A short presentation about papers published in 2014 ( about 1050 research ) showing new modalities of treatment of infantile hemangioma. Regression of role of corticosteroids, Progression of Propranolol role and Restriction of role of surgery are the most prominent points A Case report of Hypothyroidism associated with cutaneous hemangioma is also explained inside

1. New trends in treatment of
InfantileHemangiomas
By
Emad M. Qasem
6th grade
Sohag Faculty ofmedicine

2. Contents
• Overview of Infantile Hemangioma.
• Important pre treatment notes.
• Engage your Audience
• Capture Audience Attention

3. InfantileHemangiomaOverview
RiskFactors:
The various risk factors include:
• female gender.
• Prematurity.
• low birth weight.
• multiple pregnancies.
• advanced maternal age.
• in vitro fertilization.

4. InfantileHemangiomaOverview
Morphological Classification:
Superficial Type
• bright red vascular plaques
or nodules
Deep Type
• partially compressible.
• Subcutaneous.
• bluish vascular swellings
Mixed Type
• both superficial and deep
components

5. InfantileHemangiomaOverview
Distributional Classification:
Localized
• spatially confined
Segmental
• clusters of lesions confined
to a developmental
segment or a large
anatomic territory
Intermediate Multi focal
• 5 or more non-contiguous
lesions.
• often associated with
systemic involvement.

6. Distributional Classification:
• Localized • Segmental

7. Distributional Classification:
• Multi focal

8. Infantile Hemangioma:
• a characteristic natural course;
a rapid proliferative phase in infancy which is followed by a gradual
involutional phase over the next several years of life.
• Complications such as:
1. ulceration.
2. distortion of vital structures.
3. skin disfigurement
• are also expected to occur during this critical period.

9. PRE TREATMENT
Infantile Hemangioma

10. Investigations to be done:
Only in doubtful cases
• MRI.
• Doppler ultrasound.
• Tissue biopsy.

11. Segmental hemangiomas
• Associated with visceral hemangiomatosis.
• The location of visceral lesions often correlating with
the site of cutaneous involvement.
• Large segmental hemangiomas on the face are at risk
for PHACES syndrome.
• segmental hemangiomas in the perineal region may
be associated with malformations of the urogenital
or anogenital systems
Doubtful Cases

12. PHACES syndrome
• Posterior fossa anomalies.
• Haemangiomas.
• Arterial anomalies.
• Coarctation of aorta.
• Cardiac defects.
• Eye abnormalities.
• Sternal clefting and Supra-umbilical raphe.
Doubtful Cases

13. PHACES syndrome
• Ophthalmological, cardiac and neurological
evaluation.
• Magnetic resonance imaging (MRI) with angiography
of the head and neck region is usually indicated in
such infants.
Doubtful Cases

14. segmental hemangiomas in the perineal region
Doubtful Cases
Source: http://archderm.jamanetwork.com/article.aspx?articleid=406327

15. segmental hemangiomas in the perineal region
• Associated with an angioma of lumbosacral localisation:
• (SACRAL)
1. Spinal dysraphism
2. Anogenital, cutaneous, renal and urologic anomalies.
• (PELVIS)
1. perineal haemangioma
2. external genitalia malformations.
3. lipomyelomeningocele.
4. vesicorenal abnormalities.
5. imperforate anus.
Doubtful Cases

16. cervicofacial, mandibular or the 'beard'
hemangiomas
• Laryngeal involvement can occur.
• Affected infants should be watched for signs and
symptoms of airway obstruction:
1. Stridor
2. Hoarseness
• and referred for a laryngeal examination.
Doubtful Cases

17. Large cutaneous Hemangiomas
• Raised levels of iodothyronine deiodinase have been
demonstrated in large proliferative haemangiomas,
which can lead to hypothyroidism.
• most of the cases of hypothyroidism have been noted in
association with hepatic haemangiomatosis.
• though increased iodothyronine deiodinase activity has
been detected in some large cutaneous lesions as well.
• Hence, a recommendation has been made to perform
serial thyroid function tests in patients with hepatic
haemangiomatosis or large cutaneous haemangiomas
Doubtful Cases

18. Reported case
Doubtful Cases
case of a 9-week-old boy who developed
severe hypothyroidism due to occult hepatic hemangiomas.
At birth, results were normal on a routine thyroid-stimulating hormone
(TSH) screening test.
At 9 weeks, the infant had poor feeding, lethargy, jaundice, and
constipation. The TSH level was elevated, and the level of free T4 was
low. He required increasing doses of l-thyroxin; ultimately, the dosage
was 28 µg/kg/day, much higher than what is needed by an athyrotic
infant.
At 6 months of age, the patient's liver was 3 cm below the costal
margin. An ultrasound revealed multiple hepatic hemangiomas, but no
cutaneous hemangiomas or cardiovascular problems were identified. l-
thyroxin replacement was discontinued when the boy was 3 years old,
and he subsequently grew and developed normally. The authors
suggest that the hypothyroidism improved concurrently with
involution of the hepatic hemangiomas (which had not been treated).
- See more at: http://www.jwatch.org/jd200402040000003/2004/02/04/acquired-hypothyroidism-caused-
infantile#sthash.Jc0Rbgx4.dpuf

19. TREATMENT
Infantile Hemangioma

20. Indications:
Depends on the following factors:
1. Type of hemangioma.
2. Stage of the lesion.
3. Location and extent.
4. Number and distribution of the lesion
(segmental/non-segmental).
5. Associated systemic involvement.
6. Presence or absence of ulceration.
7. psychosocial distress of the parents or child.

21. Cases in need of intervention
• Function threatening
(ocular, ear, nasal tip, lip, large disfiguring facial
lesion and genitalia involvement)
• Life threatening
(airway lesion) IH, which constitute about 10-
20% of the cases

22. Cases in need of intervention

23. Other Cases:
• need only active non-intervention, which consists of:
1. education about the natural course.
2. treatment options and anticipatory guidance.

24. Treatment Options
Medical treatment
• Systemic medications:
1. Corticosteroids.
2. Propranolol.
• Other systemic Drugs.
• Topical treatment.
• Other modalities.
Surgical excision
• surgical excision as a first-
choice treatment in some
cases.
• Applied study on One
hundred fifteen cases of
surgical excision of pediatric
hemangiomas

25. CORTICOSTEROIDS VS
PROPRANOLOL
Main systemic drugs used

26. Corticosteroids
• Systemic corticosteroids (prednisolone) have been
the mainstay of treatment for IH, for several decades.
The mechanism of action of steroids:
• is not entirely clear, though it is postulated to have
an inhibitory effect on the production of vascular
endothelial growth factor A (VEGF-A) by stem cells in
haemangiomas.

27. Corticosteroids
• Steroids are most effective in the early proliferative
phase.
• The usual recommended dose is 2-4 mg/kg/day,
which should be continued until cessation of growth
or shrinkage of hemangioma followed by gradual
tapering.

28. Corticosteroids
• High dose pulse corticosteroids (methyl prednisolone
30 mg/kg/day infused over 1 hour daily for 3 days)
may be useful in IH which need immediate
therapeutic response:
1. Large peri-ocular IH with complete visual axis
occlusion.
2. Large airway hemangioma with respiratory
difficulty.
• Usually three or more monthly doses are required
followed by shorter oral steroid regimen.

29. Corticosteroids
Serial photographs of
hemangioma involving the
scalp responded to steroid
for 3 months.
(a) baseline.
(b) 3 months of
treatment.
(c) showing cushingoid
face

30. Propranolol
• a non-selective -β adrenergic receptor blocker that
recently has emerged as a good therapeutic option in
IH.
• In 2008, First report about regression of a facial IH in
a child who was treated with propranolol for
obstructive hypertrophic cardiomyopathy.
• Currently, it is widely used in IH, particularly for
complicated and ulcerated IH, and appears to be the
best therapeutic modality.

31. Propranolol
• Oral propranolol has three different pharmacological
effects:
• The early effect of a visible change in colour and
considerable softening of the lesion occurs within 1-3
days. This is related to the β2 inhibitory effect of
propranolol that decreases the release of the vasodilator
transmitters such as nitric oxide causing vasoconstriction.
• propranolol is nowadays considered as the promising
therapy in IH with ulceration or haemangiomas involving
vital structures such as eyes, airways, genitalia etc.

32. Propranolol
• The intermediate effects of propranolol are due to a
downregulation of both:
1. VEGF (vascular endothelial growth factors).
2. bFGF (basic fibroblast growth factors).
• resulting in inhibition of proangiogenic cascade and
angiogenesis.

33. Propranolol
• The long term effect of propranolol is due to
apoptosis resulting in regression of haemangiomas.
• No published evidence that early start of propranolol
therapy results in less deforming residual skin
changes.
• a target dose of 1-3 mg/kg has been recommended.

34. Propranolol
• The duration of therapy depends on:
1. The morphological type of haemangioma.
2. Extent of involvement
3. The treatment indications.
• A suggested treatment course of at least 6 months
(based on randomized controlled trial (RCT)) was
recommended which could be modified according to
the morphological subtypes.

35. Propranolol
• Propranolol also seems to be a promising drug for
ulcerated haemangiomas. Painful ulceration in
hemangioma has been reported to heal completely
within 2 months.
• Studies suggest that it is the best therapeutic option
in cases with airway and other complicated IH.

36. Propranolol
Serial photographs of
haemangioma on the right
pectoral region responded
to 30 months of
propranolol.
a: baseline;
b: 1 month after
treatment;
c: 2 years of treatment;
d: 2.5 years of treatment
(Courtesy of Somesh Gupta)

37. Propranolol
Photographs of hemangioma
on the nose showing an
excellent response to
propranolol for 10 months.
a: baseline;
b: 10 months of treatment.
(courtesy of Somesh Gupta)

38. Precautions of treatment

39. Before starting Corticosteroid treatment
• ruling out active infection or primary
immunodeficiency disease,
• (complete blood count with differential leucocyte
count, serum biochemistry, chest x-ray and urine and
stool microscopy
• a baseline anthropometric examination (height,
weight) and blood pressure, which should be
monitored serially.

40. Before starting Propranolol treatment
• Before initiating propranolol therapy, the children
need to be assessed for the following
contraindications:
1. bronchial asthma,
2. heart failure,
3. sinus bradycardia,
4. hypoglycaemia,
5. hypotension,
6. heart block and known allergy to propranolol

41. Before starting Propranolol treatment
• The initial examination should include:
1. a thorough cardiopulmonary assessment
including pulse rate, blood pressure and blood
sugar.
2. A baseline electrocardiogram (ECG) is usually
recommended.

42. Most common side effects
Corticosteroids
• cushingoid facies.
resolved spontaneously during the final few
months of tapering steroids.
• slipping off their growth
curve.
Propranolol
• hypoglycaemia especially in
infants < 3 months of age with poor
feeding.
• pulmonary symptoms.
• sleep disturbances,
• somnolence,
• cold extremities
• gastrointestinal (GI)
complaints.

43. Other Propranolol complications
• Rebound or regrowth of haemangioma:
1. Defined as increase in size, change in colour or
both, can occur after discontinuation of
treatment.
2. Studies showed that stopping propranolol before
the age of 1 year increases the risk of rebound
growth. In deeper haemangiomas,

44. Other Propranolol complications
• Propranolol-resistant IH:
1. an absence of treatment response either in the
proliferative phase or during the post-proliferative
phase,
2. after at least 4 weeks of oral propranolol at
dosage of ≥2 mg/kg/day.
3. This phenomenon needs to be investigated in a
large scale studies in order to understand the
different factors which influence the treatment
outcome in children with IH.

45. Summary of propranolol treatment in infantile
hemangioma
Source:

46. Other systemic drugs:
• Other treatment options like:
1. interferon α,
2. Vincristine
3. cyclophosphamide
• are reserved for life-threatening haemangiomas
which are unresponsive to conventional therapy.

47. TOPICAL TREATMENT
Other medications:

48. Timolol
• Timolol is a non-selective β blocker which is used for
increased intra-ocular pressure.
• In 2010, Guo and Ni first reported the clinical
response to timolol 0.5% solution in a 4-month-old
infant who had a thin haemangioma plaque on the
upper eyelid.
Source:
http://archopht.jamanetwork.com/article.aspx?articleid=424957

49. Timolol
• It has been mostly used for localized, non-ulcerated
superficial IHs.
• more effective for lesions with a mean diameter of
<11.3 mm (i.e. 100 mm3 in volume) as compared to
larger lesions.
• applied two times a day. One drop of timolol maleate
(0.5%) contains 0.25 mg of the drug.
• Treatment is more effective in the proliferative phase
than in the involution phase, and also, plaques
respond better than nodules.

50. Topical propranolol 1% ointment
• has been used successfully in the treatment of
superficial IHs, especially as an adjuvant therapy
during the wait-and-watch period.
• Concomitant use of propranolol ointment with
pulsed dye laser (PDL) in two of their cases of
ulcerated haemangioma led to healing of ulcers in 3
and 6 weeks,

51. Imiquimod
• an immune response modifier with anti-angiogenic
and pro-apoptotic properties,
• has been used in the treatment of superficial IH.
• The duration of therapy is about 4 months.
• Severe inflammatory reactions may occur with
application of imiquimod.
• the efficacy of imiquimod was comparable with
timolol. However, inflammatory changes were seen
in 13 of 20 (65%) cases in the imiquimod group while
none of cases in the timolol group had side effects.

52. Topical steroids
• Potent steroids have been used to treat flat or
minimally raised vascular plaques of IH particularly at
sites prone to ulcerations and disfigurement.
• May cause localised atrophy, hypopigmentation,
hypertrichosis and infections.
• good safety profile for lesions at all sites, including
the peri-ocular region.
• Following the successful reports of topical timolol,
topical steroids are less often prescribed in the
current practice.

53. OTHER MODALITIES OF TREATMENT
There are also

54. Pulsed Dye Laser (PDL)
• PDL has been used successfully for the treatment of
ulcerated IH, which reduces the pain and promotes
healing.
• It is also used to remove the residual telangiectasia.
However, the use of PDL in uncomplicated IH is
controversial.
• There are non-randomized studies which claim that
PDL is better than the wait-and-watch policy.

55. Pulsed Dye Laser (PDL)
• although the infants in LPDL group suffered
significantly less side-effects like:
1. hypo- or hyperpigmentation,
2. textural changes
• the period of maximal proliferation was also
significantly shortened (106 days in LPDL versus 177
days in PDL group).

56. Pulsed Dye Laser (PDL)
• There is no consensus on the optimal settings of PDL
and selection of type of haemangiomas suitable for
treatment with laser.
• Currently, the use of PDL is confined to the treatment
of ulceration and post-involution erythema and
telangiectasias.

57. Other lasers
• Frequency-doubled Nd:YAG laser was found to be
less effective than PDL in a retrospective study on 50
infants with superficial IH.
• sequential 595-nm PDL followed by 1064-nm Nd:YAG
laser led to excellent response in (72%) of infants
with IH on skin and mucous membrane in the head
and neck region.

58. Other lasers
• Good results with intralesional therapy using KTP
laser have been described in treating voluminous
haemangiomas.
• The level of evidence with respect to studies using
various treatment modalities is given in The next
table:

60. SURGICAL TECHNIQUE
Then we have

61. Surgery for hemangiomas
• in the first year of life is a technique that has not
been reviewed extensively in the literature.
• perhaps more difficult and dangerous because of the
highly vascular nature of these lesions in the
neonate.
• Operating on hemangiomas in older children is
somewhat more problematic than in the neonate.

62. Surgery for hemangiomas
• In the involuting lesion, the hemangioma is a mixture
of fibrofatty tissue and blood vessels.
• It is very difficult in many of these lesions to
distinguish between the hemangioma and normal
tissue. As a consequence, this requires resection of a
greater volume of normal tissue.

63. Emad M. Qasem
6th grade | Sohag school of medicine