AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 41 4–4 1 6
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Management of subglottic hemangioma with propranolol ☆ Mehmet Halil Celiksoy, MD a,⁎, Muhammet Sukru Paksu b , Sinan Atmaca c , Recep Sancak a , Gonca Hancioglu, MD d a
Department of Pediatric Allergy and Immunology, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey Department of Pediatric Intensive Care, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey c Department of Otolaryngology, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey d Department of Pediatrics, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey b
ARTI CLE I NFO
A BS TRACT
Article history:
Subglottic hemangioma is a rare but life- threatening condition which requires
Received 26 December 2013
intervention. It generally starts proliferating in the first and second months of lifespan and whether there is a respiration problem or not, it causes biphasic stridor. Its diagnosis generally requires direct laryngoscopy or direct screening through bronchoscopy. This case report presents a 45-day-old girl who had subglottic hemangioma presenting with wheezing and stridor. Our case took propranolol with a dose of 2 mg/kg/day and within 48 h after the start of the treatment, obstructive symptoms started to alleviate considerably. © 2014 Elsevier Inc. All rights reserved.
1.
Introduction
Congenital subglottic hemangioma is a rarely seen lesion; however, because of its anatomical location, it can potentially cause death. It makes up 1.5% of all congenital laryngeal anomalies and it is twice more common in girls than in boys [1]. 50% of the patients who have subglottic hemangioma have a comorbid skin hemangioma while 1%–2% of the patients who have skin hemangioma have a comorbid subglottic lesion [2]. Hemangiomas generally regress after a proliferative phase of three to nine months and they restrict themselves. However, hemangiomas which have subglottic location require intervention since they can threaten life [3]. This paper presents a 1,5-month-old girl who was diagnosed to have subglottic hemangioma and who was treated with propranolol.
2.
Case reports
A 1.5-month-old girl who had no previous complaints was taken to our clinic with a complaint of respiratory distress. Her history revealed that she had been healthy previously; her respiratory distress and wheezing had started about 15 days ago. She had been taken to a hospital where she was diagnosed to have bronchiolitis and she had been hospitalized and treated; however, as she did not respond to the treatment, she had been sent to our hospital. Her physical examination showed that she had no cyanoses but she looked unsettled. Her respiratory rate was 64/min, her peak heart rate was 128/min and her armpit temperature was 36.6 °C. She had intercostal and subcostal retractions. Both lungs had equal contribution to respiration, respiratory sounds were coarse and she had both inspiratory and expiratory stridors which were
☆
No competing financial interests exist. ⁎ Corresponding author at: Ondokuz Mayıs University Medical Faculty, Department of Pediatric Allergy and Immunology, 55139, Kurupelit, Samsun, Turkey. Tel.: +90 3623121919 3634; fax: +90 362 457 60 41. E-mail address: [email protected] (M.H. Celiksoy). 0196-0709/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjoto.2014.01.009
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 41 4–4 1 6
more obvious on bilateral sibilant rales, and inspiratory phase. She also had wheezing. The examinations of her circulatory system and other systems were normal. Laboratory test results were as follows: haemoglobin: 10.1 g/dl, hematocrit: 30.9%, white blood cell count: 6390/mm3, thrombocyte count: 523,000/mm3, Na: 138 mEq/L, K: 5.2 mEq/L, Cl: 109 mEq/L, AST: 47 IU/L, ALT: 37.5 IU/L, eosinophil 2.9%, Creactive protein: 2.1 mg/L, IgG: 3.6 g/L, IgA: 0.19 g/L, IgM: 0.337 g/L, IgE: 10 IU/mL. Her immunoglobulin values were normal for her age and her complete urine analysis and blood gas analysis were normal. Her posteroanterior chest radiography did not show any peculiarities. She was prediagnosed as acute laryngotracheobronchitis and she started to have beta agonist, cold-vapor, nebuliser adrenaline and systemic steroid treatment. Her follow-up showed that she was not responding to treatment and her respiratory distress was increasing, thus she had a diagnostic bronchoscopy and she was found to have subglottic hemangioma (Fig. 1). Tracheostomy was performed and 2/mg/kg/day oral propranolol was started. Two days after the propranolol treatment started, her complaints regressed and her clinical findings completely improved and she was discharged on the tenth day of the treatment.
3.
Discussion
Hemangiomas are congenital vascular lesions which grow fast within the first few months following birth, come to a standstill between 12th and 18th months and regress until the age of five [1]. Although subglottic hemangiomas are benign, they can grow fast during the growth phase and cause airway obstruction and thus have a fatal course [4]. Clinically, they show subglottic stenosis symptoms and they appear in repetitive croup and biphasic stridor. In addition, they can cause barking like cough, hoarseness, cyanosis, hemoptysis, dysphagia and weight loss [1]. It is difficult to diagnose this disease since it is rare and it is clinically similar to other common diseases [5]. The symptoms of our patient started when she was 1.5 months old and they had a comorbid wheezing. No consensus was reached about whether wheezing occurred in the patient incidentally or whether it was caused by a comorbid bronchitis. Another possible reason of this whistle like sound was the fact that hemangioma had obstructed almost the whole airway. However, to prove this argument, we need a series of cases, not only one case. The fact that the patient had wheezing was the primary reason for having difficulty in making a diagnosis. Congenital subglottic hemangiomas can coexist with other vascular lesions that are localized in the head and neck region [6]. 50% of the patients who have subglottic hemangioma have a
415
comorbid skin hemangioma while 1%–2% of the patients who have skin hemangioma have a comorbid subglottic lesion [2]. Another difficulty encountered in making a diagnosis was the fact that the patient did not have skin hemangioma. A diagnosis is made by using typical history, physical examination and endoscopic image. In the neck plain radiography, asymmetrical narrowing is observed in the subglottic region [1]. She was prediagnosed as acute laryngotracheobronchitis and she started to have oxygen, beta agonist, cold-vapor, nebuliser adrenaline and systemic steroid treatment. The fact that her follow-up showed that she was not responding to treatment and her respiratory distress was increasing guided us in our diagnosis and made us consider the possibility of congenital anomaly in the patient. She had a diagnostic bronchoscopy and she was found to have subglottic hemangioma. Whether the patients with subglottic hemangioma have tracheostomy or not, a careful follow up is necessary. Tracheostomy secures the airway until hemangioma is naturally regressed. In addition, it decreases the associated complications and provides protection until there is an improvement in the treatment and the size of the lesion gets smaller [1]. In this sense, since our patient’s respiratory distress came to a level that requires mechanical ventilation, tracheostomy was performed and our patient benefited from this. There are a great number of choices for the treatment of subglottic hemangiomas. These choices include radiotherapy, cryotheraphy, sclerotherapy, alpha 2a interferon, systemic or intralesional steroid, open surgery resection and laser ablation. Because of their high side effect risk, radiotherapy, cryotherapy and sclerotherapy are not used very frequently [1]. In 1994, Ohlms et al. treated eight patients with interferon alpha 2a. Because of the risk of spastic diplegia, this choice of treatment soon fell into disfavor in terms of being the first choice [7]. Systemic steroids have been found to be effective in 25% of all cases and treatment is important especially in the acute phase [3]. It is important to decrease steroid gradually in order to prevent regrowth. Steroid treatment is effective in very small lesions and long term treatments have complications. These side effects are Cushing syndrome, hypertension, immune deficiency and growth retardation. As well as systemic steroid, intralesional steroid can also be used in the treatment. Intralesional steroid injection has benefits in terms of the decrease in side effects depending on the systemic steroid use. However, local steroid injections require multiple treatments [1]. Medium subglottic hemangiomas which do not extend outside the larynx can respond to intralesionary steroid treatment [8]. Although our patient got 2 mg/kg/day intravenous steroid beginning from her first day in hospital, she did not benefit from this treatment.
Fig. 1 – Subglottic Hemangioma.
416
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 41 4–4 1 6
In one sided small lesions which are localized in submucosa, ablation with CO2 laser can be used. Recently, potassium titanyl phosphate laser has begun to be used. However, in both situations laryngeal stenosis is an important complication [9,10]. Open surgery resection treatment for subglottic hemagiomas was defined by Sharp in 1949 for the first time [11]. Today, this method is recommended for lesions that threaten the airway, for wide lesions that obstruct the proliferative phase, for bilateral hemangioma and for lesions that cause extralaryngeal widening [1]. Recently, propranolol treatment had been preferred for the treatment of hemangioma. Le´aute´-Labre`ze et al. treated 11 cutaneous hemangiomas with propranolol and found out that propranolol caused visible changes beginning from the first day [12]. Recommended dosages of propranolol are well tolerated; however, there may arise side effects such as bradycardia, hypotension, bronchospasm, hypoglycemia and a decrease in lethargy diet. It has recently been reported that care must be taken in terms of hypoglycemia and life-threatening hyperkalemia. Further controlled studies are needed for the safety, efficiency and treatment protocol of Propranolol [13]. In our study, the patient’s stridor improved in two days after oral propranolol was started and the patient was discharged on the tenth day of the treatment. Bronchoscopy that was taken two months later after the beginning of the treatment showed 50% degrowth in hemangioma. As a result, in patients who have wheezing and stridor the reason for which cannot be explained and which do not respond to standard treatment, congenital anomalies should be considered as a prediagnosis. In big hemangiomas that can completely fill in the airway, inspiratory wheezing can be heard along with stridor.
REFERENCES
[1] Ahmad SM, Soliman AM. Congenital anomalies of the larynx. Otolaryngol Clin North Am 2007;40:177–91. [2] Sie KCY, McGill TJ, Healy GB. Subglottic hemangioma: 10 year’s experience with the carbon dioxide laser. Ann Otol Rhinol Laryngol 1994;103:167–72. [3] Jephson CG, Manunza F, Syed S, et al. Successful treatment of isolated subglottic haemangioma with propranolol alone. Int J Pediatr Otorhinolaryngol 2009;73:1821–3. [4] Naiman AN, Ayari S, Froehlich P. Controlled risk of stenosis after surgical excision of laryngeal hemangioma. Arch Otolarygol Head Neck Surg 2003;129:1291–5. [5] Chatrath P, Black M, Jani P, et al. A review of the current management of infantile subglottic haemangioma, including a comparison of CO2 laser therapy versus tracheostomy. Int J Pediatr Otorhinolaryngol 2002;64:143–57. [6] Leung AK, Cho H. Diagnosis of stridor in children. Am Fam Physician 1999;60:2289–96. [7] Ohlms LA, Jones DT, McGill TJ, et al. Interferon a-2A therapy for airway hemangiomas. Ann Otol Rhinol Laryngol 1994;103:1–8. [8] Kilham H, Gillis J, Benjamin B. Severe upper airway obstruction. Pediatr Clin North Am 1987;34:1–14. [9] Goodman TR, McHugh K. The role of radiology in the evaluation of stridor. Arch Dis Child 1999;81:456–9. [10] Altman KW, Wetmore RF, Mash RR. Congenital airway abnormalities in patient requiring hospitalization. Arch Otolaryngol Head Neck Surg 1999;125:525–8. [11] Sharp HS. Hemangioma of the trachea in an infant, successful removal. J Laryngol Otol 1949;63:413–4. [12] Le´aute´ -Labre` ze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649–51. [13] Raol N, Metry D, Edmonds J, et al. Propranolol for the treatment of subglottic hemangiomas. Int J Pediatr Otorhinolaryngol 2011;75:1510–4.
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Management of subglottic hemangioma with propranolol ☆ Mehmet Halil Celiksoy, MD a,⁎, Muhammet Sukru Paksu b , Sinan Atmaca c , Recep Sancak a , Gonca Hancioglu, MD d a
Department of Pediatric Allergy and Immunology, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey Department of Pediatric Intensive Care, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey c Department of Otolaryngology, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey d Department of Pediatrics, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey b
ARTI CLE I NFO
A BS TRACT
Article history:
Subglottic hemangioma is a rare but life- threatening condition which requires
Received 26 December 2013
intervention. It generally starts proliferating in the first and second months of lifespan and whether there is a respiration problem or not, it causes biphasic stridor. Its diagnosis generally requires direct laryngoscopy or direct screening through bronchoscopy. This case report presents a 45-day-old girl who had subglottic hemangioma presenting with wheezing and stridor. Our case took propranolol with a dose of 2 mg/kg/day and within 48 h after the start of the treatment, obstructive symptoms started to alleviate considerably. © 2014 Elsevier Inc. All rights reserved.
1.
Introduction
Congenital subglottic hemangioma is a rarely seen lesion; however, because of its anatomical location, it can potentially cause death. It makes up 1.5% of all congenital laryngeal anomalies and it is twice more common in girls than in boys [1]. 50% of the patients who have subglottic hemangioma have a comorbid skin hemangioma while 1%–2% of the patients who have skin hemangioma have a comorbid subglottic lesion [2]. Hemangiomas generally regress after a proliferative phase of three to nine months and they restrict themselves. However, hemangiomas which have subglottic location require intervention since they can threaten life [3]. This paper presents a 1,5-month-old girl who was diagnosed to have subglottic hemangioma and who was treated with propranolol.
2.
Case reports
A 1.5-month-old girl who had no previous complaints was taken to our clinic with a complaint of respiratory distress. Her history revealed that she had been healthy previously; her respiratory distress and wheezing had started about 15 days ago. She had been taken to a hospital where she was diagnosed to have bronchiolitis and she had been hospitalized and treated; however, as she did not respond to the treatment, she had been sent to our hospital. Her physical examination showed that she had no cyanoses but she looked unsettled. Her respiratory rate was 64/min, her peak heart rate was 128/min and her armpit temperature was 36.6 °C. She had intercostal and subcostal retractions. Both lungs had equal contribution to respiration, respiratory sounds were coarse and she had both inspiratory and expiratory stridors which were
☆
No competing financial interests exist. ⁎ Corresponding author at: Ondokuz Mayıs University Medical Faculty, Department of Pediatric Allergy and Immunology, 55139, Kurupelit, Samsun, Turkey. Tel.: +90 3623121919 3634; fax: +90 362 457 60 41. E-mail address: [email protected] (M.H. Celiksoy). 0196-0709/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjoto.2014.01.009
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 41 4–4 1 6
more obvious on bilateral sibilant rales, and inspiratory phase. She also had wheezing. The examinations of her circulatory system and other systems were normal. Laboratory test results were as follows: haemoglobin: 10.1 g/dl, hematocrit: 30.9%, white blood cell count: 6390/mm3, thrombocyte count: 523,000/mm3, Na: 138 mEq/L, K: 5.2 mEq/L, Cl: 109 mEq/L, AST: 47 IU/L, ALT: 37.5 IU/L, eosinophil 2.9%, Creactive protein: 2.1 mg/L, IgG: 3.6 g/L, IgA: 0.19 g/L, IgM: 0.337 g/L, IgE: 10 IU/mL. Her immunoglobulin values were normal for her age and her complete urine analysis and blood gas analysis were normal. Her posteroanterior chest radiography did not show any peculiarities. She was prediagnosed as acute laryngotracheobronchitis and she started to have beta agonist, cold-vapor, nebuliser adrenaline and systemic steroid treatment. Her follow-up showed that she was not responding to treatment and her respiratory distress was increasing, thus she had a diagnostic bronchoscopy and she was found to have subglottic hemangioma (Fig. 1). Tracheostomy was performed and 2/mg/kg/day oral propranolol was started. Two days after the propranolol treatment started, her complaints regressed and her clinical findings completely improved and she was discharged on the tenth day of the treatment.
3.
Discussion
Hemangiomas are congenital vascular lesions which grow fast within the first few months following birth, come to a standstill between 12th and 18th months and regress until the age of five [1]. Although subglottic hemangiomas are benign, they can grow fast during the growth phase and cause airway obstruction and thus have a fatal course [4]. Clinically, they show subglottic stenosis symptoms and they appear in repetitive croup and biphasic stridor. In addition, they can cause barking like cough, hoarseness, cyanosis, hemoptysis, dysphagia and weight loss [1]. It is difficult to diagnose this disease since it is rare and it is clinically similar to other common diseases [5]. The symptoms of our patient started when she was 1.5 months old and they had a comorbid wheezing. No consensus was reached about whether wheezing occurred in the patient incidentally or whether it was caused by a comorbid bronchitis. Another possible reason of this whistle like sound was the fact that hemangioma had obstructed almost the whole airway. However, to prove this argument, we need a series of cases, not only one case. The fact that the patient had wheezing was the primary reason for having difficulty in making a diagnosis. Congenital subglottic hemangiomas can coexist with other vascular lesions that are localized in the head and neck region [6]. 50% of the patients who have subglottic hemangioma have a
415
comorbid skin hemangioma while 1%–2% of the patients who have skin hemangioma have a comorbid subglottic lesion [2]. Another difficulty encountered in making a diagnosis was the fact that the patient did not have skin hemangioma. A diagnosis is made by using typical history, physical examination and endoscopic image. In the neck plain radiography, asymmetrical narrowing is observed in the subglottic region [1]. She was prediagnosed as acute laryngotracheobronchitis and she started to have oxygen, beta agonist, cold-vapor, nebuliser adrenaline and systemic steroid treatment. The fact that her follow-up showed that she was not responding to treatment and her respiratory distress was increasing guided us in our diagnosis and made us consider the possibility of congenital anomaly in the patient. She had a diagnostic bronchoscopy and she was found to have subglottic hemangioma. Whether the patients with subglottic hemangioma have tracheostomy or not, a careful follow up is necessary. Tracheostomy secures the airway until hemangioma is naturally regressed. In addition, it decreases the associated complications and provides protection until there is an improvement in the treatment and the size of the lesion gets smaller [1]. In this sense, since our patient’s respiratory distress came to a level that requires mechanical ventilation, tracheostomy was performed and our patient benefited from this. There are a great number of choices for the treatment of subglottic hemangiomas. These choices include radiotherapy, cryotheraphy, sclerotherapy, alpha 2a interferon, systemic or intralesional steroid, open surgery resection and laser ablation. Because of their high side effect risk, radiotherapy, cryotherapy and sclerotherapy are not used very frequently [1]. In 1994, Ohlms et al. treated eight patients with interferon alpha 2a. Because of the risk of spastic diplegia, this choice of treatment soon fell into disfavor in terms of being the first choice [7]. Systemic steroids have been found to be effective in 25% of all cases and treatment is important especially in the acute phase [3]. It is important to decrease steroid gradually in order to prevent regrowth. Steroid treatment is effective in very small lesions and long term treatments have complications. These side effects are Cushing syndrome, hypertension, immune deficiency and growth retardation. As well as systemic steroid, intralesional steroid can also be used in the treatment. Intralesional steroid injection has benefits in terms of the decrease in side effects depending on the systemic steroid use. However, local steroid injections require multiple treatments [1]. Medium subglottic hemangiomas which do not extend outside the larynx can respond to intralesionary steroid treatment [8]. Although our patient got 2 mg/kg/day intravenous steroid beginning from her first day in hospital, she did not benefit from this treatment.
Fig. 1 – Subglottic Hemangioma.
416
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 41 4–4 1 6
In one sided small lesions which are localized in submucosa, ablation with CO2 laser can be used. Recently, potassium titanyl phosphate laser has begun to be used. However, in both situations laryngeal stenosis is an important complication [9,10]. Open surgery resection treatment for subglottic hemagiomas was defined by Sharp in 1949 for the first time [11]. Today, this method is recommended for lesions that threaten the airway, for wide lesions that obstruct the proliferative phase, for bilateral hemangioma and for lesions that cause extralaryngeal widening [1]. Recently, propranolol treatment had been preferred for the treatment of hemangioma. Le´aute´-Labre`ze et al. treated 11 cutaneous hemangiomas with propranolol and found out that propranolol caused visible changes beginning from the first day [12]. Recommended dosages of propranolol are well tolerated; however, there may arise side effects such as bradycardia, hypotension, bronchospasm, hypoglycemia and a decrease in lethargy diet. It has recently been reported that care must be taken in terms of hypoglycemia and life-threatening hyperkalemia. Further controlled studies are needed for the safety, efficiency and treatment protocol of Propranolol [13]. In our study, the patient’s stridor improved in two days after oral propranolol was started and the patient was discharged on the tenth day of the treatment. Bronchoscopy that was taken two months later after the beginning of the treatment showed 50% degrowth in hemangioma. As a result, in patients who have wheezing and stridor the reason for which cannot be explained and which do not respond to standard treatment, congenital anomalies should be considered as a prediagnosis. In big hemangiomas that can completely fill in the airway, inspiratory wheezing can be heard along with stridor.
REFERENCES
[1] Ahmad SM, Soliman AM. Congenital anomalies of the larynx. Otolaryngol Clin North Am 2007;40:177–91. [2] Sie KCY, McGill TJ, Healy GB. Subglottic hemangioma: 10 year’s experience with the carbon dioxide laser. Ann Otol Rhinol Laryngol 1994;103:167–72. [3] Jephson CG, Manunza F, Syed S, et al. Successful treatment of isolated subglottic haemangioma with propranolol alone. Int J Pediatr Otorhinolaryngol 2009;73:1821–3. [4] Naiman AN, Ayari S, Froehlich P. Controlled risk of stenosis after surgical excision of laryngeal hemangioma. Arch Otolarygol Head Neck Surg 2003;129:1291–5. [5] Chatrath P, Black M, Jani P, et al. A review of the current management of infantile subglottic haemangioma, including a comparison of CO2 laser therapy versus tracheostomy. Int J Pediatr Otorhinolaryngol 2002;64:143–57. [6] Leung AK, Cho H. Diagnosis of stridor in children. Am Fam Physician 1999;60:2289–96. [7] Ohlms LA, Jones DT, McGill TJ, et al. Interferon a-2A therapy for airway hemangiomas. Ann Otol Rhinol Laryngol 1994;103:1–8. [8] Kilham H, Gillis J, Benjamin B. Severe upper airway obstruction. Pediatr Clin North Am 1987;34:1–14. [9] Goodman TR, McHugh K. The role of radiology in the evaluation of stridor. Arch Dis Child 1999;81:456–9. [10] Altman KW, Wetmore RF, Mash RR. Congenital airway abnormalities in patient requiring hospitalization. Arch Otolaryngol Head Neck Surg 1999;125:525–8. [11] Sharp HS. Hemangioma of the trachea in an infant, successful removal. J Laryngol Otol 1949;63:413–4. [12] Le´aute´ -Labre` ze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649–51. [13] Raol N, Metry D, Edmonds J, et al. Propranolol for the treatment of subglottic hemangiomas. Int J Pediatr Otorhinolaryngol 2011;75:1510–4.
