Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 4  |  Page : 291-295

Effect of propranolol in cutaneous and intracavitary hemangiomas


1 Department of General Surgery, JNMC Hospital, Aligarh, Uttar Pradesh, India
2 Department of CTVS, JNMC Hospital, Aligarh, Uttar Pradesh, India
3 Department of Medicine, JNMC Hospital, Aligarh, Uttar Pradesh, India

Date of Submission08-Jun-2022
Date of Decision03-Sep-2022
Date of Acceptance05-Sep-2022
Date of Web Publication8-Nov-2022

Correspondence Address:
Sartaj Ahmad Guroo
Department of CTVS, JNMC Hospital, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_35_22

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  Abstract 


Objectives: The objective was to study the role of propranolol in decreasing the size and severity of hemangioma. Materials and Methods: This study was conducted in JNMC, AMU, Aligarh, India, on 100 patients who were divided according to their age group among infants (0–1 year), children (1–14 years), and adults (>14 years). Intracavitary hemangioma was diagnosed with ultrasonography/magnetic resonance imaging scan. Treatment with oral propranolol was started after ruling out any contraindication to therapy. The patients were assessed according to the Hemangioma Activity and Severity Index (HASI) at the start and at the end of treatment. The treatment outcome and side effects were recorded. Results: Among the total patients studied, there were more number of adult patients in this study, most of them were male. There were more number of patients of extracutaneous hemangioma, most of which were intra-abdominal. The difference of location of hemangioma and age group was observed, with intra-abdominal hemangiomas being more common in adult patients and cutaneous hemangioma being more common in infant and pediatric age group. The propranolol therapy was effective in all age groups, with mean HASI being reduced significantly between start and end of treatment at 16 weeks (P = 0.001). There was regression in a good number of patients with partial regression in 55% of patients and complete regression in 32.5% of patients. Minor side effects of hypoglycemia, palpitation, and episodic bradycardia were observed in very few patients. Conclusions: Propranolol is effective in reducing the size and severity of hemangiomas among all age group of patients without causing any severe side effect.

Keywords: Aligarh Muslim University, Jawaharlal Nehru Medical College, ultrasonography


How to cite this article:
Akhtar MS, Goel A, Guroo SA, Rabbani SS, Alim SS, Haseen MA, Abbasi A. Effect of propranolol in cutaneous and intracavitary hemangiomas. Indian J Vasc Endovasc Surg 2022;9:291-5

How to cite this URL:
Akhtar MS, Goel A, Guroo SA, Rabbani SS, Alim SS, Haseen MA, Abbasi A. Effect of propranolol in cutaneous and intracavitary hemangiomas. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 Dec 5];9:291-5. Available from: https://www.indjvascsurg.org/text.asp?2022/9/4/291/360542




  Introduction Top


Hemangioma is a type of congenital dysplasia of blood vessels mostly seen in infants and females with scalp, face, chest, and back as the most commonly involved sites.[1] The development of hemangioma in certain parts of the body may affect the appearance of the patient, have an impact on the normal function of body, and may rarely need emergent treatment in disastrous conditions.[2]

Among intra-abdominal hemangiomas, liver is the most common site and mostly presents in adulthood. Although most hemangiomas involute, some can be problematic due to their size and location.[3] Diagnosed by ultrasonography (USG), where they appear hyperechoic homogeneous nodule, with well-defined margins and posterior acoustic enhancement,[4] they range from asymptomatic self-limiting lesions to lesions causing congestive heart failure, fulminant hepatic failure, hypothyroidism, abdominal compartment syndrome, and even death.[5]

The mainstay of treatment for hemangiomas is corticosteroids with the most common route of administration being local injection.[6] Surgery can be done on small tumors.[7] Other treatment modalities include laser surgery, cryosurgery, systemic corticosteroids, vincristine, and cyclophosphamide, but all carry risk of serious side effects.[8]

Propranolol is a nonselective β blocker, which has been used in the treatment of cutaneous hemangioma with immediate change in the hemangioma from intense red to purple, with palpable softening of the lesion,[9] but less studied in intracavitary hemangioma.


  Materials and Methods Top


This is a prospective nonrandomized observational study conducted at the Department of Cardiothoracic Surgery, Jawaharlal Nehru Medical College, AMU, Aligarh. The Hemangioma Activity and Severity Index (HASI) developed by Semkova et al.[10] was used for scoring the severity of the hemangioma before and after the treatment [Table 1]. There were total of 100 patients who were included in this study and were allocated in three population groups, infants (0–1 year), children (1–14 years), and adults (>14 years), some having superficial and others having deep intracavitary hemangiomas.
Table 1: Hemangioma Activity and Severity Index score

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All participants had baseline electrocardiogram, heart rate, blood pressure, and blood sugar recorded. Prothrombin time (PT) and international normalized ratio (INR) were done to rule out any bleeding disorder. Patients with pregnancy, having cardiac pathology, asthma or diabetes mellitus, arteriovenous malformations and abnormal kidney function test, deranged blood sugar, serum electrolytes, and PT/INR were excluded from the study. Clinical and radiological (USG and/or magnetic resonance angiography) confirmation of extracutaneous hemangioma was made at initiation of therapy and at 8 and 16 weeks to assess improvement.

Oral propranolol was started with a dose of 0.5 mg/kg/day in two divided doses, and dose was gradually increased after every 2 weeks to maximum dose of 2 mg/kg/day. The efficacy of the medication was compared by assessing the decrease in the size, which was taken as no improvement as score 0, <50% involution as score 1, and >50% as score 2. Termination of medication was done when more than 75% response to treatment was achieved or the patient had completed 16 weeks of treatment or in case of any severe side effect to therapy was noted.


  Results Top


In this study, a total of 100 patients were included, of which 55 (55%) were adults (>14 year), 20 (20%) were infants (0–1 year), and 25 (25%) were pediatric (1–14 year). The male outnumbered females with a ratio of 1.35:1. The most common presenting age group was adults, with the mean age of 33.5 years. Most patients in adult age group had extracutaneous hemangioma, mostly present within the abdominal cavity (76.36% of adult patients). In the infantile age group, all hemangiomas were of cutaneous type (60% truncal and 40% on head and neck), whereas in pediatric age group, 72% were of cutaneous type and 28% were of extracutaneous type [Figure 1]. The difference in this distribution was statistically significant (P = 0.001).
Figure 1: Distribution of patients according to age and site of hemangioma

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The mean HASI score at the start of treatment was 4.23 ± 1.66 in adults, 7.38 ± 3.58 in infants, and 6 ± 1.74 in pediatric population. The mean HASI score at the start of treatment overall was 5.30 ± 2.48. The mean HASI score at the end of treatment was 1.9 ± 2.02 in adults, 3.75 ± 2.12 in infants, and 3.4 ± 2.75 in pediatric population. The mean HASI score at the end of treatment overall was 2.65 ± 2.34 [Figure 2]. The difference in mean values was significant with P = 0.001. Thirty-three (33%) patients showed complete regression, 55 (55%) patients showed partial regression, and 12 (12%) patients showed no effect to treatment [Table 2]. The difference in effect of treatment was statistically significant (P = 0.05). Eighty-eight percentage of patients had satisfactory response to treatment, while 12% had poor response to treatment.
Figure 2: Comparison between the mean HASI at start and at 16 weeks of treatment. HASI: Hemangioma Activity and Severity Index

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Table 2: Correlation of propranolol treatment among various age groups

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Side effects such as hypoglycemia, episodic bradycardia, and episodic palpitations were seen in total 20 (20%) out of 100 patients. Hypoglycemia was mainly seen among pediatric patients, and palpitations and bradycardia were seen in adult patients. The frequency of side effects was statistically significant (P = 0.02).


  Discussion Top


Hemangioma is the most frequent childhood tumor. Although it is benign and self-limiting, severe complications can arise due to its fast growth. Several factors have been proposed in the pathogenesis of hemangioma, although local hypoxia seems to be the most important factor. Three main hypotheses have been proposed, namely: (i) the theory of tissue hypoxia, (ii) the theory of embolization of placental endothelial cells, and (iii) the theory of increased angiogenic and vasculogenic activity.[11] Hemangiomas can occur in any part of the body, but in most of the cases are cutaneous, in head and neck region; it can be also present in the skeletal muscle and in deep body cavities, especially intra-abdominal.[12]

Treatment option for hemangiomas includes corticosteroids,[13] interferon alfa,[14] topical nonselective beta-blocker,[15] and surgery for intracavitary hemangiomas.[16] In 2008, Leaute-Labreze et al.[9] did a pioneering work on propranolol therapy in infantile hemangiomas, where treatment was initiated during a short hospitalization of 24 h or during a day hospital session. The drug was then given at a starting dose of 2 mg/kg/day, in 23 divided doses. This prospective parallel clinical trial was done by Siddharth Panditray et al[17], to check for the effectiveness of oral propranolol and oral itraconazole when used in conjugation with inj. sodium tetra decyl sulphate in treatment of head and neck haemangiomas in adult patients. Oral propranolol and itraconazole are both effective and safe in hemangioma in adults. Propranolol has an edge over itraconazole (more no of tumors had complete resolution).

With regard to location of hemangiomas, our study was similar to Wirth and Lowitt[12] who also mentioned about two types of hemangiomas, the superficial strawberry or capillary type (65%), and the deeper, cavernous type (15%). In our study, 44 (44%) of total patients had intra-abdominal hemangiomas, observed mainly in the adult age group 42 (76.36%); majority of which were present in liver and the patient presented either due to vague upper abdominal pain or the finding was incidental. Similar findings were reported in a study conducted by Alimoradi et al.[18] who also stated that in adults, liver hemangiomas are common. In the infantile age group, eight (40%) patients had head and neck lesions and 12 (60%) had truncal lesions in our study. Similarly, Pandey et al.[19] in their study on infantile hemangiomas stated that the most common site of involvement was the head and neck region (57%), and Gawrych et al.[20] also observed that the location of hemangioma was on the head and neck in 22 children (58%) in their study and on the trunk and upper and lower limbs in the remaining children.

On evaluating the effect of propranolol on hemangioma, the mean HASI score in adult age group was reduced from 4.23 at the start to 1.91 at the end, in pediatric age group from 6.00 at the start to 3.40 at the end, and in infantile age group from 7.38 at the start to 3.75 at the end. The mean HASI score overall was reduced from 5.30 at start to 2.65 at the end of treatment, the difference being statistically significant.

It was found that 48 out of 55 (87.18%) adult patients showed a good response to propranolol treatment. Holmes et al.[21] conducted a study on 31 patients with rapidly proliferating infantile hemangiomas with functional impairment or cosmetic disfigurement, in which they were treated with propranolol as a first-line treatment. A rapid halt in hemangioma proliferation was seen in 100% of patients with a significant reduction in 87% of the patients, similar to our study. In our study, we had 42 (76.34%) patients of intra-abdominal hemangiomas in adult age group, out of which 40 (95.2%) responded well to propranolol therapy with complete regression in most of them and partial regression in some. The results were statistically significant (P = 0.05).

We did not observe any life-threatening side effect which warranted discontinuing the therapy. Twenty out of 100 patients suffered from side effects. The most common side effect observed was hypoglycemia seen in 15 patients. Three patients had episodic bradycardia and 2 had episodic palpitation. These were similar to the observations made by Lawley et al.,[22] which reported two cases of side effects in patients receiving propranolol in the recommended dosage of 2 mg/kg/day. One of them experienced severe hypotension, and the other, severe hypoglycemia.


  Conclusions Top


We conclude that propranolol at a dose of 2 mg/kg/day in two divided doses reduced the size and severity of hemangioma in all the age groups. It resulted in partial/complete regression of most of the lesions and with a good patient/parent satisfaction. We recommend that propranolol can be used as a first-line drug in the treatment of hemangiomas without causing any serious side effect.

Acknowledgment

I feel extremely honored to have this opportunity to acknowledge those who provided immense support throughout the period of this study. I take this opportunity to thank my junior residents who help me a lot to accomplish this study. I am extremely thankful to Dr. Saif, Senior resident, Department of CTVS, for his support during this study. I gratefully acknowledge Dr. Syed Shimayil Rbbani, Dr. Mayank Yadav, Assistant Professor, Department of CTVS, JNMC, AMU, Aligarh, for their constant guidance and support.

I am thankful to Dr. Sadik Akhtar and Dr. Rizwan Ahmad Khan of general surgery department for their immense support and guidance throughout this study. I am obliged to Prof. Mohd Azam Haseen, Department of Cardiothoracic Surgery, JNMC, AMU, for his constant inspiration, timely suggestions, and never-ending support in fulfilling the needs of this study. His profound wisdom and unbeatable knowledge deserve the highest degree of appreciation. His encouraging guidance and care have made each step easy for me toward the completion of this work.

I extend my acknowledgments to my patients for being a part of the study and giving me the opportunity to work with them and learn from them in spite of all their pain and sufferings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cordisco MR. Hemangiomas of infancy: Epidemiology. In: Mattassi R, Loose DA, Vaghi M, editors. Hemangiomas and Vascular Malformations: An Atlas of Diagnosis and Treatment. Milano: Springer Milan; 2009. p. 17-21. Available from: https://doi.org/10.1007/978-88-470-0569-3_3. [Last accessed on 2021 Dec 12].  Back to cited text no. 1
    
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Greenberger S, Bischoff J. Pathogenesis of infantile haemangioma. Br J Dermatol 2013;169:12-9.  Back to cited text no. 2
    
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Oak CY, Jun CH, Cho EA, Lee DH, Cho SB, Park CH, et al. Hepatic hemangioma with Kasabach-Merritt syndrome in an adult patient. Korean J Gastroenterol 2016;67:220-3.  Back to cited text no. 3
    
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Christison-Lagay ER, Burrows PE, Alomari A, Dubois J, Kozakewich HP, Lane TS, et al. Hepatic hemangiomas: Subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg 2007;42:62-7.  Back to cited text no. 5
    
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Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: Insights into the molecular mechanisms of action. Br J Dermatol 2010;163:269-74.  Back to cited text no. 8
    
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Semkova K, Kazandjieva J, Kadurina M, Tsankov N. Hemangioma Activity and Severity Index (HASI), an instrument for evaluating infantile hemangioma: Development and preliminary validation. Int J Dermatol 2015;54:494-8.  Back to cited text no. 10
    
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Janmohamed SR, de Waard-van der Spek FB, Madern GC, de Laat PC, Hop WC, Oranje AP. Scoring the proliferative activity of haemangioma of infancy: The Haemangioma Activity Score (HAS). Clin Exp Dermatol 2011;36:715-23.  Back to cited text no. 11
    
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Wirth FA, Lowitt MH. Diagnosis and treatment of cutaneous vascular lesions. Am Fam Physician 1998;57:765-73.  Back to cited text no. 12
    
13.
Oral Corticosteroid Use Is Effective for Cutaneous Hemangiomas: An Evidence-Based Evaluation | Clinical Pharmacy and Pharmacology | JAMA Dermatology | JAMA Network. Available from: https://jamanetwork.com/journals/jamadermatology/article-abstract/478474. [Last accessed on 2022 Mar 28].  Back to cited text no. 13
    
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Therapeutic Efficacy of Interferon Alfa-2b in Infants With Life-Threatening Giant Hemangiomas | JAMA Dermatology | JAMA Network. Available from: https://jamanetwork.com/journals/jamadermatology/article-abstract/559561. [Last accessed on 2022 Jan 30].  Back to cited text no. 14
    
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Panditray S, Acharya S, Prusty N, Dany SS. Management of head and neck hemangiomas in adults: Oral propranolol versus oral itraconazole in conjugation with Injection Sodium Tetra Decyl Sulphate Indian J Otolaryngol Head Neck Surg 2019;71:566-73. doi: 10.1007/s12070-018-1410-8.  Back to cited text no. 17
    
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Alimoradi M, Sabra H, El-Helou E, Chahal A, Wakim R. Massive liver haemangioma causing Kasabach-Merritt syndrome in an adult. Ann R Coll Surg Engl 2020;102:e1-4.  Back to cited text no. 18
    
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Pandey A, Gangopadhyay AN, Gopal SC, Kumar V, Sharma SP, Gupta DK, et al. Twenty years' experience of steroids in infantile hemangioma – A developing country's perspective. J Pediatr Surg 2009;44:688-94.  Back to cited text no. 19
    
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21.
Holmes WJ, Mishra A, Gorst C, Liew SH. Propranolol as first-line treatment for infantile hemangiomas. Plast Reconstr Surg 2010;125:420-1.  Back to cited text no. 21
    
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Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: Risks and recommendations. Pediatr Dermatol 2009;26:610-4.  Back to cited text no. 22
    


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