Infantile And Congenital Haemangiomas (also Refer CME Summary)

Question 1

Classification of vascular anomalies

Answer 1

BENIGN VASCULAR TUMOURS vs VASCULAR MALFORMATIONS

BENIGN VASCULAR TUMOURS
Infantile haemangiomas (IH)
- Hepatic haemangioma
- Multifocal haemangioma
—> without systemic involvement
—> with systemic involvement

Congenital haemangiomas (CH)

• Rapidly involuting (RICH)
• Non-involuting (NICH)
• Partially involuting (PICH)

Tufted angioma
Spindle cell haemangioma
Epitheliod haemangioma
Pyogenic granuloma

VASCULAR MALFORMATIONS
High flow
- Arteriovenous

Low flow

• Capillary
• Venous
• Lymphatic

Mixed i.e.

• Capillary venous
• Capillary lymphatic
• Capillary arteriovenous

Question 2

Distinction between IH (vascular tumour) and Vascular malformations

Answer 2

INFANTILE HAEMANGIOMA (IH)
Usually evident within the 1st week of life
Proliferates rapidly
Involute over years

Girls
Low birth weight infants

IHC - GLUT-1 positive

VASCULAR MALFORMATIONS
Usually present at birth
Proportionate growth
Do not involute (persist)

No gender bias
No birth weight bias

IHC - GLUT-1 negative

Question 3

Infantile haemangioma

Answer 3

Benign
Vascular tumour
Most cases sporadic

CLINICAL FEATURES
Onset 1st week of life -
- Faint telengiectatic patch OR area of pallor OR flat pink mark “haemangioma precursor”

Proliferative phase -

• Superficial subtype —> Rapidly becomes red and raised
• Deep subtype —> Blue or purple, may have no overlying skin changes
• Rapid proliferation 1st few months of life
• firm
• Reaches 80% of final size by 3 months of age

Involution phase -

• Involution over years
• become softer
• Superficial haemangiomas —> develop islands of greying within the redness, flattening of surface
• Involution complete at 3 years (if untreated)

RISK FACTORS
Girls
First born
Breech
Low birth weight <2500g
IVF baby
Amniocentesis

SUBTYPES
Superficial —> red and raised, most rapid growth between 5.5 - 7.5 weeks of age
Deep (develops in lower dermis, subcutis) —> Blue or purple, may have no overlying skin changes, presents later, continues to grow for longer
Mixed superficial and deep
Reticular, abortive, or minimal growth —> relatively little proliferation, remain as a patch of telengiectatic vessels

PATTERNS
Focal
Multifocal
Segmental
Indeterminate

PATHOGENESIS
Unclear
? Role of GLUT-1 that is expressed in endothelial cells amd placental vasculature —> IH result of embolisation of placental endothelial cells to fetal circulation
Lack of evidence of maternal-fetal chimerism goes againt the placental theory
AD inheritance pattern in some familial cases

3 CLINICAL VARIANTS

SEGMENTAL/PLAQUE-LIKE IH
Involves broad anatomical region
Face and lumbosacral region may be assoc with underlying sructural anomalies
frontotemporal, mandibular regions highest risk for PHACES
Cerebral vasculature abnormalities, coarctation of the aorta most common extracutaneous findings in PHACES
Ix facial segmental IH (PHACES) -
- Ophthal exam (eye abnormalities)
- Head and neck MRA (arterial anomalies)
- ECHO (cardiac anomalies)
+/- otolaryngological/ENT advice (if beard region involved, esp bilateral, even in absence of overt resp symptoms —> exclude airway haemangiomas)
Ix lumbosacral/lower body segmental IH (LUMBAR) -
- Spinal USS acceptable as initial assessment for infants <3 months
- Spinal MRI with contrast ideal (urogenital anomalies, myelopathy, bony anomalies, anorectal anomalies, renal anomalies)

MULTIFOCAL CUTANEOUS IH +/- EXTRACUTANEOUS INVOLVEMENT
Most follow uncomplicated course
Assoc Liver haemangiomatosis most common if > 5

HEPATIC HAEMANGIOMA
May occur woth or without cutaneous IH
Most asymptomatic
If symptomatic, usually within age 3 months presenting with -
- Hepatomegaly
- High output cardiac failure
3 types - focal, multifocal, diffuse
Focal ? Represents RICH of the liver - GLUT-1 neg, no cutaneous IH, regress rapidly
Multifocal - GLUT-1 pos, assoc with multiple small cutaneous IH, asymptomatic, most domt require Rx
Diffuse - massive liver involvement, symptomatic AV shunting, high output cardiac failure

FACIAL SEGMENTAL HAEMANGIOMA ASSOCIATIONS (PHACES)
P - posterior fossa malformations
H - haemangiomas (facial)
A - arterial anomalies
C - cardiac anomalies
E - eye abnormalities
S - sternal/supraumbilical raphe

LOWER BODY SEGMENTAL HAEMANGIOMA ASSOCIATIONS (LUMBAR, SACRAL, PELVIS)
L - lower body haemangioma
U - urogenital anomalies, ulceration
M - myelopathy
B - bony deformities
A - anorectal anomalies, arterial anomalies
R - renal anomalies

S - spinal dysraphism
A - anogenital anomalies
C- cutaneous anomalies
R - renal and urological anomalies
A
L - lumbosacral haemangioma

P - perineal haemangioma
E - external genitalia malformations
L - lipomyelomeningocoele
V - vesicorenal abnormalities
I - imperforate anus
S

IX
Diagnosis nearly always clinical, bx rarely required to distinguish IH from other vascular anomalies
USS may be useful to distinguish from other vascular tumours/malformations
Before Rx with beta blockers for segmental IH on the face, lower trunk

HISTO
Mast cells

IHC - 
Factor VIII positive
CD31 positive
Von Willebramd factor positive
GLUT-1 positive (useful in differentiating from congenital haemangiomas)

MX
Rx for IH causing/likely to cause -
- Functional impairment
- Disfigurement
- Ulceration

TOPICALS (very small non-ulcerated, non-mucosal superficial IH) —> Reduce risk of absorption
Timolol 0.5% gel forming solution up to TDS

SYSTEMICS
Propanolol (first line)
Relapse less likely if continued for at least 12 months

SURGERY
Proliferative IH if functional impairment or ulceration cannot be managed medically
Involuting IH if size and appearance of surgical scar likely to be superior when involution ceased

RX OF COMPLICATIONS
Ulcerated IH 
- Protective non-adherent dressing
- Topical or oral antibiotics based on swab MCS
- PDL

Life threatening haemangiomas i.e. leading to CCF that has not responded to propanolol
- Embolisation

Post involution telengiectasia/erythema
- PDL

Post involution abnormal contour d/t fibrofatty residuum, distortion of important anatomical structure
- Surgery

COMPLICATIONS
Most resolve spontaneously without sequelae
Ulceration (common) - 
- Risk highest 4-6 months old
- More likely in large segmental IH
- Lip, Neck, anogenital (d/t friction and moisture)
- Painful
- Assoc bleeding, infection
- Scarring

Disfigurement -

• Esp those woth dermal component
• Central face, nose, lip

Functional impairment -

• Most common in periocular IH —> astigmatism, visual axis obstruction, strabismus —> amblyopia, permanent visual loss
• Lip —> interfere with feeding
• Nose, airway —> interfere with breathing

Structural anomalies for segmental or plaque-like IH of the head and neck (PHACES + lumbosacral region
Extensive visceral haemangiomatosis assoc with multifocal IH

COURSE/PROGNOSIS
Appears shortly after birth
Achieves 80% growth by 3 months
Completes growth by 9 months
3%, minky deep ones, show growth for longer
Involute over years, usually by 3 years
Residual skin changes in 25-60% untreated cases
Excellent prognosis for small IH without Rx, larger Ih with no functional impairment/not at aesthetically important site
Prognosis good for IH causing/likely to cause functional/aesthetic impairment if Rx started in timely fashion

Question 4

Protocol for propanolol in Rx of IH

Answer 4

BEFORE STARTING
Full hx and exam
HR
BP
Oxygen sat

+/- ECG

• If HR below normal for age
• Hx of arrhythmia
• Arrhythymia on exam
• Fam hx congenital heart condition, arrhythmia, maternal connective tissue disease

+/- ECHO

• Hx, symptoms, signs cardiovascular disease
• Suspected high output cardiac failure
• Large segmental face and neck IH —> suspected PHACES

Rx explanation
Written info to parents
Photos

DOSAGE REGIMEN
Week 1
- 1mg/kg/day divided into 3 equal doses (i.e. given TDS)

Week 2
- 2mg/kg/day divided into 3 equal doses (i.e. given TDS)

Patients with suspected PHACES pending MRA

• 0.5mg/kg/day divided into 3 equal doses (i.e. given TDS)
• Very cautious increase if dose in small increments until MRA excludes clinically significant arterial anomalies of the head and neck (risk of hypoperfusion)

OBSERVATION, MONITORING
Weight > 3.5kg, no co-morbidities
- BP and HR immediately before 1st dose
- BP and HR every 30 mins for 2 hrs post dose

Weight < 3.5kg and/or co-morbidities

• BP and HR immediately before 1st dose
• BP and HR every 30 mins for 4 hrs or more post dose

OTHER IX (propanolol can be commenced whilst results pending)
Liver, parotid haemangioma, PHACES —> TFTs (hypothyroidism)

Liver haemangioma —> LFTs

Bleeding haemangioma —> FBC (anaemia)

> 5 cutaneous haemangiomas, perianal, perineal IH extending into gluteal cleft —> abdo USS (liver haemangioma, bladder, renal anomalies)

Large segmental IH of head and neck with suspected PHACES —> MRA brain and neck (arterial anomalies)

Plaque IH in lumbosacral area crossing the midline/perianal, perineal IH extending into gluteal cleft —> MRI spine (spinal dysraphism)

REFERRALS
Periocular IH —> opthal
Suspected airway haemangioma —> ENT

RX CONTINUATION
Review
- 4 weeks after starting Rx
- Thereafter every 3-4 months

Dose Increments
- Increments > 0.5mg/kg/day —> HR, BP 2 hrs post dose

Stopping Rx

• Usually 12-14 months old, can be later
• Gradual dose reduction over 2-4 weeks

Question 5

Congenital Haemangioma

Answer 5

Benign
Vascular tumour
Proliferate in vitro —> may be evident as early as 12 weeks gestation in prenatal USS
Do not proliferate post natally
3 subtypes
All GLUT-1 neg

RAPIDLY INVOLUTING CONGENITAL HAEMANGIOMA (RICH)
Regress within 1-2 years old
Blue or purple
Telengiectases
Peripheral pallor
+/- central ulcer, scar, depression
Rapid regression —> leaves pronounced atrophy
Propanolol does not accelerate involution

Complications

• Thrombocytopenia (resolves spontaneously)
• Haemodynamic instability (large lesions)

USS

• Uniform hypoechoic mass
• Centrilobular draining channels

Histo
- Small lobules of capillaries with plump endothelium (peripheral of lesion), thin walled with surrounding fibrous tissue (centre of lesion)

Rx of ulcerated, bleeding RICH or those causing haemodynamic instability

• Embolisation
• Excision

Rx of prominent veins in areas of atrophy following involution
- Sclerotherapy

NON-INVOLUTING CONGENITAL HAEMANGIOMA (NICH)
Do not regress post natally
Violaceous plaques/tumours
Coarse telengiectases
Peripheral pallor
May be warm to touch
Grow in proportion to body

USS
- Prominent arterial flow

Histo

• Large lobules of small vessels in fibrous tissue stroma
• Abnormal appearing arteries, veins

If Rx desired —> surgery

PARTIALLY INVOLUTING CONGENITAL HAEMANGIOMA (PICH)
Intermediate type that behaves like RICH but showing only partial involution