SUCCESFULL TREATMENT OF SUBGLOTTIC HAEMANGIOMAS WITH PROPRANOLOL Gács É, Katona G, Uhereczky G, Szabó L Heim Pál Children’s Hospital, Budapest Chairmen , dear collegues. In this section – beeing pediatric pulmologist- I am the odd one out. I am working in Hungary,s biggest children Hostpital , our department is specialised in airway diseases. So we have also patient with airway haemangioma, and manage them together with ENT collegiues.

DEPARTMENT OF PULMONOLGY Heim Pál Children’s Hospital Budapest, Hungary First , let me show our hospital , this our building, and departement DEPARTMENT OF PULMONOLGY

DEPARTMENT OF PULMONOLGY Heim Pál Children’s Hospital Budapest, Hungary DEPARTMENT OF PULMONOLGY 15 BEDS 3 OUTPATIENT ROOMS 5 PULMOLOGISTS 7000 PATIENT /YEAR (asthma, wheezy bronchitis,cystic fibrosis…) CLINICAL STUDIES MAIN INTERESTS ASTHMA-CARE QOL PATIENT EDUCATION: meetings, books,website Everything of asthma: for patients and parents We have 15 beds for pulmonary diseases, and 3 outpatient rooms with 5 pulmologists, a lot of patient. Our main interest are: asthma care, find very importan the patient education , that,s why we organise meetings, writing books and website. And now, let.s see my topic:

Haemangioma beningn vascular tumors most commonly encountered in infancy incidence: 5-10 % at the end of the first year Increased risk in premature neonates and in females most of them regress spontaneously Infantile hemangioma, a benign vascular tumor, is the most common tumor of infancy, with an incidence of 5%–10% at the end of the first year. There is increased risk in premature neonates and in females. Most of has a spontan regression, and so The tumor displays a distinctive life cycle that can be separated, both clinically and histologically, into three phases: the proliferating phase starts within a few weeks from birth and ends within the first year of life, with the most growth occurring during the first 4–6 months of life. The involuting phase typically begins at 1 yr of age. Finally, at the involuted phase, tumor growth has stopped and the tumor has regressed. The regression is either complete or, more often, leaves scar tissue, telangiectasia, or redundant or anetodermic skin

Treatment In most patient no specific treatment is required In 10% of cases haemangioma has excessiv growth, or has problematic location Subglottic haemangiomas are rare but can be life-threatening in proliferation phase, during the first 4-6 months of life Corticosteroids have been the first-line treatment for IH for more than 40 years. ….. in most patients no specific treatment is required. However, in 10% of cases IH is problematic or even dangerous for he child, becaouse of excessiv growth or its location . That is the case with subglottic haemangiomas, . This manifestation is rare, but can be life treatening in proliferation phase. For more than 40 years the first line treatment was corticosteroids . In these circumstances that carry the risk of irreversible disfigurement, airway obstruction, or decreased vision, treatment is indicated. In recent years, beta-blockers, most specifically propranolol, have been shown to be an effective pharmacological treatment of proliferating IH.

The propranolol story There has been a dramatic evolution in the treatment of laryngotracheal haemangiomas 2008 discovery by „chance” of the effectiveness of propranolol (Léaute-Labreze) A french group discovered by chance, the good effect of propranolo, and so the propranolol story begun.

Effect of propranolol: vasoconstriction downregulation of proangiogenetic factors: VEGF – vascular endothelial growht factor BFGF- basic fibroblast growht factor apoptosis of capillary endothelial cells This good effect has tree elements: First, there is a rapid effect because os vasoconsctriction, and than comes - for several monts- the downregulaion os proangiogenetic factors: namely vascular endothelial grows factor and basic fibroblast growht factor. At the end apoptosis of capillary entothelial cells occurs.

First patient: girl, born 17-09-2010 Haemangioma on left arm, palm, and lips Respiratory symptoms since one month: Inspiratory stridor Stenotic cough Let me talk about our first patient, this girl had haemangioma on left arm, palm, lips, and respiratory symptoms inspiratory stridor and stenotic cough since the age of one monts. With permission of parents

Bronchoscopy 11- 2010. On bronchoscopic picture you can see the serious subglottic stenosis

Therapy: Oxygen intermittent Epinephrine inhalation Steroid 1 mg / kg Propranolol: 2mg/kg/day She was given oxygen, epinephrin inhalation and steroid with moderate effect , than propranolol was started.

Modified Westley croup-score Inspiratoric stridor Intercostal retraction Jugular retraction General condition Cough 0- 15 We created a modified score to evaluate the improvement , with this five condition , and between zero and fiveteen points

Symptom-score: days epinephrin steroid propranolol end of steroid This picture clearly shows, that epinephrin and sterois had a moderate effect, but after giving propranolol, the syptome score showed a rapid decline. Actually it was incredible for me for the first time days epinephrin steroid propranolol end of steroid

Improvement in endoscopic picture Beside the clinical improvement, there was a clear endoscopic improvemnt too, after two months and 9 months of treatment 2010. 11. 2011. 01. 2011. 09.

4 patients in our department A.S. V.H. M.M. Sz.Z. age (months) 2 stridor ++ + +++ cough skin lips, arms - face, lips lips duration of P.therapy (months) 16 6 18 12 steroid 2 weeks 4 months surgical intervention side-effects bradycardia In the last 7 years we have 4 patiens with serious subglottic stenosis , All of them were 2 months old, girl, had stenotic cough, no needfor surgical intervention . The shortest Propranolol treatment was given patient 2., she had noskin symptom, and the longest treatment was 18 months ( patient 3) , together with a long steroid treatment too. Side-effect ( temporary bradycardia) occured in patient 4.

After propranolol treatment A.S. V.H. M.M. SZ.Z. Month after cessation of P. 60 24 6 stridor - cough occasionally skin better Somatic development good slow steroid occasionally (last steroid in 2015) Surgical intervention This picture shows our follow-up period after treatment ( between half és 5 years) We can say, the girls are well.With no respiratory and mild skin symptoms

Skin symptoms of patient No3. before treatment She is our patient three, she had the most impressive skin symptoms and needed the longest treatment. With permission of parents

… and now (7 years old) After 7 years she has mild skin symptoms with no respiratory symptoms. With permission of parents

SUMMARY Carefully administered, propranolol may demonstrate efficacy as a first-line agent in most cases avoiding surgery, tracheostomy or prolonged steroids. However, some lesions may be partly resistant to propranolol and require surgery or long-term steroids. So, in summery: 1. F. Denoyelle et al: International Journal of Pediatric Otorhinolaryngology 73 (2009) 1168–1172 2.N.Raol et al: International Journal of Pediatric Otorhinolaryngology (2011) 3.L.R.Javia et al: International Journal of Pediatric Otorhinolaryngology 75 (2011) 1450–1454

Thank you for your kind attention.