SHORT COMMUNICATION
851 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Efficiency of an mTOR Inhibitor in Kasabach-Merritt Phenomenon with Indolent Tufted Angioma : A Case Report
Charlée NARDIN 1 , Olivia BOCCARA 2 , Catherine ESCHARD 3 , Michael BAYARAM 4 , Thibaud DABUDYK 5 , François AUBIN 1 and Eve PUZENAT 1 * Departments of Dermatology , 1 Centre Hospitalier University Hospital , 3 boulevard Alexandre Fleming , FR-25000 Besançon , 2 Hôpital Necker-Enfants malades , Paris and 3 Centre Hospitalier Universitaire , 4 Department of Pathology , Centre Hospitalier Universitaire , Reims , and
5
Department of Pediatry , Centre Hospitalier Universitaire Minjoz , Besançon , France . * E-mail : eve . puzenat @ chu-besancon . fr Accepted Dec 12 , 2016 ; Epub ahead of print Dec 13 , 2016
Kasabach-Merritt phenomenon ( KMP ) is a life-threatening condition characterized by thrombocytopaenia and disseminated intravascular coagulation ( DIC ), associated with kaposiform hemangioendothelioma ( KHE ) or tufted angioma ( TA ) ( 1 ). TA is a rare , benign vascular tumour , appearing as an infiltrative and erythematous skin plaque that grows and becomes inflammatory when complicated by KMP . The diagnosis is established by histopathology . Treatment of KMP remains challenging . However , mammalian target of rapamycin ( mTOR ) inhibitors have shown efficacy in this condition . We report here a case of KMP arising from TA successfully treated with sirolimus .
CASE REPORT
A 1-month-old boy presented to our clinic with epilepsy after a fall . Since birth , he had had an unresectable subcutaneous vascular abdominal tumour with 2 skin patches , diagnosed as TA on a skin biopsy . Histopathology showed a proliferation of endothelial cells aggregated in vascular lobules scattered in the dermis , with the typical “ cannonball ” appearance . Some blood cells were seen trapped in the ducts formed by tumour endothelial cells . Immunohistochemistry analysis was positive for endothelial markers , CD31 and CD34 , for the lymphatic marker , D2-40 and negative for GLUT1 . The patient was first treated by oral prednisolone , 10 mg / kg / day , and acetylsalicylic acid , 30 mg / day . When he was brought to the emergency room , he had drug-resistant epilepsy with intracranial hypertension and a palpable subcutaneous abdominal mass .
The abdominal tumour has been stable since birth , with a size of 15-cm , height and 30-cm width , extended from the abdomen to the right side of the back and associated with 2 red-bluish skin patches 3 cm in diameter ( Fig . 1 a , b ). Admission laboratory testing indicated a severe drop in platelet count ( 5 × 10 9 / l , normal range 147 – 386 × 10 9 / l ), decreased fibrinogen ( 0.5 g / l , normal range 2 – 4 g / l ), elevated D-Dimer ( 16,532 µ g / l , normal range 0 – 500 µ g / l ), elevated fibrin degradation products ( 25,000 µ g / ml , normal range < 5 µ g / ml ) and anaemia with haemoglobin down to 7 g / dl ( normal range 11.8 – 14.7 g / dl ). Abdominal magnetic resonance imaging ( MRI ) demonstrated a stable vascular tumour of the subcutaneous tissue extending from the anterior wall to the posterior abdominal wall without intra-abdominal involvement ( Fig . 1 c , d ). Furthermore , a left subdural haematoma and subarachnoid haemorrhage associated with acute left cortical , subcortical and external caspule ischaemic lesions were identified by cerebral MRI . In the intensive care unit , initial treatments consisted of platelet transfusions , management of epilepsy and interruption of acetylsalicylic acid . Based on the association of TA and disseminated intravascular coagulation ( DIC ), a diagnosis of KMP was made and platelet transfusions were interrupted , whereas intravenous corticosteroids were increased . After 24 h , brain haemorrhage stopped , but DIC remained active . Thus , prednisolone was switched to sirolimus ( 1.6 mg / m 2 / day in 2 divided oral doses per day ; dosage adjusted every week based on the serum drug level ; target dose 5 – 10 ng / ml ). Response was achieved within one week on platelet counts and DIC . Platelets increased to 0.25 × 10 9 / l at day 1 , 102 × 10 9 / l at day 10 , and reached 267 × 10 9 / l after one month of treatment . Likewise , DIC progressively regressed and disappeared after 2 weeks , with the exception of D-dimers , which levelled off at approximately 700 µ g / l . At the same time , the abdominal tumour decreased slowly . At last followup visit ( 6 months ), the patient was still being treated with sirolimus without complication , with a diminished abdominal tumour and no recurrence of DIC .
DISCUSSION
The patient had indolent TA at KMP presentation , whereas thrombocytopaenia was worsening and DIC detected . Cutaneous KHE can lack cutaneous findings , but patients with KMP usually have inflammatory symptoms , such as enlarging lesion and increased firming with a change in cutaneous colour ( 2 ). Cases of retroperitoneal and mediastinal KHE with KMP without skin change have been reported ( 2 ).
Since there is no gold-standard treatment , KMP manage ment widely varies ( 3 ). Steroids have long been considered as a first-line treatment ( 4 ) even if monotherapy is often ineffective or insufficient , as found in this case ( 5 ). Vincristine has a good efficacy ( 62 % response rate ), but is currently used as a second-line treatment because of the delay of response around 6 weeks , the need for intravenous access , and neurological toxicity ( 5 , 6 ). Recent reports have demonstrated a good safety profile and efficacy of mTOR inhibitors in multiple vascular
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2597 Acta Derm Venereol 2017 ; 97 : 851 – 852