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Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern.

Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, Schneider J, Flaig M, Krenn V, Thomas B, Summer B - Biomed Res Int (2015)

Bottom Line: We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion.Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients.The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief.

View Article: PubMed Central - PubMed

Affiliation: Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität (LMU), Frauenlobstraße 9-11, 80337 München, Germany.

ABSTRACT
We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

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(a) Example of perivascular lymphocytic infiltrate; αCD3 stain. (b) Example of scattered periprosthetic lymphocytes; αCD3 stain.
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fig1: (a) Example of perivascular lymphocytic infiltrate; αCD3 stain. (b) Example of scattered periprosthetic lymphocytes; αCD3 stain.

Mentions: We next wondered if the periprosthetic tissue analysis would help to discriminate hyperergic tissue response. For this purpose, four conditions were chosen for comparative analysis of tissue specimen. For example, periprosthetic tissue samples were obtained from (1) the 20 TKR patients with complications and metal sensitivity (Groups I and II); (2) the 5 TKR patients with complications but no metal sensitivity (Group III); (3) 12 patients with degenerative knee joint disease/osteoarthritis (OA-control group) at primary arthroplasty; and (4) the cutaneous biopsies that were performed at PT sites in 8 PT patients (PT-control group) of whom 6 had positive, eczematous PT reaction to Ni and 2 had no PT reaction to Ni. The rating of periprosthetic/(neo) capsule tissue response was done according to the standardized consensus classification initially published by Morawietz et al. in 2006 [31] and revised by Krenn et al. [24]. In addition focus was put on the presence of T-lymphocytes, B-lymphocytes, neutrophils, and macrophages—and furthermore probes of Groups I, II, and III patients were also sent to microbiology evaluation. Several unexpected findings were made: 9/11 patients in Group I and 6/9 patients in Group II had a collagen fibre rich, connective tissue resembling periprosthetic tissue reaction (Type IV/indeterminate type). And only 5 of the 20 metal sensitive patients had the overall picture of the “wear particle induced type” with macrophage dominated response. This is in contrast to the general observation of mostly wear particle/foreign body response like tissue pattern in failed arthroplasty and to the only 15% Type IV (fibrotic) response reactivity in the 370 samples analysed by Morawietz et al. [31]. There were no signs of infections in these 20 samples of our Groups I and II patients. Despite being a predominant “arthrofibrosis”-like, paucicellular reactivity, presence of lymphocytes was noted in perivascular or scattered distribution (Figures 1(a) and 1(b)). In contrast, out of the 5 patients without metal sensitivity two showed infection and lymphocytic inflammation was only seen in one of these patients. In OA-patients, again, lymphohistiocytic infiltrates were noted together with absence of neutrophils. These findings are summarized in Tables 2, 3, and 4. Figures 1(a) and 1(b) are representative histology findings of patients in Groups I and II. Biopsies from Ni-induced allergic patch test reactions were characterized by perivascular and sometimes diffuse lymphohistiocytic infiltrates together with contact allergy-typical epidermal changes as shown in a representative sample (Figure 2(a)). Witzleb et al. speculated that perivascular or diffuse presence of (T-)lymphocytes in periprosthetic tissue could be interpreted as hyperergic response [15]. However, von Domarus and coworkers [32] described T lymphocyte infiltration as a common finding in tissue samples of retrieved aseptically loosened metal-on-polyethylene arthroplasties. Thus, they conclude that neither necrobiosis nor infiltration of T-lymphocytes should be considered to be specific for metal hypersensitivity reaction.


Patients with intolerance reactions to total knee replacement: combined assessment of allergy diagnostics, periprosthetic histology, and peri-implant cytokine expression pattern.

Thomas P, von der Helm C, Schopf C, Mazoochian F, Frommelt L, Gollwitzer H, Schneider J, Flaig M, Krenn V, Thomas B, Summer B - Biomed Res Int (2015)

(a) Example of perivascular lymphocytic infiltrate; αCD3 stain. (b) Example of scattered periprosthetic lymphocytes; αCD3 stain.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383474&req=5

fig1: (a) Example of perivascular lymphocytic infiltrate; αCD3 stain. (b) Example of scattered periprosthetic lymphocytes; αCD3 stain.
Mentions: We next wondered if the periprosthetic tissue analysis would help to discriminate hyperergic tissue response. For this purpose, four conditions were chosen for comparative analysis of tissue specimen. For example, periprosthetic tissue samples were obtained from (1) the 20 TKR patients with complications and metal sensitivity (Groups I and II); (2) the 5 TKR patients with complications but no metal sensitivity (Group III); (3) 12 patients with degenerative knee joint disease/osteoarthritis (OA-control group) at primary arthroplasty; and (4) the cutaneous biopsies that were performed at PT sites in 8 PT patients (PT-control group) of whom 6 had positive, eczematous PT reaction to Ni and 2 had no PT reaction to Ni. The rating of periprosthetic/(neo) capsule tissue response was done according to the standardized consensus classification initially published by Morawietz et al. in 2006 [31] and revised by Krenn et al. [24]. In addition focus was put on the presence of T-lymphocytes, B-lymphocytes, neutrophils, and macrophages—and furthermore probes of Groups I, II, and III patients were also sent to microbiology evaluation. Several unexpected findings were made: 9/11 patients in Group I and 6/9 patients in Group II had a collagen fibre rich, connective tissue resembling periprosthetic tissue reaction (Type IV/indeterminate type). And only 5 of the 20 metal sensitive patients had the overall picture of the “wear particle induced type” with macrophage dominated response. This is in contrast to the general observation of mostly wear particle/foreign body response like tissue pattern in failed arthroplasty and to the only 15% Type IV (fibrotic) response reactivity in the 370 samples analysed by Morawietz et al. [31]. There were no signs of infections in these 20 samples of our Groups I and II patients. Despite being a predominant “arthrofibrosis”-like, paucicellular reactivity, presence of lymphocytes was noted in perivascular or scattered distribution (Figures 1(a) and 1(b)). In contrast, out of the 5 patients without metal sensitivity two showed infection and lymphocytic inflammation was only seen in one of these patients. In OA-patients, again, lymphohistiocytic infiltrates were noted together with absence of neutrophils. These findings are summarized in Tables 2, 3, and 4. Figures 1(a) and 1(b) are representative histology findings of patients in Groups I and II. Biopsies from Ni-induced allergic patch test reactions were characterized by perivascular and sometimes diffuse lymphohistiocytic infiltrates together with contact allergy-typical epidermal changes as shown in a representative sample (Figure 2(a)). Witzleb et al. speculated that perivascular or diffuse presence of (T-)lymphocytes in periprosthetic tissue could be interpreted as hyperergic response [15]. However, von Domarus and coworkers [32] described T lymphocyte infiltration as a common finding in tissue samples of retrieved aseptically loosened metal-on-polyethylene arthroplasties. Thus, they conclude that neither necrobiosis nor infiltration of T-lymphocytes should be considered to be specific for metal hypersensitivity reaction.

Bottom Line: We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion.Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients.The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief.

View Article: PubMed Central - PubMed

Affiliation: Klinik und Poliklinik für Dermatologie und Allergologie der Ludwig-Maximilians-Universität (LMU), Frauenlobstraße 9-11, 80337 München, Germany.

ABSTRACT
We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies.

Show MeSH
Related in: MedlinePlus