A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome

Summary

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

Introduction

Macrophagic myofasciitis (MMF) is a recently described histopathological lesion which is mainly, though not exclusively, diagnosed in adult patients [1], [2], [3]. Clinical manifestations of MMF include diffuse myalgia, arthralgia, chronic fatigue and muscle weakness. The prevalence in patients of musculoskeletal pain and chronic fatigue of duration in excess of six months is approximately 88% and 93%, respectively [2]. Fatigue is disabling in 87% and affects patient’s physical and mental functioning in 53% of cases [4]. The 1994 CDC and 1991 Oxford criteria for chronic fatigue syndrome (CFS) are fulfilled in 47% and 40% of patients, respectively [4]. The pathology of MMF is characterised by pathognomonic focal epi-, peri- and endo-mysial infiltration of large periodic acid-schiff (PAS)-positive macrophages, intermingled with CD8⁺ T-cells, in the absence of conspicuous muscle fibre damage [1], [2]. Electron microscopy reveals the presence of a crystalline material in the cytoplasm of macrophages which is identified as a form of aluminium hydroxide which is used as an adjuvant in vaccines to stimulate the immune response [5]. MMF is found to be concomitant with the long term persistence of aluminium hydroxide at the site of a previous intramuscular injection [5], with the time between immunisation with aluminium adjuvant (vaccine) and onset of symptoms and muscle biopsy ranging from 3 months to 10 years [2], [6]. The low detection rate of MMF in individuals who are exposed to aluminium-based adjuvants in vaccines and have undergone deltoid muscle biopsies prompted the WHO to propose the working hypothesis that MMF occurred in a predisposed subset of individuals who shared an impaired ability to clear aluminium from their muscle [7]. While there are data which suggest genetic predisposition to MMF [8], [9], [10], for example, in relation to autoimmune disease [11], the WHO’s subset of individuals remains to be identified and there are no definitive data concerning the clearance or persistence of aluminium in human muscle tissue. However, the pathology of MMF is reproduced in animal models [12], [13] and there is preliminary evidence of a role for genetically determined factors related to the immune cascade in MMF in rats [13].

The relationship between the myriad symptoms which are associated with a diagnosis of MMF and the muscle pathology is uncertain as is the role of aluminium in disease aetiology. It is, for example, unknown if MMF is a manifestation of another underlying condition or if it is the cause or source of the associated symptoms. CFS is a relatively common disease which, like MMF, can be severely disabling and is also of unknown aetiology [14]. It has also been linked with vaccination though whether or not aluminium adjuvants are involved in the aberrant immune response which is characteristic of CFS is equivocal [15]. There are already strong links between MMF and CFS and we have formed the opinion that these conditions might be exacerbated by an increased sensitivity to exposure to aluminium with the latter also being recognised as an elevated body burden of aluminium. Herein, in the first test of this hypothesis, we describe the first case of MMF and CFS coincident with an increased body burden of aluminium.