Guidelines of Care for Hemangiomas in Infancy

This report reflects the best data available at the time the report was prepared, but caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set forth in this report.

Guidelines of care for hemangiomas of infancy

Task Force: Ilona J. Frieden, MD, Chairman, Lawrence E Eichenfield, MD, Nancy B.

Esterly, MD, Roy Geronemus, MD, Susan B. Mallory, MD, and the Guidelines/Outcomes

Committee*

This report reflects the best data available at the time the report was prepared, but caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set forth in this report.

Guidelines of care for hemangiomas of infancy

Task Force: Ilona J. Frieden, MD, Chairman, Lawrence E Eichenfield, MD, Nancy B.

Esterly, MD, Roy Geronemus, MD, Susan B. Mallory, MD, and the Guidelines/Outcomes

Committee*

1. Introduction

The American Academy of Dermatology's Guidelines/Outcomes Committee is developing guidelines of care for our profession. The development of guidelines will promote the continued delivery of quality care and assist those outside our profession in understanding the complexities and scope of care provided by dermatologists. For the benefit of members of the American Academy of Dermatology who practice outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U.S. Food and Drug Administration.

11. Definition

Hemangiomas are benign tumors of the vascular endothelium. Hemangiomas of infancy are the most common type of hemangiomas, characterized by a unique natural history of growth in early infancy, followed by slow involution over the next several years. The guidelines herein refer specifically to hemangiomas of infancy, rather than those acquired later in life.

Hemangiomas may be present at the time of birth as so-called precursor lesions in approximately half of the cases. Rarely they are fully formed tumors at birth. In the remainder of cases, lesions become evident after birth, usually within the second and fourth weeks of life.

Several clinical subtypes of hemangiomas are recognized. Superficial (so-called 14 strawberry") hemangiomas are most common, constituting 50% to 60% of tumors. Those with both a superficial and deep component (previously referred to as 44capillary and cavernous or mixed") constitute approximately 25% to 35% of lesions and contain both a red dermal tumor and an underlying blue or skin-colored subcutaneous mass. Deep hemangiomas (formerly called "cavernous hemangiomas") constitute approximately 15% of hemangiomas and are usually bluish soft-tissue swellings without an overlying superficial component. Despite differences in clinical appearance, all are true hemangiomas with the same fundamental characteristics. Multiple lesions are present in 15% to 30% of infants.

A distinct subset of hemangiomas consists of multiple small lesions varying in size from a few millimeters to I to 2 cm. This form of hemangioma (so-called "multiple neonatal hemangiomatosis") has a higher risk of visceral involvement, particularly in the liver and gastrointestinal tract, but the prognosis for the skin lesions is usually good, as they often involute by 2 years of age.

111. Rationale A. Scope Hemangiomas are the most common benign tumor of infancy, present in approximately I % to 2% of newborns.

The incidence by I year of age has been

estimated to be as high as 10% to 12%.

Female infants are more frequently

affected, with a sex ratio from 5: 1 to 2: 1.

Premature infants weighing less than

1500 gm are also more commonly affect

ed. Fifty percent of lesions occur on the

head and neck.

Issue

After a period of growth, virtually all

hemangiomas of infancy undergo sponta

neous involution. Some resolve without a

trace, but a significant number leave skin

abnormalities including residual telan

giectases, atrophy, hypopigmentation, and

anetoderma-like scars. This unique natur

al history must be strongly considered in

any decision regarding treatment.

Hemangiomas are extremely heteroge

neous clinically, ranging in size from a

few millimeters to lesions involving large

areas of the body. Location can have a    IV. Diagnostic criteria

major effect on the risk of complications,            A. Clinical

results after involution, and psychosocial

impact. The ultimate size, rate of involu

tion, and results of spontaneous involu

tion are difficult to predict, particularly

early in infancy, even for the most expe

rienced of clinicians. Whatever the man

agement approach, periodic reevaluation,

particularly during the growth phase and

the late involutional phase, is imperative.

Several noncontroversial indications for

treatment include hemangiomas affecting

vision, laryngeal involvement, nasal and

auditory canal obstruction, Kasabach

Merritt syndrome, hepatic heman

giomatosis, cardiac failure, and skin

ulceration. In addition to these indica

tions, strong consideration should be

given to treating those hemangiomas that

are more likely to leave permanent dis

figurement or long-term adverse psycho

logic consequences; these include

hemangiomas of the nose, lips, ear, and

very large hemangiomas with a promi

nent dermal component with or without a

subcutaneous component.

The choice of which treatment (if any) to

use depends on a careful assessment of

journal the American Academy of Dermatology

      October 1997

the factors mentioned above along with a comparison of the risks and benefits of the treatment(s) being contemplated. When surgical excision and radiotherapy were the only options available for treatment, most hemangiomas were best left untreated because the results of treatment were usually worse than those from spontaneous involution. This historical lesson is always worth remembering when contemplating both old and new surgical or medical therapies. As new modalities emerge, an ongoing reassessment of comparative risks and benefits will be a necessary part of the decisionmaking process. A multidisciplinary approach to the management of hemangiomas that includes dermatologists, other surgical and medical specialties, as well as social and psychologic support services may be helpful, particularly in more severe cases.

In 95% of cases diagnosis can be established on the basis of history and physical examination alone. The diagnosis is confirmed by the presence of one or more typical- appearing vascular tumors in conjunction with a history of a lesion at birth or developing shortly thereafter, and with characteristic proliferation in early infancy.

1. History

a) General medical history as indicated

b) Maternal pregnancy history

c) Prematurity, neonatal complications

d) Precursor lesions such as pale macules resembling nevus anemicus, threadlike telangiectases, area of erythema resembling a port-wine stain, skin ulceration, or bruiselike area

e) Growth of lesion(s) out of proportion to child's growth, rate of growth, and/or whether growth appears to be continuing

Ulceration or bleeding lesion(s) Previous treatment(s)

Journal of the American Academy of Dermatology Volume 37, Number 4

h) Sudden growth, tenseness, tenderness, and purpuric appearance in a large hemangioma (to suggest the possibility of Kas ab ach- Merritt syndrome)

i)    Respiratory difficulty or stridor

Hemangiomas in the mandibular area increase the risk of concomitant airway hemangioma(s).

2. Physical examination

a) Cutaneous and mucosal examination for evidence of other heman

giomas

b) Measurement of hemangioma including superficial and deep components

c) Palpation of liver may be helpful in assessing presence of hepatic hemangiomas (usually seen with multiple cutaneous lesions) or evidence of congestive heart failure (occasionally seen with very large hemangiomas)

d) Ophthalmologic examination if the periorbital area is affected

3. Differential diagnosis

Several cutaneous neoplasms and anomalies may resemble hemangiomas. These include but are not limited to the following:

a) Tufted angioma

b) Port-wine stains

c) Venous malformations

d) Lymphatic malformations

e) Arteriovenous malformations

f)    Kaposiform hemangioendothe

      lioma

g) Adrenal carcinoma

h) Pyogenic granuloma

i) Nasal glioma

j) Myofibromatosis

1)

k) Spindle and epithelioid (Spitz) nevus Dermoid cysts 4. Other Photography can be an extremely important adjunct in following growth and involution of lesions. B. Diagnostic tests The diagnosis is usually made on clinical grounds. The following diagnostic tests

Frieden et al. 633

may be useful in clinically atypical cases and as an adjunct to assess for potential complications.

1. Platelet count

For large, rapidly growing, tense, or purpuric vascular tumors to evaluate for Kasabach-Merritt syndrome. The presence of Kas ab ach- Merritt syndrome suggests the possibility of other less common vascular tumors, such as tufted angioma or kaposiform hemangioendotheliorna.

Ultrasound

Helpful for diagnosis of hepatic lesions, some cutaneous lesions, as an adjunct to monitor response to therapy, and to evaluate infants with large facial hemangiomas for possible structural brain abnormalities.

3. Doppler studies to evaluate blood flow 4. Magnetic resonance imaging (MRI) Helpful in differentiating hemangiomas from venous or arteriovenous malformations; may help delineate extent of disease in very large lesions and be useful in evaluating infants with large facial hemangiomas for structural brain abnormalities

Computed tomography

Same uses as MRI, but not as specific as MRI in differentiating hemangiomas from vascular malformations

6. Biopsy (rarely necessary)

Increased risk of bleeding makes this a somewhat risky and unpopular way to diagnose most hemangiomas, but it is occasionally necessary to differentiate atypical cases from other soft-tissue tumors, such as kaposiform hemangioendothelioma (a low-grade sarcoma), myofibromatosis, and rhabdomyosarcoma.

C.    Inappropriate diagnostic tests

      Not applicable

D.    Exceptions

      Not applicable

E.    Evolving diagnostic tests

      Measurement of basic fibroblast growth

      factor may prove to be helpful in differ

      entiating hemangiomas from vascular

2.

5

Journal of the American Academy of Dermatology Volume 37, Number 4

h) Sudden growth, tenseness, tenderness, and purpuric appearance in a large hemangioma (to suggest the possibility of Kas ab ach- Merritt syndrome)

i)    Respiratory difficulty or stridor

Hemangiomas in the mandibular area increase the risk of concomitant airway hemangioma(s).

2. Physical examination

a) Cutaneous and mucosal examination for evidence of other heman

giomas

b) Measurement of hemangioma including superficial and deep components

c) Palpation of liver may be helpful in assessing presence of hepatic hemangiomas (usually seen with multiple cutaneous lesions) or evidence of congestive heart failure (occasionally seen with very large hemangiomas)

d) Ophthalmologic examination if the periorbital area is affected

3. Differential diagnosis

Several cutaneous neoplasms and anomalies may resemble hemangiomas. These include but are not limited to the following:

a) Tufted angioma

b) Port-wine stains

c) Venous malformations

d) Lymphatic malformations

e) Arteriovenous malformations

f)    Kaposiform hemangioendothe

      lioma

g) Adrenal carcinoma

h) Pyogenic granuloma

i) Nasal glioma

j) Myofibromatosis

1)

k) Spindle and epithelioid (Spitz) nevus Dermoid cysts 4. Other Photography can be an extremely important adjunct in following growth and involution of lesions. B. Diagnostic tests The diagnosis is usually made on clinical grounds. The following diagnostic tests

Frieden et al. 633

may be useful in clinically atypical cases and as an adjunct to assess for potential complications.

1. Platelet count

For large, rapidly growing, tense, or purpuric vascular tumors to evaluate for Kasabach-Merritt syndrome. The presence of Kas ab ach- Merritt syndrome suggests the possibility of other less common vascular tumors, such as tufted angioma or kaposiform hemangioendotheliorna.

Ultrasound

Helpful for diagnosis of hepatic lesions, some cutaneous lesions, as an adjunct to monitor response to therapy, and to evaluate infants with large facial hemangiomas for possible structural brain abnormalities.

3. Doppler studies to evaluate blood flow 4. Magnetic resonance imaging (MRI) Helpful in differentiating hemangiomas from venous or arteriovenous malformations; may help delineate extent of disease in very large lesions and be useful in evaluating infants with large facial hemangiomas for structural brain abnormalities

Computed tomography

Same uses as MRI, but not as specific as MRI in differentiating hemangiomas from vascular malformations

6. Biopsy (rarely necessary)

Increased risk of bleeding makes this a somewhat risky and unpopular way to diagnose most hemangiomas, but it is occasionally necessary to differentiate atypical cases from other soft-tissue tumors, such as kaposiform hemangioendothelioma (a low-grade sarcoma), myofibromatosis, and rhabdomyosarcoma.

C.    Inappropriate diagnostic tests

      Not applicable

D.    Exceptions

      Not applicable

E.    Evolving diagnostic tests

      Measurement of basic fibroblast growth

      factor may prove to be helpful in differ

      entiating hemangiomas from vascular

2.

5

634 Frieden et al.

malformations and for following therapeutic response.

V. Recommendations (see 111. B.)

Because of their natural history, hemangiomas present unique treatment issues. Untreated, they involute, but while present a minority cause functional impairment and even more cause psychosocial distress. Once resolved, a significant minority leave residual scarring, fibrofatty tissue, telangiectases, and other skin changes.

The approach to the management of hemangiomas is therefore individualized based on the size of the lesion(s), location, presence of complications, the age of the patient, and rate of growth or involution at the time of evaluation. With these factors in mind, the potential risk(s) of treatment is carefully weighed against the potential benefits. Many hemangiomas need no treatment at all, but if this approach is chosen, the patient should still be periodically reevaluated, especially during the period of growth and less often once growth has ceased and involution begins.

A. Major goals of management

1. Prevent or reverse any life-threatening or function- threatening complications of hemangiomas

2. Prevent permanent disfigurement left by residual skin changes after involution

3. Minimize psychosocial distress from the presence of hemangiomas for both patient and family

4. Avoid aggressive, potentially scarring procedures for treatment of those hemangiomas likely to have an excellent prognosis without therapy

5. Prevent or adequately treat ulcerated hemangiomas to minimize scarring, infection, and pain

B. General indications for treatment

1. Life- and function-threatening hemangiomas (e.g., those causing impairment of vision, Kasabach-Merritt coagulopathy, respiratory compromise caused by airway lesions, congestive heart failure, hepatic involvement)

2. Hemangiomas in certain anatomic locations that often leave permanent

Journal of the American Academy of Dermatology

      October 1997

scars or deformity, especially the nose, lip, ear, and glabellar area

3. Large facial hemangiomas, especially those with a prominent dermal component (more likely to leave permanent scarring)

Smaller hemangiomas in exposed areas, such as the face and hands, may be considered for treatment with modalities unlikely to cause scarring or significant side effects.

Ulceration

6. Pedunculated hemangiomas (likely to leave significant fibrofatty tissue after involution)

C. Choice of treatment modalities may vary

according to a number of factors includ

ing but not limited to the following:

1. Anatomic location

2. Location in skin (i.e., dermal vs subcutaneous vs both)

3. Size and extent of lesion(s)

4. Whether lesion is in growth, plateau, or involution phase

5. Whether functional impairment is present

6. Experience of physician with certain modalities (i.e., laser)

7. Availability of certain modalities (i.e., laser)

8. Level of parental concern

D. Treatment

The listed treatments may be used singly,

in combination with each other, or with a

surgical modality.

1. Low-risk hemangiomas (i.e., small, causing no functional impairment and unlikely to leave permanent disfigurement)

a) Medical

      1) Intralesional corticosteroids

Triamcinolone acetonide 10 to 40 mg/ml

2) Class I topical corticosteroids (sparse data in medical literature regarding this modality)

            3) Pressure occlusion b) Surgical

1) Flash-lamp pumped pulsed dye laser

2) Other lasers and light sources

Journal of the American Academy of Dermatology Volume 37, Number 4

h) Sudden growth, tenseness, tenderness, and purpuric appearance in a large hemangioma (to suggest the possibility of Kas ab ach- Merritt syndrome)

i)    Respiratory difficulty or stridor

Hemangiomas in the mandibular area increase the risk of concomitant airway hemangioma(s).

2. Physical examination

a) Cutaneous and mucosal examination for evidence of other heman

giomas

b) Measurement of hemangioma including superficial and deep components

c) Palpation of liver may be helpful in assessing presence of hepatic hemangiomas (usually seen with multiple cutaneous lesions) or evidence of congestive heart failure (occasionally seen with very large hemangiomas)

d) Ophthalmologic examination if the periorbital area is affected

3. Differential diagnosis

Several cutaneous neoplasms and anomalies may resemble hemangiomas. These include but are not limited to the following:

a) Tufted angioma

b) Port-wine stains

c) Venous malformations

d) Lymphatic malformations

e) Arteriovenous malformations

f)    Kaposiform hemangioendothe

      lioma

g) Adrenal carcinoma

h) Pyogenic granuloma

i) Nasal glioma

j) Myofibromatosis

1)

k) Spindle and epithelioid (Spitz) nevus Dermoid cysts 4. Other Photography can be an extremely important adjunct in following growth and involution of lesions. B. Diagnostic tests The diagnosis is usually made on clinical grounds. The following diagnostic tests

Frieden et al. 633

may be useful in clinically atypical cases and as an adjunct to assess for potential complications.

1. Platelet count

For large, rapidly growing, tense, or purpuric vascular tumors to evaluate for Kasabach-Merritt syndrome. The presence of Kas ab ach- Merritt syndrome suggests the possibility of other less common vascular tumors, such as tufted angioma or kaposiform hemangioendotheliorna.

Ultrasound

Helpful for diagnosis of hepatic lesions, some cutaneous lesions, as an adjunct to monitor response to therapy, and to evaluate infants with large facial hemangiomas for possible structural brain abnormalities.

3. Doppler studies to evaluate blood flow 4. Magnetic resonance imaging (MRI) Helpful in differentiating hemangiomas from venous or arteriovenous malformations; may help delineate extent of disease in very large lesions and be useful in evaluating infants with large facial hemangiomas for structural brain abnormalities

Computed tomography

Same uses as MRI, but not as specific as MRI in differentiating hemangiomas from vascular malformations

6. Biopsy (rarely necessary)

Increased risk of bleeding makes this a somewhat risky and unpopular way to diagnose most hemangiomas, but it is occasionally necessary to differentiate atypical cases from other soft-tissue tumors, such as kaposiform hemangioendothelioma (a low-grade sarcoma), myofibromatosis, and rhabdomyosarcoma.

C.    Inappropriate diagnostic tests

      Not applicable

D.    Exceptions

      Not applicable

E.    Evolving diagnostic tests

      Measurement of basic fibroblast growth

      factor may prove to be helpful in differ

      entiating hemangiomas from vascular

2.

5

634 Frieden et al.

malformations and for following therapeutic response.

V. Recommendations (see 111. B.)

Because of their natural history, hemangiomas present unique treatment issues. Untreated, they involute, but while present a minority cause functional impairment and even more cause psychosocial distress. Once resolved, a significant minority leave residual scarring, fibrofatty tissue, telangiectases, and other skin changes.

The approach to the management of hemangiomas is therefore individualized based on the size of the lesion(s), location, presence of complications, the age of the patient, and rate of growth or involution at the time of evaluation. With these factors in mind, the potential risk(s) of treatment is carefully weighed against the potential benefits. Many hemangiomas need no treatment at all, but if this approach is chosen, the patient should still be periodically reevaluated, especially during the period of growth and less often once growth has ceased and involution begins.

A. Major goals of management

1. Prevent or reverse any life-threatening or function- threatening complications of hemangiomas

2. Prevent permanent disfigurement left by residual skin changes after involution

3. Minimize psychosocial distress from the presence of hemangiomas for both patient and family

4. Avoid aggressive, potentially scarring procedures for treatment of those hemangiomas likely to have an excellent prognosis without therapy

5. Prevent or adequately treat ulcerated hemangiomas to minimize scarring, infection, and pain

B. General indications for treatment

1. Life- and function-threatening hemangiomas (e.g., those causing impairment of vision, Kasabach-Merritt coagulopathy, respiratory compromise caused by airway lesions, congestive heart failure, hepatic involvement)

2. Hemangiomas in certain anatomic locations that often leave permanent

Journal of the American Academy of Dermatology

      October 1997

scars or deformity, especially the nose, lip, ear, and glabellar area

3. Large facial hemangiomas, especially those with a prominent dermal component (more likely to leave permanent scarring)

Smaller hemangiomas in exposed areas, such as the face and hands, may be considered for treatment with modalities unlikely to cause scarring or significant side effects.

Ulceration

6. Pedunculated hemangiomas (likely to leave significant fibrofatty tissue after involution)

C. Choice of treatment modalities may vary

according to a number of factors includ

ing but not limited to the following:

1. Anatomic location

2. Location in skin (i.e., dermal vs subcutaneous vs both)

3. Size and extent of lesion(s)

4. Whether lesion is in growth, plateau, or involution phase

5. Whether functional impairment is present

6. Experience of physician with certain modalities (i.e., laser)

7. Availability of certain modalities (i.e., laser)

8. Level of parental concern

D. Treatment

The listed treatments may be used singly,

in combination with each other, or with a

surgical modality.

1. Low-risk hemangiomas (i.e., small, causing no functional impairment and unlikely to leave permanent disfigurement)

a) Medical

      1) Intralesional corticosteroids

Triamcinolone acetonide 10 to 40 mg/ml

2) Class I topical corticosteroids (sparse data in medical literature regarding this modality)

            3) Pressure occlusion b) Surgical

1) Flash-lamp pumped pulsed dye laser

2) Other lasers and light sources

Journal of the American Academy of Dermatology

Volume 37, Number 4

may be useful in selected cases; however, current lasers other than the flash-lamp pumped pulse dye laser have a greater risk of permanent hypopigmentation and scarring. With the exception of the argon laser, information in the medical literature regarding the use of other lasers for treating hemangiomas is sparse.

3) Cryosurgery

4) Surgical excision (especially of small pedunculated hemangiomas)

2. High-risk lesions (i.e., large, prognostically poor location, likely to leave permanent disfigurement, causing functional impairment, or involving extracutaneous structures)

a) Medical

1) Systemic corticosteroids (indicated mainly during the growth period of hemangiomas)

Prednisone (or equivalent dose of prednisolone) 2 to 4 mg/kg per day in a single morning dose or divided doses in emergent cases

2) Triamcinolone acetonide 10 to 40 mg/ml, sometimes mixed with dexamethasone sodium phosphate 4 mg/ml (eye, other well-localized lesions)

3) Interferon alfa-2a subcutaneous, initial dose I million U/m 2 per day, which is increased to 3 million U/m 2 per day if tolerated (generally reserved for corticosteroid treatment failure)

4) Combined therapy (i.e., pulsed dye laser plus systemic corticosteroids)

b) Surgical

1) Flash-lamp pumped pulsed dye laser

2) Other lasers and light sources may be useful in selected cases; however, current lasers other than the flash-lamp pumped pulse dye laser have a greater

Frieden et al. 635

C)

risk of permanent hypopigmentation and scarring. With the exception of the argon laser, information in the medical literature regarding the use of other lasers for treating hemangiomas is sparse.

3) Early surgical excision (especially nasal, eyelid lesions)

4) Combined therapy (i.e., pulsed dye laser plus systemic corticosteroids or interferon alfa)

5) Cryosurgery

Other

The following may be used only in exceptional cases failing other therapies:

      1) Cyclophosphamide

      2) Embolization

      3) Radiotherapy

d) Evolving therapy

      1) Leuprolide acetate

      2) Ketotifen

      3) Other, new selective lasers

4) Other inhibitors of angiogenesis that are under development

E.    Patient education

      Parent education may include the follow

2.

4

ing:

1. The expected natural history without treatment

A demonstration whenever possible of before and after photographs of both natural involution and the results of the treatment being contemplated

The risks, potential benefits, and alternatives to contemplated therapy

In cases in which the hemangioma is in an exposed area (e.g., face), anticipatory guidance regarding ways in which to handle comments and queries from family members and others

VI.   Supporting evidence

      See Bibliography (Appendix)

VIL   Disclaimer

Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of

Journal of the American Academy of Dermatology

Volume 37, Number 4

Morelli JG, Tan OT, Yohn JJ, et al. Treatment of ulcerated

      hemangiomas in infancy. Arch Pediatr Adolesc Med

      1994; 148:1104-5.

Moroz B. The course of haemangiomas in children. In: Ryan

      TJ, Cherry GIO, editors. Vascular birthmarks: pathogenesis

      and management. Oxford: Oxford Medical Publications;

      1987. p. 55-69.

Mulliken JB. A plea for a biologic approach to hemangiomas

      of infancy. Arch Dermatol 1991;127:243-4.

Mulliken JB, Glowacki J. Hemangiomas and vascular mal

      formations in infants and children: a classification based on

      endothelial characteristics. Plast Reconstr Surg

      1982;69:412-22.

Mulliken JB, Young AE. Vascular birthmarks: hemangiomas

      and malformations. Philadelphia: WB Saunders; 1988.

Nakayama H. Clinical and histological studies of the classi

      fication and the natural course of the strawberry mark. J

      Dermatol 1981;8:277-91.

Nelson LB, Melick JE, Harley RD. Intralesional corticos

      teroid injections for infantile hemangiomas of the eyelid.

      Pediatrics 1984;74:241-5.

Ozsoylu S, Irken G, Gurgey A. High dose intravenous   White CW, Sondheimer HM, Crouch EC, et al. Treatment of

      methylprednisolone for Kasabach-Merritt syndrome. Eur J           pulmonary hemangiomatosis with recombinant interferon

      Pediatr 1989; 148:403-5.            alfa-2a. N Engl J Med 1989;320:1197-200.

Reese V, Frieden IJ, Paller AS, et al. Association of facial      Zak TA, Morin JD. Early local steroid therapy of infantile

      hemangiomas with Dandy-Walker and other posterior fossa           eyelid hemangiomas (local steroid therapy of lid heman

      malformations. J Pediatr 1993;122:379-84.       giomas). J Pediatr Ophthalmol Strabismus 1981;18:25-7.

Frieden et al. 637

Rekant SI, Katz R. Perianal hemangioma appearing as an ulcer. Arch Dermatol 1972;106:382-3.

Reyes BA, Vazquez-Botet M, Capo H. Intralesional steroids in cutaneous hemangioma. J Dermatol Surg Oncol 1989;15:828-32.

Shikhani AH, Jones MM, Marsh BR, et al. Infantile subglottic hemangiomas: an update. Ann Otol Rhinol Laryngol 1986;95:336-47.

Simpson JR. Natural history of cavernous haemangiomata. Lancet 1959;2:1057-9.

Sloan GM, Reinisch JF, Nichter LS, et al. Intralesional corticosteroid therapy for infantile hemangiomas. Plast Reconstr Surg 1989;83:459-67.

Stern JK, Wolf JE Jr, Jarrett M. Benign neonatal hemangiomatosis. J Am Acad Dermatol 198 1;4:442-5.

Takahashi K, Mulliken JB, Kozakewich HP, et al. Cellular markers that distinguish the phases of hemangioma during infancy and childhood. J Clin Invest 1994;93:2357-64.

van der Meulen JC, Gilbert M, Roddi R. Early excision of nasal hemangiomas: the L-approach. Plast Reconstr Surg 1994;94:465-73.

Journal of the American Academy of Dermatology

Volume 37, Number 4

Morelli JG, Tan OT, Yohn JJ, et al. Treatment of ulcerated hemangiomas in infancy. Arch Pediatr Adolesc Med 1994; 148:1104-5.

Moroz B. The course of haemangiomas in children. In: Ryan TJ, Cherry GIO, editors. Vascular birthmarks: pathogenesis and management. Oxford: Oxford Medical Publications; 1987. p. 55-69.

Mulliken JB. A plea for a biologic approach to hemangiomas of infancy. Arch Dermatol 1991;127:243-4.

Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412-22.

Mulliken JB, Young AE. Vascular birthmarks: hemangiomas and malformations. Philadelphia: WB Saunders; 1988.

Nakayama H. Clinical and histological studies of the classification and the natural course of the strawberry mark. J Dermatol 1981;8:277-91.

Nelson LB, Melick JE, Harley RD. Intralesional corticosteroid injections for infantile hemangiomas of the eyelid. Pediatrics 1984;74:241-5.

Ozsoylu S, Irken G, Gurgey A. High dose intravenous methylprednisolone for Kasabach-Merritt syndrome. Eur J Pediatr 1989; 148:403-5.

Reese V, Frieden IJ, Paller AS, et al. Association of facial hemangiomas with Dandy-Walker and other posterior fossa malformations. J Pediatr 1993;122:379-84.

Frieden et al. 637

Rekant SI, Katz R. Perianal hemangioma appearing as an ulcer. Arch Dermatol 1972;106:382-3.

Reyes BA, Vazquez-Botet M, Capo H. Intralesional steroids in cutaneous hemangioma. J Dermatol Surg Oncol 1989; 15:828-32.

Shikhani AH, Jones MM, Marsh BR, et al. Infantile subglottic hemangiomas: an update. Ann Otol Rhinol Laryngol 1986;95:336-47.

Simpson JR. Natural history of cavernous haemangiomata. Lancet 1959;2:1057-9.

Sloan GM, Reinisch JF, Nichter LS, et al. Intralesional corticosteroid therapy for infantile hemangiomas. Plast Reconstr Surg 1989;83:459-67.

Stern JK, Wolf JE Jr, Jarrett M. Benign neonatal hemangiomatosis. J Am Acad Dermatol 198 1;4:442-5.

Takahashi K, Mulliken JB, Kozakewich HP, et al. Cellular markers that distinguish the phases of hemangioma during infancy and childhood. J Clin Invest 1994;93:2357-64.

van der Meulen JC, Gilbert M, Roddi R. Early excision of nasal hemangiomas: the L-approach. Plast Reconstr Surg 1994;94:465-73.

White CW, Sondheimer HM, Crouch EC, et al. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 1989;320:1197-200.

Zak TA, Morin JD. Early local steroid therapy of infantile eyelid hemangiomas (local steroid therapy of lid hemangiomas). J Pediatr Ophthalmol Strabismus 1981;18:25-7.

Journal of the American Academy of Dermatology Volume 37, Number 4

h) Sudden growth, tenseness, tenderness, and purpuric appearance in a large hemangioma (to suggest the possibility of Kas ab ach- Merritt syndrome)

i)    Respiratory difficulty or stridor

Hemangiomas in the mandibular area increase the risk of concomitant airway hemangioma(s).

2. Physical examination

a) Cutaneous and mucosal examination for evidence of other heman

giomas

b) Measurement of hemangioma including superficial and deep components

c) Palpation of liver may be helpful in assessing presence of hepatic hemangiomas (usually seen with multiple cutaneous lesions) or evidence of congestive heart failure (occasionally seen with very large hemangiomas)

d) Ophthalmologic examination if the periorbital area is affected

3. Differential diagnosis

Several cutaneous neoplasms and anomalies may resemble hemangiomas. These include but are not limited to the following:

a) Tufted angioma

b) Port-wine stains

c) Venous malformations

d) Lymphatic malformations

e) Arteriovenous malformations

f)    Kaposiform hemangioendothe

      lioma

g) Adrenal carcinoma

h) Pyogenic granuloma

i) Nasal glioma

j) Myofibromatosis

1)

k) Spindle and epithelioid (Spitz) nevus Dermoid cysts 4. Other Photography can be an extremely important adjunct in following growth and involution of lesions. B. Diagnostic tests The diagnosis is usually made on clinical grounds. The following diagnostic tests

Frieden et al. 633

may be useful in clinically atypical cases and as an adjunct to assess for potential complications.

1. Platelet count

For large, rapidly growing, tense, or purpuric vascular tumors to evaluate for Kasabach-Merritt syndrome. The presence of Kas ab ach- Merritt syndrome suggests the possibility of other less common vascular tumors, such as tufted angioma or kaposiform hemangioendotheliorna.

Ultrasound

Helpful for diagnosis of hepatic lesions, some cutaneous lesions, as an adjunct to monitor response to therapy, and to evaluate infants with large facial hemangiomas for possible structural brain abnormalities.

3. Doppler studies to evaluate blood flow 4. Magnetic resonance imaging (MRI) Helpful in differentiating hemangiomas from venous or arteriovenous malformations; may help delineate extent of disease in very large lesions and be useful in evaluating infants with large facial hemangiomas for structural brain abnormalities

Computed tomography

Same uses as MRI, but not as specific as MRI in differentiating hemangiomas from vascular malformations

6. Biopsy (rarely necessary)

Increased risk of bleeding makes this a somewhat risky and unpopular way to diagnose most hemangiomas, but it is occasionally necessary to differentiate atypical cases from other soft-tissue tumors, such as kaposiform hemangioendothelioma (a low-grade sarcoma), myofibromatosis, and rhabdomyosarcoma.

C.    Inappropriate diagnostic tests

      Not applicable

D.    Exceptions

      Not applicable

E.    Evolving diagnostic tests

      Measurement of basic fibroblast growth

      factor may prove to be helpful in differ

      entiating hemangiomas from vascular

2.

5

634 Frieden et al.

malformations and for following therapeutic response.

V. Recommendations (see 111. B.)

Because of their natural history, hemangiomas present unique treatment issues. Untreated, they involute, but while present a minority cause functional impairment and even more cause psychosocial distress. Once resolved, a significant minority leave residual scarring, fibrofatty tissue, telangiectases, and other skin changes.

The approach to the management of hemangiomas is therefore individualized based on the size of the lesion(s), location, presence of complications, the age of the patient, and rate of growth or involution at the time of evaluation. With these factors in mind, the potential risk(s) of treatment is carefully weighed against the potential benefits. Many hemangiomas need no treatment at all, but if this approach is chosen, the patient should still be periodically reevaluated, especially during the period of growth and less often once growth has ceased and involution begins.

A. Major goals of management

1. Prevent or reverse any life-threatening or function- threatening complications of hemangiomas

2. Prevent permanent disfigurement left by residual skin changes after involution

3. Minimize psychosocial distress from the presence of hemangiomas for both patient and family

4. Avoid aggressive, potentially scarring procedures for treatment of those hemangiomas likely to have an excellent prognosis without therapy

5. Prevent or adequately treat ulcerated hemangiomas to minimize scarring, infection, and pain

B. General indications for treatment

1. Life- and function-threatening hemangiomas (e.g., those causing impairment of vision, Kasabach-Merritt coagulopathy, respiratory compromise caused by airway lesions, congestive heart failure, hepatic involvement)

2. Hemangiomas in certain anatomic locations that often leave permanent

Journal of the American Academy of Dermatology

      October 1997

scars or deformity, especially the nose, lip, ear, and glabellar area

3. Large facial hemangiomas, especially those with a prominent dermal component (more likely to leave permanent scarring)

Smaller hemangiomas in exposed areas, such as the face and hands, may be considered for treatment with modalities unlikely to cause scarring or significant side effects.

Ulceration

6. Pedunculated hemangiomas (likely to leave significant fibrofatty tissue after involution)

C. Choice of treatment modalities may vary

according to a number of factors includ

ing but not limited to the following:

1. Anatomic location

2. Location in skin (i.e., dermal vs subcutaneous vs both)

3. Size and extent of lesion(s)

4. Whether lesion is in growth, plateau, or involution phase

5. Whether functional impairment is present

6. Experience of physician with certain modalities (i.e., laser)

7. Availability of certain modalities (i.e., laser)

8. Level of parental concern

D. Treatment

The listed treatments may be used singly,

in combination with each other, or with a

surgical modality.

1. Low-risk hemangiomas (i.e., small, causing no functional impairment and unlikely to leave permanent disfigurement)

a) Medical

      1) Intralesional corticosteroids

Triamcinolone acetonide 10 to 40 mg/ml

2) Class I topical corticosteroids (sparse data in medical literature regarding this modality)

            3) Pressure occlusion b) Surgical

1) Flash-lamp pumped pulsed dye laser

2) Other lasers and light sources

Journal of the American Academy of Dermatology

Volume 37, Number 4

may be useful in selected cases; however, current lasers other than the flash-lamp pumped pulse dye laser have a greater risk of permanent hypopigmentation and scarring. With the exception of the argon laser, information in the medical literature regarding the use of other lasers for treating hemangiomas is sparse.

3) Cryosurgery

4) Surgical excision (especially of small pedunculated hemangiomas)

2. High-risk lesions (i.e., large, prognostically poor location, likely to leave permanent disfigurement, causing functional impairment, or involving extracutaneous structures)

a) Medical

1) Systemic corticosteroids (indicated mainly during the growth period of hemangiomas)

Prednisone (or equivalent dose of prednisolone) 2 to 4 mg/kg per day in a single morning dose or divided doses in emergent cases

2) Triamcinolone acetonide 10 to 40 mg/ml, sometimes mixed with dexamethasone sodium phosphate 4 mg/ml (eye, other well-localized lesions)

3) Interferon alfa-2a subcutaneous, initial dose I million U/m 2 per day, which is increased to 3 million U/m 2 per day if tolerated (generally reserved for corticosteroid treatment failure)

4) Combined therapy (i.e., pulsed dye laser plus systemic corticosteroids)

b) Surgical

1) Flash-lamp pumped pulsed dye laser

2) Other lasers and light sources may be useful in selected cases; however, current lasers other than the flash-lamp pumped pulse dye laser have a greater

Frieden et al. 635

C)

risk of permanent hypopigmentation and scarring. With the exception of the argon laser, information in the medical literature regarding the use of other lasers for treating hemangiomas is sparse.

3) Early surgical excision (especially nasal, eyelid lesions)

4) Combined therapy (i.e., pulsed dye laser plus systemic corticosteroids or interferon alfa)

5) Cryosurgery

Other

The following may be used only in exceptional cases failing other therapies:

      1) Cyclophosphamide

      2) Embolization

      3) Radiotherapy

d) Evolving therapy

      1) Leuprolide acetate

      2) Ketotifen

      3) Other, new selective lasers

4) Other inhibitors of angiogenesis that are under development

E.    Patient education

      Parent education may include the follow

2.

4

ing:

1. The expected natural history without treatment

A demonstration whenever possible of before and after photographs of both natural involution and the results of the treatment being contemplated

The risks, potential benefits, and alternatives to contemplated therapy

In cases in which the hemangioma is in an exposed area (e.g., face), anticipatory guidance regarding ways in which to handle comments and queries from family members and others

VI.   Supporting evidence

      See Bibliography (Appendix)

VIL   Disclaimer

Adherence to these guidelines will not ensure successful treatment in every situation. Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of

636 Frieden et al.

care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient. For the benefit of members of the American Academy of Dermatology who practice in countries outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U.S. Food and Drug Administration.

Appendix. Bibliography

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Amir J, Metzker A, Krikler R, et al. Strawberry hemangioma in preterm infants. Pediatr Dermatol 1986;3:331-2.

Apfelberg DB, Lane B, Marx MP. Combined (team) approach to hemangioma management: arteriography with superselective embolization plus YAG laser/sapphire-tip resection. Plast Reconstr Surg 1991;88:71-82.

Ashinoff R, Geronemus RG. Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser. Arch Dermatol 1991;127:2025.

Ashinoff R, Geronemus RG. Failure of the flashlamppumped pulsed dye laser to prevent progression to deep hemangioma. Pediatr Dermatol 1993;10:77-80.

Blei F, Orlow SJ, Geronemus RG. Supraumbilical midabdominal raphe, sternal atresia, and hemangioma in an infant: response of hemangioma to laser and interferon alfa-2a. Pediatr Dermatol 1993;10:71-6.

Bowers RE, Graham EA, Tomlinson KM. The natural history of the strawberry nevus. Arch Dermatol 1960;82:667-80.

Burton BK, Schulz CJ, Angle B, et al. An increased incidence of haemangiomas in infants born following chorionic villus sampling. Prenat Diagn 1995; 15:209-14.

Byard RW, Burrows PE, Izakawa T, et al. Diffuse infantile haemangiomatosis: clinicopathological features and management problems in five fatal cases. Eur J Pediatr 199 1; 150:224-7.

Castro-Ron G. Cryosurgery of angiomas and birth defects. In: Zacarian SA, editor. Cryosurgery for skin cancer and cutaneous disorders. St. Louis: Mosby; 1985. p. 77.

Cremer HJ, Djawari D. Fruhtherapie der kutanen hamangiome mit der kontaktkryochirurgie. Chir Praxis 1995;49: 295-312.

Deans RM, Harris GJ, Kivlin JD. Surgical dissection of capillary hemangiomas: an alternative to intralesional corticosteroids. Arch Ophthalmol 1992; 110: 1743-7.

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Enjolras 0, Mulliken JB. The current management of vascular birthmarks. Pediatr Dermatol 1993; 10:311-3.

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Enjolras 0, Riche MC, Merland JJ, et al. Management of alarming hemangiomas in infancy: a review of 25 cases. Pediatrics 1990;85:491-8.

Enjolras 0, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas. J Pediatr 1997;130:631-40.

Esterly NB. Cutaneous hemangiomas, vascular stains and malformations, and associated syndromes. Curr Probl Dermatol 1995;7:65-108.

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Goette DK, Detlefs RL. Postirradiation angiosarcoma. J Am Acad Dermatol 1985; 12:922-6.

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Morelli JG, Tan OT, Weston Wl. Treatment of ulcerated hemangiomas with the pulsed tunable dye laser. Am J Dis Child 199 1; 145:1062-4.