Clinical Reviews in Allergy & Immunology

, Volume 41, Issue 2, pp 163–168 | Cite as

Macrophagic Myofaciitis a Vaccine (alum) Autoimmune-Related Disease

  • Eitan Israeli
  • Nancy Agmon-Levin
  • Miri Blank
  • Yehuda ShoenfeldEmail author


Macrophagic myofasciitis (MMF) is an immune-mediated condition first reported in 1998. MMF is characterized by post-vaccination systemic manifestations as well as local-stereotyped and immunologically active lesion in the site of inoculation (deltoid muscle). MMF systemic symptoms included myalgias, arthralgias, marked asthenia, muscle weakness, chronic fatigue, and fever. Recently, studies demonstrated that the local lesion is due to persistence for years at site of injection of an aluminum (Al(OH)3) adjuvant commonly used in human vaccines. Time elapsed from last immunization with an Al(OH)3-containing vaccine to muscle biopsy range from 3 months to 8 years; in rare cases, MMF may be diagnosed even 10 years post-vaccination. The discrepancy between the wide applications of aluminum hydroxide-containing vaccines and the very limited number of MMF cases reported may be resolved by observations suggesting that aluminum-containing vaccinations may trigger MMF in genetically susceptible subjects carrying the HLA-DRB1*01. Thus, MMF may be defined as an emerging novel condition that may be triggered by exposure to alum-containing vaccines, in patients with a specific genetic background, and this temporal association may be exhibited from a few months up to 10 years.


Macrophagic myofaciitis Vaccines Aluminum Autoimmunity Adjuvant 


  1. 1.
    Gherardi RK, Coquet M, Cherin P et al (1998) Macrophagic myofasciitis: an emerging entity. Groupe d’Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l’Association Francaise contre les Myopathies (AFM). Lancet 352:347–352PubMedCrossRefGoogle Scholar
  2. 2.
    Gherardi RK (2003) Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome. Rev Neurol (Paris) 159:162–164Google Scholar
  3. 3.
    Gherardi RK, Coquet M, Cherin P et al (2001) Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain 124:1821–1831PubMedCrossRefGoogle Scholar
  4. 4.
    Gherardi RK, Authier FJ (2003) Aluminum inclusion macrophagic myofasciitis: a recently identified condition. Immunol Allergy Clin North Am 23:699–712PubMedCrossRefGoogle Scholar
  5. 5.
    Lacson AG, D’Cruz CA, Gilbert-Barness E, Sharer L, Jacinto S, Cuenca R (2002) Aluminum phagocytosis in quadriceps muscle following vaccination in children: relationship to macrophagic myofasciitis. Pediatr Dev Pathol 5:151–158PubMedCrossRefGoogle Scholar
  6. 6.
    Thomas HV, Stimpson NJ, Weightman AL, Dunstan F, Lewis G (2006) Systematic review of multi-symptom conditions in Gulf War veterans. Psychol Med 36:735–747PubMedCrossRefGoogle Scholar
  7. 7.
    Cherin P, Gherardi RK (2000) Macrophagic myofasciitis. Curr Rheumatol Rep 2:196–200PubMedCrossRefGoogle Scholar
  8. 8.
    Authier FJ, Cherin P, Creange A et al (2001) Central nervous system disease in patients with macrophagic myofasciitis. Brain 124:974–983PubMedCrossRefGoogle Scholar
  9. 9.
    Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y (2009) Adjuvants and autoimmunity. Lupus 18:1217–1225PubMedCrossRefGoogle Scholar
  10. 10.
    Eisenbarth SC, Colegio OR, O’Connor W, Sutterwala FS, Flavell RA (2008) Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122–1126PubMedCrossRefGoogle Scholar
  11. 11.
    Kool M, Soullie T, van Nimwegen M et al (2008) Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med 205:869–882PubMedCrossRefGoogle Scholar
  12. 12.
    Kool M, Petrilli V, De Smedt T et al (2008) Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 181:3755–3759PubMedGoogle Scholar
  13. 13.
    Authier FJ, Sauvat S, Christov C et al (2006) AlOH3-adjuvanted vaccine-induced macrophagic myofasciitis in rats is influenced by the genetic background. Neuromuscul Disord 16:347–352PubMedCrossRefGoogle Scholar
  14. 14.
    Exley C, Swarbrick L, Gherardi RK, Authier FJ (2009) A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses 72:135–139PubMedCrossRefGoogle Scholar
  15. 15.
    Guis S, Mattei JP, Nicoli F et al (2002) Identical twins with macrophagic myofasciitis: genetic susceptibility and triggering by aluminic vaccine adjuvants? Arthritis Rheum 47:543–545PubMedCrossRefGoogle Scholar
  16. 16.
    Guis S, Pellissier JF, Nicoli F et al (2002) HLA-DRB1*01 and macrophagic myofasciitis. Arthritis Rheum 46:2535–2537PubMedCrossRefGoogle Scholar
  17. 17.
    Lach B, Cupler EJ (2008) Macrophagic myofasciitis in children is a localized reaction to vaccination. J Child Neurol 23:614–619PubMedCrossRefGoogle Scholar
  18. 18.
    Kalil RK, Monteiro A Jr, Lima MI et al (2007) Macrophagic myofasciitis in childhood: the role of scanning electron microscopy/energy-dispersive spectroscopy for diagnosis. Ultrastruct Pathol 31:45–50PubMedCrossRefGoogle Scholar
  19. 19.
    Ryan AM, Bermingham N, Harrington HJ, Keohane C (2006) Atypical presentation of macrophagic myofasciitis 10 years post vaccination. Neuromuscul Disord 16:867–869PubMedCrossRefGoogle Scholar
  20. 20.
    Verdier F, Burnett R, Michelet-Habchi C, Moretto P, Fievet-Groyne F, Sauzeat E (2005) Aluminium assay and evaluation of the local reaction at several time points after intramuscular administration of aluminium containing vaccines in the Cynomolgus monkey. Vaccine 23:1359–1367PubMedCrossRefGoogle Scholar
  21. 21.
    Park JH, Na KS, Park YW, Paik SS, Yoo DH (2005) Macrophagic myofasciitis unrelated to vaccination. Scand J Rheumatol 34:65–67PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Eitan Israeli
    • 1
  • Nancy Agmon-Levin
    • 1
    • 2
  • Miri Blank
    • 1
  • Yehuda Shoenfeld
    • 1
    • 2
    • 3
    Email author
  1. 1.Center for Autoimmune DiseasesSheba Medical CenterTel-HashomerIsrael
  2. 2.Department of Medicine ‘B’ and Center for Autoimmune DiseasesChaim Sheba Medical CenterTel-HashomerIsrael
  3. 3.Sackler Faculty of Medicine, Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune DiseasesTel-Aviv UniversityTel-AvivIsrael

Personalised recommendations