Persistent Knee Monoarthritis as a Lyme Disease Presentation: A Diagnostic Challenge – Case Report

Abstract

There are several differential diagnoses for knee monoarthritis. We report a patient with recurrent episodes of knee effusion, in which the non-specific clinical condition implied several diagnostic hypotheses, therapeutic inaccuracies, and a delay in implementing adequate treatment.

For more than 2 years, the patient underwent different Orthopedics and Rheumatology visits. She received multiple therapies, including a knee arthroscopy with partial meniscectomy with transient improvement of the complaints but not a definitive diagnosis. After collecting synovial fluid samples and successively negative microbiological tests, we established the diagnosis of overlap of septic arthritis by atypical microorganisms isolated from synovial tissue (Pantoea spp. and Staphylococcus saprophyticus) and Lyme arthritis. Washing and surgical debridement followed by targeted antibiotic therapy resulted in a transient response due to persistent infection (stage 3).

This case demonstrates the need for a multidisciplinary approach to knee monoarthritis.

Keywords

arthritis, septic - case report - gonalgia - Lyme disease - monoarthritis

Introduction

Knee monoarthritis has several causes, implying a complex differential diagnosis[1] [2] ([Table 1]). Despite the wide literature recognition, Lyme monoarthritis remains a diagnostic challenge requiring high clinical suspicion due to the lack of epidemiological context (tick bite) or positive cultural tests.[1] [2] [3] [4] The authors present a case of monoarthritis secondary to Lyme disease with a late diagnosis.

Table 1

Infectious	Bacterial (gonococcal and non-gonococcal) Viral Spirochetes (Lyme, Syphilis) Fungal
Microcrystalline	Drop Pseudogout Hydroxyapatite/Basic calcium phosphate Calcium oxalate
Traumatic	Occult/stress fracture Meniscal and/or ligament lesion Foreign body
Inflammatory/Autoimmune	Reactive arthritis Psoriatic arthritis Ankylosing spondylitis Rheumatoid arthritis Lupus Sarcoidosis Behçet disease
Metabolic	Hyperparathyroidism Hypothyroidism Hemochromatosis Acromegaly Amyloidosis
Tumoral	Osteochondroma Osteoid osteoma Pigmented villonodular synovitis Malignancy (primary or metastatic tumor)
Miscellaneous	Arthrosis Coagulopathy Vasculitis Osteonecrosis

Case Report

A 39-year-old female with no relevant history presented a sudden onset of joint effusion and pain with a mixed rhythm in the right knee in May 2019. She denied complaints in other joints, fever, skin lesions, additional symptoms, tick bites, or exposure to other agents ([Fig. 1]).

Fig. 1 Timeline of the clinical course of the reported case.Description: Clinical evolution since the beginning of the condition. Complaints recurred in May 2022, with persistent effusion, functional impotence, and residual pain in August 2022. MRI, Magnetic resonance imaging.

Given the predominantly inflammatory complaints, two rheumatologists evaluated the patient and performed a therapeutic trial with methotrexate and prednisolone for 4 months with no improvement.

After 17 months, the patient underwent a magnetic resonance imaging (MRI) which confirmed joint effusion, a Baker cyst, a focus of medullary edema at the external plateau, and rupture of the internal meniscus ([Fig. 2]). On this occasion, she had no meniscal-related complaints.

Fig. 2 Magnetic resonance images.Description: A MRI from October 3, 2020, revealed intra-articular effusion, external tibial plateau injury, irregularity of the posterior horn of the internal meniscus, and a Baker cyst.A: T1-weighted sagittal section.B: T1-weighted coronal section.C: T2-weighted coronal section.D: T2-weighted axial section.

Eighteen months after symptom onset, persistent complaints and slightly worse mechanical issues led to a knee arthroscopy with synovial fluid sampling (negative bacteriological examination).

At the same time, the patient underwent microfractures of the external plateau injury, partial internal meniscectomy, excision of the valve system of the Baker cyst, and intra-articular infiltration with betamethasone. She presented a significant improvement in the postoperative period, with decreased edema and recovered range of motion.

Six months later, the patient had two recurrences of monoarthritis, interpreted as residual inflammation and controlled with new infiltrations. She underwent a new MRI revealing only the previously known chondral lesion. A third evaluation by Rheumatology was requested since the structural lesion did not justify the clinical condition.

In that assessment, 2.5 years after the condition onset, the patient underwent a laboratory follow-up to clarify the chronic knee monoarthritis of undetermined cause. Highlights included increased sedimentation rate (36 mm/h) and C-reactive protein (CRP) level, in addition to a negative autoimmunity panel and blood cultures. A new arthrocentesis and ultrasound-guided biopsy of the synovial membrane removed six membrane fragments for histopathological examination and five for bacteriological examination (including anaerobes, aerobes, mycobacteria, fungi, and parasites), and studies for Neisseria gonorrhoeae, Chlamydia trachomatis, and Borrelia burgdorferi. The synovial fluid was cloudy citrine yellow, and biochemistry results suggested chronic inflammatory arthropathy (22,240 cells/uL, 4.9 g/dL protein), with no casts and negative cultures. Histological examination of the synovial membrane suggested chronic synovitis with moderate inflammatory activity and predominantly lymphoid infiltrate, in addition to positive aerobic cultures for Pantoea spp. and oxacillin-sensitive Staphylococcus saprophyticus. The diagnosis of chronic septic arthritis with surgical indication was assumed. The patient underwent lavage and debridement, synovectomy, and arthroscopic sampling of tissue and synovial fluid for bacteriological examination (eight negative samples). She completed 2 weeks of intravenous flucloxacillin with a progressive resolution of effusion and pain, maintaining negative CRP during hospitalization. After discharge, the patient continued the oral antibiotic therapy for another 8 weeks after surgery (flucloxacillin, 2 g every 6 hours).

Six weeks after arthroscopic lavage, B. burgdorferi serology, performed in a reference laboratory, was positive for IgG and IgM by the ELISA method and confirmed by a positive IgM test by immunoblot. After multidisciplinary discussion (Rheumatology, Infectious Diseases, and Orthopedics), the antibiotic therapy switched to doxycycline for 28 days due to the diagnosis of Lyme disease. A new synovial biopsy was requested to detect B. burgdorferi DNA, which was negative (under antibiotic therapy).

The patient evolved favorably, with a progressive resolution of the condition. She resumed her work activity and walking without limitations. Six months after lavage, debridement, and initiation of antibiotic therapy, she presented a new episode of effusion with no pain or functional impotence. Repeated arthrocentesis revealed a negative B. burgdorferi DNA study, inconclusive serology for IgG and IgM by the ELISA method, and a confirmatory test by immunoblot showing positive IgM and negative IgG ([Table 2]).

Table 2

Date	Sampling method	Sample	Result
November 22, 2020	Arthroscopy	Synovial fluid	Negative
November 03, 2021	Ultrasound-guided arthrocentesis	Synovial fluid	Negative (aerobes, anaerobes, mycobacteria, parasites, fungi and screening for N. gonorrhoeae and C. trachomatis)
		Synovial biopsy	Pantoea spp. and S. saprophyticus
22/11/2021	Arthroscopy	Synovial fluid Synovial biopsy	Negative (total of 8 samples: anaerobes, aerobes, and mycobacteria)
November-December 2021	Serology	Serology	Positive IgM and IgG for B. burgdorferi (ELISA) and positive IgM (Immunoblot)
January 13, 2022	Ultrasound-guided arthrocentesis	Synovial fluid	Negative B. burgdorferi DNA screening (under antibiotic therapy)
May 26, 2022	Ultrasound-guided arthrocentesis	Synovial fluid	Negative B. burgdorferi DNA screening
	Serology	Serology	Inconclusive IgM and IgG results for B. burgdorferi (ELISA). Confirmatory test: positive IgM and negative IgG (Immunoblot)

Discussion

The reported case illustrates the complexity of the differential diagnosis of knee monoarthritis due to Lyme disease.[1] [2] Multiple negative samples and the lack of sensitive methods for B. burgdoferi identification led to the attribution of the patient's complaints to meniscal pathology, Baker cyst, cartilage damage, and postoperative residual inflammation. There was an overlap of septic arthritis and Lyme disease, and non-specific complaints implied a significant diagnostic delay. The identification of negative S. coagulase in deep biopsy is valuable, and contamination by Pantoea spp is a possibility. Only a multidisciplinary approach allowed adequate diagnosis and treatment more than 2 years after the symptom onset.

In Lyme disease, monoarthritis is frequently located in the knee and affects up to 60% of untreated patients; joint effusion is the most significant clinical finding.[5] [6] [7] Tick bites are often not documented.[5] [6] The absence of erythema and heat, the analytical evaluation, and the biochemical and histological examinations findings also suggest Lyme arthritis.[1] [5] [7] [8] It is noteworthy that, given the time, positivity for B. burgdorferi IgG was also expected in the confirmatory analysis (immunoblot).[6] The screening for B. burgdorferi DNA in synovial fluid after starting antibiotic therapy is usually negative.[5] [6] In addition, culturing this pathogen is difficult, and culture sensitivity limits its use for diagnostic purposes.[1] [5] Similarly to this case, the diagnosis usually relies on the seropositivity associated with arthritis.[5] Doxycycline is indicated in Lyme arthritis and results in excellent clinical response in most patients.[5] [6] [8]

This persistent infection (stage 3) commonly affects the knee and causes frequent episodes of arthritis alternating with periods of remission.[7] [8] [9] This clinical course is relatively frequent, and it suggests that joint inflammation may persist despite the eradication of B. burgdoferi, leading to synovial damage and findings similar to those observed in other forms of chronic inflammatory arthritis.[7] [9]

Thus, in this case, the complex diagnostic strategy reiterates the importance of taking a multidisciplinary approach to patients with knee monoarthritis.

Conflito de Interesses

Dra. Bárbara Flor de Lima declarou bolsa ou contrato com o Hospital Prof. Doutor Fernando Fonseca como especialista em doenças infecciosas. A autora também declarou pagamento da Escola Médica de Lisboa por ter atuado como assistente de microbiologia convidada.

Os outros autores declaram não haver conflito de interesses.

Work carried out at the Sant'Ana Orthopedic Hospital, Parede, Portugal.

• Referências

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• 4 Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician 2003; 68 (01) 83-90
• 5 Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis Clin North Am 2015; 29 (02) 269-280
• 6 Matzkin E, Suslavich K, Curry EJ. Lyme Disease Presenting as a Spontaneous Knee Effusion. J Am Acad Orthop Surg 2015; 23 (11) 674-682
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• 9 Bennett JE, Dolin R, Blaser MJ. Mandell. Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia: Elsevier; 2020

Publikationsverlauf

Eingereicht: 10. August 2022

Angenommen: 27. Februar 2023

Artikel online veröffentlicht:
22. April 2024