Keys To Addressing Periprosthetic Joint Infections After Total Ankle Arthroplasty

Periprosthetic joint infection after total joint replacement can be a severe complication with significant morbidity and extensive health-care costs. In this review, the authors propose a clinical guideline for initial evaluation and diagnosis of prosthetic joint infection of the ankle. 

Periprosthetic joint infection (PJI) after total joint replacement is a severe complication resulting in significant morbidity and extensive cost for the health-care system.^1-3 Surgical site infections remain one of the most common causes for emergency department visits and readmission following joint arthroplasty.⁴ The estimated incidence of periprosthetic joint infection after total ankle arthroplasty is 1.2 to 8.6 percent, exceeding the rate for total hip and knee replacements.^5-13 Deep infection of the ankle prosthesis is the leading cause of failure of total ankle arthroplasties, comprising 80.6 percent of all failures, and is classified as a “high-grade” complication.²

There is a large body of literature regarding periprosthetic joint infection after total hip and knee arthroplasty. However, there are limited guidelines that are specific to the initial workup, management and treatment of infection after total ankle arthroplasty. These infections are unique from hip and knee periprosthetic joint infections due to the tenuous surrounding soft tissue and compromised peripheral vascular supply. There is also a higher proportion of patients requiring total ankle arthroplasty as a result of previous trauma in comparison to osteoarthritis.¹¹ Thus, many patients may have had previous surgeries, such as open reduction with internal fixation, increasing the risk of soft tissue complications. 

In addition, there are limited revision options for total ankle arthroplasty after periprosthetic joint infection in comparison to the hip and knee.⁶ There can be significant morbidity associated with  ankle periprosthetic joint infections, including the need for amputation.¹⁴ A study evaluating ankle applications of a treatment algorithm developed for hip and knee periprosthetic joint infection revealed an infection-free outcome in only 67.6 percent of patients.⁶ Most of the ankle patients were not able to meet the criteria set forth for the current hip and knee algorithm. This was secondary to the need of a treatment algorithm requiring grading of the soft tissue quality.⁶ Thus, despite established methods of treatment for hip and knee periprosthetic joint infection, one cannot extrapolate these algorithms uncritically to replacements of the ankle or other anatomic sites.^4,6,15 

The purpose of this review is to provide a clinical guideline of the initial evaluation and diagnosis of periprosthetic joint infection of the ankle. Treatment and surgical management are outside the scope of this article as they may vary substantially based on the acute versus chronic nature of the infection as well as its severity.

Which Patients Are At Risk For Periprosthetic Joint Infection?

In any patient with persistent pain following total ankle arthroplasty, infection is a consideration. The surgeon must assess for the presence of well-established risk factors for periprosthetic joint infection that raise the suspicion of septic failure.¹⁶ The most critical risk factor for periprosthetic joint infection in the ankle is a surgical history of the ipsilateral ankle. According to a study by Patton and colleagues, the rate of infection for revision total ankle arthroplasty is approximately double the rate for primary replacement (4.7 versus 2.5 percent).¹⁴ Several studies identify risk factors for postoperative infection that include diabetes, peripheral vascular disease, inflammatory arthritis, obesity, hypothyroidism and wound healing problems for greater than 14 days.^11,14,17 

Two recent meta-analyses identified additional patient-related factors for periprosthetic joint infection that include smoking, body mass index (BMI) greater than 30 kg/m², depression, steroid use, albumin level less than 34 g/L, wound drainage, a National Nosocomial Infections Surveillance Score greater than 2, coagulopathy and frailty.^18,19 Previous studies involving joint arthroplasty in other areas of the body have shown an increased risk of periprosthetic joint infection in patients with a history of prior joint infection.^20-22 Therefore, prior ankle infection has historically been a contraindication to total ankle arthroplasty. 

However, in a recent study assessing total ankle arthroplasty in 22 patients with a history of ankle joint infection, Shi and coworkers noted 100 percent survival of the prothesis at a mean follow-up of 29 months.²³ Despite these results, one should still consider a history of prior ankle infection as a risk factor for periprosthetic joint infection after total ankle replacement.

Classifying Periprosthetic Joint Infections: What You Should Know

One classifies periprosthetic joint infections as acute versus chronic and direct inoculation versus hematogenous.^16,24 Direct inoculation may include a sinus tract directly through the joint capsule or a wound dehiscence. Hematogenous infections may occur in a patient with a long-standing, infection-free joint replacement. A remote source, such as dental work or an infected upper body pathology, can cause a sudden onset of symptoms.^16,24 It is critical to determine the timing of infection from the original ankle arthroplasty as the time frame of presentation can require different treatment protocols.²⁵ The periprosthetic joint infection that occurs within six weeks of the original surgery is considered an acute infection while chronic infections present months to years postoperatively.²⁵

Chronic, or late, infections often present as an “acute septic arthritis syndrome with sudden onset of pain in the setting of concomitant or recent infection occurring elsewhere in the body.”^26,27 These late infections may occur greater than one to two years after the index arthroplasty surgery. Hematogenous seeding of the prosthesis or late manifestation of an indolent infection are reported causes of late presentation.²⁸ 

In hip and knee literature, chronic cases account for approximately 56 percent of periprosthetic joint infections, followed by acute postoperative infections at 31 percent and acute hematogenous infections at 13 percent.^25,29 There is limited data on periprosthetic ankle infections but Myerson and colleagues reported on a small retrospective case series including 19 infected total ankle arthroplasties.³⁰ These 19 cases included 15 chronic infections, three acute postoperative infections and one acute hematogenous infection.30 Yet in another study of 34 patients, Kessler and colleagues found that 19 (55.9 percent) of their periprosthetic joint infections were acute and 15 (44.1 percent) were chronic.¹¹ This study also showed that 82.4 percent of their cases were from exogenous causes and 17.6 percent were hematogenous.¹¹

Key Aspects Of The Clinical Presentation And Examination

Evaluation of a patient with a periprosthetic joint infection should include a thorough history and physical examination. During the history, it is important to identify the timeline of the total ankle replacement surgery and the patient’s postoperative course. More specifically, one should evaluate for the presence of acute onset of pain within the first few months of implantation, any new onset of pain following a pain-free interval in the first few years post-implantation or a history of prior wound healing complications.¹⁵ The most common reasons for persistent pain following total ankle arthroplasty include impingement, infection, aseptic loosening, instability, fracture, malposition of the prosthesis, arthrofibrosis and cyst formation.^2,31

The provider should be aware of clinical presentations that may masquerade as periprosthetic joint infection. For example, peri-incisional erythema may be consistent with normal postoperative inflammation and physiologic healing. Additionally, a local granulomatous response to a foreign body, such as absorbable suture or staple abscess, is not considered a sign for superficial infection nor periprosthetic joint infection.³² Patients may also react to adhesives placed around the incisional area that may mimic an infectious presentation. Thus, distinguishing these entities from true periprosthetic joint infection can be challenging. Although superficial wound drainage after total joint arthroplasty is not uncommon, persistent wound drainage, defined as “continued drainage from the operative incision site for greater than 72 hours,” warrants further investigation.^33-35

A sinus tract communicating with the joint is a major diagnostic criterion for periprosthetic joint infection (see first photo above). Other findings, such as joint tenderness, joint effusion or wound dehiscence, should raise clinical suspicion for periprosthetic joint infection but are not independently specific.³⁵ Additional signs may include warmth, tenderness, erythema, edema, drainage and induration. Depending on the severity of the infection, constitutional or systemic symptoms may or may not be present.^36-38

Chronic infections often present as vague pain without systemic symptoms. Patients may present with functional deterioration and progressing ankle pain over time. The alternative diagnoses for patients with nontraumatic, progressive ankle pain following total ankle arthroplasty may be aseptic in nature (i.e. aseptic loosening, osteolysis, failure of the implant). This scenario can be difficult to differentiate from aseptic loosening by history and physical examination alone. However, a history of prior wound healing complications, superficial or deep, should raise suspicion for periprosthetic joint infection.¹⁵ Serological and joint aspiration tests are useful in distinguishing septic from aseptic etiologies.

Pearls And Pitfalls With Lab Testing Of Post-TAR Infections

Laboratory evaluation of a suspected ankle periprosthetic joint infection consists of complete blood count with differential, basic metabolic panel, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and blood cultures with acute or hematogenous presentations followed by joint aspiration. 

Inflammatory markers of CRP and ESR are cost-effective tests that have a high sensitivity and high negative predictive value.^39-41 Both inflammatory markers are very useful for ruling out periprosthetic joint infection.^25,42 However, serum ESR and CRP have relatively poor specificity.^43-45 When ESR and CRP are negative, the negative likelihood ratio becomes 0-0.06 for periprosthetic joint infection.^25,42 Erythrocyte sedimentation rate is less useful in the acute setting as it peaks later in comparison to CRP.¹⁶ When one uses ESR and CRP in combination, the diagnosis of periprosthetic joint infection becomes more reliable in comparison to isolated elevations.^25,43-45

Synovial fluid from the joint aspiration requires evaluation for aerobic and anaerobic culture, synovial white blood cell (WBC) count, and polymorphonuclear (PMN) cell percentage as well as crystal analysis.^46-50 A synovial fluid WBC count of greater than 3,000 cells/µL and percentages of neutrophils greater than 80 percent is suggestive of periprosthetic joint infection.^51-53 The literature shows that synovial fluid WBC count greater than 3,000 in chronic periprosthetic joint infection cases in the hips and knees is 100 percent sensitive and 98.1 percent specific for periprosthetic joint infections  with a positive predictive value of 97.6 percent and negative predictive value of 100 percent.^51-53 For chronic infections, a synovial polymorphonuclear percentage greater than 80 percent is 97 percent sensitive and 94 percent specific with a positive predictive value of 94 percent and a negative predictive value of 99 percent.^46-49

These values are significantly useful in diagnosing a periprosthetic joint infection in a chronically infected total ankle replacement. However, a higher threshold for white blood cell count and polymorphonuclear cell percentage values are necessary in the acute phase. In the first six weeks postoperatively, a synovial WBC count less than 10,000 cells/µL and a percentage of polymorphonuclear cells under 90 percent is thought to be normal with values greater than these suggestive of periprosthetic joint infection.^47,54 Cutoff values of serological and synovial markers do not change in the setting of systemic inflammatory disease.³⁵

A retrospective study reported 19 cases of infection in a series of 613 total ankle arthroplasties.³⁰ Coagulase-negative staphylococcus species isolated from 26 percent of cases, and methicillin-sensitive staphylococcus aureus (MSSA) in 21 percent of cases.³⁰ Only one case (five percent) was polymicrobial.³⁰ A single cohort series of 34 cases revealed similar findings with staphylococcus as the most commonly identified species at 70 percent and 18 percent of cases were polymicrobial.¹¹ Mycobacteria and fungi are rare causes of periprosthetic joint infection, and recent evidence shows that routine acid-fast bacillus (AFB) and fungal evaluation does not yield clinically important findings nor is it cost-effective.^55-58 Therefore, even in cases of proven or suspected periprosthetic joint infection, testing for acid-fast bacillus or fungi is not warranted in patients without unusual suspicion or risk factors for atypical infection.

A new marker for diagnosing ankle periprosthetic joint infection is serum interleukin-6. In hip and knee literature, it is a very specific marker for acute periprosthetic joint infection.^59-61 In a prospective, case-control study involving patients who had hip or knee arthroplasty, Di Cesare and colleagues found that interleukin-6 had high accuracy (97 percent), negative predictive value (1.0), positive predictive value (0.89), sensitivity (1.0), and specificity (0.95) in evaluating patients for perirprosthetic joint infection.⁵⁹ 

There are other synovial fluid biomarkers that are highly sensitive and specific for periprosthetic joint infections. Alpha-defensin is a natural peptide released by leukocytes in response to bacteria and has shown up to 100 percent sensitivity and specificity for periprosthetic joint infections.⁶² However, alpha-defensin requires approximately 24 hours for results. Synovial C-reactive protein and leukocyte esterase reagent strips are other synovial fluid tests that one can use to aid in diagnosis.^62,63

How To Master The Joint Aspiration Technique

Joint aspiration provides the most diagnostic information to rule in or rule out periprosthetic joint infections. One must still ensure prudent patient selection for aspiration based around elevated laboratory markers and clinical presentation because there are still risks of pain, joint inoculation of bacteria, bleeding and disruption of soft tissue structures at the aspiration site (saphenous nerve, great saphenous vein and tibialis anterior tendon). It is important to try and avoid aspirating through cellulitic areas, which can potentially seed the joint with bacteria although this risk has not been proven to date in the literature.⁶⁴ 

Joint aspiration after total ankle arthroplasty may be difficult due to the potential joint spaces being small and filled with soft tissue. Ultrasound-guided aspiration may be useful after an unsuccessful attempt. We recommend that only experienced providers perform this procedure on periprosthetic ankle infections.

To aspirate the ankle joint, first ensure supine positioning of the patient with his or her knee extended and the ankle in the neutral dorsiflexed position. One can see the recommended materials for aspiration (see the second photo above). Identify the aspiration site along the medial shoulder of the ankle joint by measuring one cm proximal to the tip of the medial malleolus and mark just medial to the tibialis anterior tendon (see the third photo above). One can utilize either an iodine or alcohol prep at the aspiration site. 

The physician subsequently raises a wheal of 1% lidocaine plain to anesthetize the skin and subcutaneous tissue (see the fourth photo above). Be sure to dorsiflex the ankle to protect the polyethelene and the prosthesis. Aspirate the joint utilizing an 18-gauge needle placed in the anterior to posterior direction and slightly laterally in order to be just medial to the polyethylene (see fifth photo above). Two to five mL of aspiration fluid is ideal and one may employ a 10 mL syringe for easier manipulation. If unsuccessful at retrieving synovial fluid, the surgeon can use the same aspiration site and redirect the needle laterally approximately 45 degrees in order to aspirate deep to the anterior ankle capsule. 

What Is The Role Of Radiographs And Other Imaging In Diagnosing Periprosthetic Joint Infection?

Plain radiographs are an integral part in the evaluation of a painful total ankle arthroplasty. Radiographs are able to detect periprosthetic fracture, obvious implant loosening, dislocation of the joint, soft tissue edema, bone lucency and osteolysis.⁵⁰ While findings may be suggestive of periprosthetic joint infection, radiographs lack adequate sensitivity and specificity, and thus have limited diagnostic value in the presence of such infection.⁶⁵ Computed tomography (CT) and magnetic resonance imaging (MRI) testing provide limited diagnostic value due to image distortion due to the prosthesis. Furthermore, these tests carry high costs and are not readily available in all facilities.³³ 

Nuclear medicine studies provide important diagnostic information. Single-photon emission computed tomography (SPECT) can reveal talar-sided prosthetic loosening and a high incidence of talar non-integration not evident on radiographs.³¹ Despite these advantages, further research is necessary to determine the role of SPECT in the evaluation of periprosthetic joint infection. Single-photon emission computed tomography is expensive, time-consuming and not available in all centers.³¹ However, there is evidence to support SPECT if a patient has chronic medial side ankle pain.³¹

Pertinent Considerations With Diagnostic Pathways And Challenges

The development of periprosthetic joint infection protocols for the hip and knee has attained 100 percent sensitivity and 96 percent specificity in diagnosis.⁴ This proposed protocol is a modification of the diagnostic algorithm from the Musculoskeletal Infection Society and Proceedings of the International Consensus Meeting on Periprosthetic Joint Infection for ankle periprosthetic joint infection.^50,66

The diagnostic algorithm consensus states that for diagnosis of a periprosthetic joint infection, the patient must meet at least one of the following major criteria.^33,35

1. Two positive periprosthetic tissue or fluid specimens with at least one matching organism identified through microbiologic testing. Culture or non-culture based microbiologic testing should identify this organism for clinical diagnosis and treatment, and not active surveillance culture/testing.
2. A sinus tract (narrow opening or passageway that can extend in any direction and results in dead space with potential for abscess formation) that communicates with the joint evident on physical exam.

Alternately, one may ascertain a diagnosis of periprosthetic joint infection from meeting three of the following minor criteria.^33,35

1. Elevated serum C-reactive protein (CRP).

• Acute (less than six weeks): greater than 100 mg/L
• Chronic (more than six weeks): 10 to 100 mg/2. Elevated (greater than 30 mm/hour) 

2. Erythrocyte sedimentation rate (ESR), relevant in chronic infections of more than six weeks only.

3. Elevated white blood cells in the synovial fluid.

• Acute (less than six weeks): greater than 10,000 cells/µL
• Chronic (more than six weeks): greater than 3,000 cells/µL

4. Elevated polymorphonuclear neutrophil percentage in synovial fluid.

• Acute (less than six weeks): greater than 90 percent
• Chronic (greater than six weeks): greater than 80 percent.

These minor criteria are traditional tests that clinicians utilize in the workup that have a proven, reproducible accuracy in diagnosis yet are not independently pathognomonic for periprosthetic joint infection. 

When there is an index of suspicion for periprosthetic joint infection, one should not immediately administer antibiotic therapy prior to joint aspiration or ascertaining culture specimens unless the patient is hemodynamically unstable from severe sepsis or septic shock.^35,41,42 In the scenario in which the patient develops severe sepsis or septic shock, empiric antibiotic therapy and resuscitation should occur on an inpatient basis.

All cases of suspected periprosthetic joint infection should result in surgical consultation. Initial management of persistent wound drainage in the emergency department should include wound care. However, we recommend against the administration of oral or intravenous antibiotics to these same patients.³⁵ Although the rationale for initial antibiotic therapy appears logical, the  administration of an antibiotic may mask the infection or impede proper culture results.³⁵ Additionally, providers should not obtain superficial wound cultures from the skin, incisional wound or superficial wounds to avoid misleading identification of nonpathogenic microorganisms and potentially unwarranted antibiotic therapy.^34,67 The surgical management and treatment algorithm for periprosthetic joint infection is outside the scope of this article.

In Conclusion

Patients with periprosthetic joint infection of the ankle will frequently present to the emergency department. Accordingly, emergency providers as well as consulting foot and ankle surgeons play critical roles in the initial evaluation and management of these patients. By using the suggested algorithm to gather pertinent clinical, radiographic and serological data, the provider may reliably diagnose ankle periprosthetic joint infection and has a working guideline that allows for clear discharge or admission criteria.

Dr. So is a fellowship-trained foot and ankle surgeon and is an Associate of the American College of Foot and Ankle Surgeons. He is in private practice in Lincoln, Neb.

Dr. Juels is a fellowship-trained foot and ankle surgeon and is an Associate of the American College of Foot and Ankle Surgeons.  He practices in Cookeville, Tenn.

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