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Possible Involvement of Aluminum Salts in Erythema Multiforme, Encephalopathy, or Other Adverse Events After Pertussis Immunization

DPT vaccine preparations regularly contain aluminum salts (aluminum hydroxide, aluminum potassium sulfate, or aluminum phosphate) that are intended to serve as adjuvants (British National Formulary, 1988; Physicians' Desk Reference, 1989). Orlans and Verbov (1982) suggested that DPT-associated rashes could be due to aluminum hydroxide. Other more significant local reactions including nodules at the site of injection, itching, eczema, and circumscribed hypertrichosis over nodules have been observed more frequently following administration of aluminum hydroxide-adsorbed DPT vaccine than after administration of unadsorbed DPT vaccine (Pembroke and Marten, 1979).

Interest has developed recently in the potential health effects of aluminum, particularly in the setting of chronic renal failure, in which aluminum is not excreted from the body normally (Alfrey, 1984; Monteagudo et al., 1989). A severe, often fatal encephalopathy found in patients undergoing long-term dialysis was attributed to aluminum deposition in the brain (Alfrey et al., 1976). Reduction of aluminum in dialysate has largely eliminated this condition, but dialysis patients may still have subtle psychomotor defects that may be due to aluminum toxicity (Altmann et al., 1989). Animal studies have shown that aluminum can increase the rate of transmembrane diffusion across the blood—brain barrier (Banks and Kastin, 1989), which could possibly permit greater access of toxins to the brain.

Patients receiving long-term injections of aluminum-containing allergenic



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OCR for page 347
Page 347 E Possible Involvement of Aluminum Salts in Erythema Multiforme, Encephalopathy, or Other Adverse Events After Pertussis Immunization DPT vaccine preparations regularly contain aluminum salts (aluminum hydroxide, aluminum potassium sulfate, or aluminum phosphate) that are intended to serve as adjuvants (British National Formulary, 1988; Physicians' Desk Reference, 1989). Orlans and Verbov (1982) suggested that DPT-associated rashes could be due to aluminum hydroxide. Other more significant local reactions including nodules at the site of injection, itching, eczema, and circumscribed hypertrichosis over nodules have been observed more frequently following administration of aluminum hydroxide-adsorbed DPT vaccine than after administration of unadsorbed DPT vaccine (Pembroke and Marten, 1979). Interest has developed recently in the potential health effects of aluminum, particularly in the setting of chronic renal failure, in which aluminum is not excreted from the body normally (Alfrey, 1984; Monteagudo et al., 1989). A severe, often fatal encephalopathy found in patients undergoing long-term dialysis was attributed to aluminum deposition in the brain (Alfrey et al., 1976). Reduction of aluminum in dialysate has largely eliminated this condition, but dialysis patients may still have subtle psychomotor defects that may be due to aluminum toxicity (Altmann et al., 1989). Animal studies have shown that aluminum can increase the rate of transmembrane diffusion across the blood—brain barrier (Banks and Kastin, 1989), which could possibly permit greater access of toxins to the brain. Patients receiving long-term injections of aluminum-containing allergenic

OCR for page 347
Page 348 extracts had slightly increased levels of serum and urinary aluminum compared with those in age-matched controls receiving aqueous extracts, but aluminum levels in these patients did not fall outside the broad range of normal values (Glinert and Burnatowska-Hledin, 1988). Patients were estimated in this study to receive, on average, about 2.5 mg of aluminum per injection, with injections being given every 2 to 4 weeks for a period of 3 to 5 years. The DPT vaccines used in the United States are reported to contain not more than 0.25 to 0.8 mg of aluminum per 0.5-ml injection (Physicians' Desk Reference, 1989). One study suggested that use of aluminum-adsorbed DPT was associated with fewer febrile reactions than use of unabsorbed DPT vaccine was (Waight et al., 1983). The possibility has been raised that the aluminum content of DPT vaccines might play a role in some of the adverse events that occur, or that are suspected to occur, in association with DPT immunization, particularly encephalopathy. However, there are no data to indicate that such a relationship exists. REFERENCES Alfrey AC. 1984. Aluminium intoxication. New England Journal of Medicine 310:1113-1115. Alfrey AC, LeGendre GR, Kaehny WD. 1976. The dialysis encephalopathy syndrome. New England Journal of Medicine 294:184-188. Altmann P, Hamon C, Blair J, Dhanesha U, Cunningham J, Marsh F. 1989. Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity. Lancet 2:7-11. Banks WA, Kastin AJ. 1989. Aluminum-induced neurotoxicity: alterations in membrane function at the blood-brain barrier. Neuroscience & Biobehavioral Reviews 13:47-53. British National Formulary. 1988. London: British Medical Association/Pharmaceutical Society of Great Britain. Glinert RJ, Burnatowska-Hledin M. 1988. Serum and urinary aluminum levels in patients receiving alum-precipitated allergenic extracts. Annals of Allergy 61:433-435. Monteagudo FSE, Cassidy MJD, Folb PI. 1989. Recent developments in aluminium toxicology. Medical Toxicology 4:1-16. Orlans D, Verbov J. 1982. Skin reactions after triple vaccine. Practitioner 226:1295-1296. Pembroke AC, Marten RH. 1979. Unusual cutaneous reactions following diphtheria and tetanus immunization. Clinical Experimental Dermatology 4:345-348. Physicians' Desk Reference, 43rd edition. 1989. Oradell, NJ: Medical Economics Co. Inc. Waight PA, Pollock TM, Miller E, Coleman EM. 1983. Pyrexia after diphtheria/tetanus/pertussis and diphtheria/tetanus vaccines. Archives of Disease in Childhood 58:921-923.