Sex: F
Vaccine: COVID19
Symptoms: Haemophagocytic lymphohistiocytosis, Inflammatory marker test, Interleukin level, Interleukin-2 receptor assay, Investigation
Clinical narrative: Macrophage activation syndrome; This is a literature report.  A 15-year-old female patient received BNT162b2 (BNT162B2), as dose 1, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history and concomitant medications were not reported.  The following information was reported: HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (medically significant), 10 days after the suspect product(s) administration, outcome "unknown", described as "Macrophage activation syndrome". The patient underwent the following laboratory tests and procedures: Biopsy bone marrow: (unspecified date) hemophagocytosis; Blood fibrinogen: (unspecified date) hypofibrinogenemia; Blood triglycerides: (unspecified date) hypertriglyceridemia; Epstein-Barr virus antibody: (unspecified date) Positive; Haemoglobin: (unspecified date) anemia; Inflammatory marker test: (unspecified date) significantly elevated; Interleukin level: (unspecified date) extremely high; Interleukin level: (24Mar2022) 100000 pg/mL; (29Mar2022) 200000 pg/mL; (19Apr2022) 150000 pg/mL; (16May2022) 400000 pg/mL; (31May2022) 400000 pg/mL; (15Jun2022) 100000 pg/mL; (23Aug2022) 100000 pg/mL; (13Oct2022) 50000 pg/mL; Interleukin level: (29Mar2022) 2500 IU/ml; (19Apr2022) 1000 IU/ml; (31May2022) 2500 IU/ml; (31May2022) 500 IU/ml; (15Jun2022) 500 IU/ml; (23Aug2022) 2500 IU/ml; Interleukin-2 receptor assay: (unspecified date) extremely high; CXCL9: (unspecified date) extremely high; CXCL9: (16May2022) 60000 pg/mL; (31May2022) 90000 pg/mL; Serum ferritin: (unspecified date) hyperferritinemia; Whole-genome sequencing: (unspecified date) heterozygous variant, notes: of uncertain significance in UNC13D c.962C>A (p.Thr321Asn. Therapeutic measures were taken as a result of haemophagocytic lymphohistiocytosis.  Clinical course: A 15-year-old previously healthy female developed fatigue, fevers,myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work upwas negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron; however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators.Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine.; Sender's Comments: Based on the available information and the known product safety profile, a causal relationship between the reported event haemophagocytic lymphohistiocytosis and BNT162B2 is considered possible. 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.,Linked Report(s) : US-PFIZER INC-202300210174 Same article/ patient/ Event and different dose.;