Trauma-related Lyme arthritis

Abstract

A man in his 40s with no prior orthopaedic history presented to an infectious disease clinic with persistent left knee pain and swelling following a traumatic meniscal tear and ensuing prodromal period of fever and chills. Aspiration of the left knee joint revealed a white cell count of 21.0 ×10⁹/L (83% neutrophils) with negative Gram stain and culture. However, Lyme PCR was positive and accompanied by serologies consistent with Lyme arthritis. He was treated with a standard course of antibiotic therapy with subsequent resolution of joint effusion and significant improvement in pain.

This is to our knowledge the first report in the literature of Lyme arthritis seemingly provoked by traumatic knee injury. We propose disruption of normal joint anatomy and ensuing inflammation in response to acute injury incited and accelerated migration of previously latent Borrelia burgdorferi spirochetal infection into surrounding synovial tissue, leading to enhanced inflammatory activity and exacerbation of knee pain.

Background

Lyme disease (Lyme borreliosis) is the most commonly reported vector-borne illness in the USA with an estimated annual incidence of 476 000 cases between 2010 and 2018, increased from ~329 000 annual cases between 2005 and 2010.^1–3 Infection with Borrelia burgdorferi, the causative spirochetal agent, tends to be seasonal with cases most frequently reported in the months of June through August.¹ In the USA, B. burgdorferi is transmitted to humans through the tick vector Ixodes scapularis, particularly in the northeastern, mid-Atlantic, and north-central states and, more rarely, Ixodes pacificus in western states.⁴ Infection with B. burgdorferi can cause multisystem manifestations that vary with the stage of infection.⁴ Early Lyme disease conventionally presents with erythema migrans, an expanding erythematous rash accompanying the spread of spirochetes superficially through the skin, sometimes associated with fatigue, fever, headache, arthralgias and myalgias.⁴ However, this characteristic rash is not present or easily identifiable in all causes of Lyme borreliosis and failure to recognise and treat early Lyme disease leads to risk for dissemination to the nervous, cardiac and musculoskeletal systems resulting in manifestations including facial nerve palsies, meningitis, atrioventricular heart block and arthritis.⁴

In the USA, Lyme arthritis is one of the most common manifestations of disseminated disease with surveillance data from the Centers for Disease Control suggesting roughly 25% of patients with a confirmed Lyme diagnosis present with arthritis.⁵ Initial spread of the spirochete to joints during early infection is often asymptomatic but may present as transient or migratory arthralgias with inflammatory arthritis subsequently developing months later in the setting of host immune responses to the bacteria.⁶ Joint involvement is usually monoarticular or oligoarticular and most commonly involves the knees, often presenting with large effusions and warmth.⁶ In patients with Lyme arthritis, B. burgdorferi is rarely cultured from synovial fluid, though DNA can be isolated from synovial fluid in up to 70% of untreated cases by PCR.⁷ Based on this, it has been suggested that the live spirochete remains confined to the extrasynovial joint spaces and is eradicated on invasion into the synovial fluid by acute inflammatory responses, which are in turn believed to contribute to tissue damage and arthritis.⁷ Untreated, Lyme arthritis may persist or be intermittent for years, hypothesised to result from spirochetal re-entry into the synovial tissue and subsequent induction of the inflammatory response.⁷ A key mechanism in this long-term persistence of the spirochete and its ability to evade the host immune response is through antigenic variation mediated by variable expression of the surface lipoprotein-encoding vlsE gene.⁸

In this report, we describe the case of a man in his 40s with a positive Lyme titre and no prior history of joint disease who presented to an infectious disease (ID) clinic with persistent left knee pain and swelling following traumatic tear of the posterior horn of the left lateral meniscus, found to have Lyme arthritis seemingly triggered by the injury.

Case presentation

Our patient, with no known significant medical history, was in his usual state of health when he sustained a moderate-impact lateral trauma to his left knee resulting in significant pain, swelling and limited mobility, for which he did not seek immediate evaluation. The pain persisted, and approximately 10 days later he began to experience chills, night sweats and a throbbing sensation in both knees, which prompted initial presentation to his primary care physician. He was given a compressive brace and scheduled for an MRI; however, worsening pain and swelling prompted presentation to an emergency department 3.5 weeks after the initial injury, where 65 mL of yellowish synovial fluid was aspirated from his left knee but not sent for analysis. Due to persistent pain with increasing stiffness and inability to bear weight, he was evaluated by orthopaedics 10 days later, noted to have a large left knee effusion without erythema or ecchymosis, with passive range of motion limited by pain.

Investigations

An MRI showed a tear of the posterior horn of the left lateral meniscus, thought to be related to the trauma 5 weeks prior. An additional 140 mL of clear-yellowish fluid was aspirated, which revealed a white cell count of 21,000 cells/µL (83% neutrophils) with no crystals and negative Gram stain and cultures. However, Lyme PCR from the synovial fluid was positive. On further interviewing, our patient revealed he has lived all his life in New England and denied any previous Lyme disease diagnosis, prior orthopaedic problems or history of known tick exposure for both him and his indoor cat, although he was a trail-runner. However, as these events occurred during the wintertime, he had not been running outside for several months. Additional serological evaluation revealed a positive Lyme antibody screen with reflex immunoblot Lyme IgG positive (10 of 10 bands positive; 18 kD, 23 kD, 28 kD, 30 kD, 39 kD, 41 kD, 45 kD, 58 kD, 66 kD and 93 kD), IgM negative (1 of 3 bands positive; 23 kD positive, 39 kD and 41 kD negative).

Differential diagnosis

The patient’s systemic symptoms and inflammatory synovial fluid suggested an infectious contribution to his arthritis. Given the isolated knee arthritis, autoimmune disorders were felt to be unlikely, and lack of crystals on microscopy suggested against gout or pseudogout. Septic arthritis was unlikely given negative synovial Gram stain and cultures. Serologies were negative for hepatitis B and C viruses, HIV, and syphilis. Additionally, site-appropriate PCR testing was negative for gonorrhoea and chlamydia, suggesting against reactive arthritis.

Outcome and follow-up

At his orthopaedics appointment, he was started on doxycycline. When seen in our ID clinic 2 weeks later, he reported improvement in both knee pain and constitutional symptoms. He was prescribed an additional 2 weeks of doxycycline with resolution of the effusion and improvement in pain. He did have some residual pain with instability and crepitus with ambulation, which was thought to be secondary to the meniscal tear, for which he has continued to follow-up with his orthopaedic surgeon.

Discussion

Here, we present a case of Lyme arthritis apparently provoked by an inciting traumatic joint injury. Based on the timing of his presentation, we postulate that he had acquired Lyme disease at least 6–8 months prior to his injury (corresponding with the summer months). As is typical for the infection, any initial acute joint involvement in our patient was apparently asymptomatic, consistent with the theory that B. burgdorferi first establishes latent infection outside of the synovium.⁹ The estimated time lapse prior to presentation is consistent with the typical natural history of Lyme arthritis, which occurs on average 6 months after initial infection, at which time migration of the spirochete into the synovial tissue is thought to trigger responses from the innate and adaptive immune systems.^{9 10} Our patient’s presentation was closely correlated with the traumatic injury with no symptoms prior to the event and acute onset of symptoms immediately after, including systemic inflammatory symptoms 10 days following the injury. Additionally, symptoms improved significantly with treatment. We postulate that trauma accelerated migration of spirochetes into the joint via inflammatory changes or disruption of synovial space, resulting in an enhanced inflammatory response that subsequently improved with eradication of the infection following antibiotic therapy.

Our patient had multiple laboratory findings supporting a diagnosis of Lyme arthritis. First, his synovial fluid cell count and differential were more consistent with an inflammatory arthritis than one of traumatic aetiology. Second, synovial fluid PCR for B. burgdorferi was positive, which in one study was found in 96% of cases of untreated Lyme arthritis and 0% of control patients.¹¹ His serological testing was also consistent with a diagnosis of Lyme arthritis. Serological testing for Lyme arthritis most commonly involves initial use of ELISA to identify anti-B. burgdorferi antibodies, which returned positive in our patient.⁹ Confirmatory testing is then performed via immunoblot.⁹ As recommended by the Centers for Disease Control, a positive IgM immunoblot requires presence of 2 of 3 bands (24 kDa, 39 kDa and/or 41 kDa) and a positive IgG immunoblot requires presence of 5 of 10 bands (18 kDa, 21 kDa, 28 kDa, 30 kDa, 39 kDa, 41 kDa, 45 kDa, 58 kDa, 66 kDa and 93 kDa).¹² In our patient’s immunoblot, only a single IgM band (23 kD) was present, but all 10 IgG bands were identified. Steere et al performed a prospective study evaluating serological testing in patients with suspected Lyme disease, identifying 30 patients with arthritis, who presented a median of 12 months (range, 3–60) following onset.¹³ Arthritis was the first clinically apparent symptom in 20 (67%) of these patients. Approximately one-third had evidence of an IgM immune response on immunoblot (median two bands identified), whereas all patients had evidence of an IgG immune response (median nine bands identified). These findings of strong IgG response with weaker IgM response are in general agreement with the results identified in our patient.

A review of PubMed and Embase failed to identify any previously published cases of post-traumatic Lyme arthritis or onset of Lyme arthritis following meniscal tear. Jennings et al identified cases of rheumatic diseases, including ankylosing spondylitis and rheumatoid arthritis, that presented initially as trauma-related or sports-related musculoskeletal pain.¹⁴ A case report from Seldes et al discussed a male athlete in his 20s who presented with atraumatic left knee spontaneous haemarthrosis and was subsequently diagnosed with serologically confirmed Lyme arthritis, which symptomatically improved with 14-day course of intravenous antibiotics.¹⁵ An additional case report from Tran and Milewski described a young teenager who presented with refractory chronic Lyme arthritis and was found to have a concomitant medial meniscal tear; however, the onset of Lyme arthritis in this case was not known to be temporally related to the injury.¹⁶

To our knowledge, this is the first report in the literature of a serologically and PCR-confirmed Lyme arthritis presenting in close association with an identifiable inciting traumatic event. We propose that the inflammation and associated increased vascularity secondary to the mechanical trauma to the left knee accelerated spirochetal migration into the synovial tissue. While the onset of knee pain and joint effusion immediately following our patient’s injury was likely attributable to the mechanical trauma he experienced, we believe the persistence and worsening of his initial presenting symptoms were the direct result of a trauma-enhanced B. burgdorferi accelerated translocation into the synovium.

Learning points.

• It is important to avoid premature closure, as there can be more than one simultaneous disease process causing a presentation (in this case meniscal tear and Lyme arthritis).

• There may be unrecognised associations between trauma and activation of chronic infectious or inflammatory processes.

• Lyme disease remains a difficult infection to diagnose and can present in a myriad of ways.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).