Sex: F
Vaccine: COVID19
Symptoms: Complement factor, Complement factor C3, Complement factor C4, Cryoglobulinaemia, Cryoglobulins
Clinical narrative: Systemic vasculitides; systemic lupus erythematosus; antiphospholipid syndrome; cryoglobulinemia; This is a literature report.  A 64-year-old female patient received BNT162b2 (BNT162B2), on 03Mar2021 as dose 1, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history included: "Raynaud's disease" (unspecified if ongoing); "hand arthritis" (unspecified if ongoing); "Sjogren's syndrome", start date: Aug2020 (unspecified if ongoing); "leukocytoclastic vasculitis", start date: Jan2021 (unspecified if ongoing). The patient's concomitant medications were not reported. Past drug history included: Prednisone, start date: Jan2021, for leukocytoclastic vasculitis, notes: for 2 weeks. The following information was reported: VASCULITIS (hospitalization) with onset 11Mar2021, outcome "recovering", described as "Systemic vasculitides"; ANTIPHOSPHOLIPID SYNDROME (hospitalization, medically significant) with onset Mar2021, outcome "recovering"; CRYOGLOBULINAEMIA (hospitalization, medically significant) with onset Mar2021, outcome "recovering", described as "cryoglobulinemia"; SYSTEMIC LUPUS ERYTHEMATOSUS (hospitalization, medically significant) with onset Mar2021, outcome "recovering". The patient was hospitalized for systemic lupus erythematosus, antiphospholipid syndrome, cryoglobulinaemia, vasculitis (discharge date: 04Jun2021). The event "systemic vasculitides" required emergency room visit. The patient underwent the following laboratory tests and procedures: Activated partial thromboplastin time (24-33): (Mar2021) 25.6 seconds, notes: admission; Alanine aminotransferase (normal high range 33): (Mar2021) 15.0 IU/l, notes: admission; Antibody test (0-99): (Mar2021) 10, notes: unit: AU/mL admission; Anti-cyclic citrullinated peptide antibody (0-20): (Mar2021) 2, notes: unit: units admission; Antineutrophil cytoplasmic antibody: (Mar2021) Negative, notes: admission; Antinuclear antibody (normal high range 80): (Mar2021) 640, notes: (dilution) admission; (Mar2021) less than 80, notes: (dilution) admission; (Mar2021) less than 80, notes: (dilution) admission; Antinuclear antibody (0-99): (Mar2021) 31, notes: admission; (Mar2021) 167, notes: unit: AU/mL admission; (Mar2021) 15, notes: unit: AU/mL admission; (Mar2021) 9, notes: unit: AU/mL admission; (Mar2021) 25, notes: unit: AU/mL admission; Antiphospholipid antibodies (normal high range 20): (Mar2021) less than 4.0, notes: unit:CU admission; (Mar2021) less than 6.4, notes: unit:U/MN admission; Antiphospholipid antibodies (normal high range 20): (Mar2021) less than 1.1, notes: admission; Aspartate aminotransferase (normal high range 32): (Mar2021) 26.0 IU/l, notes: admission; Biopsy: (Jan2021) proven leukocytoclastic vasculitis; Blood creatinine (0.5-0.9): (Mar2021) 0.86 mg/dl, notes: admission; (2021) 0.71 mg/dl, notes: discharge; Blood immunoglobulin A (0-20): (Mar2021) 1.0, notes: unit: APS IgA admission; Blood immunoglobulin A (70-400): (Mar2021) 96 mg/dl, notes: admission; Blood immunoglobulin G (0-11): (Mar2021) 1.0, notes: unit:  GPS IgG admission; Blood immunoglobulin M (0-25): (Mar2021) 85, notes: unit: MPS IgM admission; Blood immunoglobulin M (30-230): (Mar2021) 124 mg/dl, notes: admission; Cardiolipin antibody (normal high range 20): (Mar2021) less than 1.4, notes: unit: CU admission; Cardiolipin antibody (normal high range 20): (Mar2021) less than 2.6, notes: admission; (Mar2021) less than 1.0, notes: admission; Complement factor (normal low range 41): (Mar2021) less than 10, notes: admission; Complement factor C3 (90-180): (Mar2021) 101 mg/dl, notes: admission; Complement factor C4 (10-40): (Mar2021) less than 4, notes: admission; (2021) 3 mg/dl, notes: discharge; Cryoglobulins: (Mar2021) Positive at 14%, notes: admission; (2021) Positive at 1%, notes: discharge; Double stranded DNA antibody (0-99): (Mar2021) 2, notes: admission; Electrophoresis protein (3.8-5.7): (Mar2021) 3.48 g/dl, notes: admission; Electrophoresis protein (0.08-0.23): (Mar2021) 0.26 g/dl, notes: admission; Electrophoresis protein (0.45-0.92): (Mar2021) 1.06 g/dl, notes: admission; Electrophoresis protein (0.5-1.03): (Mar2021) 0.87 g/dl, notes: admission; Electrophoresis protein (0.54-1.03): (Mar2021) 0.52 g/dl, notes: admission; Electrophoresis protein (normal low range 0): (Mar2021) 0.03 g/dl, notes: admission; Electrophoresis protein (6.4-8.3): (Mar2021) 6.2 g/dl, notes: admission; Flow cytometry: (Mar2021) No leukemia or non-Hodgkin lymphoma cells, notes: admission; Haemodynamic test: (Mar2021) stable; Haemoglobin (11.5-15.5): (Mar2021) 11.1 g/dl, notes: admission; (2021) 9.4 g/dl, notes: discharge; Hepatitis B core antibody: (Mar2021) Non-reactive, notes: admission; Hepatitis B surface antibody: (Mar2021) Non-reactive, notes: admission; Hepatitis C antibody: (Mar2021) Non-reactive, notes: admission; Histone antibody (0-99): (Mar2021) 19, notes: admission; HIV antibody: (Mar2021) Non-reactive, notes: admission; Immunology test (700-1600): (Mar2021) 323 mg/dl, notes: admission; Immunology test: (Mar2021) IgMk paraprotein at b/r interface, notes: admission; (Mar2021) No paraprotein detected, notes: admission; International normalised ratio: (Mar2021) 0.97, notes: admission; (2021) 2.11, notes: discharge; cryocrit: (Mar2021) 14 %; (2021) dropped to 1; dRVVT (normal high range 1.20): (Mar2021) 1.101, notes: admission; Hexagonal phase phospholipid neutralization (normal high range 8.0): (Mar2021) 0.1 seconds, notes: admission; Platelet neutralization (normal high range 1.0): (Mar2021) 0.0 seconds, notes: admission; Rheumatological work-up: (Mar2021) SLE, APS, and cryoglobulinemia, notes: photosensitivity, malar rash, bilateral symmetrical leg purpura, positive ANA, low complement levels with undetectable C4, elevated IgM antiphospholipid antibody directed to phosphatidylserine (aPL-PS), cryocrit of 14%; physical exam: (Mar2021) there was a bluish discoloration of all fingertips, notes: the right third distal phalanx was showing signs of necrosis, and purpuric rash was seen on her legs; Platelet count (150-400): (Mar2021) 437.0 x10 3/mm3, notes: admission; (2021) 338 x10 3/mm3, notes: discharge; Protein total (normal low range 6.4): (Mar2021) 6.6 g/dl, notes: admission; Protein urine: (Mar2021) Protein concentration too low for fractionation, notes: admission; Red blood cell sedimentation rate (normal high range 30): (Mar2021) 59, notes: unit: mm/hr admission; (2021) less than 1, notes: unit: mm/hr discharge; Rheumatoid factor (normal high range 14): (Mar2021) 463 IU/ml, notes: admission; SARS-CoV-2 antibody test: (15Apr2021) Negative; White blood cell count (normal low range 4): (Mar2021) 6.7 x10 3/mm3, notes: admission; (2021) 11.2 x10 3/mm3, notes: discharge. Therapeutic measures were taken as a result of systemic lupus erythematosus, antiphospholipid syndrome, cryoglobulinaemia, vasculitis.  Clinical course: On 03/11/21 she saw her dermatologist for the bluish discoloration of her fingertips, when her right third distal phalanx started to turn black for the first time, which was accompanied by overall worsening upper extremity Raynaud's disease. She was again started on prednisone, 10 mg daily, which did not help with the fingertip lesions. Eventually, the patient presented to the Emergency Department (ED) on 03/20/21 with stabbing pain and decreased sensation in all her fingertips. She was hemodynamically stable. She was started on intravenous methylprednisolone (500 mg/day for 3 days) and heparin infusion. The purpuric rash on her legs resolved but the discoloration and pain in the fingertips worsened with necrosis affecting all fingertips. Therefore, therapeutic plasma exchange (TPEX) was initiated for removal of cryoglobulins. Patient received TPEX (6 sessions every other day) after which her cryocrit dropped to 1%. She was also given intravenous epoprostenol that improved her skin color and reduced fingertip pain. She was discharged home on 4/6/2021.; Sender's Comments: As there is limited information in the case provided, the causal association between the reported events: "Systemic lupus erythematosus", "Antiphospholipid syndrome", "Cryoglobulinaemia", "Vasculitis" and the suspect drug BNT162B2 cannot be excluded. The case will be reassessed once new information is available.   The impact of this report on the benefit/risk profile of the Pfizer drug 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.