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ORIGINAL ARTICLE
Year : 2020  |  Volume : 21  |  Issue : 2  |  Page : 116-118

A study on the treatment of infantile hemangiomas with topical timolol


Consultant Dermatologist, Department of Dermatology, Punjab Health Systems Corporation, Mohali, Punjab, India

Date of Submission01-Jan-2020
Date of Decision20-Jan-2020
Date of Acceptance10-Feb-2020
Date of Web Publication01-Apr-2020

Correspondence Address:
Neerja Puri
House No. 626, Phase II, Urban Estate, Dugri Road, Ludhiana, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_2_20

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  Abstract 


Introduction: With the advent of topical timolol, there has been a tremendous change in the management of infantile hemangiomas. Aims: The aim of the study was to evaluate the treatment response with topical 0.5% timolol drops in 20 children of infantile hemangiomas. Methods: The response to treatment was seen as regression of growth or flattening of lesion or lightening of the surface. Timolol drops 0.5% were applied over the hemangiomas and three drops were applied twice daily. Results: Head-and-neck involvement was seen in 40% of the infants, the trunk was involved in 30% of the infants, the limbs were involved in 25% of the infants, and the genitalia were involved in 5% of the infants. Response to treatment with timolol was excellent in 60% of the infants, very good in 20% of the infants, good in 15% of the infants, average in 5% of the infants, and none of the infants showed poor response. Regarding the side effects of topical timolol, sleep disturbances and poor feeding were seen in 5% of the infants. Discussion: Timolol is used for hemangiomas that do not involute spontaneously or for infected or ulcerated hemangiomas or those hemangiomas in which there is a risk of scarring, disfigurement, or impairment of vital structures.

Keywords: Hemangiomas, impairment, regression, timlol, vascular malformation


How to cite this article:
Puri N. A study on the treatment of infantile hemangiomas with topical timolol. Indian J Paediatr Dermatol 2020;21:116-8

How to cite this URL:
Puri N. A study on the treatment of infantile hemangiomas with topical timolol. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Dec 4];21:116-8. Available from: https://www.ijpd.in/text.asp?2020/21/2/116/281733




  Introduction Top


Hemangiomas are infantile tumors also known as strawberry angiomas which usually appear in the first 4–6 weeks of life.[1] They have three phases – rapidly proliferating phase, stabilization phase, and involuting phase. It is important to keep in mind that all hemangiomas do not require active intervention. Treatment is required in the following hemangiomas:

  • Hemangiomas with ulceration or secondary infection
  • Hemangiomas over vital structures such as the ears, lips, nose, or eyes
  • Hemangiomas which are interfering with vision, feeding, hearing, or breathing.


However, it is important to note that different hemangiomas vary in terms of size and the rate of proliferation and involution, and the treatment schedules cannot be generalized in all infants and have to be individualized. Beta-blockers are efficacious in the treatment of hemangiomas. Topical timolol 0.5% is available in India as eye drops, though gel formulation is not freely available everywhere.[2]

Aims

The aim of the study was to evaluate the treatment response with topical 0.5% timolol drops in twenty children of infantile hemangiomas.


  Methods Top


The response to treatment was seen as regression of growth or flattening of lesion or lightening of the surface. Timolol drops 0.5% were applied over the hemangiomas and three drops were applied twice daily. Vaseline was applied around the hemangiomas to prevent the trickling of drops over the normal skin. Heart rate, respiratory rate, and blood glucose levels were monitored daily for the first 5 days. The patients were followed up every 2 weeks up to 4 months. Clinical photographs of the patients were taken at each visit. The decrease in erythema and volume of hemangioma was noted at 6 weeks, 12 weeks, and 16 weeks. The photographs were taken to see the size of hemangiomas and color intensity. At each visit, the physician global assessment scale was used to see the regression of hemangiomas, which is as follows:

  • Excellent response – >90% regression of hemangiomas
  • Very good response – Between 75% and 90% regression of hemangiomas
  • Good response – Between 50% and 74% regression of hemangiomas
  • Average response – Between 25% and 49% regression of hemangiomas
  • Poor response – <25% decrease in size of hemangiomas.


All the patients were asked to note the regression in hemangiomas using subjective assessment score. Doppler ultrasound of hemangiomas was done in all the patients who were affording before the start of the treatment to differentiate between hemangiomas and vascular malformations. Institutional ethics committee approval was obtained prior to initiation of the study.

Inclusion criteria

The following patients were included in our study:

  • Hemangiomas which bleed or ulcerate
  • Hemangiomas showing any signs of secondary infection
  • Hemangiomas over important anatomical areas including the face, eyelids, and ears.


Exclusion criteria

Uncooperative patients or patients who were unwilling for the study were excluded from the study.


  Results Top


The data were collected and tabulated, and the results were analyzed statistically.


  Discussion Top


Head-and-neck involvement was seen in 40% of the infants, the trunk was involved in 30% of the infants, the limbs were involved in 25% of the infants, and the genitalia were involved in 5% of the infants [Table 1]. The response to the treatment with timolol was excellent in 60% of the infants [Figure 1]a and [Figure 1]b, very good in 20% of the infants [Figure 2]a and [Figure 2]b, good in 15% of the infants [Figure 3]a and [Figure 3]b, average in 5% of the infants, and none of the infants showed poor response [Table 2]. Regarding the side effects of topical timolol, sleep disturbances and poor feeding were seen in 5% of the infants [Table 3].
Table 1: Site of hemangiomas

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Figure 1: (a and b) Hemangioma before and after treatment showing excellent response with timolol

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Figure 2: (a and b) Hemangima on scalp showing very good response with timolol

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Figure 3: (a and b) Hemangima showing good response with timolol

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Table 2: Response to treatment with timolol

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Table 3: Side effects of timolol

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Hemangiomas are the most common tumors of infancy. Normally, by the age of 10 years, most of the hemangiomas regress. Of all the hemangiomas, 50% occur on the head and neck. Out of these, only complicated hemangiomas require treatment. However, in some cases, in spite of continuous reassurance, a clinician is pressed by the parents of the infants to treat some uncomplicated hemangiomas also since it can be emotionally disturbing to the patients. In such cases, a clinician has to weigh the situation and parents of infants have to be given proper counseling across the table after discussing all the treatment options along with the pros and cons.

About 8 years back, oral propranolol was found to be effective for the treatment of infantile hemangiomas.[3] This opened the doors for topical timolol being investigated for use in infantile hemangiomas. Timolol is a beta-blocker, which is licensed to be used in ophthalmology to reduce intraocular pressure.[4] In fact, the use of timolol in hemangiomas is an off-label indication. Timolol is well tolerated, and most of the studies using timolol are done for superficial infantile hemangiomas. Topical timolol decreases the erythema component of infantile hemangiomas along with a reduction in their size. Topical timolol solution has many advantages – it is freely available, easy to administer, and cost-effective with minimal side effects. Regarding the dosing of timolol, there are various schools of thought – 1–3 drops can be given two times a day up to maximum of five times a day.[5]

If timolol is absorbed systemically, it can cause cardiovascular and pulmonary side effects as seen with other oral beta-blockers. There are various adverse effects of topical timolol such as hypoglycemia, bradycardia, weakness, and sleep disturbances.[6]

In a study by Yu et al., 125 patients of infantile hemangiomas were taken up.[7] Of these, 101 infants received topical 0.5% drops applied three times a day. The other 23 infants were controls. A photographic evaluation was done to see the changes in color, size, and texture. At 4 months, regression of hemangiomas was seen in 57 (56%) patients, whereas in the control group, regression was seen in 4% of the patients.

In a study by Chan et al., no local or systemic adverse effects such as bradycardia or hypotension was noted with timolol.[8] In another retrospective study by Chakkitakandiyil, sleep disturbance was noted in one infant.[9]

The mechanism of action of timolol is by vasoconstriction and inhibition of growth factor responsible for proliferative phase. Systemic beta-blockers such as propranolol also cause vasoconstriction, but it can cause some serious complications such as bradycardia, hypoglycemia, respiratory distress, and chynestokes breathing.[10] Hence, with the use of systemic drugs, thorough monitoring is required. Topical timolol is safe as it has minimal systemic absorption. However, still, caution needs to be exercised while treating large-sized hemangiomas in asthmatic infants or infants with other associated cardiorespiratory morbidities.[11],[12] It is important that infants on timolol should be given frequent feeds to prevent any risk of hypoglycemia resulting from the systemic absorption of timolol.


  Conclusions Top


As such, all the studies on timolol conducted so far are not standardized and use different scoring systems to evaluate the response, and moreover, most of the studies are conducted with small sample sizes. One should not forget that the use of timolol to treat infantile hemangiomas is still an off-label use, the efficacy and safety of which is still under trials. Although timolol is effective in reducing the size of infantile hemangiomas and facilitates its early regression, long-term studies need to be conducted to evaluate its safety in infants, especially the risk of systemic absorption.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Re Miller T, Frieden IJ. Vascular tumours. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw Hill; 2008.  Back to cited text no. 1
    
2.
Khunger N, Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol 2011;164:886-8.  Back to cited text no. 2
    
3.
Ovadia SA, Landy DC, Cohen ER, Yang EY, Thaller SR. Local administration of β-blockers for infantile hemangiomas: A systematic review and meta-analysis. Ann Plast Surg 2015;74:256-62.  Back to cited text no. 3
    
4.
Ni N, Langer P, Wagner R, Guo S. Topical timolol for periocular hemangioma: Report of further study. Arch Ophthalmol 2011;129:377-9.  Back to cited text no. 4
    
5.
Park KH, Jang YH, Chung HY, Lee WJ, Kim DW, Lee SJ. Topical timolol maleate 0.5% for infantile hemangioma; it's effectiveness and/or adjunctive pulsed dye laser – Single center experience of 102 cases in Korea. J Dermatolog Treat 2015;26:389-91.  Back to cited text no. 5
    
6.
Weibel L, Scheer HS, Barysch M. Topical beta-blockers for infantile hemangiomas are effective but systemically absorbed. Eur J Pediatr Dermatol 2012;22:10-11.  Back to cited text no. 6
    
7.
Yu L, Li S, Su B, Liu Z, Fang J, Zhu L, et al. Treatment of superficial infantile hemangiomas with timolol: Evaluation of short-term efficacy and safety in infants. Exp Ther Med 2013;6:388-90.  Back to cited text no. 7
    
8.
Chan H, McKay C, Adams S, Wargon O. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Pediatrics 2013;131:e1739-47.  Back to cited text no. 8
    
9.
Chakkittakandiyil A, Phillips R, Frieden IJ, Siegfried E, Lara-Corrales I, Lam J, et al. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: A retrospective, multicenter, cohort study. Pediatr Dermatol 2012;29:28-31.  Back to cited text no. 9
    
10.
Kumar MG, Coughlin C, Bayliss SJ. Outpatient use of oral propranolol and topical timolol for infantile hemangiomas: Survey results and comparison with propranolol consensus statement guidelines. Pediatr Dermatol 2015;32:171-9.  Back to cited text no. 10
    
11.
McMahon P, Oza V, Frieden IJ. Topical timolol for infantile hemangiomas: Putting a note of caution in “cautiously optimistic”. Pediatr Dermatol 2012;29:127-30.  Back to cited text no. 11
    
12.
Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: A pilot study. Arch Dermatol 2010;146:564-5.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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