Abstract
Subglottic haemangiomas are benign vascular malformations presenting in early infancy with respiratory distress due to progressive airway obstruction. The lesion, after undergoing proliferation during the first few months, naturally involutes by an age of 2–3 years. Due to high incidence of mortality, therapy should be initiated immediately. Multiple therapeutic options, such as steroids, interferon, surgery and laser ablation, are available but the best treatment is controversial. This report describes an infant presenting with respiratory distress and cutaneous haemangioma who was detected to have airway obstructive haemangioma from the subglottis to the carina. Due to the massive size, surgical and laser ablation could not be exercised. Also, the infant showed no response to dexamethasone, prednisolone or interferon. Following failure of these modalities, the infant was successfully managed with concurrent administration of daily interferon and pulse methylprednisolone. The regime resulted in rapid shrinkage of the haemangioma and resolution of symptoms, with no recurrence up to 24 months of age.
BACKGROUND
Haemangiomas are vascular malformations presenting most commonly in the first year of life.1 Though benign, they may be hazardous because of their size or anatomical location. Airway, especially subglottic, haemangiomas may prove fatal by compromising the airway. Despite the availability of numerous options, there is no consensus on the choice of treatment. We report a case of subglottic haemangioma that was successfully managed with intermittent pulses of methylprednisolone (MP) combined with interferon (IFN) α-2a (IFNα-2a).
CASE PRESENTATION
A 40-day-old female infant presenting to us with facial reddish skin lesion over the chin was diagnosed as having capillary haemangioma. Two weeks later, she developed respiratory distress and refused feeding. Upon examination, the haemangioma was found to have spread to involve the “beard” portion of face, neck and chest on their anterior aspects (fig 1). The patient had biphasic stridor that worsened on crying, and tachypnoea, suprasternal retractions and low oxygen saturations.
Figure 1.
Subglottic haemangioma presenting cutaneously in “beard” distribution over the face, and over the neck and chest.
INVESTIGATIONS
Considering the cutaneous distribution of the haemangioma and the respiratory symptoms, a diagnosis of obstructive airway haemangioma was considered. Bronchoscopy revealed haemangioma involving the oral, pharyngeal and tracheal mucosae. CT of the airway showed a circumferential haemangioma extending from the subglottis to the carina, with variable indentation of the airway (figs 2 and 3).
Figure 2.
CT showing a circumferential haemangioma extending from the subglottis to the carina.
Figure 3.
CT showing circumferential subglottic haemangioma.
DIFFERENTIAL DIAGNOSIS
Congenital laryngeal stenosis, croup.
TREATMENT
Dexamethasone (intravenous, 2 mg/kg/day in four divided doses) was started, but the respiratory distress persisted even after a 2 week course. Therefore, the corticosteroid was gradually tapered off over the next 2 weeks and, simultaneously, IFNα-2a (subcutaneously, 0.3 MU/m2/day), was initiated. However, the respiratory distress continued to worsen, despite 2 weeks of IFNα-2a, and because of this prednisolone (per orally, 2 mg/kg/day) was added to the treatment. Despite a 2 week course of IFNα-2a and prednisolone, the patient’s obstructive symptoms persisted and she required respiratory support with nasal continuous positive airway pressure (NCPAP) and oxygen. The treatment was modified to IFNα-2a (daily; subcutaneous) with MP (pulse; intravenous) and prednisolone (alternate day; oral). There was improvement in respiratory symptoms within 24 h of the first dose of MP. The infant’s oxygen requirements decreased gradually over first week and she was removed from NCPAP 10 days later. After 2 weeks, the biphasic stridor was reduced to inspiratory, and that also gradually disappeared at 9 months of age.
MP was administered intravenously at a dose of 30 mg/kg, daily for 3 days, then weekly for 4 weeks, fortnightly for the next 4 weeks, and finally monthly during the next 3 months. Oral prednisolone was administered concurrently as every other day therapy at a dosage of 1.5 mg/kg. IFNα-2a, also being administered simultaneously, was continued to 12 months of age.
OUTCOME AND FOLLOW-UP
The child was followed up until 24 months of age and no recurrence of symptoms was observed. The vascularity of cutaneous haemangioma also decreased synchronously, though its distribution remained unchanged. There were no adverse effects noted in the child, of any of the drugs administered.
DISCUSSION
Airway haemangiomas, including congenital subglottic haemangiomas, account for 1.5% of all laryngeal anomalies. As with the case described here, there are more incidents in females, with a female/male ratio of 2:1; in half of the cases they are associated with cutaneous haemangioma in “beard distribution”. These patients present at a median age of 6 weeks. The most common symptom at presentation is intermittent inspiratory stridor that gradually becomes constant and biphasic.2 Airway haemangiomas are confirmed by endoscopy/CT imaging of the airway. Imaging of the neck may show an asymmetric narrowing of the subglottis and demonstrate the extent of the lesion, while flexible endoscopy is useful in ruling out other laryngeal abnormalities. Histological confirmation carries the risk of haemorrhage, and up to 50% of biopsies may be too superficial and therefore inconclusive.2 Thus, many believe biopsy is not necessary, as the appearance of the lesion is itself diagnostic.
The airway symptoms gradually worsen over the first year of life as the haemangioma proliferates. However, the growth of the larynx and the natural involution of the haemangioma result in the resolution of the airway symptoms by an age of 2–3 years. Therapeutic interventions aim to maintain the airway before the lesion naturally involutes, hasten the involution process, and even completely terminate the lesion. Numerous options are available, but there is no consensus on the modality of choice. Corticosteroids are the first line of treatment, with IFN and vincristine as options, while surgical excision, cryotherapy, sclerotherapy, low-dose radiation, embolisation and laser vaporisation are the invasive alternatives.3,4 The most commonly used steroids include prednisolone/prednisone administered in a dose of 2–3 mg/kg/day initially and continued at a tapering schedule until the age of 10–12 months. This, however, has been associated with several adverse effects including growth retardation, and immunodeficiency. The mechanism of action of the steroids is uncertain, but they may be modulating haemangiogenesis via an upregulation of cytochrome b, and/or interleukin 6.5 Successful treatment of airway haemangioma by intralesional corticosteroid injections has been reported, but has not been easily reproducible. Also, this option is reserved for small and localised lesions.2,3,6
Systemic treatment with IFNα-2a, an antiviral agent, has been used to treat haemangiomas due to its ability to inhibit angiogenesis by blocking fibroblast growth factor.7 Significant adverse effects of IFN include neurological problems such as seizures, personality changes and spastic diplegia.2
A recent report has thrust propanolol into the limelight, with good results shown in 11 cases of infantile capillary haemangioma.8 However, experience beyond this preliminary data is unavailable.
Open surgical excision has been advocated for bilateral or large haemangiomas, but has been associated with subglottic stenosis, and can result in prolonged intubation and hospitalisation.2 Laser ablation has evolved with availability of carbon dioxide, potassium titanyl phosphate and neodymium:YAG lasers, but they may be associated with transmural injury and subglottic stenosis.2,3 Also, these interventions frequently require repeated sittings that further increase their hazards. Cryotherapy, sclerotherapy and radiation therapy have met with little success and have been overshadowed by their adverse effects.2,3
There were two challenging aspects in the treatment of the infant reported here. First, she had a massive haemangioma all along the trachea, to be managed with surgery/laser ablation successfully without complications. The massive cutaneous haemangioma over the neck also ruled out tracheostomy. Second, the lesion showed a poor response to steroids (dexamethasone/prednisolone) and IFN given either as monotherapy or in combination. Hence, a decision was made to try MP in combination with IFN. It was administered in a pulse fashion to minimise the adverse effects of steroids while capitalising on lesion regression. MP has been used in management of large cutaneous, periocular, and “problematic” haemangiomas9,10 with variable success, but, to our knowledge, this is the first report of pulse therapy with MP combined with IFN to treat congenital subglottic haemangioma. We were able to successfully induce regression of vascularity of the lesion along with resolution of symptoms with this regimen. We did not observe any complications resulting from either steroids or IFN during the therapy. Also, there was no relapse of the lesion after the discontinuation of drugs for at least the 12 months that the case was followed.
LEARNING POINTS
Cutaneous hemangioma in “beard distribution” of face and neck should alert the physician to a possible associated airway haemangioma that may produce obstructive symptoms later.
The conventional treatment for airway haemangioma is corticosteroids and/or laser ablation, succeeded by interferon for the more severe cases.
For stubborn unresponsive lesions, methylprednisolone in conjunction with interferon may be tried to achieve resolution by their add-on benefit.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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