Kaposiform lymphangiomatosis: Diagnosis, pathogenesis, and treatment

Abstract

Kaposiform lymphangiomatosis (KLA) is a life‐threatening rare disease that can cause substantial morbidity, mortality, and social burdens for patients and their families. Diagnosis often occurs long after initial symptoms, and there are few centers in the world with the expertise to diagnose and care for patients with the disease. KLA is a lymphatic anomaly and significant advancements have been made in understanding its pathogenesis and etiology since its first description in 2014. This review provides multidisciplinary, comprehensive, and state‐of‐the‐art information on KLA patient presentation, diagnostic imaging, pathology, organ involvement, genetics, and pathogenesis. Finally, we describe current therapeutic approaches, important areas for research, and challenges faced by patients and their families. Further insights into the pathogenesis of KLA may advance our understanding of other vascular anomalies given that similar signaling pathways may be involved.

Regression of kaposiform lymphangiomatosis and chronic disseminated intravascular coagulation after inhaled budesonide‐formoterol treatment

“…It is often a progressive disease with a poor prognosis. [1][2][3][4] A previously healthy 10-year-old male was found to be thrombocytopenic (70,000/µL) in a preoperative examination for acute appendicitis. He was diagnosed with immune thrombocytopenia by a local physician.…”

“…1 Previous reports indicated that various medical treatments, including corticosteroids, vinblastine, interferon-alpha, doxycycline, thalidomide, and octreotide, as well as surgical interventions such as pleurodesis, chest tube ligation, and tumor resection, have been transient. [1][2][3][4] RAS/PI3K/mTOR (mammalian target of rapamycin) signaling pathway activation has been observed in KLA tissues. 5 Although sirolimus, an mTOR inhibitor, is reportedly effective, 6 its efficacy rate is insufficient, with a partial response, stable disease, and disease progression in 58.3%, 25%, and 16.7% patients, respectively.…”

How we use angiopoietin‐2 in the diagnosis and management of vascular anomalies

“…32 However, the pathophysiology of this rare disease remains poorly understood. 33,34 KHE is classified as a locally aggressive vascular tumor that is associated with Kasabach-Merritt phenomenon (KMP), a coagulopathy characterized by severe thrombocytopenia and hypofibrinogenemia. 1 KHE classically presents as a solitary, ill-defined purpuric cutaneous lesion or mass, most commonly on the extremities, trunk, or neck, in infants and young children, although rare cases have been reported in adults.…”

“…reported that the addition of zoledronic acid to sirolimus therapy, in a patient with KLA and osteolytic bone lesions, resulted in not only clinical improvement but also a further decline in serum Ang‐2 levels 5 . For KLA patients who have suboptimal response to sirolimus or have an identified activating NRAS mutation, trametinib, a MAPK/MEK pathway inhibitor, may be considered, but clinical trials evaluating safety and efficacy have yet to be performed 34 …”

“…A somatic activating mutation in the proto‐oncogene NRAS (neuroblastoma ras viral oncogene homolog: NRAS Q61R ) has been identified in a small cohort of KLA patients and has been studied in human endothelial cells in vitro as a potential disease driver 32 . However, the pathophysiology of this rare disease remains poorly understood 33,34 …”