Sex: F
Vaccine: COVID19
Symptoms: Haemoglobin, Haemophagocytic lymphohistiocytosis, Inflammatory marker test, Interleukin level, Investigation
Clinical narrative: Macrophage Activating Syndrome After Covid-19 Vaccine; Her symptoms recurred 10 days after receiving the second dose; This is a literature report.  A 15-year-old female patient received BNT162b2 (BNT162B2), as dose 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history and concomitant medications were not reported. Vaccination history included: Bnt162b2 (DOSE 1, SINGLE), for COVID-19 immunisation, reaction(s): "Macrophage activation syndrome". The following information was reported: HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (medically significant), 10 days after the suspect product(s) administration, outcome "unknown", described as "Macrophage Activating Syndrome After Covid-19 Vaccine"; DISEASE RECURRENCE (medically significant), 10 days after the suspect product(s) administration, outcome "unknown", described as "Her symptoms recurred 10 days after receiving the second dose". The patient underwent the following laboratory tests and procedures: Biopsy bone marrow: (unspecified date) revealed hemophagocytosis; Blood fibrinogen: (unspecified date) hypofibrinogenemia; Blood triglycerides: (unspecified date) hypertriglyceridemia; Epstein-Barr virus antibody: (unspecified date) negative; Haemoglobin: (unspecified date) anemia; Inflammatory marker test: (unspecified date) significantly elevated; Interleukin level: (unspecified date) extremely high; CXCL9: (unspecified date) extremely high; CXCL9: (16May2022) 60000 pg/mL; (31May2022) 90000 pg/mL; (24Mar2022) 100000 pg/mL; (29Mar2022) 200000 pg/mL; (19Apr2022) 1500000 pg/mL; (16May2022) 400000 pg/mL; (31May2022) 400000 pg/mL; (23Aug2022) 100000 pg/mL; (13Oct2022) 5000 pg/mL; IL2-R: (unspecified date) extremely high; (29Mar2022) 2500 IU/ml; (19Apr2022) 1000 IU/ml; (31May2022) 2500 IU/ml; (15Jun2022) 500 IU/ml; (23Aug2022) 2500 IU/ml; (unspecified date) negative; (unspecified date) negative; (unspecified date) negative; Serum ferritin: (unspecified date) hyperferritinemia; Whole-genome sequencing: (unspecified date) revealed a heterozygous variant of uncertain, notes: significance in UNC13D c.962C>A (p.Thr321Asn). Therapeutic measures were taken as a result of haemophagocytic lymphohistiocytosis, disease recurrence.  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 up was 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 events haemophagocytic lymphohistiocytosis, disease recurrence 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-PV202300098652 Same article/drug/patient and different Event;