Global Vaccine Safety

Questions and Answers about macrophagic myofasciitis (MMF)

Q1. What is MMF and how is it related to aluminium in vaccines?

A. Deltoid muscle biopsies performed in France in patients with a variety of complaints have revealed in a small number the presence of a minute inflammatory focus of macrophages, along with crystal inclusions and associated microscopic muscle necrosis. These localized lesions have been shown to contain aluminium salts. Since the location of the lesions in the deltoid muscle coincides with the usual site of injection for vaccines, it would appear that these microscopic lesions are likely to be related to immunization with vaccines that contain aluminium adjuvants.

Q2. Is MMF a general disease or syndrome?

A. There is no evidence to suggest that MMF is a specific illness. MMF is a lesion containing aluminium salts, identified by histopathological examination, found at the site of previous vaccination with an aluminium-containing vaccine (like a residual "tattoo" left behind). The World Health Organization (WHO)'s Global Advisory Committee on Vaccine Safety (GACVS) has been reviewing evidence since the findings emerged and has concluded that there is no evidence to suggest a resulting clinical illness or disease.

Q3. Do patients with the MMF lesion have any specific clinical symptoms?

A. It has been suggested that vaccination and localized MMF lesions might be associated with a multi-system disorder. However, the linkage of MMF with a multi-system disorder has been suggested by comparing an unmatched population of similar patients who underwent biopsies of the deltoid muscle and patients with the MMF lesion suffering from diffuse muscle pain. However, the prevalence of MMF in the general population is not known, and the patients studied were not matched with a control group - a necessary step to rule out confounding factors and other possible explanations. It is also unclear whether patients without biopsy evidence of MMF, who had previously received an aluminium-containing vaccine, might have the typical lesion of MMF elsewhere in the muscle, with it being missed on biopsy.

Q4. Does everyone vaccinated with an aluminium-containing vaccine have the MMF lesion?

A. Since muscle biopsies have only been carried out in patients with myopathic symptoms, there is currently no information on whether the characteristic localized histological pattern would be found in the healthy population after vaccination. It has been suggested that there might be a predisposed subset of individuals with impaired ability to clear aluminium from the deltoid muscle. Whether this reflects macrophagic dysfunction, or the tail-end of a normal population distribution of aluminium clearance and local tissue response, has not been determined.

The GACVS recommended that to further understand MMF, additional research studies needed to be undertaken to evaluate the clinical, epidemiological, immunological and basic science aspects of MMF. Studies have been conducted in monkeys and rats to examine the long-term persistence of aluminium and histopathological changes at the injection site, and macrophagic function is being compared between patients with MMF and healthy controls. Initial results support the idea that MMF may represent a simple marker of vaccination with long-term persistence of aluminium at the injection site and local inflammatory response to it, without other symptoms or consequences.

Q5. The Agence française de sécurité sanitaire des produits de santé conducted a study on MMF. What did this study show?

A. This study, initiated in 2002, compared control patients (who had muscle biopsies that did not show MMF) with patients with MMF, by biopsy site, gender, and approximate age and date of biopsy, to determine whether there is an association between MMF and a distinct clinical syndrome. The study confirmed that patients with MMF are more likely to have received vaccines containing aluminium hydroxide adjuvants. Fatigue and related functional limitations were more prevalent in patients with MMF compared with the control group, and fatigue was more prevalent at the beginning of the illness that led to the muscle biopsy. Myalgia and arthralgia were reported infrequently among patients with MMF, contrary to previous reports, and no other differences in symptoms or risk factors were identified that were specific to patients with MMF.

Q6. What were the conclusions reached by the Global Advisory Committee on Vaccine Safety (GACVS)?

A. From the most recent evidence, there is no reason to conclude that a health risk exists as a result of administration of aluminium-containing vaccines. Neither is there any good scientific or clinical basis for recommending any change in vaccination practice. The GACVS reviewed the data of the case-control study performed in France and concluded that the evidence does not support an association between the persistence of aluminium-containing macrophages at the site of a previous vaccination and clinical symptoms or disease.

Q7. Does any scientific evidence to date change any conclusions about MMF and any recommendations on the use of aluminium-containing vaccines?

A. At present there is no evidence of a health risk from aluminium-containing vaccines or any justification for changing current vaccination practices. The independent advice provided to the French Ministry of Health with respect to the most recent study results concurred with GACVS and, furthermore, did not recommend that additional epidemiological research be initiated at this time.

Q8. Why did this issue appear to surface only in France?

A. Different biopsy practices may explain why MMF has predominantly been observed in France. In France biopsies are performed in the deltoid muscle whereas in most other countries biopsies are not taken from that muscle. The apparent increase in the number of cases diagnosed in France might also be explained by the change of vaccine administration from the subcutaneous to the intramuscular route, along with the widespread promotion of the hepatitis B vaccine to adults.

Q9. Have cases of MMF been reported from other countries or from other groups of patients?

A. Yes, there are few case reports originating from other countries as well as reports of MMF lesions found in muscle biopsies of adults or children with other clinical presentations than those described above. In other countries, quadriceps muscle is more commonly biopsied than deltoid muscle. Quadriceps muscle is a traditional site of infant and early childhood immunizations, while deltoid muscle is preferred site for late childhood, adolescence and adulthood immunizations. Muscular biopsy is a frequent diagnostic procedure performed in evaluation of various neuromuscular, metabolic and some genetic disorders of infancy and childhood. Based on current knowledge, MMF lesions findings are considered coincidental and independent of condition under evaluation.

Page last updated: 23 October 2008
Page last reviewed: 3 December 2008