1. Fred Vilson, DO Pigmented Villonodular Synovitis and Lyme Disease: A Case Report – Saint Elizabeth Youngstown Hospital Department of Orthopedics
2. Hayley Shasteen Pigmented Villonodular Synovitis and Lyme Disease: A Case Report – Kent State University
3. Thomas Boniface, MD Pigmented Villonodular Synovitis and Lyme Disease: A Case Report – Saint Elizabeth Youngstown Hospital Department of Orthopedics

Abstract

We describe an unusual late presentation of Lyme Disease associated with knee diffusion and aspiration and subsequent arthroscopy. Pathophysiology of Lyme Disease for joint disease is discussed.

Abbreviations
LD – Lyme Disease
PVNS – Pigmented Villonodular Synovitis
MRI – Magnetic Resonance Imaging
LMAC – Local Monitored Anesthesia Care

Keywords: Lyme Disease, Knee

Introduction
Lyme Disease (LD) is the most common vector-borne illness in the United States affecting 476,000 patients between 2010 and 2018¹.  There are multiple manifestations of the disease including poorly defined musculoskeletal system presentations.  We illustrate an atypical, late presentation of LD and discuss the place of LD in the differential diagnosis and treatment of patients.

Case Presentation
A 23-year-old male without significant past medical history or previous knee problems presented with a six-month history of chronic right knee pain and swelling of spontaneous onset.  As the swelling progressed, he experienced mechanical episodes of inability of full knee flexion and extension. Mild improvement was noted with rest; formal physical therapy did not alleviate symptoms. He reported using occasional over-the-counter pain medication without relief. Fever, chills, sweats, and other systemic symptoms were denied, along with any other joint complaint. Social history indicates the patient is sexually monogamous.  Previous x-rays were negative. MRI prior to orthopedic consultation reported synovitis. Radiology impression was extensive enough to provide a provisional diagnosis of pigmented villonodular synovitis (PVNS).

Approximately 1 year prior to evaluation, he had presented to the emergency department with severe fatigue, muscle and joint pain, low grade fever, and two erythema migrans skin lesions on the right lower leg. The patient reported that he spent time in a wooded area, albeit he denied findings of ticks or bites. Serologic testing at that time was negative for Lyme Disease IgG and IgM but was reactive for 41KD (IgG) band. After a 2-week course of doxycycline 100 mg daily, the majority of his systemic symptoms resolved, other than mild arthralgias managed with ibuprofen as needed. Onset of right knee symptoms with significant swelling and mechanical instability began 6 months after completing doxycycline treatment.

Physical examination revealed a healthy young adult male with isolated findings seen in the right knee with a moderate effusion. There was no discrepancy in warmth compared to the contralateral knee. Mild and diffuse tenderness to palpation was experienced about the right knee with normal range of motion, albeit discomfort with deep flexion.  Patellar tracking appeared normal, neutral, negative apprehension and no crepitus.  No specific joint line tenderness was noted. McMurray’s was negative; there was no ligamentous laxity to medial, lateral, or AP stress.

Radiography
X-rays showed no joint space narrowing or periarticular erosions.  MRI revealed diffuse generalized and localized proliferative villous appearing synovial masses. Meniscal and ligamentous structures were intact.

Figures 3-6 depict MRI imaging of the right knee that were read as large joint effusion. In the inferior and lateral aspect of the infrapatellar joint space is a 2.1 x 2.8 x2.2 cm oval solid lesion that demonstrates susceptibility artifact on the gradient imaging; predominately hypointense on the T2 MRI.

Diagnostic impression was effusion secondary to synovial process, possibly reactive, autoimmune, or PVNS. See Figures 3-6. The knee was aspirated for 20 cc of chronically blood-tinged synovial fluid with decreased viscosity, and sent CBC differential, gram stain, and crystal analysis.  At the time of aspiration, the knee was injected with 80 mg of triamcinolone and 7.5 mg of bupivacaine. Fluid analysis revealed RBC 36,000, WBC 1,471, and 92% monocytes. Crystal analysis and gram stain returned negative.

Although he reported significant relief of his knee swelling, he continued with disabling pain and instability, especially with flexion. He opted for recommended arthroscopic intervention, after counseling on the expected risks, benefits and outcomes depending upon findings and tissue analysis. Arthroscopy of the right knee under LMAC revealed generalized but mild non-proliferative non- villous synovitis and a significant large fibrous ovoid loose body in the anterior compartment, as well as smaller hyaline debris in the medial and lateral compartments. There was no evidence of hemosiderin staining, marginal erosions, or articular damage. Removal of these bodies was performed without difficulty via arthroscopic portals with conventional shaving instruments.  The patient was discharged the same day, and he committed to a home exercise plan post operatively. On follow up, he experienced dramatic and complete pain relief and resolution of mechanical symptoms, recovering from preoperative quadricep weakness.

Discussion
Musculoskeletal pain and manifestations are the most frequently reported symptom of LD patients, appearing as migratory arthralgias which can lead to the onset of frank arthritis or Lyme arthritis if left untreated^2,3. Lyme arthritis is characterized by monoarthritis or oligoarthritis typically present in the knees and accompanied by large effusions that are not particularly painful with range of motion or weight bearing⁴. Untreated LD can lead to a host of orthopedic consequences; similar case reports are highlighted in Table 1.

Table 1. Orthopedic consequences of untreated LD

Source	Reported Outcome
Coulin and Landin, 20215	Supraspinatus tendinopathy
Fiacco and Clancy, 20196	Spontaneous rupture of several lower extremity tendons
Pandya et al., 20087	Patellar tendon rupture
Weise et al., 20218	Acute arthritis of temporomandibular joint

Less commonly reported are orthopedic manifestations as latent consequences of LD infection following successful antibiotic treatment as in the current case. There is a lack of CDC tracking and reporting of LD outcomes and persistent symptoms post-treatment⁹. Lack of post-treatment LD consequences could also be attributed to the clinical disbelief in post-treatment LD symptoms. Johnson and Feder¹⁰ report that up to 50% of physicians do not believe in post-treatment or chronic LD symptoms. However, Arvikar et al.¹¹ reported on 30 patients who developed systemic autoimmune joint disorders a median of 4 months after successful LD treatment, particularly after early-stage infection; disorders included rheumatoid arthritis, psoriatic arthritis, and peripheral spondyloarthropathy. Interestingly, these patients differed from a Lyme arthritis comparison group; they did not benefit from antibiotic treatment, which is typically prescribed for Lyme arthritis, suggesting that the infection triggered autoimmune sequelae rather than active joint infection^11,12. More commonly, research on groups of people experiencing post-treatment LD symptoms are restricted to patient-reported symptomatology which often reveals increased pain, fatigue, and sleep disturbances¹³. Although useful in classifying the physiological consequences of LD infection, these reports are limited in understanding in the pathological manifestations of other disorders and diseases.

In the current case, the patient presented with non-proliferative, non-villous synovitis, accompanied by a large, fibrous oovid loose body, potentially a consequence of successful LD treatment not attributable to Lyme arthritis; the patient tested negative for the presence of Borrelia burgdorferi. During diagnosis and treatment, the patient reported significant and lasting musculoskeletal pain. Infection and inflammation may have led to aberrant immune system functioning, contributing to his orthopedic manifestation. Lochhead et al.¹⁴ report that patients with post-infectious Lyme arthritis develop marked proliferative synovitis, noted by distinct extracellular mRNA profiles in synovial fluid which indicate the presence of arthritis evolving from an infection-induced inflammatory response to an immune-mediated inflammatory response. Notably, Brouwer et al.¹⁵ and Lochhead et al.¹⁴ propose that post-infectious Lyme arthritis is the result of pathogenic fibroblast-like synoviocytes which differentiate into potent immune effector cells with co-stimulatory signals to lymphocytes, producing tissue-damaging proteases and inflammatory molecules. Disrupted repair of damaged tissue results with persistent autoimmune responses, synovitis, and fibrosis. Similarly, Shin, Glickstein, and Steere¹⁶ reported that even when antibiotic treatment reduces or clears infection, patients with Lyme arthritis have high synovial fluid levels of proinflammatory chemokines and cytokines.

Factors such as excessive inflammation during infection, infection-induced autoimmunity, failure to downregulate inflammatory responses after successful treatment, and genetic factors, such as TLR1 polymorphism 1805GG all contribute to the possibility and presentation of post-treatment LD symptoms and manifestations⁴. Further research is needed to fully understand the pathogenesis of orthopedic consequences of LD following successful treatment, as well as the cellular mechanisms responsible for such outcomes. With the limited availability of literature surrounding this topic, there is a paucity of information discussing treatment options. This case highlights the potential surgical modality in patients who are diagnosed with post infectious Lyme arthritis. In orthopedic practice, past medical history of LD and other infectious diseases should be ascertained to accurately diagnose and treat patients. The current case was provisionally diagnosed with PVNS, which can be misdiagnosed due to its similarity to other inflammatory conditions. Orthopedic sequelae following LD treatment should be tracked and reported to quantitate post-infection consequences and improve orthopedic knowledge.

Figure 1 | Figure 2 | Photo 1

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