2020-2022), at the Clinical Hospital of Obstetrics and Gynecology, "Prof. Dr. P. Sârbu", in Bucharest, Romania. (3) Results: During this period, 12,206 newborns were born and we identified 14 infants with infantile hemangioma. In our study, the prevalence of infantile hemangioma was 0.11%. The prevalence of IH in pregnancies obtained through in vitro fertilization was 1%, in twin pregnancies it was 2.27%, and in those with placenta previa, it was 4.16%. (4) Conclusions: Our findings provide a solid image of the prevalence of IH in our country and underline that the development of IH is strongly connected to maternal and perinatal variables, such as: preterm newborns, in vitro fertilization, high blood pressure, anemia, hypothyroidism, placenta previa, and twin pregnancy.
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Affiliation(s)
- Florica Sandru
- Dermatology Department, “Elias” University Emergency Hospital, 011461 Bucharest, Romania;
- Department of Dermatovenerology, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
| | | | - Andreea Teodora Constantin
- Pediatrics Department, National Institute for Mother and Child Health “Alessandrescu-Rusescu”, 20382 Bucharest, Romania;
- Department of Pediatrics, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
| | - Alexandru Dinulescu
- Department of Pediatrics, Grigore Alexandrescu Emergency Hospital for Children, 011743 Bucharest, Romania;
| | - Andreea-Maria Radu
- Dermatology Department, “Elias” University Emergency Hospital, 011461 Bucharest, Romania;
| | - Ioana Rosca
- Department of Neonatology, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania;
- Neonatology Department, Clinical Hospital of Obstetrics and Gynecology “Prof. Dr. P. Sârbu”, 060251 Bucharest, Romania
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21
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Filaj V, Kola I, Gjonaj F. Overview of the Head and Neck Hemangiomas: a 5-year Retrospective Study. Mater Sociomed 2023; 35:244-247. [PMID: 37795158 PMCID: PMC10545920 DOI: 10.5455/msm.2023.35.244-247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 08/29/2023] [Indexed: 10/06/2023] Open
Abstract
Background Infantile hemangiomas (IHs) are benign vascular tumors commonly observed in children. The pathogenesis of hemangiomas is complex and poorly understood. IH occur most commonly on the head and neck. There are different classification of them according to the depth, number, distribution and locations. A multidisciplinary approach is needed for the diagnosis and treatment of hemangiomas because it is easy to misdiagnose or decide on a wrong treatment in the existing single-treatment system. Objective In this retrospective study between 2018 and 2022 we provided an overview of the hemangiomas located in the head and neck in 232 patients, and the different treatment approaches used. Results Of the 232 patients 60.3 % were females and 38.7% males. The youngest age was 10 weeks old and the oldest age who underwent treatment was 79 years old. The most common lesion sites were the mid-cheek, the upper lip and the upper eyelid. 104 patients (53.4 %) underwent surgical intervention due to the location of the lesion, size and functional reasons. Meanwhile 128 patients (46.6 %) were observed and treated with propranolol and pulsed dye laser. Conclusion Hemangiomas are generally benign tumors. Hemangiomas present a number of diagnostic and therapeutic challenges; thus, early diagnosis by a specialist clinic is key in preventing associated morbidity with these vascular tumors.
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Affiliation(s)
- Vladimir Filaj
- University of Medicine, Department of Surgery, Tirana, Albania
| | - Ina Kola
- Department of Burns and Plastic Surgery, Tirana, Albania
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22
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Hermans MM, Pasmans SGMA, De Graaf M, Ragamin A, Mendels EJ, Breur JMPJ, Langeveld HR, Raphael MF, De Laat PCJ, De Wildt SN, Rietman AB, Breugem CC, Schappin R. Prognostic Factors for Long-term Aesthetic Outcome of Infantile Haemangioma Treated with Beta-blockers. Acta Derm Venereol 2023; 103:adv5286. [PMID: 37649330 PMCID: PMC10506515 DOI: 10.2340/actadv.v103.5286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/16/2022] [Indexed: 09/01/2023] Open
Abstract
Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed the influence on the long-term aesthetic outcome of characteristics of the infantile haemangioma, the beta-blocker treatment, and the infant. The study included 103 children aged 6-12 years, treated with beta-blockers (propranolol or atenolol) for infantile haemangioma during infancy (age at treatment initiation ≤1 year) for ≥6 months. Dermatologists and parents scored the Patient Observer Scar Assessment Scale, and the child scored a visual analogue scale. Dermatologists identified whether telangiectasia, fibrofatty tissue, and atrophic scar tissue were present. The long-term aesthetic outcome of infantile haemangioma was judged more negatively by dermatologists and parents in case of a superficial component, ulceration, older age at treatment initiation, higher cumulative dose, and/or shorter follow-up time. According to children, infantile haemangioma located on the head had better aesthetic outcome than infantile haemangioma located elsewhere. Close monitoring, particularly of infantile haemangioma with a superficial component, is essential for early initiation of treatment, and to prevent or treat ulceration. These outcome data can support parental counselling and guide treatment strategy.
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Affiliation(s)
- Mireille M Hermans
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands
| | - Suzanne G M A Pasmans
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands.
| | - Marlies De Graaf
- Department of Dermatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, UMC Utrecht Center for Vascular Anomalies, The Netherlands
| | - Aviël Ragamin
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands
| | - Elodie J Mendels
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Dermatology - Center of Pediatric Dermatology, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands
| | - Johannes M P J Breur
- Department of Pediatric Cardiology, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands
| | - Hester R Langeveld
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Intensive Care and Pediatric Surgery, Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands
| | - Martine F Raphael
- Department of Dermatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, UMC Utrecht Center for Vascular Anomalies, The Netherlands
| | - Peter C J De Laat
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Pediatrics (-Hemato-oncology), Center of Rare Skin Diseases, Vascular Anomaly Center Erasmus MC Rotterdam, member of the ERN-SKIN-Mosaic group and ERN-VASCERN-VASCA group, The Netherlands
| | - Saskia N De Wildt
- Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - André B Rietman
- Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Department of Child and Adolescent Psychology/Psychiatry, the Netherlands
| | - Corstiaan C Breugem
- Department of Plastic Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, UMC Utrecht Center for Vascular Anomalies, The Netherlands
| | - Renske Schappin
- Department of Surgery, Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands
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23
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Raicu AM, Danila GF, Secheli IF, Bratu EC, Minca DG. Infantile Haemangioma in the Romanian Paediatric Population-Characteristics and Therapeutic Approaches. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1314. [PMID: 37628313 PMCID: PMC10453925 DOI: 10.3390/children10081314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/20/2023] [Accepted: 07/27/2023] [Indexed: 08/27/2023]
Abstract
Infantile haemangioma (IH) is the most common benign tumour in childhood, with an incidence of 4% to 12%. Aim: to describe the characteristics of infantile haemangioma in a sample of Romanian children <2 years old at diagnosis, types of treatment applied, recorded complications and the response to the therapeutic approach. A two-year prospective case series study (August 2019 to August 2021) was carried out. Sample: 117 patients <24 months of age diagnosed with IH at the Emergency Hospital for Children "Marie Sklodowska Curie", in Bucharest, Romania. Five therapeutic approaches were used: oral treatment with propranolol, local treatment with timolol, surgical treatment, topical treatment with steroids and no treatment ("wait and see"). Recorded factors mentioned in the literature were also present in this study population: female patients-68.4%; phototype I-58%. In 53% of cases, IHs had a head and neck location and 10% developed local complications (traumatic bleeding). The majority of patients (86%) required one type of therapy: oral propranolol (51%). A low relapse rate was recorded (4%). We consider that any child with a vascular anomaly should be referred to a highly specialised medical service for therapeutic approach.
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Affiliation(s)
- Anca-Maria Raicu
- Department of Public Health and Management, “Carol Davila” University of Medicine and Pharmacy, 050463 Bucharest, Romania; (E.C.B.); (D.G.M.)
- Department of Paediatric Surgery, Emergency Hospital for Children “M.S.Curie”, 041451 Bucharest, Romania
| | - George-Florin Danila
- Department of Paediatric Surgery, Emergency Hospital for Children “M.S.Curie”, 041451 Bucharest, Romania
| | - Ionut Fernando Secheli
- Department of Paediatric Surgery, Emergency Hospital for Children “M.S.Curie”, 041451 Bucharest, Romania
| | - Eugenia Claudia Bratu
- Department of Public Health and Management, “Carol Davila” University of Medicine and Pharmacy, 050463 Bucharest, Romania; (E.C.B.); (D.G.M.)
| | - Dana Galieta Minca
- Department of Public Health and Management, “Carol Davila” University of Medicine and Pharmacy, 050463 Bucharest, Romania; (E.C.B.); (D.G.M.)
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24
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Incidence and clinical factors associated with ulceration in infantile hemangiomas. J Am Acad Dermatol 2023; 88:414-420. [PMID: 36404484 DOI: 10.1016/j.jaad.2022.10.047] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 10/14/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Ulceration is an important complication in infantile hemangiomas (IHs). Prior to the use of β-blockers, the estimated incidence of this complication in a referral population was between 15% and 30%. The incidence and factors associated with ulceration have not been systematically studied since the emergence of β-blocker therapy. OBJECTIVE Examine the incidence and clinical predictors for ulceration in IHs. METHODS Retrospective study at tertiary referral centers. RESULTS Compared with a previous large pre-propranolol cohort study, ulceration occurred at a significantly lower incidence of 11.4%. Clinical factors associated with ulceration included partial segmental morphology, location in the diaper area, and size greater than 5 cm. Higher risk of ulceration in Black patients was observed, suggesting barriers to care including delayed diagnosis and referral to specialty care. LIMITATIONS Retrospective design at tertiary referral centers. CONCLUSION Compared with reports before the use of β-blockers became widespread, the incidence of ulceration in IHs has decreased. However, it continues to be a relatively frequent complication of IH.
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25
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Long-term neurocognitive functioning of children treated with propranolol or atenolol for infantile hemangioma. Eur J Pediatr 2023; 182:757-767. [PMID: 36478294 PMCID: PMC9899165 DOI: 10.1007/s00431-022-04674-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/13/2022] [Accepted: 10/22/2022] [Indexed: 12/13/2022]
Abstract
UNLABELLED The purpose of this study was to compare long-term neurocognitive functioning (working memory, processing speed, and attention) between children who had been treated with either propranolol or atenolol for infantile hemangioma during infancy. All eligible children (n = 158) aged 6 years or older and treated with propranolol or atenolol as infants were invited to participate in this two-center cross-sectional study. The primary outcome was the Wechsler Intelligence Scale for Children-V Cognitive Proficiency Index (CPI), a measure of working memory, processing speed, and attention. Secondary outcomes were general intelligence, auditory, visuospatial, and narrative memory, as well as executive functioning and sleep. A total of 105 children, of whom 36 had been treated with propranolol (age 6.0-11.8 years, follow-up time 1.6-9.7 years, 19% male) and 69 had been treated with atenolol (age 6.9-9.7 years, follow-up time 4.5-8.4 years, 19% male), were analyzed. The CPI and other neurocognitive outcomes did not differ between the propranolol and atenolol groups and were in line with general population test norms. Post hoc analyses revealed lower CPI scores for males, both compared to participating females (10.3 IQ points, medium effect size) and compared to matched test norms (12.4 IQ points, medium effect size). CONCLUSIONS Long-term neurocognitive functioning did not differ between children treated with propranolol and those treated with atenolol for IH. Overall, propranolol and atenolol appear to be safe treatments for IH regarding long-term neurocognitive functioning. The substantially lower CPI scores in males warrant further investigation. TRIAL REGISTRATION Netherlands Trial Register, NL7703 https://www.trialregister.nl/trial/7703 What is Known: • Infants with infantile hemangioma are effectively treated with propranolol or atenolol. • Parents and professionals are concerned about long-term neurocognitive effects. WHAT IS NEW • No long-term (≥ 6 years) differences in neurocognitive functioning were found between children treated with propranolol or atenolol. • Males treated with beta-blockers had substantially lower IQ scores than treated females and males from the general population, which is a matter of concern and should be considered when evaluating the risk/benefit ratio in less severe forms of infantile hemangioma.
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26
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Zhao B, Li B, Zhang J, Qi Y, Chen B, Chen L. Construction of miRNA-mRNA Regulatory Network to Identify Potential Biomarkers in Infantile Hemangioma by Integrated Bioinformatics Analysis. Crit Rev Eukaryot Gene Expr 2023; 33:61-71. [PMID: 37199314 DOI: 10.1615/critreveukaryotgeneexpr.v33.i5.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Infantile hemangioma (IH) is the most common vascular tumor among infants and children. However, the understanding of pathogenesis about IH has not been fully elucidated, and the potential diagnostic maker remains further explored. In this study, we aimed to find miRNAs as potential biomarkers of IH through bioinformatic analysis. The microarray datasets GSE69136, GSE100682 were downloaded from the GEO database. The co-expressed differential miRNAs were identified by analyzing these two datasets. The downstream common target genes were predicted by the ENCORI, Mirgene, miRWalk, and Targetscan databases. GO annotation and KEGG pathway enrichment analysis for target genes were performed. The STRING database and Cytoscape software were used to construct the protein-protein interaction network and screen hub genes. Then potential diagnostic markers for IH were further screened and identified by using Receiver operating characteristic curve analysis. A total of thirteen co-expressed up-regulated miRNAs were screened out in the above two datasets, and 778 down-regulated target genes were then predicted. GO annotation and KEGG pathway enrichment analysis indicated that the common target genes strongly correlated with IH. Through the DEM-hub gene network construction, six miRNAs associated with the hub genes were identified. Finally, has-miR-522-3p, has-miR-512-3p, has-miR-520a-5p with high diagnostic values were screened out by receiver operating characteristic analysis. In the study, the potential miRNA-mRNA regulatory network was firstly constructed in IH. And, the three miRNAs might be used as potential biomarkers for IH, which also provided novel strategies for the therapeutic intervention of IH.
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Affiliation(s)
- Boming Zhao
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Bin Li
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Jun Zhang
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Yongjian Qi
- Department of Spine Surgery and Musculoskeletal Tumor, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Biao Chen
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Liaobin Chen
- Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
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27
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Kabagenyi F, Anena SP, Seguya A. 19 Months Toddler with a Giant Oral Capillary Hemangioma, a Case Report. Int Med Case Rep J 2023; 16:287-291. [PMID: 37213705 PMCID: PMC10198171 DOI: 10.2147/imcrj.s406901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/09/2023] [Indexed: 05/23/2023] Open
Abstract
Head and neck vascular tumors are common in children. Capillary hemangiomas are often easily confused with pyogenic granulomas due to histopathological resemblance. Furthermore, predisposing factors to pyogenic granulomas include an existing hemangioma, which may be co-existing entities. Surgical excision of large unsightly tumors causing functional deficits is a feasible management option. We report a case of a rapidly growing oral lesion in a toddler with feeding difficulties and anemia. It triggered a diagnostic dilemma as it was clinically consistent with a pyogenic granuloma but histologically diagnosed as a capillary hemangioma. It was successfully excised with no recurrence after 6 months.
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Affiliation(s)
- Fiona Kabagenyi
- Department of Ear Nose and Throat, Makerere University, Kampala, Uganda
| | | | - Amina Seguya
- Department of Ear Nose and Throat, Mulago National Referral Hospital, Kampala, Uganda
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28
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MacDougall MS, Afzal SY, Freedman MS, Han P. Infant in extremis: respiratory failure secondary to lower airway infantile hemangioma. BMC Pediatr 2022; 22:744. [PMID: 36581920 PMCID: PMC9801545 DOI: 10.1186/s12887-022-03821-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 12/24/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Infantile hemangiomas (IHs) are vascular tumors that commonly affect infants and usually regress spontaneously or can be easily treated as an outpatient with topical beta-blockers. However, IHs that present in the airway may cause life-threatening symptoms due to airway obstruction or risk of bleeding. Here we present the first documented case of an infant with rapid deterioration and acute respiratory failure secondary to a lower airway hemangioma. CASE PRESENTATION This 3-month-old male initially presented in respiratory distress with symptoms consistent with a viral respiratory infection, however showed no clinical improvement with standard therapies. An urgent CT scan revealed a mass occluding the right mainstem bronchus. Upon transfer to a tertiary care facility, he developed acute respiratory failure requiring emergent intubation and single lung ventilation. The availability of multiple subspecialists allowed for stabilization of a critically ill child, expedited diagnosis, and ultimately initiation of life-saving treatment with beta blockers. After 17 total hospital days, he was extubated successfully and discharged home in good condition. CONCLUSIONS While IH is a rare cause of infantile respiratory distress, we present multiple pearls for the general pediatrician for management of IHs of the airway.
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Affiliation(s)
- Matthew S MacDougall
- Lucile Packard Children's Hospital, Palo Alto, California, USA.
- Stanford University School of Medicine, Department of Pediatrics, Palo Alto, California, USA.
| | - Sarah Y Afzal
- Lucile Packard Children's Hospital, Palo Alto, California, USA
- Stanford University School of Medicine, Department of Pediatrics, Palo Alto, California, USA
| | - Michael S Freedman
- Lucile Packard Children's Hospital, Palo Alto, California, USA
- Stanford University School of Medicine, Department of Pediatrics, Division of Pediatric Critical Care Medicine, Palo Alto, California, USA
| | - Peggy Han
- Lucile Packard Children's Hospital, Palo Alto, California, USA
- Stanford University School of Medicine, Department of Pediatrics, Division of Pediatric Critical Care Medicine, Palo Alto, California, USA
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29
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Bajpai S, Naranje KM, Gautam A, Singh A. A Case of Unilateral Facial Swelling. Neoreviews 2022; 23:771-773. [PMID: 36316257 DOI: 10.1542/neo.23-10-e771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Affiliation(s)
- Shivani Bajpai
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Kirti M Naranje
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Arun Gautam
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anita Singh
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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30
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Zhang AJ, Lindberg N, Chamlin SL, Haggstrom AN, Mancini AJ, Siegel DH, Drolet BA. Development of an artificial intelligence algorithm for the diagnosis of infantile hemangiomas. Pediatr Dermatol 2022; 39:934-936. [PMID: 36164801 DOI: 10.1111/pde.15149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/11/2022] [Indexed: 11/28/2022]
Abstract
Prompt and accurate diagnosis of infantile hemangiomas is essential to prevent potential complications. This can be difficult due to high rates of misdiagnosis and poor access to pediatric dermatologists. In this study, we trained an artificial intelligence algorithm to diagnose infantile hemangiomas based on clinical images. Our algorithm achieved a 91.7% overall accuracy in the diagnosis of facial infantile hemangiomas.
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Affiliation(s)
- April J Zhang
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | | | - Sarah L Chamlin
- Department of Pediatrics and Dermatology, Northwestern University Feinberg School of Medicine/Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - Anita N Haggstrom
- Department of Pediatrics and Dermatology, Indiana University, Indianapolis, Indiana, USA
| | - Anthony J Mancini
- Department of Pediatrics and Dermatology, Northwestern University Feinberg School of Medicine/Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - Dawn H Siegel
- Department of Dermatology, and by courtesy, Pediatrics, Stanford University School of Medicine, Stanford, California, USA
| | - Beth A Drolet
- Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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Huang B, Zhang P, Zhong YY, Wang K, Chen XM, Yu DJ. Transcriptional data analysis reveals the association between infantile hemangiomas and venous malformations. Front Genet 2022; 13:1045244. [PMID: 36338963 PMCID: PMC9626979 DOI: 10.3389/fgene.2022.1045244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/10/2022] [Indexed: 11/14/2022] Open
Abstract
Background: Infantile hemangiomas (IH) and venous malformations (VM) are the most common types of vascular abnormalities that seriously affect the health of children. Although there is evidence that these two diseases share some common genetic changes, the underlying mechanisms need to be further studied. Methods: The microarray datasets of IH (GSE127487) and VM (GSE7190) were downloaded from GEO database. Extensive bioinformatics methods were used to investigate the common differentially expressed genes (DEGs) of IH and VM, and to estimate their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Trough the constructing of protein-protein interaction (PPI) network, gene models and hub genes were obtained by using Cytoscape and STRING. Finally, we analyzed the co-expression and the TF-mRNA-microRNA regulatory network of hub genes. Results: A total of 144 common DEGs were identified between IH and VM. Functional analysis indicated their important role in cell growth, regulation of vasculature development and regulation of angiogenesis. Five hub genes (CTNNB1, IL6, CD34, IGF2, MAPK11) and two microRNA (has-miR-141-3p, has-miR-150-5p) were significantly differentially expressed between IH and normal control (p < 0.05). Conclusion: In conclusion, our study investigated the common DEGs and molecular mechanism in IH and VM. Identified hub genes and signaling pathways can regulate both diseases simultaneously. This study provides insight into the crosstalk of IH and VM and obtains several biomarkers relevant to the diagnosis and pathophysiology of vascular abnormalities.
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Affiliation(s)
- Biao Huang
- Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China
- West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China
| | - Ping Zhang
- Department of Plastic Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yuan-Yuan Zhong
- Department of Health Management Center, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Kuan Wang
- Department of Plastic Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xiao-Ming Chen
- Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China
- *Correspondence: Dao-Jiang Yu, ; Xiao-Ming Chen,
| | - Dao-Jiang Yu
- Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China
- West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China
- *Correspondence: Dao-Jiang Yu, ; Xiao-Ming Chen,
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32
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Goldenberg DC, Zatz RF. Surgical Treatment of Vascular Anomalies. Dermatol Clin 2022; 40:473-480. [DOI: 10.1016/j.det.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Pensabene M, Di Pace MR, Baldanza F, Grasso F, Patti M, Sergio M, La Placa S, Giuffre' M, Serra G, Casuccio A, Cimador M. Quality of life improving after propranolol treatment in patients with Infantile Hemangiomas. Ital J Pediatr 2022; 48:140. [PMID: 35927685 PMCID: PMC9351120 DOI: 10.1186/s13052-022-01334-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 07/28/2022] [Indexed: 11/13/2022] Open
Abstract
Infantile hemangiomas may affect the quality of life (QoL) of patients and their family members, as anxiety and worry may commonly occur in parents, also linked to the social adversion they experience. We underline the beneficial impact of oral propranolol therapy on QoL of patients with infantile hemangiomas (IH) and of their relatives. A specific questionnaire measuring QoL was administered to parents of IH patients at beginning and end of a treatment with oral propranolol. Different aspects were investigated: site of the lesion, age of patients at starting therapy, length of treatment, occurrence of adverse effects and persistence/recurrence of the vascular anomaly. In all cases the questionnaire revealed a significant improvement of QoL, which was independent from all analyzed factors. It showed that oral propranolol administration in these patients combines optimal clinical results with relevant improvement of QoL, especially in cases of early management. The improvement of QoL seems unrelated to site of lesion, timing and duration of therapy, occurrence of drug-related adverse effects and persistence/recurrence of disease.
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Affiliation(s)
- Marco Pensabene
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Maria Rita Di Pace
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Fabio Baldanza
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Francesco Grasso
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Maria Patti
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Maria Sergio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Simona La Placa
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Mario Giuffre'
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Gregorio Serra
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
| | - Alessandra Casuccio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Marcello Cimador
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
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Kaulanjan-Checkmodine P, Oucherif S, Prey S, Gontier E, Lacomme S, Loot M, Miljkovic-Licina M, Cario M, Léauté-Labrèze C, Taieb A, Moisan F, Rezvani HR. Is Infantile Hemangioma a Neuroendocrine Tumor? Int J Mol Sci 2022; 23:ijms23095140. [PMID: 35563552 PMCID: PMC9104933 DOI: 10.3390/ijms23095140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 02/04/2023] Open
Abstract
Infantile hemangioma (IH) is the most common infantile tumor, affecting 5–10% of newborns. Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is currently the first-line treatment for severe IH; however, both its mechanism of action and its main cellular target remain poorly understood. Since betablockers can antagonize the effect of natural ADRB agonists, we postulated that the catecholamine produced in situ in IH may have a role in the propranolol response. By quantifying catecholamines in the IH tissues, we found a higher amount of noradrenaline (NA) in untreated proliferative IHs than in involuted IHs or propranolol-treated IHs. We further found that the first three enzymes of the catecholamine biosynthesis pathway are expressed by IH cells and that their levels are reduced in propranolol-treated tumors. To study the role of NA in the pathophysiology of IH and its response to propranolol, we performed an in vitro angiogenesis assay in which IH-derived endothelial cells, pericytes and/or telocytes were incorporated. The results showed that the total tube formation is sensitive to propranolol only when exogenous NA is added in the three-cell model. We conclude that the IH’s sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.
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Affiliation(s)
| | - Sandra Oucherif
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
| | - Sorilla Prey
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Service de Dermatologie Adulte et Pédiatrique, CHU de Bordeaux, F-33000 Bordeaux, France
| | - Etienne Gontier
- Electron Microscopy Unit, Bordeaux Imaging Center, F-33076 Bordeaux, France; (E.G.); (S.L.)
| | - Sabrina Lacomme
- Electron Microscopy Unit, Bordeaux Imaging Center, F-33076 Bordeaux, France; (E.G.); (S.L.)
| | - Maya Loot
- CHU de Bordeaux, Service de Chirurgie Pédiatrique, F-33000 Bordeaux, France;
| | - Marijana Miljkovic-Licina
- Department of Pathology and Immunology, University of Geneva Medical School, Rue Michel-Servet 1, CH-1211 Geneva, Switzerland;
| | - Muriel Cario
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France
| | - Christine Léauté-Labrèze
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Service de Dermatologie Adulte et Pédiatrique, CHU de Bordeaux, F-33000 Bordeaux, France
- Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France
| | - Alain Taieb
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Service de Dermatologie Adulte et Pédiatrique, CHU de Bordeaux, F-33000 Bordeaux, France
- Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France
| | - François Moisan
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Correspondence: (F.M.); (H.R.R.)
| | - Hamid Reza Rezvani
- BRIC, UMR 1312, Inserm, University Bordeaux, F-33076 Bordeaux, France; (P.K.-C.); (S.O.); (S.P.); (M.C.); (C.L.-L.); (A.T.)
- Centre de Référence pour les Maladies Rares de la Peau, CHU de Bordeaux, INSERM U1312, F-33000 Bordeaux, France
- Correspondence: (F.M.); (H.R.R.)
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Kashiwagura Y, Hakamata A, Shirai M, Endoh A, Tanaka S, Inui N, Watanabe H, Namiki N, Uchida S. Topical Formulations of Propranolol for Infantile Hemangiomas: Characteristics of Formulations and Three Cases of Infants Administered Topical Propranolol Cream. Chem Pharm Bull (Tokyo) 2022; 70:277-282. [DOI: 10.1248/cpb.c21-00997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Yasuharu Kashiwagura
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
| | | | | | | | - Shimako Tanaka
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
| | - Naoki Inui
- Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine
| | - Hiroshi Watanabe
- Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine
| | - Noriyuki Namiki
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
| | - Shinya Uchida
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
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Bleve C, Conighi ML, Valerio E, Cutrone M, Iannucci G, Segna A, Chiarenza SF. Surgical management of large scalp infantile hemangioma in 30-month-old infant. LA PEDIATRIA MEDICA E CHIRURGICA 2022; 44. [DOI: 10.4081/pmc.2022.279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 03/08/2022] [Indexed: 11/23/2022] Open
Abstract
Infantile Hemangiomas (IH) are the most common benign tumor of infancy, occurring in over 10% of newborns. The head and neck is the most frequently affected area (60%), and the scalp is a typical site for such large lesions. Scalp-IHs are usually focal lesions that can be both disfiguring and may lead to complications such as ulceration and bleeding. We describe a case of a 30-months old female who presented a large scalp-IH at birth that rapidly grew in the first year of life. Topical and systemic treatments (with timolol ointment and oral propranolol, respectively) were not effective in reducing dimensions of the hemangioma. After vascular imaging study, the patient underwent surgical resection of the IH and primary closure with excellent cosmetic outcome. When medical therapy is ineffective or cosmetic and functional integrity is threatened, early surgery allows to completely removing large scalp-IHs, with good cosmetic results.
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Meyer-Mueller C, Nicholson C, Polcari I, Boull C, Maguiness S. Worsening ulceration of infantile hemangioma after initiation or escalation of propranolol. Pediatr Dermatol 2022; 39:255-259. [PMID: 35178750 DOI: 10.1111/pde.14933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 01/01/2022] [Accepted: 01/15/2022] [Indexed: 11/30/2022]
Abstract
For infantile hemangiomas (IH) requiring treatment, including those in high-risk locations or in the setting of ulceration, oral propranolol is first-line therapy. Here, we present three cases of infantile hemangioma with worsening ulceration following initiation or escalation of oral propranolol at standard doses.
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Affiliation(s)
- Cameron Meyer-Mueller
- Department of Dermatology, Division of Pediatric Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Cynthia Nicholson
- Department of Dermatology, Division of Pediatric Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Ingrid Polcari
- Department of Dermatology, Division of Pediatric Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Christina Boull
- Department of Dermatology, Division of Pediatric Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Sheilagh Maguiness
- Department of Dermatology, Division of Pediatric Dermatology, University of Minnesota, Minneapolis, Minnesota, USA
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Hadrawi M, Alghamdi A, Alageel N, Abudawood G, Alshareef F, Abuauf M. Early vascular embolization of large orbital and periorbital infantile capillary hemangiomas; A case report. Am J Ophthalmol Case Rep 2022; 25:101377. [PMID: 35198806 PMCID: PMC8851098 DOI: 10.1016/j.ajoc.2022.101377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 01/28/2022] [Indexed: 12/02/2022] Open
Abstract
Purpose Infantile hemangiomas (IH) are the most common benign vascular tumors in childhood. Although they tend to have a benign nature, some hemangiomas may be complicated with astigmatism or deprivation amblyopia. We report a unique case of using an interventional radiological vascular embolization treatment modality for the early management of amblyogenic large right orbital and periorbital infantile capillary hemangiomas. Observations After the confirmation of the diagnosis using a magnetic resonance imaging (MRI) of the brain and orbit, and an initial trial of systemic propranolol, an early interventional radiological vascular embolization was done. This was combined with the use of a tapering systemic corticosteroid. The functional and cosmetic outcomes were satisfactory. Conclusions and Importance The use of arterial embolization is a promising modality of treatment as a possible alternative or adjunct to medical and surgical treatment cases of IH. To the authors’ knowledge, this is one of the rare cases reported in the ophthalmic literature addressing the use of this technique for early management of orbital and periorbital capillary hemangiomas.
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Affiliation(s)
- Manal Hadrawi
- Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Amer Alghamdi
- Department of Family Medicine, Ministry of National Guard - Health Affairs, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Nourah Alageel
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Ghufran Abudawood
- Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Fawaz Alshareef
- Department of Radiology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Mawahib Abuauf
- Department of Pediatrics, Neonatal Division, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
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Mariani LG, Ferreira LM, Rovaris DL, Bonamigo RR, Kiszewski AE. Infantile hemangiomas: risk factors for complications, recurrence and unaesthetic sequelae. An Bras Dermatol 2022; 97:37-44. [PMID: 34848114 PMCID: PMC8799848 DOI: 10.1016/j.abd.2021.05.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/03/2021] [Accepted: 05/11/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Infantile hemangiomas (IH) occur in approximately 4% to 10% of the pediatric population. The identification of clinical subtypes and conditions that indicate increased risk for complications is essential for therapeutic success. OBJECTIVES To identify risk factors for complications, recurrence and unaesthetic sequelae. METHODS Retrospective cohort of patients with infantile hemangiomas undergoing follow-up at the Dermatology Service of Universidade Federal de Ciências da Saúde de Porto Alegre, between 2006 and 2018. RESULTS 190 patients were included; 24% had some type of complication, ulceration being the most frequent, and 86% required treatment. On correlation, ulceration was statistically related to mixed IH (p = 0.004), segmental IH (p < 0.01) and location in the gluteal region (p = 0.001). The mean time of treatment with propranolol was 12.7 months. Patients with PHACES syndrome and segmental infantile hemangioma required longer treatment (p < 0.001 and p = 0.0407, respectively), as well as those who started treatment after five months of life (p < 0.0001). Recurrence occurred in 16.6% of the treated patients, all-female; 94% were located on the head and neck (mainly on the upper eyelid, cyrano, S3 segment, and with parotid involvement); 61% and 38.8% were of the mixed and deep subtypes, respectively. Approximately 1/3 of the patients had some unaesthetic sequelae. STUDY LIMITATIONS As this is a retrospective study, data and photos of some patients were lost. CONCLUSIONS Mixed and segmental hemangiomas are risk factors for ulceration and sequelae. Recurrence occurs more often in females and segmental hemangiomas. Segmental infantile hemangioma and PHACES syndrome require a longer time of treatment. Specific protocols are required for infantile hemangiomas with a high risk of recurrence.
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Affiliation(s)
- Letícia Gaertner Mariani
- Postgraduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | | | - Diego Luiz Rovaris
- Department of Physiology and Biophysics, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Renan Rangel Bonamigo
- Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Service of Dermatology, Santa Casa de Misericórdia de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | - Ana Elisa Kiszewski
- Service of Dermatology, Santa Casa de Misericórdia de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil; Department of Internal Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
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Peng W, Liu H, Chen J, Zheng Y, Xu X, Tang H, Liu Q. Development and validation of psychological status questionnaire for parents of infantile hemangiomas. Transl Pediatr 2021; 10:3261-3272. [PMID: 35070840 PMCID: PMC8753469 DOI: 10.21037/tp-21-554] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 12/16/2021] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Infantile hemangioma (IH) is the most frequent benign tumor of infancy which impacts the psychological status of parents of affected children. Parental psychological status has a significant effect on the therapeutic effect and long-term prognosis of IH children. However, no standard questionnaires had been established previously to assess the psychological status of Chinese parents of children with IH. METHODS This study prospectively developed and validated a psychological status instrument for the assessment of parents of patients with IH and to identify clinical features with effects on the psychological status. A total of 350 parents completed the 35-item Psychologic Status Questionnaire for parents of Infantile Hemangiomas (IH-PSQ) and provided demographic information. The IH-PSQ was refined via item analysis, validity analysis (including exploratory factor analysis and criterion-related validity) and reliability analysis (including internal consistency reliability, split half reliability, and test-retest reliability). RESULTS The dimensionality of the items was evaluated using factor analysis, with results suggesting 5 factors: anxiety, depression, psychological imbalance, disease shame, and disease fear. The final instrument consists of 4 scales with a total of 23 items. Construct validity was demonstrated and IH-PSQ showed good internal coherence (Cronbach's α: 0.957), good split half reliability (0.971), and good test-retest reliability (correlation coefficient: 0.967). The correlation coefficient between the Self-Rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) of children with IH was 0.874 and 0.754, respectively. Multiple linear regression analysis found that some characteristics will affect the score of IH-PSQ. CONCLUSIONS The IH-PSQ contains 5 dimensions and 23 entries, and with good reliability and validity, can objectively and effectively evaluate the psychological status of IH parents. Certain clinical characteristics of IH families, including parents' own factors (including their monthly income and cultural level) and disease-related factors of affected children (including the duration of illness, tumor size, with or without complications, single or multiple, whether being treated or not), were associated with a greater impact on IH-PSQ.
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Affiliation(s)
- Wei Peng
- Department of Graduate School, China Medical University, Shenyang, China.,Department of Pediatric Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.,Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province, Ganzhou, China
| | - Haijin Liu
- Department of Graduate School, China Medical University, Shenyang, China.,Department of Pediatric Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.,Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province, Ganzhou, China
| | - Jincai Chen
- Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yanan Zheng
- Department of Medical Psychology, Gannan Medical University, Ganzhou, China
| | - Xianyun Xu
- Department of Basic Medical Science, Gannan Medical University, Ganzhou, China
| | - Hong Tang
- Department of Medical Psychology, Gannan Medical University, Ganzhou, China
| | - Qian Liu
- Department of Graduate School, China Medical University, Shenyang, China.,Department of Graduate School, Jiangxi University of Chinese Medicine, Nanchang, China.,Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Hemangioma, Jiangxi University of Chinese Medicine, Nanchang, China
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Cai Y, Ge Y, Ung COL, Li F, Wang J, Xia C, Hu H. Treatment patterns and outcomes in children with infantile hemangiomas: A retrospective observational analysis. SAGE Open Med 2021; 9:20503121211056844. [PMID: 34938569 PMCID: PMC8685728 DOI: 10.1177/20503121211056844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 10/13/2021] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE This study aimed to make use of real-world medical records to explore the clinical characteristics, treatments, and outcomes of infantile hemangiomas in southeastern China. METHODS This study applied a retrospective observational method using real-world data derived from the electronic medical records of the Foshan Women and Children Hospital, southeastern China dated between June 2014 and June 2019. RESULTS A total of 2427 patients with infantile hemangiomas were recruited in this study, including 942 (38.8%) males and 1485 (61.2%) females. Among the participants, 620 (25.5%) were high-risk infantile hemangioma, 449 (18.5%) were medium risk, and 1358 (56.0%) were low risk. A total of 14 treatment patterns in clinical practice were identified. The top 3 treatment patterns in each group of risk levels were the same: laser therapy, a combination of laser therapy and topical timolol maleate, and topical timolol maleate. The outcomes of the top 3 treatment patterns were significantly (P < 0.05) different in each risk group. CONCLUSION Among the top 3 treatment patterns, laser therapy or a combination of laser therapy and topical timolol maleate were more likely to have an "Excellent" outcome.
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Affiliation(s)
- Yantao Cai
- Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China
| | - Ying Ge
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
| | - Carolina Oi Lam Ung
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
| | - Fuli Li
- Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China
| | - Jiaqi Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
| | - Chenglai Xia
- Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, China
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Hao Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
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Propranolol Suppresses Proliferation and Migration of HUVECs through Regulation of the miR-206/VEGFA Axis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:7629176. [PMID: 34697590 PMCID: PMC8541866 DOI: 10.1155/2021/7629176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 09/24/2021] [Indexed: 01/08/2023]
Abstract
Propranolol has been used in the first-line therapy of infantile hemangioma (IH) for a number of years; however, the mechanisms through which propranolol regulates IH are not yet fully understood. In the present study, microRNA (miRNA/miR) sequencing analysis was performed to identify differentially expressed miRNAs in human umbilical vascular endothelial cells (HUVECs) treated with propranolol. Cell viability and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. Cell migration was assessed using wound healing, Transwell, and tube formation assays. Methylation-specific PCR was then used to investigate the promoter methylation status. The levels of oxidative stress indicators, including superoxide dismutase, glutathione, and malondialdehyde were also detected. Finally, cell cycle analysis was performed using flow cytometry and western blotting. It was observed that propranolol induced the upregulation of miR-206 in HUVECs, which was caused by demethylation of the miR-206 promoter. Moreover, propranolol significantly inhibited the proliferation of HUVECs by inducing apoptosis, while these phenomena were reversed by miR-206 antagomir. VEGFA was found to be a target gene of miR-206. In addition, propranolol notably inhibited the migration and induced G1 arrest of the HUVECs, whereas these results were eliminated by miR-206 antagomir. Collectively, the findings of the present study demonstrated that propranolol may inhibit the proliferation and migration in HUVECs via modulating the miR-206/VEGFA axis. These findings suggest a novel mechanism through which propranolol suppresses the progression of IH.
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Liu C, Zhao Z, Guo S, Zhang L, Fan X, Zheng J. Exosomal miR-27a-3p derived from tumor-associated macrophage suppresses propranolol sensitivity in infantile hemangioma. Cell Immunol 2021; 370:104442. [PMID: 34634611 DOI: 10.1016/j.cellimm.2021.104442] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 09/18/2021] [Accepted: 09/20/2021] [Indexed: 12/14/2022]
Abstract
Propranolol is the first-line drug for infantile hemangioma (IH) therapy, whereas propranolol resistance is clinically observed. Tumor-associated macrophages (TAMs)-derived exosomes may deliver biological molecules to promote tumor progression. Here, we aimed to investigate the relationship between TAMs-derived exosomal miR-27a-3p and propranolol sensitivity in IH. Human peripheral blood monocytes (PBMCs) were cultured with macrophage colony-stimulating factor (M-CSF) for 7 days to get unactivated macrophages (Un-Mac), which were further treated with IL-4 and IL-13 to induce M2 polarized macrophages. Exosomes were isolated from the conditioned medium of M2 macrophage, followed by identification. Cell co-culture and/or transfection were performed to explore whether M2 polarized macrophage-derived exosomes (M2-exos) could mediate the crosstalk between TAMs-derived miR-27a-3p and hemangioma stem cells (HemSCs). In addition, nude mice were subcutaneously transplanted with HemSCs pretreated with or without M2-Exos to examine the effects of M2-Exos on IH in vivo. M2 polarized macrophages inhibited propranolol sensitivity of HemSCs, as shown by the increased cell viability and decreased apoptosis. miR-27a-3p was upregulated in M2 polarized macrophages and M2-Exos. Moreover, M2-exos delivered miR-27a-3p from macrophages to HemSCs and subsequently reduced propranolol sensitivity. Luciferase reporter and biotin-RNA pulldown assay proved that dickkopf-related protein 2 (DKK2) was the direct target of miR-27a-3p. These results demonstrate that M2-exos could deliver miR-27a-3p from macrophages to HemSCs to reduce the sensitivity of HemSCs to propranolol by down-regulating DKK2 expression, and exosomal miR-27a-3p and DKK2 in HemSCs could be considered as treatment targets.
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Affiliation(s)
- Chao Liu
- Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
| | - Zeliang Zhao
- Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Shikai Guo
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
| | - Ling Zhang
- Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Xindong Fan
- Department of Interventional Therapy, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jiawei Zheng
- Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
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Kowalska M, Dębek W, Matuszczak E. Infantile Hemangiomas: An Update on Pathogenesis and Treatment. J Clin Med 2021; 10:4631. [PMID: 34682753 PMCID: PMC8539430 DOI: 10.3390/jcm10204631] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 09/25/2021] [Accepted: 10/05/2021] [Indexed: 12/13/2022] Open
Abstract
Infantile hemangiomas are the most common benign vascular tumors in infancy. This review includes an update on the current knowledge on pathogenesis, a discussion on indications for treatment, and a review of the mechanisms underlying the different treatment methods. Although most infantile hemangiomas require only active observation because of their natural course, which results in involution, about 10% present with complications that require immediate treatment. The basic treatment includes systemic and topical options. In cases of insufficient response or rebound growth, other forms of treatment should be considered. In some cases, combined therapy might be initiated.
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Affiliation(s)
- Małgorzata Kowalska
- Department of Pediatric Surgery and Pediatric Urology, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland; (W.D.); (E.M.)
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Cuenca-Barrales C, Baselga-Torres E, del Boz-González J, Vicente A, Palencia-Pérez S, Campos-Domínguez M, Valdivieso-Ramos M, Martín-Santiago A, Montserrat-García M, Azón-Masoliver A, Feito-Rodríguez M, Domínguez-Cruz J, Roé-Crespo E, Salas-Márquez C, Giacaman A, Lorente-Lavirgen A, Quintana-Castanedo L, de Vega-Martínez M, García-Doval I, Bernabéu-Wittel J. Baseline Description of the Spanish Academy of Dermatology Infantile Haemangioma Nationwide Prospective Cohort. Comparison of Patients Treated with Propranolol in Routine Clinical Practice with Previous Pivotal Clinical Trial Data. ACTAS DERMO-SIFILIOGRAFICAS 2021. [DOI: 10.1016/j.adengl.2021.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Abstract
BACKGROUND Propranolol, a nonselective β-adrenergic receptor antagonist, is approved by the U.S. Food and Drug Administration to treat problematic infantile hemangiomas, but a subset of patients experience treatment complications. Parents wary of long-term use and side effects consult plastic surgeons on surgical options or as a second opinion. Understanding the mechanism(s) of action of propranolol will allow plastic surgeons to better inform parents. METHODS A systemic literature search was performed to query published translational and basic science studies on propranolol effects on infantile hemangiomas and cells derived from these lesions. RESULTS In experimental studies, propranolol was antiproliferative and cytotoxic against hemangioma endothelial and stem cells and affected infantile hemangioma perivascular cell contractility. Propranolol inhibited migration, network formation, vascular endothelial growth factor A production, and vascular endothelial growth factor receptor 2 activation and down-regulated PI3K/AKT and mitogen-activated protein kinase signaling in hemangioma endothelial cells, but it increased ERK1/2 activity in hemangioma stem cells. At effective clinical doses, measured propranolol plasma concentration is 100 times higher than necessary for complete β-adrenergic receptor blockade, yet was 10 to 100 times less than required to induce hemangioma stem cell death. CONCLUSIONS Propranolol targets multiple cell types in infantile hemangiomas by means of β-adrenergic receptor-dependent and -independent mechanisms. Plasma concentration played a significant role. At clinically relevant doses, incomplete infantile hemangioma suppression may explain the rebound phenomenon and worsening ulceration, and propranolol off target effects may lead to commonly reported adverse effects, such as sleep and gastrointestinal disturbances. Propranolol limitations and complications underscore the importance of surgical treatment options in cases of rebound and severe adverse effects. Surgical intervention remains an important treatment choice when parents are hesitant to use propranolol.
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Fang SX, Montez KG. Periorbital Mass in a 2-month-old Girl. Pediatr Rev 2021; 42:146-150. [PMID: 34470896 DOI: 10.1542/pir.2019-0261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Shi Xun Fang
- Wake Forest School of Medicine, Winston-Salem, NC
| | - Kimberly G Montez
- Wake Forest School of Medicine, Winston-Salem, NC.,Wake Forest Baptist Medical Center, Winston-Salem, NC
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Infantile hemangioma. Part 1: Epidemiology, pathogenesis, clinical presentation and assessment. J Am Acad Dermatol 2021; 85:1379-1392. [PMID: 34419524 DOI: 10.1016/j.jaad.2021.08.019] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/25/2021] [Accepted: 08/03/2021] [Indexed: 02/08/2023]
Abstract
Infantile hemangioma (IH) is the most common pediatric vascular tumor. Its pathogenesis is poorly understood but thought to represent an aberrant response of pluripotent stem cells to stimuli such as hypoxia and the renin-angiotensin-system. IH usually appears during the first few weeks of life and follows a characteristic natural trajectory of proliferation and involution. Their clinical appearance depends on their depth and distribution. Classification comprises superficial, mixed and deep IH as well as IH with minimal or arrested growth. Multifocal IHs are more likely to be associated with infantile hepatic hemangioma, and although the need for screening based on a specific number of IH has been recently debated, 5 remains the most widely acceptable cut off point. Large facial or lumbar IH warrants investigation for PHACE and LUMBAR syndrome, respectively. Complications of IH include ulceration, obstruction or functional impairment, hypothyroidism, and cosmetic sequelae. Differential diagnoses mostly consist of other vascular tumors and vascular malformations, though IH may sometimes mimic non-vascular tumors or developmental anomalies. Diagnosis is usually clinical and biopsy rarely indicated. High-frequency ultrasonography may help with the differential diagnosis, particularly with subcutaneous lesions. Referral to other specialists may be required in specific cases.
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Larson AS, Brinjikji W, Anderson KR, Tollefson M, Michelle Silvera V, Guerin JB. Imaging of benign cervicofacial vascular anomalies and associated syndromes. Interv Neuroradiol 2021; 28:364-374. [PMID: 34397285 DOI: 10.1177/15910199211034989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Cervicofacial vascular anomalies can result in morbidity, pain, and cosmetic concerns in affected individuals. Each anomaly has its own unique natural history, treatment, and associations with underlying genetic syndromes. For optimal patient care, it is important for the neuroradiologist to accurately recognize and characterize these entities to ensure appropriate treatment and management. In this review, we discuss the general characteristics, classifications, and imaging features associated with the most common vascular anomalies such as hemangiomas, arteriovenous malformations and fistulas, capillary malformations, venous malformations, and lymphatic malformations in the context of associated syndromes. Additionally, we discuss novel imaging techniques that aid in identifying these vascular anomalies.
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Affiliation(s)
| | - Waleed Brinjikji
- Department of Radiology, 6915Mayo Clinic, USA.,Department of Neurosurgery, 6915Mayo Clinic, USA
| | | | - Megha Tollefson
- Department of Dermatology, 6915Mayo Clinic, USA.,Department of Pediatric & Adolescent Medicine, 6915Mayo Clinic, USA
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Infantile Hemangiomas Cleared by Combined Therapy With Pulsed Dye Laser and Propranolol. Dermatol Surg 2021; 47:1052-1057. [PMID: 34397540 DOI: 10.1097/dss.0000000000003018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Oral propranolol is the first-line therapy for infantile hemangioma. Combining it with pulse dye laser (PDL) (595nm-long PDL) could reduce treatment duration and sequelae incidence and severity. OBJECTIVE To determine the effect of PDL-propranolol treatment on duration to cure and sequelae. METHODS All consecutive patients with infantile hemangioma who were cured by PDL-propranolol treatment were identified. RESULTS In the 27 cases, average age at treatment start was 4.3 ± 3.8 months, mean tumor diameter was 11.1 ± 14.0 cm2, and tumor-type was most common (72.4% of lesions). The patients received 9.8 ± 10.5 PDL sessions. After ensuring patients had no physical contraindications, including heart disease, oral propranolol was started at 1 mg/kg/d, increased up to 3 mg/kg/d as a maintenance dose. Mean propranolol treatment duration was 11.1 ± 4.9 months. Total treatment duration was 15.3 ± 10.8 months. CONCLUSION Our data in the context of recent literature suggest combining propranolol with PDL may reduce propranolol duration without increasing harms.
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