Rheumatoid arthritis current diagnosis and treatment

latest ACR guidelines included

1. Dr. Ankur Nandan VarshneyDr. Ankur Nandan Varshney
Institute of Medical SciencesInstitute of Medical Sciences
Banaras Hindu UniversityBanaras Hindu University
Rheumatoid ArthritisRheumatoid Arthritis
Diagnosis and Current Management Diagnosis and Current Management

2. Introduction Introduction
Commonest inflammatory joint disease seen in clinical Commonest inflammatory joint disease seen in clinical
practice affecting approx 1% of population.practice affecting approx 1% of population.
Chronic multisystem disease of unknown cause.Chronic multisystem disease of unknown cause.
Characterized by persistent inflammatory synovitis Characterized by persistent inflammatory synovitis
leading to cartilage damage, bone erosions, joint leading to cartilage damage, bone erosions, joint
deformity and disability. deformity and disability.

3. OnsetOnset
Although Rheumatoid arthritis may present at any age, patients most Although Rheumatoid arthritis may present at any age, patients most
commonly are first affected in the commonly are first affected in the third to sixth third to sixth decades. decades.
Female: male 3:1Female: male 3:1
Initial pattern of joint involvement could be:-Initial pattern of joint involvement could be:-
1)1)Polyarticular : most commonPolyarticular : most common
2)2)OligoarticularOligoarticular
3)3)MonoarticularMonoarticular
Morning joint stiffness > 1 hour Morning joint stiffness > 1 hour and easing with physical activity is and easing with physical activity is
characteristic.characteristic.
Small joints of hand and feet Small joints of hand and feet are typically involved.are typically involved.

4. Clinical ManifestationsClinical Manifestations
ArticularArticular
Extra-articularExtra-articular

5. Articular manifestationArticular manifestation
Pain in affected Pain in affected
joint aggravated by joint aggravated by
movemnt is the movemnt is the
most common most common
symptom.symptom.
Morning stiffness Morning stiffness
≥1 hr≥1 hr
Joints involved -Joints involved -

6. Relative incidence of joint Relative incidence of joint
involvement in RAinvolvement in RA
MCP and PIP joints of hands & MTP of feet 90%MCP and PIP joints of hands & MTP of feet 90%
Knees, ankles & wrists- 80%Knees, ankles & wrists- 80%
Shoulders- 60%Shoulders- 60%
 Elbows- 50%Elbows- 50%
TM, Acromio - clavicular & SC joints- 30%TM, Acromio - clavicular & SC joints- 30%

7. Joints involved in RAJoints involved in RA
Don’t forget the Don’t forget the cervical spinecervical spine!! !!
Instability at cervical spine can lead to Instability at cervical spine can lead to
impingement of the spinal cord. impingement of the spinal cord.
Thoracolumbar, sacroiliac, and distal Thoracolumbar, sacroiliac, and distal
interphalangeal joints (DIP)of the hand are interphalangeal joints (DIP)of the hand are
NOTNOT involved.involved.

8. PIP SwellingPIP Swelling

9. Ulnar Deviation, MCP Swelling, Ulnar Deviation, MCP Swelling,
Left Wrist SwellingLeft Wrist Swelling

12. Extra-articular Extra-articular
manifestationsmanifestations
Present in 30-40% Present in 30-40%
May occur prior to arthritisMay occur prior to arthritis
Patients that are more likely to get are:Patients that are more likely to get are:
High titres of RF/ anti-CCPHigh titres of RF/ anti-CCP
HLA DR4+HLA DR4+
Male Male
Early onset disabilityEarly onset disability
History of smokingHistory of smoking

13. Constitutional symptoms Constitutional symptoms ( most common)( most common)
Rheumatoid nodulesRheumatoid nodules(30%)(30%)
HematologicalHematological--
 normocytic normochromic anemianormocytic normochromic anemia
 leucocytosis /leucopenialeucocytosis /leucopenia
 thrombocytosisthrombocytosis
Felty’s syndrome-Felty’s syndrome-
 Chronic nodular Rheumatoid ArthritisChronic nodular Rheumatoid Arthritis
SpleenomegalySpleenomegaly
NeutropeniaNeutropenia
Extraarticular InvolvementExtraarticular Involvement

14. RespiratoryRespiratory- pleural effusion, pneumonitis , - pleural effusion, pneumonitis ,
pleuro-pulmonary nodules, ILDpleuro-pulmonary nodules, ILD
CVSCVS-asymptomatic pericarditis , pericardial -asymptomatic pericarditis , pericardial
effusion, cardiomyopathy effusion, cardiomyopathy
Rheumatoid vasculitisRheumatoid vasculitis- mononeuritis multiplex, - mononeuritis multiplex,
cutaneous ulceration, digital gangrene, visceral cutaneous ulceration, digital gangrene, visceral
infarction infarction
CNSCNS- peripheral neuropathy, cord-compression - peripheral neuropathy, cord-compression
from atlantoaxial/midcervical spine subluxation, from atlantoaxial/midcervical spine subluxation,
entrapment neuropathiesentrapment neuropathies
EYEEYE- kerato cunjunctivitis sicca, episcleritis, - kerato cunjunctivitis sicca, episcleritis,
scleritisscleritis

15. Rheumatoid noduleRheumatoid nodule

16. Laboratory investigations in RALaboratory investigations in RA
CBC- TLC, DLC, Hb, ESR & GBPCBC- TLC, DLC, Hb, ESR & GBP
Acute phase reactantsAcute phase reactants
Rheumatoid Factor (RF)Rheumatoid Factor (RF)
Anti- CCP antibodiesAnti- CCP antibodies

17. Rheumatoid Factor (RF)Rheumatoid Factor (RF)
Antibodies that recognize Fc portion of IgGAntibodies that recognize Fc portion of IgG
Can be IgM , IgG , IgACan be IgM , IgG , IgA
85% of patients with RA over the first 2 years become RF+85% of patients with RA over the first 2 years become RF+
•A negative RF may be repeated 4-6 monthly for the first two year of A negative RF may be repeated 4-6 monthly for the first two year of
disease, since some patients may take 18-24 months to become disease, since some patients may take 18-24 months to become
seropositive.seropositive.
• PROGNISTIC VALUEPROGNISTIC VALUE - Patients with high titres of RF, in general, - Patients with high titres of RF, in general,
tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR
MANIFESTATION.MANIFESTATION.

18. Causes of positive test for RFCauses of positive test for RF
Rheumatoid arthritisRheumatoid arthritis
Sjogrens syndromeSjogrens syndrome
Vasculitis such as polyarteritis nodosaVasculitis such as polyarteritis nodosa
SarcoidosisSarcoidosis
Systemic lupus erythematosusSystemic lupus erythematosus
CryoglobulinemiaCryoglobulinemia
Chronic liver diseaseChronic liver disease
Infections- tuberculosis , bacterial endocarditis, infectious Infections- tuberculosis , bacterial endocarditis, infectious
mononucleosis, leprosy, syphilis, leishmaniasis.mononucleosis, leprosy, syphilis, leishmaniasis.
MalignanciesMalignancies
Old age(5% women aged above 60)Old age(5% women aged above 60)

19. Anti-CCPAnti-CCP
IgG against synovial membrane peptides IgG against synovial membrane peptides
damaged via inflammationdamaged via inflammation
Sensitivity (65%) & Specificity (95%)Sensitivity (65%) & Specificity (95%)
Both diagnostic & prognostic valueBoth diagnostic & prognostic value
Predictive of Erosive DiseasePredictive of Erosive Disease
Disease severityDisease severity
Radiologic progressionRadiologic progression
Poor functional outcomesPoor functional outcomes

20. Acute Phase Reactants Acute Phase Reactants
Positive acute phase reactants (­)Negative acute phase reactants (¯)
Mild elevations
– Ceruloplasmin
– Complement C
3
& C
4
Moderate elevations
– Haptoglobulin
– Fibrinogen (ESR)
– a
1
– acid glycoprotein
– a
1
– proteinase inhibitor
Marked elevations
– C-reactive protein (CRP)
– Serum amyloid A protein
– Albumin
– Transferrin

21. Elevated APRs( ESR, CRP )Elevated APRs( ESR, CRP )
ThrombocytosisThrombocytosis
LeukocytosisLeukocytosis
ANAANA
30-40%30-40%
Inflammatory synovial fluidInflammatory synovial fluid
HypoalbuminemiaHypoalbuminemia

22. Radiographic FeaturesRadiographic Features
Peri-articular osteopeniaPeri-articular osteopenia
Uniform symmetric joint space narrowingUniform symmetric joint space narrowing
Marginal subchondral erosionsMarginal subchondral erosions
 Joint Subluxations Joint Subluxations
Joint destructionJoint destruction
CollapseCollapse
Ultrasound Ultrasound detects early soft tissue lesions.detects early soft tissue lesions.
MRI MRI has greatest sensitivity to detect has greatest sensitivity to detect
synovitis and marrow changes.synovitis and marrow changes.

26. Diagnostic CriteriasDiagnostic Criterias

27. ACR Criteria (1987)ACR Criteria (1987)
1.Morning Stiffness ≥1 hour1.Morning Stiffness ≥1 hour
2.Arthritis of ≥ 3 joints observed by physician 2.Arthritis of ≥ 3 joints observed by physician simulteneously-simulteneously-
Rt/Lt-PIP, MCP,wrist, elbow, Rt/Lt-PIP, MCP,wrist, elbow, knee, ankle, MTPknee, ankle, MTP
3.Arthritis of hand joints-PIP,MCP,wrist3.Arthritis of hand joints-PIP,MCP,wrist
4. Symmetric arthritis4. Symmetric arthritis
5. Rheumatoid nodules5. Rheumatoid nodules
6. Positive Rheumatoid Factor6. Positive Rheumatoid Factor
7. Radiographic Erosions or periarticular 7. Radiographic Erosions or periarticular osteopenia in hand or wrist osteopenia in hand or wrist
jointsjoints
Criteria 1-4 must be present for ≥6 wksCriteria 1-4 must be present for ≥6 wks
Must have ≥4 criteria to meet diagnosis of RAMust have ≥4 criteria to meet diagnosis of RA

28. 2010 ACR/EULAR Classification Criteria2010 ACR/EULAR Classification Criteria
a score of ≥6/10 is needed for classification of a patient as having definite RAa score of ≥6/10 is needed for classification of a patient as having definite RA
A. Joint involvement A. Joint involvement
SCORESCORE
1 large joint 1 large joint
00
2−10 large joints 2−10 large joints
1 1−3 small 1 1−3 small
joints (with or without involvement of large joints) 2joints (with or without involvement of large joints) 2
4−10 small joints (with or without involvement of large joints) 34−10 small joints (with or without involvement of large joints) 3
>10 joints (at least 1 small joint)†† >10 joints (at least 1 small joint)††
55

B. Serology B. Serology (at least 1 test result is needed for classification(at least 1 test result is needed for classification))
Negative RF Negative RF and negative ACPA 0and negative ACPA 0
Low-positive RF Low-positive RF or low-positive ACPA 2or low-positive ACPA 2
High-positive RF High-positive RF or high-positive ACP or high-positive ACP
33
C. Acute-phase reactants C. Acute-phase reactants (at least 1 test result is needed for classification(at least 1 test result is needed for classification))
Normal CRP Normal CRP and normal ESR 0and normal ESR 0
Abnormal CRP Abnormal CRP or normal ESR 1or normal ESR 1
D. Duration of symptomsD. Duration of symptoms
<6 weeks 0<6 weeks 0
≥≥6 weeks 1 6 weeks 1

29. ManagementManagement

30. Goals of managementGoals of management
Focused on relieving pain Focused on relieving pain
Preventing damage/disabilityPreventing damage/disability
Patient education about the diseasePatient education about the disease
Physical Therapy for stretching and range of motion Physical Therapy for stretching and range of motion
exercisesexercises
Occupational Therapy for splints and adaptive Occupational Therapy for splints and adaptive
devicesdevices
Treatment should be started early and should be Treatment should be started early and should be
individualised .individualised .
EARLY AGGRESSIVE TREATEMNTEARLY AGGRESSIVE TREATEMNT

31. Treatment modalities for RATreatment modalities for RA
NSAIDSNSAIDS
SteroidsSteroids
DMARDsDMARDs
Immunosuppressive therapyImmunosuppressive therapy
Biological therapiesBiological therapies
SurgerySurgery

32. NSAIDSNSAIDS
Non-Steroidal anti-inflammatories Non-Steroidal anti-inflammatories
(NSAIDS) / Coxibs for symptom control(NSAIDS) / Coxibs for symptom control
1)1)Reduce pain and swelling by inhibiting COXReduce pain and swelling by inhibiting COX
2)2)Do not alter course of the disease. Do not alter course of the disease.
3)3)Chronic use should be minimised.Chronic use should be minimised.
4)4)Most common side effect related to GI tract.Most common side effect related to GI tract.

33. Corticosteroids in RACorticosteroids in RA
Corticosteroids , both systemic and intra-articular are Corticosteroids , both systemic and intra-articular are
important adjuncts in management of RA.important adjuncts in management of RA.
Indications for systemic steroids are:-Indications for systemic steroids are:-
1.1.For treatment of rheumatoid flares.For treatment of rheumatoid flares.
2.2.For extra-articular RA like rheumatoid vasculitis and For extra-articular RA like rheumatoid vasculitis and
interstitial lung disease.interstitial lung disease.
3.3.As As bridge therapy bridge therapy for 6-8 weeks before the action of for 6-8 weeks before the action of
DMARDs begin.DMARDs begin.
4.4.Maintainence dose of 10mg or less of predinisolone daily Maintainence dose of 10mg or less of predinisolone daily
in patients with active RA.in patients with active RA.
5.5.Sometimes in pregnancy when other DMARDs cannot be Sometimes in pregnancy when other DMARDs cannot be
used. used.

34. Disease Modifying Anti-rheumatic AgentsDisease Modifying Anti-rheumatic Agents
Drugs that actually alter the disease course .Drugs that actually alter the disease course .
Should be used as soon as diagnosis is made.Should be used as soon as diagnosis is made.
Appearance of benefit delayed for weeks to Appearance of benefit delayed for weeks to
months.months.
NSAIDS must be continued with them until true NSAIDS must be continued with them until true
remission is achieved .remission is achieved .
Induction of true remission is unusual .Induction of true remission is unusual .

35. DMARDsDMARDs
Commonly used Less commonly used
Methotrexate Chloroquine
Hydroxychloroquine Gold(parenteral &oral)
Sulphasalazine CyclosporineA
Leflunomide D-penicillamine/bucillamine
Minocycline/Doxycycline
Levamisole
Azathioprine,cyclophosphamide,
chlorambucil

36. Clinical information about DMARDsClinical information about DMARDs
NAME DOSE SIDE EFFECTS MONITORING ONSET OF
ACTION
1)Hydroxycloro
quine
200mg twice daily
x 3 months, then
once daily
Skin pigmentation
, retinopahy
,nausea, psychosis,
myopathy
Fundoscopy&
perimetry yearly
2-4 months
2) Methotrexate7.5-25 mg once a
week orally,s/c or
i/m
GI upset,
hepatotoxicity,
Bone marrow
suppression,
pulmonary
fibrosis
Blood counts,LFT
6-8 weekly,Chest
x-ray annually,
urea/creatinine 3
monthly;
Liver biopsy
1-2 months

37. Clinical information about DMARDs contnd..Clinical information about DMARDs contnd..
NAME DOSE SIDE EFFECTS MONITORING ONSET OF
ACTION
3)Sulphasala- 2gm daily p.oRash,
myelosuppression,
may reduce sperm
count
Blood counts
,LFT 6-8 weekly
1-2 months
4)LeflunomideLoading 100 mg
daily x 3 days,
then 10-20 mg
daily p.o
Nausea,diarrhoea,
alopecia,
hepatotoxicity
LFT 6-8 weekly1-2 months
zine

38. When to start DMARDs?When to start DMARDs?
DMARDs are indicated in all patients with RA who DMARDs are indicated in all patients with RA who
continue to have active disease even after 3 months continue to have active disease even after 3 months
of NSAIDS use.of NSAIDS use.
The period of 3 months is arbitary & has been The period of 3 months is arbitary & has been
chosen since a small percentage of patients may go in chosen since a small percentage of patients may go in
spontaneous remission.spontaneous remission.
The vast majority , however , need DMARDs and The vast majority , however , need DMARDs and
many rheumatologists start DMARDs from many rheumatologists start DMARDs from Day Day 1.1.

39. How to select DMARDs?How to select DMARDs?
There are no strict guidelines about which DMARDs There are no strict guidelines about which DMARDs
to start first in an individual.to start first in an individual.
Methotrexate has rapid onset of action than other Methotrexate has rapid onset of action than other
DMARD.DMARD.
Taking in account patient tolerance, cost Taking in account patient tolerance, cost
considerations and ease of once weekly oral considerations and ease of once weekly oral
administration administration METHOTREXATEMETHOTREXATE is the is the DMARD DMARD
of choiceof choice, most widely prescribed in the world., most widely prescribed in the world.

40. Should DMARDs be used singly or Should DMARDs be used singly or
in combination?in combination?
Since single DMARD therapy (in conjunction with Since single DMARD therapy (in conjunction with
NSAIDS) is often only modestly effective , combination NSAIDS) is often only modestly effective , combination
therapy has an inherent appeal.therapy has an inherent appeal.
DMARD combination is specially effective if they include DMARD combination is specially effective if they include
methotrexate methotrexate as an anchor drug.as an anchor drug.
Combination of methotrexate with leflunamide Combination of methotrexate with leflunamide are are
synergestic since there mode of action is different.synergestic since there mode of action is different.

41. Limitations of conventional DMARDsLimitations of conventional DMARDs
1)1)The onset of action takes several months.The onset of action takes several months.
2)2)The remission induced in many cases is partial.The remission induced in many cases is partial.
3)3)There may be substantial toxicity which There may be substantial toxicity which
requires careful monitoring.requires careful monitoring.
4)4)DMARDs have a tendency to lose effectiveness DMARDs have a tendency to lose effectiveness
with time-(slip out).with time-(slip out).
These drawbacks have made researchers look These drawbacks have made researchers look
for alternative treatment strategies for RA- for alternative treatment strategies for RA- The The
Biologic Response Modifiers.Biologic Response Modifiers.

42. ImmunosuppresiveImmunosuppresive therapy therapy
Agent Usual dose/route Side effects
Azathioprine 50-150 mg orally GI side effects ,
myelosuppression, infection,
Cyclosporin A 3-5 mg/kg/day Nephrotoxic , hypertension ,
hyperkalemia
Cyclophosphamide50 -150 mg orally Myelosuppression , gonadal
toxicity ,hemorrhagic cystitis ,
bladder cancer
.
.

43. BIOLOGICS IN RABIOLOGICS IN RA
Cytokines such as TNF-Cytokines such as TNF-αα ,IL-1,IL-10 etc. are key ,IL-1,IL-10 etc. are key
mediators of immune function in RA and have mediators of immune function in RA and have
been major targets of therapeutic manipulations in been major targets of therapeutic manipulations in
RA.RA.
Of the various cytokines,TNF-Of the various cytokines,TNF-αα has attaracted has attaracted
maximum attention.maximum attention.
Various biologicals approved in RA are:-Various biologicals approved in RA are:-
1)1)Anti TNF agents : Anti TNF agents : Infliximab Etanercept AdalimumabInfliximab Etanercept Adalimumab
2)2) IL-1 receptor antagonist : IL-1 receptor antagonist : AnakinraAnakinra
3)3) IL-6 receptor antagonist : IL-6 receptor antagonist : TocilizumabTocilizumab
4)4)Anti CD20 antibody : Anti CD20 antibody : RituximabRituximab
5)5)T cell costimulatory inhibitor : T cell costimulatory inhibitor : AbataceptAbatacept

44. Agent Usual dose/route Side effects Contraindications
Infliximab
(Anti-TNF)
3 mg/kg i.v infusion at
wks 0,2 and 6 followed
by maintainence dosing
every 8 wks
Has to be combined
with MTX.
Infusion reactions,
increased risk of
infection, reactivation
of TB ,etc
Active
infections,uncontrolled
DM,surgery(with hold for 2
wks post op)
Etanercept
(Anti-TNF)
Active
infections,uncontrolled
DM,surgery(with hold for 2
wks post op)
Adalimumab
(Anti-TNF)
40 mg s/c every 2
wks(fornightly)
May be given with MTX
or as monotherapy
Same as that of
infliximab
Active infections
.
25 mg s/c twice a wk
May be given with MTX
or as monotherapy.
Injection site
reaction,URTI ,
reactivation of
TB,development of
ANA,exacerbation
of demyelenating
disease.

45. Abatacept
(CTLA-4-IgG1
Fusion protien)
Co-stimulation
inhibitor
10 mg/ kg body wt.
At 0, 2 , 4 wks &
then 4wkly
Infections, infusion
reactions
Active infection
TB
Concomittant with other
anti-TNF-α
Rituximab
(Anti CD20)
1000 mg iv at
0, 2, 24 wks
Infusion reactions
Infections
Same as above
Tocilizumab
( Anti IL-6)
4-8 mg/kg
8 mg/kg iv monthly
Infections, infusion
reactions,dyslipidemia
Active infections
Agent Usual
dose/route
Side effects
.
Anakinra100 mg s/c once
daily
May be given with
MTX or as
monotherapy.
Injection site
pain,infections,
neutropenia
Active infections
Contraindications
(Anti-IL-1)

46. 2012 ACR Update2012 ACR Update

48. How to monitor Tt in RA?How to monitor Tt in RA?
Disease activity is assesed by several parameters…Disease activity is assesed by several parameters…
duration of morning stiffness,tender joint count,swollen duration of morning stiffness,tender joint count,swollen
joint count,observer global assessment,patient global joint count,observer global assessment,patient global
assessment,visual analogue scale for pain,health assessment,visual analogue scale for pain,health
assessment questionnaire,ESR,NSAID pill count,DAS assessment questionnaire,ESR,NSAID pill count,DAS
score etc..score etc..
•Patient on MTX,SSZ or leflunamide show clinical Patient on MTX,SSZ or leflunamide show clinical
improvement in 6-8 wks.improvement in 6-8 wks.
•Patient should be observed for 6 months before Patient should be observed for 6 months before
declaring a DMARD ineffective. declaring a DMARD ineffective.

49. How long should Tt. be continued?How long should Tt. be continued?
Once remission is achieved , maintenance dose for Once remission is achieved , maintenance dose for
long period is recommended.long period is recommended.
Relapse occurs in 3-5 months (1-2 months in case of Relapse occurs in 3-5 months (1-2 months in case of
MTX) if drug is discontinued in most instances.MTX) if drug is discontinued in most instances.
DMARDs are discontinued by patients because of DMARDs are discontinued by patients because of
toxicitytoxicity or or secondary failuresecondary failure(common after 1-2 yrs) (common after 1-2 yrs)
and such patients might have to shift over different and such patients might have to shift over different
DMARDs over 5-10 yrs.DMARDs over 5-10 yrs.
Disease flare may require escalation of DMARD dose Disease flare may require escalation of DMARD dose
with short course of steroids. with short course of steroids.

50. Surgical ApproachesSurgical Approaches
Synovectomy is ordinarily not recommended for patients with Synovectomy is ordinarily not recommended for patients with
rheumatoid arthritis, primarily because relief is only transient.rheumatoid arthritis, primarily because relief is only transient.
However, an exception is synovectomy of the wrist, which is However, an exception is synovectomy of the wrist, which is
recommended if intense synovitis is persistent despite medical recommended if intense synovitis is persistent despite medical
treatment over 6 to 12 months. Persistent synovitis involving treatment over 6 to 12 months. Persistent synovitis involving
the dorsal compartments of the wrist can lead to extensor the dorsal compartments of the wrist can lead to extensor
tendon sheath rupture resulting in severe disability of hand tendon sheath rupture resulting in severe disability of hand
function.function.
Total joint arthroplasties , particularly of the knee, hip, wrist, Total joint arthroplasties , particularly of the knee, hip, wrist,
and elbow, are highly successful.and elbow, are highly successful.
 Other operations include release of nerve entrapments (e.g., Other operations include release of nerve entrapments (e.g.,
carpal tunnel syndrome), arthroscopic procedures, and, carpal tunnel syndrome), arthroscopic procedures, and,
occasionally, removal of a symptomatic rheumatoid nodule.occasionally, removal of a symptomatic rheumatoid nodule.

51. Thank you.