COEUR D’ALENE, IDAHO – Early therapeutic intervention in children with lymphatic malformations appears to reduce the risk of lesion progression and symptomatic complications, according to a large retrospective study.
"Lymphatic malformations are progressive, but early intervention makes a difference in terms of volume increase and the complication rate. Early intervention should definitely be considered when functional impairment due to local extension is a concern," Dr. Joyce Teng said at the annual meeting of the Society for Pediatric Dermatology.
Dr. Joyce Teng
Lymphatic malformations (LMs) are benign, low-flow congenital vascular anomalies due to abnormal formation of lymphatic vessels in utero. The lesions consist of sequestered lymphatic cysts lined with lymphatic epithelium surrounded by connective tissue stroma. These cysts don’t drain. The result is soft, doughy masses underlying normal-looking epidermis.
Close to two-thirds of LMs occur on the head and neck. They commonly cause pain and swelling, especially during an upper respiratory infection. These head and neck lesions not only cause unsightly facial asymmetry, but as they progress they can press on the airway. Truncal lesions not infrequently send affected patients to the emergency department with acute abdominal pain, explained Dr. Teng, director of pediatric dermatology at Stanford (Calif.) University.
There is no ideal therapy for LMs. Management options include conservative observation, surgical excision, sclerotherapy, and potentially disease-modifying medications, with sildenafil and sirolimus among the agents under study.
In children, sclerotherapy is a particularly attractive alternative to surgical excision. The Stanford experience as described by Dr. Teng indicates that doxycycline and ethanolamine are equally safe and effective sclerosants for this purpose, as is the Japanese agent OK-432, unavailable in North America or Europe.
Dr. Teng presented a retrospective chart review of 336 patients under age 20 years with LMs in Stanford’s large clinical database. Half were female. The LMs were first noted at a mean age of 2.1 years and a median of 2 months. Forty-three percent were macrocystic as defined by septated cystic spaces in excess of 2 cc, while another 35% of patients had a mix of macro- and microcysts.
Disease progression was defined as lesion enlargement at a rate greater than the patient’s growth rate or worsening signs and symptoms. The LM progression rate was 47% in childhood.
The median age at the time of progression was 4.9 years. Consistent with the findings of an earlier study by investigators at Harvard University, Boston, the rate of rapid progression in the Stanford study was greater among 15- to 20-year-olds than in children, probably due to the influence of pubertal hormonal changes. In the retrospective 441-patient Harvard study, the LM progression rate was 40% in childhood, 64% in adolescence, and 95% lifetime (J. Craniofac. Surg. 2012;23:149-52).
Dr. Teng and coworkers found that observation without active treatment was associated with a 2.1-fold increased risk of progression. Also, older age at the time of diagnosis was associated with a higher risk of complications. Indeed, the odds of progression rose by 17% per year of age at diagnosis of LM.
In contrast, factors not associated with progression risk in the Stanford study were gender, lesion location or subtype, or having LMs at multiple sites.
Forty-one children with LMs on the head and neck underwent sclerotherapy at a median age of 1-2 years.
Among 19 patients treated with doxycycline, there were two recurrences. Outcomes were rated as excellent in 53% of cases, meaning two investigators agreed that the two sides of the face looked nearly the same post treatment. Outcomes of doxycycline sclerotherapy were rated good in another 26%. Among 12 ethanolamine-treated patients, outcomes were rated excellent in 42% and good in 25%. One of the 12 patients experienced an LM recurrence, as did 3 of 10 treated with OK-432. No procedural complications occurred in the ethanolamine group. One doxycycline-treated patient experienced a treatment-related hemorrhage.
In a multivariate analysis, doxycycline and ethanolamine didn’t differ in effectiveness. Both performed best in treating macrocystic lesions, where 90% of patients experienced marked LM volume reduction, as did 73% of patients with mixed lesions. The success rate was lowest when treating purely microcystic lesions.
"I’ve talked to lots of interventional radiologists. These cases aren’t all that common, and their choice of sclerosant seems to really depend upon their training and comfort level," Dr. Teng said.
She advised getting a baseline magnetic resonance image (MRI) to confirm the diagnosis of LM and to determine the baseline extent of disease in order to guide future decisions about intervention. In addition, a post-treatment MRI showing LM volume reduction provides objective evidence of therapeutic success.