What lab test can diagnose metal hypersensitivity in a patient with a knee replacement?

Laboratory Testing for Metal Hypersensitivity After Knee Replacement

The most reliable approach combines patch testing with lymphocyte transformation testing (LTT), as medical history alone is insufficient to diagnose metal hypersensitivity in patients with painful knee replacements. 1, 2

Diagnostic Algorithm

Step 1: Initial Clinical Assessment

• Document specific symptoms: persistent pain, swelling, effusion, or instability in an otherwise well-positioned and stable prosthesis 1, 3
• Exclude common causes first: infection (via joint aspiration with culture and inflammatory markers), mechanical loosening, malalignment, and instability must be ruled out before considering metal hypersensitivity 2, 3
• Review patient history: prior metal allergies, jewelry reactions, or previous metal implant complications (particularly metal-on-metal hip replacements) 3

Step 2: Laboratory Testing Protocol

Patch Testing (Epicutaneous Testing)

• Primary screening test for type IV delayed hypersensitivity reactions to metals 2, 4
• Tests for nickel-II-sulfate, cobalt, chromium, and palladium chloride sensitivity 4
• Performed when medical history suggests possible metal sensitization 2
• Demonstrates skin reaction patterns consistent with metal allergy 4

Lymphocyte Transformation Testing (LTT)

• Confirmatory blood test that measures T-cell proliferation in response to metal antigens 5, 3
• More specific than patch testing for identifying metal-specific immune reactions 5
• Can detect sensitization even when patch testing is equivocal 3
• Particularly useful for nickel, cobalt, and chromium sensitivity 5, 3

Serum Metal Ion Levels

• Measure serum cobalt and chromium levels when metal hypersensitivity is suspected 3
• Elevated levels support diagnosis but are not diagnostic alone 3
• Most useful in metal-on-metal implants but can be elevated in standard TKA with hypersensitivity 3

Step 3: Tissue Analysis (If Revision Surgery Performed)

Intraoperative Histopathology

• Synovial tissue biopsy showing lymphoplasmacellular fibrinous tissue indicates type IV allergic reaction 4
• ALVAL score (Aseptic Lymphocyte-dominated Vasculitis-Associated Lesion): score ≥4 with elevated CD4+ lymphocytes confirms metal sensitization 5
• Tissue analysis provides definitive diagnosis when combined with positive LTT 5, 3

Critical Diagnostic Considerations

When to Suspect Metal Hypersensitivity

• Pain and dysfunction in radiographically well-positioned prosthesis 1, 2
• Persistent symptoms despite normal alignment and no evidence of infection 3
• History of metal sensitivity or previous metal implant complications 3
• Severe osteolysis with implant loosening in absence of infection 3
• Early postoperative persistent pain with limited range of motion 4

Common Pitfalls to Avoid

• Do not diagnose metal hypersensitivity without excluding infection: joint aspiration with culture and inflammatory markers (ESR, CRP) is mandatory 2, 3
• Do not rely on medical history alone: only 16.6% of patients with suspected metal allergy actually demonstrate true hypersensitivity on testing 2
• Do not skip patch testing: it remains the primary screening tool despite limitations 2, 4
• Do not interpret elevated metal ions as diagnostic: they support but do not confirm hypersensitivity without immunologic testing 3

Prevalence and Clinical Context

• Metal hypersensitivity occurs in approximately 15% of the general population 1
• Among patients undergoing TKA with suspected metal allergy, only 16.6% demonstrate confirmed hypersensitivity on comprehensive testing 2
• The condition is increasingly recognized as a cause of painful, well-functioning TKA after exclusion of common failure mechanisms 1, 2

Testing Sequence Summary

1. Rule out infection and mechanical causes (joint aspiration, radiographs, inflammatory markers) 2, 3
2. Perform patch testing for initial screening of metal sensitivity 2, 4
3. Order lymphocyte transformation testing for confirmation 5, 3
4. Measure serum metal ion levels (cobalt, chromium) as supportive evidence 3
5. Obtain tissue histopathology during revision surgery if performed 4, 5