Borrelia Arthritis - a Hidden Cause of Arthritis in Danish Patients?

NCT07351721 | Not Yet Recruiting DMC

• 1 other identifier: S-20240040
• Study Type: observational
• Target: 350
• Locations: 0 countries
• Sites: N/A

Brief Summary

Why is this study being done? Borrelia arthritis is a joint infection caused by Borrelia bacteria transmitted by tick bites. It often affects the knee and can cause prolonged pain and swelling if not diagnosed and treated in time. While well recognized in North America, Borrelia arthritis is considered rare in Europe. Recent findings from the investigators in Denmark suggest it may be more common than previously thought and frequently diagnosed late. The aim of this study is to improve knowledge about how often Borrelia arthritis occurs in Denmark, how it presents, how long diagnosis takes, and how patients recover. This may help ensure faster diagnosis and better treatment for future patients. Who can take part? Patients referred to an including rheumatology department with inflammation in one or a few joints (mono- or oligoarthritis) may be invited to participate. What does participation involve? If a patient choose to participate:

• A blood sample will be taken to test for antibodies against Borrelia.
• Fluid from the affected joint(s) will be tested for Borrelia DNA.
• Blood and joint fluid samples will be stored in a secure research biobank for future analyses related to this study.
• The patient will complete a questionnaire about symptoms, health history, possible tick exposure, and the diagnostic process.
• Relevant information from the patients medical record (tests, treatments, and outcomes) will be collected. All procedures are part of standard clinical care or involve minimal additional testing. How will the information be used? The study will investigate:
• How common Borrelia arthritis is among patients with joint inflammation in Denmark.
• Differences in symptoms, test results, diagnostic delays, treatment, and outcomes between patients with Borrelia arthritis and other forms of arthritis. Risks and benefits Risks are minimal and mainly related to routine blood sampling and joint aspiration. The patient may not benefit directly, but the results may improve care for future patients. Confidentiality and voluntary participation All personal data will be handled confidentially according to data protection regulations. Participation is voluntary, and patients may withdraw at any time without affecting their medical care. Study period The study runs from January 1, 2026, to December 31, 2027 and includes patients from eight hospitals in Denmark.

Conditions

Lyme Arthritis

Keywords

Lyme arthritis; Borrelia arthritis; Borreliosis; Monoarthritis; Oligoarthritis

Outcome Measures

Primary Outcomes (2)

• Sub-study 1: 1-year cure rate Borrelia arthritis vs. control group

  Number of patients recovered drug-free (antibiotic treatment and/or DMARDs) one year after inclusion, in the Borrelia arthritis group and in the control group. Difference between the groups.

  1 year after inclusion

• Sub-study 2: Serum-Borrelia IgG antibodies

  Statistical difference between the 2 groups (Borrelia arthritis vs. control group) at baseline of number of patients with a serum-Borrelia IgG antibody.

  At study inclusion

Secondary Outcomes (4)

• Sub-study 1: Borrelia arthritis incidence and Borrelia burgdorferi genospecies

  At study inclusion

• Sub-study 1: 6-month cure rate Borrelia arthritis vs. control group

  6 months after study inclusion

• Sub-study 2: Difference between groups in which joints are affected

  At study inclusion

• Sub-study 2: Difference between groups in amount of synovial fluid.

  At study inclusion

Other Outcomes (12)

• Age

  At study inclusion

• Sex

  At study inclusion

• Number of tick-bites 1 year

  At study inclusion

Study Arms (1)

Patients with mono/oligoarthritis

All patients 18 years or older presenting at 8 rheumatological departments across Denmark with oligo/monoarthritis between 1.1.26-31.12.27.

Diagnostic Test: Synovial fluid Borrelia burgdorferi PCR

Interventions

Synovial fluid Borrelia burgdorferi PCR DIAGNOSTIC_TEST

All patients will have a pan-Borrelia burgdorferi PCR performed on synovial fluid from joints with arthritis. The PCR-positive patients will be deemed to have Borrelia arthritis, all other patients will be deemed as not having Borrelia arthritis.

Patients with mono/oligoarthritis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients presenting to one of 8 Rheumatological departments: Aalborg, Gødstrup, Silkeborg, Esbjerg, Vejle, Odense, Slagelse or Frederiksberg Hospital within the studyperiod.

You may qualify if:

• Adults ≥ 18 years old
• Presenting with mono/oligoarthritis at one of the including Departments of Rheumatology between 1/1-26 and 31/12-27
• Oral and written consent including biobank

You may not qualify if:

• Diagnoses of other inflammatory arthritis in relation to current arthritis episode (gout, pseudo-gout, rheumatoid arthritis, psoriatic arthritis, peripheral spondyloarthritis)

Sponsors & Collaborators

• Fredrikke Christie Knudtzen: lead
• Odense University Hospital: collaborator
• Slagelse Hospital: collaborator
• Gødstrup Hospital: collaborator
• Aalborg University Hospital: collaborator
• Regionshospitalet Silkeborg: collaborator
• Vejle Hospital: collaborator
• Frederiksberg University Hospital: collaborator
• Esbjerg Hospital - University Hospital of Southern Denmark: collaborator

Related Publications (11)

• Unlu AM, Andersen NS, Larsen SL, Skarphedinsson S, Chrysidis S, Knudtzen FC, Lage-Hansen PR. Differentiating Lyme arthritis: a case-based review. Rheumatol Int. 2024 Nov;44(11):2671-2678. doi: 10.1007/s00296-024-05618-0. Epub 2024 May 25.

  PMID: 38795123 BACKGROUND

• Arvikar SL, Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis Clin North Am. 2015 Jun;29(2):269-80. doi: 10.1016/j.idc.2015.02.004.

  PMID: 25999223 BACKGROUND

• Tory HO, Zurakowski D, Sundel RP. Outcomes of children treated for Lyme arthritis: results of a large pediatric cohort. J Rheumatol. 2010 May;37(5):1049-55. doi: 10.3899/jrheum.090711. Epub 2010 Apr 1.

  PMID: 20360182 BACKGROUND

• Corre C, Coiffier G, Le Goff B, Ferreyra M, Guennic X, Patrat-Delon S, Degeilh B, Albert JD, Tattevin P. Lyme arthritis in Western Europe: a multicentre retrospective study. Eur J Clin Microbiol Infect Dis. 2022 Jan;41(1):21-27. doi: 10.1007/s10096-021-04334-y. Epub 2021 Aug 20.

  PMID: 34417687 BACKGROUND

• Steere AC. Treatment of Lyme Arthritis. J Rheumatol. 2019 Aug;46(8):871-873. doi: 10.3899/jrheum.190320. No abstract available.

  PMID: 31371661 BACKGROUND

• Steere AC, Angelis SM. Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum. 2006 Oct;54(10):3079-86. doi: 10.1002/art.22131. No abstract available.

  PMID: 17009226 BACKGROUND

• Stanek G, Reiter M. The expanding Lyme Borrelia complex--clinical significance of genomic species? Clin Microbiol Infect. 2011 Apr;17(4):487-93. doi: 10.1111/j.1469-0691.2011.03492.x.

  PMID: 21414082 BACKGROUND

• Cerar T, Strle F, Stupica D, Ruzic-Sabljic E, McHugh G, Steere AC, Strle K. Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains from Europe and the United States. Emerg Infect Dis. 2016 May;22(5):818-27. doi: 10.3201/eid2205.151806.

  PMID: 27088349 BACKGROUND

• Haugeberg G, Hansen IJ, Skarpaas T, Noraas S, Kjelland V. Lyme arthritis in Southern Norway--an endemic area for Lyme borreliosis. BMC Infect Dis. 2014 Apr 5;14:185. doi: 10.1186/1471-2334-14-185.

  PMID: 24708707 BACKGROUND

• Berglund J, Hansen BU, Eitrem R. Lyme arthritis--a common manifestation in a highly endemic area in Sweden. J Rheumatol. 1995 Apr;22(4):695-701.

  PMID: 7791166 BACKGROUND

• Muller T, Locht H, Panum I, Nielsen L, Jensen B. Lyme arthritis is rare in Eastern Denmark. Dan Med J. 2021 Oct 26;68(11):A05210423.

  PMID: 34983732 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

For each patient, blood samples and synovial fluid from joints with arthritis will be retained in a biobank

MeSH Terms

Conditions

Lyme Disease; Borrelia Infections; Arthritis

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Joint Diseases; Musculoskeletal Diseases

Study Officials

• Fredrikke C Knudtzen, MD

  Odense University Hospital, Department of Infectious Diseases

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fredrikke C Knudtzen, MD

CONTACT

004529178083; fredrikke.christie.knudtzen@rsyd.dk

Philip R Lage-Hansen, MD

CONTACT

004579182000; philip.rask.lage-hansen3@rsyd.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Specialist in Infectious Diseases, PhD

Study Record Dates

• First Submitted: December 30, 2025
• First Posted: January 20, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share