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

2. 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.

3. 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)

4. 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

5. 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)

6. 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

7. 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

8. 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)

9. 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

10. 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.

11. 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.

12. 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.

13. 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.

14. 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

15. 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

16. 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

17. 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

18. 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)

19. 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

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

21. 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

22. 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

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

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

25. 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!

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