New-generation metal-on-metal bearings made from cobalt-chromium alloys for use in total hip arthroplasty are now being utilized worldwide. A hypersensitivity reaction to a metal-on-metal bearing is a rare but reported complication and is thought to be a novel mode of failure of these implants1,2. These reactions were initially observed in patients with first-generation bearings and are now being reported in association with the second-generation metal-on-metal bearings currently in use3-5. Characteristic histological changes in the periprosthetic tissues obtained during revision surgical procedures in these patients have suggested the development of an immunological response2,6.
Reports have suggested that the possibility of such a reaction should be considered when a patient presents with persistent, or the early reappearance of, preoperative pain symptoms, including a marked joint effusion, and the development of early osteolysis or radiolucent lines in the absence of infection2,7. Fever and elevated serum levels of inflammatory markers have routinely been reported to not occur in these patients.
We describe two patients with failure of metal-on-metal implants who presented with signs that mimicked a deep-seated hip infection. To our knowledge, this has not been reported previously. Although the two cases were similar in terms of the clinical presentation, each ultimately represented a different pathological condition and etiology.
The patients were informed that data concerning the case would be submitted for publication, and they consented.
CASE 1. A fifty-three-year-old man presented to our emergency department because of bilateral hip pain and episodes of low-grade fever three years after a bilateral metal-on-metal total hip arthroplasty. A Pinnacle acetabular component with a cobalt-chromium metal bearing surface (DePuy Orthopaedics, Warsaw, Indiana) had been implanted bilaterally. The pain had been present since the surgery, and the patient had never stopped using a cane. He had had only short-term relief of the bilateral hip pain after a tapered one-month trial of prednisone, prescribed by his primary care physician. The patient subsequently had several episodes of low-grade fever, four weeks prior to presenting to our facility, and a local physician had prescribed oral antibiotics.
Physical examination at presentation to us demonstrated a shuffling gait with the aid of two canes. The range of motion of both hips was limited to approximately 0° to 75° of flexion with pain on internal and external rotation. The neurovascular status was intact distally, and there were no external signs of infection, such as erythema, warmth, or swelling, over either incision. The soft tissues about both hips were firm on palpation, and there was no cellulitis. Radiographs of both hips revealed well-seated uncemented metal-on-metal total hip prostheses without evidence of loosening, osteolysis, or implant failure. The cup abduction angle was 47° on the left side and 50° on the right.
Levels of inflammatory biomarkers were elevated. The erythrocyte sedimentation rate was 34 mm/hr (normal, 0 to 22 mm/hr), the C-reactive protein level was 126 mg/L (normal, <8.0 mg/L), and the blood leukocyte count was 23.8 × 109/L (normal, 3.5 to 10.5 × 109/L). Two image-guided hip aspirations were done after the patient had not taken antibiotics for at least four weeks, and no organisms grew on culture of the aspirate. The patient underwent extensive workups for inflammatory, rheumatologic, spine, and infectious etiologies, but no cause of the signs and symptoms was identified. Serum metal-ion testing done at that time showed elevated levels of cobalt (1.4 ng/mL [normal, 0.0 to 0.9 ng/mL]) and chromium (0.4 μg/L [normal, <0.3 μg/L]), whereas the level of titanium was within normal limits (<5 ng/mL [normal, <0 ng/mL]).
Because of continued symptoms, the patient was taken to the operating room for exploration of the possibilities of a culture-negative infection or a hypersensitivity reaction to debris from the metal-on-metal bearing of the left hip prosthesis. Surgical exploration revealed stiff soft tissues and capsule with a “milk-stained” fluid within the joint. The metal liner was exchanged for a highly cross-linked polyethylene liner. Pathological examination of intraoperative tissue specimens revealed perivascular lymphocytic aggregates and chronic inflammation consistent with aseptic lymphocytic vasculitis-associated lesions (ALVAL) (Fig. 1). No organisms grew on culture of three intraoperative tissue samples and one fluid sample.
Postoperatively, the patient underwent skin testing, which revealed a cutaneous allergic response to cobalt. Eight months postoperatively, the patient reported substantial resolution of the left hip pain (decreasing from a grade of 10 to a grade of 1 on a scale of 0 [no pain] to 10 [worst pain in one's life]), and he had stopped taking all opiate pain medications. Additionally, the patient reported resolution of the fevers. He used a cane when he was outside but not around the house. He was working on his farm and was able to get on and off of his tractor without difficulty.
CASE 2. A fifty-five-year-old man presented to our institution with pain in the left hip three months after undergoing a left metal-on-metal total hip arthroplasty. The patient did not recall any inciting trauma. The patient also reported that he had a severe limp due to the pain and occasionally noted a loud squeaking that could be heard throughout the room. A review of his history revealed a metal allergy with an inability to wear jewelry such as watches and rings. Physical examination demonstrated a severely antalgic gait. He had a well-healed surgical incision but notable swelling and induration around the entire left hip. There was no evidence of cellulitis or erythema, and the neurovascular status was intact distally. Radiographs of the left hip revealed a well-seated, uncemented, metal-on-metal total hip prosthesis without evidence of loosening, osteolysis, or implant failure. He had an ASR XL acetabular component with a cobalt-chromium metal bearing surface (DePuy Orthopaedics). The femoral head seemed to almost cover the entire socket (Fig. 2).
The levels of inflammatory biomarkers were elevated, with an erythrocyte sedimentation rate of 46 mm/hr (normal, 0 to 22 mm/hr), a C-reactive protein level of 53.5 mg/L (normal, <8.0 mg/L), and a blood leukocyte count of 6.9 × 109/L (normal, 3.5 to 10.5 × 109/L). The patient underwent two image-guided hip aspirations after having ceased any antibiotic therapy for at least four weeks, and no organisms grew on culture of the aspirate. Because of continued symptoms, the patient was then taken to the operating room for exploration of the possibilities of a culture-negative infection or a possible hypersensitivity reaction to debris from the metal-on-metal bearing of the hip prosthesis.
Gross intraoperative examination revealed extensively necrotic tissue with scattered pigment and a metallosis reaction similar to that seen with failure of a metal-backed patellar component. Pathological examination of frozen sections of two intraoperative samples showed acellular tissue without major inflammation. Pathological examination of permanent histological preparations revealed scattered pigment but no obvious evidence of metallosis.
The intraoperative cultures were negative. A lymphocyte proliferation assay subsequently showed no reactivity. A highly cross-linked polyethylene bearing surface was implanted.
The postoperative course was complicated by wound dehiscence in the left hip, which required evacuation of a hematoma and revision of the wound approximately two weeks after the procedure. At three months postoperatively, the patient was essentially symptom-free, did not use gait aids, and presented for evaluation for an elective right total hip arthroplasty. Overall, the patient was very pleased with the postoperative course.
A review of the surgical notes on the patient's original total hip arthroplasty and the manufacturer's stickers from the implant components suggested that a larger-than-recommended femoral head component had been paired with the acetabular component. A femoral head component with a 55-mm bearing diameter had been used with an acetabular component that had a 60-mm outer diameter, even though a 53-mm-bearing-diameter femoral head component is the correct size to match a 60-mm-outer-diameter acetabular component in this system.
We report on two patients who presented with signs and symptoms of deep-seated hip infection in the presence of metal-on-metal implants. The cause of these symptoms differed between the cases. The first patient had what we believe was a so-called hypersensitivity reaction to the metal-on-metal implant, and the second patient had mismatch between the sizes of the femoral head and the acetabular socket that led to a rapid increase in the production of local metal debris and tissue hyperreactivity to the metal. The two cases had in common relentless pain in the hip with elevated levels of inflammatory markers suggesting infection, and one of the patients (Case 1) had fever episodes of unknown origin for several months.
Metal-on-metal hypersensitivity reactions are considered to be local hypersensitivity Type-IV reactions2, also referred to as aseptic lymphocytic vasculitis-associated lesions (ALVAL)2. Constituents of metal alloys or bone cement, such as benzoyl peroxide, have been shown to be potential allergens in patients treated with total hip arthroplasty8. Previously reported clinical presentations have included pain within ten months to five years following the surgery or early radiographic signs of loosening, but to our knowledge no report has specifically described patients with constitutional symptoms or elevated serum levels of inflammatory biomarkers, as we reported. Tissues retrieved during revision arthroplasties in patients without infection have shown distinct histomorphological changes such as perivascular lymphocytic infiltrates without evidence of a foreign body reaction2, as was seen in Case 1. Tissue specimens from this patient were reportedly positive for B and T lymphocytes, which could be consistent with an active proliferative reaction9 and could possibly account for the febrile response.
Although a hypersensitivity reaction to the metal-on-metal prosthesis was suspected in Case 2, it was not confirmed histologically. Furthermore, proliferation assays of lymphocytes exposed to implant metals indicated no reactivity to the tested metals, which included cobalt and chromium. In contrast to the chronic inflammation identified in Case 1, the samples from Case 2 revealed acellular necrotic tissue. The notable tissue reaction and metal staining suggested a metallosis similar to what is sometimes seen in association with a worn metal-backed patellar component and suggested local tissue hyperreactivity to metal. The absence of changes suggestive of metallosis on pathological examination may have been due to inadequate sampling. A review of the patient's preoperative surgical report and the manufacturer's implant stickers revealed that the pairing of the acetabular and femoral components was erroneous. Therefore, we believe that because the outer diameter of the femoral head component was larger than the inner diameter of the acetabular component the patient had extreme metal wear secondary to equatorial contact between the femoral head and acetabular components. This more than likely led to the squeaking sounds that the patient heard and eventually led to the substantial pain and tissue necrosis. The tissue hyperreactivity also led to elevated levels of inflammatory markers, which have not been classically seen with failure of metal-on-metal implants. More than likely, the large amount of metal debris caused an inflammatory reaction leading to these elevated marker levels, which were probably potentiated by some form of metal hypersensitivity as the patient was unable to tolerate any type of metals on the skin.
From a technical standpoint, the inappropriate pairing of the acetabular and femoral components likely led to the large inflammatory reaction seen in Case 2. It is imperative for a surgeon implanting metal-on-metal implants to know the difference in diameter between the outer diameter of the acetabular component and the bearing diameter of the femoral head component in their preferred system. This difference in the diameters of matching components is different for each company, with the devices of some companies having a difference of 6 mm for midsized bearings, 5 mm for lower sizes, and 7 mm for larger-diameter bearings.
Hypersensitivity reactions and failure of metal-on-metal implants will become more common as more metal-on-metal implants are used. These reactions are still rare, with reported estimated prevalences of 1% to 2% and up to 5% for certain alloys such as cobalt and chromium10. To our knowledge, the presentation of this entity with fevers of unknown origin and elevated levels of inflammatory biomarkers has not been previously reported. In the absence of occult infection, this diagnosis should be considered. Both of our patients had complete resolution of symptoms following exchange of the metal liner for a highly cross-linked polyethylene component, and we recommend this as the treatment of choice.
Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Investigation performed at the Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota
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