IH are heterogeneous tumours. Their classification is important to guide in the prognosis, potential complications and treatment. IH can be classified clinically according to two criteria: depth of the affected vessel and shape-distribution pattern2,9 (Table 1).

IH, particularly of the head, neck and lumbosacral region, may be associated with underlying structural alterations. In this regard, 2 symptoms typically associated with IH have been described: PHACES syndrome (Posterior fossa malformations/Hemangiomas/Arterial anomalies/Cardiac defects/Eye abnormalities/Sternal cleft/Supraumbilical raphe syndrome) (OMIM #606519) describes alterations associated with large facial and segmental haemangiomas whose diagnostic criteria were established in 2009.10 Between 20% and 31% of large and segmental IH of the face are known to be associated with PHACES syndrome.11 PELVIS syndrome (Perineal hemangioma/External genitalia malformations/Lipomyelomeningocele/Vesicorenal abnormalities/Imperforate anus/Skin tag), also known as SACRAL or LUMBAR syndrome, has been proposed to refer to the group of alterations associated with large or segmental IH in the lumbosacral region.12,13Table 2 presents the anomalies that may be presented by patients with PHACES and PELVIS/SACRAL/LUMBAR syndrome.

Most IH are diagnosed by means of a physical examination and the lesion's evolutive history.

The medical history should collect data related to pregnancy, the perinatal period and the lesion's evolutive details. Between 30% and 50% of IH present a precursor lesion in the form of a pink or telangiectasia-like macule, which may be confused with capillary malformations, nevus anemicus, hypochromic nevus or traumatism.

A differential diagnosis must be performed of deep IH with nasal gliomas, dermoid cysts, infantile myofibromatosis, neuroblastomas, plexiform neurofibromas, pilomatricomas, lipomas and other sarcomas, although imaging techniques usually suffice to make the diagnosis.14,15 In turn, multifocal IH must be distinguished from multifocal lymphangioendotheliomatosis,16 Bean syndrome or Langerhans cell histiocytosis. Finally, superficial IH may be confused with tufted haemangiomas and Kaposiform haemangioendotheliomas, hemangiopericytomas or angiosarcomas.

The internal involvement of an IH need not be anatomically related to the haemangioma of skin although segmental or large haemangiomas have a greater risk of association with internal haemangiomas.17 In this regard, the existence of 5 or more haemangiomas of skin should constitute justified cause to perform an abdominal ultrasound.18 Visceral IH are usually asymptomatic and may appear in different sites, being the liver the most frequent location. However, on certain occasions, clinical symptoms may assist in the diagnosis of internal haemangiomas: stridor, cough or loss of voice in airway IH; intestinal haemorrhage in gastrointestinal tract IH; heart failure, respiratory distress or signs and symptoms of hypothyroidism in large or multifocal hepatic haemangiomas.

Imaging studies can be very useful in making a correct diagnosis, although there is no consensus about when they should be indicated in order to determine the internal extent of an IH. Generally speaking, analytical tests are not of great help in the diagnosis of IH.

Fig. 1 displays the recommendations formulated with regard to the diagnosis of IH in the form of an algorithm.

Figure 1.

Infantile haemangioma diagnostic algorithm. PC: primary care; IH: infantile haemangioma; LOC: location; NMR: nuclear magnetic resonance, PHACES: posterior fossa malformations/hemangiomas/arterial anomalies/cardiac defects/eye abnormalities/sternal cleft/supraumbilical raphe síndrome. PELVIS: inglés Perineal hemangioma/External genitalia malformations/Lipomyelomeningocele/Vesicorenal abnormalities/Imperforate anus/Skin tag.

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Most IH have a predictable clinical course, tending towards total or partial spontaneous involution. However, certain IH may become complicated at local level, causing aesthetic sequelae or compromising vital organs.19 In this regard, the classification of IH according to the risk of sequelae or complications (Table 3) is useful.

Local complications include ulceration, infection, bleeding and pain. Ulceration is the most frequent complication being predisposing factors: size of the IH, segmental distribution, the appearance of a superficial greyish surface area, and location in regions of sustained friction and humidity.14,20

IH located in the periorbital area may produce astigmatism, strabismus and the obstruction of the visual axis presenting amblyopia and the risk of permanent loss of sight. Other IH, particularly bilateral ones and located in the chin, present a high risk of affecting the airways.

The risk of psychological impairment deserves special attention due to the aesthetic sequelae of IH, particularly in IH located in visible areas. Even though the future appearance of a haemangioma is difficult to predict, superficial IH do not usually cause sequelae, whereas mixed and voluminous IH tend to leave residual fibroadipose tissue.21

Location, size, complications, treatment or association with other conditions may have a negative impact on the quality of life of patients and their families. A recent study reported no significant differences in the quality of life indices of patients with and without IH,22 although other studies indicate that children between 3 and 7 years could be the most susceptible in terms of impact on self-esteem.23 Recently, a specific instrument has been developed for the assessment of the impact of IH on the quality of life of patients and their families consisting in a survey of 29 questions divided in four scales that asses the morbidity caused by IH, its consequences on the child social interactions, and the impact on the family emotional and psychosocial functioning.24

The protocolisation as to when and how an IH should be treated is complex. Not all haemangiomas of the same size and location undergo the same clinical evolution; and the psychological impact of the IH on the child and the family cannot be extrapolated between patients with the same tumour.

Even so, there are absolute indications for the treatment of IH: (1) Potentially lethal IH or those that endanger functional capacity, (2) Ulcerated IH with pain and/or absence of response to basic wound-care measures and (3) IH with risk of permanent scarring or disfigurement.

Until the year 2008, oral corticoids were the treatment of choice for complicated IH, despite their side effects at high doses and the absence of response to treatment in one third of the cases.

Currently, oral propranolol is the treatment of choice for IH and is the only one that has been approved for this indication.

Propranolol's efficacy is greater than that of any other treatment from the onset and at any location of the body.25 Moreover, a positive effect on the quality of life of patients with IH and their families has been described.26 The approved dose of propranolol is 3mg/kg, which has shown greater efficacy than 1mg/kg, with no increase in toxicity.25 The exact toxic doses of propranolol are unknown, but children with hypertrophic cardiomyopathy have been treated with doses of 5mg/kg/day, with low incidence of complications.27 The intake of doses 2 or 3 times the therapeutic dose may be life-threatening for patients.28

There is certain controversy as to whether the administration of propranolol in patients with PHACES syndrome with alterations of the big intracranial vessels and aorta coartation for the potential risk of cerebral ischaemia that may cause hypotension. For this reason, at least a cardiological study should be performed in these patients, and ideally a magnetic resonance angiogram before treatment with propranolol is initiated. In cases where the magnetic resonance angiogram with sedation is not advised, starting treatment with lower-dose propranolol and slowly scaling is recommended.

Other beta-blockers have also demonstrated their efficacy (acebutolol,29 atenolol30 and nadolol31), although they have shown no significant advantages over propranolol.

The side effects of beta-blocking drugs are well known28: (1) cardiovascular (bradycardia and hypotension), (2) bronchial (reduction in bronchodilatory tone and increased resistance of the medium-sized airways), (3) metabolic32 (hypoglycemia), (4) renal (reduction in glomerular filtration) and (5) central nervous system33 (possible impairment of memory, sleep quality, mood and psychomotor functions).

The recommendations issued by the specialists for the treatment of IH, the use of propranolol and the prevention of its adverse effects are detailed in Table 4. Similarly, an action algorithm is presented for the treatment of IH (Fig. 2).

Figure 2.

Infantile haemangioma treatment algorithm. PC: primary care; AE: adverse event; dis: disease; HR: heart rate; bpm: beats per minute; BP: blood pressure; IPL: intense pulsed light.

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Another effective systemic treatment for the treatment of IH is interferon-alpha, although it can cause spastic diplegia in infants.34 Timolol maleate, in topical form, has shown effectivity in superficial lesions,35 without presenting significant side effects.36 Topical corticoids and 5% imiquimod have also been used anecdotally. Finally, PDGF (Platelet Derived Growth Factor) appears to be useful in the topical treatment of ulcerated IH,37 although it might be associated with a greater incidence of cancer (Table 5).

Treatment of IH with laser is indicated in three cases: treatment of the proliferative phase, albeit not as a first option, treatment of ulcerated IH, and treatment of telangiectasias and residual textural alterations.

Surgery is fundamentally indicated in the treatment of sequelae, although thanks to propranolol, the sequelae that require surgical correction have diminished considerably. Surgery may be the first treatment option in pedunculated IH, IH with painful and persistent ulceration, compression of the eyeball and progressive facial deformity. Once the surgical indication has been established, the child should be operated preferably before the age of four years.

Finally, the psychological repercussion of a haemangioma on the family environment is significant and may require specialised psychological care. Proper treatment of IH can avoid subsequent risk behaviours, such as social isolation, depression or anxiety.

The Primary Care Paediatrician (PCP) is a medical professional who is closer and more accessible to the child and the family. Their role is fundamental in the early diagnosis and referral to the dermatologist of IH susceptible of treatment, ideally within the first 3 months of life. Referral circuits between the two healthcare levels must be flexible and waiting times short within at least 15–21 days at most. In this regard, the shared use of virtual resources (telemedicine with photographic control of evolution) may greatly facilitate the referral of patients and treatment follow-up.

Treatment with propranolol may be initiated at ambulatory level, provided that the resources required to solve possible post-administration complications are available. The dermatologist may decide, together with the PCP, for the beginning of treatment and dose titration to be performed in the PCP's office.

The monitoring of patients receiving oral treatment with propranolol must be carried out in Primary Care, hence the PCP must be conversant with the relevant treatment aspects: dose, duration, possible side effects and how to proceed if they occur, and in the event of intercurrent symptoms that may affect treatment.

The PCP should inform the parents and caregivers of the possible side effects of propranolol. This information should be conveyed in a simple and understandable way, and may be reinforced by the use of written material.

The formation of multidisciplinary teams in hospitals for vascular anomalies care is important in the management of IH patients and in particular is necessary for the diagnosis and management of patients with complex haemangiomas.38 The multidisciplinary team may be comprised of different specialists: dermatologists, paediatricians, cardiologists, anatomical pathologists, radiologists, surgeons, otolaryngologists, ophthalmologists, neurologists and neurosurgeons. Although there is no universally accepted guide for the intrahospital management of IH,19,39 the following steps are suggested:

• 1.

  Confirmation of the clinical diagnosis, usually in the dermatology department.

• 2.

  Assessment of the risk of functional impairment, aesthetic impairment, associated anomalies, complications and sequelae.

• 3.

  Consultations with paediatricians: otolaryngologists in chin-area IH; surgeon for pedunculated IH and for the evaluation of aesthetic sequelae; radiologist, neurologist and neurosurgeon in suspected PHACES or LUMBAR syndrome; ophthalmologist in IH with risk of visual impairment.

• 4.

  Treatment decision in agreement with the specialists involved. Start in day hospital or hospitalisation, as necessary. Consultation with a paediatrician or a cardiologist in the event of side effects.

• 5.

  Scheduling of clinical controls in dermatology and the outpatient departments of the other specialities involved. Photographic record for control of evolution and response to treatment.

• 6.

  Periodic meetings of the multidisciplinary team to address complex cases of IH.