Approach to the Achy Patient in her shoulders, knees and feet. - PDF document

Clinical Case # 1 • 52 year old woman with 5 months of joint pain. Initially she had pain in her hands. Over time, she developed pain Approach to the Achy Patient in her shoulders, knees and feet. Ibuprofen has been helpful for the pain. • Review of systems is notable for Andrew J. Gross, MD moderately severe fatigue, and occasional sharp chest pains. She Rheumatology Clinic Chief Associate Clinical Professor also reports symptoms of Raynaud’s phenomenon. University of California, San Francisco • Past medical, family and social history are unremarkable. Clinical Case # 1 Differential Diagnosis • General physical examination is unremarkable. Inflammatory Non-Inflammatory • On musculoskeletal exam, you are uncertain if there • Autoimmune • Osteoarthritis are any swollen joints. Many joints are tender, – Lupus/Scleroderma • Endocrine particularly her PIP and MCP joints, her wrists and – Rheumatoid Arthritis – Thyroid Disease knees. – Spondyloarthritis – Diabetes • Crystal Disease – Calcium metabolism What is the diagnosis? • Infectious • Overuse – Viral • Somatic/Fibromyalgia – Chronic bacterial – Hypermobility • Neoplastic 1

Approach to Arthritis Pattern of Joint Involvement (clinical clues) • age All of the following conditions commonly involve PIP & MCP joints, wrists and knees EXCEPT: • gender A. Osteoarthritis • family history B. Rheumatoid Arthritis • onset of disease (acute/chronic) C. SLE • pattern of joint involvement D. CPPD disease (“pseudogout”) (& presence of enthesitis) E. Parvovirus B19 induced arthritis Approach to Arthritis Clinical Case # 1 (clinical clues) • age • Re-examination of the skin is • gender remarkable for mild Lupus/MCTD/ • family history erythema of her scleroderma fingers, particularly • onset of disease (acute/chronic) Rheumatoid between the • pattern of joint involvement knuckles. Arthritis (& presence of enthesitis) Psoriatic • extra-articular manifestations Arthritis • diagnostic testing Peri-menopausal What is the diagnosis? osteoarthritis Photo courtesy of Maria Dall’era 2

What is the Diagnosis? Tip A. Dermatomyositis B. Psoriasis • To help diagnose Inflammatory Arthritis C. Lupus Search for CLINICAL CLUES D. Granuloma Annulare E. Eczema Classification Criteria for Classification Criteria for Systemic Lupus Erythematosus Systemic Lupus Erythematosus Malar rash : Fixed erythema, flat or raised, over the malar eminences Discoid rash : Erythematous circular raised patches with adherent keratotic scaling • Rashes (~85%) • Glomerulonephritis (50- and follicular plugging; atrophic scarring may occur 70%) Photosensitivity : Exposure to ultraviolet light causes rash – Malar rash Oral ulcers : Includes oral and nasopharyngeal ulcers, observed by physician – Discoid rash (scarring) • CNS disease (25-35%) Arthritis : Nonerosive arthritis of two or more peripheral joints, with tenderness, – Photosensitive (seizures, chorea, stroke) swelling, or effusion • Hematologic disorder Serositis : Pleuritis or pericarditis documented by ECG or rub or evidence of effusion • Oral/nasal ulcers (painless) Leukopenia, Lymphopenia, Renal disorder : Proteinuria >0.5 g/d or 3+, or cellular casts • Arthritis (80-90%) Thrombocytopenia, AIHA Neurologic disorder : Seizures or psychosis without other causes (usually small joints) • Immunologic disorder Hematologic disorder : Hemolytic anemia, leukopenia (<4000/L) or lymphopenia (<1500/L) or thrombocytopenia (<100,000/L) in the absence of offending drugs • Serositis (~45%) dsDNA, Sm, APL Antibodies Immunologic disorder : Anti-dsDNA, anti-Sm, and/or anti-phospholipid • Antinuclear antibodies Antinuclear antibodies : An abnormal titer of ANA by immunofluorescence or an equivalent assay in the absence of drugs known to induce ANAs Any combination of 4 or more of 11 criteria, well-documented at any time during a patient's history, makes it likely that the patient has SLE (95% specificity; 75% sensitivity) Any combination of 4 or more of 11 criteria, well-documented at any time during a patient's Tan EM, et al, Arthritis Rheum 1982 history, makes it likely that the patient has SLE (95% specificity; 75% sensitivity) 3

Anti-Nuclear Antibody (ANA) Clinical Case # 1 – Alternative Scenario • General physical examination is unremarkable. • On musculoskeletal exam, you are unsure if there are any swollen joints. Many joints are tender, particularly her PIP and MCP joints, her wrists and knees. • Skin exam is unremarkable In the absence of clinical clues Are there diagnostic tests that will help identify the diagnosis? How will an ANA test help me to determine if the patient has “a rheum thing” (like SLE)? a. Although an ANA is not specific for any particular How does an ANA test help me autoimmune disease, the presence of it does suggest the patient has a connective tissue disease. to determine if the patient has b. A positive ANA indicates the patient has a defect in tolerance mechanisms and will develop an “a rheum thing” (like SLE)? autoimmune disease. c. By examining the pattern of the ANA, you can determine the diagnosis. d. Testing for additional autoantibodies can increase the specificity of testing. 4

ANA is highly sensitive for Lupus & ANA Frequencies Somewhat sensitive for other autoimmune conditions 100% 50% 0% • SLE 95-99% • Thyroid disease 30-50% • Systemic Sclerosis • Multiple Sclerosis 25% (Scleroderma) 60-80% • ITP 10-30% • Sjögrens 40-70% • Infectious diseases & Healthy Rheumatoid malignancies - varies widely • Polymyositis & Scleroderma Fibromyalgia Arthritis & Dermatomyositis 30-80% Lupus Thyroid Disease • Rheumatoid 1° relatives Arthritis 30-50% of SLE Pts Kavanaugh A, et al, Arch Pathol Lab Med 2000 Kavanaugh A, et al, Arch Pathol Lab Med 2000, PMID 10629135 Among 100,000 American Women People without Autoimmune Disease can Who has a positive ANA? have a positive ANA Condition Number ANA+ Calculated with Prevalence of condition ANA+ people per 100,000 per 100,000 • Fibromyalgia 15-25% Women with SLE 50 99% ~50 • Relatives of SLE Pts 5-25% Patients w/ Autoimmune Thyroid Dz 250 40% ~100 • Healthy People Women with Fibromyalgia 3500 20% ~700  > 1:40 20-30%  > 1:80 10-12% Healthy women with ANA ≥ 1:160 -- 5% ~5,000  > 1:160 5%  > 1:320 3% ANA is not really helpful to screen for autoimmune disease Kavanaugh A, et al, Arch Pathol Lab Med 2000 Data extrapolated from Kavanaugh A, et al, Arch Pathol Lab Med 2000 & Tan EM, et al, Arthritis Rheum 1997 5

Speckled Nucleolar ANA patterns How • ANA patterns are not highly predictive of: about – Disease Types the – Autoantibody subsets ANA Pattern? Cytoplasmic Centromere Disease Suspicion: SLE Back to Our Patient’s Diagnostic Testing useful lab tests • ESR 19 mm/hr • CRP 3.2 (nl <6.3) • ANA – 95-99% sensitive • ANA 1:160 speckled pattern • anti dsDNA – seen in 70% of patients (95-100% Specific) • C3 89, C4 21 (both borderline low) • Smith – only seen in 15-30% of patients (95-100% Specific) • C3 & C4 levels – depressed in 60% of patients (Sensitive) • Anti-dsDNA Ab, Sm Ab, RNP negative • Elevated ESR (CRP usually normal in SLE) • WBC 3.2, 0.8 lymphocytes, Hgb 11.1, PLT 104 • Lymphopenia, AIHA, thrombocytopenia, leukopenia • Urine Analysis normal This is consistent with mild SLE Kavanaugh A, et al, Arch Pathol Lab Med 2000, PMID 10629135 6

Tips to help diagnose SLE Clinical Case # 2 • 52 year old woman with 5 months of • Search for CLINICAL CLUES! joint pain. Initially she had pain in her hands. Over time, she developed pain • Biopsy persistent skin rashes in her shoulders, knees and feet. It • Check complement levels takes a couple of hours for her joint • Check urine for hemoglobin & protein, stiffness to improve in the mornings. especially if the patient has dsDNA Ab • General physical examination is unremarkable. • Look for lymphopenia and thrombocytopenia • On musculoskeletal exam, you think a few fingers and her right wrist might be swollen. Many joints are tender, particularly her PIP and MCP joints, her wrists and shoulders. Approach to Arthritis Part 2 – Patient’s Diagnostic Testing (clinical clues) • age • WBC 7.1, Hgb 11.8, PLT 291 • ESR 19 mm/hr • gender Lupus/MCTD/ • CRP 7.8 (nl <6.3) • family history scleroderma • ANA 1:40 speckled pattern • onset of disease (acute/chronic) • C3 128 (normal), C4 36 (slightly elevated) Rheumatoid • pattern of joint involvement • Anti-dsDNA Ab, Sm Ab, RNP negative Arthritis (& presence of enthesitis) • Urine Analysis normal Psoriatic • extra-articular manifestations Arthritis Does not seem like Lupus or Scleroderma. • diagnostic testing Peri-menopausal Could this be Rheumatoid Arthritis? osteoarthritis 7