There are very few reports on hypersensitivity reactions in association with titanium-based materials so that the existence of allergy to titanium is still put in question. We report on a patient in whom impaired fracture healing and eczema localized to the perioperative area developed upon titaniumbased osteosynthesis. Patch testing gave no reactions to titanium nor to nickel, chromium, or cobalt. However, in the lymphocyte transformation test, the patient's lymphocytes showed markedly enhanced proliferation in vitro to titanium. After removal of the titanium material, fracture healing was achieved and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium disappeared. Although contact allergic reactions to titanium have been very rarely reported, these findings support a diagnosis of titanium allergy in our patient. Metallic alloys are used in large number for osteosynthesis and long-term implants. In association with stainless-steel-based and cobalt-based materials, contact hypersensitivity reactions have been described and were mostly attributed to chromium, cobalt, nickel, and occasionally to molybdenum. In contrast, due to its excellent biocompatibility (1), titanium is not considered to provoke allergic reactions. However, in view of the few reports on contact dermatitis or granulomatous reactions to titanium upon its use in pacemakers or implants (2-4), the discussion about 'titanium allergy' is still ongoing. Patients and MethodsA 35-year-old male was referred for evaluation of suspected hypersensitivity to implant materials. He presented with a several months history of hand eczema and failure of healing of a hand fracture. Eczema had started within few weeks after an osteosynthesis of right metacarpal fracture by use of a pure titanium miniplate and screws. The patient had gradually developed itching, erythema, and scaling of the right hand together with a vesiculopapular eruption on several fingers, mainly on their ventral parts. Over the next weeks, lesions extended also to the left hand ( Fig. 1) and proximal part of the forearms. There was a history of seasonal rhinoconjunctivitis and asthma but not of previous contact or atopic eczema or hypersensitivity reactions to metals. The patient was otherwise healthy. Under the diagnosis of contact dermatitis, a corticosteroid-containing cream was prescribed and patch testing was planned. Patch testing was performed according to the guidelines of the German Contact Dermatitis Research Group on the patient's upper back with the following series: standard, vehicles, disinfectants, and preservatives. In addition, TiO 2 was tested. Evaluation of the reactions was done after 2, 3, and 7 days. Removed implant materials were not available for subsequent, additional testing.For the lymphocyte transformation test, peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood samples of the patient and a healthy control, as well as of 49 additional controls over the next months. Within

Nickel, chromium, and cobalt released from stainless steel and CoCrMo alloys have been postulated to trigger hypersensitivity reactions. The objective of this study was to assess the ion release from a CoCrMo alloy and stainless steel in vitro and the cutaneous reactivity to it by patch test. 52 metal-allergic patients and 48 non-allergic controls were patch tested to stainless steel and CoCrMo discs. In addition, using atomic absorption spectrometry, the release of nickel, cobalt, and chromium from both materials was assessed upon 2-day exposure to distilled water, artificial sweat (AS), and cell culture medium. There was low nickel ion release from stainless steel (0.3-0.46 microg/cm(2)/2 days) and CoCrMo discs (up to 0.33 microg/cm(2)/2 days) into the different elution media. Chromium release from the 2 materials was also very low (0.06-0.38 microg/cm(2)/2 days from stainless steel and 0.52-1.36 microg/cm(2)/2 days from CoCrMo alloy). In contrast, AS led to abundant cobalt release (maximally 18.94 microg/cm(2)/2 days) from the CoCrMo discs, with concomitant eczematous reaction upon patch testing: 0 of the 52 metal-allergic patients reacted to stainless steel discs and 5 of the 52 patients to CoCrMo discs (all 5 patients were cobalt allergic and 3 also nickel and chromium allergic). None of the controls reacted to the discs. Apart from nickel being a focus of allergological research, our results point to the possibly underestimated association of cobalt release and potential hyperreactivity to CoCrMo alloy.

Upon surgery only transient inflammatory response may be observed in contrast to some developing immune response to metal implants as result of material characteristics or individual reagibility. This is predominantly a macrophage-driven foreign body like response to particulate debris. Metal implant allergy may develop as result of preexisting allergy or upon newly induced lymphocyte sensitisation. Clinical manifestations encompass eczema, recurrent swelling, seroma formation and impaired wound healing. Allergydependent implant loosening is also suspected. We discuss more detailed clinical-allergological testing, the analysis of periimplantar immune reaction and report about an interdisciplinary data collection (metal implant allergy register).Key words: Allergy -implant -metal -lymphocyteWährend eine operationsbedingte Entzündungsantwort meist in Tagen abklingt, kann bei individuell erhöhter Reaktionsbereitschaft und in Abhängigkeit von Materialeigenschaften eine Immunantwort auf Metallimplantate entstehen. Am häufigsten sind Makrophagen-dominierte Fremdkörperreaktionen auf Abriebpartikel. Besteht eine Metallkontaktallergie oder bildet sich eine spezifische Lymphozytensensibilisierung neu aus, so kann dies zu Metallimplantatallergie führen. Klinische Korrelate sind Ekzeme, rezidivierende Schwellung, Ergußbildung und Wundheilungsstörungen. Allergie-bedingte Implantat-Lockerung wird ebenfalls vermutet. Eine Erweiterung der klinisch-allergologischen Diagnostik, Analysemöglichkeiten der periimplantären Immunreaktion und eine begonnene interdisziplinäre epidemiologische Datenerfassung (Metallimplantatallergie-Register) werden vorgestellt.

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After excluding causes such as infection or mechanical failure, allergy diagnosis using a patch test with implant metals and bone cement components is recommended in cases of suspected implant allergy.