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Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease. SUBJECTS: Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.zirconium and Crohn's disease.doc

The action of Zirconium (Zr) on biological systems presents an enigma. It is ubiquitous, being present in nature in amounts higher than most trace elements. It is taken up by plants from soil and water and accumulated in certain tissues. The entry into animal systems in vivo is related to the mode of exposure and the concentration in the surrounding environment. Retention is initially in soft tissues and then slowly in the bone. The metal is able to cross the blood brain-barrier and is deposited in the brain and the placental barrier to enter milk. The daily human uptake has been known to be as high as 125 mg. The level of toxicity has been found to be moderately low, both in histological and cytological studies. The toxic effects induced by very high concentrations are nonspecific in nature. Despite the presence and retention in relatively high quantities in biological systems, Zr has not yet been associated with any specific metabolic function. Very little information is available about its interaction with the compounds of the genetical systems, such as nucleic acids. Apparently, the metal is neither an essential nor toxic element in the conventional sense. However, the increasing exposure to this element through its increasing use in new materials and following radioactive fallout, has increased the importance of the study of its effects on living organisms. The tetravalent nature of the ionic state and the high stability of the compounds formed are important factors that need to be considered, as also the accumulation of this element in the brain, reminiscent of the relationship between Al3+ and Alzheimer's disease. zirconium--abnormal trace element.doc

The beryllium (Be) and zirconium (Zr) salts, BeSO4 and Zr(SO4)2, each exerted a concentration-dependent stimulation of mouse spleen cell proliferation as measured by an increase in [3H]thymidine incorporation into lymphocyte DNA, although the maximal response induced by Zr(SO4)4 (4-5 fold at 100-200 microM) was greater than that by BeSO4 (2-3 fold at 1-5 microM). Preincubation of splenocytes with low concentrations of BeSO4 (less than 1 microM) or a broad range of Zr(SO4)2 concentrations (2-100 microM) was also found to assist subsequent lectin (concanavalin A; ConA)-mediated lymphocyte proliferation. The results indicate that at defined concentrations Be and Zr salts can both act as lymphocyte mitogens and augment the functional responsiveness of immune cells, which may help explain the characteristic induction of delayed hypersensitivity and production of immunological granulomas by these metals in vivo.zirconium and spleen.doc

Title Cutaneous granulomas caused by an aluminum-zirconium complex: an ingredient of antiperspirants.

Author Montemarano AD; Sau P; Johnson FB; James WD

Address Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C., USA.

Source J Am Acad Dermatol, 37(3 Pt 1):496-8 1997 Sep