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.
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:
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

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More from @AnnKumfer

4 Feb
#medtwitter Can you have a completely normal CSF profile in autoimmune encephalitis? (answer forthcoming)
This table is from a 2019 review. Interestingly in LG11, IgLON5, and GlyR the majority have a completely normal CSF profile including oligoclonal bands. (ncbi.nlm.nih.gov/pmc/articles/P…)
What about MRI? In what percentage of autoimmune encephalitis is the MRI of the head normal?
Read 8 tweets
16 Dec 20
1/#tweetorial coagulopathy in liver disease and the role of vit K

Thanks to all who responded to the poll.
2/ Pts with cirrhosis are at higher risk of bleeding d/t ⬇️ factors, right? Not necessarily. In cirrhosis, there are ⬇️ in both anticoagulant and procoagulant factors in the liver. Additionally, factor VIII and VWF are usually increased.
3/ INR is only measuring a small part of the coagulation cascade, the extrinsic pathway (Factor VII). Additionally, variceal bleed is driven by ⬆️ portal pressure primarily.
Read 7 tweets
15 Dec 20
Do you give vitamin K to pts with cirrhosis presenting with elevated INR? I would love to hear your thoughts about the topic.
Here are a few questions about Vit K in cirrhosis I wanted to answer. Please post additional articles on the topics that you know of. Question 1: Is there proof that patients with cirrhosis are Vit K deficient?
3/ It is proposed that patients w/ cirrhosis are at ⬆️ risk for Vit K def. I could find very few studies about this. This study of pediatric pts w/ cholestatic liver disease had high prevalence, but very different pop from most adults w/ cirrhosis. pubmed.ncbi.nlm.nih.gov/19502999/
Read 19 tweets
7 Dec 20
#tweetorial To obtain blood cultures or not to culture? This was inspired by the ? from @reverendofdoubt and @GermHunterMD reply.

A pt w/ a hip fracture on POD1 has fever of 100.8. HR 90, BP 110/75, SpO2 96% ambient air. No localizing symptoms. Do you obtain blood cultures?
2/My reflex when I hear fever is to order blood cultures. It’s not wrong to make sure, right? As a resident, I remember grumbling at the ED for not ordering cultures on that CAP patient. First, what are the harms of ordering unnecessary blood cultures?
3/ Aside from the cost, there is a high rate of contamination on blood cultures from 0.6% to over 6%. In conditions with a low pretest probability of bacteremia, this represents a large prob that a + culture is contamination. ncbi.nlm.nih.gov/pmc/articles/P…
Read 15 tweets
8 Nov 20
1/ #tweetorial Next on the skeptical diagnosis series, I wanted to address cellulitis. I always feel a little angst when I am called to admit a patient w/ cellulitis. Does the patient really have cellulitis? In what % of pts diagnosed with cellulitis is the diagnosis incorrect?
2/ Here, I will focus and diagnosis and mimics. I plan to discuss mng of cellulitis later. Studies show that in 30-33% in patients diagnosed with cellulitis, the diagnosis is incorrect.
3/ Of those with an incorrect diagnosis, around 85% percent do not need hospitalization and 92% did not need antibiotics. Misdiagnosis is associated with millions in increased healthcare costs and up to 9000 nosocomial infections.
pubmed.ncbi.nlm.nih.gov/27806170/
pubmed.ncbi.nlm.nih.gov/29453874/
Read 15 tweets
6 Nov 20
1/Recapping some teaching points from @CPSolvers VMR today to keep me from refreshing NYT and 538 every 2 minutes. Thanks to @Flower_freeland for presenting an awesome case today.
clinicalproblemsolving.com/morning-report…
2/ Case: A 28yM diagnosed w/uveitis about 4-5 weeks prior p/w N/V, weight loss, diffuse weakness. Most uveitis is anterior involving the iris (iritis). Anterior usually painful (front of eye in innervated). Infections commonly unilateral, autoimmune may be bilateral Image
3/ Up to 50% of anterior uveitis is HLA-B27+. Lymphoma is an important mimic. Because the patient is from Vietnam, TB is the first thing that came to my mind. With TB, you should also thing of histo (and other funi). Knowing an immune status is important is working-up infection
Read 9 tweets

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