Treatment Options
Decide whether treatment intervention is indicated or if initial observation is reasonable r3
- Most infantile hemangiomas follow benign course without need for therapeutic intervention; approximately 12% of lesions are complex, requiring referral for specialist evaluation r8
- Indications for intervention r3
- Emergency treatment of potentially life-threatening complications (eg, obstructing airway lesions, liver lesions associated with high-output heart failure and severe hypothyroidism)
- Urgent treatment of existing or imminent functional impairment, pain, or bleeding (eg, due to ulceration, ocular complications, impaired feeding from perioral lesions, or reduced mobility)
- Elective treatment to reduce likelihood of long-term or permanent disfigurement (eg, scarring from severe ulceration; certain anatomic areas including eyelid, nasal tip, lip, breast, and genitalia)
- Evaluation to identify associated structural anomalies (eg, spinal malformations associated with lumbosacral lesions, anomalies related to PHACE syndrome)
Therapeutic interventions are individualized; appropriate therapy and timing of intervention depends on various factors: r3
- Age of patient
- Location, size, and growth phase of lesion(s)
- Degree of skin involvement
- Intervention urgency and complication severity
- Potential for adverse psychosocial consequences
- Physician experience
- Initiate systemic therapy in consultation with a clinician with expertise in managing infants with hemangioma (eg, pediatric dermatologist) r2
- Multidisciplinary team composed of experts in treating significantly complicated hemangiomas may be key to obtaining optimal results in complex cases r5
- Parental preference (especially in elective cases)
- If decision is made to treat, outcomes are improved r10
- If treatment is initiated within proliferation phase
- With earlier treatment r25
Treatment modalities include pharmacologic, laser, and surgical options r3
- Pharmacologic treatment
- Systemic therapy is usually indicated for patients with lesions that are: r3
- Large or medically complex
- At high risk for functional impairment or disfigurement
- Refractory to other initial therapies
- β-Adrenergic blockers are typically first line medical therapy r1r3
- Systemic propranolol is the most effective and is associated with the fewest treatment-related complications r1r10r26r27
- Effective in reducing size and color intensity of lesions; treats both deep and superficial components
- Reported overall response rates range from 86% to 98%;r3r1r4early response often occurs within 1 to 3 days of treatmentr9
- Rate of success, as high as 86%, RR 1.6, increases with earlier treatment (before 10 weeks) at higher dose of 3 mg/kg/day r25
- Atenolol and nadolol appear to have similar efficacy as and fewer adverse events than propranolol, but use of these is limited r28r29
- Contraindications to propranolol therapy r3
- Cardiogenic shock
- Heart failure
- Heart block greater than first degree
- Hypotension
- Sinus bradycardia
- Asthma or reactive airway disease
- Known hypersensitivity to the drug
- Caution suggested for patients with PHACE syndrome and significant intracranial vascular anomalies r3
- Pretreatment risk assessment r3
- Document complete history and physical examination, with special attention to cardiac and pulmonary systems r3
- Recommendations for extent of pretreatment assessment are evolving and vary between clinicians r3
- Some clinicians obtain ECG and/or cardiologist consult before starting propranolol
- Of uncertain value in patients with unremarkable history or examination
- Relative risks that require further evaluation (eg, ECG, cardiologist consultation) before propranolol initiation include: r2
- Heart rate below reference range for age
- Family history of congenital heart conditions or arrhythmias (eg, heart block, long QT syndrome, sudden death)
- Maternal history of connective tissue disease
- History of or auscultation of an arrhythmia
- PHACE syndrome diagnosis r4
- Initiation of treatment
- Recommendations for optimal setting may vary between clinicians
- Inpatient initiation of treatment is suggested for patients who: r3
- Are aged 8 weeks or younger
- Are preterm infants younger than 48 weeks of postconceptional age
- Have inadequate social support
- Have significant comorbidity (eg, cardiac or pulmonary risk factors)
- Outpatient clinic treatment recommendations (for infants older than 8 weeks)
- Assess heart rate and blood pressure at 1 and 2 hours after first dose and with any new dose increase of more than 0.5 mg/kg/day r3
- Adverse effects r3
- Serious adverse effects are rare
- Bradycardia and hypotension (typically asymptomatic)
- Bronchospasm
- Hypoglycemia/seizures
- Reduce risk of hypoglycemia by giving medication after feeding, avoiding prolonged intervals between feedings, and holding doses when oral intake is decreased (eg, illness, vomiting, fasting) r3r10
- Common adverse effects include sleep disturbancesr30r31, acrocyanosis, diarrhea, and bronchial hyperreactivity
- Duration of treatment r3
- Varies with age of initiation and clinical response
- Discontinue medication by gradual tapering over 1 to 3 weeks to prevent rebound sinus tachycardia
- Rebound growth of hemangioma
- Observed in 6% to 25% of cases (notably in those with long proliferative phase and large subcutaneous component)
- Highest risk of rebound growth occurs in patients in whom treatment was discontinued before 12 months r32
- Consider tapering propranolol over weeks to months
- May require reinitiation of therapy for variable periods
- Topical β-adrenergic blockers
- Useful when treatment is desired, but risks are considered too high to justify systemic β-blocker therapy
- Topical propranolol and topical timolol were as effective as oral propranolol in treating superficial infantile hemangiomas, and topical timolol was associated with fewer adverse effects r33
- Consider topical timolol for treatment of small, thin, uncomplicated, superficial lesions r3r10
- Use of topical timolol after oral propranolol may allow reduced duration of systemic β-blocker therapy and minimize the potential adverse effects r34
- Available in extended-release gel forming solution with less systemic absorption than regular solution
- Concerns remain regarding bioavailability in neonates and infants, especially with large or ulcerated lesions and those involving mucous membranes
- Consider topical propranolol as an alternative for patients who experience adverse effects from oral propranolol administration r35
- Topical propranolol is not commercially available in the United States r4r36
- Propranolol 0.5% and 1% ointment have been used in studies r33r35
- Intralesional propranolol administration is reported, but efficacy data are limited r4
- Corticosteroids
- Alternative therapy if propranolol cannot be used or is ineffective r3
- Systemic (oral) corticosteroids r10
- Overall response rate (43%-84%) is inferior to propranolol, and rate of relapse is higher with corticosteroids r3r4r37
- More adverse effects are associated with oral administration of corticosteroids (23%) than with propranolol (9.6%) r4
- Potential adverse effects include hypothalamic-pituitary-adrenal axis suppression, growth deceleration, hypertension, gastric irritation, mild behavioral changes, cushingoid facies, and immunosuppression r3
- Periodic monitoring of infants with attention to growth and blood pressure is suggested r3
- Duration of therapy r3
- Varies with clinical response, patient age, and growth phase of lesion
- Intralesional corticosteroids r3
- Consider intralesional injection of triamcinolone and/or betamethasone to treat focal, bulky lesions during proliferation phase or in certain critical anatomic locations (eg, lip) r10
- Often requires multiple injections
- Complications include local hypopigmentation, fat and/or dermal atrophy, and systemic effects at large doses
- Use in lesions of upper eyelid may cause retinal embolization
- Topical corticosteroids
- Consider use of high-potency topical formulations for small (less than 5 cm), thin, superficial lesions
- Other medical therapies r3
- Typically reserved for recalcitrant lesions owing to limited safety profiles
- Sirolimus has potent antiangiogenic activity but is not well studied for infantile hemangiomas r22
- Vincristine and interferon-alfa are rarely used owing to adverse effects r22
- Laser treatment
- Pulsed dye laser therapy provides selective photothermolysis of vascular tumor while sparing normal surrounding tissue r4
- Primary use is to treat residual skin changes (eg, telangiectasia and refractory ulceration) after involution r22
- Other uses may include: r3
- As a component in multimodal therapy
- To treat early, nonproliferating superficial lesions and areas of critical skin (eg, nasal tip, facial lesion)
- Controversial; use of laser on early proliferating and superficial lesions may lead to ulceration r3
- Surgical treatment
- Surgical resection may be necessary for up to 40% of patients requiring treatment overall r4
- Suggested criteria for intervention are somewhat vague owing to difficulty in predicting some final tumor manifestations r4
- Base timing of surgery on patient age, location and degree of deformity, and stage of tumor growth r3
- Elective resection during proliferative phase is not usually indicated r3
- Vascularity of tumor can place infant at greater risk of anesthetic morbidity, blood loss, and iatrogenic injury; cosmetic result is usually superior with fewer interventions after growth of lesion has stopped r3
- Early surgical intervention may be indicated for certain patients with significant, recalcitrant complications or functional impairment
- Preferred timing for repair for most lesions requiring surgical intervention is during the involution stage between the ages of 3 and 4 years r5
Treatment is often multimodal r4
- Combining various treatment methods to optimize different components of individual lesions is common
- For example, a common treatment approach for compound lesions includes systemic propranolol to address deep component and laser therapy to treat superficial component; surgery and/or additional laser therapy may be used for any unacceptable, residual cosmetic issues r4
- Aggressive early multimodal therapy is often used for lesions in sensitive anatomic areas prone to significant complications, such as: r5
- Periorbital, tip of nose, and lip lesions
- Airway lesions
- Large segmental or nodular lesions in trauma-prone areas at high risk for ulceration
Management for lesions in specific anatomic locations
- Periorbital
- Early consultation with ophthalmologist is essential; extent and depth of periorbital lesions intruding into the orbit is often unappreciated on routine physical examination r3
- Manage aggressively with multimodal therapy; early systemic pharmacotherapy is imperative for most lesions, even when surgical therapy is unavoidable r5
- Tip of nose
- Tissue in this area is difficult to excise without considerable cosmetic consequence; lesions are prone to injure underlying cartilage and may obstruct nasal airway
- Aggressive multimodal therapy with early initiation of systemic pharmacotherapy is recommended to avoid poor outcome r3
- Lip
- Distortion of lip contour is common and difficult to reconstruct; lesions are highly prone to complications such as ulceration, scarring, and disfigurement
- Aggressive multimodal therapy with early initiation of systemic pharmacotherapy is recommended to avoid poor outcome r3
- Perineal
- Early pharmacotherapy may be appropriate given high risk for ulceration and complications associated with ulceration in this region (eg, infection) r3
- Those obstructing auditory canal
- Manage aggressively with trial of systemic pharmacotherapy r5
- Early multimodal approach may be necessary with laser therapy and surgical resection r5
- Those prone to ulceration
- Lesions over pressure points (eg, back), near mucosa (eg, lip, perineum), and intertriginous areas are prone to ulceration and require meticulous local care r14
- Consider early pharmacotherapy and/or multimodal approach to lesions at high risk for ulceration
- Hepatic
- Management is based on type of lesion (ie, focal, multifocal, or diffuse), presence and degree of vascular shunting, and presence of complications (eg, high-output heart failure, abdominal compartment syndrome, consumptive hypothyroidism) r19
- Suggested algorithm for management of infantile hepatic hemangioma is available; multimodal therapy is often used, beginning with pharmacotherapy r19
- Additional specific surgical management may include embolization, hepatic artery ligation, resection, and even transplant for patients with failure of medical therapy or recalcitrant heart failure r5
- Associated consumptive hypothyroidism requires thyroid hormone replacement, sometimes intravenously, until hepatic hemangioma has involuted
- Airway
- Manage life-threatening lesions with immediate surgical resection; temporary tracheostomy may be required r5
- Manage lesions causing significant airway obstruction with carbon dioxide laser treatment r5
- For lesions that are not immediately life-threatening, initial management is systemic pharmacotherapy r5
Drug therapy
- β-Adrenergic blockers
- Propranolol c189
- Outpatient initiation
- Propranolol Hydrochloride Oral solution [Hemangioma]; Infants: 0.5 to 1 mg/kg/day PO in 2 to 3 divided doses, initially. May increase the dose by 0.5 mg/kg/day every 3 to 7 days based on clinical response and tolerability. Target dose: 2 to 3 mg/kg/day. Continue treatment for at least 6 months and up to 12 months of age.
- Inpatient initiation
- Propranolol Hydrochloride Oral solution [Hemangioma]; Neonates†: 0.33 mg/kg/dose PO every 8 hours, initially. May increase the dose to 0.66 mg/kg/dose PO every 8 hours based on clinical response and tolerability. Alternatively, 0.25 mg/kg/dose PO twice daily, initially. May increase the dose by 0.5 mg/kg/dose every 24 hours based on clinical response and tolerability. Target dose: 2 to 3 mg/kg/day. Continue treatment for at least 6 months and up to 12 months of age.
- Propranolol Hydrochloride Oral solution [Hemangioma]; Infants: 0.33 mg/kg/dose PO every 8 hours, initially. May increase the dose to 0.66 mg/kg/dose PO every 8 hours based on clinical response and tolerability. Alternatively, 0.25 mg/kg/dose PO twice daily, initially. May increase the dose by 0.5 mg/kg/dose every 24 hours based on clinical response and tolerability. Target dose: 2 to 3 mg/kg/day. Continue treatment for at least 6 months and up to 12 months of age.
- Some experts recommend extending treatment until patient is 15 months of age r10r38
- Timolol 0.5% gel forming solution c190
- Timolol Maleate Ophthalmic gel forming solution; Neonates: 1 drop topically to the lesion twice daily.
- Timolol Maleate Ophthalmic gel forming solution; Infants: 1 drop topically to the lesion twice daily.
- Corticosteroids
- Prednisolone c191
- Prednisolone Oral solution; Neonates: 2 to 3 mg/kg/day PO for 4 to 12 weeks, then gradually taper dose to complete therapy by 9 to 12 months of age.
- Prednisolone Oral solution; Infants: 2 to 3 mg/kg/day PO for 4 to 12 weeks, then gradually taper dose to complete therapy by 9 to 12 months of age.
- Some experts aim to discontinue by age 11 months in effort to avoid interference with 12-month immunization schedule r3
- Triamcinolone c192
- Triamcinolone Acetonide Suspension for injection; Infants: 1 to 5 mg/kg/dose (Max: 60 mg/dose) intralesionally once monthly for 3 to 9 months. Alternatively, 40 to 80 mg intralesionally as a single dose in combination with betamethasone. May repeat dose once after at least 4 weeks if needed.
- Betamethasone
- Betamethasone Acetate, Betamethasone Sodium Phosphate Suspension for injection; Infants: 6 to 12 mg intralesionally as a single dose in combination with triamcinolone. May repeat dose once after at least 4 weeks if needed.
- Clobetasol
- Clobetasol Propionate Topical cream; Infants: Apply a thin layer topically to the lesion once to twice daily for 4 to 16 weeks for superficial hemangioma and 2 to 22 weeks for mixed hemangioma. Alternatively, apply a thin layer topically to the lesion twice daily for 2 weeks, followed by a 1-week drug-free interval for 3 cycles.
Nondrug and supportive care
Active observation c193
- Majority of lesions do not require medical or surgical treatment r4
- Small, focal, nonfacial lesions without ulceration are safely managed with active observation alone r5
- Allowing lesions to follow natural course of involution often results in the best cosmetic outcome r5
- Manage with parental reassurance, close follow-up with photographic documentation, and routine clinical monitoring for changes requiring treatment r4r5
Wound care of ulcerated infantile hemangiomas c194
- Barrier dressings can prevent drying, control pain, reduce chance of trauma and bleeding, and reduce risk of bacterial colonization or infection r3
- Dressing choices include hydrocolloid dressings, silver impregnated dressings, and petroleum gauze
- Topical agents may include barrier creams or ointments (eg, petroleum, zinc oxide) and antibiotics (eg, mupirocin, bacitracin ointment)
Procedures
General explanation- Emission of short pulses of light between 585 and 595 nm are absorbed by oxyhemoglobin, resulting in destruction of vascular tumor component while sparing unaffected surrounding tissue r4
- Standard pulsed dye laser is capable of only 1.2 mm depth penetration r4
- Requires a series of treatment at 2- to 6-week intervals until desired response is achieved r9
- Larger lesions or lesions in sensitive anatomic areas often require general anesthesia r3
Indication- Removal of telangiectasias, treatment of residual flat components of lesions, or smoothing contour irregularities after involution r3r14
- Treatment of ulceration refractory to other therapies r3r4
- Treatment of early, nonproliferating superficial lesions or superficial component of compound lesion r3
- Controversial; use of laser on proliferating and superficial lesions may lead to ulceration
- Treatment of critical skin regions (eg, nasal tip, face) in effort to preserve overlying skin r3
Complications- Temporary local swelling r4
- Hyper- or hypopigmentation r4
- Scarring, ulceration, or hemorrhage are rare r4
Interpretation of results- When applied to proliferating lesion, results in reduced redness and limitation in overall growth (size) r4
- Excellent or good results are expected in up to 86% of superficial lesions r4
- Deep components of mixed hemangiomas are not amenable to treatment r4
- When applied to ulcerating lesion, results in improved healing and diminished pain r4
General explanation- Some lesions are amenable to single resection; lesions involving lips, glabella, cheek, and scalp often require a staged approach r5
Indication- Limited to the following during infancy (proliferative phase): r3
- Failure of or contraindication to pharmacotherapy
- Focal involvement in an area anatomically favorable for resection
- High likelihood that resection ultimately will be needed and scar will be the same, regardless of timing
- During involution, may be indicated for: r3
- Reconstruction of damaged structures
- Resection of scarring or excess skin
- Excision of residual fibrofatty tissue
Comorbidities
- PHACE syndrome c206
- Treat in close consultation with cardiologist and/or neurologist owing to prevalence of underlying vascular malformations and potential risk for ischemic stroke with use of propranolol r16
- Propranolol use is controversial r16
- May be contraindicated in the presence of severe cerebrovascular and/or cardiovascular arterial abnormalities r3
- Alterations in propranolol treatment, when indicated, are recommended and may include:
- Lowest possible dosing r4
- Slow up-titration of dosing on inpatient unit r4
- Strict 3-times-daily dosing with meals to minimize blood pressure effects r4