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1
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Mulinda C, Yun S, Fenner J, Garzon MC, Scollan ME, Levin LE. How many is too many? A review of the significant numbers in pediatric skin lesions and their recommended evaluation. Pediatr Dermatol 2024; 41:1021-1029. [PMID: 39235117 DOI: 10.1111/pde.15687] [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] [Received: 09/28/2023] [Accepted: 06/16/2024] [Indexed: 09/06/2024]
Abstract
Pediatric dermatologists are frequently consulted to evaluate children for cutaneous signs of systemic disorders. Numerical thresholds of significance have been described in the dermatologic literature for various skin findings where the likelihood of an associated extracutaneous abnormality or known genetic syndrome increases significantly. Knowledge of these numerical thresholds facilitates diagnosis and management, which improves clinical outcomes and avoids severe complications. This review highlights the clinical presentation, complications, evaluation, and numerical significance, when applicable, for the following skin findings: infantile hemangiomas, capillary malformations, café-au-lait macules, hypopigmented macules, juvenile xanthogranulomas, pilomatricomas, and angiofibromas.
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Affiliation(s)
- Carly Mulinda
- Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Sonora Yun
- Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Justine Fenner
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Maria C Garzon
- Department of Dermatology, Columbia University, New York, New York, USA
- Department of Pediatrics, Columbia University, New York, New York, USA
| | - Margaret E Scollan
- Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Laura E Levin
- Department of Dermatology, Columbia University, New York, New York, USA
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2
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Hall C, Friedmann AM, Handorf A, Lenehan PJ, Sagar P, Bank H, Lee CD. A 6-Week-Old Boy With Irritability and Abdominal Distension. Pediatrics 2024; 154:e2023065290. [PMID: 39444364 DOI: 10.1542/peds.2023-065290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 10/25/2024] Open
Abstract
A 6-week-old boy is brought to the hospital for fussiness and abdominal distension. He was febrile on presentation and was admitted to the hospital for further evaluation. On subsequent examinations, he continued to demonstrate abdominal distension and tenderness to palpation. Ultrasonography of the abdomen was performed and revealed a heterogeneous liver mass. With further diagnostics, a diagnosis was made and treatment initiated, with the infant experiencing resolution of his symptoms. Our panel of experts first discuss the management of an infant with abdominal distension, then discuss the evaluation of a liver mass in an infant, including oncologic, vascular, and infectious etiologies.
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Affiliation(s)
- Celeste Hall
- Tufts University School of Medicine, Boston, Massachusetts
| | | | - Anna Handorf
- Pediatric Hospital Medicine
- Harvard Medical School, Boston, Massachusetts
- Department of Pediatrics, Newton-Wellesley Hospital, Newton, Massachusetts
| | | | | | - Hannah Bank
- Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Clement D Lee
- Tufts University School of Medicine, Boston, Massachusetts
- Department of Pediatrics, Newton-Wellesley Hospital, Newton, Massachusetts
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3
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Sharma A, Gupta M, Mahajan R. Infantile hemangiomas: a dermatologist's perspective. Eur J Pediatr 2024; 183:4159-4168. [PMID: 39052139 DOI: 10.1007/s00431-024-05655-8] [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] [Received: 05/06/2024] [Revised: 05/31/2024] [Accepted: 06/15/2024] [Indexed: 07/27/2024]
Abstract
Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.
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Affiliation(s)
- Apoorva Sharma
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Manavi Gupta
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Rahul Mahajan
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
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4
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Holm A, Mulliken JB, Bischoff J. Infantile hemangioma: the common and enigmatic vascular tumor. J Clin Invest 2024; 134:e172836. [PMID: 38618963 PMCID: PMC11014660 DOI: 10.1172/jci172836] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024] Open
Abstract
Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of newborns. The tumor follows a life cycle of rapid proliferation in infancy, followed by slow involution in childhood. This unique life cycle has attracted the interest of basic and clinical scientists alike as a paradigm for vasculogenesis, angiogenesis, and vascular regression. Unanswered questions persist about the genetic and molecular drivers of the proliferating and involuting phases. The beta blocker propranolol usually accelerates regression of problematic IHs, yet its mechanism of action on vascular proliferation and differentiation is unclear. Some IHs fail to respond to beta blockers and regrow after discontinuation. Side effects occur and long-term sequelae of propranolol treatment are unknown. This poses clinical challenges and raises novel questions about the mechanisms of vascular overgrowth in IH.
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Affiliation(s)
- Annegret Holm
- Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
- Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Freiburg, VASCERN-VASCA European Reference Center, Freiburg, Germany
| | - John B. Mulliken
- Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
- Department of Plastic and Oral Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Joyce Bischoff
- Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
- Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA
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5
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Cohen-Cutler S, Detterich JA, Miller JM, Anselmo DM, Luu M, Mascarenhas L. Mediastinal infantile hemangioma with spinal canal extension and extensive gastrointestinal involvement complicated by respiratory failure. Pediatr Blood Cancer 2022; 69:e29934. [PMID: 36094157 DOI: 10.1002/pbc.29934] [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: 08/03/2021] [Revised: 07/18/2022] [Accepted: 08/01/2022] [Indexed: 11/08/2022]
Abstract
Infantile hemangioma is the most common soft tissue tumor of infancy. Extensive organ involvement is rare. This report describes an infant with biopsy confirmed infantile hemangioma with diffuse organ involvement causing anemia and failure to thrive. Treatment was initiated with propranolol and led to initial improvement; however, course was complicated by several episodes of respiratory failure secondary to pulmonary edema. Propranolol therapy was interrupted for several months while patient was maintained on a diuretic regimen and treated with vincristine and high-dose corticosteroids. Patient was transitioned back to propranolol and is clinically thriving with objective improvement on radiographic imaging.
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Affiliation(s)
- Sally Cohen-Cutler
- Cancer and Blood Disease Institute, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.,Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jon A Detterich
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,Heart Institute, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Joseph M Miller
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Dean M Anselmo
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Minnelly Luu
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA.,Department of Dermatology, Children's Hospital Los Angeles, Los Angeles, California, USA
| | - Leo Mascarenhas
- Cancer and Blood Disease Institute, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.,Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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6
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Kleinman EP, Blei F, Adams D, Greenberger S. Sirolimus for diffuse intestinal infantile hemangioma with PHACE features: systematic review. Pediatr Res 2022; 93:1470-1479. [PMID: 36180586 DOI: 10.1038/s41390-022-02325-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/01/2022] [Accepted: 09/13/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND We report a 3-month-old female with cardiovascular anomalies and diffuse intestinal infantile hemangioma (IIH) of the small bowel suggesting possible diagnosis of PHACE syndrome (posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of the aorta, eye anomalies). The GI symptoms persisted under treatment with propranolol, whereas the addition of sirolimus led to regression of the IIH. METHODS A systematic review was conducted using PubMed, EMBASE, and Ovid MEDLINE databases between 1982 and 2021. RESULTS A total of 4933 articles were identified; 24 articles met inclusion criteria with 46 IIH cases. The most common GI presentations were unspecified GI bleed (40%) and anemia (38%). The most common treatments were corticosteroids (63%), surgical resection (32.6%), and propranolol (28%). Available outcomes were primarily bleeding arrest (84%). Nine cases (19.5%) were diagnosed with definite PHACE, 5 (11%) with possible PHACE, and 32 (69.5%) no PHACE. Our case presented with symptoms most consistent with those of possible PHACE and definite PHACE. No cases in this review underwent treatment with sirolimus. CONCLUSIONS This is the first reported case of successful treatment of IIH with sirolimus. Our case, along with other patients who present with IIH and PHACE features, suggests consideration of IIH as a diagnostic criterion for PHACE syndrome. IMPACT This is the first reported case in which sirolimus showed regression of an intestinal infantile hemangioma. This study serves to demonstrate the presentation, treatment, outcomes of intestinal infantile hemangioma, and correlation with PHACE. The potential correlation between intestinal infantile hemangioma and PHACE deserves more study in consideration of intestinal infantile hemangioma as a diagnostic criterion of PHACE.
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Affiliation(s)
| | - Francine Blei
- Hassenfeld Children's Hospital, NYU Langone, New York, NY, USA
| | - Denise Adams
- Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Shoshana Greenberger
- Sackler School of Medicine, Tel Aviv, Israel.,Pediatric Dermatology Service, The Department of Dermatology, Sheba Medical Center, Ramat Gan, Israel
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7
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Gong X, Li Y, Yang K, Chen S, Ji Y. Infantile hepatic hemangiomas: looking backwards and forwards. PRECISION CLINICAL MEDICINE 2022; 5:pbac006. [PMID: 35692445 PMCID: PMC8982613 DOI: 10.1093/pcmedi/pbac006] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/28/2022] [Accepted: 02/06/2022] [Indexed: 02/05/2023] Open
Abstract
Infantile hepatic hemangiomas (IHHs) are common benign tumors seen in the liver of infants. IHHs are true infantile hemangiomas (IHs) and have phases of proliferation and involution parallel to those of cutaneous IHs. The definition and classification of IHH are still confusing in the literature. The mechanisms during the pathogenesis of IHH have yet to be discovered. The clinical manifestations of IHH are heterogeneous. Although most IHH lesions are asymptomatic, some lesions can lead to severe complications, such as hypothyroidism, consumptive coagulopathy, and high-output congestive cardiac failure. Consequently, some patients can possibly encounter a fatal clinical condition. The heterogeneity of the lesions and the occurrence of disease-related comorbidities can make the treatment of IHH challenging. Oral propranolol is emerging as an effective systemic approach to IHH with obvious responses in tumor remission and symptom regression. However, the precise clinical characteristics and treatment strategies for patients with severe IHH have not yet been well established. Here, we summarize the epidemiology, pathogenic mechanism, clinical manifestations, diagnosis, and treatment of IHH. Recent updates and future perspectives for IHH will also be elaborated.
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Affiliation(s)
- Xue Gong
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yanan Li
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Kaiying Yang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Siyuan Chen
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
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8
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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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9
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Ugwu N, Atzmony L, Ellis KT, Panse G, Jain D, Ko CJ, Nassiri N, Choate KA. Cutaneous and hepatic vascular lesions due to a recurrent somatic GJA4 mutation reveal a pathway for vascular malformation. HGG ADVANCES 2021; 2. [PMID: 33912852 PMCID: PMC8078848 DOI: 10.1016/j.xhgg.2021.100028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The term “cavernous hemangioma” has been used to describe vascular anomalies with histology featuring dilated vascular spaces, vessel walls consisting mainly of fibrous stromal bands lined by a layer of flattened endothelial cells, and an irregular outer rim of interrupted smooth muscle cells. Hepatic hemangiomas (HHs) and cutaneous venous malformations (VMs) share this histologic pattern, and we examined lesions in both tissues to identify genetic drivers. Paired whole-exome sequencing (WES) of lesional tissue and normal liver in HH subjects revealed a recurrent GJA4 c.121G>T (p.Gly41Cys) somatic mutation in four of five unrelated individuals, and targeted sequencing in paired tissue from 9 additional HH individuals identified the same mutation in 8. In cutaneous lesions, paired targeted sequencing in 5 VMs and normal epidermis found the same GJA4 c.121G>T (p.Gly41Cys) somatic mutation in three. GJA4 encodes gap junction protein alpha 4, also called connexin 37 (Cx37), and the p.Gly41Cys mutation falls within the first transmembrane domain at a residue highly conserved among vertebrates. We interrogated the impact of the Cx37 mutant via lentiviral transduction of primary human endothelial cells. We found that the mutant induced changes in cell morphology and activated serum/glucocorticoid-regulated kinase 1 (SGK1), a serine/threonine kinase known to regulate cell proliferation and apoptosis, via non-canonical activation. Treatment with spironolactone, an inhibitor of angiogenesis, suppressed mutant SGK1 activation and reversed changes in cell morphology. These findings identify a recurrent somatic GJA4 c.121G>T mutation as a driver of hepatic and cutaneous VMs, revealing a new pathway for vascular anomalies, with spironolactone a potential pathogenesis-based therapy.
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Affiliation(s)
- Nelson Ugwu
- Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA
| | - Lihi Atzmony
- Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.,Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.,Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA
| | - Katharine T Ellis
- Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
| | - Gauri Panse
- Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.,Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA
| | - Dhanpat Jain
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.,Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Christine J Ko
- Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.,Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA
| | - Naiem Nassiri
- Division of Vascular and Endovascular Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA.,Senior author
| | - Keith A Choate
- Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06510, USA.,Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.,Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.,Vascular Malformations Program (VaMP), Yale New Haven Hospital, New Haven, CT, USA.,Senior author
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10
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Kilmister EJ, Hansen L, Davis PF, Hall SRR, Tan ST. Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies. Front Surg 2021; 7:610758. [PMID: 33634164 PMCID: PMC7900499 DOI: 10.3389/fsurg.2020.610758] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 12/31/2020] [Indexed: 12/31/2022] Open
Abstract
Treatment of vascular anomalies (VAs) is mostly empirical and, in many instances unsatisfactory, as the pathogeneses of these heterogeneous conditions remain largely unknown. There is emerging evidence of the presence of cell populations expressing stemness-associated markers within many types of vascular tumors and vascular malformations. The presence of these populations in VAs is supported, in part, by the observed clinical effect of the mTOR inhibitor, sirolimus, that regulates differentiation of embryonic stem cells (ESCs). The discovery of the central role of the renin-angiotensin system (RAS) in regulating stem cells in infantile hemangioma (IH) provides a plausible explanation for its spontaneous and accelerated involution induced by β-blockers and ACE inhibitors. Recent work on targeting IH stem cells by inhibiting the transcription factor SOX18 using the stereoisomer R(+) propranolol, independent of β-adrenergic blockade, opens up exciting opportunities for novel treatment of IH without the β-adrenergic blockade-related side effects. Gene mutations have been identified in several VAs, involving mainly the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways. Existing cancer therapies that target these pathways engenders the exciting possibility of repurposing these agents for challenging VAs, with early results demonstrating clinical efficacy. However, there are several shortcomings with this approach, including the treatment cost, side effects, emergence of treatment resistance and unknown long-term effects in young patients. The presence of populations expressing stemness-associated markers, including transcription factors involved in the generation of induced pluripotent stem cells (iPSCs), in different types of VAs, suggests the possible role of stem cell pathways in their pathogenesis. Components of the RAS are expressed by cell populations expressing stemness-associated markers in different types of VAs. The gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways interact with different components of the RAS, which may influence cell populations expressing stemness-associated markers within VAs. The potential of targeting these populations by manipulating the RAS using repurposed, low-cost and commonly available oral medications, warrants further investigation. This review presents the accumulating evidence demonstrating the presence of stemness-associated markers in VAs, their expression of the RAS, and their interaction with gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways, in the pathogenesis of VAs.
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Affiliation(s)
| | - Lauren Hansen
- Gillies McIndoe Research Institute, Wellington, New Zealand
| | - Paul F. Davis
- Gillies McIndoe Research Institute, Wellington, New Zealand
| | | | - Swee T. Tan
- Gillies McIndoe Research Institute, Wellington, New Zealand
- Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
- Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia
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11
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Foong SC, Tan ML, Foong WC, Ho JJ. The 'Pink herring'. Arch Dis Child Educ Pract Ed 2020; 105:372-373. [PMID: 31073039 DOI: 10.1136/archdischild-2018-316682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 03/27/2019] [Indexed: 11/04/2022]
Affiliation(s)
- Siew Cheng Foong
- Department of Paediatrics, Royal College of Surgeons Ireland and University College Dublin Malaysia Campus, George Town, Malaysia
| | - May Loong Tan
- Department of Paediatrics, Royal College of Surgeons Ireland and University College Dublin Malaysia Campus, George Town, Malaysia
| | - Wai Cheng Foong
- Department of Paediatrics, Royal College of Surgeons Ireland and University College Dublin Malaysia Campus, George Town, Malaysia
| | - Jacqueline Judith Ho
- Department of Paediatrics, Royal College of Surgeons Ireland and University College Dublin Malaysia Campus, George Town, Malaysia
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12
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Al-Musalhi B, Al-Balushi Z. PHACES Syndrome with Intestinal Hemangioma Causing Recurrent Intussusceptions: A Case Report and Literature Review of Associated Intestinal Hemangioma. Oman Med J 2020; 35:e204. [PMID: 33403127 PMCID: PMC7749928 DOI: 10.5001/omj.2020.99] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 11/30/2019] [Indexed: 12/01/2022] Open
Abstract
PHACES syndrome comprises posterior fossa malformations, segmental hemangioma, arterial anomalies, cardiac defects, eye anomalies and less commonly, sternal cleft, or supraumbilical raphe. We report a case of PHACES syndrome associated with intestinal hemangioma causing recurrent intussusceptions. A full-term infant female presented at the age of three months with segmental distribution of telangiectatic patch with red swelling involving the right periorbital area, right forehead, and lips. After a full workup and evaluation, the diagnosis of PHACES syndrome was confirmed based on the presence of facial segmental hemangioma, hypoplastic right internal carotid artery, intracranial hemangioma, and right optic disc anomaly. At the time of workup, she developed typical symptoms of intussusception. Diagnostic laparoscopy was performed, and she was found to have hemangioma covering the whole ileal wall and a thickened circumferential hemangioma covering the mid ilium causing the lead point of the intussusception. Control of this patient’s hemangiomas was achieved by surgical resection of the thickened circumferential hemangioma covering the mid ilium along with oral propranolol. We reviewed the literature to explore the relationship between gastrointestinal (GI) hemangioma and PHACES syndrome and compared other associated extracutaneous hemangioma of the same series. We found 18 (58%) reported cases of GI hemangioma compared to other visceral hemangiomas on the same series of confirmed PHACE syndrome. All of the reported cases in this series present with anemia and GI bleeding except our patient who had intussusception. This might indicate the significant association of GI hemangioma as extracutaneous hemangioma in PHACES syndrome, emphasizing the importance of investigating
symptomatic patients.
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13
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Abstract
PURPOSE OF REVIEW There is a growing understanding of complications and anomalies associated with infantile hemangiomas. The current review will discuss recent clinical advances in syndromes associated with segmental hemangiomas, including PHACE and LUMBAR syndrome. In addition, the importance of recognizing visceral hemangiomatosis is highlighted. RECENT FINDINGS Ongoing longitudinal studies of PHACE and LUMBAR syndromes associated with segmental infantile hemangiomas have led to improved diagnosis and recommendations for screening for associated anomalies. Characterization of a growing spectrum of associated anomalies as well as better classification of at-risk patients will improve diagnosis and outcomes. In addition, visceral hemangiomatosis recognition and understanding of the potential association with consumptive hypothyroidism will improve initiation of appropriate screening. SUMMARY Clinicians should be aware of infantile hemangiomas associated with potential syndromic complications and recognize the need to initiate appropriate work-up. Segmental hemangiomas of the head and neck region may indicate a risk of PHACE syndrome and associated developmental anomalies. Although LUMBAR syndrome is the association of lower body segmental hemangioma with developmental anomalies. Visceral hemangiomas most commonly affect the liver and may be associated with complications such as consumptive hypothyroidism and heart failure.
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14
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Kieswetter L, Walters TD, Lara-Corrales I, Carcao MD, Ngan B, Pope E. Dieulafoy lesions and PHACE syndrome. Pediatr Dermatol 2019; 36:902-905. [PMID: 31359449 DOI: 10.1111/pde.13922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Dieulafoy's lesion (DL) is a small gastrointestinal (GI) mucosal erosion due to an abnormally large caliber and persistent submucosal arteriole. Typically occurring in adults, they are an extremely rare cause of GI bleeding in pediatrics. We report a case of multiple jejunal DLs in a 9-year-old girl with posterior fossa brain malformations, hemangiomas, arterial lesions, cardiac abnormalities, eye abnormalities (PHACE) syndrome, and the first described use of rapamycin in the treatment of pediatric DLs.
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Affiliation(s)
- Lukas Kieswetter
- Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Thomas D Walters
- Division of Gastroenterology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Irene Lara-Corrales
- Division of Dermatology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Manuel D Carcao
- Division of Haematology/Oncology, Department of Paediatrics, Child Health Evaluative Sciences, Research Institute, Toronto, Ontario, Canada
| | - Bo Ngan
- Division of Pathology, Department of Pediatric Laboratory, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Elena Pope
- Division of Dermatology, Hospital for Sick Children, Toronto, Ontario, Canada
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15
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Peterman CM, Gibson RS, Lillis AP, Fishman SJ, Liang MG. Clinical and radiological characteristics of patients with retroperitoneal infantile hemangiomas. Pediatr Dermatol 2019; 36:823-829. [PMID: 31600835 DOI: 10.1111/pde.13982] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Infantile hemangiomas (IHs) are the most common tumors of infancy. The objective was to identify clinical and radiological patterns in patients with retroperitoneal IHs. METHODS We reviewed patients from our Vascular Anomalies Center database with IHs and abdominal imaging presenting from 1999 to 2017 to identify retroperitoneal involvement. RESULTS Eleven patients (10 females, one male) with retroperitoneal IHs were found. Cutaneous IHs were present in eight patients (five segmental (45%), three multifocal (27%)) and absent in 1 (9%). Segmental hemangiomas involved the face in 2/5 (40%) and lower body in 3/5 (60%). The most common symptoms were dyspnea (n = 4), hematochezia (n = 3), and/or ulceration (n = 2). Three patients were asymptomatic. Involved retroperitoneal organs included the duodenum (n = 4), pancreas (n = 3), and adrenal glands (n = 1). Non-retroperitoneal organ involvement included the liver (n = 5), non-duodenal small intestine (n = 4), and large intestine (n = 3). Perivascular retroperitoneal hemangiomas were seen in 6/11 patients (55%), most commonly surrounding the aorta (n = 5), iliac vessels (n = 2), and/or inferior vena cava (n = 2). Three of 11 patients (27%) had LUMBAR based on a segmental, sacral hemangioma with tethered cord or anorectal malformation. Follow-up information was available in 6/11 patients (55%): 5 symptomatically improved with treatment (propranolol, corticosteroids, and/or vincristine), while one succumbed from extensive hepatic involvement. CONCLUSION Retroperitoneal IHs are rare and tend to involve organs or surround vessels. Associated cutaneous IHs, if present, lack anatomical predilection and may be segmental or multifocal.
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Affiliation(s)
- Caitlin M Peterman
- Tufts University School of Medicine, Boston, Massachusetts.,Department of Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ruby S Gibson
- Department of Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.,Long School of Medicine, University of Texas Health San Antonio, San Antonio, Texas
| | - Anna P Lillis
- Division of Interventional Radiology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio.,Division of Vascular and Interventional Radiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Steven J Fishman
- Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Marilyn G Liang
- Department of Dermatology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
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Yang K, Peng S, Chen L, Chen S, Ji Y. Efficacy of propranolol treatment in infantile hepatic haemangioma. J Paediatr Child Health 2019; 55:1194-1200. [PMID: 30628130 DOI: 10.1111/jpc.14375] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 12/15/2018] [Accepted: 12/16/2018] [Indexed: 01/21/2023]
Abstract
AIM The aim of this study was to assess the efficacy of propranolol treatment in multifocal and diffuse infantile hepatic haemangioma (IHH). METHODS A retrospective study of symptomatic or potentially symptomatic IHH was performed in our hospital between 2011 and 2016. RESULTS Thirteen patients were identified: 2 patients had diffuse lesions, and 11 patients had multifocal lesions, including 2 patients who had combined lesions that shared features of both multifocal and diffuse lesion patterns. Eleven (84.6%) patients had cutaneous infantile haemangioma. Hepatomegaly was the predominant clinical presentation. Hypothyroidism was identified in three patients, including one patient who had documented congestive heart failure (CHF). The median age at diagnosis and the median duration of treatment were 2.0 months (range 1.2-26.0) and 24.0 months (range 4.0-30.0). The median duration of follow-up was 30.0 months (range 3.0-48.0). For patients with hypothyroidism, the thyroid hormone level was normal after 4 weeks of propranolol and levothyroxine treatment. All but one patient responded well to propranolol treatment. The patient who failed to respond to treatment died of CHF and abdominal compartment syndrome induced by hepatomegaly. No significant side effects of propranolol were observed during follow-up. CONCLUSIONS Most multifocal and diffuse IHH respond well to propranolol. However, progressive cases may be fatal despite aggressive treatments. Our data suggest that propranolol may be considered the first-line treatment for multifocal and diffuse IHH due to its efficacy.
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Affiliation(s)
- Kaiying Yang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Suhua Peng
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Linwen Chen
- College of Clinical Medicine, North Sichuan Medical College, Nanchong, China
| | - Siyuan Chen
- Pediatric Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
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17
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Chaturvedi A, Klionsky NB, Saul D. Ultrasound with Doppler evaluation of congenital hepatic vascular shunts. Pediatr Radiol 2018; 48:1658-1671. [PMID: 30194461 DOI: 10.1007/s00247-018-4247-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 06/19/2018] [Accepted: 08/24/2018] [Indexed: 12/17/2022]
Abstract
Congenital aberrant hepatic vascular communications result from intrahepatic or extrahepatic errors in vascular development or involution during the transition from fetal to newborn hepatic circulation. These hepatic vascular shunts can be fortuitously discovered and asymptomatic, or can cause symptoms of varying severity, often presenting diagnostic dilemmas. Some hepatic vascular shunts resolve spontaneously while others require interventional radiologic or surgical closure. Affected patients are often first studied with real-time and Doppler ultrasound, so radiologists should familiarize themselves with the expected ultrasound findings of these vascular shunts for effective diagnosis, triage and management. In this review, the authors focus on ultrasound and Doppler findings of hepatic vascular shunts with underlying embryology, clinical features and management strategies. Broadly, these aberrant hepatic vascular communications include portosystemic venous shunts (which can be intra- or extrahepatic and include persistent patent ductus venosus), arterioportal, arteriovenous or mixed shunts.
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Affiliation(s)
- Apeksha Chaturvedi
- Pediatric Imaging Section, Department of Imaging Sciences, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY, 14642, USA.
| | - Nina B Klionsky
- Pediatric Imaging Section, Department of Imaging Sciences, Golisano Children's Hospital, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY, 14642, USA
| | - David Saul
- Department of Pediatric Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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18
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Key Words
- CTA, computed tomography angiography
- IH, infantile hemangiomas
- LUMBAR, lower body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies ()
- MRA, magnetic resonance angiogram
- MRI, magnetic resonance imaging
- PELVIS, perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, skin tag
- PHACE, posterior fossa, hemangioma, arterial abnormalities, cardiac abnormalities, eye abnormalities, sternal cleft
- connective tissue
- extracutaneous involvement
- infantile hemangioma
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Destro F, Maestri L, Vella C, Baraldini V, Riccipetitoni G. Infantile hemangioma as cause of neonatal gastrointestinal bleeding. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2018. [DOI: 10.1016/j.epsc.2018.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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20
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Baselga Torres E, Bernabéu Wittel J, van Esso Arbolave DL, Febrer Bosch MI, Carrasco Sanz Á, de Lucas Laguna R, del Pozo Losada J, Hernández Martín Á, Jiménez Montañés L, López Gutiérrez JC, Martín-Santiago A, Redondo Bellón P, Ruíz-Canela Cáceres J, Torrelo Fernández A, Vera Casaño Á, Vicente Villa MA. Consenso español sobre el hemangioma infantil. An Pediatr (Barc) 2016; 85:256-265. [DOI: 10.1016/j.anpedi.2015.10.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 09/30/2015] [Accepted: 10/01/2015] [Indexed: 10/22/2022] Open
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21
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Baselga Torres E, Bernabéu Wittel J, van Esso Arbolave DL, Febrer Bosch MI, Carrasco Sanz Á, de Lucas Laguna R, del Pozo Losada J, Hernández Martín Á, Jiménez Montañés L, López Gutiérrez JC, Martín-Santiago A, Redondo Bellón P, Ruíz-Canela Cáceres J, Torrelo Fernández A, Vera Casaño Á, Vicente Villa MA. Spanish consensus on infantile haemangioma. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2016. [DOI: 10.1016/j.anpede.2015.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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22
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Garzon MC, Epstein LG, Heyer GL, Frommelt PC, Orbach DB, Baylis AL, Blei F, Burrows PE, Chamlin SL, Chun RH, Hess CP, Joachim S, Johnson K, Kim W, Liang MG, Maheshwari M, McCoy GN, Metry DW, Monrad PA, Pope E, Powell J, Shwayder TA, Siegel DH, Tollefson MM, Vadivelu S, Lew SM, Frieden IJ, Drolet BA. PHACE Syndrome: Consensus-Derived Diagnosis and Care Recommendations. J Pediatr 2016; 178:24-33.e2. [PMID: 27659028 PMCID: PMC6599593 DOI: 10.1016/j.jpeds.2016.07.054] [Citation(s) in RCA: 160] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Revised: 05/23/2016] [Accepted: 07/29/2016] [Indexed: 11/26/2022]
Affiliation(s)
- Maria C. Garzon
- Departments of Dermatology and Pediatrics, Columbia University, New York, NY
| | - Leon G. Epstein
- Departments of Pediatrics and Neurology, The Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Geoffrey L. Heyer
- Departments of Pediatrics and Neurology, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH
| | - Peter C. Frommelt
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI
| | - Darren B. Orbach
- Division of Neurointerventional Radiology, Boston Children’s Hospital, Boston, MA
| | - Adriane L. Baylis
- Department of Plastic Surgery, Nationwide Children’s Hospital, Columbus, OH
| | - Francine Blei
- Department of Pediatrics/ Hematology, Lenox Hill Hospital, Northwell Health, Great Neck, NY
| | | | - Sarah L. Chamlin
- Division of Pediatric Dermatology, The Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
| | - Robert H. Chun
- Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI
| | - Christopher P. Hess
- Departments of Radiology and Neurology, University of California, San Francisco, San Francisco, CA
| | - Shawna Joachim
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI
| | | | - Wendy Kim
- Division of Dermatology, Departments of Medicine and Pediatrics, Loyola University Medical Center, Maywood, IL
| | | | - Mohit Maheshwari
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI
| | - Garrett N. McCoy
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI
| | - Denise W. Metry
- Department of Dermatology, Texas Children’s Baylor, Houston, TX
| | - Priya A. Monrad
- Department of Neurology, Medical College of Wisconsin, Milwaukee, WI
| | - Elena Pope
- Section of Pediatric Dermatology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Julie Powell
- Department of Dermatology, University of Montreal, Montreal, Québec, Canada
| | | | - Dawn H. Siegel
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI
| | | | - Sudhakar Vadivelu
- Department of Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Sean M. Lew
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI
| | - Ilona J. Frieden
- Department of Dermatology, University of California, San Francisco, San Francisco, CA
| | - Beth A. Drolet
- Departments of Dermatology and Pediatrics, Medical College of Wisconsin, Milwaukee, WI
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Kang E, Friedman N, Mamoun I, Tamburro J, Golden A. Beta Blockade as Treatment for Intracranial Infantile Hemangioma: Case Report and Literature Review. Pediatr Neurol 2016; 59:13-7. [PMID: 27068061 DOI: 10.1016/j.pediatrneurol.2016.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 01/20/2016] [Accepted: 01/22/2016] [Indexed: 11/29/2022]
Abstract
BACKGROUND Intracranial infantile hemangiomas are extremely rare, with only 36 patients reported in literature. Treatment for intracranial infantile hemangiomas has been mostly limited to surgery, steroids, and interferon therapy. Propranolol, which is often used to treat cutaneous infantile hemangiomas, is not currently standard treatment for intracranial infantile hemangiomas. PATIENT DESCRIPTION We present a one-month old boy with an intracranial infantile hemangioma treated with propranolol. RESULTS This boy was being treated with oral propranolol for a supraclavicular infantile hemangioma. Subsequent brain magnetic resonance imaging (MRI) scan showed evidence of an associated intracranial infantile hemangioma in the right cerebellopontine angle. Repeat brain MRI scan after two months of propranolol treatment demonstrated a significant reduction in the size of the intracranial infantile hemangioma. CONCLUSIONS This is the first report of successful therapy of an intracranial infantile hemangioma with propranolol.
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Affiliation(s)
- Elise Kang
- School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Neil Friedman
- Center for Pediatric Neurology, Neurologic Institute and Cleveland Clinic Children's Hospital, Cleveland Clinic, Cleveland, Ohio
| | - Ihsan Mamoun
- Pediatric and Neuroimaging, Cleveland Clinic Imaging Institute, Cleveland, Ohio
| | - Joan Tamburro
- Department of Pediatric Dermatology, Cleveland Clinic Children's Hospital, Cleveland, Ohio
| | - Alex Golden
- Department of Pediatric Cardiology, Cleveland Clinic Children's Hospital, Cleveland, Ohio.
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24
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Does hypoxia play a role in infantile hemangioma? Arch Dermatol Res 2016; 308:219-27. [PMID: 26940670 DOI: 10.1007/s00403-016-1635-x] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Revised: 10/13/2015] [Accepted: 02/15/2016] [Indexed: 12/17/2022]
Abstract
Infantile hemangioma (IH), the most common tumor of infancy, is characterized by rapid growth during infancy, followed by spontaneous involution over 5-10 years. Certain clinical observations have led to the suggestion that IH is triggered and maintained by hypoxia. We review the literature on the possible role of hypoxia in the etiology of IH, in particular, (1) the role of hypoxia inducible factor-1α (HIF-1α) and its downstream targets including GLUT-1 and VEGF; (2) the pathophysiological link between IH and retinopathy of prematurity; (3) hypoxic events in the early life including placental insufficiency, pre-eclampsia and low birthweight that have the potential to promote hypoxic stress; and (4) the evidence supporting the development of IH independent of HIF-1α. We also discuss these observations in the context of recent evidence of the crucial role of stem cells and the cytokines niche that governs their proliferation and inevitable differentiation, offering novel insights into the biology of IH. We propose that various triggers may simultaneously up-regulate HIF-1α, which is downstream of the renin-angiotensin system, specifically angiotensin II, which promotes production of HIF-1α. These developments shed light to the understanding of this enigmatic condition.
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25
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Moyakine AV, Vleuten CJMVD. Propranolol for infantile hemangioma: Current state of affairs. World J Dermatol 2016; 5:4-16. [DOI: 10.5314/wjd.v5.i1.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 10/19/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Infantile hemangioma (IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating on associated anomalies, such as PHACE(S) syndrome and LUMBAR syndrome. Because of the benign and self-limiting characteristics seen in more than 90% of cases of IH, a conservative approach is usually chosen. However, some circumstances, such as ulceration, vision loss, breathing difficulties, or potential disfigurement, will require treatment during the proliferative phase. For decades, treatment of IH has primarily consisted of corticosteroids or surgery. Since 2008, propranolol has become the treatment of first choice. In this article, we bring to light the crucial changes in the treatment of IH over the past years. To date, there is still a lack of data on the possible long-term effects of propranolol treatment in young infants. A theoretical probability of the central nervous system being affected (that is, impairment of short- and long-term memory, psychomotor function, sleep quality, and mood) has recently been suggested. This review highlights research topics concerning these long-term adverse effects. Finally, information is provided on the potential instruments to measure IH severity and activity in clinical trials and/or in clinical practice and the recently developed and first-validated IH-specific quality-of-life questionnaire.
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26
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Vredenborg AD, Janmohamed SR, de Laat PCJ, Madern GC, Oranje AP. Multiple Cutaneous Infantile Hemangioma and the Risk of Internal Hemangioma. PRACTICAL PEDIATRIC DERMATOLOGY 2016:79-89. [DOI: 10.1007/978-3-319-32159-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Abstract
Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its purpose is to update the pediatric community regarding recent discoveries in IH pathogenesis, treatment, and clinical associations and to provide a basis for clinical decision-making in the management of IH.
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Abstract
OBJECTIVES The aim of the present study was to document the clinical presentation, diagnostic studies, and therapy of gastrointestinal infantile hemangiomas. METHODS This is a retrospective analysis of children with gastrointestinal hemangiomas culled from our Vascular Anomalies Center database. We detailed the location of visceral and cutaneous tumors, as well as radiologic and procedural methods used for diagnosis and treatment. RESULTS A total of 9 of the 16 children (14 girls and 2 boys) with hollow visceral hemangiomas also had cutaneous lesions. The most common extravisceral sites were regional facial lesions (n = 6), multifocal lesions (n = 2), and a solitary chest lesion (n = 1). Presenting symptoms were melena and hematochezia in the first 4 months of life (n = 14); several infants required multiple blood transfusions. The most frequent locations were small bowel and mesentery. One-half of the patients (n = 8) were diagnosed by laparotomy; the majority (n = 12) had suspicious radiologic findings. Corticosteroid and/or propranolol were the most common therapies. CONCLUSIONS Melena and hematochezia, sometimes with profound anemia, in the first 4 months of life, suggest the possibility of intestinal infantile hemangioma even in the absence of cutaneous tumor. Intestinal bleeding, particularly in association with a regional facial lesion, should initiate workup: ultrasonography, computed tomography, and magnetic resonance imaging display diagnostic features. First-line treatment is medical management; bowel resection may be necessary, particularly for perforation.
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Abstract
Haemangiomas are the commonest type of vascular tumour in infancy. This article summarizes the pathophysiology and classification of the subtypes as early identification of high-risk lesions is essential for consideration of treatment to prevent short- and long-term complications from the condition.
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Affiliation(s)
- Sue Ann Chan
- Dermatology Specialty Registrar in the Department of Dermatology, Queen Elizabeth Hospital, University Hospital Birmingham, Birmingham B15 2TH
| | - Helen M Goodyear
- Associate Postgraduate Dean and Consultant Paediatrician, Health Education West Midlands, Birmingham
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Sethuraman G, Yenamandra VK, Gupta V. Management of infantile hemangiomas: current trends. J Cutan Aesthet Surg 2014; 7:75-85. [PMID: 25136206 PMCID: PMC4134656 DOI: 10.4103/0974-2077.138324] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Infantile hemangiomas (IH) are common vascular tumours. IH have a characteristic natural course. They proliferate rapidly during the early infantile period followed by a period of gradual regression over several years. Most of the uncomplicated IH undergo spontaneous involution, with a small proportion of cases requiring intervention. These are children with IH in life-threatening locations, local complications like haemorrhage, ulceration and necrosis and functional or cosmetic disfigurements. Systemic corticosteroids have been the first line of treatment for many years. Recently, non-selective beta-blockers, such as oral propranalol and topical timolol, have emerged as promising and safer therapies. Other treatment options include interferon α and vincristine which are reserved for life-threatening haemangiomas that are unresponsive to conventional therapy. This review mainly focuses on the current trends and evidence-based approach in the management of IH.
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Affiliation(s)
- Gomathy Sethuraman
- Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India
| | - Vamsi K Yenamandra
- Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India
| | - Vishal Gupta
- Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India
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Fernandez-Pineda I, Cabello-Laureano R. Differential diagnosis and management of liver tumors in infants. World J Hepatol 2014; 6:486-495. [PMID: 25068000 PMCID: PMC4110540 DOI: 10.4254/wjh.v6.i7.486] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/21/2014] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
During the first year of life, most of the liver neoplasms are benign in origin, but some of these histologically benign lesions may be challenging in their management. Although most hepatic hemangiomas can be safely observed until involution is documented, some patients will need treatment due to progressive hepatomegaly, hypothyroidism and/or cardiac failure. Large mesenchymal hamartomas may require extensive hepatic resection and an appropriate surgical plan is critical to obtain good results. For malignant neoplasms such as hepatoblastoma, complete surgical resection is the mainstay of curative therapy. The decision about whether to perform an upfront or delayed resection of a primary liver malignant tumor is based on many considerations, including the ease of resection, surgical expertise, tumor histology and stage, and the likely chemosensitivity of the tumor. This article reviews the initial management of the more common hepatic tumors of infancy, focusing on the differential diagnosis and treatment options.
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32
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Vredenborg A, Janmohamed S, de Laat P, Madern G, Oranje A. Multiple cutaneous infantile haemangiomas and the risk of internal haemangioma. Br J Dermatol 2013; 169:188-91. [DOI: 10.1111/bjd.12229] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Porto FHDG, Silva MNMD, Domingues JRS, Porto GCLM, Davagnaman I, Nitrini R. The missed missing hole. ARQUIVOS DE NEURO-PSIQUIATRIA 2012; 70:467-469. [PMID: 22699546 DOI: 10.1590/s0004-282x2012000600015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 04/16/2012] [Indexed: 06/01/2023]
Abstract
At times in clinical neurology, the identification of a subtle clinical or radiological sign can lead to prompt diagnosis of a very rare or difficult case. We report on a patient who presented with untreatable headache and unilateral ptosis. Computed tomography (CT) scan of the head did not reveal any structural cause. Magnetic resonance angiogram showed absence of left internal carotid artery, which was eventually confirmed by a catheter angiography. Reviewing the case, it emerged that a feature on the initial CT scan "bone window" would have confirmed the diagnosis, had it been searched for: the underdeveloped carotid canal, which is a consequence and a marker of internal carotid artery agenesis.
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Affiliation(s)
- Fábio Henrique de Gobbi Porto
- Behavorial and Cognitive Neurology Unit, Department of Neurology, Cognitive Disorders Reference Center, Hospital das Clínicas, University of São Paulo, São Paulo, SP, Brazil
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Hepatic haemangioma-prenatal imaging findings, complications and perinatal outcome in a case series. Pediatr Radiol 2012; 42:298-307. [PMID: 21928049 DOI: 10.1007/s00247-011-2214-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2011] [Revised: 05/11/2011] [Accepted: 05/28/2011] [Indexed: 10/17/2022]
Abstract
BACKGROUND The clinical presentation of foetal hepatic haemangioma (HH) is highly variable, from asymptomatic to life-threatening. OBJECTIVE The aim of this study was to describe foetal hepatic haemangioma and identify prognostic factors. MATERIALS AND METHODS Antenatal and postnatal imaging studies, clinical and biological records of infants with antenatally diagnosed HH (2001-2009) were reviewed. RESULTS Sixteen foetuses had one focal lesion, with a mean volume of 75 ml (5-240 ml). One had multifocal HH. Most presented as a focal well-delimited heterogeneous vascular mass. Four had associated cardiomegaly, five had cardiac failure. Eight of the nine foetuses with cardiac disorders were symptomatic at birth: cardiac failure with pulmonary hypertension (9), consumptive coagulopathy (8), compartmental syndrome (2). All received supportive medical treatment, four embolisation. Five of these died. The remaining eight had a normal cardiac status. Two became symptomatic after birth: one with a large porto-hepatic shunt and one with significant mass effect. Prenatal cardiac abnormality (univariate, P = 0.031), enlargement of more than one hepatic vein (P = 0.0351) and large volume (P = 0.0372) were associated with symptomatic disease. CONCLUSION Hepatic haemangioma associated with prenatal cardiac disorders, large volume and more than one enlarged hepatic vein have poorer outcome and require specific perinatal multidisciplinary management.
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Glick ZR, Frieden IJ, Garzon MC, Mully TW, Drolet BA. Diffuse neonatal hemangiomatosis: an evidence-based review of case reports in the literature. J Am Acad Dermatol 2012; 67:898-903. [PMID: 22341467 DOI: 10.1016/j.jaad.2012.01.018] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2011] [Revised: 01/17/2012] [Accepted: 01/20/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND The term "diffuse neonatal hemangiomatosis" has been used historically to describe multifocal vascular lesions affecting the skin and viscera in infants. OBJECTIVE We hypothesized that many cases reported as diffuse neonatal hemangiomatosis did not have infantile hemangiomas (IH), but represented more recently described neonatal vascular diseases. METHODS A literature search was performed using PubMed database (1950-2009) with the terms "neonatal hemangiomatosis," "benign hemangiomatosis," and "diffuse hemangiomatosis." A total of 180 articles were identified. Exclusion criteria included disease onset later than 3 years of age and absence of multifocal skin involvement. In all, 73 cases were selected and categorized into 3 groups: IH/probable IH; multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT)/probable MLT; and multifocal vascular lesions, not otherwise specified. RESULTS Of the 73 cases, 43 had IH/probable IH, 17 had MLT/probable MLT, and 13 had multifocal vascular lesions, not otherwise specified. The clinical outcomes of these groups differed in that two of 43 (5%) patients with IH died whereas 11 of 17 (65%) patients with MLT died (odds ratio 37.6, confidence interval 5.6-387.6, P value < .0001). LIMITATIONS This was a literature-based meta-analysis, which inherently has limitations of incomplete and inconsistently presented information. CONCLUSIONS Many cases reported in the literature as diffuse neonatal hemangiomatosis represent newly described multifocal vascular anomalies such as MLT, which has a strikingly higher mortality than IH. We propose the term "multifocal infantile hemangioma-with or without extracutaneous disease" instead of "diffuse neonatal hemangiomatosis" for multiple cutaneous IH. Accurate diagnosis of multifocal neonatal vascular lesions is imperative to facilitate appropriate evaluation, treatment, and prognosis.
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Affiliation(s)
- Zoey R Glick
- University of Alabama at Birmingham, Department of Dermatology, Birmingham, Alabama 35294-0009, USA.
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Itinteang T, Tan ST, Guthrie S, Tan CES, McIntyre BC, Brasch HD, Day DJ. A placental chorionic villous mesenchymal core cellular origin for infantile haemangioma. J Clin Pathol 2011; 64:870-4. [DOI: 10.1136/jclinpath-2011-200191] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
AimsTo investigate the expression of the placental cell-specific associated proteins in infantile haemangioma (IH).MethodsImmunohistochemical staining was used to investigate the expression of human chorionic gonadotrophin (hCG), human placental lactogen (hPL), human leucocyte antigen-G (HLA-G), cytokeratin 7 (CK7) and smooth muscle actin in paraffin-embedded sections of proliferating and involuted IHs.ResultsThe proteins hCG and hPL were expressed by the endothelium but not the pericyte layer of proliferating IH, but these proteins were not detected in involuted lesions. There was no expression of CK7 and HLA-G in IH.ConclusionsThe expression of hCG and hPL, but not CK7 or HLA-G, by the endothelium of proliferating IH supports a placental chorionic villous mesenchymal core cellular origin for IH rather than a trophoblast origin.
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Nahed BV, Ferreira M, Babu MA, Terry AR, Walcott BP, Kahle KT, Smith ER. Dural scalp and intracranial hemangiomas causing hydrocephalus and venous sinus thrombosis in an infant. J Child Neurol 2011; 26:777-81. [PMID: 21325128 DOI: 10.1177/0883073810390694] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cutaneous scalp hemangiomas may herald the presence of occult intracranial hemangiomas. A previously healthy 4-month-old girl presented with a bleeding scalp hemangioma, a bulging fontanel, and anemia. Magnetic resonance imaging (MRI) of the brain revealed hydrocephalus along with multiple intracranial hemangiomas. These lesions compressed the jugular foramina, resulting in venous sinus thrombosis involving the right transverse sinus, the left sigmoid sinus, and the torcular herophili. The patient had no family history of phakomatoses or other genetic abnormalities. A thrombophilia work-up result was unremarkable. The patient was treated with prednisolone (10 mg twice daily) and low molecular weight heparin (1 mg/kg/dose) twice daily. This treatment decreased the size of her cutaneous and intracranial hemangiomas and led to the resolution of her venous sinus thromboses and hydrocephalus. Innocuous scalp hemangioma in an infant may herald more concerning intracranial pathology, which can be treated effectively if diagnosed with appropriate imaging studies.
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Affiliation(s)
- Brian V Nahed
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Léauté-Labrèze C, Prey S, Ezzedine K. Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venereol 2011; 25:1245-53. [PMID: 21569112 DOI: 10.1111/j.1468-3083.2011.04102.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infantile haemangioma (IH) is the most common tumour of infancy. Its typical natural history is characterized by an early rapid growth following birth and a slow spontaneous regression phase within a period of 3 to 7 years. The exact aetiopathogeny underlying IH is still to be fully understood, but the role of fetal hypoxic stress is strongly suggested as a triggering signal in epidemiological studies. IH are composed of a complex mixture of cells including multipotent stem cells, a majority of immature endothelial cells, pericytes, dendritic cells and in the late stage, adipocytes. Most of IH are nodular and are not associated with malformations. However, in some cases, IH referred to as segmental may be associated with developmental abnormalities such as PHACES and PELVIS/SACRAL syndromes.
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Affiliation(s)
- C Léauté-Labrèze
- Unité de Dermatologie Pédiatrique et Centre de Référence des Maladies Rares de la Peau, CHU de Bordeaux, Hôpital Pellegrin-Enfants, and Université de Bordeaux, Biothérapies des Maladies Génétiques et Cancers, Bordeaux, France.
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Horii KA, Drolet BA, Frieden IJ, Baselga E, Chamlin SL, Haggstrom AN, Holland KE, Mancini AJ, McCuaig CC, Metry DW, Morel KD, Newell BD, Nopper AJ, Powell J, Garzon MC. Prospective study of the frequency of hepatic hemangiomas in infants with multiple cutaneous infantile hemangiomas. Pediatr Dermatol 2011; 28:245-53. [PMID: 21517952 DOI: 10.1111/j.1525-1470.2011.01420.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Multiple cutaneous infantile hemangiomas have been associated with hepatic hemangiomas. Screening of infants with five or more cutaneous infantile hemangiomas with abdominal ultrasound is often recommended. The aim of this study was to determine the frequency with which hepatic hemangiomas occur in infants with five or more cutaneous infantile hemangiomas compared to those with one to four cutaneous infantile hemangiomas and to characterize the clinical features of these hepatic hemangiomas. A multicenter prospective study of children with cutaneous infantile hemangiomas was conducted at pediatric dermatology clinics at Hemangioma Investigator Groups sites in the United States, Canada, and Spain between October 2005 and December 2008. Data were collected, and abdominal ultrasonography was performed on infants younger than 6 months old with five or more cutaneous infantile hemangiomas and those with one to four cutaneous infantile hemangiomas. Twenty-four (16%) of the 151 infants with five or more cutaneous infantile hemangiomas had hepatic hemangiomas identified on abdominal ultrasound, versus none of the infants with fewer than five (p = 0.003). Two of the 24 infants with hepatic hemangiomas received treatment specifically for their hepatic hemangiomas. Infants with five or more cutaneous infantile hemangiomas have a statistically significantly greater frequency of hepatic hemangiomas than those with fewer than 5. These findings support the recommendation of five or more cutaneous infantile hemangiomas as a threshold for screening infants younger than 6 months old for hepatic hemangiomas but also demonstrate that the large majority of these infants with hepatic hemangiomas do not require treatment.
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Affiliation(s)
- Kimberly A Horii
- Section of Dermatology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
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Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for multiple hepatic and cutaneous hemangiomas with deranged liver function. Pediatrics 2011; 127:e772-6. [PMID: 21357335 DOI: 10.1542/peds.2010-1703] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
We report here the case of an infant with multiple hepatic and cutaneous infantile hemangiomas (IHs) associated with deranged liver function who was treated successfully with low-dose propranolol. We also discuss our recent data that show that IH is a developmental anomaly of hemogenic endothelium derived from primitive mesoderm with a neural crest-cell phenotype. We previously presented evidence that this hemogenic endothelium is governed by the renin-angiotensin system, which we propose can account for both the action of propranolol and the process of spontaneous involution of IH. We further speculate on the possibility of using inhibitors of angiotensin-converting enzyme and that of angiotensin II receptor 2 as potential alternative therapies.
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Affiliation(s)
- Swee Thong Tan
- Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, High Street, Private Bag 31-907, Lower Hutt, New Zealand.
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Fulkerson DH, Agim NG, Al-Shamy G, Metry DW, Izaddoost SA, Jea A. Emergent medical and surgical management of mediastinal infantile hemangioma with symptomatic spinal cord compression: case report and literature review. Childs Nerv Syst 2010; 26:1799-805. [PMID: 20405131 DOI: 10.1007/s00381-010-1153-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2010] [Accepted: 04/07/2010] [Indexed: 10/19/2022]
Abstract
PURPOSE We report an extremely rare case of a patient with a large, cervical, and upper thoracic cutaneous hemangioma associated with a separate, underlying mediastinal hemangioma extending to the epidural space causing significant spinal cord compression. CASE REPORT A 6-week-old female presented with decreased movement of her right arm and bilateral lower extremity hyperreflexia. Her arm weakness progressed to paralysis over the course of 24 h. She underwent emergent surgical decompression and medical therapy with propranolol and systemic corticosteroids. CONCLUSION While several recent reports have described dramatic responses of hemangiomas to propranolol, this is the first case in which it was used as part of a multimodal approach to symptomatic spinal cord compression. The infant improved immediately after surgery. She is neurologically intact and has radiographic regression of the hemangiomas on follow-up examination 6 months later.
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Affiliation(s)
- Daniel H Fulkerson
- Division of Pediatric Neurosurgery, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin Street, CCC 1230.01, 12th Floor, Houston, TX 77030, USA.
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Schwartz RA, Sidor MI, Musumeci ML, Lin RL, Micali G. Infantile haemangiomas: a challenge in paediatric dermatology. J Eur Acad Dermatol Venereol 2010; 24:631-8. [PMID: 20565561 DOI: 10.1111/j.1468-3083.2010.03650.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Infantile haemangiomas, common benign vascular tumours of childhood, are characterized by rapid growth during the first year of life and a slow regression that is usually completed at 7-10 years of age. These tumours are composed of endothelial cells with high mitotic rates and stromal components such as fibroblasts, mast cells and pericytes. Haemangiomas become a challenge when they are part of a syndrome, are located in certain areas of the body or when complications develop. The above-mentioned factors also influence the treatment modality used. However, although there remain many uncertainties regarding management, the beta-adrenergic receptor blocker propranolol is a promising new candidate for first-line systemic therapy. It produces such a dramatic and rapid response that the appearance of an infantile haemangioma should impart expeditious consideration of the risks and benefits of its use.
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Abstract
PURPOSE OF REVIEW Advances have been made in the pathogenesis, diagnosis and management of vascular tumors of infancy in the past year. Propranolol therapy for infantile hemangiomas (IH) is now being used widely, and case reports, series, and adverse effects are reviewed. Kaposiform hemangioendothelioma and tufted angioma are less common than IH but more often associated with coagulopathy (Kasabach-Merritt phenomenon). RECENT FINDINGS Recent work suggests that stem cells, mediated by the Notch signaling pathway, may become proliferating endothelial cells that comprise IH. Large, segmental IH are more likely to develop complications that can include life-threatening bleeds; however, solitary large IH do not appear to increase the risk of hepatic IH. Segmental IH may herald underlying structural anomalies of the brain, cerebral, and cardiac vessels (PHACE syndrome--Posterior fossa defects, Hemangiomas, Arterial anomalies, Cardiac defects and Coarctation of the aorta, Eye anomalies), and new criteria aid in diagnosis. Propranolol therapy is effective in life-threatening IH and appears to stop growth and hasten involution in proliferative and plateau phase IH. Adverse effects include bradycardia, hypotension, hypoglycemia, and bronchospasm. A recent review of kaposiform hemangioendothelioma finds that an associated coagulopathy (Kasabach-Merritt phenomenon) occurs in 72%. SUMMARY Propranolol appears to be tremendously efficacious with fewer side effects than systemic corticosteroids, but its proper place in the therapeutic algorithm for IH and other vascular tumors awaits controlled study.
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Dubois J, Alison M. Vascular anomalies: what a radiologist needs to know. Pediatr Radiol 2010; 40:895-905. [PMID: 20432007 DOI: 10.1007/s00247-010-1621-y] [Citation(s) in RCA: 146] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Accepted: 02/08/2010] [Indexed: 01/19/2023]
Abstract
Most haemangiomas and vascular malformations are identified according to clinical criteria. A good knowledge of the classification and clinical characteristics of the vascular anomalies is necessary when managing these patients. However, some cases are challenging either because of an atypical presentation (e.g., soft-tissue mass with normal overlying skin) or because of classification difficulties. Doppler US and MRI are the two main imaging modalities that allow classification of the vascular anomalies and are useful in those clinically uncertain cases to establish the correct diagnosis. This aids the choice of the most appropriate treatment and to inform the parents of the prognosis. High-resolution grey-scale and Doppler US allow excellent visualization of most superficial masses. Doppler US is the easiest way to assess the haemodynamics of a vascular lesion and to clarify a doubtful diagnosis between a haemangioma and vascular malformation. MRI is the best technique for evaluating the extent of the lesions and their relationship to adjacent structures. While newly developed drugs from angiogenesis research labs are awaited, radiologists have an important role in the treatment of haemangiomas and vascular malformations. Intervention remains crucial in cases of alarming haemangiomas and venous malformations (VM), lymphatic malformations (LM) and arteriovenous malformations (AVM). A multidisciplinary team, including paediatricians, haematologists, surgeons and radiologists, must manage the problem cases both in terms of diagnostic work-up and therapeutic options. This paper will briefly discuss the imaging findings and treatment of vascular anomalies.
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Affiliation(s)
- Josée Dubois
- Department of Medical Imaging, Sainte-Justine Hospital, 3175 Cote Ste-Catherine, Montreal, QC H3T 1C5, Canada.
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Léauté-Labrèze C, Sans-Martin V. [Infantile hemangioma]. Presse Med 2010; 39:499-510. [PMID: 20207100 DOI: 10.1016/j.lpm.2009.10.015] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2009] [Revised: 10/06/2009] [Accepted: 10/14/2009] [Indexed: 11/19/2022] Open
Abstract
Infantile hemangioma is the most common tumor in children, but its pathophysiology is still not well understood. Infantile hemangioma develops during the first weeks of life, usually builds up over 3 to 6 months, and then regresses very slowly over a period of 3 to 7 years. Three quarters of these hemangiomas are lobular and are not associated with malformations. On the other hand, the hemangiomas referred to as segmental may be associated with developmental abnormalities (PHACES and PELVIS/SACRAL syndromes). Because of their spontaneous involution, most infantile hemangiomas do not require therapeutic intervention. In 10 to 15 % of cases, treatment is necessary because of complications when life or physiological functioning is threatened, or there are local complications or the long-term esthetic risk is too high. Until now, the standard first-line treatment has been general corticosteroid therapy. The usual choice for second-line treatment is interferon or vincristine. The efficacy of propranolol, a non-cardioselective beta-blocker, was recently reported.
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Affiliation(s)
- Christine Léauté-Labrèze
- Unité de dermatologie pédiatrique, centre de référence maladies rares de la peau, hôpital Pellegrin-Enfants, CHU de Bordeaux, F-33076 Bordeaux cedex, France.
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Metry D, Heyer G, Hess C, Garzon M, Haggstrom A, Frommelt P, Adams D, Siegel D, Hall K, Powell J, Frieden I, Drolet B. Consensus Statement on Diagnostic Criteria for PHACE Syndrome. Pediatrics 2009; 124:1447-56. [PMID: 19858157 DOI: 10.1542/peds.2009-0082] [Citation(s) in RCA: 241] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES A subgroup of patients with infantile hemangiomas have associated structural anomalies of the brain, cerebral vasculature, eyes, sternum, and/or aorta in the neurocutaneous disorder known as PHACE syndrome. The diagnosis has been broadly inclusive by using a case definition of a facial hemangioma plus >or=1 extracutaneous features, leading to numerous reports of potential associated disease features, many of uncertain significance. This consensus statement was thus developed to establish diagnostic criteria for PHACE syndrome. METHODS A multidisciplinary group of specialists with expertise in PHACE syndrome drafted initial diagnostic criteria on the basis of review of published, peer-reviewed medical literature and clinical experience. The group then convened in both executive and general sessions during the PHACE Syndrome Research Conference held in November 2008 for discussion and used a consensus method. All conflicting recommendations were subsequently reconciled via electronic communication and teleconferencing. RESULTS These criteria were stratified into 2 categories: (1) PHACE syndrome or (2) possible PHACE syndrome. Major and minor criteria were determined for the following organ systems: cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline. Definite PHACE requires the presence of a characteristic segmental hemangioma or hemangioma >5 cm on the face or scalp plus 1 major criterion or 2 minor criteria. Possible PHACE requires the presence of a hemangioma >5 cm on the face or scalp plus 1 minor criterion. The group recognized that it may be possible to have PHACE syndrome with a hemangioma affecting the neck, chest, or arm only or no cutaneous hemangioma at all. In such cases, fulfillment of additional required criteria would also lead to a possible PHACE diagnosis. CONCLUSIONS These criteria represent current knowledge and are expected to enhance future assessments of PHACE syndrome. It is understood that modifications are to be expected over time to incorporate new research findings.
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Affiliation(s)
- Denise Metry
- Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA
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Connelly EA, Viera M, Price C, Waner M. Segmental hemangioma of infancy complicated by life-threatening arterial bleed. Pediatr Dermatol 2009; 26:469-72. [PMID: 19689527 DOI: 10.1111/j.1525-1470.2009.00955.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. IH of "segmental" morphology, are clusters of hemangiomas with a configuration involving a broad anatomic territory of skin. They are the least common of all types and generally larger than regular hemangiomas, morphologically characterized as plaque-like lesions. Head and neck segmental hemangiomas have a higher risk of causing life-threatening complications and of having associated structural anomalies, i.e., PHACES syndrome (Posterior fossa malformations, hemangiomas, arterial anomalies, coartation of the aorta and other cardiac defects, eye abnormalities and sternal clefting or supra abdominal raphe). We present a patient with a segmental IH over the right anterior neck complicated by ulceration and life threatening arterial bleeding. Although segmental hemangiomas of head and neck have high incidence of ulceration, fortunately life threatening bleeding events are rare with only 7 previously recorded cases. We recommend that large, neck IH be followed closely for evidence of ulceration and that MRI/MRA be performed to adequately assess their vascular supply. Direct extension of the ulceration into arterial vessels is a possibility and can lead to severe bleeding. Life-threatening bleeding is an unusual complication of IH and may represents a surgical emergency. In such cases we recommend a multidisciplinary approach to their treatment.
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Abstract
PHACE syndrome is a multisystem disorder presenting with facial hemangiomas, arterial anomalies, cardiac anomalies, posterior fossa malformations and eye abnormalities. The eye abnormalities include microphthalmos, cataracts, optic atrophy and iris hypoplasia. Amongst the neurological anomalies, posterior fossa malformations are common. Fourth nerve palsy has been reported with PHACE syndrome. We report a child presenting with a triad of congenital third nerve palsy, cerebellar hypoplasia and facial capillary hemangioma.
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Affiliation(s)
- Ramesh Murthy
- Strabismus and Pediatric Ophthalmology, L V Prasad Eye Institute, Kallam Anji Reddy Campus, Banjara Hills, Hyderabad, India.
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Affiliation(s)
- V Madan
- Dermatology Centre, Salford Royal Hospitals Foundation Trust, Hope Hospital, Salford, Manchester, UK.
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