Hypersensitivity to titanium is an ever-increasing reportable complication in medicine today. There exist many case reports of titanium alloy hypersensitivity including failed total hip prostheses 1 , titanium-implanted cardiac pacemakers, 2 surgical clips, 3 and dental implants. With respect to dental implants, there appears to be an allergic correlation with titanium implants, which unfortunately is not fully understood with minimal research.
Dental Implants vs. Medical Titanium Devices
Most of the clinical studies and evidence of titanium hypersensitivity is derived from the orthopedic literature, which has been shown to be statistically significant. Orthopedic sensitivity appears to occur with a higher risk in comparison to dental implants for many reasons. First, bone has been shown to have a rather low reactivity potential and the intraosseous contact of dental implants is much smaller than in orthopedic implants. Secondly, the oral mucosa has many benefits as it is less permeable than skin and contains less antigen acting Langerhans’ cells. Studies have shown that the antigen concentrations of the oral mucosa have to be 5-12 times greater than skin to cause a hypersensitivity reaction. 4 And lastly, it has been shown that dental implants and prostheses in the oral cavity are coated with a layer of salivary glycoprotein, which act as a protective barrier.
Studies
In the dental literature, reports of allergic reactions to titanium implants are rather minimal. However, many authors recently have suggested a higher incidence of titanium alloy allergy with respect to dental implants. It is widely accepted that the true incidence of titanium hypersensitivity is underreported, mainly from a poor understanding of failure or allergy. Sicilia et al. evaluated over 1500 patients and reported a 0.6 % prevalence of titanium failure.
Possible Etiology
The use of titanium alloys (aluminum, beryllium, palladium, vanadium, etc.) are most commonly used in oral implantology today because of the higher strength in comparison to the lower strength pure titanium. It has been postulated that small amounts of titanium alloys may act systemically as “impurities”, which may lead to triggering allergic reactions. 7 Because all metal alloys undergo a slow release of ions from their implant surface, corrosion risks and detrimental effects from the byproducts are possible. The sensitivity to the titanium ions has been shown to be directly related to the presence of macrophages and T-lymphocytes, which may result in a type IV hypersensitivity reaction.
Clinical Symptoms
Titanium hypersensitivity is usually diagnosed by signs and symptoms which may include a rash urticaria, pruritus, localized soft tissue inflammation, swelling in the orofacial region, oral or facial erythema, eczema lesions of the face, or hyperplastic peri-implant mucosa. In some cases, implant failure may result, usually as early implant failure (rapid exfoliation). Clinical reports have associated titanium allergy with multiple implant failure in the same patient (cluster phenomenon). Suspected association of an allergic reaction with titanium dental implants: A clinical report , Hiroshi Egusa, DDS, PhD, J Prosthet Dent 2008;100:344-347
Hypersensitivity Testing
Patients who present with a history of metal or titanium allergy, a hypersensitivity evaluation is suggested. At this time, two tests are available.
1. Patch Test:
Titanium hypersensitivity may be diagnosed using a ‘patch-test’ , where various metal allergens are applied to the skin for 3–4 days. Usually an erythematous reaction is considered positive. However, patch tests have been associated with false-positive or false- negative results. Current patch tests have been shown to be approximately 75% accurate for type IV metal allergy.
2. Blood Test
The lymphocyte transformation test (LTT) or Memory Lymphocyte Immuno- Stimulation Assay (MELISA) has been shown to detect sensitization to titanium in some patients. In addition, the MELISA test is capable of determining which metals may be tolerated and initiate undesirable immune responses. Muller, K.E. (2006) Hypersensitivity to titanium: Clinical and laboratory evidence. Neuro Endocrinology Letters 27 (Suppl. 1): 31–35.
Treatment
If a known hypersensitivity is determined, an alternative dental implant material should be utilized. The most common alternatives today are zirconia and polyetheretherketone (PEEK) dental implants. Currently, zirconia is an accepted material, which has been shown to have high success rates along with recent improvements in physical properties, osseointegration, and clinical applications. PEEK implants have a similar elastic modulus to that of bone, therefore have numerous biomechanical advantages. Currently not clinically available, they are currently being studied with numerous clinical studies. How prevalent titanium dental implant titanium hypersensitivity is in oral implantology today is a contentious issue. More studies are required to establish the incidence and associated complications with these types of hypersensitivity reactions. The biologic effects of the dental implant corrosion and the presence of ions/particles systemically is becoming a more commonly discussed subject. Until then, clinicians must be conscious of the signs and symptoms of potential titanium hypersensitivity and be able to utilize alternative dental implant materials if needed.
References
1 Granchi D, Sensitivity to implant materials in patients undergoing total hip replacement. J Biomed Mater Res B Appl Biomater 2006;77:257-64
2 Yamauchi R, Morita A, Tsuji T. Pacemaker dermatitis from titanium. Contact Dermatitis 2000;42:52-3.
3 Tamai K, A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy. Breast Cancer 2001;8:90-2.
4 Schramm M, Pitto RP. Clinical relevance of allergological tests in total hip joint replacement. In: Willmann G, Zweymuller K, editor. Bioceramics in Hip joint replacement. New York, USA: Thieme; 2000. p. 101-6.
5 Bass JK, Fine H, Cisneros GJ. Nickel hypersensitivity in the orthodontic patient. Am J Orthod Dentofacial Orthop 1993;103:280-5.
6 A. Sicilia, S. Cuesta, G. Coma, I. Arregui, C. Guisasola, E. Ruiz, et al. Titanium allergy in dental implant patients: a clinical study on 1500 consecutive patients Clinical Oral Implants Research, 19 (2008), pp. 823–835
7 Chaturvedi, T. P. “Allergy related to dental implant and its clinical significance.” Clinical, cosmetic and investigational dentistry 5 (2013): 57.
8 Goutam, Manish, et al. “Titanium allergy: a literature review.” Indian journal of dermatology 59.6 (2014): 630.
9 Forte G, Petrucci F, Bocca B. Metal allergens of growing significance: epidemiology, immunotoxicology, strategies for testing and prevention. Inflamm Allergy DrugTargets. 2008;7(3):145–162.