Journal club review: Impact of Screening for Hepatic Hemangiomas in Patients with Multiple Cutaneous Infantile Hemangiomas

1. Journal Club Presentation
Impact of Screening for Hepatic
Hemangiomas in Patients with Multiple
Cutaneous Infantile Hemangiomas
Pediatric Dermatology 1-5, 2015
Authors: Kristy L. Rialon, Rudy Murillo, Rebecca D. Fevurly, et. al.
By
Ext. Sripada Kriangkhajorn
Faculty of Medicine, Srinakharinwirot University

2. Abstract
• Several studies have documented the association between
multiple cutaneous IHs with hepatic hemangiomas (HHs)
• HHs can be clinically silent or serious symptom like mortality,
congestive heart failure
• Screen abdominal ultrasonography has been recommended
for patient with five or more cutaneous hemangioma lesions

3. Abstract
• The study aim to determine whether the hemangiomas found
through screening had improved clinical outcomes in children
with multiples cutaneous IHs

4. BACKGROUND

5. Infantile Hemangiomas
• Most common tumors of infancy
• Rarely life threatening, but can be if located in cervicofacial regions,
causing airway obstruction, or within liver, which can cause
congestive heart failure, hypothyroidism, hepatic failure, and
abdominal compartment syndrome
• Several studies have documented the association between multiple
cutaneous IHs with hepatic hemangiomas (HHs)

6. Hepatic hemangiomas(HH)
• Recently, HH was thought to have no clear patterns of presentation
and natural history
• HHs can be clinically silent or can cause serious symptom
• Mortality rates have been reported 11%-18%, but historically it has
been much higher
• There are many studies about several patterns, predict outcomes,
and guides therapy

7. Hepatic hemangiomas(HH)
• Focal HHs are consider as rapidly involuting congenital
hemangiomas (RICHs), which are distinct from typical
hemangiomas, and less associated with cutaneous
hemangiomas
HHs
CHs Focal
IHs
Multifocal
Diffuse

8. Study Objective
‘To determine whether the hemangiomas found
through screening had improved clinical outcomes
in children with multiples cutaneous IHs’

9. METHODS

10. Population Study
Population Study
Setting place at Boston’s Children
Hospital
213 patients with HHs were identified
from database and online registry
Database from Vascular Anomalies
Center and online registry
Study period from January 1, 1995 to
December 31, 2012

11. Methods
Study Design Methods
Retrospective Case Control Database from Vascular Anomalies
Center and Online Registry between
January1, 1995-December 31, 2012
Non-randomized selective case All patients with five or more
cutaneous IHs were included
Exclusional Criteria Patients without diagnosed
information
Indication for initiative
ultrasonography screening
Patients who presented with
cutaneous lesions and were
suspected of visceral lesions
Prior to ultrasound, the patients must
had no signs or symptom suggested
of HHs

12. Methods
Method
Study Procedure Analysis
Data Recorded
Age, date of presentation, type of HH,
symptom, treatment, and
outcome(death)
Bivariate analysis
Fisher exact tests, chi-square tests,
Mann-Whitney U-tests
95% confidence intervals(CIs) using
Wilson’s method
Multivariable logistic regression
analysis, two-tailed p<0.05, IBM ,IPSS

13. RESULTS

14. Results
Initial Abdominal Ultrasound Screening
43(60%) had HHs detected by screening
29(40%) had HHs be found incidentally, by
development of symptoms, or another indication
72 Patients were case with exposure
Multifocal or diffuse HHs >,= 5 cutaneous IHs
Enough data to determine
screening status
213 Patients with HHs was identified
Database and Online Registry Jan 1, 1995-Dec 31.2012

15. TABLE 1. Analysis of Differences Between Patients with Hepatic
Hemangiomas Detected Through Screening Abdominal
Ultrasonography and Those Who Were Not Screened
Not screened
(n = 29)
Screened
(n = 43)
p
Variable
Age at presentation,
days, median (IQR)
53 (18–112) 41 (12–90) 0.26
Diagnosis, n (%)
Multifocal
Diffuse
18 (62)
11 (38)
40 (93)
3 (7)
0.002
CHF, n (%)
Yes
No
14 (48)
15 (52)
2 (5)
41 (95)
<0.001
Hypothyroidism, n (%)
Yes
No
Unknown
10 (34)
15 (52)
4 (14)
4 (9)
36 (84)
3 (7)
0.01
Treatment, n(%)
Yes
No
25 (86)
4 (14)
16 (37)
27 (63)
<0.001
Mortality, n (%)
Yes
No
8 (28)
21 (72)
0 (0)
43 (100)
<0.001
Follow-up, mos,
median (IQR)
12 (3–40) 10 (4–23) 0.87
IQR, interquartile range

16. Results
• Children identified by screening were less likely to have
serious clinical sequalae from the liver hemangioma
• Almost half of children in the non-screened group developed
CHF, while only two who were screen developed CHF
• Hypothyroidism was also less prevalent in the screened group

17. Results
• Three of the diffuse patients on the non-screened group
progressed to abdominal compartment syndrome, compared
with none of the diffuse patients who were screened
• None of the patients who screened died
• HHs detected through screening were less likely to require
treatment

18. Results
TABLE 3. Variations in Treatment Types for Those Who Were
Screened and Not Screened
Treatment Not screened (n = 25) Screened (n =16)
n (%)
Steroids 21 (84) 9 (56)
Propranolol 7 (28) 7 (44)
Interferon 3 (12) 1 (6)
Vincristine 1(4) 0 (0)
Embolization 4 (16) 1 (6)
Radiation 1 (4) 0 (0)
Multiple 13 (52) 2 (13)

19. Results
• Only 1 patient who was screened required embolization for
shunts causing heart failure, while 4 of the non-screened
group underwent this procedure
• Multiple treatments were more common in non-screened
than in those who were screened

20. TABLE 4. Analysis of Differences Between Treated Patients Who Were
Screened and Not Screened
Variable Not screened
(n = 25)
Screened
(n = 16)
p
Age at presentation,
days, median (IQR)
45 (15–109) 14 (8–66) 0.08
Diagnosis, n (%)
Multifocal
Diffuse
14 (56)
11 (44)
14 (88)
2 (12)
0.04
CHF, n (%)
Yes
No
14 (56)
11 (44)
2 (12)
14 (88)
0.008
Hypothyroidism, n (%)
Yes
No
Unknown
10 (40)
11 (44)
4 (16)
2 (12.5)
12 (75)
2 (12.5)
0.12
Mortality, n (%)
Yes
No
8 (32)
17 (68)
0 (0)
16 (100)
0.01
Follow-up, mos,
median (IQR)
12 (3–40) 9 (3–20) 0.95
IQR, interquartile range.

21. Results
• Screened children were more often diagnosed with multifocal
lesions and had lower incidence of CHF
• Multivariable logistic regression analysis confirmed that,
independent of the presence of CHF and disease pattern,
screening was a significant predictor of reduced mortality

22. DISCUSSION

23. Discussion
Aim
• Because of there had been long known of the association of IHs and HHs,
the recommendation of the screening was created.
• This study aim to find the outcome of the recommendation to be
screened in the patients with multiple cutaneous and HHs
Methods
• The patients to be studied was grouped based on the recent study, said
that 16% incidence of HHs in infants <6 months with 5 or more
cutaneous hemangioma lesions
• The case was grouped to be screened or non-screened depended the
screening purposed or for another indication for initial screening

24. Strenght
Results Discussion
Those who were screened were less
likely to develop CHF or
hypothyroidism and less likely to
have been treated for HHs It is likely that by early detect the lesions,
and referring to specialists, patients are
followed,
and treated appropriately before the
lesions become progress or symptomatic
Screening may detect lesions that
would have been clinically silent
and never be discovered
The most serious type of HH is
diffuse, as these can lead to
abdominal compartment
syndrome and death.
No deaths occurred in the group
identified through screening
Screening was a significant predictor
of lower mortality in treated
patients
Ultrasonography is a noninvasive,
inexpensive, and widely available for use
as a screening tool for children with
multiple cutaneous IHs.

25. Discussion
Weak Points
Discussion
Retrospective It is impossible to perform a
prospective randomized trial
because screening would be
withheld from some patients.
Careful analysis of the
registry provides the best
chance to find out,
whether screening gives
better outcomes than
simply detection.
Selective Bias By separately analyzing just
patients who required
therapy, the study excluded
those that would likely have
never been detected in the
non-screening.

26. Discussion
Weak Points
Discussion
Sampling Error There were only a few diffuse
HHs in the screened group. One may surmise that
some of multifocal
lesions patients detected
by screening were treated,
to prevent progression to
the diffuse pattern.
Informative Bias Outside the setting hospital,
there are many patients with
HHs, but the database were
incomplete
We do not know the
specific indication for
treatment.
There may be another
selective bias for some
patients
The patients were selected
with 5 or more cutaneous
lesions to match the number
that the Hemangioma
Investigator Group
recommends for screening
The study does not address
whether five is the best
screening threshold.

27. CONCLUSION

28. Conclusion
‘Infants HHs detected through screening were less
likely to develop serious clinical symptoms and had
reduced mortality’
‘Screening was an independent predictor of lower
mortality in severe symptomatic children’
‘Screening may result in earlier treatment, early
referral, and closure follow-up before the
progression of the lesions‘

29. STUDY APPLICATIONS

30. Study Applications
Study Application
Study Discussions Applicationns
Hemangiomas are the most common
tumors found in infants
Incidence of the findings was 10%. In
Thailand ratio between girl and boy is
2.1:1 and 58% is CHs
Early detection of lesions, early suspect
of probable of complication and early
referral to appropriated physician
may be the best way to reduce morbid
& mortality
Clinical characteristics of hemangiomas
Progression of hemangiomas
Complication
Associated Syndromes
Treatment

31. THANK YOU

32. References
• คู่มือโรคผิวหนังเด็ก; อมรศรี ชุณหรัศมิ์. ชมรมแพทย์ผิวหนังเด็กแห่งประเทศไทย. พิมครั้งที่ 1
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• ตารา โรคผิวหนังเด็ก เล่ม 1; ศิริวรรณ วนานุกูล. ภาควิชากุมารเวชศาสตร์. คณะแพทยศาสตร์
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