The Utility of Ultrasound-Guided Synovial Biopsy in the Diagnosis of Crystal-Induced Arthritis
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
In this manuscript, authors aim to examine the utility of ultrasound-guided synovial biopsy in the diagnosis of crystal-induced arthritis, describing the procedure and recommending best practices for specimen handling and tissue processing. The manuscript is interesting and original.
Some aspects could be addedd or discussed further:
- a small table summarizing the positive and negative aspects of the different methods used to perform synovial biopsy (unguided, fluoroscopy, ultrasound-guided) could be of help to the reader.
- a scheme reporting recommendations for specimen handling and tissue processing to perform a correct analysis of the samples, also considering the characteristics of the different types of crystals, could be useful.
Author Response
Reviewer # 1:
In this manuscript, authors aim to examine the utility of ultrasound-guided synovial biopsy in the diagnosis of crystal-induced arthritis, describing the procedure and recommending best practices for specimen handling and tissue processing. The manuscript is interesting and original.
Some aspects could be added or discussed further:
- a small table summarizing the positive and negative aspects of the different methods used to perform synovial biopsy (unguided, fluoroscopy, ultrasound-guided) could be of help to the reader.
- a scheme reporting recommendations for specimen handling and tissue processing to perform a correct analysis of the samples, also considering the characteristics of the different types of crystals, could be useful.
Author Response: Thank you for reviewing our manuscript.
Point 1: Incorporation of table comparing methods used for synovial biopsy – We added this as Table 1.
|
Method |
Positive Aspects |
Negative Aspects |
|
Landmark Guided |
Does not require rheumatologist to have access to ultrasound or fluoroscopy |
Lower yield compared to other methods
Increased risk of non-synovial tissue injury
Increased risk and lower yield in small joints and joints with less inflammation. |
|
Fluoroscopic guided biopsy |
Higher Yield of synovial tissue as compared to landmark guided biopsy |
Radiation exposure
Increased cost and require investment in fluoroscopy system
Typically requires collaboration with radiology or orthopedics |
|
Ultrasound Guided-Portal and forceps |
Higher Yield of synovial tissue as compared to landmark guided biopsy
Can obtain tissue from multiple angles withing in the joint space |
Requires initial investment in autoclavable reusable equipment
Requires operator to be experienced in ultrasound and in synovial biopsy
|
|
Ultrasound Guided Guillotine Needle |
Higher yield of synovial tissue as compared to landmark guided biopsy
Ease of use of guillotine needle
Guillotine needle is disposable
Cost is more favorable than other methods of obtaining tissue |
Requires operator to be experienced in ultrasound and in synovial biopsy
Size of tissue sample is limited by size of guillotine needle
Shape of the guillotine needle can limit access to certain areas of joint space
|
Point 2: Incorporation of scheme for specimen handling and tissue processing – this is described in section …. Because there are multiple options of how to handle tissue for optimal processing and no data to demonstrate that one is superior to another, we chose to include general recommendations rather than a rigid protocol
Reviewer 2 Report
Comments and Suggestions for Authors
This is a narrative review focusing on the role of ultrasound-guided synovial biopsy in the diagnosis of crystal-induced arthropathies. The authors analysed the most important technical procedures for sampling and tissue handling, and discussed the positioning of this procedure in the diagnostic pathway. The manuscript is simple and clear, however some points should be better discussed and evaluated in the context of existing literature.
Major comments
The authors assessed the role of synovial biopsy in the diagnosis of MSU- or CPP-induced arthritis. However, they did not mention the actual classification criteria of both the diseases (doi: 10.1136/annrheumdis-2015-208237; doi: 10.1136/ard-2023-224575), which are not diagnostic criteria, but emerge as useful tools to help clinicians in providing a correct diagnosis. This should be updated in the text, and the contact points between these criteria and what suggested by the authors should be evaluated.
The authors did not cite the relevant suggestions provided by the OMERACT and the EULAR to homogenize synovial tissue sampling and synovial tissue research (doi: 10.1136/annrheumdis-2021-221875; doi: 10.1186/s13075-018-1762-1). This should be updated in the text.
The authors should provide a summary table describing the main pros and cons for each technical aspect related to specific tissue handling for crystals analysis.
The authors provided a figure showing H/E staining in the case of a synovial sample in the context of CPPD-D. However, no images were provided with reference to gout. This should be updated.
Minor comments
The term “crystalline arthritis” should be replaced throughout the manuscript with other terms (e.g. “crystal-induced” arthritis).
Comments on the Quality of English Language
n.a.
Author Response
Reviewer # 2
This is a narrative review focusing on the role of ultrasound-guided synovial biopsy in the diagnosis of crystal-induced arthropathies. The authors analysed the most important technical procedures for sampling and tissue handling, and discussed the positioning of this procedure in the diagnostic pathway. The manuscript is simple and clear, however some points should be better discussed and evaluated in the context of existing literature.
Major comments
1)The authors assessed the role of synovial biopsy in the diagnosis of MSU- or CPP-induced arthritis. However, they did not mention the actual classification criteria of both the diseases (doi: 10.1136/annrheumdis-2015-208237; doi: 10.1136/ard-2023-224575), which are not diagnostic criteria, but emerge as useful tools to help clinicians in providing a correct diagnosis. This should be updated in the text, and the contact points between these criteria and what suggested by the authors should be evaluated.
2) The authors did not cite the relevant suggestions provided by the OMERACT and the EULAR to homogenize synovial tissue sampling and synovial tissue research (doi: 10.1136/annrheumdis-2021-221875; doi: 10.1186/s13075-018-1762-1). This should be updated in the text
3) The authors should provide a summary table describing the main pros and cons for each technical aspect related to specific tissue handling for crystals analysis.
4) The authors provided a figure showing H/E staining in the case of a synovial sample in the context of CPPD-D. However, no images were provided with reference to gout. This should be updated.
Minor comments
5) The term “crystalline arthritis” should be replaced throughout the manuscript with other terms (e.g. “crystal-induced” arthritis).
Author Response: Thank you for your review of our manuscript
Major Comments
- The 2015 ACR/EULAR diagnostic criteria for gout doesn’t include synovial tissue analysis in the diagnostic criteria for gout. This set of criteria places significant importance on the presence of monosodium urate (MSU) crystals found in synovial fluid or in a tophi. In patients with a swollen/tender peripheral joint or bursa but do not have evidence of tophi or MSU crystals found in a tophus or in synovial fluid (either due to a negative fluid aspiration or absence of a fluid aspiration) the criteria relies upon other factors such as duration and characteristics of the joint pain/swelling/tenderness, imaging (x-ray, ultrasound, DECT), presence of a tophi and uric acid levels. (citation)
- The EULAR Synovitis and OMERACT Synovial Tissue Biopsy Groups have provided recommendations for clinical biopsies. These recommendations are used to evaluate tissue for multiple processes including gout. The expert panel does not recommend anhydrous processing to look for crystals, but we recommend requesting anhydrous processing when available if there is a suspicion of crustal induced arthritis.
- Author Response: Thank you and we also considered creating this table but given the nuacnes and variations in tissue processing we believe that this information is better represented in the text as presented and would not be appropriate for a table.
- Author Response: The authors do not have ownership/permissions for synovial tissue containing MSU crystals. We would like to include Image 10 (page 779) from the reference: O’Connell JX. Pathology of the synovium. American journal of clinical pathology. 2000 Nov 1;114(5):773-84. – Will the publisher be able to get permissions for this image to be included? And if so we will write a description for the image.
Minor Comments
- We have replaced “crystalline arthritis” with “crystal-induced” arthritis
Thank you for considering our manuscript and we look forward to publishing this article
Round 2
Reviewer 2 Report
Comments and Suggestions for Authors
The authors should complete the list of references by adding the following citation, since they added only the classification criteria for gout: doi: 10.1136/ard-2023-224575.
Author Response
Thank you for your assistance with this manuscript. We have added both the ACR/EULAR guidelines for gout and CPPD diagnosis. This adds value to the paper because neither of these guidelines incorporate synovial tissue analysis in diagnosis. As our paper outlines the value of synovial tissue in evaluating patients for crystal induced arthritis, it is important to discuss the current guidelines.
