Rheumatoid Arthritis destroy Meibomian Glands Also

Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune condition in which your own immune system mistakenly attacks your own body: it’s cells, tissues, and organs. It is characterized by localized destruction of bone, cartilage, joint interfaces, and periarticular areas. RA has increased mortality risk and a reduced life expectancy of about 3 to 10 years compared with the general population. New treatment has decreased complications and mortality, which is great news. 

RA also causes dry eye and sclera melts. 

With our meibography we have seen 14 adult patients with severe Meibomian Gland Atrophy who have RA. I have personally seen 8 patients who had minimal to no symptoms of RA with SMGA, who on a work up I ordered, have a positive Rheumatoid Factor on their blood work up: they are now being followed by Rheumatology for the full RA work up. Of these 8 patients 3 were children that had no joint or systemic symptoms. Two of these 3 children have severe scar tissue on their cornea now requiring corneal transplant. 

Yesterday a patient who was self-pay (had no insurance) from Central America came in for a consult of chronic eye pain. He is 70. His finger joints were deformed in both hands. I asked him and his daughter about his hand deformity, and they were adamant it was from an old car accident injury he had in his country. When the meibography showed severe meibomian gland loss, I had to convince him to get the Rheumatoid Factor test. It came back positive. Now he needs a full rheumatological work up, but he is here only visiting and will return to his remote farm in El Salvador. 

What is the best way to diagnose Rheumatoid Arthritis in adults & kids?

ACR/EULAR (2010) Classification Criteria for RA

ACR/EULAR (2009) Classification Criteria for Rheumatoid Arthritis
Symptom Duration (as reported by patient)                                                Points
  • < 6 weeks                                                                                                    0
  • > 6 weeks                                                                                                    1
Joint Distribution                                                                                           Points
  • 1 large joint                                                                                                 0
  • 2-10 large joints                                                                                          1
  • 1-3 small joints (with or without involvement of large joints)                       2
  • 4-10 small joints (with or without involvement of large joints)                     3
  • > 10 joints (at least 1 small joint)                                                                5
Serology                                                                                                         Points
  • RF- and CCP-                                                                                             0
  • Low RF+ or CCP+                                                                                      2
  • High RF+ or CCP+                                                                                     3
Acute Phase Reactants                                                                                Points
  • Normal ESR or CRP                                                                                  0
  • Abnormal ESR or CRP                                                                              1
RF: rheumatoid factor.  CCP: anti-citrullinated citric peptide.  ESR: erythrocyte sedimentation rate.  CRP: C-reactive protein.  Low: < 3 x upper limit of normal (ULN).  High: > 3 x ULN
Requirements: patients who have at least 1 swollen joint, and not better explained by another diseaseto be applied.  A score ≥ 6 points is required for classification as definite RA.
Reference:   Aletaha et al.  2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology / European League Against Rheumatism collaborative initiative.  Ann Rheum Dis 2010;69:1580-1588.   

Newer Ways to Diagnose Any Arthritis: Is it Rheumatoid Arthritis or something else?
1. global assessment on visual analogue scales (VAS), 
2. Health Assessment Questionnaire Disability Index (HAQ-DI) 
3. Medical Outcomes Study Short Form-36 (SF-36). 
4. Erythrocyte sedimentation rate (ESR) 
5. C reactive protein (CRP) levels  
6. Anticitrullinated protein antibodies (ACPA)
7. Rheumatoid factor (RF)
8. HLA-B27
9. Serum uric acid, 
10. Joint fluid analyses
11. Microbial tests 
12. Ultrasound 
13. ACPA: anticyclic citrullinated peptide 2 test (Inova Diagnostics, San Diego, California, USA (886 patients), and Phadia, Freiburg, Germany (113 patients))
14. Immunoglobulin M and immunoglobulin A RF (ELISA) 

Symptoms of Rheumatoid Arthritis

If a patient has just a positive Rheumatoid Factor and no symptoms of arthritis, it is not Rheumatoid Arthritis yet. It could be an early marker but I do not know of any MD that will treat only the marker (yet: don’t forget that Dr. Judah Folkman at Harvard fought the fight of having cancer doctors treat the marker and not the objective sign of the cancer: he won, but it was a hard fight to prove; for Endocrinology & RA, it is very early in the understanding if a marker alone should be treated. I personally think, a positive marker that is truly positive and not a false positive should be a reason to change your lifestyle [go organic, avoid gluten, avoid environmental risks like smokers/smoking. But starting hard drugs like Plaquenil and Methotrexate that have risks: likely I would wait until the symptoms of joint aches are truly, consistently present or the symptoms below). The big question for me will be is IF Severe Meibomian Gland Atrophy is directly due to the sub-microscopic scarring from Rheumatoid Arthritis, do they need to be treated 
Signs and symptoms of rheumatoid arthritis may include:
  • Tender, warm, swollen joints
  • Joint stiffness that is usually worse in the mornings and after inactivity
  • Fatigue, fever and weight loss
Early rheumatoid arthritis tends to affect your smaller joints first — particularly the joints that attach your fingers to your hands and your toes to your feet.
As the disease progresses, symptoms often spread to the wrists, knees, ankles, elbows, hips and shoulders. In most cases, symptoms occur in the same joints on both sides of your body.
About 40 percent of the people who have rheumatoid arthritis also experience signs and symptoms that don’t involve the joints. Rheumatoid arthritis can affect many nonjoint structures, including:
  • Skin
  • Eyes
  • Lungs
  • Heart
  • Kidneys
  • Salivary glands
  • Nerve tissue
  • Bone marrow
  • Blood vessels
Rheumatoid arthritis signs and symptoms may vary in severity and may even come and go. Periods of increased disease activity, called flares, alternate with periods of relative remission — when the swelling and pain fade or disappear. Over time, rheumatoid arthritis can cause joints to deform and shift out of place.

How to Best Treat Rheumatoid Arthritis:

DMARDs and biologics

Disease-modifying antirheumatic drugs (DMARDs) are used to decrease inflammation. Unlike other medications that temporarily ease pain and inflammation, DMARDs can slow the progression of RA. This means that you may have fewer symptoms and less damage over time.
The most common DMARDs used to treat RA include:
  • hydroxychloroquine (Plaquenil)
  • leflunomide (Arava)
  • methotrexate (Trexall)
  • sulfasalazine (Azulfidine)
  • minocycline (Minocin)
Biologics are injectable drugs. They work by blocking specific inflammatory pathways made by immune cells. This reduces inflammation caused by RA. Doctors prescribe biologics when DMARDs alone aren’t enough to treat RA symptoms. Biologics aren’t recommended for people with compromised immune systems or an infection. This is because they can raise your risk of serious infections.
The most common biologics include:
  • abatacept (Orencia)
  • rituximab (Rituxan)
  • tocilizumab (Actemra)
  • anakinra (Kineret)
  • adalimumab (Humira)
  • etanercept (Enbrel)
  • infliximab (Remicade)
  • certolizumab pegol (Cimzia)
  • golimumab (Simponi)

Janus associated kinase inhibitors

Your doctor may prescribe these drugs if DMARDs or biologics don’t work for you. These medications affect genes and the activity of immune cells in the body. They help prevent inflammation and stop damage to joints and tissues.
Janus associated kinase inhibitors include:
  • tofacitinib (Xeljanz, Xeljanz XR)
  • baricitinib
Baricitinib is a new drug that’s being tested. Studies suggest that it works for people who don’t have success with DMARDs.
The more common side effects of these drugs include:
  • headache
  • upper respiratory infections, like sinus infections or the common cold
  • congested nose
  • runny nose
  • sore throat
  • diarrhea


Acetaminophen is available over the counter (OTC) without a prescription from your doctor. It comes as an oral drug and a rectal suppository. Other drugs are much more effective at reducing inflammation and treating pain in RA. This is because acetaminophen can treat mild to moderate pain, but it doesn’t have any anti-inflammatory activity. This means it doesn’t work very well to treat RA.
This drug carries the risk of serious liver problems, including liver failure. You should only take one drug that contains acetaminophen at a time.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs are among the most commonly used RA drugs. Unlike other pain relievers, NSAIDs seem to be more effective in treating symptoms of RA. This is because they prevent inflammation.
Some people use OTC NSAIDs. However, stronger NSAIDs are available with a prescription.
Side effects of NSAIDs include:
  • stomach irritation
  • ulcers
  • erosion or burning a hole through your stomach or intestines
  • stomach bleeding
  • kidney damage
In rare cases, these side effects can be fatal (cause death). If you use NSAIDs for a long time, your doctor will monitor your kidney function. This is especially likely if you already have kidney disease.

Ibuprofen (Advil, Motrin IB, Nuprin)

OTC ibuprofen is the most common NSAID. Unless instructed by your doctor, you should not use ibuprofen for more than several days at a time. Taking this drug for too long can cause stomach bleeding. This risk is greater in seniors.
Ibuprofen is available in prescription strengths as well. In prescription versions, the dosage is higher. Ibuprofen may also be combined with another type of pain drug called opioids. Examples of these prescription combination drugs include:
  • ibuprofen/hydrocodone (Vicoprofen)
  • ibuprofen/oxycodone (Combunox)

Naproxen sodium (Aleve)

Naproxen sodium is an OTC NSAID. It’s often used as an alternative to ibuprofen. This is because it causes slightly fewer side effects. Prescription versions of this drug offer stronger dosages.

Aspirin (Bayer, Bufferin, St. Joseph)

Aspirin is an oral pain reliever. It’s used to treat mild pain, fever, and inflammation. It can also be used to prevent heart attack and stroke.

Prescription NSAIDs

When OTC NSAIDs don’t relieve your RA symptoms, your doctor may prescribe a prescription NSAID. These are oral drugs. The most common options include:
  • celecoxib (Celebrex)
  • ibuprofen (prescription-strength)
  • nabumetone (Relafen)
  • naproxen sodium (Anaprox)
  • naproxen (Naprosyn)
  • piroxicam (Feldene)
Other NSAIDs include:

  1. diclofenac (Voltaren, Diclofenac Sodium XR, Cataflam, Cambia)
  2. diflunisal
  3. indomethacin (Indocin)
  4. ketoprofen (Orudis, Ketoprofen ER, Oruvail, Actron)
  5. etodolac (Lodine)
  6. fenoprofen (Nalfon)
  7. flurbiprofen
  8. ketorolac (Toradol)
  9. meclofenamate
  10. mefenamic acid (Ponstel)
  11. meloxicam (Mobic)
  12. oxaprozin (Daypro)
  13. sulindac (Clinoril)
  14. salsalate (Disalcid, Amigesic, Marthritic, Salflex, Mono-Gesic, Anaflex, Salsitab)
  15. tolmetin (Tolectin)

Diclofenac/misoprostol (Arthrotec)

Diclofenac/misoprostol (Arthrotec) is an oral drug that combines the NSAID diclofenac with misoprostol. NSAIDs can cause stomach ulcers. This drug helps prevent them.

Topical capsaicin (Capsin, Zostrix, Dolorac)

Capsaicin topical OTC cream can relieve mild pain caused by RA. You rub this cream on painful areas on your body.

Diclofenac sodium topical gel (Voltaren 1%)

Voltaren gel 1% is an NSAID for topical use. This means you rub it on your skin. It’s approved to treat joint pain, including in your hands and knees.
This drug causes similar side effects to oral NSAIDs. However, only about 4 percent of this drug is absorbed into your body. This means that you may be less likely to have side effects.

Diclofenac sodium topical solution (Pennsaid 2%)

Diclofenac sodium (Pennsaid 2%) is a topical solution used for knee pain. You rub it on your knee to relieve the pain.


Corticosteroids are also called steroids. They come as oral and injectable drugs. These drugs can help reduce inflammation in RA. They may also help reduce the pain and damage caused by inflammation. These drugs aren’t recommended for long-term use.
Side effects can include:
  • high blood sugar
  • stomach ulcers
  • high blood pressure
  • emotional side effects, such as irritability and excitability
  • cataracts, or clouding of the lens in your eye
  • osteoporosis
Steroids used for RA include:
  • betamethasone
  • prednisone (Deltasone, Sterapred, Liquid Pred)
  • dexamethasone (Dexpak, Taperpak, Decadron, Hexadrol)
  • cortisone
  • hydrocortisone (Cortef, A-Hydrocort)
  • methylprednisolone (Medrol, Methacort, Depopred, Predacorten)
  • prednisolone


These drugs fight off the damage caused by autoimmune diseases such as RA. However, these drugs can also make you more prone to illness and infection. If your doctor gives you one of these drugs, they’ll watch you closely during treatment.
These drugs come in oral and injectable forms. They include:
  • cyclophosphamide (Cytoxan)
  • cyclosporine (Gengraf, Neoral, Sandimmune)
  • azathioprine (Azasan, Imuran)
  • hydroxychloroquine (Plaquenil)

Opioid pain drugs

Opioids are the strongest pain drugs on the market. Avoid these at all costs as they are very addictive. They are only available as prescriptions drugs. They come in oral and injectable forms. Opioids are only used in RA treatment for people with severe RA who are in intense pain. These drugs can be habit-forming. If your doctor gives you an opioid drug, they should watch you closely and try to get you off Opioids.
People with RA who take opioids should also use other treatments. This is because opioids only change the way you experience pain. They don’t slow the disease down or prevent inflammation.
Opioids include:
  • codeine
  • acetaminophen/codeine
  • fentanyl
  • hydrocodone (Vicodin)
  • hydromorphone
  • morphine
  • meperidine (Demerol)
  • oxycodone (Oxycontin)
  • tramadol (Ultram)

 2018 Jan 4. doi: 10.1111/1756-185X.13248. [Epub ahead of print]

Long-term efficacy and safety of add-on tacrolimus for persistent, active rheumatoid arthritisdespite treatment with methotrexate and tumor necrosis factor inhibitors.



To assess the long-term efficacy and safety of adding tacrolimus for patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor (TNF) therapy with methotrexate.


Consecutive patients who were treated with adding tacrolimus onto anti-TNF therapy with methotrexate for active RA despite anti-TNF therapy with methotrexate, were retrospectively analyzed in terms of treatment response, achieving remission, subsequent treatment tapering and adverse events.


Fifteen patients could be analyzed. Median symptom duration was 2.9 years and prior duration of anti-TNF therapy was 40 weeks. Median value of Disease Activity Score in 28 joints was 4.6. Five, eight and two were on infliximab, etanercept and adalimumab at the onset of tacrolimus, respectively. At 2 years, the proportions of patients achieving responses of American College of Rheumatology 50, 70 and 90, were 80%, 73% and 40%, respectively, and those achieving remission as defined by Simplified Disease Activity Index ≤ 3.3 were 67%. All patients could discontinue oral glucocorticoids and 10 had been successfully withdrawn from anti-TNF therapy for more than 1 year at the final observation.


Adding tacrolimus onto anti-TNF therapy is a promising therapeutic option with sustained benefit for refractory RA patients despite treatment with anti-TNF therapy combined with methotrexate.

 2018 Jan 6. doi: 10.1002/jcb.26659. [Epub ahead of print]

MiR-548a-3p regulates inflammatory response via TLR4/NF-κB signaling pathway in rheumatoid arthritis.

Wang Y1,2Xu D2Yan S3Zhang L4Wang L2Cai X2Wang X2Wang J1.


Currently published studies have implicated that microRNAs (miRNAs) including exosomes-encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes-encapsulated miR-548a-3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR-548a-3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR-548a-3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of miR-548a-3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down-regulated compared with healthy controls (n = 20). Serum exosomal miR-548a-3p was negatively associated with levels of CRP, RF and ESR in serum of patients with RA. MiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells by regulating the TLR4/NF-κB signaling pathway. Accordingly, exosomes-delivered miR-548a-3p may be a critical factor predicting the disease activity of RA. MiR-548a-3p/TLR4/NF-κB axis can serve as promising targets for RA diagnosis and treatment. This article is protected by copyright. All rights reserved

 2017 Dec 20. doi: 10.1002/acr.23497. [Epub ahead of print]

Is ACPA-positive RA still a more severe disease than ACPA-negative RA? A longitudinal cohort study in RA-patients diagnosed from 2000 onwards.

Author information

Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Rheumatology, Maastricht University Medical Center, and Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
Department of Rheumatology, Erasmus Medical Center, Rotterdam, the Netherlands.



Anti-citrullinated-protein antibodies (ACPA)-positive rheumatoid arthritis (RA) is considered as more severe than ACPA-negative RA, because of its association with joint destruction. Clinically relevant joint destruction is now infrequent, thanks to adequate disease suppression. According to patients, important outcomes are pain, fatigue and independence. We evaluated if ACPA-positive RA-patients diagnosed ≥2000 have more severe self-reported limitations and impairments including restrictions at work than ACPA-negative RA-patients.


492 ACPA-positive, 450 ACPA-negative 2010-criteria-positive RA-patients included in the Leiden Early Arthritis Clinic cohort ≥2000 were compared for self-reported pain, fatigue, disease activity, general wellbeing (measured by numerical rating scales) and physical function (measured by the health assessment questionnaire, HAQ) and work restrictions including absenteeism at baseline and during 4-year follow-up. Linear mixed models were used.


At disease presentation, ACPA-negative patients had more severe pain, fatigue, self-reported disease activity-scores and functional disability (p<0.05), although absolute differences were small. During follow-up ACPA-negative patients remained somewhat more fatigued (p=0.002), whereas other patient-reported impairments and limitations were similar. 38% ACPA-negative and 48% ACPA-positive patients reported absenteeism (p=0.30), with median 4 days missed in both groups in the last 3 months. Also restrictions at work among employed patients and restrictions with household work were not statistically different at baseline and during follow-up.


In current rheumatology practice, ACPA-positive RA is not more severe than ACPA-negative RA in terms of for patients relevant outcomes including physical functioning and restrictions at work. This implies that effort to further improve the disease course should be proportional to both disease subsets. This article is protected by copyright. All rights reserved.
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