**4.5.2 Metal exposure**

340 Recent Advances in Arthroplasty

symptomatic joint implants but not in Ni allergic patients with well-functioning joint implants (Summer et al. 2010) have been reported. Tissues near metal devices in those with metal hypersensitivity may have elevated immune cells/markers including: CD3þ Tlymphocytes, CD4þ cells, CD11cþ macrophages/dendritic cells, and cells with abundant MHC class II (HLA-DR) expression (dendritic cells), (Cadosch et al. 2009). Foreign body giant cell formation is often noted when phagocytosis of foreign particles by macrophages, including metals. Ingesting macrophages then secrete the proinflammatory cytokines TNFα, IL-6 and IL1-α and –β (Cadosch et al. 2009). At high concentrations, Ti and V cause production of superoxide anions in neutrophils and nickel ions break down neutrophil cell

A novel mechanism for aseptic loosening of metal implants was suggested recently (Cadosch et al. 2010a). Osteoclasts mature and grow on titanium metals, leading to degradation, uptake and eventual release of the metal ions by the osteoclasts. This might explain increases in metal ion in systemic circulation, increased recruitment of osteoclast precursors via synthesis of specific chemokines, and also it can contribute to osteoclast differentiation. CCL17/TARC, CCL22/MDC, RANK-L, M-CSF and pro-inflammatory cytokines (CCR4) are elevated in the peri-implant environment (Cadosch et al. 2010b). This leads to loosening of the device as supporting surrounding bone is resorbed. In addition to being present in joint loosening, CCR4 is involved in the inflammatory reaction in cutaneous allergic contact dermatitis reactions (Vocanson et al. 2009). The link between cutaneous dermatitis and CCR4 is not proven, but is an area for further inquiry. While this evidence specifically address Ti metal, these same mechanisms could be relevant for other metal ions as well. Below, a description of the epidemiology of metal allergy and recommendation for

membranes at high levels (Kumazawa et al. 2002).

clinical practice will be provided.

**Cutaneous: Extra-cutaneous:**  Localized allergic (contact) dermatitis Implant loosening

populations and are general infrequent in dermatitis patients.

Urticaria Swelling/tumor formation Bullous reactions Chronic inflammation

Table 1. Selected clinical manifestations of delayed type hypersensitivity reactions

Metal allergy, as defined by a positive patch reaction to a given metal, is frequent in the general population since up to 17% of adult women and 3% of adult men are nickel sensitized (Thyssen et al. 2007). Chromium and cobalt allergy are less frequent and occur in about 1-2%. Other prevalent causes of metal allergy include gold and palladium resulting in positive patch test reactions in about 10% of dermatitis patients albeit these are rarely clinically relevant (Faurschou et al. 2011). The prevalence of other metals, e.g. titanium, platinum, molybdenum, manganese and other has not yet been evaluated in general

Systemic allergic (contact) dermatitis Pain

**Reactions** 

Vasculitis

Impaired wound healing

**4.5.1 Epidemiology** 

In addition to metallic devices and prostheses, metal exposure is also related to intake of food and water, dental work, tattooing, and prolonged skin contact with metal objects. These exposures may all result in metal sensitization although oral intake sometimes may lead to tolerance. Oral intake of food and water as well as implantation seems rarely to result in allergic complications or clinical disease. However, skin contact with metal objects e.g. jewellery often results in skin sensitization and dermatitis at the site of skin contact. Several field studies have recently demonstrated that nickel release in concentrations that result in sensitization and dermatitis remains common in Europe and the United States (Thyssen and Menne 2010; Thyssen et al. 2011b).
