title: Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle.
abstract: Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.
authors.affiliation: Equipe mixte INSERM E 0011/Université Paris XII, France. romain.gherardi@hmn.ap-hop-paris.fr
authors.forename: R K
authors.initials: RK
authors.lastname: Gherardi
authors.forename: M
authors.initials: M
authors.lastname: Coquet
authors.forename: P
authors.initials: P
authors.lastname: Cherin
authors.forename: L
authors.initials: L
authors.lastname: Belec
authors.forename: P
authors.initials: P
authors.lastname: Moretto
authors.forename: P A
authors.initials: PA
authors.lastname: Dreyfus
authors.forename: J F
authors.initials: JF
authors.lastname: Pellissier
authors.forename: P
authors.initials: P
authors.lastname: Chariot
authors.forename: F J
authors.initials: FJ
authors.lastname: Authier
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000536:Aluminum Hydroxide / Q000009:adverse effects* / Q000276:immunology / Q000493:pharmacokinetics; D000818:Animals; D002648:Child; D004577:Electron Probe Microanalysis; D005208:Fasciitis / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry; D007273:Injections, Intramuscular; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D009220:Myositis / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D015995:Prevalence; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D014761:Viral Hepatitis Vaccines / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D014761:Viral Hepatitis Vaccines; D000536:Aluminum Hydroxide