In the Grey Rheumatology labs and consultation guidelines Neera S Narang, MD Rheumatology RWC and SSF

Disclosure of Relevant Financial Relationships Under the ACCME Standards for Commercial Support, everyone who is in a position to control the content of an education activity must disclose all relevant financial relationships with any commercial interest. A “commercial interest” includes any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME does not consider providers of clinical service directly to patients to be commercial interests. A financial relationship is “relevant “ if it pertains to the activity’s content matter including any related health care products or services to be discussed or presented. ACCME considers financial relationships of the person involved to also include those of a spouse or partner. Dr. Narang has disclosed that she has no relevant relationships with commercial interest. The CME Department has reviewed the disclosure information for the planner and/or committee/faculty for this program and they do not have relationships that present a relevant conflict of interest.

Objectives 1.Discuss when to order autoimmune work-up 2. Discuss interpretation behind common autoantibody labs 3. Review guidelines for rheumatology referrals Identify and apply cultural and ethnic clinical data for evidence based treatment of rheumatologic health in men and women patients as appropriate (examples: see slides 8 and 17)

Core Rheumatology Labs Does NOT mean antibodies for every patient! CBC, creatinine, AST/ALT, TSH, ESR/CRP, and hepatitis serologies These + more specific labs (RF etc) if indicated give us the information we need to move forward with treatment when we see the patient. Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies

ANA Terrible at “ruling out” autoimmune disease Really dependent on pre-test probability Two methods: IFA and ELIZA (bioplex screening) Significant false + with bioplex screening ANA in the elderly – helpful for scleroderma or raynaud’s evaluation - not helpful if you suspect PMR or RA Subserologies: seeing likely false + with RNP (low titer)

Percent ANA+ in healthy individuals: 1:40 – 20-30% of healthy individuals can be + 1:80 – 10-15% 1:160 – 5% 1:320 – 3% Healthy relative of an SLE patient – 5-25% positive Age > 70 – 70% + for ANA 1:40 Rheumatology Secrets, 3rd Edition. Sterling G. West, MD

RF/CCP Rheumatoid Factor - CHRONIC CH – chronic disease – hepatic (PBC), pulmonary (IPF, silicosis, asbestosis) R – rheumatoid arthritis Other rheumatic disease (SLE, etc) Neoplasm Infection Cryoglobulinemia Incidence of +RF in healthy pt goes up with age: Age 20-60: 2-4%+ Age 60-70: 5% Age >70: 10-25% CCP – Sensitivity 67%, Specificity 95% Can help distinguish cause of +RF from other diseases such as hep C

ESR/CRP Get both ESR – distance in mm that RBCs fall within 1 hour Indirect measure of acute phase reactants and immunoglobulins Rise in acute phase reactants or hypergammaglobulinemia  RBCs stick together more  fall faster  elevated ESR Age-adjusted upper limit of normal: Male = age/2, Female = (age +10)/2 CRP – specific acute phase reactant produced by liver Age-adjustment: Male = age/50, Female = (age+30)/50 Rises and falls more quickly than ESR Not affected by Ig levels. CRP>1.0 in ~ 10% of normal population (esp with African Am, Female, elderly)

Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies “Pain all over” AM stiffness > 30 minutes? Joint swelling? Symptoms >6 weeks? Other symptoms such as Raynaud’s or photosensitivity? Key in distinguishing between inflammatory causes (RA, PMR etc) versus non-inflammatory (OA, fibromyalgia) If inflammatory cause suspected, consider additional lab workup ANA, RF, CCP, ESR, CRP, quantiferon/PPD SPEP (or other clinically indicated malignancy work up) *particularly for PMR If not, but still would like rheum input – consider holding off on labs, or consider the following: TSH, vitamin D, CK, PTH

Low Back Pain Inflammatory back pain for at least 3 months When do we suspect spondyloarthropathy? (Ank spond and related conditions) Inflammatory back pain for at least 3 months Age of onset < 45 90% of AS patients are HLA b27+, but only only 5% of individuals with the gene have AS (unless there is a family Hx of AS). The gene is present in 6-9% of most populations while the prevalence of AS is 1% or less. Hence, it has a very low predictive value in the absence of signs or symptoms or a positive family history.

Low Back Pain Inflammatory back pain for at least 3 months When do we suspect spondyloarthropathy? (Ank spond and related conditions) Inflammatory back pain for at least 3 months Onset less than age 40 Insidious onset Improvement with exercise No improvement with rest Pain at night (gets better on arising) Age of onset < 45 90% of AS patients are HLA b27+, but only only 5% of individuals with the gene have AS (unless there is a family Hx of AS). The gene is present in 6-9% of most populations while the prevalence of AS is 1% or less. Hence, it has a very low predictive value in the absence of signs or symptoms or a positive family history.

Low Back Pain Inflammatory back pain for at least 3 months When do we suspect spondyloarthropathy? (Ank spond and related conditions) Inflammatory back pain for at least 3 months Onset less than age 40 Insidious onset Improvement with exercise No improvement with rest Pain at night (gets better on arising) Age of onset < 45 Order sacroiliac joint films. If there is sacroiliitis on imaging, you need only 1 of the additional feature below for diagnosis. If no sacroiliitis, 2 additional features are needed for diagnosis. 90% of AS patients are HLA b27+, but only only 5% of individuals with the gene have AS (unless there is a family Hx of AS). The gene is present in 6-9% of most populations while the prevalence of AS is 1% or less. Hence, it has a very low predictive value in the absence of signs or symptoms or a positive family history.

Low Back Pain Inflammatory back pain for at least 3 months When do we suspect spondyloarthropathy? (Ank spond and related conditions) Inflammatory back pain for at least 3 months Onset less than age 40 Insidious onset Improvement with exercise No improvement with rest Pain at night (gets better on arising) Age of onset < 45 Order sacroiliac joint films. If there is sacroiliitis on imaging, you need only 1 of the additional feature below for diagnosis. If no sacroiliitis, 2 additional features are needed for diagnosis. Inflammatory back pain Arthritis Enthesitis Uveitis Dactylitis Psoriasis Inflammatory bowel disease Good response of back pain to NSAIDs Family history of spondyloarthropathy Positive HLA-B27 Elevated CRP Sensitivity of above criteria: 83%, specificity: 84% 90% of AS patients are HLA b27+, but only only 5% of individuals with the gene have AS (unless there is a family Hx of AS). The gene is present in 6-9% of most populations while the prevalence of AS is 1% or less. Hence, it has a very low predictive value in the absence of signs or symptoms or a positive family history.

Low Back Pain Inflammatory back pain for at least 3 months When do we suspect spondyloarthropathy? (Ank spond and related conditions) Inflammatory back pain for at least 3 months Onset less than age 40 Insidious onset Improvement with exercise No improvement with rest Pain at night (gets better on arising) Age of onset < 45 Order sacroiliac joint films. If there is sacroiliitis on imaging, you need only 1 of the additional feature below for diagnosis. If no sacroiliitis, 2 additional features are needed for diagnosis. Inflammatory back pain Arthritis Enthesitis Uveitis Dactylitis Psoriasis Inflammatory bowel disease Good response of back pain to NSAIDs Family history of spondyloarthropathy Positive HLA-B27 Elevated CRP Sensitivity of above criteria: 83%, specificity: 84% 90% of AS patients are HLA b27+, but only only 5% of individuals with the gene have AS (unless there is a family Hx of AS). The gene is present in 6-9% of most populations while the prevalence of AS is 1% or less. Hence, it has a very low predictive value in the absence of signs or symptoms or a positive family history. Without these features, please do not order an HLA B27

Myalgia/Muscle Weakness Weakness is more characteristic of inflammatory myositis Consider CK, aldolase, LDH + Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies

Gout Need to have data on their disease and be well prepared for treatment Uric acid + Above labs (other than ESR/CRP) should be checked q6 months while on urate lowering therapy Goal – uric acid< than 6. (not 6.1) CBC Creatinine AST/ALT ESR/CRP

Raynauds Concerning features: Age of onset > 40 years old Male Painful with signs of tissue ischemia (ulceration) Asymmetric attacks Other symptoms of a connective tissue disorder (SLE, scleroderma) For these cases, consider checking ANA and refer to rheumatology

SLE – it can look like ANYTHING! (well…yes and no…) 1. Malar rash (spares nasolabial folds) 2. Discoid rash 3. Photosensitivity (skin rash as result of reaction to sunlight) 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal disorder 8. Neurologic disorder 9. Hematologic disorder 10. Immunologic disorder (positive antiphospholipid antibody or anti DNA or anti Smith or false positive serologic test for syphilis) 11. Antinuclear antibody (titer greater than 1:80)

SLE If strong probability – consider the following labs before referral: + ANA, nuclear antibody screen, C3, C4, lupus anticoagulant, cardiolipin Ab, G2P1 UA, urine protein/cr ratio Quantiferon/PPD HIV if clinically indicated Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies

Palpable Purpura Common symptoms suggestive of vasculitis: Mononeuritis multiplex Palpable purpura Hemoptysis with CXR findings Abnormal/rising creatinine with an active urinary sediment

Palpable Purpura Common symptoms suggestive of vasculitis: Check Mononeuritis multiplex Palpable purpura Hemoptysis with CXR findings Abnormal/rising creatinine with an active urinary sediment Check Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies

Palpable Purpura Common symptoms suggestive of vasculitis: Check Mononeuritis multiplex Palpable purpura Hemoptysis with CXR findings Abnormal/rising creatinine with an active urinary sediment Check + PPD or QFT ANA ANCA SPEP, UPEP C3, C4 CPK Cryoglobulins UA with micro RF, CCP CXR HIV (if clinically indicated) Core Rheumatology Labs CBC Creatinine AST/ALT TSH ESR/CRP Hepatitis Serologies

Synovial Fluid Analysis Please consider for monoarthritis (*particularly to rule out septic joint) Key labs cell count/diff, crystals, gram stain and culture

Imaging If it hurts, please take xrays beforehand Particularly hands, feet, low back/pelvis

Take home message Autoantibody testing is useful if rheumatologic disease are suspected- pre-test probability is key. Age and chronic illness significantly increase chance of + antibodies If RF/CCP are indicated, please check both If ESR/CRP are indicated, please check both If it hurts, get an xray Feel free to call and ask!

References Rheumatology Secrets, 3rd Edition. Sterling G. West, MD Pages 48-57 http://www.rheumatology.org/ Patient/Caregiver- factsheets on disease, drugs Image library Classification criteria, ACR guidelines on management of various diseases