Approach to diagnosis of Rheumatoid arthritis Iraj Salehi Abari MD., Internist Rheumatologist salehiabari@sina.tums.ac.ir

In the name of God

Introduction: . The most common inflammatory arthritis I. Salehi A. Introduction: . The most common inflammatory arthritis . A chronic progressive systemic disease . Autoinflammatory/Autoimmune disease . Hallmark: Chronic erosive polyarthritis Iran Criteria of RA

. Prevalence in old women: 5% . F/M ratio: 2-3/1 I. Salehi A. Epidemiology: . All races . Overal prevalence: 1% . Prevalence in old women: 5% . F/M ratio: 2-3/1 Iran Criteria of RA

Clinical categories: . Articular: almost all . Peri-articular I. Salehi A. Clinical categories: . Articular: almost all . Peri-articular . Extra-articular (systemic) Iran Criteria of RA

Articular involvement: I. Salehi A. Articular involvement: . Peripheral synovial joints . Polyarthritis: common in course . Oligoarthritis: common in initiation . Monoarthritis: rare . No axial involvement except neck Iran Criteria of RA

Clinical articular hallmarks: I. Salehi A. Clinical articular hallmarks: . Chronic symmetric polyarthritis . Small > Small + Large > Large joints . Hand (wrist, MCP, PIP) joints: Key joints . Morning stiffness > 1 hour . DIP involvement: uncommon . Deformities in advanced (very late) phase Iran Criteria of RA

Extra-articular manifestations: I. Salehi A. Extra-articular manifestations: . Rheumatoid nodules . Eyes: Epi/scleritis, Sjogren’s syndrome . Lungs: ILD,…, Pleural effusion . Cardiac: Coronary/non-Coronary . Vascular: Vasculitis, Atherosclerosis,… . Hematologic: Anemia, Felty’s syndrome,… . Muscular: Myopathy, Myositis . Nervous system . Kidney Iran Criteria of RA

Paraclinical hallmarks: I. Salehi A. Paraclinical hallmarks: . Serology: . High titer RF or Anti-CCP (ACPA) . Both RF and Anti-CCP positivity . Imaging: . Erosion in X-ray or MRI of joints Iran Criteria of RA

Attention please: . Negative RF or Anti-CCP: 20-30% I. Salehi A. Attention please: . Negative RF or Anti-CCP: 20-30% . Both RF and Anti-CCP negativity: . In initial presentation: up to 50% . In course of RA: up to 20% . Anti-CCP specificity > 95% Iran Criteria of RA

Acute polyarthritis: I. Salehi A. . Viral: B19, HBV, HCV,… . Reactive: Reiter’s syndrome . SLE . Sarcoidosis . Enteropathic (IBD) arthropathy . Psoriatic arthritis . Crystals: Gout, CPPD,… . Lyme arthritis . Brucellosis Iran Criteria of RA

I. Salehi A. Our research Iran Criteria of RA

Introduction: I. Salehi A. . More than 14 years of clinical practice in Rheumatology . Visiting more than 2000 Cases of “Rheumatoid arthritis.” . Expert opinion-based Criteria . Understanding of the problems and failures of the ACR Criteria in clinical practice . Newly identified ACPA (Anti-CCP) . The role of MRI in RA for early detection of erosion . Literature review and extensive studies . Iran Criteria for early diagnosis of ‘’RA’’ Iran Criteria of RA

Material and methods: I. Salehi A. . Outpatient Rheumatology Clinic of the author . Between 2001 and 2010 . The medial records of the patients with diagnosis of RA were reviewed . The diagnosis was made by a Rheumatologist (Iraj Salehi Abari) upon clinical judgment Iran Criteria of RA

Material and methods: I. Salehi A. . SPSS software (SPSS Inc., Chicago, IL) was used for statistical analysis . Sensitivity: number of the patients classified as RA by the Criteria/ number of the patients diagnosed as RA by a Rheumatologist (clinical Judgment) Iran Criteria of RA

Material and methods: . Inclusion criteria: . Exclusion criteria: I. Salehi A. Material and methods: . Inclusion criteria: . The patients with diagnosis of “RA” in the first year of disease . Exclusion criteria: . The patients with Overlap disease . The patients Under classic RA treatment from before . The patients that have been followed up < 6 weeks . The patients with incomplete medical records . Finally 243 cases have been included in this research Iran Criteria of RA

Material and methods: . Demographic and clinical data: I. Salehi A. . Gender . Age at diagnosis . Disease duration . Follow up duration . Data regarding . Iran Criteria . ACR Criteria . ACR/EULAR Criteria Iran Criteria of RA

Demographic data in 243 cases*: mean + SD/n (%) I. Salehi A. Demographic data in 243 cases*: mean + SD/n (%) . Female/Male ratio 180 (74.1)/63 (25.9) . Mean age at diagnosis 49.16 + 15.38 (16-87) Years ( min-max ) . Mean disease duration 7.04 + 6.87 (2-85) Months (min-max) . Mean follow up duration 28.24 + 50.19 (2-630) .F/M ratio # 3/1 .Peak onset age # 50 + 15 years *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

Demographic and clinical data in 243 cases*: I. Salehi A. Demographic and clinical data in 243 cases*: . Arthritis of > 2 joints 228 (93.8%) . Hand arthritis 211 (86.8%) . Symmetric involvement 205 (84.4%) . Morning stiffness > 1 hour 131 (53.9%) . Duration of arthritis or morning stiffness > 6 w 219 ( 90%) . Subcutaneous nodules 4(1.6%) *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

Initial clinical presentations*: I. Salehi A. Initial clinical presentations*: . Oligo/polyarthritis (> 2 joints): 94% . Duration > 6 weeks: 90% . Hand involvement: 87% . Symmetric involvement: 85% . Morning stiffness > 1 hour: 54% . No extra-articular involvement: . Only olecranon Rheumatoid nodules: 1.6% *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

Demographic and paraclinical data in 243 cases*: I. Salehi A. Demographic and paraclinical data in 243 cases*: . Positive RF or ACPA 98 (40.3%) . Positive RF and ACPA 48 (19.8%) . High titer RF or ACPA 92 (37.9%) . Juxta-articular osteoporosis 170 (70%) . Erosion in X-ray or MRI 65 (26.7%) *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

Initial paraclinical findings* : I. Salehi A. Initial paraclinical findings* : . Positive RF or Anti-CCP: 40% . Positive RF and Anti-CCP: 20% . High titer RF or Anti-CCP: 38% . Juxta-articular osteoporosis:70% . Erosion in X-ray or MRI: 27% *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

I. Salehi A. Selection of 10 golden Criterias upon 14 years of clinical practice and visiting > 2000 cases of RA . Arthritis of > 2 joints . Hand arthritis . Symmetric involvement . Morning stiffness > 1 hour . Duration of > 6 weeks . Elbow-forearm Rheumatoid nodule . RF positivity and high titer . Anti-CCP positivity and high titer . Juxta-articular osteoporosis in X-ray . Erosion in X-ray or MRI of joint Iran Criteria of RA

I. Salehi A. Selection of 10 golden Criterias upon 14 years of clinical practice and visiting > 2000 cases of RA . Arthritis of > 2 joints . Hand arthritis . Symmetric involvement . Morning stiffness > 1 hour . Duration of > 6 weeks . Elbow-forearm Rheumatoid nodule . RF positivity and high titer . Anti-CCP positivity and high titer . Juxta-articular osteoporosis in X-ray . Erosion in X-ray or MRI of joint *: 2 points *: 1 point Iran Criteria of RA

Iran criteria for early diagnosis of RA*: I. Salehi A. Iran criteria for early diagnosis of RA*: . Entry criteria: . No other prominent diagnosis is proposed according to the patient’s history and physical examination . Articular involvement: (up to 7) . Arthritis of > 2 joints 1 . Hand arthritis (wrist, MCP, PIP) 2 . Symmetric involvement 1 . Morning stiffness > 1 hour 1 . Duration of arthritis or morning stiffness > 6 weeks 2 *. Salehi I et al (2012) Early diagnosis of rheumatoid arthritis: an introduction to the newly designed Iran Criteria for Rheumatoid Arthritis. Rheumatol Int. doi: 10.1007/s00296-011-2349-1 Iran Criteria of RA

Iran criteria for early diagnosis of RA: I. Salehi A. Iran criteria for early diagnosis of RA: . Serology: (Up to 2) . Positive RF or ACPA 1 . Positive RF and ACPA 2 . High titer RF or ACPA 2 . Subcutaneous nodule: (1) . Elbow or forearm 1 . Involved joints imaging: (Up to 2) . Juxta-articular osteoporosis 1 . Erosion in X-ray or MRI 2 Iran Criteria of RA

Iran criteria for early diagnosis of RA: I. Salehi A. Iran criteria for early diagnosis of RA: . Articular involvement 7 . Serology 2 . Subcutaneous nodule 1 . Involved joints imaging 2 = 12 . 6 points out of 12 make a diagnosis of RA . All peripheral joints included . By using 66/68 joints count Iran Criteria of RA

I. Salehi A. The Iran Criteria for RA has been candidate to oral presentation in multiple International Congresses: . Rheumatology-2012, Aug. 14-15, Chicago, USA. . Orthopedic-2012, Aug. 13-15, Chicago, USA. . International Microbiology and Immunology Symposium-2012, Toronto, Canada. . International Forum on Clinical Medicine Development-2012, Lanzhou, China. . World Biotechnology Congress-2013, Jun 3-6, Boston, USA. . 4th Latin American Congress on Autoimmunity-2013, Sept. 18-21, Rio de Janeiro, Brazil. . Etc., Iran Criteria of RA

I. Salehi A. The 1987 American College of Rheumatology (ACR) criteria for classification of Rheumatoid arthritis (RA): . Arthritis of > 3 joints . Hand arthritis (Wrist, MCP, PIP) . Symmetric involvement . Morning stiffness > 1 hour . Rheumatoid nodule . Positive RF . Juxta-articular osteoporosis or erosion in X-ray of hands Iran Criteria of RA

The ACR criteria for RA: I. Salehi A. The ACR criteria for RA: . Arthritis among right or left PIP, MCP, Wrist, Elbow, Knee, Ankle and MTP joints . Arthritis must be present for at least 6 weeks . With at least 4 criteria out of 7, RA is classified Iran Criteria of RA

The 2010 ACR/EULAR* classification criteria for RA: I. Salehi A. The 2010 ACR/EULAR* classification criteria for RA: . Target population (who should be tested?) . Patients who have at least 1 joint with definite clinical synovitis (swelling) . With the synovitis not better explained by another disease *. European League Against Rheumatism Iran Criteria of RA

The 2010 ACR/EULAR classification criteria for RA: I. Salehi A. The 2010 ACR/EULAR classification criteria for RA: Joint involvement: . 1 Large joint 0 . 2-10 Large joints 1 . 1-3 Small joints (+ Large joints) 2 . 4-10 Small joints (+ Large joints) 3 . > 10 joints (at least 1 small joint) 5 Iran Criteria of RA

The 2010 ACR/EULAR classification criteria for RA: I. Salehi A. The 2010 ACR/EULAR classification criteria for RA: B. Serology (at least 1 test result is needed for classification): . Negative RF and ACPA* 0 . Low-positive RF or Low-positive ACPA 2 . High-positive RF or High-positive ACPA 3 *. Anti Citrullinated Protein Antibody Iran Criteria of RA

The 2010 ACR/EULAR classification criteria for RA: I. Salehi A. The 2010 ACR/EULAR classification criteria for RA: C. Acute-phase reactants (at least 1 test result is needed for classification) . Normal CRP or Normal ESR 0 . Abnormal CRP or raised ESR 1 D. Duration of symptoms . < 6 weeks 0 . > 6 weeks 1 Iran Criteria of RA

The 2010 ACR/EULAR classification criteria for RA: I. Salehi A. The 2010 ACR/EULAR classification criteria for RA: . The highest score in each domain is used . Small joints: . MCPs, PIPs, MTP2-5, thumb IP joints and wrist . Large joints: . Shoulder, elbow, hip, knees and ankles . The MTP1, CMC1 and DIP joints must be ignored . At least 6 points out of 10 is needed for classification of RA Iran Criteria of RA

Sensitivity of different RA Criterias in 243 cases: I. Salehi A. Sensitivity of different RA Criterias in 243 cases: . 1987 ACR criteria 145 (59.7%) . 2010 ACR/EULAR criteria 161 (66.3%) . 2012 Iran criteria 239 (98.4%) Iran Criteria of RA

Comparing of different RA criterias: I. Salehi A. Comparing of different RA criterias: . Sensitivity: . ACR criteria < 60% (59.7%) . ACR/EULAR < 70% (66.3%) . Iran criteria: # 100% (98.4%) . Specificity: . Iran criteria > ACR > ACR/EULAR . We guess Iran criteria > 95% Iran Criteria of RA

Amir Alam Hospital Approach to diagnosis of RA: I. Salehi A. Amir Alam Hospital Approach to diagnosis of RA: A. Diagnosis must be made by a Rheumatologist B. In History looking for: . Articular pain + swelling . Morning stiffness . Duration of symptoms C. In Physical examination looking for: . Arthritis (Synovitis) . Features: number, symmetry, hand . Rheumatoid nodule Iran Criteria of RA

Amir Alam Hospital Approach to diagnosis of RA: I. Salehi A. Amir Alam Hospital Approach to diagnosis of RA: D. Ruling out other diagnosis by Hx. and Ph. Exam. E. In serology looking For: . RF and ACPA F. In imaging looking for: . Juxta-articular osteoporosis in X-ray . Erosion in X-ray or MRI . Synovial thickening in MRI G. Using Iran Criteria Iran Criteria of RA

Amir Alam Hospital guideline for serology in RA: I. Salehi A. Amir Alam Hospital guideline for serology in RA: For all patients with RA or suspected to having RA . RF and Anti-CCP must be ordered . At a standard clinical immunolog Laboratory . Positive tests: Titers > upper limit of normal (ULN) . High titer tests: Titers > 3 times ULN Iran Criteria of RA

Amir Alam Hospital guideline for imaging in RA: I. Salehi A. Amir Alam Hospital guideline for imaging in RA: For all patients with RA or suspected of having ‘’RA’’ . Step I: The X-ray of hands must be ordered If there is not enough points for diagnosis of RA and the X-ray of hands is normal . Step II: The X-ray of herald involved joint must be ordered and if it is normal . Step III: The MRI of hands must be ordered and if it is normal . Step IV: The MRI of herald involved joint must be ordered The X-rays were interpreted by both expert Radiologist and Rheumatologist while the MRI only by MRI man. Iran Criteria of RA

Case 1 (chronic oligoarthritis): I. Salehi A. Case 1 (chronic oligoarthritis): . A female, 55 years . Wrist pain and swelling from 2 months ago . Arthritis (Synovitis) of both wrists . No other findings in Hx. and Ph. Ex. . Lab.: Nl, Hand X-ray: Nl . Clinical judgment: RA . ACR (2/7) and ACR/EULAR (3/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 2 (acute oligoarthritis): I. Salehi A. Case 2 (acute oligoarthritis): . A female, 65 years . Wrist pain and swelling from 2 weeks ago . Morning stiffness # 2 hours . Arthritis of both wrists . Positive RF . No other findings . Clinical judgment: RA . ACR and ACR/EULAR (4/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 3 (acute oligoarthritis): I. Salehi A. Case 3 (acute oligoarthritis): . A female, 70 years . Wrist pain and swelling from 4 weeks ago . Morning stiffness # 3 hours . Arthritis of both wrists . Juxta-articular osteoporosis in Hand X-ray . No other findings . Clinical judgment: RA . ACR and ACR/EULAR (2/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 4 (acute oligoarthritis): I. Salehi A. Case 4 (acute oligoarthritis): . A female, 50 years . Wrist pain and swelling from 3 days ago . Arthritis of both wrists . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR and ACR/EULAR (4/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 5 (chronic monoarthritis): I. Salehi A. Case 5 (chronic monoarthritis): . A female, 60 years . Right wrist pain from 2 months ago . Arthritis of right wrist . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR (2/7) and ACR/EULAR (5/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 6 (chronic monoarthritis): I. Salehi A. Case 6 (chronic monoarthritis): . A male, 55 years . Right knee pain and swelling from 6 months ago . Morning stiffness # 2 hours . Arthritis of right knee . Juxta-articular osteoporosis in knee X-ray . High titer Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR (2/7) and ACR/EULAR (4/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 7 (acute monoarthritis): I. Salehi A. Case 7 (acute monoarthritis): . A female, 70 years . Left wrist pain and swelling from 1 month ago . Arthritis of left wrist . Erosion in wrist MRI . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR and ACR/EULAR (4/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 8 (PIP monoarthritis): I. Salehi A. Case 8 (PIP monoarthritis): . A female, 28 years . PIP2 joint pain and swelling from 2 months ago . Arthritis of PIP2 in right hand . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR (2/7) and ACR/EULAR (5/10): No RA . Iran criteria (6/12) : RA Iran Criteria of RA

Case 9 (DIP arthritis): . A female, 72 years I. Salehi A. Case 9 (DIP arthritis): . A female, 72 years . DIP3 joint pain and swelling from 2 months ago . Morning stiffness # 2 hours . Arthritis of DIP3 in right hand . Juxta-articular osteoporosis of DIP3 in hand X-ray . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR and ACR/EULAR: No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 10 (Large joint polyarthritis): I. Salehi A. Case 10 (Large joint polyarthritis): . A female, 72 years . Elbow and knee pain and swelling from 2 months ago . Arthritis of right and left elbows and knees . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR (3/7) and ACR/EULAR (4/10): No RA . Iran criteria (6/12): RA Iran Criteria of RA

Case 11 (subclinical RA): I. Salehi A. Case 11 (subclinical RA): . A female, 53 years . Polyarthralgia of hands and elbows from 2 months ago . Morning stiffness # 5 hours . No synovitis in Ph. Ex. . Erosion and synovial thickening in wrist MRI . Both RF and Anti-CCP positivity . No other findings . Clinical judgment: RA . ACR (3/7) and ACR/EULAR: No RA . Iran criteria (7/12): RA Iran Criteria of RA

I. Salehi A. Conclusion: . Iran Criteria for RA is the most sensitive criteria . With sensitivity of 98.4% (# 100%) . It can diagnose RA in either forms of: . Early or late stage . Mono/ oligo and polyarticular type . Acute or chronic forms . Clinical or subclinical forms Iran Criteria of RA

I. Salehi A.

I. Salehi A. Iran Criteria of RA