Propranolol Treatment of Complicated Hemangiomas - Springer Link

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Jul 6, 2013 - Propranolol Treatment of Complicated Hemangiomas. Derya Özyörük & Emine Zengin. Received: 31 July 2012 /Accepted: 5 June 2013 ...

Indian J Pediatr (April 2014) 81(4):368–370 DOI 10.1007/s12098-013-1125-5

ORIGINAL ARTICLE

Propranolol Treatment of Complicated Hemangiomas Derya Özyörük & Emine Zengin

Received: 31 July 2012 / Accepted: 5 June 2013 / Published online: 6 July 2013 # Dr. K C Chaudhuri Foundation 2013

Abstract Objectives To evaluate laboratory and radiological features of hemangiomas in childhood in addition to efficacy and safety of propranolol as a first-line treatment of complicated hemangiomas retrospectively. Methods The files of 60 patients who were diagnosed as capillary hemangioma were evaluated retrospectively. Fourteen children with complicated hemangiomas treated with propranolol were analysed, in terms of side effects, efficacy and duration of treatment. Results These fourteen patients (23 %) were treated with propranolol because of ulcerated, infected and/or deep seated localisations. The duration of treatment with propranolol were between 3 and 12 mo (median: 6 mo). Bronchospasm was observed in one patient during treatment. Except for two patients, all of them responded to propranolol treatment with limited side effects. Conclusions The present results support that propranolol is safe and effective treatment choice for complicated infantile hemangiomas, because of minimal side effects and encouraging response rates (80 %). In addition, the authors suggest that routine cranial radiological imagings might not be necessary for hemangiomas without any neurological symptoms. Keywords Propranolol . Corticosteroids . Hemangioma

hemangiomas remains unclear. Vasoconstriction, downregulation of angiogenic factors and up-regulation of apoptosis of capillary endothelial cells may be responsible for the reduction of hemangiomas [2]. In addition to propranolol, systemic or intralesional corticosteroids, chemotherapeutic agents such as α interferon and vincristine, laser therapy, surgical resection or a combination of these treatments had been reported as treatment modalities in clinical practice [3]. This study was conducted to retrospectively evaluate the laboratory and radiological features of hemangiomas in childhood, in addition to efficacy and safety of propranolol as a first-line treatment of complicated hemangiomas like ulcerated, infected and/or deep seated localisation. Informed consent was taken from each family.

Material and Methods The files of 60 patients who were diagnosed as capillary hemangioma were evaluated retrospectively (36 girls, 24 boys). The initial laboratory paramaters, radiological imagings were evaluated. Also, fourteen children with complicated hemangiomas treated with propranolol (9 girls; 5 boys) in this group were analysed in terms of side effects, efficacy and duration of treatment. Descriptive statistics was conducted by SPSS 15.0 version statistical programme for windows.

Introduction Results After being discovered in 2008 [1], propranolol has been used as a first-line treatment choice for hemangiomas. The exact mechanism of action of propranolol in the treatment of D. Özyörük : E. Zengin Department of Pediatric Hematology and Oncology, The Ministry of Health, Şanlıurfa Children’s Hospital, Şanlıurfa 63000, Turkey D. Özyörük (*) Mebusevlerimahallesi, İllersokak, 31/4, Çankaya, Ankara, Turkey e-mail: [email protected]

Fourteen children (23 %) required treatment with propranolol because of ulcerated, infected and/or deep seated localisation. Before treatment with propranolol, two hemangiomas had been treated with high-dose methylprednisolone. The median age of the patients treated with propranolol was 4 mo (ranged 1–16 mo). Nine (64 %) were girls and five (36 %) were boys. Their initial laboratory, radiological, electrocardiographic and echocardiographic evaluations were normal. Propranolol was started 2 mg/kg per day in 2 divided doses. The dose were not

Indian J Pediatr (April 2014) 81(4):368–370 Table 1 Clinical features and treatment results of patients with complicated hemangiomas who were administered propranalol

F Female; M Male; NA Not available a

The patients who were administered high-dose methylprednisolone before propranalol treatment

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Gender

Age (mo)

Location of hemangioma

Dose (mg/kg/d)

Duration of treatment (mo)

Reduction in size (80 %)

Side effect

F F F F F F M F M F

4 1 2 6 4 3 6 4 9 8

Neck Inguinal Nose, lip, mouth Nose, lip, mouth, parotid Inguinal Face, parotid Parotid, leg Arm, shoulder, hand Buttock Neck

2 2 2 2 2 2 2 2 2 2

3 6 12 6 6 12 4 12 6 6

Regressed Regressed Relapsed Regressed Regressed Regressed Regressed Regressed Regressed Regresseda

NA NA Bronchospasm NA NA NA NA NA NA NA

F M M M

16 8 4 4

Between eyes, nose Parotid Suborbital, leg Leg

2 2 2 2

6 9 4 4

Regressed Refractarya Regressed Regressed

NA NA NA NA

increased or modified later. No side effects were observed during the first 48 h of treatment at hospital setting. Their propranolol treatment were continued at home. Patients were re-evaluated at 7th day and every 15th day of treatment. Treatment duration were between 3 and 12 mo (median: 6 mo). During the treatment, only one patient developed bronchospasm three times, that required discontinuation of treatment for 10 d in each episod. Propranolol was stopped at 9th mo of treatment after hemangioma regressed 80 % in size. After cessation of treatment, hemangioma increased in size, thus propranolol was re-started. Two complicated hemangiomas treated with high-dose methylprednisolone did not respond. After propranolol was started, the hemangioma located on neck involuted but the hemangioma located on parotid region in the other patient did not regress any more than a little discoloration and shrinkage (Table 1). Ten patients responded well with little discoloration sequele on the skin. When complicated hemangioma reduced 80 % in size, propranolol treatments were cessated. Three of them are still on propranolol treatment with good response. The discoloration and shrinkage of one of the patients’ hemangioma at 15th day and 3rd month of treatment are shown in Fig. 1. Fig. 1 Hemangioma in the patient a: before propranalol treatment, b: 15 d of propranalol treatment c: 3rd mo of propranalol treatment

Discussion Infantile hemangiomas are common vascular tumors that grow during the first 3 to 12 mo of age. They involute spontaneously between 3 to 7 y of age [4]. In contrary with that, one of the patients who was seven years old still had hemangioma (7×7 cm in diameter) located on the temporoparietal region of occiput. It has been reported that aproximately 10 % of hemangiomas can cause serious or life threatening complications requiring treatment [5]. Because of ulcerated, infected and/or deep seated localisation, 14 (23 %) of the total hemangiomas were treated with propranolol. The higher rate of complicated hemangiomas might be the result of poor hygienic and low socio economic status of families in that region. According to previous studies, relapse had been observed in patients after discontinuation of propranolol treatment especially before 12 mo of age [4, 6]. Also, relapse had been described in patients older than 12 to 14 mo after discontinuation of propranolol therapy [7]. In the present study, one of patients treated with propranolol relapsed after discontinuation of treatment before 12 mo of age; one patient’s hemangioma located on parotid region involuted less than 50 % in size. Others responded to propranolol treatment with discoloration sequele

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and/or shrinkage of the tumor volume. These results are similiar with previous studies [8]. The previous reports have suggested that propranolol is more effective than corticosteroids not only in stopping hemangioma growth, but also in decreasing the tumor volume [9]. In the index study, high-dose methylprednisolone were not found effective. Since β 2 adrenoreceptors are located in the lungs and propranolol is a nonselective β-blocker, it can cause bronchospasm by acting on the airways. There have been reports of bronchospasm in adults with no asthma history being treated with propranolol [10]. One of the index patient treated with propranolol presented wheezing for three times probably due to viral infection. It is thought that propranolol might be the cause to increase the sensitivity of the airway. The radiological imagings (cranial ultrasound and/or MRI) and laboratory analysis did not reveal any abnormalities. It is suggested that radiological investigations may not be necessary to evaluate all the cases routinely, if they do not have any neurological symptoms. In conclusion, although there were limited number of patients in the index study, the results support that propranolol may be a safe and effective treatment choice for complicated infantile hemangiomas, because of minimal side effects and encouraging response rates (80 %). Conflict of Interest None. Role of Funding Source None.

Indian J Pediatr (April 2014) 81(4):368–370

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