Age: 16.0
Sex: F
Vaccine: MENB, MNQ, MENB, MENB, MNQ
Symptoms: Pain in extremity, Paroxysmal nocturnal haemoglobinuria, Purpura, Resuscitation, Stupor
Clinical narrative: This case was reported by a pharmacist and described the occurrence of vaccination failure in a 16-year-old female patient who received BEXSERO. Co-suspect products included BEXSERO, MENACTRA, MENACTRA and eculizumab for paroxysmal nocturnal hemoglobinuria. On 8th April 2016, the patient received 1st dose of BEXSERO. On 13th May 2016, the patient received the 2nd dose of BEXSERO. On 8th April 2016, the patient received MENACTRA. On 13th May 2016, the patient received MENACTRA. On 19th November 2016, the patient started eculizumab 600 mg weekly. On 25th November 2016, the dose was changed to 600 mg weekly. In April 2016, less than a month after receiving BEXSERO and not applicable after receiving BEXSERO, the patient experienced paroxysmal nocturnal hemoglobinuria (serious criteria death and GSK medically significant). In November 2016, the patient experienced vaccination failure (serious criteria death and GSK medically significant), meningococcemia (serious criteria death and GSK medically significant), bone pain (serious criteria death), joint pain (serious criteria death), back pain (serious criteria death), pain in extremity (serious criteria death), headache (serious criteria death), cardiac arrest (serious criteria death and GSK medically significant), hemorrhage purpuric (serious criteria death) and unresponsive stimuli (serious criteria death and GSK medically significant). The patient was treated with BENADRYL, TORADOL, ROCEPHIN, intravenous fluid (nos) and COMPAZINE. On an unknown date, the outcome of the vaccination failure, meningococcemia, paroxysmal nocturnal hemoglobinuria, bone pain, joint pain, back pain, pain in extremity, headache, cardiac arrest, hemorrhage purpuric and unresponsive to stimuli were fatal. The patient died on 27th November 2016. The reported cause of death was bone pain, joint pain, back pain, pain in extremity, headache, unresponsive to stimuli, cardiac arrest, hemorrhage purpuric and meningococcemia. An autopsy was performed. The autopsy determined cause of death was Waterhouse-Friderichsen syndrome, Neisseria meningitidis infection nos, hypovolemic shock, adrenal hemorrhage, hypotension, stupor, purpuric rash, adrenal crisis and toxemia. It was unknown if the reporter considered the vaccination failure, meningococcemia and paroxysmal nocturnal hemoglobinuria to be related to BEXSERO. It was unknown if the reporter considered the vaccination failure, meningococcemia, bone pain, joint pain, back pain, pain in extremity, headache, cardiac arrest, hemorrhage purpuric and unresponsive to stimuli to be related to BEXSERO. Additional details were provided as follows: Over the past 6 months from the date of reporting, the patient had approximately 4 hemolytic crisis and several hospital admissions. The patient received a MENACTRA booster on 8th April 2016 and 13th May 2016. The patient had not require any blood transfusions since spring 2016 until the prior 2 months when the patient required two transfusions for symptomatic anemia associated with ongoing hemolysis which were done on 21st October 2016 and 25th October 2016. Because of the increased need for transfusions, the patient was started on eculizumab with 1st dose of 600 mg on 19 November 2016. The patient tolerated it and was discharged on 21st November 2016 and her 2nd dose was given on 25th November 2016. The patient was presented on 26th November 2016 to emergency department with diffuse bone and joint pains, back and extremities ache, posterior headache with no associated visual changes or fever. The patient was treated symptomatically with IV fluids, IV COMPAZINE, TORADOL, and BENADRYL with improvement of symptoms. There was no evidence of papilledema and no evidence of significant hemolysis. The white blood count and absolute neutrophil count increased from 5.3 and 2.74 on 25th November 2016 to 8.9 and 8.46 on 26th November 2016. Hemology or oncology was consulted and it was believed that this presentation was consistent with her prior eculizumab side effects. The patient was discharged home on close observation. Sometime later at home, emergency medical service was called for progressive deterioration. In the ambulance the patient became unresponsive and went into cardiac arrest and went to an outside hospital. The patient was noted to have hemorrhagic purpura of head and neck and was given 2g IV of ROCEPHIN to cover possible meningococcemia. There was no sustained return of spontaneous circulation despite resuscitation efforts and the patient was pronounced dead on 27th November 2016 at 3AM. Autopsy revealed that, the patient's acute clinical decompensation, hemorrhagic purpura on head and neck and the post-mortem findings including the adrenal hemorrhage or necrosis, and positive N. meningitidis serotype B culture from meninges are all consistent with N. meningitidis included Waterhouse-Friderichsen syndrome. Waterhouse-Friderichsen syndrome is a well-described clinical entity that is characterized by a fulminant course of headache, purpuric eruption, hypotension, stupor and death if not treated timely. It was typically caused by N. meningitidis infection. In these cases of Waterhouse-Friderichsen syndrome with adrenal hemorrhage, the direct cause of rapid death typically results from hypovolemic shock/adrenal crisis from the bacterial toxin release rather than direct suppurative meningitis. The toxemia was induced most often by the outer membrane glycolipid, lipooligosaccharide which results in injury of the endothelial cells resulting in microhemorrhages, particularly of the skin and adrenal gland along with extravasation of fluid into the serous cavities and often with pulmonary edema and causes a disseminated intravascular (DIC) type picture. It was unknown if the reporter considered the vaccination failure, meningococcemia, bone disorder, joint pain, back pain, pain in extremity, headache, cardiac arrest, hemorrhage purpuric and unresponsive to stimuli to be related MENACTRA and eculizumab.