Age: 0.81
Sex: F
Vaccine: DTAP, PNC
Symptoms: Oedema peripheral, Otitis media acute, Ultrasound scan normal, White blood cell count
Clinical narrative: This is a report from a Non-Pfizer sponsored interventional study. A 10-month-old female patient was enrolled in the sirolimus clinical trial, starting sirolimus on 25Sep2010 at 0.13 mg twice daily for Kaposiform Hemangioendothelioma with Kasabach-Merritt Syndrome. At the time of the event she was receiving 0.32 mg twice daily. Additional suspect medication included PREVNAR, dose number 2 on 16Jun2011 at 1 dose form and DTaP at 1 dose form on 16Jun2011. Relevant medical history included a previous history of Clostridium difficile infection and exposure to chicken pox in Jun2011 prior to the event. Relevant concomitant medication included BACTRIM oral since 25Sep2010 for infection prophylaxis. The subject suffered from Kaposiform Hemangioendothelioma with Kasabach-Merritt phenomenon since birth, extending from her foot all the way up into her inguinal area and lower abdomen, back and buttocks. Due to her significant Kasabach-Merritt phenomenon, her baseline issues included decreased platelets, hemoglobin, fibrinogen and increased D-dimers. On 16Jun2011, the subject received immunizations. The following day, she was seen by her primary care physician due to increased fussiness and fever of 102F. The physician prescribed OMNICEF for supposed acute suppurative otitis media and possible immunization reaction. On 19Jun2011, the subject was noted by parents to have increased swelling of her right leg. She remained afebrile. On 20Jun2011, she was brought to the emergency department, where an ultrasound and labs were performed. The ultrasound showed normal appearance of the major veins of the right leg without evidence of thrombus. The subject was discharged from the emergency department with instructions to loosely wrap an ace bandage around the affected leg. On 21Jun2011, the subject's right leg continued to be swollen. On 22Jun2011, it was noted that she had increased swelling now into her foot, as well as increased fussiness. She reported to the emergency department where she was admitted for possible cellulitis, though there was no erythema or increased temperature. Her sirolimus was held as of 22Jun2011 PM dose. A dose of intravenous CLEOCIN 120 mg every 4 hours was administered. Chest x-ray was normal. Blood and urine cultures had no growth. On 23Jun2011, she remained afebrile. A dose of intravenous CLEOCIN 120 mg every 4 hours was administered. On 24Jun2011 she remained afebrile. MRI of right leg was performed which showed diffuse edema associated with the malformation. A dose of intravenous clindamycin 120 mg every 4 hours was administered. On 25Jun2011, the subject was transferred to another hospital. There was no evidence of cellulitis, but since intravenous clindamycin treatment was already started, the decision was made to continue treatment for 7 days. There was a new discovery of exposure to chicken pox 11 days previous. Due to varicella exposure and immunosuppresion from sirolimus, the subject was treated with 6 days of intravenous and 1 day of oral ZOVIRAX per Infectious Disease. On 26Jun2011, she remained afebrile, but received a dose of oxycodone overnight due to fussiness. Stool cultures including Clostridium difficile were negative; the subject had a previous history of C. difficile infection. Lab work included white blood cell count 26Jun2011 5.6 K/mcL normal range is 6.0 to 17.5; hemoglobin 27Jun2011 10.2 Gm/dL normal range 10.5 to 13.5. On 27Jun2011, the subject remained afebrile, but received three doses oxycodone overnight due to fussiness. Right leg swelling had decreased in regards to twice daily girth measurements. On 28Jun2011, the subject remained afebrile, but received a dose of oxycodone overnight due to fussiness. Her edema had improved, but the KHE lesion was still purpuric and taut; thus treatment needed to be continued. In addition, one dose of steroids was given due to worsening of KHE lesion. No signs of varicella to date. On 29Jun2011, the subject remained afebrile and was restarted on sirolimus 0.32 mg orally twice daily. On 30Jun2011, she remained afebrile and leg was softer in upper thigh area. Intravenous clindamycin was discontinued. Since swelling decreased during hospital stay, she was discharged from the hospital on oral ZOVIRAX on 01Jul2011. At the time of the report, the subject was recovering. Study drug action due to the event was withdrawn temporarily. Per the investigator, there is not a reasonable possibility that the event was related to study drug or to a clinical trial procedure. It was felt that the lymphedema was secondary to PREVNAR and DTaP vaccination response and not secondary to sirolimus, as edema has occurred in KHE lesion after immunizations. Additionally resolution of edema is lengthy due to underlying KHE. Follow-up (27Jul2011): Additional information received from the site. The subject received the following immunizations on 16JUn2011: PCV number two and DTaP. The immunizations were just prior to increased swelling reaction. Per the investigator, edema has been known to occur in KHE lesions after immunizations.