Opportunistic Infections with Iron Overload
Withholding iron from potential pathogens is a host defense strategy. Transferrin's
extremely high affinity for iron, coupled with the fact that two-thirds
of the iron binding sites of the protein normally are unoccupied, essentially
eliminates free iron from plasma and extracellular tissues. Both transferrin
and the structurally related protein, lactoferrin, are bacteriostatic in
vitro for a number of bacteria. Lactoferrin is a prominent component of
the granules of polymorphonuclear leukocytes. The protein is released at
high concentrations by the cells in areas of infection. There is also evidence
that iron overload per se compromises the ability of phagocytes
to kill microorganisms. A combination of problems likely contribute to
the increase in susceptibility to infection in these patients.
The very high transferrin saturations attained in patients with iron
overload compromise the bacteriostatic properties of the protein. Iron
sequestration is not a frontline defense against microbes. Therefore, iron
overload does not produce the susceptibility to infection seen with defects
in more central systems (e.g., chronic granulomatous disease). Nonetheless,
a number of infections, often with unusual organisms, have been reported
in patients with iron overload (Bullen, Spaulding et al. 1991); (Abbott,
Galloway et al. 1986); (Christopher 1985). Patients with sideroblastic
anemia are often neutropenic or have neutrophil dysfunction. Iron overload
in these patients adds to an already compromised defensive network. Some
of the infections that have been reported are listed in Table 1. Although
aggressive antimicrobial therapy is occasionally successful, some infections,
such as the mucormycosis produced by Rhizopus oryazae, are almost uniformally
fatal (Daly, Velazquez et al. 1989).
Table 1- Infections Associated with Iron Overload (partial
Mucormycosis (Rhizopus oryazae)
The iron chelator, desferrioxamine, has also been implicated in the
development of opportunistic infections in some patients with iron overload
and Prpic 1985); (Boelaert, van Roost et al. 1988); (Windus, Stokes et
al. 1987). Streptomyces pilosis synthesizes the siderophore when grown
in an iron-deficient environment. Desferrioxamine is released in the vicinity
of the microbes, binds iron, and returns the element to the microorganisms
where it is used for growth and replication. Some pathogenic bacteria and
fungi can utilize the iron bound by desferrioxamine to promote their growth,
thereby enhancing the risk of severe infection.
The question of when to begin chelation therapy in a patient with transfusional
hemochromatosis lacks a simple answer. The decision must be carefully individualized.
Serious infection in patients treated with desferrioxamine is uncommon,
and the benefits of therapy to prevent iron-induced organ damage generally
outweigh the risk of infectious complications.
Abbott, M., A. Galloway, et al. (1986). Haemochromatosis presenting with
a double Yersinia infection. Journal of Infection 13: 143-145.
Boelaert, J., G. van Roost, et al. (1988). The role of desferrioxamine
in dialysis-associated mucormycosis: report of three cases and review of
the literature. Clinical Nephrology 29: 261-266.
Bullen, J. J., P. B. Spaulding, et al. (1991). Hemochromatosis, iron and
septicemia caused by Vibrio vulnificus. Archives of Internal Medicine 151:
Christopher, G. (1985). Escherichia coli bacteremia, meningitis, and hemochromatosis.
Archives of Internal Medicine 145: 1908.
Daly, A., L. Velzquez, et al. (1989). Mucormycosis: association with deferoxamine
therapy. American Journal of Medicine 87: 468-471.
Robins-Browne, R. and J. Prpic (1985). Effects of iron and desferrioxamine
on infections with Yersinia enterocolitica. Infection and Immunity 47:
Windus, D., T. Stokes, et al. (1987). Fatal Rhizopus infections in hemodialysis
patients receiving deferoxamine. Annals of Internal Medicine 107: 678-680.