Thread by @AnnKumfer

1/ Understanding #ANA #tweetorial a collab w/ @MithuRheum
You are seeing a 30yo patient in the clinic who is ? an elevated ANA titer. A few months ago she had 2 weeks of joint pains & a rash. As part of the evaluation, an ANA was+ with a titer of 1:80. What do you do next?

2/ The goal of this tweetorial is to understand the significance of ANA
What is ANA?
What are the rheumatological and non-rheumatologic causes of ANA elevation?
What is the significance of the ANA titer?
What is the significance of the pattern of ANA elevation?

3/ ANA stands for antinuclear antibodies. What is in the nucleus? @sargsyanz reminds us that there are a lot of things in the nucleus, so a positive ANA could indicate antibodies targeting any of these structures.

https://twitter.com/sargsyanz/status/1402328207148433419?s=20

4/ ANA is usually detected using IFA (EIA can be used, but more ✖️+). The fluorescence pattern is 👀 interpreted and indicates specific ANA subtypes, such as homogenous, speckled, peripheral, and nucleolar.

5/These subtypes are associated with certain antibodies, but interpretation is subjective so ANA pattern alone is not diagnostic of specific diseases.

6/ How common is it to have an elevated ANA in the healthy population?

7/ Using EIA, 25% of the population has an elevated ANA, via IFA about 15% of health pts have elevation >1:80. +ANA F>M. It is really important to ask about clinical symptoms and interpret ANA in the context of clinical symptoms.
pubmed.ncbi.nlm.nih.gov/21366908/

8/- Does titer matter? Yes.
1:40 - up to 33% of the healthy pop
1:80 - 10-15% of healthy pop
1:160 - 5% of healthy pop
1:320 - 3% of healthy pop

Titer of ≥1:160, pathology more likely (but about 5% of healthy individuals still have high titers) pubmed.ncbi.nlm.nih.gov/9324014/

9/ Another study showed that about 1% of healthy pop had titers ≥ 1:2560. Does pattern matter with ANA+? While the most common pattern is nuclear fine speckled in both healthy and pts w/ ARD, nuclear dense fine speckled was only seen in healthy ppl. pubmed.ncbi.nlm.nih.gov/20954189/

10/ In another study, 90% of pts referred to rheum clinics for +ANA ✖️ rheumatologic dz. Symptoms associated w/ autoimmunity include Raynaud and inflammatory arthritis (w/ morning stiffness). +ANA does NOT = autoimmune disease.
pubmed.ncbi.nlm.nih.gov/23395534/

11/ In the 1st poll ANA is low titer and may have been due to viral infection. Can ask more about symptoms .

12/10/ ANA is ⬆️ in many autoimmune diseases. Highest sens in SLE, systemic sclerosis, mixed connective tissue disorder, and JIA. All these conditions have low specificity. Greater chance of autoimmune disease with high titers of ANA (>1:1280) pubmed.ncbi.nlm.nih.gov/22267099/

13/ ANA can also + w/ organ specific autoimmune diz like: Hashimoto’s/Graves dz, IBD, autoimmune hepatitis, and PBC. ANA is found in 70-80% of Type 1 AIH. Other causes: Infections such as EBV, parvovirus, syphilis, and subacute bacterial endocarditis and lymphoproliferative dz.

14/ So the ANA+ and concern for autoimmune disease. What is next? ENA (Extractable Nuclear Antigen) panel checks for specific autoantibodies, depending on institution, such as anti-SSA/SSB, anti-Sm & anti-RNP. Further autoantibody testing can be sent based on autoimmune dz.

15/ Conclusions
-ANA- anti-nuclear antibodies, often detected by IFA where various patterns can be seen
ANA is ⬆️ in about 25% of healthy ppl (depending on assay).
⬆️ titer, more likely autoimmune disease (but can still see high titers in healthy patients)

16/ Don’t check ANA unless compatible symptoms of autoimmune disease are present. Don’t be this person:

https://twitter.com/DGlaucomflecken/status/1371901346413117442?s=20

17/ Nuclear dense fine speckled ✖️associated w/ autoimmune dz
ANA highest sens for SLE, JIA, systemic sclerosis, and MCTD, low specificity for all diseases
Don’t forget that organ specific AD and infections can also causes elevated ANA

18/ Check out this @MithuRheum graphic for a summary

https://twitter.com/MithuRheum/status/1416005546885500937?s=20