1. Does my patient have Lupus?
Jammie Barnes, MD
Assistant professor
Department of Medicine, Division of Rheumatology

2. It’s Lupus

3. Dr. House or Dr. Warner LBJ referral: +ANA with aches and pains
Dr. Barnes: It’s Lupus
Dr. Warner: Wrong
Another referral: same story
A retrospective chart review at LBJ (1yr)
104 +ANA referrals…. ONLY 6 cases of confirmed SLE

4. Objectives
Understand the limitations of sensitivity and specificity of ANA
Determine who needs to be evaluated for SLE
Describe the systemic signs and symptoms of SLE
Apply the American College of Rheumatology criteria for SLE
Apply to cases

5. ANA is 100% sensitive
Lupus
Diabetes

6. Sensitivity & Specificity
Prevalence = 10/1000 = 1%
Yes- SLE
No- SLE
+ test 10
390
400
- test
600
990
1000
SnNout: high sensitivity – negative test is good at ruling out the disease
Negative ANA – very unlikely to have SLE
SpPin: high specificity –positive test good at ruling in disease
Sensitivity – 100%
Specificity – 60%
PPV: 10/400 = 2.5%
Prevalence = 500/1000 = 50%
Yes – Dz
No - Dz
+ test
500
200
700
- test
300
1000
PPV: 500/700 = 71.4%

7. The nomogram
LR: 2.5
Reminder:
+LR=
sens/(1-spec)

8. Pretest probability Consider prevalence
Clinical scenario in your patient
If you order a test – expect a result
Positive ANA, now what!!

9. ANA Autoabs directed against DNA or snRNP Positive test: >1:80
Best to order test by immunofluorescence (IF)
ELISA enzyme linked assays are cheaper but have 80-98% agreement with IF
ACR recommends ordering ANA by IF

10. Other problems with ANA
1/3 of healthy people have an ANA 1:40
5% of healthy people have ANA 1:160
3.3% of healthy people have ANA 1:320
Healthy 1st degree relatives can have + ANA
Healthy older people increased + ANA
ANA linked to thyroid dz, hepatitis, environmental exposure, cancer, infections and drugs
Southern Medical Journal. Vol 105, no 2, Feb 2012

11. Making the ANA better 2 possibilities
Raise the threshold of positive test
High titers do warrant more investigation > 1:1280
Couple the test with more specific signs and symptoms of rheumatic disease
High risk - low occurrence

12. When to order an ANA

14. CNS/PNS Criteria – seizures and psychosis Question: Have you ever
Both in absence of offending drugs
Question:
Have you ever
had a seizure
or convulsion?
Orphanet Journal of Rare Disease :6

15. Skin/Mucocutaneous
4 criterion for skin: malar rash, discoid rash, photosensitivity and oral ulcers
Do you get sores in your mouth or nose for more than 2 weeks at a time
Rash on your cheek for more than a month
Skin breakout (rash) after being in the sun (not a sunburn)
Others:
Alopecia
Have you had rapid loss of hair
Raynauds
Have your fingers ever shown unusual color changes in the cold
Purpura, urticaria and vasculitis

16. Hematologic Hemolytic anemia
Leukopenia <4000 on > 2times or lymphopenia <1500 on > 2 times
Thrombocytopenia <100k in absence of drugs
All meet hematologic criteria (only get 1 point)
Questions: Have you ever been told that you have anemia, low blood count, low platelet count

17. Cardio/Pulm Criteria: Others:
Pericarditis – documented by ECG, rub or pericardial effusion
Pleuritis – convincing h/o pleuritic chest pain, rub or pleural effusion
Question: Do you get chest pain with deep breath?
1 point
Others:
Endo and myocarditis, pulmonary arterial hypertension, valvular, CAD
Chronic interstitial pneumonitis, acute lupus pneumonitis, acute alveolar hemorrhage, acute reversible hypoxemia, PE, shrinking lung syndrome

18. Renal
Criteria:
Persistent proteinuria >0.5gm per day or 3+ on dipstick or cellular cast
Have you have been told you have protein in your urine
Class 1-6 of lupus nephritis
Microangiopathic glomerular disease
Renal vein thrombosis

19. GI No criteria for diagnosis
None specific abd pain, nausea and vomitting
Rare mesenteric vasculitis

20. Reticuloendothelial
Not a criteria
LAD
HSM

21. MSK
Criteria:
Arthritis – tenderness, swelling or effusion in 2 or more joints witnessed
Typically non-erosive
Jacouds arthopathy
Others:
Myositis

22. Constitutional Not a criteria
Profound fatigue (disabling fatigue) – in absence of depression
Fever (no signs of infection)
Weight loss

23. Immunologic Criteria: Positive ANA >1:80
Positive anti-dsDNA OR Anti-Smith OR antiphospholipid antibody
Abnl IgG or IgM cardiolipin, + lupus anticoagulant, false positive RPR
Others:
SSA/B (anti-Ro and La), RNP

24. Applying Signs and Sxs Upon screening:
Two or more organs systems involved – order CBC, CMP, UA to evaluate for systemic disease
If above reveals possible systemic disease then order an ANA and possible other antibodies
If 4 or more criteria by ACR or suspect SLE refer to Rheumatology

26. Case 21 y/o college student with two months of joint pain worse in AM
Notices faint rash on face for last month
Very tired and finds it difficult to concentrate in class
Denies fevers, abd pain, chest pain, diarrhea or constipation
On exam: malar rash, decreased breath sounds at bases, no murmurs, diffuse cervical LAD and mild synovitis in the MCPs and PIPs

27. What next Order labs/studies: CBC, UA, CMP, CXR
What other labs do you want?
ANA, RF, CCP and TSH
WBC count 3.2, nl Hgb and platelets, neg RF and CCP, UA 2+ proteinuria, no cast or red cells, UPC 0.3, ANA 1:640, +dsDNA, +smith and chest xray with effusions
Does she meet criteria?
YES!

28. Case 36 y/o stay at home Mom presents with joint pains for 3 months
She has no swelling, but she has tenderness all over in the upper and lower body
She tells you she has anemia, severe fatigue but she can still take care of her children
She has occasional HA, some weight gain, but other ROS is negative
On exam she is overweight with BMI of 32, multiple tender points but no synovitis

29. What next Order CMP,CBC, UA and TSH
Her labs are normal with exception of HGB of 10.2 and MCV of 76
What next:
Iron studies
Low ferritin, smear: hypochromic RBCs, low iron and high TIBC
Do you need to do more?
Treat IDA

30. Case
32 y/o man with long standing history of epilepsy. He has been on anti-seizure medication for many years. Initially he was on phenytoin and now on oxcarbazepine
He has developed a photosensitive rash and joint pain
In ROS he also has pleuritic chest pain
On exam he has a erythematous rash on the face and upper chest, synovitis of the bilateral wrist but rest of exam is normal

31. What next CBC, CMP, UA, CXR and ANA
He has positive ANA, nl CMP, CMP, UA and chest xray
What does he have?
Drug induced lupus
Do you need histone antibodies? No
How do you proceed?
Discuss changing anti-convulsant medication, may add NSAIDs, steroid cream for rash and hydroxychloroquine

32. Thank you for time Remember ANA does not equal lupus
Need careful history and physical
Lupus is RARE disease but high morbidity and mortality if missed
Please remember your packet!!
I need to contact you again in 3months for post test!!!