Vascular Anomalies: Hemangiomas and more
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1 Workshop Pädiatrische Dermatologie Thalwil 17. und 18. März 2016 Vascular Anomalies: Hemangiomas and more Lisa Weibel Head of Pediatric Dermatology University Children s Hospital, Zurich
2 CONTENT 1. Classification 2. Hemangiomas 3. Some vascular malformations
3 ISSVA Classification of Vascular Anomalies Vascular Tumors Benign Infantile hemangioma Congenital hemangioma (RICH, NICH, PICH) Tufted angioma Pyogenic granuloma Locally aggressive or borderline Kapos. Hemangioendothelioma Malignant Vascular Malformations Simple Capillary malformation Lymphatic malformation Venous malformation Arteriovenous malformation Combined Associated with other anomalies Dasgupta R, Fishman SJ. ISSVA Classification. Semin Pediatr Surg 2014
4 Clinical clues for diagnosis To ask the right questions: 1. Present at birth? When first noticed? 2. Changes over time? 3. Pain? 4. Any similar lesions in the family? Clinical examination: 1. Macule or raised / with swelling? Hot? 2. Multiple lesions? Other birthmarks? 3. Symmetry: midline lesion?
5 ISSVA Classification of Vascular Anomalies Vascular Tumors Benign Infantile hemangioma Congenital hemangioma (RICH, NICH, PICH) Tufted angioma Pyogenic granuloma Locally aggressive or borderline Kapos. Hemangioendothelioma Malignant Vascular Malformations Simple Capillary malformation Lymphatic malformation Venous malformation Arteriovenous malformation Combined Of major vessels Associated with other anomalies Dasgupta R, Fishman SJ. ISSVA Classification. Semin Pediatr Surg 2014
6 DD Myofibroma, Fibrosarcoma, Rhabdomyosarcoma DD Fibrosarcoma, Rhabdomyosarcoma, DFSP Dasgupta R, Fishman SJ. ISSVA Classification. Semin Pediatr Surg 2014
7 Infantile hemangiomas 1 of 15 all infants affected unique biology (GLUT1-positiv) some risk factors pathogenesis? 1. Somatic mutation of hemangioma stem cells 2. Placental theory 3. Hypoxia-induced proliferation Chen TS. Pediatrics 2013 Greenberger S. Brit J Dermatol 2013
8 Infantile hemangiomas Dasgupta R, Fishman SJ. ISSVA Classification. Semin Pediatr Surg 2014
9 Infantile hemangioma: growth pattern in 50% precursor lesions at birth! 80% of definite size reached at 3 months (cave: deep lesions) spontaneous involution between 2 and 4 years appr. 15% need therapy Jahre Luu M and Frieden. Br J Dermatol 2013 Tollefson MM. Pediatrics 2012
10 Spontanous involution (mainly between age 2-4 years) 30 to 65% of infantile hemangioma leave residual changes permanent skin changes and psychosocial impact of hemangioma residua are increasingly appreciated Bauland CG. Plast Reconstr Surg 2011
11 LUMBAR Syndrome (PELVIS / SACRAL) L ower body hemangioma U rogenital anomalies M yelopathy B ony deformities A norectal malformations R enal anomalies Drolet BA. J Pediatr 2010 Iacobas I. J Pediatr 2010 Schumacher WE. Pediatr Radiol 2012
12 PHACES Syndrom P posterior fossa anomalies H emangioma (plaque-type, face, neck, trunk, extremity) > 5 cm A rterial anomalies (cerebrovascular, neck, aorta) C ardiac anomalies E ye abnormalities S ternal defects MRA head&neck Echocardiography Ophthalmology TSH Metry D. Pediatrics 2009 Haggstrom AN. Pediatrics 2010
13 Propranolol 1st-line treatment Schiestl, Weibel, Eur J Pediatr 2011
14 Systemic treatment options for IH other than betablockers Hoeger P. Eur J Pediatr 2015
15 Treatment of infantile hemangiomas today major challenge today is the identification of which hemangiomas require treatment and which can be left to involute spotaneously to identify hemangiomas at risk early! approximately 15% need therapy today lower threshold for treatment than a few years ago permanent skin changes and psychosocial impact of hemangioma residua have increasingly been appreciated Liang MG, Frieden IJ. Semin Pediatr Surg 2014 Hoeger PH et al. Eur J Pediatr 2015
16 Hemangiomas at risk Systemic or topical treatment? Liang MG, Frieden IJ. Semin Pediatr Surg 2014
17 Current data... Swiss Guidelines for the treatment of infantile hemangiomas with propranolol A. Smith, M. Theiler, D. Klima Lange, V. Hauser, R. Angst, M. Seeger, P. Esslinger, D. Cholewa, E. Brönnimann, S. Christen-Zaech, A. De Buys, K. Neuhaus, C. Schiestl, AM. Calza, G. La Scala und L. Weibel in press PAEDIATRICA April 2016
18 Most rapid growth: between 5.5 und 7.5 weeks at birth 2 weeks 4 weeks 6 weeks 8 weeks 2.5 months Referral for therapy: at 4 weeks Need for quick appointments and teledermatology! Tollefson MM. Pediatrics 2012 Hoeger P. Eur J Pediatr 2015
19 Treatment with propranolol today Where and by whom? prescribers should be experienced in vascular anomalies and in evaluation young children treatment should be initiated only in clinical settings equipped and qualified for the safe and immediate management of any adverse event, in particular cardiovascular events Hemangiol is licensed and reimbursed in CH Drolet et al, Pediatrics 2013 Hoeger P. Eur J Pediatr 2015
20 Contraindications for propranolol treatment age < 4 weeks (except rapidly growing, life/function threatening IH) potential drug interactions bronchial asthma AV-block II to III, sick sinus syndrome bradycardia, hypotension cardiac failure proneness to hypoglycemia phaeochromocytoma Raynaud s syndrome Hoeger P. Eur J Pediatr 2015
21 Propranolol treatment for IH pre-treatment checks treatment start monitoring dose / - intervall treatment duration stop of treatment history, clinical exam, +/- ECG, HR, BP, photo in-patient: age < 8 weeks (correct. age), weight <3.5kg, comorbidities, social issues otherwise out-patient setting HR and BP 1 and 2 h after first dose and each dose increase;; HR 1x/month thereafter 2 (3) mg/kg/d in 2 (3) doses/day after feeding min. 6 months, often longer (12 mths or longer) no dose tapering needed, sometimes advised, further follow up needed (relapse 15%) Hoeger P. Eur J Pediatr 2015
22 Side effects of propranolol treatment Propranolol treatment should be interrupted in case of poor oral intake and intercurrent obstructive bronchitis Hoeger P. Eur J Pediatr 2015
23 Side effects of propranolol treatment Sleep disorders, bronchitis/wheezing... propranolol crosses the blood-brain barrier long-term follow-up studies are needed with respect to neurodevelopment there is no evidence to date of any long-term issues from its use in cardiology hydrophilic beta blockers such as nadolol and atenolol seem to be as effective for IH with less central nervous side effects and atenolol with less risk of bronchitis Pope E. Br J Dermatol 2013 Abarzua-Araya A. J Am Acad Dermatol 2014 Bernabeu-Wittel J. Pediatr Dermatol 2015
24 40 infants (<35 weeks old);; small proliferating IH: median size 3cm 2 Timolol-Gel 0.5% 2x daily
25 Topical Betablockers for IH Increasing experience with topical timolol 0.5% effective for the treatment of superficial and small hemangiomas Great potential for early therapy if appropriate! Cave: systemic absorption in young babies, large hemangiomas, large ulceration!
26 small superficial IH may be treated with topical betablockers (timolol) ulcerations benefit from oral or topical betablockers;; severe ulcerations may benefit from additional laser treatment (PDL) surgical excision is indicated for disfiguring residua or exophytic IH laser treatment (PDL) is ideal to treat residual erythema/telangiectasia in the involuted phase
27 Pyogenic granuloma (Botryomycoma) Lobular capillary hemangioma (GLUT1 negative) Rapid growth, bleeds easily Infants and toddlers Treatment: excision with histology;; pulsed dye laser, cryotherapy
28 ISSVA Classification of Vascular Anomalies Vascular Tumors Benign Infantile hemangioma Congenital hemangioma (RICH, NICH, PICH) Tufted angioma Pyogenic granuloma Locally aggressive or borderline Kapos. Hemangioendothelioma Tufted Angioma Malignant usually not present at birth early growth phase present at birth at max. size Dasgupta R, Fishman SJ. ISSVA Classification. Semin Pediatr Surg 2014
29 Congenital vascular tumor Most important investigation? full blood count at birth (platelets) at birth coagulation screen incl D-dimers and fibrinogen Cave: Kasabach-Meritt phenomenon! Ultrasound Doppler
30 Congenital hemangioma RICH 1 NICH 2 PICH 3 1 Rapidly involuting congenital hemangioma 2 Non involuting congenital hemangioma 3 Partially involuting congenital hemangioma Usually not associated with marked coagulopathy GLUT1 negative Warm to touch Highly vascularized ( high-flow on early ultrasound) Propranolol without effect (and usually not needed)
31 RICH (rapidly involuting congenital hemangioma) Marked spontaneous involution within the first 6 months of life (and thereafter) Decrease of vascularization Residua: some discoloration, lipoatrophy
32 Kasabach-Meritt Phenomenon (KMP) profound thrombocytopenia (platelet trapping within the tumor) raised D-dimers low fibrinogen Kaposiform Hemangioendothelioma (KHE) Tufted angioma (TA)
33 Kaposiform hemangioendothelioma with Kasabach-Meritt Phenomenon (KMP) infiltrative vascular tumor of endothelial and lymphatic derivation usually presents in infancy: enlarging vascular tumor with KMP on extremities associated with disabling fibrosis and contractures surgical resection often impossible treatment of choice today: sirolimus Comenero, Hoeger. Br J Dermatol 2014 Drolet. J Pediatr 2013
34 Tufted angioma + / - Kasabach-Meritt Phenomenon (KMP) congenital or appear within first 5 years of life solitary solid firm pink-red-purple lesion tenderness, hypertrichosis, hyperhidrosis histology indicated may resolve spontaneously -> watch & wait strategy aspirin, surgical excision;; sirolimus Comenero, Hoeger. Br J Dermatol 2014
35 Capillary malformation (port wine stain, nevus flammeus) 1 of 300 newborns affected malformation of dermal capillaries and venules Shirley MD. N Engl J Med, Mai 2013
36 Sturge-Weber malformation Capillary malformation in fronto-temporal ( forehead ) region Leptomeningeal angiomatosis +/- glaucoma epilepsie, developmental delay, hemiparesis fronto-temporal ( forehead ) region Zurich: brain MRI (incl. contrast) age 3-6 months Waelchli R. Br J Dermatol 2014 Mazereeuw-Hautier et al. Arch Dermatol 2006
37 Capillary malformation: treatment of choice Pulsed-dye laser (585nm/595nm) Alternative: IPL, Nd:YAG Anderson RR et al. Science 1983 Tan OT et al. N Engl J Med 1989 Van der Horst CM et al. N Engl J Med 1998 Faurschou A et al. Cochrane Database Syst Rev. 2011
38 PDL for nevus flammeus: at what age? Until the age of approximately 7-9 years under GA (iv-sedation) Face, neck, chest: start at age 10 to 12 months Extremities: usually start > 7-9 years under local anesthesia* *Ametop Gel 4%
39 Venous malformations Usually sporadic From birth, may be noted later Mucosa and skin Bluish swellings Joint- and muscle involvement Phleboliths, pain bleeding in joints Localized/disseminated intravasal coagulopathy!
40 Diagnostic test for venous malformations Localized intravasal coagulopathy - D-Dimers - Fibrinogen D-Dimers: Sensitivität 43% Spezifität 96% Ultrasound-Doppler + MRI Dompmartin et al. Arch Dermatol 2009
41 Management of venous malformations Conservative - pain management, Compression - Aspirine, low-molecular heparin - Rapamycin? Surgical - Sclerotherapie ( first-line therapy ) - surgical resection Greene A et al. Clin Plastic Surg 2011 Burrows et al. J Vasc Interv Radiol 2001 Berenguer et al. Plast Reconstr Surg 1999
42 Lymphatic malformations (Lymphangioma) microcystic macrozystic Complications Bleeding in cysts Infections (cellulitis) disfigurement
43 Management of lymphatic malformations Sclerotherapy (zb. OK432, Ethibloc, Bleomycin or Picibanil) Surgical excision Laser: CO2 / pulsed dye for lymphangioma circumscriptum Drugs: Rapamycin (Sirolimus) Greene et al. Clin Plast Surg 2011
44 Management of AVM Intervention: ¾ of patients need treatment until adolescence Primary goal: to prevent progression and destruction Embolisation Resection Combination of 1. embolisation and 2. resection Drugs: Rapamycin (Sirolimus), Thalidomid Greene et al. Clin Plast Surg 2011
45 PI3K-AKT-mTOR signalling pathway mtor inhibitors are a promising new treatment in vascular anomalies PROS (PI3K related overgrowth syndrome) lymphatic malformation Klippel-Trenaunay syndrome CLOVES Macrocephaly-CM PTEN hamartoma tumor syndrome Proteus syndrome Sirolimus Luks et al, J Pediatrics, 2015 Keppler-Noreuil et al, Am J Med Gen 2015
46 Summary Read the early signs for hemangiomas early! Most rapid growth of hemangioma: between 4 and 8 weeks - consider treatment early! consider histology of congenital vascular tumors and know the mimickers of congenital hemangiomas investigate early for Kasabach-Meritt phenomenon in congenital vascular tumors Capillary malformation with risk for Sturge Weber malformation - > fronto-temporal region (forget V1)! Multidisciplinary management for vascular malformations sgvac@hispeed.ch
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