Lyme Arthritis After Knee Replacement: A Case Mistaken for Joint Infection

Q: Why are routine joint cultures negative?

Borrelia burgdorferi does not grow in the routine bacterial cultures generally used to evaluate prosthetic joint infections. Targeted Lyme PCR on joint fluid or periprosthetic tissue may help identify the organism.

Knee swelling after joint replacement can mimic infection
Lyme arthritis may present with culture-negative joint effusions
Targeted testing may help avoid diagnostic delays

An 83-year-old man from Pennsylvania developed knee pain, swelling, erythema, and fever years after a knee replacement. Initially believed to have a prosthetic joint infection, he was ultimately diagnosed with Lyme arthritis.

The case highlights how Lyme arthritis can resemble a prosthetic joint infection, particularly when a replaced knee becomes markedly swollen and inflamed.

Upon examination, physicians noted “a moderate effusion and limited range of motion,” explains Collins. Routine bacterial cultures were negative. Nevertheless, the patient met the Musculoskeletal Infection Society’s criteria for periprosthetic joint infection.

As a result, the prosthetic knee was removed. “The patient underwent resection arthroplasty with insertion of a static antibiotic spacer, as purulence and synovitis were noted intraoperatively,” writes Collins in the Journal of the American Academy of Orthopaedic Surgeons Global Research & Reviews. The patient was initially prescribed intravenous antibiotics.

Lyme Disease Can Mimic a Culture-Negative Joint Infection

Following surgery, the patient’s Lyme antibody test and synovial fluid Lyme PCR returned positive. His Lyme IgG immunoblot was also positive, with 8 of 10 significant bands present.

The diagnosis was changed to disseminated Lyme disease. His symptoms improved after 2 weeks of oral doxycycline followed by 4 weeks of intravenous ceftriaxone.

“He subsequently underwent removal of the antibiotic cement spacer and reimplantation using revision TKA components,” writes Collins.

This case illustrates the importance of appropriate Lyme disease testing in patients with unexplained culture-negative joint effusions, particularly in Lyme-endemic regions.

Clinical Insight: Routine bacterial cultures do not detect Borrelia burgdorferi. When a replaced knee or hip is painful and swollen but conventional cultures remain negative, targeted Lyme testing may be worth considering in an endemic region.

Lyme Arthritis in a Replaced Knee Treated Without Surgery

A 2025 case report described a 68-year-old woman who developed pain and substantial swelling in a knee that had been replaced 10 years earlier. She also reported malaise, muscle aches, and a mildly elevated temperature.

The prosthesis appeared well fixed, but aspiration produced cloudy joint fluid. Routine aerobic and anaerobic cultures were negative. Lyme serology was strongly positive, with all 10 IgG immunoblot bands present, and synovial fluid PCR detected Borrelia burgdorferi.

The patient received oral doxycycline for 28 days without surgery or intravenous antibiotics. Her knee pain and effusion largely resolved, and she remained asymptomatic at the 6-month and 2-year follow-ups.

The authors described this as the first published case of Lyme disease involving a prosthetic joint that was treated with oral doxycycline alone, without surgery, and documented with adequate post-treatment follow-up.

This outcome suggests that selected patients with Lyme arthritis involving a replaced joint may not require the same treatment used for a conventional bacterial prosthetic joint infection. However, one successful case cannot establish that surgery can safely be avoided in every patient with a painful and swollen joint replacement.

2026 Review Expands the Evidence to 10 Cases

A 2026 review described 2 additional patients and evaluated 8 previously reported cases—including the successfully treated 2025 case. All 10 patients presented with pain and swelling, and all had negative routine bacterial cultures.

Only 2 patients recalled a tick exposure, and none reported an erythema migrans rash. In every case, the diagnosis was supported by a positive Borrelia-targeted PCR performed on synovial fluid or tissue surrounding the prosthetic joint.

The review also included the first reported case involving a prosthetic hip. Earlier reports had involved replaced knees.

Treatment varied considerably. Six patients underwent a surgical procedure, while 4 were managed without surgery. All experienced clinical resolution, and no relapses were reported during the available follow-up.

However, only 10 cases have been described. These outcomes should not be interpreted to mean that suspected prosthetic joint infections can routinely be treated without surgery. Management requires individualized assessment involving orthopedic and infectious disease specialists.

Why Lyme Disease Should Be Considered After Joint Replacement

Lyme arthritis most commonly affects the knee. In endemic regions, Lyme disease should remain in the differential diagnosis when a replaced knee—or, more rarely, a replaced hip—develops unexplained pain, swelling, effusion, or inflammation.

The possibility becomes especially relevant when:

Routine bacterial cultures remain negative
The prosthesis appears well fixed
There is no wound drainage, dehiscence, or sinus tract
The patient lives in or has visited a Lyme-endemic area

A remembered tick bite or previous rash is not required. The 2026 review found that most patients recalled neither.

This presentation is another example of Lyme disease misdiagnosis, in which inflammatory Lyme arthritis may initially be attributed to another orthopedic or infectious condition.

Frequently Asked Questions

Can Lyme disease affect a replaced knee?

Yes. Although rare, Lyme arthritis can involve a knee that has previously undergone joint replacement and may cause pain, swelling, warmth, stiffness, and effusion.

Can Lyme disease affect an artificial hip?

Yes, but it appears to be extremely rare. A 2026 report described the first published case involving a prosthetic hip.

Can Lyme disease mimic a prosthetic joint infection?

Yes. Lyme arthritis involving a replaced joint may produce symptoms and inflammatory test results that resemble a conventional bacterial prosthetic joint infection.

Why are routine joint cultures negative?

Borrelia burgdorferi does not grow in the routine bacterial cultures generally used to evaluate prosthetic joint infections. Targeted Lyme PCR on joint fluid or periprosthetic tissue may help identify the organism.

Does Lyme disease involving a joint replacement always require surgery?

Not necessarily. Several reported patients were treated without surgery, including one who remained asymptomatic two years after receiving oral doxycycline. However, the evidence is limited to a small number of cases. Suspected prosthetic joint infection requires individualized orthopedic and infectious disease evaluation.

Clinical Takeaway

Lyme disease should be considered when a replaced knee or hip becomes painful and swollen but routine bacterial cultures remain negative, particularly in a Lyme-endemic region.

Recent reports suggest that targeted Lyme serology and synovial fluid PCR may identify cases missed by the conventional prosthetic joint infection workup. Some patients have recovered with antibiotics without surgery, but the evidence remains limited and does not support a single treatment approach for every patient.

Successful treatment of Lyme arthritis after knee surgery

Preventing unnecessary surgery for children with Lyme arthritis

Diagnosing Lyme arthritis of the hip in children

Lyme disease symptoms guide