Rheumatoid Arthritis Pc Set DMARD.120109

8/3/2019 Rheumatoid Arthritis Pc Set DMARD.120109

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Definition and EpidemiologyRheumatoid Arthritis (RA) is a chronic, multisystem disease of unknown etiology characterized bypersistent, systemic inflammation and erosion of articular and extra-articular tissue and the presence ofcirculating IgG antibodies (rheumatoid factors [RF]).

Primarily affects synovial joints but can also affect cardiac, nervous, reticuloendothelial, pulmonaryand integumentary systems.

Association with HLA- D4, DR4 and DRB1 has been noted

Prevalence: 1% of adults; female to male ratio = 3 : 1; onset occurs between 35 and 50 years of age

American College of Rheumatology RA Diagnosis CriteriaCriteria Definition

Diagnosis of RA requires 4 of 7 of the criteria

1 Morning stiffness In and around the joints, lasting at least 1 hour before maximal

improvement, lasting >6 weeks; often initial complaint2 Arthritis of 3 or more

jointsAt least 3 joint areas* simultaneously; soft-tissue swelling or effusionlasting >6 weeks

3 Arthritis of hand joints At least 1 area swollen in wrist, MCP or PIP joints, lasting >6 weeks

4 Symmetric arthritis Simultaneous involvement of at least 1 area* on both sides of thebody lasting >6 weeks

5 Rheumatoid nodules Subcutaneous nodules over bony prominences, extensor surfaces, orjuxta-articular regions, as observed by a physician

6 Rheumatoid factor (RF) High RF titer as assessed by any method for which the results have

been positive in < 5% of healthy control subjects7 Radiographic changes Erosions or bone decalcification in/around the involved joints

* left or right MCP joints, PIP joints, wrist, elbow, shoulder, hip, knee, ankle, MTP joints

Clinical ManifestationsSymptoms

Joint pain and swelling Stiffness following inactivity Systemic flu-like features

Abnormal fatigue Lethargy, malaise Mild fever

Weight loss Night sweats Myalgia

Articular Features Extra-articular FeaturesJoint pain, tenderness,swelling: MCP, PIP, MTP, wrist Hip, shoulder, knee, ankle

Cutaneous: Subcutaneous rheumatoid nodules over bonyprominences, vasculitis

Pulmonary: Pulmonary nodules, interstitial fibrosis, pleuraleffusions, pleuritis, bronchiolitis

Pannus formation Renal and GI: Not directly affected by RA; effects secondary to meds

Ankylosis, decreased mobility Ocular: Keratoconjunctivitis sicca, episcleritis, corneal melt;RA is often associated with Sjgren syndromeInstability, loss of function

Characteristic deformities:

Ulnar deviation Swan-neck deformity Boutonnire deformity Hammer toe

Cardiac: Pericarditis, pericardial effusion, myocardial infarction,

myocarditis, conduction defects, arteritis, aortitis, endocarditis,cardiomyopathy, aortic regurgitation

Neurologic: Mononeuritis multiplex, entrapment neuropathy, distalsensory neuropathy, cervical myelopathy

Atlantoaxial subluxation canlead to spinal cord compression

Hematologic: Anemia, lymphoma, leukemia

Other: Myositis, amyloidosis, osteoporosis

Disease Activity Measurement1

Disease Activity Score Score Range Low Activity Mod. Activity High Activity

Disease Activity Score in 28 joints 09.4 [ 3.2 > 3.2 and [ 5.1 > 5.1

Simplified Disease Activity Index 0.186.0 [ 11 > 11 and [ 26 > 26

Clinical Disease Activity Index 076.0 [ 10 > 10 and [ 22 > 22

RA Disease Activity Index 010 < 2.2 m 2.2 and [ 4.9 > 4.9

PAS or PASII 010 < 1.9 m 1.9 and [ 5.3 > 5.3

Routine Assessment Patient Index Data 030 < 6 m 6 and [ 12 > 121 2008 American College of Rheumatology DMARD RA Treatment Guidelines

Adverse Prognostic Features in Early RA Risk Factors Many active joints, nodules, and erosions

High ESR, CRP, anti-CCP Abs1 Positive for RF Early erosions determined by radiography Male sex, advanced age

Female

Advanced age Exposure to infection Heredity (specific genes) Long-time smoker

1 CRP = ESR = erythrocyte sedimentation rate, C-reactive protein, anti-CCP Abs = anti-cyclic citrullinated peptide antibodies

2009 Brm Bruckmeier Publishing LLC .

Rheumatoid Arthritis pocketcard Set


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Diagnostic WorkupRA Initial Assessment Algorithm

Laboratory Tests Findings

Rheumatoid factor (RF) 70%80% of RA patients; prevalencem with age; also in HCV, Sjgren (70%),SLE (20%-30%), and normals (5%10%); levels not affected by disease activity

Anti-cyclic citrullinatedpeptide Abs (anti-CCP)

90%96% specificity, 47%-76% sensitivity for RA by ELISA; predictive of erosivedisease; anti-CCP Abs plus IgM-RF is best test for RA exclusion

Acute phase reactants ESR and CRP: Not specific to RA but useful in exclusion of noninflammatoryconditions such as osteoarthritis; also used to assess disease activity level

Anti-nuclear Ab (ANA) 30%-40% of RA patients, most commonly those with severe, chronic diseaseHematologic findings Anemia: Chronic disease (mferritin with o transferrin and Fe), iron deficiency

(50%-75% of RA patients, sec. to prednisone-induced gastritis or NSAID-induced ulcers), or macrocytic (may be caused by low folic acid or vit B12)

Leukocytosis: May be directly caused by RA or by glucocorticoids Thrombocytosis: Secondary to inflammatory state Hypoalbuminemia: Due to increased catabolic state

Synovial fluid analysis Inflammatory findings: WBC count > 2000/L, o glucose, C3, and C4, nl. protein

Early Radiologic Features Late Radiologic Features

Soft-tissue swelling Periarticular osteoporosis Periostitis Erosions: periarticular and articular cysts

Narrowed joint spaces Articular surface irregularity Osteoporosis Subluxation and ankylosis Secondary osteoarthritis

Differential Diagnoses Other Rheumatic Diseases

Fibromyalgia Behcet syndrome Vasculitic syndromes (polymyalgia rheumatica,

Churg-Strauss syndrome)

Collagenoses (SLE, scleroderma, Sjogren, poly/dermatomyositis, mixed conn. tissue diseases)

Seronegative spondyloarthropathy (psoriatic,ankylosing spondylitis, inflammatory boweldisease, enteropathic arthritis)

Infectious arthritis: Viral (parvovirus, rubella, HBV) or bacterial (Lyme, borreliosis); monoarticular

Postinf. arthritis: Reactive arthritis/Reiter (h/o urethritis or enteric inf.), rheumatic fever; asymmetric

Medical conditions presenting with arthropathy: Thyroid disease, sarcoidosis, infective endocarditis,diabetic cheiroarthropathy, hemochromatosis, multiple myeloma, paraneoplastic syndromes

Nonrheumatic conditions of bones and joints: Polyarticular gout

Miscellaneous: Sarcoidosis, familial Mediterranean fever, villonodular synovitis

Rheumatoid Arthritis Osteoarthritis Psoriatic Arthritis

Determining the Effectiveness of Therapy Regular assessment of disease activity (eg HAQ, AIMS2, DAS28, ACR20 scores) Monitoring of radiologic progression (eg total Sharp score) Regular baseline laboratory evaluations (eg ESR and CRP level) Determine functional status by questionnaire (eg AIMS or HAQ)

ACR Definition of Improvement ACR Classification Criteria of Functional Status in RA

Class I Fully able to perform usual activities of daily living(self-care, vocational, avocational)*

Class II Able to perform usual self-care and vocationalactivities but limited in avocational activities

Class III Able to perform usual self-care activities but limitedin vocational and avocational activities

Class IV Limited ability to perform usual self-care, vocational,and avocational activities

* Self-care activities include dressing, feeding, bathing, grooming and toileting.Avocational (recreational and/or leisure) and vocational (work, school,homemaking) activities are patient-desired and age- and gender-specific.

Initial arthritis presentation

Number & spread of affected jointsSymptom duration (>6 weeks?)

Pain/Stiffness timing/quality/duration

(RA: activity o sympt.; OA: activity m sympt.)Extrarticular & systemic symptoms

IgM RFanti-CCP Abs

CRP, ESRANA

Addn'l clinical assessment Labs Imaging

X-Ray/MRI: Bone errosions (PIP,MCP manifest early)

MRI: Synovial inflammationMRI more sensitive than X-Ray

PIP

MCP

Wrist

DIP(Heberden)

PIP(Bouchard)

1st CMC

DIP

MCP

PIP

- Patient assessment

- Physician assessment- ESR

- Pain scale

- Functional questionnaire

plus Improvement

in 3 of the following:

Improvement in the joint count

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ACR Classification Criteria for Determining Progression of Rheumatoid Arthritis

Stage Progression

I Early No destructive changes on radiographic examination* Radiographic evidence of osteoporosis may be present

II Moderate Radiographic evidence of osteoporosis, with or without slight subchondral bonedestruction; slight cartilage destruction may be present*

No joint deformities, limitation of joint mobility may be present* Adjacent muscle atrophy

Extra-articular soft-tissue lesions, such as nodules or tenosynovitisIII Severe Radiographic evidence of cartilage and bone destruction in addition to osteoporosis

Joint deformity, such as subluxation or ulnar deviation or hyperextension, withoutfibrous or bony ankylosis*

Extensive muscle atrophy Extra-articular soft-tissue lesions, such as nodules or tenosynovitis

IV Terminal Fibrosis or bony ankylosis* Stage III criteria

*These criteria describe either spontaneous remission or a state of drug-induced disease suppression

ACR Classification Criteria for Determining Clinical Remission of RAFive or more of the criteria should be present for at least 2 consecutive months

Morning stiffness [ 15 minutes No fatigue No pain

No joint tenderness or pain in motion No soft-tissue swelling in joints or tendon

sheaths

TreatmentMedical Treatment

Drug Name Dosage Information Common Adverse Effects

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) (Warning: NSAIDs e MTX levels m e liver toxicity)

Naproxen 250-500 mg PO bid, max 1.5 g/d headache (HA), edema, dizziness, GI upsetIndomethacin 25-50 mg PO bid/tid, max 200 mg/d HA, dizziness, GI distress

Diclofenac 150 mg/d PO in 2-4 div doses nausea, diarrhea, HA, ulcer

Ibuprofen 400-800 mg PO q4-6h, max 3.2 g/d nausea, heartburn, ulcer, rash

Corticosteroids

Prednisolone init 5-7.5 mg/d PO, adjust asnecessary

eg steroid diabetes, truncal obesity,moon facies, corneal ulcer, glaucoma

Triamcinoloneacetonide

intra-articular inj. 10-40 mg per jointdepending on joint size

risk of local infection

Disease-Modifying Antirheumatic Drugs (DMARDs)Azathioprine1 init 1 mg/kg/d PO qd x6-8wks,

thenmby 0.5 mg/kg/d q4wks to2.5 mg/kg/d as necessary

nausea, vomiting, diarrhea,pancytopenia,mrisk of neoplasia, renaland hepatic toxicity, alopecia, rashes

Cyclosporine1 init 2.5 mg/kg/d PO div 12h x8wks,mby 0.5-0.75 mg/kg/d at 8 and 12wks if necessary; max 4 mg/kg/d

HTN, edema, nausea, diarrhea, gumhyperplasia, hirsutism, renal toxicity,tremors, m risk of acute infection

Hydroxychloroquine2 init 310-465 mg PO qd; maint 1/2 init macular damage, nausea, HA

Leflunomide3,4 init 100 mg PO qd x3d

maint 10-20 mg PO qd

myelosuppression, diarrhea, nausea,

headache, teratogenic, hepatic toxicityMethotrexate3,4 7.5-20 mg PO/IV/IM/SC qwk myelosuppression, hep/pulm fibrosis,nausea, diarrhea, teratogen, renal tox

Minocycline 200 mg init dose then 100mg PO q12h dizziness, vertigo, photosensitivity

Sulfasalazine3 init 0.5-1 g PO tid/qidmaint 2 g PO qd div 2 doses; max 3 g/d

nausea, vomiting, diarrhea, HA, photo-sensitivity, reversible oligospermia

Etanercept 25 mg SC biw or 50 mg SC qwk HA, inj site rxn, m inf risk, dizziness

Infliximab (with MTX) 3 mg/kg IV on wks 0, 2, 6, then q4-8wk HA, nausea, diarrhea, m inf risk, m LFT

Adalimumab 40 mg SC q2wk, up to 40 mg SC qwk m inf risk, HA, rash, inj site rxn, mCPK

Anakinra 100 mg/d SC same time dailym

inf risk, neutropenia, HAAbatacept 100kg: 1g IV on wk 0, 2, 4, then q4wkHA, nausea, nasopharyngitis, infection,cough, dizziness, HTN

Rituximab 1 g IV x 2 doses, 2 wks apart + MTX cytopenia, infection, rash, GIsymptoms, fever, HA, PML risk

1The 2008 ACR DMARD guidelines for RA treatment do not recommend use of azathioprine, cyclosporine, and organic gold;cyclophosphamide, D-penicillamine, staph. immunoab. column, and tacrolimus were not considered due tom side effects2Recipients should receive opthalmologic examination at baseline, on resuming therapy, or dose changes3Require monitoring of CBCs, LFTs, and serum creatinine; 4Recipients should be tested for HBV and HCV

Surgical or Other Procedures

Joint surgery Indications: Intractable pain and functional decline due to joint destructionCI: Active systemic infection or articular infection

Ex: (Teno)synovectomy, tendon repair, osteotomy, joint fusion, contracturecorrection, nodule removal, small joint arthroplasty, total joint replacement

Physical therapy Joint protection techniques, heat/cold treatments, splints

Radiosynoviorthesis Administration of radioactive dysprosium-165 ferric hydroxide macroaggregates



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Nonbiologic DMARD Treatment Guidelines

Biologic DMARD Treatment Guidelines

Disease activity

Features ofpoor prognosis

with

with

without

without

low

moderateor high

LEF, MTX, SSZ

HCQ, MIN

MTX + SSZ (+ HCQ)

Disease activity

with

with

without

without

low

moderateor high

LEF, MTX, SSZ

HCQ

Disease activity

with

with

without

without

low

moderateor high

LEF, SSZ, MTX (+ HCQ)

LEF, MTX (+ HCQ)

SSZ

MTX + SSZ + HCQ

LEF, MT, SSZ, MTX + HCQ/LEF,MTX + SSZ (+ HCQ)

SSZ + HCQ

MTX + LEF, MTX + SSZ + HCQ

LEF, MTX, SSZ, MTX+ HCQ/LEF,MTX + SSZ (+ HCQ)

SSZ

Fig 1C: RA > 24 months






LEF = Leflunomide, HCQ = Hydroxychloroquine, MIN = Minocyline, MTX = Methotrexate, SSZ = Sulfasalazine

Fig. 1A: RA < 6 months

Fig 1B: RA 6 to 24 months

anti-TNF

Disease activity

Cost or insurnce

coverage limitations

anti-TNFand MTXHigh for 3-6 mo

Low or moderate < 6 mo

High for < 3 mo

without

with

Non-biologicDMARDs

Fig. 1A

Features of

poor prognosis

without

with

Disease activityFeatures of

poor prognosis

Non-biologicDMARDs

Fig. 1B, 1CModeratewithout

with

Low

High

Disease activity

Non-biologic DMARDsFig. 1B, 1C

Features of

poor prognosis

Non-biologic DMARDsFig. 1B, 1COR

anti-TNF

Abatacept OR anti-TNFOR Rituximab

Low

Moderate or highwithout

with

Use of biologic DMARDs is only recommended after failure of non-biologic DMARD

RA < 6 months

RA 6 to 24 months

RA > 24 months


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Rheumatoid Arthritis Pc Set DMARD.120109