Differential Diagnosis of Inflammatory Arthropathies by PAINWeek

Differential Diagnosis of Inflammatory Arthropathies Ronald J . Rapoport, MD

Disclosure • Grant/Research Support: AstraZeneca, Abbott Laboratories • Speakers Bureau: Abbott laboratories, Amgen Inc., Forest Laboratories, Pfizer Inc., Lilly, UCB Inc.

Learning Objectives • Differentiate between the various types of inflammatory arthritis conditions • Review diagnostic criteria for inflammatory arthritis conditions • Describe treatment options for inflammatory arthritis conditions

Rheumatoid Arthritis

Rheumatoid Arthritis: Epidemiology  Prevalence 1% in varied ethnic groups  Female predominance  Associated with HLA-DR4 and the DR– associated alleles, DRB1*0401 and DRB1*0404  Variable age of onset Harris ED. Clinical features of rheumatoid arthritis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds). Textbook of Rheumatology, 6th edition. Philadelphia: WB Saunders 2001

ACR 1987 Criteria for the Classification of Acute Rheumatoid Arthritis  Need at least four of seven criteria:

– Morning stiffness lasting at least 1 hr – Soft- tissue swelling or fluid in at least 3 joint areas simultaneously – At least one area swollen in a wrist, MCP, or PIP joint* – Symmetric arthritis* – Rheumatoid nodules – Abnormal amounts of serum rheumatoid factor – Erosions or bony decalcification on radiographs of the hand and wrist

*for classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at least 4 or these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.

ACR Preliminary Definition of Improvement in Rheumatoid Arthritis (ACR-20, 50, 70)  Required

– Improvement in tender joint count* – Improvement in swollen joint count*

 Improvement in 3 of the 5 following measures* – Patient pain assessment – Patient global assessment – Physician global assessment – Patient self-assessed disability – Acute-phase reactant (ESR or CRP)

*20%, 50%, or 70%

Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35

Radiographic Features of Rheumatoid Arthritis Periarticular soft-tissue swelling Juxtaarticular osteopenia Marginal erosions Joint-space narrowing Symmetric involvement Deformities in advanced disease Weissman BN, Resnick D, Kaushik S, et al. Imaging. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds). Textbook of Rheumatology, 6th edition. Philadelphia: WB Saunders 2001

Rheumatoid Arthritis: Extensor Tendon Rupture

Rheumatoid Arthritis: Fusiform Swelling, Hand

Rheumatoid Arthritis: Hand

Rheumatoid Arthritis: Subluxation and Muscle Atrophy, Hands

Rheumatoid Arthritis: Ulnar Deviation and Muscle Atrophy, Hands

Rheumatoid Arthritis: Subcutaneous Nodules, Fingers

Rheumatoid Arthritis: Subcutaneous Nodule, Olecranon

Rheumatoid Arthritis: Popliteal Cyst

Rheumatoid Arthritis: Protruding Metatarsal Heads

Rheumatoid Arthritis: Foot Deformities

Rheumatoid Arthritis: Episcleritis

Rheumatoid arthritis: Scleromalacia Perforans

Rheumatoid Arthritis: Vasculitis and Gangrene, Fingers

Rheumatoid Arthritis: Cervical Spine, Atlantoaxial Subluxation (radiograph)

Rheumatoid Arthritis: Wrist Erosion (radiographs)

Rheumatoid Arthritis: Hand, Inflammation (bone scan)

Rheumatoid Arthritis: Hand, Progressive Metacarpophalangeal Erosion (radiographs)

Rheumatoid Arthritis: Hands, Advanced Deformity (radiograph)

Rheumatoid Arthritis: Hip, Late Erosions (radiographs)

Rheumatoid Arthritis: Hip, Protrusio Acetabuli (radiograph)

Rheumatoid Arthritis: Knees (radiograph)

Rheumatoid Arthritis: Metatarsal Erosion (radiograph)

Rheumatoid Arthritis: Pulmonary Nodules (radiograph)

Sjogrenâ&#x20AC;&#x2122;s Syndrome

Criteria for the Classification of Sjögren’s Syndrome  Ocular Symptoms  Oral Symptoms  Ocular Signs

– Schirmer test ≤ 5 mm – Rose Bengal score ≥ 4

 Histopathology ≥ 1 agglomeration of 50 or more mononuclear cells/4mm tissue (focus score)  Objective evidence of salivary gland involvement  Autoantibodies – SSA/Ro, SSB/La, ANA, RF

 (4 or > high sensitivity and specificity)  Exclusions: lymphoma, sarcoid, GVH, acquired immune deficiency Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjögren’s syndrome. Arthritis Rheum 1993;36:340-347.

Sjögren’s Syndrome: Clinical Features  Exocrine gland dysfunction – Sicca syndrome – Salivary gland enlargement

 Hypergammaglobulinemic purpura  Central and peripheral neurologic manifestations  Nephropathy – Distal renal tubular acidosis – Interstitial nephritis

 Pseudolymphoma and lymphoma  Pulmonary disease  Joint symptoms

Sicca Syndrome Manifestations  Keratoconjunctivitis sicca – Ocular dryness – Corneal injury

 Xerostomia – – – –

Oral dryness Dysphagia Dental caries Thrush

 Nasal dryness and epistaxis  Vaginal dryness – Dyspareunia – Candidiasis

Sjögren’s Syndrome: Associated Conditions Connective tissue diseases –SLE –RA –Systemic sclerosis

Hypothyroidism Cryoglobulinemia Autoimmune hepatitis

Sjögren’s Syndrome: Evaluation           

Schirmer test Rose Bengal or fluorescein stain Slit lamp exam Salivary flow Scintigraphy Dental evaluation Minor salivary gland (lip) biopsy Serologic tests (SSA(Ro), SSB(La), ANA, RF) SPEP, cryoglobulins Lymph node biopsy Evaluation for renal tubular acidosis

Sjögren’s Syndrome: Parotid Gland

SjĂśgrenâ&#x20AC;&#x2122;s Syndrome: B-cell Lymphoma, Parotid Gland (clinical and photomicrograph)

The risk of lymphoma in pSS is approximately 5 %

SjĂśgrenâ&#x20AC;&#x2122;s Syndrome: Cornea (Rose Bengal stain)

Sjögren’s Syndrome: Schirmer Test

SjĂśgrenâ&#x20AC;&#x2122;s Syndrome: Xerostomia

SjĂśgrenâ&#x20AC;&#x2122;s Syndrome: Parotid Gland (photomicrograph)

Traditional Treatment Pyramid for RA experimental drugs and procedures traditional DMARDs: immunosuppressants, gold-based drugs, and antibiotics

NSAIDs and analgesics

self-management: education, rest, exercise Adapted from Weinblatt ME. Cleve Clin J Med. 2004;71:409-413.

Remission is the New Goal in RA Management early diagnosis

early treatment

DMARDs/biologics preserve function AND quality of life

remission

Adapted from Weinblatt ME. Cleve Clin J Med. 2004;71:409-413.

Clinical and Laboratory Findings That Correlate With a Poor Outcome  Disease severity

– Level of inflammation, more joints involved at onset – Early joint damage – Functional limitation, loss of work – Constitutional symptoms

 Presence of

– Rheumatoid factor – Anti-CCP antibodies – Elevated ESR, CRP – Anemia – Genetic markers (eg, HLA-DR4 and DR1)

CCP=cyclic citrullinated peptide; CRP=C-reactive protein; ESR=erythrocyte sedimentation rate.

Rheumatoid Factor Antibody directed against the Fc portion of IgG Present in approximately 80% of RA patients May be involved in disease pathogenesis Higher levels tend to be associated with poorer prognosis Found in other rheumatologic and non-rheumatologic conditions

Tighe H, Carson DA. Rheumatoid factor. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds). Textbook of Rheumatology, 6th edition. Philadelphia: WB Saunders 2001.

Carson DA. Rheumatoid factor. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1989.

Anti-Cyclic Citrullinated Peptide Antibodies  Anti-CCP abs have a sensitivity of up to 80-90% and a specificity of 90% for RA. This specificity increases to > 95% if combined with the presence of IgM RF.  May be present in other inflammatory conditions such as PsA, auto-immune hepatitis, and pulmonary TB.  They are a risk factor for more aggressive disease and may be found early on in the disease

Early, Aggressive Therapy Can Prevent the Long-term Effects of RA and Improve Cardiovascular Outcomes  Functional Decline  Progression of functional decline appears greatest in the early stages of disease  Declines in functional status increase burden of disease

Physical Joint Deformity Results in pain and loss of mobility Leads to joint replacement surgery Associated with premature mortality (eg, cardiovascular risks/comorbidities)

Wolfe F, Sharp JT. Arthritis Rheum. 1998;41:1571-1582. Pincus T. Drugs. 1995;50(suppl 1):1-14.

Mortality Due to Cardiovascular Events is Increased in Patients With RA

Goodson N et al. Ann Rheum Dis. 2005;64:1595-1601.

Mortality Due to Infections is Increased in Patients With RA

Allebeck P. Scand J Rheumatol. 1982;11:81-86; Wolfe F et al. Arthritis Rheum. 1994;46:2294-2300; Bjornadal L et al. J Rheumatol. 2002;29:906-912; Thomas E et al. J Rheumatol. 2003;30:958-965; Sihvonen S et al. Scand J Rheumatol. 2004;33:221-227.

Mortality Due to Cancer is Increased in Patients With RA

Thomas E et al. Int J Cancer. 2000;88:497-502.

Spondyloarthropathies

Spondyloarthropathies Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Enteropathic arthritis –Crohn’s disease –Ulcerative colitis

Juvenile ankylosing spondylitis Undifferentiated spondyloarthropathies

Criteria for Classification of Spondyloarthropathy  Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs) plus more than 1 of the following: – Positive family history – Psoriasis – Inflammatory bowel disease – Urethritis, cervicitis, or acute diarrhea < 1 mo. before arthritis – Buttock pain alternating between right and left gluteal areas – Enthesopathy – Sacroiliitis

 Sensitivity 78.4% and specificity 89.6% Dougados M, Van Der Linden S, JuhlinR, et al. The European spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum 1991;34:1218-1227.

New York Criteria for Diagnosis of Ankylosing Spondylitis ď&#x201A;§Definite ankylosing spondylitis: criterion 4 or 5 plus 1, 2, or 3 1. Limited lumbar motion 2. Low back pain for 3 months improved with exercise not relieved by rest 3. Reduced chest expansion 4. Bilateral, grade 2 to 4, sacroiliitis on X-ray 5. Unilateral, grade 3 to 4, sacroiliitis on X-ray The HSG, Steven MM, van der Linden SM, et al. Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and Modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol. 1985;24:242-249.

Ankylosing Spondylitis: Characteristics of Back Pain Onset of back discomfort before age 40 Insidious onset Duration longer than 3 months Associated with morning stiffness Improvement with exercise

Spondyloarthropathies: Nonvertebral Manifestations  Asymmetric peripheral arthritis  Sausage digits  Enthesopathy

 Nail involvement  Fatigue, weight loss  Amyloidosis – Achilles Tenosynovitis  Apical pulmonary fibrosis – Plantar fasciitis  Immunoglobulin A – Costochondritis nephropathy  Acute anterior uveitis/iridocyclitis  Cardiac involvement Mucocutaneous lesions

HLA-B27 Disease Associations Ankylosing spondylitis –with uveitis or aortitis

>90% (white males) 100%

Reactive arthritis 50-80% –with sacroiliitis or uveitis 90% Juvenile spondyloarthropathy 80%

HLA-B27 Disease Associations (cont’d)  Inflammatory bowel disease –Peripheral Not increased –Axial •Crohn’s disease 50% •Ulcerative colitis 70% Psoriasis –Peripheral –Axial

Not increased 50%

Psoriatic Arthritis: Musculoskeletal Characteristics Asymmetrical arthritis Dactylitis/Sausage digit Tenosynovitis Enthesitis Heel pain Sacroiliitis Spondylitis

Psoriatic Arthritis: Cutaneous and other Manifestations Psoriasis Erythroderma Nail pitting Onycholysis Conjunctivitis/iritis Valvular heart disease

Psoriatic Arthritis: Radiographic Characteristics  Erosive arthritis (usually asymmetric)  Pencil-in-cup deformity  Ray phenomenon  Arthritis mutilans  Bony ankylosis  Spurs/periosteal reaction  Non-marginal asymmetric syndesmophytes  Asymmetric sacroiliitis

Reactive Arthritis Seronegative asymmetric arthritis following: –Urethritis or cervicitis –Infectious diarrhea

Often associated with: –Inflammatory eye disease –Enthesopathy –Circinate balanitis, oral ulceration or keratoderma

Criteria for Reactive Arthritis: Sensitivity and Specificity Method 1. Arthritis > 1 mo. with urethritis and/or cervicitis

Sensitivity 84.3%

Specificity 98.2%

2. Arthritis > 1 mo. and either urethritis or cervicitis, or bilateral conjunctivitis

85.5%

96.4%

3. Episode of arthritis conjunctivitis, and urethritis

50.6%

98.8%

4. Episode of arthritis of more than 1 month, urethritis and conjunctivitis

48.2%

98.8%

Ankylosing Spondylitis: Postural Changes

Ankylosing Spondylitis: Ankylosis, Lumbar Spine

Ankylosing Spondylitis: Progression of Deformities

Ankylosing Spondylitis: Iridocyclitis With Synechiae

Psoriatic Arthritis: Nail Changes, Rash, and Arthritis, Hands

Psoriatic Arthritis: Hands

Psoriatic Arthritis: Nail Dystrophy and Arthritis

Psoriatic Arthritis: Opera Glass Hand

Psoriasis and Psoriatic Arthritis: Pre- and Post-Treatment, Hands

Psoriatic Arthritis: Nail Pitting

Psoriatic Arthritis: Asymmetric Synovitis, Knees

Psoriatic Arthritis: “Sausage” Digits and Rash

Reactive Arthritis: Tendinitis, Heels

Reactive Arthritis: Nail Dystrophy and Arthritis

Reactive Arthritis: Rash and Pustules, Foot

Reactive Arthritis: Keratoderma Blennorrhagica, Foot

Reactive Arthritis: Pustules and Keratoderma Blennorrhagica, Feet

Reactive Arthritis: Balanitis Circinata

Reactive Arthritis: Erosions, Tongue

Reactive Arthritis: Erosion, Palate

Reactive Arthritis: Conjunctivitis

Ankylosing Spondylitis: Bamboo Spine, Lumbar Vertebrae (radiograph and gross specimen)

Ankylosing Spondylitis: Early Sacroiliitis (radiograph)

Ankylosing Spondylitis: Advanced Sacroiliitis (radiograph)

Ankylosing Spondylitis: Apophyseal Disease and Ossification, Cervical Vertebrae (radiographs)

Ankylosing Spondylitis: Thoracic and Lumbar Vertebrae “Squaring,” Osteopenia, and Ossification (radiographs)

Ankylosing Spondylitis: Lumbar Vertebrae, Bamboo Spine (radiograph)

Ankylosing Spondylitis: Thoracic & Lumbar “Squaring,” Osteopenia, and Ossification

Spine Examination: Schรถber Test for Spinal Mobility

Spine Exam: Mobility Examination

Therapeutic Exercise Goals in Ankylosing Spondylitis –Preserve optimum posture –Maintain chest expansion –Maintain flexibility of axial skeleton and other involved joints

Psoriatic Arthritis: Hand (radiograph)

Psoriatic Arthritis: Progressive Joint Changes (radiographs)

Psoriatic Arthritis: Feet (radiograph)

Reactive Arthritis: Sacroiliitis (radiographs)

Antinuclear and Other Antibodies  In young women ANA occur in about 2% of normals  ANAs are not useful in assessing disease activity  ANAs found in > 90% of pts with SLE  dsDNA abs found in 40-60 % and have major diagnostic implications, esp renal involvement, and may reflect disease activity (inc with flare)  Anti-Sm abs diagnostically important-do not gauge disease activity

Antibodies  Anti-SSA/Ro ( 30-45%), Anti SSB/La (10-15%) assoc with Sjogren’s, SCLE, neonatal lupus, photosensitivity  Anti-RNP (30-40 %) – Raynaud’s, musculoskeletal  Antiribosomal P (10-20 %) – Diffuse CNS, Psychosis, major depression  Antiphospholipid (30%) – clotting diathesis, fetal loss, thrombocytopenia Copyright © 1972-2004 American College of Rheumatology Slide Collection. All rights reserved.

Polymyalgia Rheumatica  Rare in non Caucasian and adults < 50 years old  Common, incidence 17 per 100,000  Twice as common in women  Proximal muscle pain neck, shoulders, low back, hips and thighs  Significant AM stiffness  Occasional synovitis and carpal tunnel syndrome  Elevated ESR/CRP, anemia of chronic disease  Occasional normal markers of inflammation

Treatment of PMR  Corticosteroids only effective treatment  Average length of treatment is 2 years, some need indefinite low doses  Prednisone 10-20 mg day initially  If dose exceeds 20 mg per day question the diagnosis  Prompt resolution of pain in a few days, if not, question the diagnosis  Taper prednisone 2.5 mg per month until 10mg then 1 mg per month (one of many tapers)

PMR ď&#x201A;§ Remember temporal arteritis