treatment modalities hemangiomas of infancy

Treatment modalities of infantile

hemangioma

S. Farajzadeh

professor of Dermatology & pediatric Dermatology

Pediatric dermatology department of KMUS

Aims

• Introduction

• Indication of treatment

• Therapeutic modalities

Definition of a infantile hemangioms

(IHs)

• A benign developmental vascular tumor

• Most common vascular tumor of infancy

Phases of IHs

• precursor

• Proliferation

• Stabilization

• Involution

Hemangioma types

• Superficial

• Deep

• Mixed

Superficial hemangioma

vivid red, sharply circumscribed plaques or nodules

Deep

skin‐coloured or bluish purple, less well circumscribed

Mixed haemangiomas

combine the features

of both superficial & deep tumours

Diagnosis

• In most instances: history & physical exam

• Imaging techniques:

- Color Doppler ultrasonography

- MRI

- CT

• Skin biopsy: rare instances

*Zheng JW, et al. practical guide to treatment of infantile

hemangiomas of the head and neck Int J Clin Exp Med 2013

Treatment vs observation

• 20-30% need medical attention

• The rest needs close observation

Close observation

(Active nonintervention)

- Regular visits with reassurance

- Serial photography, measurement

- More observation during active growth phase

Consider Treatment

• Worrisome Hemangiomas

Worrisome Hemangiomas

• Scarring and disfigurement

• Complications

• Association with syndromes

• Functional problems

* Wedgeworth E, et al. Propranolol in the treatment of infantile

haemangioma. British Journal of Dermatology. 2016

I. Scarring & disfigurement

-Large facial, central of face

-Rapid growth (10-20% increase in 2-4 wks)

Scalp lesion

Lip hemangioma esp when cross vermillion border

Nasal tip

Auricular

Forehead hemangioma

Segmental hemangioma

Genital & flexural hemangioma

Pedunculated lesions

II. Syndromatic hemangiomas

Large facial segmental hemangioma

PHACES

Hallmark of PHACEs syndrome

• Large (> 5 cm) Segmental Hemangioma

• Usually on face

• Other site:

• Neck, upper trunk, trunk & proximal upper ext

PHACEs(Harper 2020)

• Posterior fossa malformations

• Haemangioma (usually Facial)

• Arterial anomalies

• Coarctation of the aorta &

cardiac defects

• Eye abnormalities

• Sternal defects

Work up for PHACEs

• MRI/MRA imaging of the brain & neck & aortic arch

• Periodic developmental & neurological assessments

• Cardiac evaluation with echocardiogram

• Ophthalmological evaluation

* Harper 2020

Work up for PHACEs (cont)

• Endocrine abn.: thyroid, pituatory abn (↓GH)

• Hearing screening & early dental examination

• Airway hemangioma (esp. mandible & neck lesion)

• * Harper 2020

Lower body hemangioma

PELVIS, SACRAL, LUMBAR syndrome

Lower body haemangiomas & structural malformations

• Site: lumbosacral spine or perianal extending to gluteal

cleft, segmental haemangioma of the lower extremity

• Work up for structural malformations

• MRI spinal cord & sonography urinary tract

* Harper 2020

III. Complications

Local complication

Ulceration, bleeding, infection

1. Airway hemangioma

2. External compression

✺Air way obstruction✺

Beard area & central neck

H. associated with airway hemangioma

Large parotid hemangioma

External compression

Systemic complication

Disseminated neonatal hemangiomatosis

multiple hemangiomas => 5

Visceral involvement

Kasabatch merrit syndrome

Hepatic hemangioma

Focal, multifocal, diffuse

VI. Functional problem

Periorbital and retro bulbar

Upper medial lid

Others

• Ext. auditory canal: speech development abn:

• perioral, air way: feeding difficulty

• Calvarium, orbit, mandible: deformation of bone

• Compression of vital structures

• Breast in girl

• Darrow D, et al. Diagnosis and Management of Infantile Hemangioma.

PEDIATRICS. 2015.

Type of therapy

Medical

Topical

Systemic

Combination

Non medical

Laser

Surgery

Embolization

Systemic treatments

Systemic treatment modalities*Chen T. S. Infantile Hemangiomas: An Update on Pathogenesis

and Therapy. PEDIATRICS. 2013

𝜷-Adrenergic Blockers

Propranolol

Atenolol

Nadolol

Other treatments

Corticosteroid

Interferone alfa

Vincristine, sirulimus

𝜷-Adrenergic Blockers

Propranolol

non selective betablocker

• First line therapy

• Darrow D,et al. Diagnosis & Management of Infantile Hemangioma.

PEDIATRICS. 2015

• *Prasad et al. Individualized dosing of oral propranolol for treatment of infantile hemangioma The Pan African Medical Journal. 2019

Indication of propranolol

• General indication

• Prior to surgery for residual hemangioma: for a few

months, for a better cosmetic result

• After growth phase

Pretreatment assessment

• HX & PE with special attention to cardiopulmonary

systems, maternal Hx of connective tissue dis

• Cardiologist consult

• Lab tests: ±

*Manish K Shah Use of Propranolol in Infantile Hemangioma. Indian

Journal of Drugs in DermatType equation here.ology 2017

Prepropranolol work up in pts at risk for

PHACEs

• Cardiac ultrasound or MRI to rule out severe aortic

coarctation (a contraindication for propranolol)

• Baseline head & neck MRI with angiography to R/O brain

involvement → acute ischemic attack

• In urgent condition: p. initiated at a lower dose, slowly

titrated up to a max dose of 1 mg/kg/day


Journal of Drugs in Dermatology 2017

Contraindication

• Cardiac abnormalities (some)

• Bronchial asthma

• Hypersensitivity to propranolol

• Preterm infants with corrected age <5 wk (postnatal age

in wks minus number of wks preterm)

*infantile hemangioms: management-Up to Date. 2017

Relative contraindication

• HX of anaphylaxis that require epinephrine: risk-benefit

ratio considered

• Use with caution in PHACEs: since potentially

hypoperfusion of the brain is a small possibility

SPECIAL ATTENTION

• Low birth weight: careful monitoring of their vital signs

• Subglottic IHs may resistant to propranolol:

combination with steroids & occasionally surgery may be

required for worsening stridor

Side effects

• Excellent safety profile

• Most common: sleep disturbance, cold ext, acrocyanosis,

diarrhea

* Infantile hemangiomas: Management – Up To Date.2017

Side effects (con)

• Cardiac effects: bradycardia & hypotension

asymptomatic & do not require intervention

• Less common: hypoglycaemia (seizures), resp infection,

bronchospasm, AV block, H. worse, hypokalemia

Hypoglycemia effects

• Sweating: most reliable early sign of hypoglycemia (only

sign that is not blocked by a beta-blocker)

• Routine screening of serum glucose: not indicated as

hypoglycemic events is variable & unpredictible



Practical tips for the use of propranolol

• Administer P only after feeds

• Frequent feeding

• Administer night dose P at least 3 hrs before sleep

Practical tips for the use of propranolol

• The baby should not go without feed for >6 h

• If the baby refuses feeds, skip the P dose

• Administer the exact dose prescribed by doctor

practical tips for the use of propranolol

• Doses should be at least 6 h apart

• If baby spits out a dose or there is uncertainty of how

much medicine went in, wait for next dose

practical tips for the use of propranolol

• If you miss one dose, do not increase next dose

• If the child is sick (diarrhea, vomiting) or not eating

adequately or bronchiolitis stop it temporarily



Indication of hospitalization for initiation

of oral propranolol

• Infants ≤5 (8) weeks of age

• Preterm infants with corrected age ≥5 weeks (postnatal

age in weeks minus number of weeks preterm)

• Infants with inadequate social support

Indication of hospitalization for initiation

of oral propranolol

• Infant with cardiopulmonary risk factor, airway H.

• Infant with conditions affecting blood glucose



Dosage

• Initiating at a dose of 0.25 to 0.5 mg/kg/day

• Twice increment every week

• Target dose of 2 to 3 mg/kg per day (1 in PHACES)

• 2 to 3 divided doses

*Shah S. Rebound Growth of Infantile Hemangiomas After Propranolol

Therapy. Pediatriscs. 2017

Duration of treatment

• At least 6 to 12 months

• At least until age 12 months

• Maybe longer



Should propranolol be tapered off or can

it be abruptly stopped?

• Reduced gradually over of 2 wks to prevent:

- cardiac complications

- rebound growth


Journal of Drugs in Dermatology. 2017

Rebound Growth After Propranolol Therapy

• Rebound growth: 25%

• Predictive factors for rebound growth:

- age of discount., female, deep IH component, segmental

• Pts with these factors: prolonged course

*Shah S. Rebound Growth of Infantile Hemangiomas After Propranolol

Therapy. Pediatriscs. 2017

* Shah M K Use of Propranolol in Infantile Hemangioma. Indian

Journal of Drugs in Dermatology. 2017

•

Response to propranolol

• IH typically becomes softer & color lighter within 48 h

• IH growth stops within 24 h to 2 wks at the most

Propronalol resistance

• Proliferative phase: continued growth after 2 wks*

• Postproliferative: no involution after >4 wks*

*when propranolol reached dose >2 mg/kg/day

• Most of propranolol-resistant IHs: subglottic

Why other beta blockers?

• Important side effects of propranolol:

- hypoglycemia & bronchospasm: due to β2-AR blockade

- probable effects on the developing CNS specifically

learning & memory: due to being non hydrophilic

*Mahon C, et al. Oral propranolol for infantile haemangioma may be associated

with transient gross motor delay. Br J Dermatol 2018;178:1443–4.

*Ji. Y. Oral atenolol therapy for proliferating infantile hemangioma. A prospective

study. Medicine (Baltimore). 2016; 95(24): e3908.

Atenolol & nadolol

• Atenolol & nadolol are hydrophilic & do not cross blood

brain barrier; theoretically ↓ risk of CNS adverse effects

• Atenolol selective β1 blocker: good choice if resp side

effects are of concern

• Nadolol: non selective beta blocker

A New Successful Combination Therapy with

Atenolol and Prednisolone for Kasabach-

Merritt Syndrome

• S. Farajzadeh, et al. Iranian Journal of Dermatology, Vol

20, Issue 82, 2017, 20 Page(s) 127-130

Indication of other oral beta blockers in IHs

• In the case of propranolol adverse effects like - sleep

disturbances ( if reduction in dose or giving few hours

before sleep dose not work)

• Bronchospasm

*Atenolol as an alternative to propranolol for management of sleep disturbances in treatment of infantile hemangiomas. Ped Dermatol. 2019

*Chamlin SL. Atenolol Treatment for Infantile Haemangioma. Dermatology. Journal Scan. 2017

Other systemic therapies

• Corticosteroids with or without beta blockers

• Interferone alfa

• Sirulimus

• Vincristine

*Chen T. S. Infantile Hemangiomas: An Update on Pathogenesis

and Therapy. PEDIATRICS. 2013

Topical treatment

Indication of topical therapy

• Small superficial proliferating H. without aggressive growth or

threat of functional impairment esp:

- face & other cosmetically concern area & anogenital

• Parent desire

• ↓ need to systemic therapy

Indication of topical therapy

(cont)

• When systemic therapy is contraindicated

• Small ulcerated IHs

• Preventing rebound growth in children who are being tapered

off oral propranolol

Topical agents

Beta blockers

Propranolol

Timolol

others

Topical & intralesional steroids

Sirulimus (rapamycin)

Topical Timolol

• Caution: ulceration > 3 cm, mucosal, large lesions

• Parents should be advised to contact their physician if

rapid growth occurs despite treat

• Dose: 1 drop 2-3 times/day

*Püttgenn K. Topical Timolol Maleate Treatment of Infantile Hemangiomas.

Pediatrics. 2016, 138 (3) e20160355.

*Boos MD, Castelo-Soccio L. Experience with topical timolol maleate for

treatment of ulcerated infantile hemanngioma (IH). AAD. 2016; 74: 567.

Topical propranolol for IHs

• No systemic adverse effects

• Low minor local reactions

*Price A. J Eur Acad Dermatol Venereol. 2018;32(12):2083-2089. Topical propranolol for infantile haemangiomas: a systematic review.

Combination therapy

Sequential therapy

Oral propranolol followed by topical timolol

• Facilitating successful taper at a younger age without an

increase in treatment failures

• Decrease rebound

*Mannschreck DB, et al. Topical timolol as adjunct therapy to shorten oral

propranolol therapy for infantile hemangiomas. Pediatr Dermatol 2019; 36: 283.

Combination therapy

Combined therapy of oral propranolol &

topical timolol for compound IHs

• Method: oral propranolol 2mg/kg/day & timolol

maleate 0.5% gel 3 times/day

*JingGe, JiaweiZheng, LingZhang, WeienYuan, HaiguangZhao. Oral

propranolol combined with topical timolol for compound infantile hemangiomas:

a retrospective study. Scientific Reports | 6:19765 |

PDL

• Ulcerated lesions not responded to topical or systemic therapy

• Residual telangiectasias & redness

• Early superficial IHs, esp ulcerated or near mucous membrane

*Darrow D. Diagnosis & Management of Infantile Hemangioma. pediatrics 2015

Cryotherapy

• Especially for IH with a diameter of up to 15 mm and a

depth of up to 3 mm

Surgical excision

• Residual skin changes due to involuted hemangoma

• IHs no longer involuting after preschool age

• Pedunculated IHs

* Infantile hemangiomas: Management – Up To Date.2017

Surgical excision (cont)

• Slowly involuting lesion in cosmetically concerning area

• Persistent bleeding or ulcer if lesion can be readily excised

• Haemangiomas of eyelid that do not respond to medical

management

Embolization

• Life‐threatening haemangiomas that have not responded

to medical management including:

• Hepatic lesions causing severe congestive heart failure

• Rare cases of severe bleeding

Approaching school age

• Reconsider surgical or laser treatment of haemangioma

or residual skin changes

• Surgical concern:

- risks of surgery

- resulted surgical scar

- potential for further involution

- child’s concern about the haemangioma

Conclusion

Individualized treatment based upon:

• Size, morphology, location

• Presence/possibility of complication, scar, disfig

• Age of the patient

• Rate of growth or involution at time of evaluation

• Potential risks of treat weighed against benefits

*Léauté-Labrèze C, et al. Infantile haemangioma. Lancet 2017

treatment modalities hemangiomas of infancy

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