Management

Treatment is usually individualized based on lesions and symptoms. Medical management includes bisphosphonates to limit bone resorption and alleviate pain. Pegylated interferon has also been shown to improve symptoms. More recently, sirolimus has shown promise, as has been the case for GLA. In some cases, pleural effusions respond to treatment with mTOR inhibitors, but the pulmonary parenchymal disease rarely improves with therapy [69, 70].

Surgical resection with bone grafting for GSD can also be performed; however, it carries considerable morbidity and is often complicated by recurrence and graft failure when medical therapy for disease control is not also instituted [40]. The same caveat applies to surgical intervention for CSF leak.

Radiation has historically been used in the treatment of the highest risk GSD cases(often cervical spine). The dose used is typically in the range 25–45 Gy. The side effects including risk of malignancies limit its usefulness, especially in the young. It may be useful as a palliative option especially for intractable pain associated with bone destruction [40, 68].

Course/Prognosis

GSD has the most favorable outcomes compared to GLA and KLA. A systematic review of 89 publications showed 5 deaths, however, suggested half of patients with GSD have persistent disease despite treatment [71]. A separate cohort out of Japan demonstrated a mortality of 28.6% (10/35 patients) [32].

Due to the rarity of the disease, only limited longitudinal follow-up data are available, making it dif cult to compare different interventions. In addition, the disease course is often unpredictable and can be remitting/relapsing with some reports of spontaneous resolution or long-term stability after an initial aggressive course. Intrathoracic involvement, particularly pleural effusion, is associated with worse outcomes. There is anecdotal evidence that exacerbations can occur with puberty and pregnancy.

and their major tributaries. Failure of the conducting lymphatics results in refux and leakage of the lymphatic fuid into pleural, pericardial and peritoneal spaces [21].

Etiopathogenesis

The etiology is poorly understood and likely varies within the umbrella term of CCLA. Genetic mutations in EPHB4 [72]and ARAF mutations [73] have been identi ed and more recently the JAG-1 gene has also been implicated [72, 74].

Clinical Presentation and Diagnosis

Patients present with chylothorax, chylous pulmonary congestion, chyloptysis and plastic bronchitis, chylous ascites, protein-losing enteropathy, chyluria, chylorrhea, stulous communications with abdominal viscera (Fig. 21.13), cutaneous vesicles, or super cial chylous leaks. A de nitive diagnosis can be made with lymphangiography and dynamic magnetic resonance lymphangiography. As presentations vary widely, an individualized approach is needed for diagnosis and treatment.

Management

Traditionally, supportive therapy with albumin and immunoglobulin therapy and surgical correction have been utilized. Mutations in EPHB4 and ARAF suggest a role for mTOR or MAPK/MEK inhibition, and several groups have reported responses with the use of sirolimus and trametinib [73]. Other groups [75, 76], however, report a lack of success with sirolimus in CCLA; some of these differences in responses may be related to the genotypically heterogeneous nature of this disorder. Surgical interventions, including lymphaticovenous bypass of the thoracic duct, have not been consistently successful [39]. Mapping of sites of lymphatic leak followed by embolization have been reported to control lymphatic leak by some centers with particular expertise [2, 6].

Channel-Type LM/Central Conducting LM

The central conducting lymphatic anomalies (CCLA) are a family of lymphatic anomalies, encompassing many disorders that cause dysfunction of the paraxial lymphatic system including the lumbar trunks, cisterna chyli, thoracic duct,

Course/Prognosis

Long-term follow-up studies are lacking, particularly with different interventions. Common clinical complications include chronic edema and recurrent infections.