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Elevated serum rheumatoid factor, anti-citrullinated protein antibodies and active rheumatoid arthritis disease are not associated with chronic periodontitis

Che Rahim MJ, Wan Mohamad WM, Saddki N, Taib H, Wan Abhamid WZ, Wong KK, et al.

Malays J Pathol, 2019 Dec;41(3):267-272.
PMID: 31901911

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of the joints with the involvement of other systems. Previous studies have demonstrated its association with chronic periodontitis (CP), a chronic inflammatory disease of tooth-supporting tissues. Positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) in RA patients have been found to be associated with CP. The aim of this study is to determine the prevalence of CP in RA patients, and to investigate the association of ACPA, RF status and RA disease activity with CP and non-CP RA patients.
MATERIALS AND METHODS: A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed.
RESULTS: Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients.
CONCLUSION: In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis
Salivary and serum cathelicidin LL-37 levels in subjects with rheumatoid arthritis and chronic periodontitis

Cheah CW, Al-Maleki AR, Vadivelu J, Danaee M, Sockalingam S, Baharuddin NA, et al.

Int J Rheum Dis, 2020 Oct;23(10):1344-1352.
PMID: 32743970 DOI: 10.1111/1756-185X.13919

INTRODUCTION: Rheumatoid arthritis (RA) is associated with chronic periodontitis (CP) due to shared risk factors, immuno-genetics and tissue destruction pathways. Human cathelicidin LL-37 has been suggested as a possible mechanistic link for these diseases. This study investigated the levels of salivary and serum LL-37 in subjects with RA and CP and their correlation with disease parameters.
METHOD: Subjects were allocated into RA (n = 49) or non-RA (NRA) (n = 55) groups, where 3 subgroups were further established; chronic periodontitis (CP), gingivitis (G) and periodontal health (H). Demographic and periodontal parameters were collected. Rheumatology data were obtained from hospital records. Serum and salivary LL-37 levels were measured using enzyme-linked immunosorbent assay and compared for all groups.
RESULTS: For salivary LL-37, RA-CP was significantly higher than NRA-G and NRA-H (P = .047). For serum LL-37, all RA and NRA-CP were significantly higher than NRA-G and NRA-H (P = .024). Salivary LL-37 correlated negatively with clinical attachment loss (CAL) (P = .048), but positively with erythrocyte sedimentation rate (ESR) in RA-H (P = .045). Serum LL-37 showed positive correlation with ESR (P = .037) in RA-G, with C-reactive protein (P = .017) in RA-H, but negative correlation with number of teeth (P = .002) in NRA-CP. Rheumatology data correlated positively with periodontal parameters in RA-CP group.
CONCLUSION: NRA-CP subjects with high serum LL-37 should receive comprehensive periodontal therapy. Positive correlation between rheumatology data and periodontal parameters showed that RA disease stability may be obtained by assessing the periodontal condition. Periodontal therapy is necessary to compliment RA treatment to achieve optimum outcome for RA patients with concurrent CP.

Matched MeSH terms: Arthritis, Rheumatoid/complications; Arthritis, Rheumatoid/metabolism*
Fulltext Determinants of comorbidity in rheumatoid arthritis: influence of demographic and duration of illness

Chin SN, Abdullah N, Poh LP

Journal of Advanced Research Design, 2015;22(1):13-22.
MyJurnal

Rheumatoid arthritis (RA) is a chronic, disabling autoimmune disease which affects about 5 in 1000 people in Malaysia. Patients with RA are at increased risk of developing comorbid conditions. This research aims at determining these relationships between demographic, duration of illness and comorbidity in RA via a multiple binary logistic (MBL) regression analysis based on the 102 patients’ information (23 males; 79 females) obtained from the rheumatoid clinic of the Queen Elizabeth Hospital in Kota Kinabalu. The relationship of the RA patients with comorbid conditions was studied with focus on the demographic and duration of illness. The variables obtained for analysis were the comorbid conditions namely, hypertension and hyperlipidemia, age, duration of illness, gender, ethnicity, household income and education level. From six independent variables, two were quantitative would be analyzed, while four were categorical, and would be transformed into dummy variables. Four phases in a model-building approach were executed where two models were formed where Model I predicted the probability of occurrence of hypertension with age of patients and first order interaction between duration of illness before diagnosis and household income of less than RM1000 had positive effects on the model, while Model II predicted the occurrence of hyperlipidemia among the RA patients with age of patients and first order interaction variable between gender(female) and age were the contributing factors.
Study site: Rheumatoid clinic, Queen Elizabeth Hospital (QEH), Kota Kinabalu, Sabah, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Osteonecrosis with renal damage in HIV patients undergoing HAART

Chitra P, Bakthavatsalam B, Palvannan T

Biomed Pharmacother, 2014 Sep;68(7):881-5.
PMID: 25194446 DOI: 10.1016/j.biopha.2014.07.017

Rheumatoid arthritis in HIV patients undergoing HAART is associated with increased risk of side effect. Elevation of uric acid (UA) is important in tissue damage, deposition of crystal in joints leads to the development of rheumatoid arthritis in the HAART complaint group. This study was carried out to investigate the relationship of uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group. Moreover; the ratio of uric acid/cystatin C, uric acid/urea and uric acid/creatinine were also studied. To analyze the progression of HIV, the immunological parameters were correlated with uric acid. Our result showed a statistically high significant increase in uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group when compared to HAART non-complaint group, early stage and control. The ratio of uric acid/cystatin C, uric acid/urea, uric acid/creatinine were significantly increased in the HAART complaint group. Statistically significant positive correlation was observed between uric acid and cystatin C, urea, creatinine, absolute CD4 and CD8 count. The increased level of uric acid, RA factor, ANA, ESR, cystatin C and increased ratio of uric acid/cystatin C in the HAART complaint group might conclude the mechanism underlying the increased risk for rheumatoid arthritis in the HAART complaint group which may relate to the combined effects of low-grade inflammation and renal dysfunction.

Study done in India

Matched MeSH terms: Arthritis, Rheumatoid/chemically induced; Arthritis, Rheumatoid/metabolism
Rheumatoid arthritis management in the APLAR region: Perspectives from an expert panel of rheumatologists, patients and community oriented program for control of rheumatic diseases

Chopra A, Lin HY, Navarra SV, Saeed MA, Sockalingam S, Thongpooswan S, et al.

Int J Rheum Dis, 2021 Sep;24(9):1106-1111.
PMID: 34375036 DOI: 10.1111/1756-185X.14185

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/drug therapy*; Arthritis, Rheumatoid/epidemiology
Prevalence and correlates of self-reported depression in Malaysian patients with rheumatoid arthritis

Chow SK, Guan YK, Chong HY, Zainal NZ, Yeap SS

Malaysian Journal of Psychiatry, 2002;10(2):9-14.

Objectives: To determine the prevalence of self-reported depression among Malaysian patients with rheumatoid arthritis (RA) and to study the correlates and independent predictors for depression. Methods: The Hospital Anxiety and Depression Scale (HADS) questionnaire wasused to assess depressive symptoms. Disease activity was determined by theduration of morning stiffness, visual analogue scale for pain and fatigue, numberof swollen/tender joint and the modified disease activity score (DAS). The Health Assessment Questionnaire (HAQ) was used to assess the patients' functionalstatus. Results: Depression was recorded in 17.2% of the 93 patients. Painful joints(p<0.001), active disease (p<0.001) and poor joint function (p<0.001) correlatedsignificantly with depression. Poor functional status assessed by the HAO was themost significant Independent predictor for depression in RA patients, (OR=5.4,p=0.028). Conclusion: The prevalence of depression In this cohort of Asian RA patients was17.2%. Painful joints and functional disability were associated with a higherIncidence of depression. RA Patients with severe functional disability should beassessed for depression that may need to be treated Independently.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study

Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.

Medicine (Baltimore), 2015 Jan;94(4):e468.
PMID: 25634192 DOI: 10.1097/MD.0000000000000468

Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/genetics
Fulltext Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss

Crotti TN, Dharmapatni AA, Alias E, Haynes DR

J Immunol Res, 2015;2015:281287.
PMID: 26064999 DOI: 10.1155/2015/281287

The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR).

Matched MeSH terms: Arthritis, Rheumatoid/metabolism
Fulltext Interleukin-23 and its correlation with disease activity, joint damage, and functional disability in rheumatoid arthritis

Dalila AS, Mohd Said MS, Shaharir SS, Asrul AW, Low SF, Shamsul AS, et al.

Kaohsiung J. Med. Sci., 2014 Jul;30(7):337-42.
PMID: 24924839 DOI: 10.1016/j.kjms.2014.02.010

The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire-Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.

Study site: Rheumatology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)

Matched MeSH terms: Arthritis, Rheumatoid/blood*; Arthritis, Rheumatoid/physiopathology; Arthritis, Rheumatoid/radiography
Fulltext Role of radiosynovectomy in the treatment of rheumatoid arthritis and hemophilic arthropathies

Das B

Biomed Imaging Interv J, 2007 Oct;3(4):e45.
PMID: 21614297 DOI: 10.2349/biij.3.4.e45

Radiosynovectomy is a novel method of treatment for several acute and chronic inflammatory joint disorders. A small amount of a beta-emitting radionuclide is injected into the affected joint delivering a radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is destroyed, secretion of fluid and accumulation of inflammation causing cellular compounds stops and the joint surfaces become fibrosed, providing long term symptom relief. The radionuclides are injected in colloidal form so that they remain in the synovium and are not transported by lymphatic vessels causing radiation exposure to other organs. Complete reduction of knee joint swelling has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow, shoulder, ankle and hip joints showed significant improvement in 50-60% and restoration of normal function and long term pain relief has been achieved in about 70% of small finger joints. In hemophilic arthropathies complete cessation of bleeding in about 60% and improved mobility in 75% of patients has been reported.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext Predictors of frequent oral analgesic use in rheumatoid arthritis

Das Gupta E, Tee HS, Sakthiswary R

Pak J Med Sci, 2014 Sep;30(5):976-81.
PMID: 25225510 DOI: 10.12669/pjms.305.5112

Objective: The main objective of this study was to determine the predictors of frequent oral analgesic use among Rheumatoid Arthritis (RA) patients who were prescribed with the above medication on an ‘as needed’ basis.
Methods: Patients with RA were recruited consecutively from the Rheumatology outpatient clinics in this cross-sectional study. The sociodemographic data, frequency of oral analgesic intake, Patient Global Assessment (PGA) scores and HAQ (Health Assessment Questionnaire) scores were determined by interviewing the subjects. Subjects were divided into 2 groups; frequent users (3 days and above in a week) and less frequent users (less than 3 days in a week).
Results: In a total of 112 subjects, 39 (34.8%) were frequent analgesic users. Both the HAQ and PGA scores were significantly higher among the frequent users (p < 0.05). Using multivariate analysis, the HAQ scores (p=0.015, odds ratio 3.161 [95% confidence interval of 1.246-8.015]) and PGA scores (p=0.039 odds ratio 1.291 [95% confidence interval of 1.012-1.646]) were found to be independent predictors of frequent analgesic use.
Conclusions: Our study confirms that the frequency of analgesic intake in Rheumatoid Arthritis has a significant relationship with patient-reported functional capacity and well being.
KEY WORDS: Analgesic, Rheumatoid arthritis.

Study site: Rheumatology clinic, Hospital Tunku Jaafar, Seremban, Negeri Sembilan, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid*
Fulltext Early referral of newly diagnosed rheumatoid arthritis

Das Gupta E, Gun SC, Abdul Rahman YR

Family Physician, 2003;12(1):16-8.

1. Revised ARA criteria (1987) the diagnosis of RA requires presence of at least 4 of the following 7 features: 1) morning stiffness> 1 hour 2) swelling of 2 or more joints (of 6 weeks duration) 3) symmetrical joint involvement 4) arthritis of more than 1 hand joints (of at least 6 weeks duration) 5) positive rheumatoid factor, 6) presence of rheumatoid nodule 7) X-ray changes. 2. Use of DMARD should start early, along with pain control by non steroidal anti inflammatory drugs (NSAID) 3. Early referral to rheumatologists is the current recommendation 4. Indications for early referral include: i. Early morning stiffness (EMS) of 30 mins ;- ii. Metatarsophalangeal (MTP) / metacarpophalageal (Mep) involvement. iii. 2 or more swollen joints.

Matched MeSH terms: Arthritis, Rheumatoid
Fulltext The difficult rheumatology diagnosis

Devaraj NK

Ethiop J Health Sci, 2018 Jan;28(1):101-102.
PMID: 29622913 DOI: 10.4314/ejhs.v28i1.13

Background: Rheumatoid arthritis is a devastating condition. More so, the diagnosis of seronegative rheumatoid arthritis is often fraught off with much uncertainty and that leads to further suffering to the unfortunate patient.

Case Details: This is a case of Madam A, who presented with many non-specific symptoms and signs involving many systems which was finally diagnosed as seronegative rheumatoid arthritis. This case explores the challenges in reaching this uncommon diagnosis and how anti-inflammatory drugs can bring a miraculous relief to the patient's suffering.

Conclusion: The diagnosis of seronegative rheumatoid arthritis often presents a real challenge to the medical practitioner and often requires multiple visits and/or shared multidisciplinary care for confirmation of the diagnosis. Once diagnosed and treated with disease modifying anti- rheumatic drugs, often there is a miraculous relief to the patient's suffering.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/drug therapy
Fulltext The atypical presentation of rheumatoid arthritis in an elderly woman: a case report

Devaraj NK

Ethiop J Health Sci, 2019 Jan;29(1):957-958.
PMID: 30700964 DOI: 10.4314/ejhs.v29i1.18

The diagnosis of rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen. This includes conditions such as rheumatoid arthritis which needs early diagnosis to start disease modifying drugs (DMARDs) which can improve the prognosis and prevent further joint erosion and organ damage. This case report focused on a similar scenario in an elderly woman initially thought to have osteoarthritis but was diagnosed later with rheumatoid arthritis which brought much relief to her current predicament.

Matched MeSH terms: Arthritis, Rheumatoid/blood; Arthritis, Rheumatoid/diagnosis*; Arthritis, Rheumatoid/drug therapy
Fulltext Early results of total knee replacements: "a clinical and radiological evaluation"

Dhillon KS, Jamal A, Bhupinderjeet S

Med J Malaysia, 1993 Dec;48(4):427-35.
PMID: 8183167

From March 1986 to June 1992, 100 primary total knee arthroplasties were done in 69 patients. The demographic data and complications were analysed in these 69 patients. The first 50 knees with a minimal follow-up of one year (range 1-6 years) were analysed in more detail according to the International Knee Society Rating System. Detailed radiological evaluation was also carried out to assess positioning of the components. There were 79 knees with osteoarthritis, 20 knees with rheumatoid arthritis and one with Systemic Lupus Erythromatosus (SLE). The knee score was poor in all knees pre-operatively. Post-operatively 78% had good to excellent score and the other 22% had fair knee score. However the functional score remained poor in 50% of the knees. Ideal tibio-femoral alignment was obtained in 68% of the knees. Twenty four percent of the knees had 0.4 degrees of varus and eight percent had 10-12 degrees valgus. Complication rate was low with 1% of infection (one knee). Overall early results were satisfactory.
Study site; University Hospital Kuala Lumpur (University Malaya Medical Centre)

Matched MeSH terms: Arthritis, Rheumatoid
Anti-CCP antibodies: A better diagnostic tool for rheumatoid arthritis

Dollah R, Yaacob A, Ismail AH, Che Hussin CM

International Medical Journal (Tokyo), 2011;18(1):53-57.

Objective: The assay for anti-cyclic citrullinated peptide (anti-CCP) antibody is a recent test of interest due to low diagnostic specificity of rheumatoid factor in the diagnosis of rheumatoid arthritis. To determine the sensitivity and specificity of anti-CCP antibodies in rheumatoid arthritis patients using American College of Rheumatology (ACR) criteria as a gold standard.
Design: A cross sectional study was conducted from January 2008 to December 2008 on 100 patients with rheumatoid arthritis and 153 patients with arthritis or arthralgia but not fulfilling ACR criteria for rheumatoid arthritis.
Materials and Methods: Serum from each subject was tested for anti-CCP antibodies and IgM rheumatoid factor (IgM RF) by an enzyme linked immunosorbent assay (ELISA). Sensitivity and specificity of the tests were evaluated using the ACR criteria as the gold standard. Data was analyzed using SPSS version 12.0 software. The association between the two categorical variables were tested using chi-square test. The differences between the two groups were tested using independent t-test. Results: The sensitivity of anti-CCP antibodies was 71% with 94.8% of specificity. For rheumatoid factor the sensitivity was 85% and the specificity was 74.5%. Positive predictive value for anti-CCP antibodies was 89.9% whereas for rheumatoid factor it was 68.5%. The sensitivity of ACR criteria with inclusion of anti- CCP antibodies was 100% and specificity of 94.8% (95%CI: 91.3%, 98.2%).
Conclusion: Anti-CCP antibody has a higher diagnostic accuracy compared to the RF. Anti-CCP antibody is a useful laboratory marker to support the diagnosis of rheumatoid arthritis and to differentiate patients with rheumatoid arthritis from rheumatoid arthritis-like symptoms. Therefore, it is suggested that anti-CCP antibodies should be included as another laboratory supportive criterium besides RF test in ACR criteria in the diagnosis of RA.
Study site: family medicine clinic, rheumatology clinic and immunology laboratory of Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia

Matched MeSH terms: Arthritis, Rheumatoid
Influence of periodontitis on levels of autoantibodies in rheumatoid arthritis patients: A systematic review

Eezammuddeen NN, Vaithilingam RD, Hassan NHM

J Periodontal Res, 2023 Feb;58(1):29-42.
PMID: 36317493 DOI: 10.1111/jre.13065

BACKGROUND AND OBJECTIVE: Periodontitis (PD) is a dysbiotic disease of tooth-supporting structures that has been associated with various systemic diseases including rheumatoid arthritis (RA). To date, evidence demonstrated increased prevalence of RA among PD patients and postulated PD to have a role in the development of autoantibodies in RA patients. Therefore, a systematic review was conducted to assess the available evidence to ascertain the effect of PD on levels of autoantibodies in the serum, saliva and gingival crevicular fluid (GCF) of RA patients.
MATERIAL AND METHODS: The systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Relevant literature was searched from PubMed, Web of Science, Scopus and Ebscohost databases from inception until 31 August 2020. The risk of bias in each study was determined based on the Newcastle-Ottawa Scale tool. Results from random-effect meta-analyses were presented as summary estimates of odds ratios (ORs) for seropositivity and standardised mean difference (SMD) of autoantibody levels with 95% confidence intervals. Sensitivity tests and meta-regression were performed to assess the robustness of the results and potential cause of heterogeneity.
RESULTS: The electronic and manual searches gathered 932 articles. Following screening and full-text assessment, a total of 29 studies were included in the analysis. Twenty-eight published observational studies were included in the quantitative analysis in the form of random-effect meta-analysis which revealed that PD was associated with anti-citrullinated proteins autoantibodies (ACPAs) and Rheumatoid Factor (RF) seropositive RA patients (OR for ACPA seropositivity: 1.82; 95% CI: 1.13-2.93) (OR for RF seropositivity: 1.53; 95% CI: 1.05-2.24). Also, RA patients with PD had increased serum levels of ACPA and RF. However, high heterogeneity among studies' results, partially ascribed to the unstandardised case definition of PD and laboratory testing of autoantibodies. Apart from ACPA and RF in serum, studies which reported on other RA-related autoantibodies, as well as autoantibody levels in saliva and GCF were scarce.
CONCLUSION: RA patients with PD tend to have greater ACPA and RF levels in their serum when compared with the RA patients without PD supporting the plausible role of PD in the development of systemic autoimmunity in RA patients.

Matched MeSH terms: Arthritis, Rheumatoid*
Disease-modifying antirheumatic drugs and organising pneumonia

Faisal M, Roslan A, Nik Abeed NN, Ban Yu-Lin A

BMJ Case Rep, 2021 Jan 06;14(1).
PMID: 33408105 DOI: 10.1136/bcr-2020-238173

Organising pneumonia (OP) in rheumatoid arthritis (RA) may be part of pulmonary manifestation (disease related) or disease-modifying antirheumatic drugs (DMARDs) related. We report a case series of RA patients with DMARDs related OP. A 65-year-old woman developed OP 3 weeks after initiation of methotrexate (MTX). High-resolution CT (HRCT) scan of the thorax revealed bilateral consolidations in the lung bases. She had complete radiological resolution 6 months after corticosteroid therapy with cessation of MTX. The second case was of a 60-year-old woman on MTX with recent addition of leflunomide due to flare of RA. She developed worsening cough 4 months later and HRCT scan revealed consolidation in the left upper lobe with biopsy proven OP. She responded within 6 months of corticosteroid therapy with clinical and radiological resolution. This case series highlights that OP may developed with low-dose MTX (as early as 3 weeks) and leflunomide and the diagnosis requires a high index of suspicion.

Matched MeSH terms: Arthritis, Rheumatoid/diagnosis; Arthritis, Rheumatoid/drug therapy*
Budget impact analysis of medicines: estimated values versus real-world evidence and the implications

Faleiros DR, Alvares-Teodoro J, Nunes da Silva E, Godman BB, Gonçalves Pereira R, Gurgel Andrade EI, et al.

Expert Rev Pharmacoecon Outcomes Res, 2021 May 27.
PMID: 33971778 DOI: 10.1080/14737167.2021.1927716

Objectives: Budget Impact Analyses (BIA) of medicines helps managers in promoting health systems' sustainability when assessing the role and value of new medicines. However, it is not clear whether BIAs typically underestimate or overestimate the impact on real-world budgets. This retroactive analysis seeks to compare estimated values obtained by a BIA and Real-World Evidence (RWE) to guide discussions.Methods: The estimated values were obtained through a BIA concerning the incorporation of adalimumab for the treatment of Rheumatoid Arthritis into the Brazilian Unified Health System (SUS) carried out retroactively and per international guidelines. RWE data was extracted from SUS computerized systems. We subsequently compared the number of treatments, costs, and Incremental Budget Impact (IBI).Results - The total number of treatments was underestimated by 10% (6,243) and the total expenditure was overestimated by 463% (US$ 4.7 billion). In five years, the total difference between the estimated values and real IBI reached US$ 1.1 billion. A current expenditure of US$ 1.0 was observed for every US$ 5.60 of estimated expenditure.Conclusion - The higher estimates from the BIA might cause decision makers to be more cautious with the introduction of a new medicine to reduce the opportunity costs for other interventions.

Matched MeSH terms: Arthritis, Rheumatoid
Nanomedicines for improved targetability to inflamed synovium for treatment of rheumatoid arthritis: Multi-functionalization as an emerging strategy to optimize therapeutic efficacy

Fang G, Zhang Q, Pang Y, Thu HE, Hussain Z

J Control Release, 2019 06 10;303:181-208.
PMID: 31015032 DOI: 10.1016/j.jconrel.2019.04.027

Owing to its intricate autoimmune pathophysiology and significant risks of progression to other rheumatic co-morbidities (i.e., osteoporosis and osteoarthritis), a plausible therapeutic regimen is mandatory for early-stage management of rheumatoid arthritis (RA). Nevertheless, the conventional therapeutic agents particularly the corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) have shown grander success in the treatment of RA; however, long-term use of these agents is also associated with serious adverse events. To combat these issues and optimize therapeutic efficacy, nanotechnology-based interventions have been emerged as viable option. While, nanomedicines signposted superiority over the conventional pharmacological moieties; there are still many pharmacokinetic and pharmacodynamic challenges to nanomedicines following their intravenous or intra-articular administration. To circumvent these challenges, significant adaptations such as PEGylation, surface conjugation of targeting ligand(s), and site- responsive behavior (i.e., pH-, biochemical-, or thermal-responsiveness) have been implemented. Besides, multi-functionalization of nanomedicines has been emerging as an exceptional strategy to overcome pharmacokinetic challenges, improve targetability to inflamed synovium, maximise internalisation into the activated macrophages, and improved therapeutic outcomes for treatment of RA. Therefore, this review aims to conceptualize and recapitulate the substantial evidences regarding the pharmacokinetic and pharmacodynamic superiority of multi-functionalized nanomedicines over the naked nanomedicines for site-selective targeting to inflamed synovium and rational treatment of RA and other rheumatic co-morbidities. Pharmaceutical sustainability of the multi-functionalized nanomedicines for improved biocompatibility, profound interaction with the targeting tissue/cells/sub-cellular domain, and diminished systemic toxicity has also been pondered.

Matched MeSH terms: Arthritis, Rheumatoid/drug therapy*

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