Tuesday, January 22, 2013

Treatment of Peripheral Neuropathy in Sjogren's Syndrome

Image found here

Reader Nancy asked this excellent question recently:
..."As I was reading through your earlier blogs I came across your posting about your experience with peripheral neuropathy.  Though many of us experience many additional autoimmune effects, the problem of peripheral neuropathy can be one of the worst.  The constant search for ways to deal with the daily pain that never goes away can sometimes be overwhelming. I'm sure many of us would love to hear how you have developed coping strategies to deal with the non-stop pain of daily life with this symptom - anything from shoes to medications would be of interest."
Peripheral neuropathy and it's uncomfortable symptoms are caused by damage to the nerves that carry information to and from the brain and spinal cord. PN has several specific causes and can cause hundreds of symptoms, as described in this excellent neuropathy fact sheet from NINDS found here.
More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves -- motor, sensory, or autonomic -- that are damaged.  Some people may experience temporary numbness, tingling, and pricking sensations, sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. Peripheral neuropathy may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are caused by systemic disease, trauma from external agents, or infections or autoimmune disorders affecting nerve tissue. Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. (bolding mine)
Sjogren's syndrome related peripheral neuropathy is well-documented, unfortunately. Read this patient fact sheet from the Sjogren's Syndrome Foundation authored by Dr. Julius Birnbaum:

There are many different types of neuropathies in Sjogren's syndrome. These neuropathies can have different causes and may require different diagnostic techniques and different therapeutic strategies. Unlike other autoimmune disorders, in which the neuropathies predominantly cause weakness, the neuropathies in Sjogren's primarily affects sensation and also can cause severe pain. recognition of unique patterns and causes of neuropathies in Sjogren's is important in arriving at appropriate therapies. 
  • Recognize that neuropathic pain is a chronic disease. Just as most causes of neuropathies and neuropathic pain in Sjogren's do not come on suddenly, reduction of neuropathic pain can take a while. 
  • Initial and predominant neuropathies in Sjogren's can occur anywhere - in the feet, thighs, hands, arms, torso and/or face.
  • Many different symptomatic therapies for neuropathic pain are available. Both physician and patient awareness of potential benefits and side-effects can help tailor an appropriate approach. 
  • While the class of tricyclic anti-depressants (TCAs) often constitute and first-line tier of therapy in other neuropathy syndromes, the TCAs can increase mouth and eye dryness and therefore are not routinely used as front-line therapies in most Sjogren's patients.
  • Electrophysiologic tests may help in the diagnosis of neuropathies affecting larger nerves which are coated by an insulator called myelin. However, neuropathies affecting smaller-fiber nerves that lack this myelin coating cannot be detected with these tests. 
  • Special diagnostic tests, including the technique of superficial, punch skin biopsies (small biopsies of 3 millimeters and not requiring any stitches), can help in the diagnosis. 
  • A relatively rare neuropathy can cause significant weakness in Sjogren's patients. In contrast to other neuropathies which develop slowly, this neuropathy can present with very abrupt-onset of weakness. This so-called "mononeuritis multiplex" occurs because the blood flow through vessels which nourishes nerves is suddenly compromised.
  • In general, immunosuppresive medications are almost always warranted to treat "mononeuritis multiplex" neuropathy. In contrast, the rol of immunosuppressives is not well-established in other neuropathies, including neuropathies that cause pain but are not associated with weakness.
  • Sjogren's patients frequently wonder whether pain associated with a neuropathy means they are at an increased risk for more severe motor weakness. While there are exceptions, if weakness is not present at onset, it most likely will not occur. 
  • Neuropathic pain can be alleviated and assuaged, although there may initially be a 'trial-and-error" process with different and perhaps multiple agents. 

As in the the treatment of all causes of PN, good treatment of Sjogren's related peripheral neuropathy addresses first the optimization of reducing the autoimmune activity of the disease, and secondly focuses on the specific location and severity of symptoms.

For me, PN probably accounts for the pain and burning that I experience in my feet which is more severe at night. Dr. Young Guy and I have discussed this, and since I also experience restless leg syndrome, I am taking medication to ease some of these symptoms. I take Klonopin, having tried and not tolerated other more commonly used drugs for restless leg syndrome.

I also have realized that good socks and excellent shoes are vital to decreasing my foot pain. In our climate here in the Pacific Northwest, good wool socks such as Smartwool brand are particularly comfortable for me. In warmer months, cushiony pure cotton feels best. And, I've reluctantly realized that I need to wear shoes Every. Minute. Of. Every. Day. Here's advice offered by another Sjogren's syndrome patient found in the Sjogren's Self Help Booklet courtesy of the Sjogren's Syndrome Foundation:

...The biggest change I made was my shoes. I found that with shoes that accommodated thick fluffy socks I felt a lot less pain. My personal favourite is SAS® brand, Free Time with Thorlos® walking socks. Wearing socks all the time was really a new concept for me too. I thought wearing even 100% cotton light-weight socks at night would make my feet hotter, but they didn’t and even made me more comfortable. Some people get relief from wearing tight socks. Mild support knee highs might be worth a try and I found these the most helpful.
If my feet are really hurting, I first try soaking them for a while in really cool water. I then try to talk my husband into massaging them for a few minutes before I go to bed since this seems to be my worst time of day. Neutrogena® Foot Cream works well for massage and is really good for dry skin too. The massage often gives me several hours of relief. If anyone needs convincing, just read what the Mayo Clinic says, “A massage helps improve circulation, stimulates nerves and may temporarily relieve pain.”

Treatment suggestion from the  Mayo Clinic website include:

Pain Relievers:

  • Mild symptoms may be relieved by over-the-counter pain medications. For more-severe symptoms, your doctor may recommend prescription painkillers. Drugs containing opiates, such as codeine, can lead to dependence, constipation or sedation, so these drugs are generally prescribed only when other treatments fail.
  • Anti-seizure medications. Drugs such as gabapentin (Gralise, Neurontin), topiramate (Topamax), pregabalin (Lyrica), carbamazepine (Carbatrol, Tegretol) and phenytoin (Dilantin, Phenytek) were originally developed to treat epilepsy. However, doctors often also prescribe them for nerve pain. Side effects may include drowsiness and dizziness.
  • Capsaicin. A cream containing this naturally occurring substance found in hot peppers can cause modest improvements in peripheral neuropathy symptoms. Like spicy foods, it may take some time and gradual exposure to get used to because of the hot sensation this cream creates. Generally, you have to get used to the heat before you can experience pain relief. Doctors may suggest you use this cream with other treatments.
  • Lidocaine patch. This patch contains the topical anesthetic lidocaine. You apply it to the area where your pain is most severe, and you can use up to four patches a day to relieve pain. This treatment has almost no side effects except, for some people, a rash at the site of the patch.
  • Antidepressants. Tricyclic antidepressant medications, such as amitriptyline and nortriptyline (Aventyl, Pamelor), were originally developed to treat depression. However, they have been found to help relieve pain by interfering with chemical processes in your brain and spinal cord that cause you to feel pain. The serotonin and norepinephrine reuptake inhibitor duloxetine (Cymbalta) also has proved effective for peripheral neuropathy caused by diabetes. Side effects may include nausea, drowsiness, dizziness, decreased appetite and constipation.

Transcutaneous electrical nerve stimulation (TENS) may help to relieve symptoms. In this therapy, adhesive electrodes are placed on the skin, and a gentle electric current is delivered through the electrodes at varying frequencies. TENS has to be applied regularly.
For a few PN sufferers, the pain and burning can become so severe that it interferes with their ability to function in spite of commonly used treatments. In these instances, some rheumatologist prescribe the use of IVIg: intravenous immunoglobulin therapy:

What is IVIG?IVIG, also called gamma globulin or antibodies, is a highly purified blood product preparation that is derived from large pools of plasma donors. Plasma from approximately 1,000 to 10,000 persons is present in each unit or “lot” of IVIG. While this is a blood product, IVIG available in the United States, is purified and carefully screened to be free of all known transmissible diseases, including HIV, hepatitis, malaria, syphilis and many, many others. This medication is used to treat a variety of neurological and neuromuscular autoimmune disorders that affect the central nervous system, peripheral nerves, neuromuscular junction and muscles.
The Benefits of IVIG:The underlying problem in all autoimmune diseases is often similar. One part of your immune system has decided to attack part of your body, instead of defending your body from bacteria and viruses. While the cause of this damage is unknown, IVIG contains antibodies which are believed to block this attack.

IVIg use specifically for neuropathy in Sjogren's syndrome was the topic of a timely recent Medscape article entitled IVIg for Sjogren's Neuropathy: Worth the Price? by Kevin Deane, MD Jan 17, 2013 found here. Dr. Deane's viewpoint on the issue:
These results suggest that IVIg may be useful in treating some neuropathic manifestations of SS, although the investigators' conclusions are limited as a result of the small sample and the retrospective, uncontrolled nature of the study. IVIg is expensive and has some toxicity, including risk for thrombosis and renal injury;[4] therefore, more data from controlled trials are needed before we can be certain of its precise role in treatment of SS-related neuropathy. Furthermore, clear guidelines on how to classify the various types of SS-related neuropathy and a better understanding of the underlying pathophysiologic mechanisms of SS-related neuropathy may help guide treatment.

 Two small studies, read this and this, conducted in 2009 would support the consideration of use of IVIg in treatment resistant PN, although as Dr. Deane noted above, the use of this treatment is not without risk.

I'm fortunate in that my symptoms of PN at this point, while bothersome, are not severe.

Do you struggle with peripheral neuropathy? What advice would you offer to Nancy?


Heda said...

Thank you for blogging about neuropathies. Most of the time I feel like a freak because I'm riddled with them. They are the bane of my primary sjogren's existence. The least of my worries is the little burning sensations that skip across the skin of my legs whenever I sit to relax in the evenings. They make me twitch and tense and challenge all my will power to stop scratching! The worst is the autonomic cardiovascular dysfunction that gives me extremely labile blood pressure. There is a plus side - any visit to ER gets me straight in because with pain or illness my blood pressure is always through the roof! I do have a lot of hand weakness and back ache but I am extremely grateful that my neuropathies have not stolen my ability to walk. I sound like a crock but I still function at an almost acceptable level. Life ain't at all bad!

Unknown said...

Julia - if IVIG works for PN, wouldn't Rituxin as well?

Joe said...

Hello, I have small fiber neuropathy due to Sjogren's.

I have 24x7 burning and stinging nerve pain in my feet. I also have nerve pain on the left side of mouth lips and left side of head.

I have tried IVIG and Rituxan and it did not help. IVIG gave me the worst headaches imaginable.

Please give me any advice as pain can be unbearable at times. I am trying to meditate. Thanks.

I am featured on the Sjogren's website.


Joe said...

I am now taking Imuran since June of 2012. Nerve pain has decreased a little in the head but not the feet and calves.

Julia Oleinik said...

Hi Joe -- Ouch. So sorry to hear about your pain, which seems to be very resistant to treatment. I wish I could offer some advice that would relieve your pain, but the best advice that I can share at this time is that you would continue this conversation with your rheumatologists, your primary care physicians, and perhaps a chronic pain clinic. As you continue to learn more about PN, please keep me posted, and I look forward to the day that you can tell us that you have found significant relief!

Julia Oleinik said...

Hi Heidi -- Good question. There are significant differences in IVIg and rituximab treatment. Both are antibody proteins, but here's the thing: IVIg is a pooled plasma protein harvested from a thousand donors. The mechanism by which it suppresses inflammation and it's exact target is still unknown. If IVIg was a paintbrush, it would be one of those heavy duty commercial SPRAYER. It throws a great deal of antibody at a large non specific surface. Rituximab, on the other hand, is highly specific. It's antibody target is a very small subset of specific B cell lymphocytes. If rituximab were a paintbrush, it would be one of those micro brushes used to fill in pixel by pixel on photoshop.

Since we don't know exactly what the causative factors of PN are, it's not possible to determine specifically if these antibodies will be of use in ALL PN patients.

Joe said...

If you are contemplating between IVIG and Rituxan, do the Rituxan.

IVIG was so painful. I thought I was going to die with the headaches. Thanks Julia, I will keep you posted.


Unknown said...

It is important to recognise and correctly diagnose autonomic neuropathy because successful treatments and management can be offered, so neuro muscular stimulator is must.

what is physical therapy said...

My uncle has headache for many months and he want to get relief. I think this IVIG is gainful for him. I am going to tell him about it.

Unknown said...

Doctors will usually prescribe a combination of medication and therapy to assist the patient with the pain. Medications can include over-the-counter pain relievers, antidepressants and anti-seizure medications.
Transcutaneous Electrical Nerve Stimulation (TENS) therapy is used to assist patients with their symptoms. Adhesive electrodes are placed on the skin and a gentle electric current is delivered through the electrodes at varying frequencies.

spine and pain

Anonymous said...

I am driven almost crazy with neuropathy all over my body...possibly due to SS. My rheumatologist does not point to this, but I think it is so...my antibodies show Sjogrens. I went to a neurologist & he prescribed gabapentin which helps a little at night (can't take it in the daytime...makes me to weak & tired). I would like to know if a TENS unit could help with all over body neuropathy? I am at my wits end with this pain.

Unknown said...

If this will help any one. My wife has Sjogren's on going for 6 years with neuropathic complications having lost feeling in her right legs, right arms and left side of her face resulting extreme pain. Her daily pain medication are Methadone 52 mg, Lyrica 500 mg, Nortripiline 50 mg, plus Clonazapam 1 mg to control Trembling and Tizanadine 4 mg to control Muscle Spasms. This medication reduces the pain from 9 down to a bearable 3.

Unknown said...

The diagram is pretty informational for me. It has enhanced my knowledge, now I can individual part of the body which is infected.
physical therapist in bergen county

Unknown said...
This comment has been removed by the author.
Unknown said...

very good diagram and explanation. thanks

Peripheral neuropathy

Unknown said...

I have peripheral neuropathy and getting treatment of this. It is getting better; this diagram has increased my knowledge about it, now I am able to treat it more nicely.
physical therapy center

Chris S said...

I found this site while searching for information regarding itchy skin on my feet. I was diagnosed with RA after sudden major depressive and anxiety episodes (hospitalized twice in two weeks). Leading up to that was incredible nerve pain in both feet...kept awake at night. I am currently taking Lyrica, Tofranil (just learned from your site that tricyclics are used for nerve pain), methotrexate, and using topical steroid ointment for huge red sores on my feet, which were dxd as a form of vasculopathy caused by a clotting disorder. I also have erythema nodosum on my shins. As I think back, I can now recognize that minor symptoms started years ago, such as flu symptoms, chills, nausea that would come and go. This itchy skin on my feet has me looking again. I have a hard time thinking it is the RA causing this too. There have been times over the years, where my whole body would become itchy and I'd have to take an anti-histamine to get it to stop. One med years ago said it was prescribed as an anti-histamine for stress??? Would love to hear if my symptoms sound familiar to anyone with RA or anything else. Thank you

Annette said...

Hi Julia

Is your neuropathy any better now that you take Rituxan? My friend thinks it might be helping her autonomic problems but so far it's more hope than reality since it has been a short time since her infusion


Unknown said...

Joe, others

Can anyone give me some advice for small fiber problems?

Bob Nelson said...

Thank you so much for posting this. I'm so glad you were able to go steroid free.

John S said...

For anyone looking for either relief to PN or to simple Sjogren's, or Sjogren's with PN, the answer is the same, Interferon Alpha. My doctor has put me on this med orally, which is much easier to deal with rather than IM. My symptoms are going away, one by one, first the dry eyes, then then neuropathy and other neurological issues and finally, dry mouth, though not 100% yet. He found all this info in Pubmed with clinical trials going back to the 90's. Ask your rheumy about this and they will not know anything, as usual. Do the research, print out the studies and shove them in your doctors face!!! This is the only way you are going to get better.

Pam said...

John S:
What is the side effect profile of Oral Interferon Alpha. I have Sjogren's with SFN (just in the top of thighs usually when seated end of day) and Restless Legs Syndrome.

Anonymous said...

To John S. I can't thank you enough for your comment!!! I found the trials you referred to and did exactly what you suggested. Of course my rheumatologist knew nothing, same as my neurologist. I've been on IVIG for the past year, and recently Rituxan. My neurologist sent me an email the day after my last appointment letting me know he researched the studies on interferon a, and told me we have to let the Rituxan work for a bit, and if we don't get the results we want, then he's willing to treat with interferon a! For the first time in years, I have more hope for a better future!!!

Anonymous said...

Is it possible to have neuropathy in the perineal area ? I have burning....worse in the evening and when sitting.

Unknown said...

Here I get some foot massager reviews .Who are not familiar with the benefits of foot massager can take it of no use.But foot massager is a machine of great use.The most significant is that it revives dead cells in our body.

Natural Herbs Clinic said...

Peripheral Neuropathy Treatment is usually directed at the underlying cause. On the off chance that the condition is because of a specific medication, the medication can be exchanged. On the off chance that the condition is brought about by a vitamin insufficiency, vitamin supplements may improve symptoms.

Carl Stone said...

When I read this story I realized just how similar it was to my condition. One day, while taking a short walk, I suddenly and inexplicably started experiencing intense burning and prickly sensations in the soles of my feet.

These symptoms persisted for many months before I was forced to accept the unavoidable truth that I was a peripheral neuropathy sufferer. I visited a podiatrist who told me there was no effective medical treatment for this condition. All he could do was write me a prescription for something that would help to take the edge off.

His offer was tempting, but deep inside I just knew there had to be a better answer. No way did I want to get hooked on dangerous painkillers for the rest of my life and risk damaging my health even more with the unwanted side effects.

Long story short, I came across some simple natural remedies and stimulating techniques that gently soothed my irritated nerves and woke up my numb, sleepy legs, feet, and hands.

In fact, you might want to check out this article, it really helped me a lot:


Unknown said...

Reading all your posts have been so incredibly helpful. In the last two months I've been diagnosed with Sjogren's, peripheral neuropathy and cry about you lightest. My first symptom was on May 9 with a stroke! Then I had three more strokes that week! I'm in my 40s and very healthy. I went to the ER nine times and was hospitalized five times and finally got a diagnosis. Although I heard sometimes it takes years to get this kind of rare diagnosis. They put me on Rituxan on Father's Day now they're switching me to IV IG starting Monday and Tuesday. Right now I am burning, very weak, and have numbness in both feet.

Unknown said...

Cryo- vasculitis. Sorry don't know how to go in and edit this post?

Unknown said...

Reading all your posts have been so incredibly helpful. In the last two months I've been diagnosed with Sjogren's, peripheral neuropathy and cry about you lightest. My first symptom was on May 9 with a stroke! Then I had three more strokes that week! I'm in my 40s and very healthy. I went to the ER nine times and was hospitalized five times and finally got a diagnosis. Although I heard sometimes it takes years to get this kind of rare diagnosis. They put me on Rituxan on Father's Day now they're switching me to IV IG starting Monday and Tuesday. Right now I am burning, very weak, and have numbness in both feet.

Jackie said...

I am 73. Have had what I now know is Sjogrens Syndrome for 60 yes. PN is now my worst issue. I was given a patch called Neupro, which has helped more than anything. With a patch you wear 24-7, you don't have so many ups and downs. I also take tramadol four times daily for autonomic problems and depression. It has really helped since my body will not tolerate antidepressants. I also have restless legs since puberty and the patch fi ally helps that. I seem to have sciatica and have just started adding Perkocet at night when my pain really cranks up and I am sleeping better. I had two sisters . one had RA and the other Lupus. I would like to know if others have intolerance for antidepressants and what would help.

amanda hungerford said...

I have diagnosed with Sjogrens with many of the typical symptoms. My doctor has put me on Low dose naltrexone. I am curious if others are on this and what the experience is.

Anonymous said...

Have you been checked for Lupus?

Rick said...

I’ve been on IVIG for several years now for Sjogren’s neuropathy, or Autonomic Neuropathy. However the doc’s want to label, dissect, study etc, I have quite a painful experience from the pain. It is widespread, but always affects the feet, legs, low back and hip the most. I am able to walk (although when it’s really flared up, I try not to).
I’ve had two infusions of Rituxan. I’m wiped out after those! But as my body begins to rebuild all the cells that stuff wipes out, I start to gain strength and feel better.
I’m also on Lyrica. I’ve run the gamut on the dosage. I’m currently on 400 mg’s daily, but have been on as high as 600 mg’s.
Additionally, I take opioid pain relievers.
On the days my pain is low enough I function rather well, I always question the drug therapies I’m on. When my pain flares, I fear how much therapies I might need to alleviate an amount of pain to feel minimally productive. It definitely seems that fronts producing rain have an affect.
I’m quite a mess, as my SS has given me every symptom listed for SS, and more.
As a note, when my feet are really flaring, I can’t wear socks of any kind. I wear the most comfortable shoes with the addition of New Balance inserts. I put them in any and every shoe I wear daily. I also use ice packs, heating pads, and TENS therapies, I go to a chiropractor, and have acupuncture treatments. I’ve added meditation, and listening to my favorite music to relax.
I’ve learned more about pain than I would have ever thought!
Family and friends, in their attempt to help tend to attempt to get me to downplay the pain. (As many of us have experienced, the comment “but you look fine” rings so hollow). At times the pain is at distressing levels. It is that pain I make myself remember, so that when it’s anything less than that, I’m grateful. What family and friends don’t get, is that when this type of pain is constant 24/7, it wears on one’s mental ability to cope. But that is my challenge. I truly don’t complain much. But when someone asks out of truly wanting to know and learn, I’ll share some of my story. Being male, my story is a little unique.

Rick said...

To John,
I’ve researched Interferon A orally as a treatment. I’ve read the studies. Printed them and handed them to my neurologist. He, and every doctor I mention it to say they have no idea as to where to even get oral Interferon A, much less prescribe it!
I’ve asked about it for the past 2 years to no avail.
Would you share how you were able to be on this therapy?
Thanks in advance!

Unknown said...

Rick -
I've also been intrigued about using Oral Interferon A to treat PN and other symptoms of Sjogrens. I've been doing some research and am told by another blogger on another blog site that using Oral Interferon A to treat Sjogrens is "off label" and that it wouldn't be prescribed to any Sjogrens sufferer in the US. I hope John is able to clarify for us where his doctor practices. Maybe it can be prescribed in other parts of the world but not US?

Pam W