Final Diagnosis -- Macrophagic Myofasciitis

FINAL DIAGNOSIS:   MACROPHAGIC MYOFASCIITIS

DISCUSSION:

Macrophagic myofasciitis is an intramuscular accumulation of macrophages containing vaccine-derived aluminium hydroxide. The cells are immunolabeled by antibodies against CD68 but not CD1a or S100, and a lymphoid component of CD8+ T-cells is usually observed (1, 2, 4). The deposits show a structure typical for aluminum salts at the electron microscopic level (2, 4, 5). The deposits in our patient's biopsy were by laser microprobe mass analysis (LAMMA) proven to be aluminium (the peak showing aluminium is labeled "Al" in Fig. 4). The findings are distinct from deposits found in Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia (2). The granulomatous pattern can be reproduced experimentally by intramuscular injection of vaccines in rats (4). It was suggested that individuals predisposed to develop macrophagic myofasciitis have impaired ability to clear aluminium from the site of injection (7).

The diagnosis of the patient's myopathy could not be established. The tentative diagnosis of FSHD could not be corroborated by molecular studies of the FSHD gene on chromosome 4. Our patient may have a sporadic FSHD-type neuromuscular condition unrelated to the FSHD gene on chromosome 4. The macrophagic myofasciitis in this patient is supposed to be unrelated to her chronic muscle disease. Nevertheless, aluminium-bound vaccines are believed to occasionally cause a generalized myopathy with myalgia, arthralgia, marked asthenia, muscle weakness, and fever (1). The medium delay from vaccination to onset of myalgias is 11 months, and that from vaccination to biopsy, 36 months (4,6). The underlying pathomechanism is supposed to be caused by protracted low-level immune stimulation due to long-term persistence of the adjuvant in antigen-presenting cells, resulting in systemic immune activation in the patients (3). More than 150 patients with myopathy due to macrophagic myofasciitis have been recognized since 1993 in France. A concurrent autoimmune disease is observed in one third of patients (3). Patients improved under corticosteroid and/or immunomodulatory therapy (1).

REFERENCES:

1. Chérin P, Laforet P, Gherardi RK, Authier FJ, Maisonobe T, Coquet M, Mussini JM, Pellissier JF, Eymard B, Herson S (2000) La myofasciite à macrophages. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD). Presse Med 29:203-208
2. Gherardi RK, Coquet M, Chérin P, Authier FJ, Laforêt P, Bélec L, Figarella-Branger D, Mussini JM, Pellissier JF, Fardeau M (1998) Macrophagic myofasciitis: an emerging entity. Lancet 352:347-352
3. Gherardi RK, Plonquet A, André C, Intrator L, Poron F, Coquet M, Authier FJ (2001a) Macrophagic myofasciitis: Evidence for chronic local and systemic immune activation associated with persistence of aluminum hydroxide-loaded macrophages in muscle. Neurology (Suppl 3) A62
4. Gherardi RK, Coquet M, Chérin P, Belec L, Moretto P, Dreyfus PA, Pelissier JF, Chariot P, Authier FJ (2001b) Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain 124:1821-1831
5. Harris AB (1973) Ultrastructure and histochemistry of alumina in cortex. Exp Neurol 38:33-63
6. Institut de Veille Sanitaire (2001) Myofasciite à macrophages: rapport d'investigation exploratoire de l'InVS, available at www.invs.sante.fr
7. WHO Vaccine Safety Advisory Committee (1999) Macrophagic myofasciitis and aluminum-containing vaccines. Wkly Epidemiol Rec 74:338-340

Acknowledgments:

We wish to thank A. Lindner, Stuttgart, and R. Heckl, Karlsbad-Langensteinbach, for clinical evaluation; W. Kress, Würzburg, for genetic evaluation regarding FSHD; and I. Warlo, Mainz, for technical assistance regarding electron microscopy. The work was supported by an intramural grant MAIFOR from Mainz University to HHG.

Contributed by Antje Bornemann, MD, Jürgen Bohl, MD, Hans-Michael Schneider, MD, Hans H. Goebel, MD, Peter F. Schmidt, PhD and Romain K. Gherardi, MD