- Email: [email protected]
Response from the authors of ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group’
Journal of Plastic, Reconstructive & Aesthetic Surgery (2014) 67, 411e435
CORRESPONDENCE AND COMMUNICATIONS Response from the authors of ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group’ Dear Sir,
Conflict of interest/funding
With great interest we have read the comments of Ashvin Raju and Roba Khundkar. We are pleased that the authors acknowledge atenolol as a possible alternative to propranolol. In respect to age adjustment, we included age as a categorical variable (1e6 months, 6e12 months and >12 months) in our model, so linearity between age and efficacy was not assumed. We agree that propranolol was shown to be the more efficacious option with regard to the percentage of patients with clinical involution, but this was not statistically significant (p Z 0.09). When confronted with two patients on propranolol that developed side effects, we initiated atenolol treatment.1 We hypothesized that the use of a hydrophilic, selective beta-1-blocker could be effective and prevent side effects of propranolol.2 Good results made atenolol our primary drug of choice. Patients #4 and #9 were excluded for analysis because of previous unsuccessful propranolol treatment and patient #11 because of its non-cutaneous location of IH and inability to assess quantitative outcome. They all responded well to atenolol. Patient #1 with a periorbital IH revealed minor improvement on atenolol and partial surgical debulking was performed. Patient #2 showed minor improvement on atenolol and because of severe pain due to ulceration, surgical excision was performed. For both patients no propranolol therapy was commenced. Patient #3 did not respond to propranolol after two weeks of atenolol treatment. Subsequently an excision was performed. Ever since, no atenolol failures were seen.
DOI of original j.bjps.2013.10.025
A concurrent deficiency of epinephrine and cortisol as a direct result of both beta blockade by propranolol together with adrenal insufficiency as a result of prednisone use caused hypoglycaemia in one patient.3 Besides less administration of prednisone therapy in IH, probably beta1-selectivity of atenolol will also reduce the risk for hypoglycaemia. This study is a first indication for efficacy and safety of atenolol. We agree that more, well-designed studies are required to clearly delineate the possible differences between these beta blockers.
article:
http://dx.doi.org/10.1016/
None.
References 1. Raphae ¨l MF, de Graaf M, Breugem CC, Pasmans SG, Breur JM. Atenolol: a promising alternative to propranolol for the treatment of hemangiomas. J Am Acad Dermatol 2011 Aug;65(2):420e1. 2. Ro ¨ssler J, Haubold M, Gilsbach R, et al. b1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations. Pediatr Res 2013;73(4 Pt 1). 49e13. 3. Breur JM, de Graaf M, Breugem CC, Pasmans SG. Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. Pediatr Dermatol 2011 MareApr;28(2): 169e71.
M. de Graaf Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.F. Raphael Department of Pediatric Haematology and Oncology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands
412
Correspondence and communications
Reply to ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group.’
of infantile hemangiomas (IH).1 It is agreed that propranolol has a widely published range of side effects, more so when compared to that of atenolol especially in the treatment of hypertension. Propranolol has gained recent popularity in the treatment of IH due to its efficacy however the mechanism of action still remains unclear.1,2 Similarly the effect and mechanism of action of atenolol has not been widely studied in a pediatric population. Nevertheless we agree with the authors, that it could be a good alternative to propranolol if it has less side effects and similar efficacy. Early initiation of pharmacologic treatment such as propranolol within the proliferative phase of IH ensures the best outcomes regarding eventual involution, provided comorbid conditions have been appropriately managed beforehand.3 Given that 85% (23/27) of patients from the atenolol group were aged 1e6 months, it might be hard to compare success rates when only 50% of the propranolol group fell within the same age range. Although the authors refer to age adjustment, clarification is required as how this was done, as the age and efficacy are not related in a linear fashion. More crucially as the focus of the study was efficacy, propranolol was shown to be the more efficacious option due to 100% involution whereas atenolol failed to cause complete involution in 10%. Additionally, although the authors state the difference is not statistically significant, only the quantitative assessment was used for this. We would like to commend the authors on achieving their sample size, as it is the largest to date regarding the use of atenolol.1 It would be interesting to know the outcomes of the propranololeatenolol group of excluded patients, as well as that of the non-cutaneous lesions. We would also like to know whether all of the patients who did not respond to atenolol were then treated with propranolol. We do admit that propranolol has well-known side effects in the treatment of IH, but recent evidence allows for pediatric-tailored drug regimens resulting in a better safety profile.2e5 It is worth noting that one of the patients who suffered from hypoglycaemia following propranolol treatment did so as a result of steroid withdrawal, rather than propranolol itself. Presumably the patients in the atenolol group would not have this problem, as steroids would no longer be used as first line for IH. It is understandable that atenolol be used for its beta-1 specificity, but current evidence (including Graaf et al.’s study) shows that propranolol is still very efficacious.1,2 This study re-affirms the notion that atenolol can be used to treat IH, however data from this study alone is not sufficient to state that atenolol has similar efficacy to propranolol as concluded by the authors. Perhaps a larger sample size spanning similar age groups would allow for a fairer and more enlightening comparison.
Dear Sir,
Conflict of interest/funding
We read with great interest Graaf et al.’s comparative analysis between atenolol and propranolol in the treatment
None.
C.C. Breugem Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.J. Knol Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands C.A.F.M. Bruijnzeel-Koomen Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M. Kon Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands J.M.P.J. Breur Department of Pediatric Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands S.G.M.A. Pasmans Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands *Corresponding author. Tel.: þ31 88 7557388. E-mail address: [email protected] 14 October 2013 ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.027
a
Current affiliation: Pediatric Dermatology, Erasmus Medical Center Rotterdam, The Netherlands DOI of original article: http://dx.doi.org/10.1016/ j.bjps.2013.07.035
References 1. de Graaf M, Raphael MF, Breugem CC, et al. Treatment of infantile haemangiomas with atenolol: comparison with a
CORRESPONDENCE AND COMMUNICATIONS Response from the authors of ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group’ Dear Sir,
Conflict of interest/funding
With great interest we have read the comments of Ashvin Raju and Roba Khundkar. We are pleased that the authors acknowledge atenolol as a possible alternative to propranolol. In respect to age adjustment, we included age as a categorical variable (1e6 months, 6e12 months and >12 months) in our model, so linearity between age and efficacy was not assumed. We agree that propranolol was shown to be the more efficacious option with regard to the percentage of patients with clinical involution, but this was not statistically significant (p Z 0.09). When confronted with two patients on propranolol that developed side effects, we initiated atenolol treatment.1 We hypothesized that the use of a hydrophilic, selective beta-1-blocker could be effective and prevent side effects of propranolol.2 Good results made atenolol our primary drug of choice. Patients #4 and #9 were excluded for analysis because of previous unsuccessful propranolol treatment and patient #11 because of its non-cutaneous location of IH and inability to assess quantitative outcome. They all responded well to atenolol. Patient #1 with a periorbital IH revealed minor improvement on atenolol and partial surgical debulking was performed. Patient #2 showed minor improvement on atenolol and because of severe pain due to ulceration, surgical excision was performed. For both patients no propranolol therapy was commenced. Patient #3 did not respond to propranolol after two weeks of atenolol treatment. Subsequently an excision was performed. Ever since, no atenolol failures were seen.
DOI of original j.bjps.2013.10.025
A concurrent deficiency of epinephrine and cortisol as a direct result of both beta blockade by propranolol together with adrenal insufficiency as a result of prednisone use caused hypoglycaemia in one patient.3 Besides less administration of prednisone therapy in IH, probably beta1-selectivity of atenolol will also reduce the risk for hypoglycaemia. This study is a first indication for efficacy and safety of atenolol. We agree that more, well-designed studies are required to clearly delineate the possible differences between these beta blockers.
article:
http://dx.doi.org/10.1016/
None.
References 1. Raphae ¨l MF, de Graaf M, Breugem CC, Pasmans SG, Breur JM. Atenolol: a promising alternative to propranolol for the treatment of hemangiomas. J Am Acad Dermatol 2011 Aug;65(2):420e1. 2. Ro ¨ssler J, Haubold M, Gilsbach R, et al. b1-Adrenoceptor mRNA level reveals distinctions between infantile hemangioma and vascular malformations. Pediatr Res 2013;73(4 Pt 1). 49e13. 3. Breur JM, de Graaf M, Breugem CC, Pasmans SG. Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. Pediatr Dermatol 2011 MareApr;28(2): 169e71.
M. de Graaf Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.F. Raphael Department of Pediatric Haematology and Oncology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands
412
Correspondence and communications
Reply to ‘Treatment of infantile haemangiomas with atenolol: Comparison with a historical propranolol group.’
of infantile hemangiomas (IH).1 It is agreed that propranolol has a widely published range of side effects, more so when compared to that of atenolol especially in the treatment of hypertension. Propranolol has gained recent popularity in the treatment of IH due to its efficacy however the mechanism of action still remains unclear.1,2 Similarly the effect and mechanism of action of atenolol has not been widely studied in a pediatric population. Nevertheless we agree with the authors, that it could be a good alternative to propranolol if it has less side effects and similar efficacy. Early initiation of pharmacologic treatment such as propranolol within the proliferative phase of IH ensures the best outcomes regarding eventual involution, provided comorbid conditions have been appropriately managed beforehand.3 Given that 85% (23/27) of patients from the atenolol group were aged 1e6 months, it might be hard to compare success rates when only 50% of the propranolol group fell within the same age range. Although the authors refer to age adjustment, clarification is required as how this was done, as the age and efficacy are not related in a linear fashion. More crucially as the focus of the study was efficacy, propranolol was shown to be the more efficacious option due to 100% involution whereas atenolol failed to cause complete involution in 10%. Additionally, although the authors state the difference is not statistically significant, only the quantitative assessment was used for this. We would like to commend the authors on achieving their sample size, as it is the largest to date regarding the use of atenolol.1 It would be interesting to know the outcomes of the propranololeatenolol group of excluded patients, as well as that of the non-cutaneous lesions. We would also like to know whether all of the patients who did not respond to atenolol were then treated with propranolol. We do admit that propranolol has well-known side effects in the treatment of IH, but recent evidence allows for pediatric-tailored drug regimens resulting in a better safety profile.2e5 It is worth noting that one of the patients who suffered from hypoglycaemia following propranolol treatment did so as a result of steroid withdrawal, rather than propranolol itself. Presumably the patients in the atenolol group would not have this problem, as steroids would no longer be used as first line for IH. It is understandable that atenolol be used for its beta-1 specificity, but current evidence (including Graaf et al.’s study) shows that propranolol is still very efficacious.1,2 This study re-affirms the notion that atenolol can be used to treat IH, however data from this study alone is not sufficient to state that atenolol has similar efficacy to propranolol as concluded by the authors. Perhaps a larger sample size spanning similar age groups would allow for a fairer and more enlightening comparison.
Dear Sir,
Conflict of interest/funding
We read with great interest Graaf et al.’s comparative analysis between atenolol and propranolol in the treatment
None.
C.C. Breugem Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M.J. Knol Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands C.A.F.M. Bruijnzeel-Koomen Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands M. Kon Department of Pediatric Plastic Surgery, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands J.M.P.J. Breur Department of Pediatric Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands S.G.M.A. Pasmans Department of Pediatric Dermatology/Allergology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Heidelberglaan 100, Room G02.124, 3584 CX Utrecht, The Netherlands *Corresponding author. Tel.: þ31 88 7557388. E-mail address: [email protected] 14 October 2013 ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.10.027
a
Current affiliation: Pediatric Dermatology, Erasmus Medical Center Rotterdam, The Netherlands DOI of original article: http://dx.doi.org/10.1016/ j.bjps.2013.07.035
References 1. de Graaf M, Raphael MF, Breugem CC, et al. Treatment of infantile haemangiomas with atenolol: comparison with a