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Zirconium allergy

Radoslaw Spiewak^1,2

1. Institute of Dermatology, Krakow, Poland
2. Dermatology and Allergology Outpatient Clinic 'dermatolog.eu', Krakow, Poland

Key words: Zirconium allergy, contact allergy, allergic contact dermatitis.

Suggested citation format: Spiewak R. Zirconium allergy. Allergopedia. 2025; 1: 5. doi: 10.14320/allergopedia.20250105

When considering the issue of zirconium allergy, it is worth realizing the differences between three similar-sounding names, which, however, have different meanings:

1. zirconium - a metal with the chemical symbol Zr, atomic number 40, belonging to the group of transition metals,
2. zircon - a naturally occurring mineral that consists mainly of zirconium silicate (ZrSiO₄),
3. zirconia - a ceramic material consisting predominantly of zirconium dioxide (ZrO₂), which, depending on dopants and physical conditions in the production process, can take the form of a colourless, transparent synthetic ornamental stone referred to as cubic zirconia that is used in jewelry as an imitation of diamonds, or a white ceramic mass of high hardness used as a material in the production of implants and artificial dental crowns.

Zirconium

Zirconium, chemical element symbol Zr, CAS number 7440-67-7, exhibits high corrosion resistance and is therefore added to alloys used in the production of items of high durability and corrosion resistance, such as surgical instruments, dental implants, and endoprostheses. It can be found in alloys used to make wristwatch cases. Zirconium's high reactivity with oxygen is exploited in some detonators and primers of explosives, as well as in pyrotechnic compositions. In the past, zirconium was also used in disposable flashlights, in which the flash was produced by burning the material. It is also used in the production of electron tubes. Zirconium is a byproduct of titanium and tin mining and smelting. Commercial zirconium typically contains 1-3% hafnium, another transition metal that can cause sensitization.

Zircon

The mineral zircon, i.e. zirconium silicate, CAS number 1344-21-4, is used primarily as an opacifying agent in the production of decorative ceramics, and also in refractory (fire proof) materials and foundry molds.

Zirconia

Zirconia consists primarily of zirconium oxide (ZrO₂, CAS number 53801-45-9). Depending on production conditions and dopants, zirconia can be transparent or a white ceramic material characterized by high mechanical and thermal strength, as well as chemical resistance. White zirconia's main technical applications are as a component of thermal insulation coatings and as a prosthetic material in dentistry. Cubic (translucent) zirconia is used in jewelry as a diamond substitute.

Zirconium in dentistry

Zirconia implants seem to be an emerging alternative to titanium with with osseointegration comparable to the latter and a superior soft-tissue response, biocompatibility, and aesthetic features [1-3]. Successful dental restorations with zirconia-based implants and crowns have been reported in patients with titanium allergy [4]. Zirconia, used as a material in dental implantology and prosthetis, always contains admixtures of other metals, such as yttrium (Y), hafnium (Hf), aluminum (Al), or calcium next to its main component zirconium dioxide. Therefore, when analyzing the risk of allergic reactions to zirconia crowns and implants, it's important to consider not only zirconium but also other metals [5].

Zirconium in endoprostheses

Zirconium-based artificial joints are considered as a promising, however not entirely challenge-free, alternative to traditional steel, nickel, chromium and cobalt-based alloys, as well as titanium alloys [6]. Oxinium™ is the brand name (Smith+Nephew) of a zirconium-based material used for hip and knee replacement in which a zirconium alloy of the implant transitions into a hard ceramic outer surface formed by zirconium oxide [7]. It was shown to be non-inferior to traditional artificial joints made of other materials, including titanium alloys, and was suggested as an alternative material for use in patients with metal hypersensitivity [8-11]. However, cases of metallosis and failure of oxidized zirconium implants have been reported in literature, demonstrating that metallic zirconium can be released from such implants into surrounding tissues [12,13].

Clinical symptoms of zirconium allergy

Historically, the first reported cases of zirconium hypersensitivity, referred to as "zirconium granuloma" were due to zirconium-containing deodorants and zirconium-based treatments for Rhus dermatitis [14-19]. A case of "contact allergic gastritis" was reported with itchy gingiva lesions surrounding ceramic crowns on metal bridge that emerged within 2 weeks after their placement, accompanied by nose swelling and gastrointestinal symptoms (gastric and colic pain, diarrhoea) and gastroscopy-confirmed eosinophilic gastritis. On patch tesing, the patient reacted to gold, palladium and zirconium which were the components of the bridge and crowns, and their replacement resulted in a rapid spontaneous remission of the symptoms [20]. An atypical allergic reaction after total hip replacement with the use of alumina-zirconia ceramic head in a woman who developed paresthesia throughout the entire right lower extremity, swelling, and ecchymosis within the first week after the surgery, followed with polyarthralgias and continued diffuse swelling and sensitivity in the right lower extremity that eventually involved most of her body, as well as hair fall (alopecia areata) and impaired vision [21]. The implanted endoprosthesis remained functional over the entire observation period. The diagnosis of zirconium allergy was based on the lymphocyte stimulation test (stimulation index of 8.6), a method with debatable diagnostic value. Nevertheless, the symptoms completely resolved within a week following the replacement of the alumina-zirconia ceramic head and the patient remained symptom-free during following 24 months [21]. Immunoreactivity to zirconium was also observed in subgroup of sarcoidosis patients with a specific, fibrotic phenotype [22,23]. This condition, also referred to as sarcoid granulomatosis may take course with multiple organ involvement after zirconium exposure [24].

Zirconium in cosmetics

Zirconium and its compounds are relatively rarely used in cosmetics. Their ascribed functions include deodorant, antiperspirant, astringent, bulking, opacifying, and skin conditioning. As of 2025, 40 zirconium compounds were listed in the European cosmetic ingredient database CosIng, including prohibited compounds [25]. According to entry 391, Annex II to the Cosmetics Regulation 1223/2009 is applicable the of zirconium and its compounds in cosmetics is prohibited, with the exception of the substances listed under reference number 50 in Annex III, and the zirconium lakes, pigments or salts of the colouring agents when listed in Annex IV. Zirconium compounds which are allowed for use in cosmetics include:

INCI: International Nomenclature of Cosmetic Ingredients - unified, international names for cosmetic ingredients. Information about ingredients is provided on cosmetics packaging according to the INCI nomenclature. CI: Colour Index, a unique number of a dye in the Colour Index™ International (CI) reference database.

Synonyms and names for zirconium and its compounds in English and other languages

Zirconium; Zircon; Zirconia; Oxinium; Cyrkon; Cyrkonia; CAS 7440-67-7; EC 231-176-9; EC 933-703-4.

Available diagnostic methods and materials

At present, the only validated method of detecting zirconium allergy is patch test performed in line with the current guidelines by national or intenational scientific societes, e.g., European Society of Contact Dermatitis [26]. Patch test material available for testing includes:

• Zirconium (IV) chloride 1% pet. (Chemotechnique Diagnostics, cat. number Z-008)

Please note: Blood tests for zirconium allergy (mostly advertised as "lymphocyte transformation tests"), although popular in some countries, have not been approved as a diagnostic tool, and their use in allergy diagnosis is the subject of much controversy.

Positivity rate

1 in 44 (2.2%) patients with suspected metal allergy [27].

Cross-reactivities, co-positivities and co-sensitizations

To date, there is no sufficient data regarding possible cross-reactivities, co-positivities and co-sensitizations of zirconium.

References

1. Zreaqat M, Hassan R, Hanoun AF. A CAD/CAM Zirconium Bar as a Bonded Mandibular Fixed Retainer: A Novel Approach with Two-Year Follow-Up. Case Rep Dent. 2017;2017:1583403. doi: 10.1155/2017/1583403
2. Sivaraman K, Chopra A, Narayan AI, Balakrishnan D. Is zirconia a viable alternative to titanium for oral implant? A critical review. J Prosthodont Res. 2018 Apr;62(2):121-133. doi: 10.1016/j.jpor.2017.07.003.
3. Fawakhiri HA, Abboud S, Kanout S. A 3-year controlled clinical trial comparing high-translucency zirconia (cubic zirconia) with lithium disilicate glass ceramic (e.max). Clin Exp Dent Res. 2023 Dec;9(6):1078-1088. doi: 10.1002/cre2.790
4. Oliva X, Oliva J, Oliva JD. Full-mouth oral rehabilitation in a titanium allergy patient using zirconium oxide dental implants and zirconium oxide restorations. A case report from an ongoing clinical study. Eur J Esthet Dent. 2010 Summer;5(2):190-203.
5. Peng TY, Shimoe S, Tanoue N, Akebono H, Murayama T, Satoda T. Fatigue resistance of yttria-stabilized tetragonal zirconia polycrystal clasps for removable partial dentures. Eur J Oral Sci. 2019 Jun;127(3):269-275. doi: 10.1111/eos.12615
6. Munazzam SW, Rai V, Nousheen S, Ullah B, Sharif S, Mohammed C. A Narrative review of advancements in knee Arthroplasty: Analyzing diverse prosthetic materials and their implications. J Clin Orthop Trauma. 2025 Apr 24;66:103034. doi: 10.1016/j.jcot.2025.103034
7. Smith+Nephew. OXINIUM. Oxidized Zirconium. https://www.smith-nephew.com/en/health-care-professionals/products/orthopaedics/oxinium (electronic document, accessed on 12 December 2025).
8. Hofer JK, Ezzet KA. A minimum 5-year follow-up of an oxidized zirconium femoral prosthesis used for total knee arthroplasty. Knee. 2014 Jan;21(1):168-71. doi: 10.1016/j.knee.2013.08.015.
9. Puente Reyna AL, Fritz B, Schwiesau J, Schilling C, Summer B, Thomas P, Grupp TM. Metal ion release barrier function and biotribological evaluation of a zirconium nitride multilayer coated knee implant under highly demanding activities wear simulation. J Biomech. 2018 Oct 5;79:88-96. doi: 10.1016/j.jbiomech.2018.07.043.
10. Bulaïd Y, Djebara AE, Belhaouane R, Havet E, Dehl M, Mertl P. Beneficial effect of a zirconium-nitride-coated implant in total knee arthroplasty revision for suspected metal hypersensitivity. Orthop Traumatol Surg Res. 2022 Sep;108(5):103320. doi: 10.1016/j.otsr.2022.103320
11. D'Ambrosi R, Ursino N, Mariani I, Corona K, Anghilieri FM, Franchi E, Monti L. Similar clinical and radiographic outcomes after two different hypoallergenic medial unicompartmental knee in patients with metal allergy. Eur J Orthop Surg Traumatol. 2023 May;33(4):1315-1328. doi: 10.1007/s00590-022-03295-y
12. Frye BM, Laughery KR, Klein AE. The Oxinium Arthrogram: A Sign of Oxidized Zirconium Implant Failure. Arthroplast Today. 2021 Mar 7;8:103-109. doi: 10.1016/j.artd.2021.02.001
13. Ludwig M, Faschingbauer M, Reichel H, Freitag T. Arthroplast Today. Dramatic Failure of an OXINIUM Total Knee Arthroplasty With a Massive Pseudotumor Formation. 2024 Oct 14;30:101479. doi: 10.1016/j.artd.2024.101479
14. Hurley HJ Jr, Shelley WB. The Zirconium Deodorant Granuloma: An Allergic Disorder. Henry Ford Hosp Med Bull. 1958 Sep;6(3):279-90.
15. Epstein WL, Skahen JR, Krasnobrod H. Granulomatous hypersensitivity to zirconium: localization of allergen in tissue and its role in formation of epithelioid cells. J Invest Dermatol. 1962;38:223-32. doi: 10.1038/jid.1962.40
16. Epstein WL, Skahen JR, Krasnobrod H. The organized epithelioid cell granuloma: differentiation of allergic (zirconium) from colloidal (silica) types. Am J Pathol. 1963 Sep;43(3):391-405.
17. LoPresti PJ, Hambrick GW Jr. Zirconium granuloma following treatment of rhus dermatitis. Arch Dermatol. 1965 Aug;92(2):188-91. https://doi.org/10.1001/archderm.92.2.188
18. Elias PM, Epstein WL. Ultrastructural observations on experimentally induced foreign-body and organized epithelioid-cell granulomas in man. Am J Pathol. 1968 Jun;52(6):1207-23.
19. Skelton HG 3rd, Smith KJ, Johnson FB, Cooper CR, Tyler WF, Lupton GP. Zirconium granuloma resulting from an aluminum zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. J Am Acad Dermatol. 1993 May;28(5 Pt 2):874-6. doi: 10.1016/0190-9622(93)70122-a
20. Pföhler C, Körner R, Vogt T, Müller CS. Contact allergic gastritis: an underdiagnosed entity? BMJ Case Rep. 2012 Nov 28;2012:bcr2012006916. doi: 10.1136/bcr-2012-006916
21. Dawson-Amoah KG, Waddell BS, Prakash R, Alexiades MM. Adverse Reaction to Zirconia in a Modern Total Hip Arthroplasty with Ceramic Head. Arthroplast Today. 2020 Jun 19;6(3):612-616.e1. doi: 10.1016/j.artd.2020.03.009
22. Beijer E, Meek B, Bossuyt X, Peters S, Vermeulen RCH, Kromhout H, Veltkamp M. Immunoreactivity to metal and silica associates with sarcoidosis in Dutch patients. Respir Res. 2020 Jun 8;21(1):141. doi: 10.1186/s12931-020-01409-w
23. Beijer E, Kraaijvanger R, Roodenburg C, Grutters JC, Meek B, Veltkamp M. Simultaneous testing of immunological sensitization to multiple antigens in sarcoidosis reveals an association with inorganic antigens specifically related to a fibrotic phenotype. Clin Exp Immunol. 2021 Jan;203(1):115-124. doi: 10.1111/cei.13519.
24. Werfel U, Schneider J, Rödelsperger K, Kotter J, Popp W, Woitowitz HJ, Zieger G. Sarcoid granulomatosis after zirconium exposure with multiple organ involvement. Eur Respir J. 1998 Sep;12(3):750. doi: 10.1183/09031936.98.12030750
25. European Commission. CosIng - Cosmetics Ingredients. https://ec.europa.eu/growth/tools-databases/cosing/ (electronic document, accessed on 12 December 2025)
26. Johansen JD, Aalto-Korte K, Agner T, Andersen KE, Bircher A, Bruze M, Cannavó A, Giménez-Arnau A, Gonçalo M, Goossens A, John SM, Lidén C, Lindberg M, Mahler V, Matura M, Rustemeyer T, Serup J, Spiewak R, Thyssen JP, Vigan M, White IR, Wilkinson M, Uter W. European Society of Contact Dermatitis guideline for diagnostic patch testing - recommendations on best practice. Contact Dermatitis. 2015 Oct;73(4):195-221. doi: 10.1111/cod.12432
27. Spiewak R. Assessment for metal allergy: Patch testing. In: Chen JK, Thyssen JP, editors. Metal allergy. From dermatitis to implant and device failure. Cham: Springer; 2018. p. 107-24. doi: https://doi.org/10.1007/978-3-319-58503-1_11

Disclaimer

The above description does not exhaust all possible exposures and symptoms, and the hapten you are allergic to may also be present in other sources not listed above.Therefore, always check the composition of the products and substances you come into contact with, and if in doubt, consult a licensed physician, preferably a dermatologist or allergist.
The authors, reviewers, editors and publisher of this work have made every effort to ensure that the content presented reflects the current state of knowledge at the time of its preparation. However, scientific progress may render some information outdated or inaccurate. Therefore, the authors, reviewers, editors, and publishers of this work exclude all liability for damages that may arise as a result of using the information presented. Use of this work constitutes acceptance of this disclaimer and a waiver of any claims arising from its use.

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Document created: 8 November 2025, last updated: 17 December 2025
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