title: Autoimmune hemolytic anemia following MF59-adjuvanted influenza vaccine administration: a report of two cases.
abstract: OBJECTIVE
  To describe 2 cases of autoimmune hemolytic anemia (AIHA) following the administration of MF59-adjuvanted influenza vaccine.
  
  
  METHODS
  An 83-year-old white woman developed persistent hyperpyrexia, polyarthralgia, and lower limb hypostenia about 2 days after receiving influenza vaccine. Clinical signs and laboratory evaluations suggested AIHA. The patient was treated with high-dose corticosteroids and immunoglobulins, and her clinical condition improved. A 74-year-old white woman developed severe abdominal pain and asthenia 3 days after the administration of influenza vaccine. Clinical signs and laboratory evaluations disclosed AIHA. She was treated with corticosteroids, rehydration, and blood transfusion; however, she died about 48 hours after hospitalization.
  
  
  CONCLUSIONS
  AIHA has been rarely described following influenza vaccine administration. In the cases described here, the causal relationship between influenza vaccination and the occurrence of AIHA, assessed by means of World Health Organization criteria, was scored as probable. It has been proposed that the mechanism whereby vaccines induce autoimmune responses can be molecular mimicry, although a possible role of other vaccine constituents, with particular regard for adjuvants, such as MF59, can not be excluded. Squalene, a constituent of MF59, has been suggested as a causative agent of autoimmune reactions. However, it is not clear how and under what conditions squalene can cause immune responses.
  
  
  CONCLUSIONS
  Influenza vaccination may rarely trigger severe AIHA, shortly after vaccine administration. A mechanism of molecular mimicry is probably involved in the development of these reactions, although the possible role of adjuvants can not be excluded. Patients should be instructed to report signs and symptoms of autoimmune disorders occurring in the first weeks after administration of influenza vaccine.
authors.affiliation: Tuscan Regional Centre of Pharmacovigilance, Interdepartmental Centre for Research in Clinical Pharmacology and Experimental Therapeutics, University of Pisa, School of Medicine and Surgery, Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Montagnani
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardo
authors.forename: Arianna
authors.initials: A
authors.lastname: Testi
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantarro
authors.forename: Elisa
authors.initials: E
authors.lastname: Ruggiero
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy; D018771:Arthralgia / Q000209:etiology; D001247:Asthenia / Q000209:etiology; D017809:Fatal Outcome; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects*; D035002:Lower Extremity; D018908:Muscle Weakness / Q000209:etiology; D011136:Polysorbates / Q000009:adverse effects*; D013185:Squalene / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene