**4.5.3 Patch testing**

Patch testing is widely used to establish a diagnosis of delayed type hypersensitivity to metals. The reproducibility of the patch test is high but allergen dependent (Brasch et al. 1994). Patch tests are typically applied to the upper back and occluded for 48 hr. Readings should be performed at least on day 3 or 4 and if possible on more than one occasion (Wahlberg 2006). Patch test studies have suggested that 24-34.5% of positive patch test reactions potentially are missed when readings are not performed beyond day 2 (Uter et al. 1996). Ready-to-use test systems such as the Thin-layer Rapid Use Epicutaneous (TRUE) test® generally have a good concordance with conventional patch test systems using e.g. Finn Chambers®, except for cobalt (Lazarov et al. 2007). Patch testing intends to identify contact sensitized subjects by distinguishing between negative, irritant and allergic reactions. Thus, a valid positive patch test reaction typically requires a trained and experienced person that adheres to a set of valid criteria. Currently, the recommendations from the International Contact Dermatitis Research Group (ICDRG) dictate that homogeneous redness and infiltration in the entire test area is scored as a 1+ reaction, homogeneous redness, infiltration, and vesicles in the test area are scored as a 2+ reaction, and homogeneous redness, infiltration, and coalescing vesicles in the test area as a 3+ reaction (Wilkinson et al. 1970). 1+, 2+, or 3+ readings should be interpreted as positive responses indicating contact sensitization whereas irritant responses, doubtful (+?) responses, or negative readings should be interpreted as negative responses (Fig. 4). Clinicians should be aware that false positive and negative reactions may be encountered

Aseptic Loosening of Total Hip Arthroplasty as a Result of Local Failure of Tissue Homeostasis 343

remains very frequent. This obviously makes it difficult to identify the few allergic subjects at risk before developing implant failure. Although it is a matter of controversy, it seems sensible to refrain from routine patch testing/allergy testing prior to surgery unless the patient has already had implant surgery with complications suspected to be allergic or a history of clinical metal intolerance of sufficient magnitude to be of concern to the patient or a health provider (Thyssen et al. 2011a). If a patient is strongly allergic to e.g. nickel or cobalt, one should consider inserting titanium based alloys. To demonstrate causal relationship between delayed type of hypersensitivity and aseptic loosening strict criteria

**1.** Histology consistent with a delayed type hypersensitivity reaction.

**3.** Positive in vitro test to metals, e.g. the lymphocyte transformation test. **4.** Complete recovery following removal of the offending implant material. Table 2. Objective criteria that support a causative association between metal release from the implant, metal allergy and delayed type hypersensitivity reactions such as implant loosening, malfunction, pain or chronic inflammation (from Thyssen et al. 2011a)

**4.6 Aseptic loosening as a result of local failure of tissue homeostasis** *(Gallo)* 

The term "homeostasis" was coined by Claude Bernard in 1865 to describe the constancy of the internal environment as a condition of health. Metchnikoff has introduced the concept into immunology together with the term physiological inflammation to mean active maintenance of tissue harmony, tissue harmony (Medzhitov 2010). Given that the majority of patients profit from THA, it appears that low-grade periprosthetic inflammation occurring around "healthy" THA may be a normal adaptive response to the continual burden of prosthetic particles and mechanical stresses associated with implant use. For this reason, processes leading to osteolysis and aseptic loosening can be investigated as a

In reality, no one knows what are the histological and immunological parameters associated with long-term "physiological" tissue homeostasis around THA, a baseline for true understanding of periprosthetic pathology. We can only translate data from models of THA (animal *in vivo* or *in vitro*) to the human situation (El-Warrak et al. 2004; Ma et al. 2009) and compare these with analyses of tissues from failed THAs. Unfortunately, tissues retrieved during revision surgery reflect late stages of the process when local homeostasis has long

What parameters are typical for physiological equilibrium between implant derived signals and healthy status of periprosthetic tissues in terms of maintenance of at least their architecture and function? The first and inevitable condition is *stable interface between implant and bone* which protects tissues from the deleterious effects of mechanical stimuli (stable equilibrium of implant-bone interface). The ideal condition is when the bone around the implant is protected from excessive mechanical stresses and strains and at the same time can undergo bone remodelling. The next critical step is *the ability to resolve inflammation induced by surgical trauma together with prevention of biofilm formation* on the prosthetic surface. Both the inability to achieve a steady very low-inflammatory status as early as possible and the

**2.** Positive patch test reaction to a metal used in the implant (often strong

(Tab. 2) should be followed (Thyssen et al. 2011a).

**Criteria Description** 

problem of maladaptation.

failed in the majority of cases.

reactions).

(Wahlberg 2006). Albeit there is raising concern that the patch test mainly measures cutaneous metal allergy rather than allergic reactions caused and effectuated by systemic immune cells, the patch test has worked well to establish an association between metal ion concentrations in the blood and urine, metal allergy and loosening of 1st generation metalon-metal hip implants. It is clear that a system test, e.g. the lymphocyte transformation test that measures immune reactivity in bone near structures or the blood may have a higher sensitivity and it is therefore warranted. However, no such test system is currently available for allergist and surgeons in most centres and countries.

Fig. 4. Patch test reactions following 48 hours of occluded 5% nickel sulphate exposure. Upper line from left to right: irritative reaction, doubtful reaction (+?), and doubtful reaction (+?). Lower line from left to right: weak positive (1+), moderate positive (2+), and strong positive (3+) allergic reactions.
