Overview of Rheumatoid Overview of Rheumatoid Arthritis Arthritis

Naureen Mirza, MD Naureen Mirza, MD

May 10, 2010 May 10, 2010

Epidemiology Epidemiology

An annual incidence of approximately 0.2 per An annual incidence of approximately 0.2 per 1000 in males and 0.4 per 1000 in females 1000 in males and 0.4 per 1000 in females A prevalence of 0.5-1% is reported in diverse A prevalence of 0.5-1% is reported in diverse populations worldwidepopulations worldwideTwin studies show the disease to have a Twin studies show the disease to have a heritability of 60%heritability of 60%Hormonal and reproductive factors contribute to Hormonal and reproductive factors contribute to the female excess and paritythe female excess and parityObesity, smoking, coffee consumption, and prior Obesity, smoking, coffee consumption, and prior blood transfusion have also been identified as blood transfusion have also been identified as potential risk factorspotential risk factors

1. Morning stiffness1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 Morning stiffness in and around the joints, lasting at least 1 h before maximal improvementh before maximal improvement

2. Arthritis in three or 2. Arthritis in three or more joint areasmore joint areas

Soft tissue swelling or fluid (not bony overgrowth) observed Soft tissue swelling or fluid (not bony overgrowth) observed by a physician, present simultaneously for at least 6 by a physician, present simultaneously for at least 6 weeksweeks

3. Arthritis of hand 3. Arthritis of hand jointsjoints

Swelling of wrist, MCP or PIP joints for at least 6 weeksSwelling of wrist, MCP or PIP joints for at least 6 weeks

4. Symmetric arthritis4. Symmetric arthritis Simultaneous involvement of the same joint areas (defined Simultaneous involvement of the same joint areas (defined in 2) on both sides of the body (bilateral involvement of in 2) on both sides of the body (bilateral involvement of PIP, MCP or MTP joints is acceptable without absolute PIP, MCP or MTP joints is acceptable without absolute symmetry) for at least 6 weekssymmetry) for at least 6 weeks

5. Rheumatoid nodules5. Rheumatoid nodules Subcutaneous nodules over bony prominences, extensor Subcutaneous nodules over bony prominences, extensor surfaces or in juxta-articular regions, observed by a surfaces or in juxta-articular regions, observed by a physicianphysician

6. Rheumatoid factor6. Rheumatoid factor Detected by a method positive in fewer than 5% of normal Detected by a method positive in fewer than 5% of normal controlscontrols

7. Radiographic 7. Radiographic changeschanges

Typical of RA on posteroanterior hand and wrist Typical of RA on posteroanterior hand and wrist radiographs; it must include erosions or unequivocal radiographs; it must include erosions or unequivocal bony decalcification localized in or most marked bony decalcification localized in or most marked adjacent to the involved joints (OA changes alone do adjacent to the involved joints (OA changes alone do not qualify)not qualify)

New criteria for the diagnosis of RA New criteria for the diagnosis of RA

Joint involvement Joint involvement 1 med-lg joint1 med-lg joint

00

2-10 Med-Lg joints2-10 Med-Lg joints 11

1-3 small joints1-3 small joints 22

4-10 small joints4-10 small joints 33

>10 small joints>10 small joints 55

SerologySerologyNeither RF or Anti ccp Neither RF or Anti ccp

00

At least one + with low titer At least one + with low titer 22

Atleast one with high titer Atleast one with high titer 33

Duration of synovitis Duration of synovitis <6 weeks <6 weeks

00

>6 weeks >6 weeks 11

Acute phase reactantsAcute phase reactantsNeither CRP or ESR abnormal Neither CRP or ESR abnormal

00

Abnormal CRP or abnormal ESRAbnormal CRP or abnormal ESR 11

Score >Score >=6 indicates =6 indicates “definite RA”“definite RA”

History In RAHistory In RA Chronological account of illness from the onsetChronological account of illness from the onset

Onset: acute or gradual, with detailsOnset: acute or gradual, with details

Location of pain (local or referred): precise anatomy, Location of pain (local or referred): precise anatomy, presence/absence of swellingpresence/absence of swelling

Pattern of joint involvement: axial, peripheral, symmetricPattern of joint involvement: axial, peripheral, symmetric

Type of pain: quality and characterType of pain: quality and character

Severity: pain threshold effects, interference with activities of daily Severity: pain threshold effects, interference with activities of daily living, range of joint movementliving, range of joint movement

Radiation of pain: local or deep referred typeRadiation of pain: local or deep referred type

Clinical course: duration, frequency, periodicity, persistenceClinical course: duration, frequency, periodicity, persistence

Modifying factors: aggravating, relieving, medication effectsModifying factors: aggravating, relieving, medication effects

Associated symptoms: fatigue, other systemic symptomsAssociated symptoms: fatigue, other systemic symptoms

Duration of morning stiffness: non-restorative sleep patternDuration of morning stiffness: non-restorative sleep pattern

Present status: regional review of joints, extra-articular features, Present status: regional review of joints, extra-articular features, functional class, activities of daily living, psychologic statefunctional class, activities of daily living, psychologic state

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Extra-articular featuresExtra-articular features

Record presence of nodules, Raynaud's phenomenon, Record presence of nodules, Raynaud's phenomenon, digital infarcts, episcleritis, peripheral neuropathy, palmar digital infarcts, episcleritis, peripheral neuropathy, palmar erythema, leg ulcerserythema, leg ulcers

Note tendon sheath involvement, or tendon nodules, Note tendon sheath involvement, or tendon nodules, subluxation or rupturesubluxation or rupture

Check for anemia, splenomegaly, leukopenia, pleuritis or Check for anemia, splenomegaly, leukopenia, pleuritis or pericarditis, the sicca syndrome or renal involvementpericarditis, the sicca syndrome or renal involvement

Articular: measures of inflammatory activityArticular: measures of inflammatory activity

Check for tenderness, synovial effusion, grip strengthCheck for tenderness, synovial effusion, grip strength

Articular: measures of destruction and deformityArticular: measures of destruction and deformity

Check for lax collaterals, subluxation, malalignment, Check for lax collaterals, subluxation, malalignment, metatarsal prolapse, hammer toes and bone-on-bone metatarsal prolapse, hammer toes and bone-on-bone crepituscrepitus

Examination Examination

Articular manifestations Articular manifestations

Arthritis : Joint swelling, tenderness, Arthritis : Joint swelling, tenderness, warmth, limitation of motion, pain in range warmth, limitation of motion, pain in range of motion, of motion,

Morning stiffness Morning stiffness

Muscle atrophy Muscle atrophy

Chronic deformities Chronic deformities

Ankylosis of the joint Ankylosis of the joint

Rheumatoid nodules Rheumatoid nodules 20% of RA patients with +tests for blood 20% of RA patients with +tests for blood

rheumatoid factors and rarely in RF – rheumatoid factors and rarely in RF –

most commonly on pressure areas most commonly on pressure areas

central fibrinoid necrosis with surrounding central fibrinoid necrosis with surrounding fibroblasts fibroblasts

May occur in any organs as well May occur in any organs as well

May regress with treatment , but has been May regress with treatment , but has been reported to increase with Methotrexate usereported to increase with Methotrexate use

believed to occur as a result of small vessel believed to occur as a result of small vessel vasculitis with fibrinoid necrosis, which vasculitis with fibrinoid necrosis, which forms the center of the nodule, and forms the center of the nodule, and surrounding fibroblastic proliferation surrounding fibroblastic proliferation

Histology of rheumatoid noduleHistology of rheumatoid nodule

Rheumatoid nodule with granulomatous Rheumatoid nodule with granulomatous transformation.transformation. There is prominent central fibrinoid There is prominent central fibrinoid necrosis, with surrounding palisading histiocytes and an necrosis, with surrounding palisading histiocytes and an outer layer of chronic fibrosing connective tissue with outer layer of chronic fibrosing connective tissue with inflammatory cells including lymphocytes and fibroblasts. inflammatory cells including lymphocytes and fibroblasts.

Hematologic abnormalitiesHematologic abnormalities AnemiaAnemia

ThrombocytosisThrombocytosis

Thrombocytopenia ( rare ) Thrombocytopenia ( rare )

Eosinophilia(esp related to gold) Eosinophilia(esp related to gold)

Lymphadenopathy ( concomitant Sjogren’s syndrome may Lymphadenopathy ( concomitant Sjogren’s syndrome may increase the risk of Lymphoma) increase the risk of Lymphoma)

Splenomegaly ( clinically in 5-10 % with active RA and upto Splenomegaly ( clinically in 5-10 % with active RA and upto 58% by radionuclide scanning) 58% by radionuclide scanning)

Felty’s syndromeFelty’s syndrome RA in combination with splenomegaly and leukopeniaRA in combination with splenomegaly and leukopenia long-standing, seropositive, nodular, deforming RA long-standing, seropositive, nodular, deforming RA

33%33% do not have active synovitis do not have active synovitis

Lower extremity ulcers, hyperpigmentation, bacterial Lower extremity ulcers, hyperpigmentation, bacterial infections, ANAs, Also may have thrombocytopenia, infections, ANAs, Also may have thrombocytopenia, hypocomplementemia, hypocomplementemia,

an increased risk for the development of lymphomasan increased risk for the development of lymphomas

NeutropeniaNeutropeniaAnemiaAnemiaThrombocytopeniaThrombocytopeniaSplenomegaly Splenomegaly large granular large granular lymphocytes in these lymphocytes in these patients represent patients represent in in vivovivo activated activated cytotoxic T cells and cytotoxic T cells and clonality is present. clonality is present.

Large granular lymphocytes

Pulmonary manifestations Pulmonary manifestations

Pulmonary nodules Pulmonary nodules

Pleural effusions (50%)Pleural effusions (50%)

Caplan’s syndrome Caplan’s syndrome

Diffuse interstitial Diffuse interstitial pulmonary fibrosis (28%)pulmonary fibrosis (28%)

Bronchiolitis obliterans Bronchiolitis obliterans organizing pneumonia organizing pneumonia (BOOP)(BOOP)

Obliterative bronchiolitis Obliterative bronchiolitis

Drug induced Drug induced

Isolated pul. Arteritis (rare)Isolated pul. Arteritis (rare)

Pulmonary hypertension Pulmonary hypertension (rare) (rare)

Airway obstruction (38%)Airway obstruction (38%)

Caplan’s Caplan’s syndrome syndrome

Cardiac disease in RACardiac disease in RAPericarditis (50%)Pericarditis (50%)

Premature cardiovascular diseasePremature cardiovascular disease ((TNF-α is produced by cardiac TNF-α is produced by cardiac

myocytes and resident macrophages during cardiac stress and may help trigger and myocytes and resident macrophages during cardiac stress and may help trigger and perpetuate atherosclerosis)perpetuate atherosclerosis)

Myocardial and endocardial disease Myocardial and endocardial disease (clinically insignificant)(clinically insignificant)

Coronary arteritis Coronary arteritis

Valvular abnormalities Valvular abnormalities

Rheumatoid nodule in the aortic valve cuspRheumatoid nodule in the aortic valve cusp

Ocular InvolvementOcular Involvement Most common : Keratoconjuctivitis sicca (10-35%) Most common : Keratoconjuctivitis sicca (10-35%)

EpiscleritisEpiscleritis : nodular or diffuse, appears acutely and : nodular or diffuse, appears acutely and causes eye redness and paincauses eye redness and pain

Scleritis is less common than episcleritis, but is more obviously correlatedwith vasculitis, long-standing arthritis and active joint inflammation. Untreated scleritis may progress to scleromalacia

ScleromalaciaScleromalacia

Other uncommon manifestation of RA in the Other uncommon manifestation of RA in the

eyeeye UveitisUveitis

Episcleral nodulosis Episcleral nodulosis

Corneal filamentary keratitisCorneal filamentary keratitis

Peripheral ulcerative keratitisPeripheral ulcerative keratitis

Retinal detachments Retinal detachments

Macular edemaMacular edema

Glucocorticoids, Gold and Chloroquine Glucocorticoids, Gold and Chloroquine

Brown's syndrome, which is defined as diplopia upon Brown's syndrome, which is defined as diplopia upon upward and inward gaze and is believed to be the result of upward and inward gaze and is believed to be the result of inflammation and thickening of the superior tendons, and inflammation and thickening of the superior tendons, and

optic neuritisoptic neuritis

Neurological manifestationsNeurological manifestationsNerve compressionsNerve compressions

(Carpal tunnel, tarsal tunnel, atlantoaxial subluxation, (Carpal tunnel, tarsal tunnel, atlantoaxial subluxation, subaxial c-spine involvement, extradural nodules)subaxial c-spine involvement, extradural nodules)

Stroke, seizure, hemorrhage, encephalopathy and Stroke, seizure, hemorrhage, encephalopathy and meningitis as a result of cerebral vasculitis, amyloidosis or meningitis as a result of cerebral vasculitis, amyloidosis or rheumatoid nodules, or both, in the dura and choroid rheumatoid nodules, or both, in the dura and choroid

plexus of the brainplexus of the brain

Most patients have long-standing RA with other extra-Most patients have long-standing RA with other extra-

articular diseasearticular disease

Renal InvolvementRenal Involvement

The kidneys are usually spared in RA, although a low-grade The kidneys are usually spared in RA, although a low-grade membranous nephropathy, glomerulitis, vasculitis and secondary membranous nephropathy, glomerulitis, vasculitis and secondary reactive amyloidosis have all been described reactive amyloidosis have all been described

Renal abnormalities frequently result from the agents used in Renal abnormalities frequently result from the agents used in treating RA, notably gold, D-penicillamine, cyclosporin and NSAIDs, treating RA, notably gold, D-penicillamine, cyclosporin and NSAIDs, and usually manifest as membranous nephropathy and acute and usually manifest as membranous nephropathy and acute interstitial nephritis, often the result of a drug hypersensitivity interstitial nephritis, often the result of a drug hypersensitivity

reactionreaction

AmyloidosisAmyloidosis

0.7-5.8% of patients with RA 0.7-5.8% of patients with RA

Virtually every organ system may be involved in the secondary Virtually every organ system may be involved in the secondary amyloidosis that complicates RA, including the heart, kidney, liver, amyloidosis that complicates RA, including the heart, kidney, liver, spleen, intestines and skin. spleen, intestines and skin.

Renal manifestations of amyloidosis are the most common ones Renal manifestations of amyloidosis are the most common ones

Poor prognosis : 4-year survival rates of about 58% are reported Poor prognosis : 4-year survival rates of about 58% are reported

Rheumatoid vasculitisRheumatoid vasculitis Systemic vasculitis uncommon, usually with longstanding, Systemic vasculitis uncommon, usually with longstanding, poorly controlled disease poorly controlled disease

pANCA pANCA

More in patient’s with felty’s More in patient’s with felty’s

Skin: Nail fold infarcts . Leg ulcers, gangrene Skin: Nail fold infarcts . Leg ulcers, gangrene

Baker's popliteal cystBaker's popliteal cyst

Diagnosis Diagnosis

CBCCBC

RF RF

Anti ccp Anti ccp

ESRESR

X rays of affected jointsX rays of affected joints

Musculoskeletal ultrasoundMusculoskeletal ultrasound

MRI MRI

Additional testing Additional testing

PPD PPD

Chest X ray Chest X ray

Hep B and C serologies Hep B and C serologies

ANA ANA

Joint aspirationJoint aspiration

Synovial biopsy Synovial biopsy

Lyme serology Lyme serology

Treatment optionsTreatment options

NSAIDs NSAIDs

Hydroxychloroquine Hydroxychloroquine

Steroids, systemic and intra articular Steroids, systemic and intra articular

Methotrexate Methotrexate

Sulfasalazine Sulfasalazine

LeflunomideLeflunomide

More aggressive disease More aggressive disease

TNF inhibitorsTNF inhibitors

Abatacept (CTLA 4 IgG)Abatacept (CTLA 4 IgG)

Rituximab (Anti CD 20) Rituximab (Anti CD 20)