Journal Club Presentation

Impact of Screening for Hepatic Hemangiomas in Patients with Multiple

Cutaneous Infantile Hemangiomas

Pediatric Dermatology 1-5, 2015Authors: Kristy L. Rialon, Rudy Murillo, Rebecca D. Fevurly, et. al.

ByExt. Sripada Kriangkhajorn

Faculty of Medicine, Srinakharinwirot University

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

Abstract• The study aim to determine whether the hemangiomas found

through screening had improved clinical outcomes in children with multiples cutaneous IHs

BACKGROUND

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)

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

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

IHsMultifocal

Diffuse

Study Objective

‘To determine whether the hemangiomas found through screening had improved clinical outcomes

in children with multiples cutaneous IHs’

METHODS

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

MethodsStudy 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

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

RESULTS

Results

Initial Abdominal Ultrasound Screening

43(60%) had HHs detected by screening29(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

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

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

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

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)

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

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.

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

DISCUSSION

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

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.

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.

DiscussionWeak 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.

CONCLUSION

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‘

STUDY APPLICATIONS

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

THANK YOU

References• คู่มอืโรคผิวหนังเด็ก; อมรศร ีชุณหรศัมิ.์ ชมรมแพทยผ์ิวหนังเด็ก

แหง่ประเทศไทย. พมิครัง้ท่ี 1 มกราคม 2559 • ตำารา โรคผิวหนังเด็ก เล่ม 1; ศิรวิรรณ วนานุกลู. ภาควชิากมุาร

เวชศาสตร.์ คณะแพทยศาสตรจุ์ฬาลงกรณ์มหาวทิยาลัย. พมิพ์ครัง้ท่ี 1 มกราคม 2557