This document discusses vascular lesions of the head and neck. It provides classifications of vascular lesions as tumors or anomalies. It describes key differences between hemangiomas and vascular malformations. Hemangiomas are benign tumors that proliferate through endothelial cell growth, while malformations are localized defects present at birth. The document outlines diagnostic methods and considerations for different types of lesions. It focuses on hemangiomas in infants, describing presentations, subtypes, complications, and treatment indications, notably with propranolol. Propranolol treatment requires pretreatment evaluation including ECG in certain cases and has shown efficacy in resolving hemangiomas.

1. Vascular Lesions
Propranolol treatment of HOI
DR. ALI MANSOUR
ENT DEPARTMENT ALMOWASSAT HOSPITAL

2. Diagnosis
A GOOD DIAGNOSIS = BEST TREATMENT

3. Overview
• Vascular lesions of the head and neck encompass a wide range of different
lesions
• Historically, these lesions have been poorly understood, and their
nomenclature reflects this
• Over the years, this nomenclature has evolved as progress has been made
in our understanding of the histopathology, clinical behavior, treatment,
and prognosis of these lesions

4. classifications
Vascular lesion
Vascular tumor
Vascular Anomalie

5. DDx
 Vascular tumors
 grow mainly by endothelial cell hyperplasia whereas
 vascular malformations
 have a quiescent endothelium (inner lining) and are considered localized
defects of vascular morphogenesis

6. subclassifications
Tumors
hemangioma
Congenital
RICH
NICH
Infant
Focal - segmental
Superficial - Deep
pyogenic
granuloma
KHE TA Hemangiopericytoma Angiosarcoma
KHE’ Kaposiform hemangioendothelioma
TA’ Tufted angioma
RiCH’ Rapidly involuting
NiCH’ Noninvoluting

7. subclassifications
Anomalie
Single-Vessel Type
Capillary Venous Arteriovenous Lymphatic
macrocystic
microcystic
Combined
lymphaticovenous Cap. Venous
Cap. Lymph-
venous
Cap.
Arteriovenous

8. hemangioma

9. Capillary

10. Venous

11. Lymphatic

12. Arteriovenous

13. It seems difficult to
Diagnose VL ?
THE KEY FOR BEST DIAGNOSIS

14. The Key
 History
 clinical observation
 Physical examination
 Echo + Doppler
 MRI
 Rarely Biopsy _+ immunohistochemistry

15. General Consideration

16. Vascular MalformationsVascular Tumor
Congenital abnormality70% apparent during first few weeks
proportional growthProliferative
No gender predilectionFemale to male ratio 3:1
expand secondary to sepsis, trauma, or
hormonal changes- Do not involute
Rapid postnatal growth followed by slow
involution
Normal endothelial cell turnoverEndothelial cell proliferation
No response to corticosteroidsrespond dramatically to corticosteroid
Low-flow: phleboliths, ectatic channelsEcho-MRI – High Flow on proliferative phase
High-flow: enlarged, tortuous vessels with
arteriovenous shunting
Immunonegative for hemangioma biologic
markers
Immunopositive for biologic markers (including
GLUT1)

17. Hemangioma of
infant
PRESENTATION - TREATMENT

19. Hemangioma
 Infantile hemangiomas are benign vascular tumors characterized by the
proliferation of the endothelial cells
 Hemangiomas represent the most common tumor in infants, occurring in
up to 3-5% of all children
 Most hemangiomas affect the head and neck

20. Clinical Presentation
 manifest as an isolated, dark lesion of the skin
 HOIs are absent at birth and appear in infancy
 They proliferate for 6 to 9 months and involute partially or completely
over several years
 complete involution occurs in 50% of lesions by age 5 years and in 70% of
lesions by age 7 years
 Vascular lesions that do not follow this pattern should be considered for
alternative diagnose
 FM 31 – more common on premature infants - more common in whites

21.  Detection of GLUT-1 in HOI endothelium distinguishes them from other
vascular anomalies
 Improvements in image acquisition with both computed tomography
(CT) and (MRI) allow differentiation between HOIs and other
vascular anomalies

22. Congenital hemangioma
 Other hemangiomas present at birth are already mature and do not
proliferate. These are referred to as congenital hemangiomas and are
divided into
 rapidly involuting congenital hemangiomas (RICHs)
 noninvoluting congenital hemangiomas (NICHs)
 Most cases of RICH involute entirely by age 1 year.
 NICHs do not decrease in size.
 Congenital hemangiomas account for approximately 3% of all
hemangiomas
 GLUT-1 negative

23. Superficial vs Deep
 Superficial lesions 50% to 60% that affect the skin manifest as raised, red
lesions that are somewhat firm to the touch
 Subcutaneous lesions 15% tend to manifest as deeper masses with a blue
hue and an unaffected overlying skin layer
 Mixed 25-35%
 These deeper lesions are more difficult to differentiate from vascular
malformations and other masses and more often require radiographic
imaging to aid in diagnosis

26. Focal vs Segmental
 Focal Located on the bony prominences
 Segmental Cover 1 or more segments of the face and body
 Segmental HOIs are usually superficial, variably involve cutaneous
dermatomes, and have more associated morbidity than focal HOI specially
PHACES Syndrom
 Multifocal
 In children with 5 or more hemangiomas,
 the workup should include an abdominal ultrasound to evaluate for
visceral hemangiomas

28. PHACESSyndrome
 Posterior fossa intracranial abnormalitie
 Hemangiomas
 Arterial abnormalities
 Cardiac defects and coarctation of the aorta
 Eye abnormalities
 Sternal clefting
 About 20% of segmental infantile hemangioma are associated with PHACE
syndrome—88% of which are females

29. Special Sites
 Periorbital hemangioma
 cause significant problems with vision, especially during the proliferative
phase and slow involution amblyopia affects approximately 75% of
children over the age of 1 year who were untreated.
 subglottic hemangioma
 Cause airway compromise may prove fatal – may require Tracheotomy
 Auditory canal obstruction
 Lips

30. COMPLICATIONS 12%
 Local
 Ulceration and infection
 Scarring
Permanent Disfigurement or Scarring Can Occur if Left Untreated
1/3 of facial infantile hemangiomas will result in soft tissue distortion or damage
69% of infantile hemangiomas leave residual lesions when left untreated
 Systemic
 Congestive heart failure may occur in the setting of large and/or multiple
hemangiomas located in the skin, subcutaneous tissues, or viscera
 Kasabach-Merritt phenomenon this phenomenon is not associated with
infantile hemangiomas

31. ulceration

32. Treatment indication
 Treatment is indicated when functional or cosmetic complications arise (or
are predicted to arise) that are worse than the side effects of intervention.
 Lesion size, location, patient age, and phase of the lesion (proliferative,
involuting, mature) also influence the method and timing of intervention
 Side effects

33. Treatment Options
 Observation
 Medical therapy
 Propranolol – Corticosteroid (injection-Systemic) – INF - vincristine.
 Laser therapy
 pulsed -dye laser (PDL)- (CO2) laser - Nd:YAG
 Surgical therapy

35. History of propranolol
 While treating French children for congenital disease supraventricular
tachycardia in 2008,
Dr. Christine Léauté-Labréze and her colleagues discovered that propranolol
hydrochloride could also control the growth of hemangiomas. It is believed
that the drug may have an effect on proliferating infantile hemangiomas
through vasoconstriction, inhibition of angiogenesis, and induction of
apoptosis
 In 2014 this Drug had FDA approved to treat HOI
Proven Efficacy 60% of infantile hemangioma completely or nearly
completely resolved by 6 months vs 4% for placebo
88% of infantile hemangioma showed improvement after 5 weeks of
treatment

39. Propranolol in general
 Propranolol is a synthetic, b-adrenergic receptor-blocking agent that is
classified as nonselective because it blocks bothb-1 and b-2 adrenergic
receptors - inhibition of renin release by the kidneys
 resulting in a decrease in heart rate (HR) and blood pressure (BP)
 first-pass metabolism by the liver with only∼25% of oral propranolol
reaching the systemic circulation. Multiple pathways in the cytochrome
P450 system are involved in propranolol’s metabolism, making clinically
important drug interactions a potential issue

40. Mechanism of Action Hypothesis
 The mechanism of action of HEMANGEOLTM (propranolol hydrochloride) in
infantile hemangioma is not known.
 The hypothesis is that the drug’s effect on proliferating infantile
hemangioma can be attributed to 3 molecular mechanisms, leading to:
1. A local hemodynamic effect (reduction in blood flow)
2. An anti-angiogenic effect (reduction of growth factors)
3. An apoptosis triggering effect on capillary endothelial cells (increase rate
of infantile hemangioma cell death)

42.  there is significant uncertainty and divergence of opinion regarding
1. pretreatment evaluation
2. safety monitoring
3. dose escalation
4. use in PHACE syndrome

43. pretreatment evaluation

44. Pretreatment ECG - Echo
 a more indication-driven ECG strategy is likely to develop because the
incidence of ECG abnormalities that would limit propranolol use in children
with IH appears low
 congenital complete heart block is rare, with an estimated prevalence of 1
in 20 000 live births, and this is most commonly associated with maternal
connective tissue disease
 Because structural and functional heart disease have not been associated
with uncomplicated IH, echocardiography as a routine screening tool before
initiation of propranolol is not necessary in the absence of abnormal clinical
findings

45. ECG Indications
 ECG should be part of the pretreatment evaluation in any child when
 the HR is below normal for age
1. newborns (<1 month old),<70 beats per minute,
2. infants (1–12 months old), <80 beats per minute, and
3. children (more 12 months old): <70 beats per minute
 family history of congenital heart conditions or arrhythmias or maternal
history of connective tissue disease
 history of an arrhythmia or an arrhythmia is auscultated during
examination

46. contraindicated
 premature infants with corrected age < 5 weeks
 infants weighing less than 2 kg
 infants with known hypersensitivity to propranolol or any of the excipients
 infants with asthma or history of bronchospasm
 heart rate < 80 beats per minute
 greater than first-degree heart block
 decompensated heart failure
 blood pressure < 50/30 mm Hg
 pheochromocytoma

47. Administration - recommended Dosing
 initiated in infants aged 5 weeks (more than 2kg) to 5 months.
 should be given to infants during or right after a feeding
 Dose between 1-3 mgkg
 Week 1 – starting dose is 0.15 mL/kg (0.6 mg/kg) twice daily
 Week 2 – increase dose to 0.3 mL/kg (1.1 mg/kg) twice daily
 Week 3 – increase to a maintenance dose of 0.4 mL/kg (1.7 mg/kg) twice daily
 Administer twice daily doses at least 9 hours apart during or after feeding The
dose of should be skipped if the infant is vomiting or not eating
 Monitor heart rate and blood pressure for 2 hours after the first dose or
increasing dose
 Duration of treatment: 6 months

48.  Mean age at treatment initiation was 3.6 months.
 Mean dose was 2.2 mg/kg/day.
 Mean treatment duration was 7.1 months.

49. Side effects
 The following adverse events were observed with incidence of less than 1%
 Cardiac disorders -Decreased blood glucose-Decreased heart beat-Alopecia-
Urticaria
 The most common adverse reactions (occurring ≤10% of patients):
 Sleep disorders
 Aggravated respiratory tract infections
 Diarrhea
 Vomiting
 Fewer than 2% of patients discontinued treatment due to adverse reactions

52. Bradycardia and Hypotension
 Propranolol’s effects on BP and HR in children peak around 2 hours after an
oral dose
 During initiation of propranolol for IH in infants,
 bradycardia (<2 SD of normal) and hypotension (<2 SD of normal) after
the first dose (2 mg/kg/day divided 3 times daily) were infrequent and
asymptomatic

53. Hypoglycemia
 Symptomatic hypoglycemia and hypoglycemic seizures have been
reported in infants with IH treated with oral propranolol
 often associated with poor oral intake or concomitant infection
 Nonselective b-blockers, such as propranolol, may block catecholamine
induced glycogenolysis, gluconeogenesis, and lipolysis, predisposing to
hypoglycemia
 patients with IH may be at increased risk if they have received or are
concomitantly receiving treatment with corticosteroids, because adrenal
suppression may result in loss of the counterregulatory cortisol response
and increase the risk of hypoglycemia

54.  With propranolol-induced b-adrenergic blockade, early symptoms may be
masked. Therefore, because sweating is not typically blocked by b-
blockers, this may be a more reliable symptom for diagnosis

55. Bronchospasm
 Bronchial hyperreactivity, described as wheezing, bronchospasm, or
exacerbation of asthma/bronchitis, is a recognized side effect of
propranolol as the result of its direct blockade of adrenergic
bronchodilation
 The development of bronchial hyperreactivity in the setting of an acute
viral illness in patients on propranolol has necessitated temporary
discontinuation of therapy

56. Hyperkalemia
 The cause of the hyperkalemia is not known, but the authors postulate that
it was tumor lysis from the large ulcerated IH combined with impaired
potassium uptake into cells as the result of b blockade

57. Inpatient VS. Outpatient
 some centers hospitalize all children for initiation of treatment, whereas
others do so only rarely
 Some experts recommend intensive outpatient monitoring of patients,
whereas others do little to no monitoring
 Oral propranolol appears to have a favorable safety profile in children.
Deaths or acute heart failure have been associated with propranolol
initiation only in the settings of intravenous administration or drug
overdose

58. Inpatient
 Infants <8 weeks of gestationally corrected age
 any age infant with inadequate social support
 any age infant with comorbid conditions affecting the cardiovascular
system, the respiratory system including symptomatic airway
hemangiomas or blood glucose maintenance

60. Outpatient
 infants and toddlers older than 8 weeks of gestationally corrected age
 Adequate social support
 without significant comorbid conditions

62. Cardiovascular Monitoring
 Patients should be monitored with HR and BP measurement
 at baseline
 at 1 and 2 hours after receiving the initial dose
 after significant dose increase (>0.5 mg/kg/day)
 If HR and BP are abnormal
 the child should be monitored until the vitals normalize dose response is
usually most dramatic after the first dose;
 therefore, there is no need to repeat cardiovascular monitoring multiple
times for the same dose unless the child is very young or has comorbid
conditions affecting the cardiovascular system or the respiratory system
including symptomatic airway hemangiomas

63. HR vs. BP
 Bradycardia is important to recognize because the accurate measurement
of BP in infants may be challenging.
 HR is simple to measure, and normative data for inappropriate bradycardia
have been established as follows:
1. Newborns (<1 month old), <70 beats per minute
2. Infants (1–12 months old), <80 beats per minute
3. Children (>12 months old), <70 beats per minute
 Systolic BP varies significantly between1 month and 6 months of age,so
normative data are difficult to interpret

64. BP
 Newborn:<57 mm Hg (<5th percentile oscillometric) or 64 mm Hg (2 SD
auscultation)
 6 months:<85 mm Hg (<5th percentile oscillometric) or 65 mm Hg (2 SD
auscultation)
 1year:<88 mm Hg (<5th percentile oscillometric) or 66 mm Hg (2 SD
auscultation)

65. Ongoing Monitoring
 As discussed earlier, patients should be monitored with HR and BP
measurement at baseline and at 1 and 2 hours after a significant dose
increase (>0.5 mg/kg/day), including at least 1 set of measurements after
the target dose has been achieved
 Most centers represented at the conference do not perform or
recommend Holter monitoring in this setting on a routine basis
 routine screening of serum glucose is not indicated.
 Propranolol should be administered during the daytime hours with a
feeding shortly after administration. Parents should be instructed to ensure
that their child is fed regularly and to avoid prolonged fasts

66. Subglottic
 Treatment includes such varied options:
 Observation (tracheotomy, and waiting for involution)
 medical management
 endoscopic techniques (laser, microdebrider, steroid injection)
 open excision
 propranolol therapy has dramatically changed the concepts and
management of airway HOI, and as the application of this medication becomes
more widespread
 Smaller lesions that are relatively asymptomatic may be observed or treated
medically with propranolol or oral steroids.
 Symptomatic lesions are often treated with both propranolol and steroids,
 if not endoscopic laser treatment – surgery for larger lesions

69. Propranolol Use in PHACE
Syndrome
 Theoretically, propranolol may increase the risk of stroke in PHACE
syndrome patients by dropping BP and at tenuating flow through absent,
occluded, narrow, or stenotic Vessels
 Cardiac and aortic arch anomalies are also commonly seen in PHACE
syndrome and require echocardiography to assess intracardiac anatomy
and function.
 Propranolol administration in these patients should be managed in close
consultation with cardiology

70.  The potential benefits of treatment must be weighed against the risks.
 The safe use of propranolol in individuals with PHACE has been described
in several small case reports and case series, although no clinical trials have
been conducted to assess the overall safety
 If the potential benefits of propranolol outweigh the risks, the consensus
group recommends use of
1. the lowest possible dose,
2. slow dosage titration upward,
3. Close observation including inpatient hospitalization in high-risk infants,
and 3 times daily dosing to minimize abrupt changes in systolic BP

72. Drug Interactions

73. THE END
thanks for listening
DR.ALI MANSOUR