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Diseases and Conditions

Diseases and Conditions

What are the risks vs. benefits of biologic therapy?

March 8, 2017

Some of you may recall one of my previous posts where I attempted to dispel some of the myths commonly associated methotrexate.  Don’t get me wrong, I frequently use methotrexate.  It is considered gold standard for the treatment of rheumatoid arthritis.  And this is despite the armada of new fancy medications coming onto the market.  The American College of Rheumatology doesn’t call it the gold standard for nothing.

But sometimes it isn’t enough.

It’s estimated that about 30% of people achieve either remission or very minimal disease activity with methotrexate alone.  That leaves the other 70%.  Maybe this includes you?  In this situation, your rheumatologist may either recommend you to combine methotrexate with another conventional disease modifying anti-rheumatic drug (DMARD) or either to combine it with a biologic DMARD.  The decision is very complex and will vary from person-to-person and from rheumatologist-to-rheumatologist.  Were there issues with the ability to tolerate the medication, allergies, other medical conditions, insurance coverage, safety profile concerns, etc?  And then there’s just style.

DMARDs

In the best of situations, ALL people diagnosed with rheumatoid arthritis should be started on a DMARD as quickly as possible.  For those who don’t really know me, the tone of this statement is very uncharacteristic of me.  I loathe dogma and authoritarian statements in general.  But when it comes to DMARDs and rheumatoid arthritis, people that receive these medications as soon as possible do better and have less joint damage.  It’s important to achieve remission or have very minimal disease activity as soon as possible and as long as possible.

So what is a DMARD? For a medication to be considered a DMARD it has to change the course of the disease, for the better:), for at least one year.  There should be improvement in either physical function, decreased swelling, or slowing/prevention of joint damage.

To understand why your doctor may want to start a biologic medication, it’s important to understand what is meant by a conventional vs. a biologic DMARD.

I would say there are two main differences between conventional DMARDs and biologic DMARDs: mechanism of action and cost.  Conventional DMARDs do NOT directly target a specific type of inflammation.  Biologics do.  This means that biologics are a lot more molecular complex.  This also means that they are A LOT more expensive.  Even in countries like Canada, where the single payer system has the ability to negotiate prices with pharmaceutical companies, the price is still very high.  I could on and on with this subject, but I’ll leave that for another post.

Conventional DMARDs

  • Often used
    • Hydroxychloroquine
    • Methotrexate
    • Leflunomide
    • Sulfasalazine
  • Not really used
    • Azathioprine
    • Mycophenolate, sometimes used for rheumatoid arthritis affecting the lungs
    • Cyclophosphide, used for life or organ threatening disease
    • Cyclosporine
    • Gold injections

Biologic DMARDs

  • Tumor necrosis factor inhibitors
    • Etanercept
    • Adalimumab
    • Golimumab
    • Certolizumab pegol
    • Infliximab
  • Interleukin-6 inhibitors
    • Tocilizumab
  • Co-stimulation inhibitors
    • Abatacept
  • JAK inhibitors
    • Tofacitinib
  • B cell depletion
    • Rituximab

There are other medications that are coming down the pipeline, but these are the ones that are FDA approved and commercially available for the treatment of rheumatoid arthritis.  There are other biologic medications like belimumab, apremilast, ustekinumab, and secukinumab that are used for other diseases like systemic lupus erythmatosus, psoriatic arthritis, and ankylosing spondylitis.

Triple therapy vs. methotrexate + biologic

Generally triple therapy refers to the simultaneous use of methotrexate + sulfasalazine + hydroxychloroquine for the treatment of rheumatoid arthritis.  A Cochrane meta-analysis recently found that triple therapy typically is just as effective as methotrexate + a biologic or tofacitinib alone.  So why is your doctor proposing going to a biologic medication instead of going to triple therapy?  It certainly would be cheaper.

This is where I would say is one of the potential benefits of biologics: the ability to tolerate treatment long-term.  Let’s put things into perspective.  When you take an antibiotic, you may end up with some GI discomfort, diarrhea, some nausea, etc.  You receive 7 days worth of treatment, the infection is gone, it usually takes a few more days for things to settle down, but then it’s done.  When it comes to the vast majority of rheumatic conditions like rheumatoid arthritis, some form of medication is consistently needed to keep the disease in remission. If you stop, the disease flares.  Don’t get me wrong, there are exceptions.  Sometimes the disease goes into permanent remission or “burns out”.  This is rare and definitely is not the rule.

The problem with triple therapy is that it tends to be very difficult to tolerate long-term.  Most people could tolerate a few weeks, but we’re talking years, decades, lifetime.  Many people stop one or more of the medications without telling their doctor, others take them sporadically.  Basically, there’s a lot of non-compliance with treatment when people receive triple therapy.

It isn’t necessarily because those people are irresponsible.  It’s that the medicines are making them feel sicker than their actual disease!

Simply put, biologics tend to be a lot easier to tolerate long-term and to bout SOME can be used as monotherapy i.e., you don’t need to combine with methotrexate.

Onset of action

I wouldn’t say that this is necessarily the most important factor when making a decision to go with a biologic instead of sticking to conventional DMARDs but I guess it could help tip the balance in certain situations.  In general biologic DMARDs tend to work a little more quickly that conventional.  This greatly varies from biologic-to-biologic.  Generally conventional DMARDs taking between 3 – 6 months to fully work.  It tends to be closer to the 3 month mark.  For most biologics it can take up to 3 months.  Certain ones like abatacept can take up to 6 months as well.

Cost

Most biologics cost over $ 1 100 per month.  Mind you, hardly anyone actually pays $ 1,100 per month.  Before starting a biologic medication, you doctor’s office will obtain authorization from your insurance company prior to prescribing the medication.  When the medication is authorized, your doctor will send it to your prescription mail-order company, and then it will be mailed to you.  Co-pays vary from $5 a script to a few hundred dollars in extreme cases.  It really depends on your insurance coverage.  It’s very important to keep your doctor but also your doctor’s medical secretary and if your doctor is extra lucky, your doctor’s patient advocate, appraised of all changes to your insurance.  It can mean the difference between a $5 co-pay and a second mortgage.  Most pharmaceutical companies have patient assistance programs.  Some are better than others… and some are better advertised than others.

Conventional DMARDs are a lot cheaper.  For example, methotrexate comes in 2.5 mg tablets.  20 tablets cost a little over $25.  This is the price if you had no insurance and were paying completely out of pocket.  Someone taking oral methotrexate will typical take between 24 to 40 tablets per month.  For most people this is doable even without any insurance.

Conversely, if you were receiving etanercept and had no insurance, your out of pocket cost would be about $3,500 per month.  Again, your doctor’s team will work to have the medication covered, but it’s still something to think about.

Method of delivery

This may be a non-issue for many people but it may be for some.  Most biologics need to either be injected or infused.  So far, only tofacitinib (rheumatoid arthritis) and apremilast (psoriatic arthritis) are taken orally.  There are pros and cons for both injections and infusions but generally, if your needle phobic, this may be a problem.  Infusions are time consuming because you need to come to the clinic to receive the infusion.  They typically last between an hour to half a day depending on the medication.  Some are dosed every month others every 8 weeks.  Rituximab is every 6 months but this is an exception.  Most injections are either given every week or every other week.  Some are a lot less frequent like ustekinumab, but again this is an exception.

Conversely, all the conventional DMARDs are oral except for cyclosphosphamide and gold.  I’ve never prescribe cyclophosphamide for rheumatoid arthritis… ever.  First, we simply do not encounter many people with life-threatening complications caused by rheumatoid arthritis anymore because the vast majority of people with the condition are treated with DMARDs very early into their disease.  Second, there are many other medications on the market that are a whole like better.  Don’t get me wrong, there are certain very serious indicated clinical situations.  Just wrote an order for it last week… my first in a year and it wasn’t for RA!

Infection risk

One of the big differences between conventional DMARDs and biologics is the infection risk.  Biologic medications generally are a lot more immunosuppressive than conventional DMARDs.  Again there are exceptions.  For example, abatacept is generally thought to have less of an infection risk.

I have to stress that this does not mean that people taking biologics get a ton of infections.  But it becomes extra important to keep up with routine vaccinations, adhere to proper hand washing, and try to stay away from high risk situations as much as possible.  It may also not be such a great idea to be on a biologic if you are prone to getting infections.  Let’s face it, no one wants 10 sinus infections in one year.  It also may not be such a great idea to be one some of these biologics if you have very serious lung problems.  I probably will try to avoid most biologics if someone has severe COPD requiring extra oxygen.  Pneumonia could be life-threatening in this situation.

Another important noteworthy point, certain biologics can re-activate dormant infections such as tuberculosis, hepatitis B+C, and zoster.  It’s important to screen for both tuberculosis and hepatitis B+C prior to initiation of therapy.   You may need to start therapy for these latent infection prior to treatment with biologics.  For zoster also known as shingles, you may benefit from the shot one month prior to treatment with biologics.  The shingles shot is a live vaccine and should NOT be given while taking a biologic medication.  Like I said, you need to wait a month.  Please contact your rheumatologist for more information.

Miscellaneous

There are a few other items of concern but these vary from medication to medication irrespective of whether that medication is a conventional DMARD or a biologic.  The following are items to consider when choosing the most appropriate medications.

  • History of hepatitis C
  • History of HIV
  • History of a demyelinating disease like multiple sclerosis
  • History of severe congestive heart failure
  • History of lymphoma or leukemia
  • History of melanoma
  • History of a solid cancer within the last 5 years (e.g., breast cancer)
  • History serious liver disease
  • History of a serious kidney disease
  • History of serious lung disease
  • History of serious diverticulitis or bowel perforation
  • History of gastric bypass surgery
  • History of macular degeneration
  • History of organ transplant
  • Allergy history
  • Current medications.  Are there any possible drug interactions? (e.g., azathioprine and allopurinol should not be combined)

Having one of these does NOT mean you cannot take any biologic medication safely.  It simply means that certain ones may not be such a good idea.  For example, tumor necrosis inhibitors should not be taken by people suffering from multiple sclerosis.

Conclusion

I hope this helps clarify a few concerns that you may have had regarding biologic medications.  Maybe I’ve caused you to think about things you had not thought about before?  Choosing the best course of therapy can be very complex.  There are so many things to think about and the down stream effects could be very serious.

Open communication and knowledge are key!

References

Rheumatology Secrets 3rd edition

Hazlewood GS, et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis. Cochrane Database Syst Rev. 2016 Aug 29;(8):CD010227. doi: 10.1002/14651858.CD010227.pub2.

https://www.drugs.com/price-guide/methotrexate

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Diseases and Conditions When to see a rheumatologist

10 Warning signs you could have Sjögren’s syndrome

March 1, 2017
Sjögren's syndrome can cause dry eyes and dry mouth as well as many other symptoms. Read on to learn more!

Today is a most bizarre weather-related day.  It’s warm, like you don’t need a coat warm, and there’s a raging thunderstorm.  Did I mention it’s February in upstate New York?  In honor of this most bizarre day, I’d thought I’d write a few words on a somewhat bizarre and illusive autoimmune disease called Sjögren’s syndrome.

Henrich Sjögren gave Sjögren’s syndrome its name.  He was a Swedish physician who first described the disease in 1933.  Sjögren’s syndrome is a common autoimmune disease that primarily causes dryness.  But it’s a lot more complicated than that because Sjögren’s syndrome can involve almost any organ so can present with a myriad of symptoms.  The symptoms arise from infiltration of lymphocytes into glands and affected organs.  Simply put, Sjögren’s syndrome is on the differential diagnosis in any person who has a positive ANA presenting with unexplained symptoms.

10 Warning signs you may be suffering from Sjögren’s syndrome

The following are some of the common manifestations of Sjögren’s syndrome.  Believe me, there are A LOT more but these are some of the common ones.

  1. Dry eyes
  2. Dry mouth
  3. Swollen cheek(s) i.e., parotid gland enlargement
  4. Profound tiredness
  5. Joint pain, sometimes with swelling
  6. Swollen glands
  7. Numbness, tingling, burning of the skin
  8. Raynaud’s
  9. Shortness of breath with minimal work
  10. Having a child that suffered from congenital heartblock

Dry mouth symptoms

The following are some common symptoms of dry mouth.

  1. Difficulty swallowing dry foods
  2. Inability to talk continuously
  3. Change in taste
  4. Burning sensation
  5. Large dentist bill! – Cavities, cracked teeth, loose fillings
  6. Problems with your dentures
  7. Worsening heartburn
  8. Thrush

As you can see the symptoms are a little all over the place and quite frankly are kind of vague.  Furthermore, many different conditions can mimic some of these symptoms: dehydration, depression, various medications, uncontrolled diabetes, multiple sclerosis, hepatitis C, sarcoidosis, etc etc.  Literally.

Classification criteria

Now it’s important to note that the following classification criteria are used for research purposes, and not necessarily for the day-to-day clinic.  Although they are important, there is such a thing called the art of medicine.

As we all know, not everyone fits into a neat little box.

Recently the American College of Rheumatology and the European League Against Rheumatism came up with a new system to classify Sjögren’s.  Basically, a group of hot-shot Sjögren’s specialists got together, looked at the literature, probably had more than one heated discussion, and came up with the following.

To test positive you need to have a score ≥4.  There are five items but they are weighted differently.

  • 3 Points – Anti-SSA/Ro antibody positivity
  • 3 Points – Focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2
  • 1 Point – Abnormal Ocular Staining Score of ≥5 (or van Bijsterveld score of ≥4)
  • 1 Point – Schirmer’s test result of ≤5 mm/5 mi
  • 1 Point – Unstimulated salivary flow rate of ≤0.1 mL/min, each scoring = 1

The sensitivity of this score is 96% and the specificity is 95%.  The sensitivity tells you how likely you are to detect all cases of Sjögren’s syndrome and the specificity tells you how accurate you are with the diagnosis using these set of diagnostic criteria.  These are pretty good figures.

What does this mean?

As you can see, the diagnosis favors objective findings, NOT symptoms.  This is a huge change from the previous set of diagnostic criteria.  You’ll also note that positive ANA, rheumatoid factor, and positive anti-SSB/La antibody positivity are not included in the new classification criteria.

Now I don’t want people thinking that I think symptoms are unimportant.  They are VERY important.  It’s just that symptoms should prompt a workup looking for objective features of the disease.

Now, try to remember the 10 warning signs.  If you find yourself checking a few of these items, check-in to your local rheumatologist.

References

Rheumatology Secrets 3rd edition

Shiboski CH, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts.Ann Rheum Dis. 2017 Jan;76(1):9-16.

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Diseases and Conditions

10 frequently asked questions when starting methotrexate

February 22, 2017
Methotrexate is one of the mostly frequently prescribed medications in rheumatology. It has great joint-saving potential but also has a considerable list of potential side effects. In this week's edition of RheumDoctor, we address frequently asked questions when starting methotrexate.

Hands down, methotrexate is one of the most frequently prescribed medications in the field of rheumatology as it is the cornerstone medication for rheumatoid arthritis.  As a rheumatologist, I tend to classify time as, “the time before methotrexate” and“the time after methotrexate”.

Methotrexate was first reported by Sidney Farber in 1948 for the use of childhood leukemia.  By 1951, Gubner observed that people with rheumatoid arthritis and psoriasis improved while taking the medication and soon worsened after stopping it. Unfortunately and fortunately, during this time Dr. Phillip Hench received a Nobel prize for the discovery of corticosteroids.  At that point, interest for methotrexate waned.  It’s only in the mid-1980’s that a renewed interest for this paradigm-shifting medication occurred. The rest is history.I don’t believe anyone can argue the significant benefits methotrexate can give.  The scientific evidence is overwhelming.  But it also boasts a considerable list of potential side effects.

 In this week’s edition of RheumDoctor, I address frequently asked questions when starting methotrexate.

1. Why do I have to take methotrexate?  I went online and it sounds dangerous.

Methotrexate is a disease modifying anti-rheumatic drug (DMARD).  What this means, is that it potentially halts the natural progression of rheumatoid arthritis. If left untreated, rheumatoid arthritis causes joint deformities and permanent joint destruction.  Deformities can occur within 3 months of disease onset.  That’s fast!  Uncontrolled rheumatoid arthritis increases the risk of cardiovascular disease and can also directly affect major organs such as the lungs, eyes, and bone marrow.  Methotrexate has a good chance of preventing all the above.

2. Why do I have to take folic acid with methotrexate?

Methotrexate competitively inhibits dihydrofolate reductase (DHFR).  This is in turn decreases the amount of bioavailable folic acid in your body.  You need folic acid to make new cells.  What does this mean?  Side effects: mouth ulcers, hair loss,nausea, heartburn, abdominal pain, fatigue, anemia, liver problems.  By taking supplemental folic acid, you are trying to overwhelm the system with folic acid so that you don’t develop side effects.

 It’s important to note, that if you take too much folic acid, it will negate the therapeutic benefits of your medication.

3. Why must I have bloods drawn on regular intervals while I’m taking methotrexate?

Simply put, safety. Before starting methotrexate you need to screen for hepatitis B and hepatitis C. This isn’t personal, it’s just safe.  You will also need a chest x-ray done before starting the medication.  Methotrexate can cause you to develop lung nodules and rarely can cause inflammation of the lungs. Basically, you want to make sure that everything is okay before starting the medication.  

For example, if I find many lung nodules before doing anything, I’ll probably want to start treatment with a different DMARD. It’s also important to check a complete blood panel and check your liver and kidney levels before starting methotrexate.  This is for the same reasons as the chest x-ray, safety.

Now once you are on methotrexate, it’s important to watch for side effects.  Typically, you need bloods every 3-4 weeks in the beginning and then every 3 months once you are on a stable dose. This is important because you may not necessarily physically feel you are becoming more anemic or that your liver is inflamed.

On a side note, if you check the bill you received from your insurance company, you might see the code“high risk medication monitoring – Z79.899”.  This does NOT mean you are participating in questionable or “high risk activities”, if you know what I mean.  It simply means that your doctor needs to check your labs on a frequent basis because of the medications you are taking.

4. What about combining other medications with methotrexate? Is it safe?

Methotrexate is commonly combined with other medications.  About 1/3 of people treated with methotrexate for rheumatoid arthritis will either have very little symptoms or will go into remission. The other 2/3 will need to use combination therapy.  Methotrexate is commonly called the “anchor” in rheumatoid arthritis treatment regimens. Some medications are safe to combine and some are not.  This will depend on many factors like lifestyle choices, your other different medications, liver status, and your other medical conditions.

5. How much alcohol is safe for me to drink with methotrexate?

Methotrexate can potentially cause inflammation of the liver.  So technically, it’s probably not a good idea to drink any alcohol while taking methotrexate. That being said, drinking one standard glass of alcohol once a week probably is safe.  This is a bit of a touchy subject, and you should discuss this more with your doctor.  If you click the following link, I have a full article dedicated to this topic.

6. Do I have to worry about infections with methotrexate?

Whether methotrexate significantly increases your risk of infections is poorly understood and there is a lot of conflicting data out there.  Most serious infections tend to occur in people receiving both methotrexate and prednisone or with another biologic agent at the same time.  To be extra cautious I would say, low dose methotrexate (i.e., max 25 mg once weekly) could predispose you to have more infections but the risk is probably very small.  In fact, recent data even suggests that continuing methotrexate during the time around orthopedic surgeries is probably fine.  More data is needed though.  That being said, it’s important to be up-to-date with vaccines and to regularly wash your hands especially during flu season.

7. What do I do if I’m planning to become pregnant?

Methotrexate can cause miscarriages and can cause fetal abnormalities.  
You absolutely, cannot be on this medication during pregnancy. It sticks around your body for a long time.  If you plan to become pregnant, you need to come off the medication 3 months before trying to conceive.  Before making any changes, please discuss with your rheumatologist.  Open communication is key!

8. What does my husband do if we want to have children and he is on methotrexate?

Same as the above.  The rules for men are the same for women.

9. Is breast-feeding safe while taking methotrexate?

No.

10. Does methotrexate cause cancer?

To answer this question, I need to discuss methotrexate dosage.  In rheumatology, we use low doses of methotrexate(i.e., max 25 mg once a week).  When using methotrexate for cancer, we’re talking a dose of at least 500 mg/m².  The doses vary from cancer to cancer but we’re talking massively larger doses than for rheumatoid arthritis.  Increased risk of malignancy caused by methotrexate has been described in people with concurrent Epstein Barr infection and lymphoma as well as MALT (mucosa-associated lymphoid tissue) lymphomas.  Moreover, MALT lymphomas tend to regress when you stop methotrexate.  There actually isn’t any good quality data supporting the theory that low dose methotrexate directly causes solid cancer, skin cancers, or leukemias.

This isn’t to say that you will not develop cancer while taking low dose methotrexate.  It’s just that it probably wasn’t the methotrexate that caused the cancer.

It all boils down to benefit versus risk. What is the risk of not treating rheumatoid arthritis?  What is the risk of developing a serious side effect from methotrexate?  Does methotrexate have a good chance of halting the progression of rheumatoid arthritis?  The answer to these questions is different for everyone.

What I would say is that the potential benefits of methotrexate more often than not, outweigh the risks.  Again, this is an important discussion you should have with your doctor.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

References

Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc. 2013;124:16-25.

Rheumatology Secrets, 3rd edition

Saitoh M, Matsushita K. Prevention of surgical site infection for orthopedic surgery in rheumatoid arthritis. Nihon Rinsho. 2016 Jun;74(6):993-9.

Malaviya AN. Low-dose methotrexate (LD-MTX) in Rheumatology Practice – A widely misunderstood drug. Curr Rheumatol Rev. 2016;12(3):168-176. Hellgren K, et al. Rheumatoid arthritis and risk of malignant lymphoma- Is the risk still increased? Arthritis Rheumatol. 2016 Dec 19. doi: 10.1002/art.40017.

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Diseases and Conditions

Does acupuncture help neuropathy?

February 8, 2017

Does acupuncture help neuropathy?  Good question.  But before trying to answer that question, why does a rheumatologist care about neuropathy anyways?  Isn’t neuropathy more of a neurology thing?  The answer to that question is yes and no.  If you’ve read a few RheumDoctor articles, you’ve probably realized that rheumatology is not just about joints.  It’s about the immune system, and the immune system affects ALL organs including the nervous system.  That being said, innumerable autoimmune diseases affect nerves including: lupus, rheumatoid arthritis, Sjogren’s syndrome, vasculitis, ankylosing spondylitis/axial spondylitis, scleroderma, myositis, sarcoidosis, etc.  I could go on, but I think you get the point?

So what is neuropathy anyway?

In medical terms, neuropathy, more specifically peripheral neuropathy, occurs when peripheral nerves are malfunctioning for any number of reasons.  Peripheral nerves are those that DO NOT involve the brain or spinal cord.  When it involves multiple nerves, we call it polyneuropathy.  When it involves one nerve, we call it mononeuropathy.

Symptoms that are suggestive of neuropathy include:

  • Numbness
  • Tingling
  • Burning
  • Pain out of proportion to stimulation (e.g., touching intact skin should not cause pain)
  • Weakness
  • Cramping
  • Itching
  • Temperature dysregulation

Some people describe neuropathy as invisible pain.  Someone can be in terrible agonizing pain, but physically they look perfectly normal.

How do you diagnosis neuropathy?

Peripheral neuropathy can be diagnosed clinically, with nerve conduction tests, and with a special type of skin biopsy called an epidermal nerve fiber density test.  Don’t get me wrong, I’m all about history and physical exam, but when it comes to diagnostics, I like to have some hard data supporting my clinical diagnosis.  This is why a suspicion of peripheral neuropathy typically should be supported by either a nerve conduction test and/or a skin biopsy.

Nerve conduction tests are pretty much the go to test when it comes to neuropathy. The doctor measures the conduction of electrical impulses that go down the nerves.  This type of test is good to diagnose problems with large myelinated nerves.  Not so much for small, unmyelinated nerve fibers like the ones found on the skin.  When the doctor suspects the problem is coming from small fibers, a skin biopsy is the way to go.  In very special and unique cases, an actual biopsy of a large nerve may be required.  In the world of rheumatology, this can happen if there is a suspicion for systemic vasculitis.  This includes really rare diseases like Wegener’s (although we don’t it that anymore)¹, Churg-Strauss (we don’t call it that anymore either)², and microscopic polyangiitis.

What causes neuropathy?

The most common diseases in general include diabetes, chemotherapy, carpal tunnel syndrome, Lyme disease, alcohol abuse, vitamin deficiencies, low thyroid, HIV, and hepatitis C infection.  At that point, you start getting into the weird and rare diseases.  This is where rheumatic autoimmune diseases feature.  Unfortunately, despite exhaustive workups, in about one-third of cases, a specific cause is never found.  This is called idiopathic neuropathy.

Treatment of neuropathy

First, treat the underlying disease.  Unfortunately, in most situations this is not enough.  Medications that are often used include: gabapentin, pregabalin, duloxetine, amitriptyline, topiramate, and carbamazepine. In extreme situations, infusions with immunoglobulin are used particularly with demyelinating autoimmune conditions.  When all else has failed, and I mean, ALL else has failed narcotic medications for breakthrough pain be necessary.  Every person and situation is unique, so it’s important to work closely with your physician to figure out the best plan of action.

It’s important to note that all these medications have potentially serious or undesirable side effects.  Increasingly, people are searching for alternatives treatments.  Long a staple of Chinese traditional medicine, there’s recently been an increased interest in using acupuncture to treat neuropathy.

But is there any evidence and is it safe?

Acupuncture for the treatment of peripheral neuropathy: a systematic review and meta-analysis

Researchers recently sought to determine whether acupuncture was safe and efficacious for the treatment of peripheral neuropathy.  They searched multiple medical databases including Medline, AMED, Cochrane, Scopus, CINAHL, and clinitrials.gov looking for studies that matched stringent entry criteria.  About one thousand studies were identified, but only 13 made the cut.

They selected randomized controlled trials studied acupuncture for neuropathy caused by diabetes, Bell’s palsy, carpal tunnel syndrome, HIV, and idiopathic conditions.  What they found was that acupuncture generally was effective for diabetic neuropathy, Bell’s palsy, and carpal tunnel syndrome.  In these cases, they even found improvement in nerve conduction study parameters in both sensory and motor nerves.  More data was necessary to determine whether acupuncture was effective in cases of HIV-associated neuropathy but there was a positive trend.  With regards to idiopathic neuropathy, there was insufficient evidence.  Then again, there were hardly any trials that looked into this type of neuropathy.

Does this mean that everyone with diabetic neuropathy should start acupuncture ASAP?  Hold your horses.  The researchers also noted that there was A LOT of variability between studies and A LOT of bias.  Evidence-based medicine is all about comparing oranges with oranges and apples with apples in an unbiased way.  If these conditions are not met, then it really becomes difficult to determine what caused what.

The following are some of the problems that the researchers identified.

Methodological problems with standardization

  • Point selection
  • Number of needles used
  • Needle retention time
  • Needling depth
  • Needle manipulation
  • Use of moxibustion
  • Use of electroacupuncture vs. manual acupuncture

Methodological problems with sample size

  • Only two of the studies stated sample size
  • Many trials were likely underpowered (You cannot make generalizations from a small group of people)

Methodological problems with improper control and blinding

  • In many cases researchers were not blinded
  • In many cases participants were not blinded

Methodological problems with outcome measures

  • Most trials assessed improvement with subjective measures of improvement instead of hard evidence.
  • Only 4 out of 13 trials actually did nerve conduction tests before and after, to see whether anything changed.

On the up side, acupuncture was found to be safe.  Serious side effects only occurred in people suffering from HIV-associated neuropathy.  Otherwise, acupuncture seems pretty safe.

Conclusion

Basically, the meta-analysis demonstrated that acupuncture is generally safe and that it may help in people suffering from diabetic neuropathy, Bell’s palsy, and carpal tunnel syndrome.  Autoimmune disease-associated neuropathy is a big unknown.  However, these results should be taken with a grain of salt.  Although the meta-analysis in itself used good methodology, the researchers were not working with the studies with the best methodological practices in the world.

This brings me back to my first question.  Does acupuncture help neuropathy?  My answer to that questions is as follows.

As always, think for yourself!  You now have the tools to make an educated, unbiased, objective, informed decision regarding health.

References

UpToDate

Dimitrova A, Murchison C, Oken B. Acupuncture for the treatment of peripheral neuropathy: a systematic review and meta-analysis. J Altern Complement Med. 2017 Jan 23. doi: 10.1089/acm.2016.0155.

Notes

Wegener’s = granulomatosis with polyangiitis.  And they wonder why people still call it Wegener’s?

Churg-Strauss = eosinophilic granulomatosis with polyangiitis

1 Comments
Diseases and Conditions

What is Raynaud’s Phenomenon?

February 1, 2017
Raynaud's phenomenon: Classic white discoloration of the pinky

What is Raynaud’s?  They do say that a picture is worth a thousand words.

In a previous article about scleroderma, I alluded to something called Raynaud’s phenomenon.  Tis the season of the Raynaud flare, so I thought this post would be especially relevant.

This phenomenon is super common.  Some studies estimate that it occurs in 3 to 4% of the population but it’s probably a lot more than that.  In colder climates its is present in up to 30% of the population.  It’s more common in women, in younger people, and it tends to run in families.

Raynaud’s is a vasospastic disorder.  Basically the blood vessels clamp up when exposed to the cold, when there is a sudden change in temperature, or sometimes when you are extremely stressed out.  No joke!  Cigarette smoking is also a known cause.  Typically, the finger goes white, then dusky, and when the blood comes back, bright red.  If the change in color involves the palm, this is not Raynaud’s.

Raynaud’s can be associated with many conditions.  And they’re not all autoimmune.

  • Autoimmune – scleroderma, lupus, rheumatoid arthritis, Sjogren’s syndrome, myositis
  • Vibration injury – riveters, rock drillers, etc.
  • Frost bite
  • Medications and chemicals – beta blockers, cocaine, chemo
  • Arterial diseases – carpal tunnel, clots, pressure from a crutch
  • Hormonal diseases – low thyroid, pheochromocytoma
  • Hyperviscosity syndromes – paraproteinemia, polycythemia, cryoglobulinemia
  • Infections – Lyme, hepatitis, endocarditis
  • Cancers – ovarian cancer, lymphoma, leukemia

And then there’s the most common cause… just cause.  Idiopathic primary Raynaud’s.  Typically, this occurs in women during their teens or 20’s.  There are a lot more causes but these are some of the common and… not so common ones.

Primary Raynaud’s vs. Secondary Raynaud’s

When Raynaud’s is idiopathic, this means that it is NOT caused my any underlying condition.  This is primary Raynaud’s.  When there IS an underlying condition, we are dealing with secondary Raynaud’s.

In primary Raynaud’s, the blood vessels are structurally normal.  In secondary Raynaud’s, the structure of the blood vessels can deform because of the underlying cause.

Secondary Raynaud’s can cause finger ulcers, pitting, fissuring, and gangrene.  People tend to have an ANA and or antibodies.  In addition sometimes the doctor can actually see that the blood vessels above your nails look distorted using a pocket microscope.    While, you don’t see any of these things with primary Raynaud’s.

Can people with primary Raynaud’s develop secondary Raynaud’s

The simple answer is YES.  About 1% of patients with primary Raynaud’s develop some form of autoimmune disease yearly.  There are a few risk factors that increase that risk.

  • Having any specific antibody like anticentromere antibodies
  • Abnormal blood vessels above your nails
  • Having a ANA with a nucleolar pattern
  • First flare after the age of 40 years
  • Male gender
  • Finger ulcers, pits, gangrene

If you have any or a few of these, it’s important to see a rheumatologist periodically to make sure that you aren’t developing an autoimmune disease.  Early diagnosis is key.

How do you treat Raynaud’s?

Keep your hands and feet warm and, keep your core temperature warm.  Easier said than done.  I know, I grew up in Canada!  The trick is layering, mittens, scarves, and warm socks. Need to remove your gloves to answer your phone?  Don’t.  Either wear touchscreen friendly gloves or convert them.  I recently discovered nanotips.  It does the job.  Note, this is NOT an affiliate marketing link.  Basically, try to avoid triggers like the cold, stress, or any chemicals that could cause it in the first place.  Known chemicals include cigarettes, decongestants, diet pills… stimulant drugs.  Some heart medications may also worsen Raynaud’s.  Before making any changes, talk to your doctor.

Fish oil to treat Raynaud’s

When it comes to conventional medications, you do have a few options.  Provided you are not allergic to fish, omega-3 fatty acid supplementation could be beneficial.  One of my teachers/colleagues, conducted a double-blind, controlled, prospective study looking at fish oil supplementation in patients with both primary and secondary Raynaud’s phenomenon back in the 80’s.  Basically, 3 grams of fish oil daily improves tolerance to cold exposure and delays the onset of vasospasm in patients with primary Raynaud’s.  This effect was not seen in people with secondary Raynaud’s.

Medications for Raynaud’s

Finally, doctors sometimes prescribe medications like calcium channel blockers: amlodipine and nifedipine.  These are generally considered first-line and help about 35% of people.  Calcium channel blockers like verapamil and nicardipine are essentially useless.  Other medications include prazosin, sildenafil, and talalafil.  All of these can decrease your blood pressure.  For those with normal or low blood pressure, fluoxetine is a possibility.  Although this is an anti-depressent, it’s thought that the increase in serotonin dilates the blood vessels thereby alleviating Raynaud’s.  Sometimes topicals are effective: nifedpine and nitroglycerine.  But again, sometimes they can cause a drop in blood pressure.   Again, this does not constitute medical advice.  Please talk to your doctor before making any change.

What about finger or toe threatening situations

Sometimes Raynaud’s is particularly severe and refractory to medications.  This tends to happen with people suffering from scleroderma.  Sometimes, you can see gangrene because the decrease in blood flow is so severe.  Obviously, you don’t want it to get to that point.  In these situations, hospitalization often times is necessary.  Consequently doctors use medications like epoprostenol or iloprost to aggressively open up those blood vessels.  Surgical intervention may also be necessary: sympathectomy.  It can be performed at the cervical, lumbar, wrist, or digital (finger) levels.  These interventions are reserved for very severe cases.

What’s the prognosis

For primary Raynaud’s prognosis is excellent.  Simply a nuisance for the most part.  However, in high risk people, it’s important to see a rheumatologist on an annual basis to see if anything changes.  Thankfully, in about 10% of people the attacks disappear completely with time.

In contrast, things are little more complicated with secondary Raynaud’s.  It really depends on the underlying problem.  Remember this is treatable.  Not curable, but treatable.

I hope this has been informative and enlightening.  Remember, bundle up and stay warm this winter!

References

Rheumatology Secrets, 3rd Edition

DiGiacomb RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud’s phenomenon: a double-blind, controlled, prospective study. Am J Med. 1989 Feb;86(2):158-64.

4 Comments
Diseases and Conditions

10 scientifically proven ways to help gout

January 9, 2017
10 scientifically proven way to help gout

A gout flare is one of the most painful human conditions right up there with kidney stones and child-birth.  These flares result from an excessive amount of uric acid in the blood caused by diet, genetic factors, and sometimes medications.  Doctors often treat flares with anti-inflammatory medications, colchicine, or steroids.  These medications do help with the pain, but they don’t help solve the underlying problem.  To much uric acid.

Acute gout occurs when uric acid overwhelms the body’s capacity to get rid of it.  Human beings don’t have the enzyme that breaks down uric acid, so it has to get rid of it via the kidneys.  When the kidneys are at full capacity, things well, “back up” in the form of a nasty gout flare.  The actual mechanism and physiology is pretty complex and not completely understood yet.

A few medications exist to help your body get rid of uric acid but diet is probably the most important.  Unfortunately, it’s often the most neglected and yet the most healthy intervention.

If you’re interested in learning more tips to help boost your overall health please read my article 10 scientifically proven ways to improve sleep quality.

References

Vieira AT, et al. Dietary fiber and the short-chain fatty acid acetate promote resolution of neutrophilic inflammation in a model of gout in mice. J Leukoc Biol. 2016 Aug 5. pii: jlb.3A1015-453RRR.

Beyl RN Jr, Hughes L, Morgan S. Update on importance of diet in gout. Am J Med. 2016 Nov;129(11):1153-1158.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.