INTRODUCTION: A previously healthy, full-term 20-month old male presented with a “bump on his head” that was noted incidentally by his mother earlier the day of presentation.
CASE PRESENTATION: Our patient had no history of trauma but did have a history of intermittent tactile fevers, decreased intake, cough, posttussive emesis and rhinorrhea of several weeks duration that had not responded to treatment (medication unknown) from his pediatrician. On examination, the patient was ill-appearing, afebrile with a respiratory rate of 24 breaths/minute, pulse of 150 beats/minute, blood pressure of 110/68 mmHg and oxyhemoglobin saturation of 99% on room air. There was a right frontoparietal protuberance that was boggy and mildly tender to palpation. A head CT revealed a right frontal epidural hematoma and possible skull fracture. A chest radiograph further revealed cardiomegaly with pericardial effusion and pulmonary edema. The child underwent emergent epidural evacuation and, once stabilized, pericardiocentesis that produced exudative fluid with a lymphocytic predominance. Extensive investigation failed to produce evidence of child abuse nor any underlying hematologic, cardiac, rheumatologic or infectious disorder. Over the next five months, the child had multiple episodes of mild respiratory illnesses that were followed by pericardial effusions, eventually leading to placement of a pericardial window. The patient subsequently developed recurrent pleural effusions requiring placement of multiple thoracostomy tubes. Eventually, video assisted thorascopic surgery (VATS) was performed. Analysis of the recovered pleural fluid was notable for triglycerides of 298 mg/dL with chylomicrons consistent with chylothorax.The child was treated with Octreotide and placed on a low fat, medium chain triglyceride (MCT) diet. Despite treatment, the child continued to have reaccumulation of pericardial and pleural effusions. Pleurodesis with doxycycline failed to prevent recurrent pleural effusions and exacerbated the pericardial effusion due to obliteration of the pericardial window. Finally, a secondary pericardial window was made and left diaphragmatic fenestration was performed. Histopathologic analysis of the pericardial and diaphragmatic material revealed dilated and abnormal lymphatic channels consistent with a diffuse lymphatic anomaly. There were also additional findings of clusters of hemosiderotic spindled cells with occasional interspersed red cells. CT of the chest and abdomen revealed mediastinal lymphatic malformations, as well as splenic and hepatic nodules. The clinical progression, imaging and immunophenotyic features of this patient were consistent with the diagnosis of lymphangiomatosis, specifically kaposiform lymphangiomatosis.
DISCUSSION: Lymphangiomatosis is a rare disease characterized by a diffuse proliferation of lymphatic vessels involving the bones, neck, mediastinum, spleen, liver, lungs and pleura. Although affected patients may be asymptomatic, pleural and bony involvement can lead to respiratory distress and pathologic fractures, as seen in our patient. Furthermore, patients with kaposiform lymphangiomatosis are reported to have friable blood vessels, mild thrombocytopenia and hemorrhagic manifestations. Diagnosis of lymphangiomatosis is made by a constellation of clinical, radiographic and histologic features. Sharply defined, non-enhancing lesions can be seen in the lung, liver and spleen. Histopathologically, features are nonspecific and overlap with cavernous or capillary hemangiomas. There is no definitive treatment for lymphangiomatosis, rather palliative therapies such as immunosuppression, interferon-alpha, propranolol, draining of effusions, or pleurodesis are performed. Prognosis is generally poor and most often defined by the progression of pulmonary involvement.
CONCLUSIONS: Despite the surgical and medical interventions noted above, this patient continues to have periods of acute decompensation with reaccumulation of effusions following mild viral illnesses. These episodes have, however, decreased in frequency after initiation of Rapamune (Sirolimus), which has been shown to have clinical efficacy in Lymphangioleiomyomatosis (LAM), a similar disease seen in adults. The exact role of Rapamune in the treatment of lymphangiomatosis remains to be seen.
Reference #1 Shah AR, Dinwiddie R, Woolf D, Ramani R, Higgins JNP, and Matthew DJ. Generalized Lymphangiomatosis and Chylothorax in the Pediatric Age Group. Pediatric Pulmonology 1992. 14:126-130.
Reference #2 Yang DH and Goo HW. Generalized Lymphangiomatosis: Radiologic Findings in Three Pediatric Patients. Korean J Radiol. 2006. 7(4):287-291.
Reference #3 McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch III JP, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee H, Krischer JP and Trapnell BC. Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis. NEJM. 2011. 364(17): 1595-1605.
DISCLOSURE: The following authors have nothing to disclose: Christine Gould, Suraiya Kureshi, Dinesh Pillai, Anastassios Koumbourlis
The use of rapamune (sirolimus) is not FDA approved for the treatment of lymphangiomatosis in the pediatric population. - this is off label use.