The Open Orthopaedics Journal




ISSN: 1874-3250 ― Volume 13, 2019

Knee Arthritis Without Other Joint Symptoms in the Elderly With Seronegative Elderly Onset Rheumatoid Arthritis



Takatomo Mine*, Koichiro Ihara, Hiroyuki Kawamura, Ryutaro Kuriyama, Ryo Date
Department of Orthopaedic Surgery, National Hospital Organization Kanmon Medical Center, Simonoseki, Japan

Abstract

Elderly onset Rheumatoid arthritis (EORA) has important clinical distinctions when compared with younger onset RA (YORA). In knee arthritis of elderly patients, infection, crystal-induced arthritis or EORA should be suspected if elevation of CRP in the preoperative examination and turbid joint effusion in their knee joint are found. Furthermore, if joint swelling and effusion remain after performing total knee arthroplasty (TKA), the infection after TKA, implant debris-related arthritis and EORA should be considered. However, it is difficult to diagnose patients as EORA if Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are negative. The differential diagnosis is very important.

Keywords: Arthroscopy, Synovitis, Knee arthritis, Rheumatoid arthritis, Elderly person, Seronegative RA.


Article Information


Identifiers and Pagination:

Year: 2016
Volume: 10
First Page: 793
Last Page: 796
Publisher Id: TOORTHJ-10-793
DOI: 10.2174/1874325001610010793

Article History:

Received Date: 20/10/2016
Revision Received Date: 21/11/2016
Acceptance Date: 23/11/2016
Electronic publication date: 30/12/2016
Collection year: 2016

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 634
Abstract HTML Views: 556
PDF Downloads: 205
ePub Downloads: 97
Total Views/Downloads: 1492

Unique Statistics:

Full-Text HTML Views: 467
Abstract HTML Views: 311
PDF Downloads: 151
ePub Downloads: 67
Total Views/Downloads: 996
Geographical View

© Mine et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Department of Orthopaedic Surgery, National Hospital Organization Kanmon Medical Center, 1-1Choufusotoura, Simonoseki, Yamaguchi 752-8510 Japan; Tel: +81-83-241-1199; Fax: +81-83-241-1301; E-mail: minet@kanmon-mc2.hosp.go.jp




INTRODUCTION

Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, occurring most frequently in the joints. This inflammatory process frequently leads to loss of cartilage and bone erosion. The level of joint destruction is correlated with the severity of inflammation [1Wick MC, Lindblad S, Klareskog L, Van Vollenhoven RF. Relationship between inflammation and joint destruction in early rheumatoid arthritis: a mathematical description. Ann Rheum Dis 2004; 63(7): 848-52.
[http://dx.doi.org/10.1136/ard.2003.015172] [PMID: 15194582]
, 2Welsing PM, Landewé RB, van Riel PL, et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthritis Rheum 2004; 50(7): 2082-93.
[http://dx.doi.org/10.1002/art.20350] [PMID: 15248205]
]. Lipsky reported that the prevalence of RA is approximately 0.8% in the general population [3Lipsky PE. Rheumatoid Arthritis. In: Harrison’s principles of Intermedicine. 14th ed. New York: Mc Graw Hill 1998.]. In the USA, prevalence of RA is reported to be in between 0.55 and 1% with a prevalence of ~2% among persons above the age of 60 [4Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003; 48(4): 917-26.
[http://dx.doi.org/10.1002/art.10897] [PMID: 12687533]
]. RA onset is variable. A steadily increasing prevalence rate of rheumatoid arthritis with age has been reported [3Lipsky PE. Rheumatoid Arthritis. In: Harrison’s principles of Intermedicine. 14th ed. New York: Mc Graw Hill 1998.]. Cases with the disease beginning above the age of 60 are defined as having elderly onset. Elderly onset RA (EORA) has important clinical distinctions when compared with younger onset RA (YORA) [5Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28(9): 987-94.
[http://dx.doi.org/10.1002/art.1780280905] [PMID: 4038365]
, 6van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum 1994; 23(6): 367-78.
[http://dx.doi.org/10.1016/0049-0172(94)90087-6] [PMID: 7939723]
]. Several studies have reported a lower percentage of Rheumatoid factor positivity in EORA [7Terkeltaub R, Esdaile J, Décary F, Tannenbaum H. A clinical study of older age rheumatoid arthritis with comparison to a younger onset group. J Rheumatol 1983; 10(3): 418-24.
[PMID: 6411919]
, 8Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28(9): 987-94.
[http://dx.doi.org/10.1002/art.1780280905] [PMID: 4038365]
]. When the patients have severe knee pain and gait disturbance, they are advised to undergo knee arthroplasty. In RA patients, total knee arthroplasty (TKA) is performed for knee arthritis of RA. In seronegative elderly onset RA patients without other joint symptoms, it is difficult to determine whether knee pain and deformities are due to RA or osteoarthritis (OA). In patients referred with severe OA, infection, crystal-induced arthritis or EORA are suggested if elevation of CRP in the preoperative examination and turbid joint effusion are found. To perform TKA, EORA should be discriminated from infection. Seronegative EORA without other joint symptoms is difficult to diagnose clearly, and if joint swelling and effusion remain after performing TKA, the infection after TKA, implant debris-related arthritis and elderly onset RA should be considered. Patients are diagnosed as seronegative EORA without other joint symptoms if rheumatoid factor and ACPA are negative; however, these patients also have the possibility of knee joint infection. The differential diagnosis of seronegative elderly onset rheumatoid arthritis is very important.

CASE 1

A 78-year-old man exhibited pain in his right knee joint for one year without any obvious cause. He was diagnosed with osteoarthritis at a nearby hospital and received intraarticular hyaluronic acid injections, but no improvement was observed. He recently demonstrated severe pain and gait disturbance, and was therefore referred to our department with suppurative arthritis.

On physical examination, mild swelling and local heat were observed in the right knee joint. Redness was not present. His range of motion was -15 to 140°. X-ray images confirmed severe arthropathic changes (Fig. 1). Laboratory tests revealed that WBC was 9700 and CRP was 1.35 mg/dl. The aspirated synovial fluid was yellowish and slightly turbid. Bacterial culture and crystal were negative. We considered RA or infection to be possible. Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA) and anti-nuclear antibodies were negative. For arthroscopic findings, synovial hypercellularity was noted.

Fig. (1)
Anteroposterior roentgenograph of the right knee showing severe arthropathic changes.


Histological examination revealed signs of synovitis, including proliferation of synovial tissue, infiltration of plasmacytes and neutrophils, and the presence of granulation tissue. These observations were highly suggestive of rheumatoid arthritis. Rt TKA was then performed. However, pain and swelling of the left knee and right shoulder appeared. methotrexate (MTX) was increased to 8 mg/day. The symptoms persisted. Golimumab was initiated and his symptoms subsided immediately.

CASE 2

A 74-year-old female developed pain in her right knee joint and gait disturbance without any obvious cause a year prior to referral. These symptoms increased gradually. Therefore, she was referred to our department for total knee arthroplasty.

On physical examination, swelling and joint effusion were observed in the right knee joint, and tenderness was not present in the joint space. The range of motion was from 10 to 125°. The results of a meniscal test and a ligamentous instability test were negative. Radiographs showed severe arthropathic changes. Rt TKA was performed. The patient’s symptoms improved after the surgery. Six months later, she developed severe pain in her right knee joint without any obvious cause. The symptoms required transfer to an emergency room and hospitalization. Swelling, local heat and joint effusion were observed in the right knee joint, but redness was not present. Laboratory tests revealed that WBC was 4100 and CRP was 10.70 mg/dl. The aspirated synovial fluid was yellowish and slightly turbid. Bacterial culture and crystal were negative. We considered infection after TKA to be possible, and therefore performed debridement and irrigation. The patient’s symptoms improved after the surgery. However, she exhibited right knee pain and swelling 5 months later. The X-ray images showed no bone erosion or destruction of the right knee (Fig. 2). Although she had no other joint pain or swelling, we suspected she might have contracted rheumatoid arthritis. RF, ACPA and anti-nuclear antibodies were negative, while Matrix Metalloproteinase-3 (MMP3) was 173.1 μg. These findings were highly suggestive of seronegative rheumatoid arthritis. Administration of MTX was initiated at 10 mg/day, resulting in slight improvement of her right knee symptoms. No recurrence of the symptoms has been observed in six years since the surgery.

Fig. (2)
Anteroposterior roentgenograph of the right knee after performing TKA Loosening and bone erosion are not noted.


DISCUSSION

At present, EORA has important clinical distinctions if compared with younger onset. The clinical manifestations include large joint involvement, such as the knee joint and shoulder joint, acute onset of synovitis and prominent systemic complaints. In many cases, joint destruction often occurs rapidly after the onset [5Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28(9): 987-94.
[http://dx.doi.org/10.1002/art.1780280905] [PMID: 4038365]
, 6van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum 1994; 23(6): 367-78.
[http://dx.doi.org/10.1016/0049-0172(94)90087-6] [PMID: 7939723]
, 9Kavanaugh AF. Rheumatoid arthritis in the elderly: is it a different disease? Am J Med 1997; 103(6A): 40S-8S.
[http://dx.doi.org/10.1016/S0002-9343(97)90007-3] [PMID: 9455968]
]. In the knee joint, the elderly often have osteoarthritis and undergo conservative therapy such as intraarticular injections of hyaluronic acid. When the patients have severe knee pain and gait disturbance, they are advised to undergo TKA. The differential diagnosis is very important. Elderly patients may have several problems at the same time. The diagnostic process includes careful clinical history, physical examination, laboratory, and imaging examination. If mild swelling, local heat and turbid joint effusion in the knee joint are observed, acute suppurative arthritis, crystal-induced inflammation or EORA may be possible. When bacterial culture and crystal are negative, and RF and ACPA are negative, arthroscopic examination needs to be performed to discriminate the disease before performing TKA. If the diagnosis before performing TKA is osteoarthritis of the knee, the infection after TKA, implant debris-related arthritis and EORA should be considered when swelling, local heat and turbid joint effusion in the knee joint are observed and persist after performing TKA. If bacterial culture and crystal are negative, and the X-ray images show no bone erosion or destruction of the knee, rheumatoid arthritis should be considered.

In the treatment of rheumatoid arthritis, disease-modifying antirheumatic drugs (DMARDs) are the main drugs and should be administered as soon as possible. However, the associated risk of adverse effects and toxicity are elevated in elderly onset RA patients, and EORA patients may be less likely to receive intensive treatment. However, in many cases, the disease activity is high, and joint destruction often occurs rapidly after the onset. These patients should be treated immediately with appropriate DMARDs and biological agents [10Tutuncu Z, Reed G, Kremer J, Kavanaugh A. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann Rheum Dis 2006; 65(9): 1226-9.
[http://dx.doi.org/10.1136/ard.2005.051144] [PMID: 16414968]
].

CONCLUSION

In the patients who have severe knee arthritis without other joint symptoms, the differential diagnosis is very important. The diagnostic process includes careful clinical history, physical examination, laboratory and imaging examination. However, it is difficult to diagnose patients as EORA if rheumatoid factor and ACPA are negative.

LIST OF ABBREVIATIONS

ACPA  = Anti-cyclic citrullinated peptide antibody
CRP  = C- reactive protein
DMARDs  = Disease-modifying antirheumatic drugs
EORA  = Elderly onset RA
MMP3  = Matrix Metalloproteinase-3
MTX  = Methotrexate
RA  = Rheumatoid arthritis
RF  = Rheumatoid factor
TKA  = Total knee arthroplasty
YORA  = Younger onset RA

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Wick MC, Lindblad S, Klareskog L, Van Vollenhoven RF. Relationship between inflammation and joint destruction in early rheumatoid arthritis: a mathematical description. Ann Rheum Dis 2004; 63(7): 848-52.
[http://dx.doi.org/10.1136/ard.2003.015172] [PMID: 15194582]
[2] Welsing PM, Landewé RB, van Riel PL, et al. The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis. Arthritis Rheum 2004; 50(7): 2082-93.
[http://dx.doi.org/10.1002/art.20350] [PMID: 15248205]
[3] Lipsky PE. Rheumatoid Arthritis. In: Harrison’s principles of Intermedicine. 14th ed. New York: Mc Graw Hill 1998.
[4] Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum 2003; 48(4): 917-26.
[http://dx.doi.org/10.1002/art.10897] [PMID: 12687533]
[5] Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28(9): 987-94.
[http://dx.doi.org/10.1002/art.1780280905] [PMID: 4038365]
[6] van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum 1994; 23(6): 367-78.
[http://dx.doi.org/10.1016/0049-0172(94)90087-6] [PMID: 7939723]
[7] Terkeltaub R, Esdaile J, Décary F, Tannenbaum H. A clinical study of older age rheumatoid arthritis with comparison to a younger onset group. J Rheumatol 1983; 10(3): 418-24.
[PMID: 6411919]
[8] Deal CL, Meenan RF, Goldenberg DL, et al. The clinical features of elderly-onset rheumatoid arthritis. A comparison with younger-onset disease of similar duration. Arthritis Rheum 1985; 28(9): 987-94.
[http://dx.doi.org/10.1002/art.1780280905] [PMID: 4038365]
[9] Kavanaugh AF. Rheumatoid arthritis in the elderly: is it a different disease? Am J Med 1997; 103(6A): 40S-8S.
[http://dx.doi.org/10.1016/S0002-9343(97)90007-3] [PMID: 9455968]
[10] Tutuncu Z, Reed G, Kremer J, Kavanaugh A. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann Rheum Dis 2006; 65(9): 1226-9.
[http://dx.doi.org/10.1136/ard.2005.051144] [PMID: 16414968]

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open