Sex: M
Vaccine: PNC13
Symptoms: Cytogenetic analysis abnormal, Death, Dyspnoea, Gene mutation, Haemolysis
Clinical narrative: He received the Prevnar 13 vaccination and developed another hyperinflammatory episode; complicated by steroid responsive pericardial effusion and presumed inflammatory pneumonitis; complicated by steroid responsive pericardial effusion and presumed inflammatory pneumonitis; This is a literature report.  A contactable other healthcare professional reported that an approximately 7-year-old boy developed an episode of hyperinflammatory flare following vaccination with pneumococcal-13-valent-CRM197-vaccine-conjugate. Additionally, he exhibited lack of efficacy during treatment with azathioprine and methotrexate for chronic pulmonary disease and hyperinflammatory flares [dosages and routes not stated]. The boy was admitted at the age of 10 years for diagnostic lung biopsy in the setting of progressive chronic hypoxic respiratory failure and recurrent hyperinflammatory episodes. He had history of multiple hospital admissions due to infection-triggered recurrent hyperinflammatory flares. At the age of 4 months, he was admitted, for respiratory syncytial virus (RSV) infection. He was again admitted at the age of 1 year for hypospadias repair, and at the age of 3 years and 4 months he was hospitalised for another RSV infection. At the age of 3 years and 8 months he was admitted for what was thought to be mononucleosis due to Epstein-Barr virus positive IgM. Mild gross motor developmental delay was also noted. Till the age of 3 years he received regular vaccination. Subsequently, he stopped receiving vaccine. Approximately, at the age of 4 years, he was admitted with viral bronchiolitis. Respiratory symptoms slowly resolved and haematologic findings improved, thus representing a hyperinflammatory flare that recurred regularly over the following 6 years ranging from 4 to 17 weeks duration mainly treated with unspecified steroids. During the next flare he exhibited with anaemia, leucocytosis and thrombocytosis along with abdominal pain, hepatomegaly, and fevers. Infarcted spleen was also noted. This flare was associated with human herpes virus 7 viraemia. He was readmitted to hospital multiple times for such episodes. During two separate hospitalisations for flares, the diagnosis of haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) were both considered based upon his laboratory features. Overall, two bone marrow biopsies were performed approximately 1 year apart, and both demonstrated normal cellularity and markedly increased hemophagocytosis. Subsequently, he received pneumococcal-13-valent-CRM197- vaccine-conjugate [prevnar-13] vaccine, and developed an episode of hyperinflammatory flare [duration of treatment to reaction onset not stated] which lasted for 4 months. It was complicated by prednisone responsive pericardial effusion and presumed inflammatory pneumonitis. He became corticosteroid dependent weaning of which resulted into haemolysis and dark urine. By the age of 8 years, his episodes were characterized less by persistent febrile episodes but more by shortness of breath, chest discomfort and intermittent desaturations. His condition was steroid responsive and therefore he was treated with prednisone. Subsequently, he started receiving steroid sparing therapy with methotrexate and azathioprine for hyperinflammatory flares and chronic pulmonary disease (later diagnosed as interstitial lung disease). The boy stopped receiving methotrexate and azathioprine. Later, due to his progressive respiratory symptoms, he was admitted to the hospital at the age of 10 years for lung biopsy. After lung biopsy, his condition worsened with right haemothorax and pneumothorax along with respiratory distress. For treatment of his inflammatory state corticosteroid dose was increased and gradually weaned, while anakinra and ciclosporin [cyclosporine] were trialed followed by tocilizumab, with minimal benefit. He died prior to his 11th birthday due to respiratory failure. Whole exome sequencing revealed compound heterozygous paternal frame shift a HMOX1 c.264_269delCTGG (p.L89Sfs*24) and maternal splice donor HMOX1 (c.636 + 2 T > A) consistent with HMOX1 deficiency. Finally he was diagnosed with HMOX1 deficiency that had recurrent autoinflammatory episodes marked by fever, hemolysis and hyperferritinaemia with pathologic features similar to MAS and HLH. Author Comment "He received the Prevnar 13 vaccination and developed another hyperinflammatory episode lasting 4 months complicated by steroid responsive pericardial effusion and presumed inflammatory pneumonitis." "Steroid sparing therapies, such as methotrexate and azathioprine, were briefly introduced but discontinued because no benefit was observed." The outcome of the events was unknown. It was unknown whether an autopsy was performed.; Sender's Comments: The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators as appropriate.; Reported Cause(s) of Death: respiratory failure