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Cryo and Arthritis

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Cryo & arthritus

Cryoglobulinemia can cause arthralgia (arthritis-like symptoms), less frequently cryoglobulinemia can cause arthritis which is difficult to distinguish from rheumatoid arthritis This includes the erosive form of rheumatoid arthritis. Just like rheumatoid arthritis, the arthritis caused by cryoglobulinemia requires that rheumatoid factor be present. If you have type II or type III cryoglobulinemia , you are positive for RF, guaranteed… This kind of arthritis differs from the simple arthralgia that some people with cryo experience in that it is always symmetrical (both left and right side joints affected), commonly worse in the morning, and will improve , as the day progresses allowing stiff, sore joints to loosen up a bit. In general terms arthralgia involves joint pain, but not inflammation of the joints. Rheumatoid arthritis involves both pain and inflammation in the joints. Lastly, some people with cryo actually have rheumatoid arthritis AND cryo at the same time! Either way, if you have the arthritis, you can have joint inflammation and a risk for joint damage. You need to talk to your doctor about it. Sometimes milder cases of RA can be treated with aspirin or NSAIDs such as advil or naproxen sodium. In general, forcing the cryo back into remission with steroids or immunosuppressants will also force the arthritis to remit…. but once the joints are damaged, the damage is done and there is no remission from that.

Just remember, that joint pain without swelling, is not likely a significant amount of inflammation. If you are having trouble with RA, then you will most likely have pain, stiffness AND swelling from the inflammation. I have had my ankles and feet affected so badly that I could not get my shoes on. Same deal with my knees, but I don’t put shoes on my knees… tongue emoticon It is always symmetrical, that means that if one knee is hurting, swollen and inflamed, the other knee will be much the same. As far as hands and fingers go, I have problems there too, only one clue that it is RA is that the very last joint toward the end of your fingers is never affected. Basically the symptoms of arthritis caused by cryoglobulinemia are identical to those caused by rheumatoid arthritis.. so I guess we call call it “RA”, even though we might not have RA at all… but then there are some of us who do!

Cryoglobulinemia is my life but Not my Identity

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Rare Disease Day 2016.

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Cryoglobulinemia: How the body loses Heat

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Cold Soaked: Marianne

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Cryoglobulinemia: The Triple Whammy

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Triple whammy

Cryoglobulinemia: The Triple-Whammy!

Cryo has a way of hitting you from three different directions. Usually when we are flaring we only experience one or two of them. But in a big, bad flare it can really hit you hard with all three.

1) Hyperviscosity syndrome: Accumulating cryoglobulins can make your blood a lot thicker if the concentration is high. It can lead to some pretty nasty effects due to circulation being obstructed in the skin, muscles, and various organs, as circulation can rapidly become impaired in the smaller blood vessels. This can cause numerous problems. Hyperviscosity is a particularly onerous problem with type I cryo, but can also happen in types 2, 3, as well as mixed/combined types.

One problem that often occurs with hyperviscosity is damage to the eyes. In particular, the retina and optic nerve. We had a couple of people in this group experience a bad flare with effects on vision likely due to hyperviscosity syndrome last winter. You need to be alert to sudden changes in vision such as blurry vision, flashes of light in your side vision or a sudden increase in “floaters” in your eyes. This is a serious problem that could damage your vision permanently in hours if not treated right away, so be alert.

2) Autoimmune Vasculitis: Cryoglobulinemia is a vasculitis affecting small and medium blood vessels. Cryoglobulins are unusual molecules. They are large, heavy, and in the immune system they act as both antibodies and antigen. Once cryo starts, there is a tendency for it to not stop. The immune system processes the cryoglobulins and in the process a lot of inflammatory agents and autoimmune components are released which cause inflammation in small and medium blood vessels, and vasculitis results. Rashes, skin lesions, skin ulcers, and symptoms similar to rheumatoid arthritis are not uncommon. The process continues, usually until the cryoglobulins are gone or, more commonly, until the immune system is forced into remission and the inflammatory process is halted with medication.

3) Cryoprecipitation: Once the cryoglobulins have been processed by the immune system, the already large molecules tend to link up vis-a-vis a bond facilitated by immune system compliment molecules. Once this happens the cryoglobulins may rapidly begin to precipitate if the skin temperature drops below the core body temperature. This causes even more problems with outright plugging , and vasculitis in medium and small blood vessels. This will continue as long as cryoglobulins are available if the temperature is allowed to remain below the core body temperature. If cryoglobulins are present and you are not actively flaring, it is still possible to have cryoprecipitation.

Quantitative vs. Qualitative Cryoglobulinemia Testing and a Second Positive Cryo Test

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Qualitative vs Quantitative testing for Cryoglobulins

The qualitative test for cryoglobulins is a test for the presence of cryoglobulins only. It gives no indication of the level or type of cryoglobulins found. The quantitative test for cryoglobulins returns the type and level of cryoglobulins present.

A single qualitative positive test for cryoglobulins qualifies as a diagnosis for cryoglobulinemia. Some doctors like to use the quantitative cryocrit test to measure the level of cryoglobulins as a diagnositic indicator.

The level of cryoglobulins in the blood are NOT good indicators for the severity or diagnosis of cryoglobulinemia.

It is well known that the cryoglobulin levels are highly variable from one patient to the next, and in any individual patient can fluctuate greatly, and may actually be absent altogether at times. Furthermore, while many labs make claims of accuracy, the accuracy of cryocrit measurements has never been well established, and a “standard” level for cryoglobulins as a diagnostic does not exist.

The bottom line is , one patient might have 3% cryoglobulins in their blood and be extremely ill with cryoglobulinemia, and yet another patient might have 11% cryoglobulins, and be completely asymptomatic. We don’t know why. . Every now and then one encounters a doctor who insists that cryoglobulin levels must be greater than 11% for a diagnosis of cryoglbulinemia. This is completely wrong, and arbitrary, and is simply not supported by the facts. Cryoglobulinemia is defined as the presence of cryoglobulins in the blood. Because of this clear and simple definition, the mere presence of cryoglobulins is taken as the diagnostic indicator for cryoglobulinemia. If you have cryoglobulins, regardless of the level, you have cryoglobulinemia, by definition.

Some doctors like to have a second positive for cryogobulins to confirm the diagnosis. This approach is likely not workable most of the time unless you can find a facility that does the test themselves, does it correctly, does it reliably, and you don’t mind repeating the test *A LOT*. This is because the test for cryoglobulins is not done correctly by most labs, and a false negative is returned about 70-75% of the time, At the same time false positives are uncommon.

In very real terms, one positive in the face of symptoms for cryo is compelling, and this is where most doctors will make the call, and call it cryoglobulinemia. The hard part is finding what is causing the cryo…

NOTE:  putting heparin in the test tube is another way to get a false positive if the tech does not know how to tell fibrin deposits from cryoglobulins.

A second positive cryo test is something to try for, but is sometimes not possible or practical to obtain. I’ve had ONE positive qualitative test, and have been tested for quantitative cryoglobulins about 6 times. The trouble is that the only time I was tested for cryoglobulins when I was flaring, and I clearly observed that the specimen was collected and handled correctly, was the single qualitative positive. On one other occasion blood was drawn correctly and the sample was then placed in a thermos for mailing to an outside lab for a quantitative test… but at that time I was in remission and we were trying to make sure I was in remission before changing the meds…. of course it came back negative. Other attempts at getting a cryoglobulin test were clearly done incorrectly from the beginning with the blood simply being drawn, the test-tube placed in a rack and the sample shipped to an outside lab. The lab doing the test in most cases was LabCorp. My first positive was taken at Washington Adventist hospital, and it was drawn and handled carefully by a head nurse,, not just a phlebotomist. My most recent test was done at the University of Maryland Medical Center, and I had requested a test for cryogobulins while there. At no time was a blood specimen drawn and handled with regard to temperature. The hospital records reported a negative test result, but I’m not even sure the test was actually performed.

Cryo and Pain Medications

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Pain is the body’s way of alerting – please talk to your doctor about any pain so that the cause can be diagnosed.

Here are some medications some of us in the support group have tried.  Check with your doctor and report your pain to them.

  • For neuropathic pain ,
    • neurontin works for some people, and
    • Lyrica is very good (but a lot more expensive).
    • Tegretol – an anti seizure medicine that can help nerve pain.
  • If you are having joint pain from rheumatoid arthritis or from arthritis like symptoms caused by the cryo
    • NSAID such as motrin or advil, but these have a potential for interacting with certain medications so do talk to your doctor before starting on an NSAID.
    • Asprin can sometimes help a little.
  • Aspercreme is sometimes helpful for joint and muscle pain.
  • Topical creams of lidocaine or patches of lidoderm can help some nerve pain.
  • Voltarin gel is helpful for inflammation and swelling in the joints.
  • Be advised that Voltaren is an NSAID and should not be taken along with other NSAIDs.
  • You might wish to read the posting about using ADVIL for more information.

Disease Modifying Anti-Rheumatic Drugs (DMARD’s) and Monoclonal Antibody Therapy (MAB)

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Disease Modifying Anti-Rheumatic Drugs (DMARD’s)

  •  If you are being treated for cryo, chances are that you are on one of the drugs that I have listed here or are considering them as options with your doctor.
  • DMARDs are a class of drugs commonly used to treat a variety of autoimmune disorders.
  • Some were developed primarily for the treatment of cancer, malaria, or for preventing organ rejection in transplant patients.
  • DMARDs are sometimes referred to as “steroid sparing” drugs because they often allow greater overall effectiveness at maintaining remission of autoimmune disorders when used in combination with low dose prednisone. In some cases more than one DMARD may be used in combination.
  • Each DMARD is a bit different from the others, effectiveness varies from one condition to the next and the side effect profiles are also highly variable.
  • Some DMARDs have a greater risk of potentially dangerous conditions and the patient must be monitored continuously for their safety.

Below , I have listed some common DMARDs in order of their basic action on the body, this list is not complete and you will want to search the internet and find further information on your favorite DMARD with regard to risks, safety, drug interactions, and side effects.

  1. The following drugs include the antimalarial agents, are frequently slow to take effect and some have significant long-term side effects.
    1. gold (rarely used) Sometimes effective for rheumatoid arthritis). This treatment has been around since the Victorian era! It is not well understood and tends to cause increasingly severe side effects over time.
    2. hydrochloroquine (Plaquenil) An anti-malaral agent. Often used in combination with steroids, commonly used to treat Lupus.
    3. methotrexate commonly used for a variety of autoimmune disorders and may be used in cmbination with other DMARDs
    4. sulfasalazine Often used to treat Chron’s disease, may be used with other DMARDs.
    5. cyclosporine Developed to prevent organ rejection in transplant patients. This drug may have serious long term safety issues. It is sometimes used in cases where nothing else works.
  2. The following drugs are the immunosuppressants. They can be slow to take effect and carry a risk from infection due to suppression of the immune system. Side effects vary, some are not so bad, but others have *significant* risks and side effects and the patient must be closely monitored.
    1. cyclophosphamide (cytoxan) Commonly used in oral and IV form, frequently used in combination with prednisone to force remission. Has a relatively big risk and side effect profile. This is generally viewed as a serious “big gun” that suppresses the immune system deeply.
    2. Imuran (Azathioprine) Commonly used to maintain remission after remission is established. Commonly used with low dose prednisone.
      1. Less risk and fewer side effects than cytoxan. Slower to take effect than cytoxan. Does not suppress the immune system as deeply as cytoxan.
      2. Imuran carries a small, but real risk of causing the immune system to die off rather quickly, so your blood counts must be monitored carefully.  Low white blood cells and low producing neutophils are a risk.
    3. leflunomide Sometimes used alone, but may be used with another DMARD, or a biological agent.
    4. mycophenolate-mofetil (cellcept) Originally developed to prevent organ rejection in transplant patients. Often used in combination with other DMARD’s, and more recently used in combination with biological DMARDs.
  3. Biological Agents (so-called bDMARDs)
    1. Tumor Necrotic Factor (TNF) Inhibitors
    2. including etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab,
  4. Specific Biological Agents with specific targets (also called Monoclonal Antibody Therapy = MAB)
    1. These drugs are basically designer antibodies that have very specific targets.
    2. For example: rituximab (rituxin) targets B cells specifically.
    3. including anakinra, abatacept , rituximab, tocilizumab, and tofacitinib. These medications are often combined with methotrexate or other DMARDs to improve efficacy.

*Author NOTES:

  • Plaquenil is not a heavy hitter like the above immunosupressants are, but it is a lot safer and has fewer side effects, so if it works for you , it works…. and that is a good thing.
  • If you need to take the medication , you take it.
  • It is all about risk management. For a more serious situation a bigger risk may be warranted in order to gain more effectiveness. The doctor has to make this kind if decision… and so do you the patient. For example, using cyclophophamide with prednisone to force remission in a case of cryo is not unusual. Once remission is established, one can tansition to something like Imuran, methotrexate, or cellcept. Often a patient might not tolerate one of the medications very well, forcing a change to another.
  • Some get along with imuran very well, so it is a good choice, and has less risk than staying on cyclophosphamde.
  • Also, Imuran is a reasonably safe drug to stay on if you have to take it long-term. So it really boils down to risk management vs effecrtiveness and having a list of possible options.

Five Stages of Accepting: Learning to live with Cryo.

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Five stages of accepting a Diagnosis of an incurable disorder or disease.

Receiving a diagnosis of Cryoglobulinemia is scary and it is hard for our families and friends too. It is actually a grief process that we go through, not unlike the loss of a loved one, and it takes a while for us to go through it.

  1. Denial
    1. Sometimes we ignore the facts and deny that it is real. Sometimes we can fall back on strong emottions… it sort of varies from one person to the next. We are all human, so this really should be viewed as good and necessary… and temporary.
  2. Anger
    1. We become angry because we feel like we have been treated unfairly… even cheated of having a normal life. Nobody is to blame for this, it is simply something that has happened. This will also pass after a while.
  3. Bargaining
    1. We try to make a deal with ourselves, or our condition to make it “better” somehow.
    2. We pretty soon discover that this approach does not work , and so we move on.
  4. Depression
    1. Once we fully realize the truth of the situation, we sometimes hit bottom for a while… feelings of being “lost” or of “no hope” are not unusual.
    2. Be patient with yourself, once you start to learn to cope with cryo, this will improve. (ganted, some days are better than others…)
  5. Acceptance
    1. We eventually learn to accept our condition for what it is and learn to cope with it as best we can.
    2. We learn that we *CAN* win some battles, and that others we can *NOT* win.
    3. Cryoglobulinemia is simply an illness, God is not punishing you, and cryo is not some evil entity out to get you.
    4. Cryoglobulinemia is simply what it is.. an autoimmune disorder, so to move on, we need to learn to work with what we have.

Steroid Side Effects

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Common Steroid Side Effects  

→ Prednisone is commonly used to treat autoimmune disorders. The benefits of it are that it is fast-acting (takes effect within hours) and is frequently effective for bringing a flare to a speedy halt in many autoimmune disorders.  While the plus side is the good news, prednisone has an “evil” side to it!  It can cause unpleasant and damaging side effects to the body, and potentially dangerous. For this post I use prednisone as the drug but the info here is equally applicable to solumedrol, depomedrol and other brands of therapeutic steroids prescribed by a doctor.

Here I am going to list some of the more common side effects.

  1. Weight gain. You can plan on gaining weight while on prednisone. It also has the tendency to redistribute body fat such that a person ends up appearing “fatter” than they actually are. For many people this effect is less noticed at lower doses of prednisone.
  2. Sweating. Sudden, apparently random sweatng. It can be profuse. for me I have noticed a tendency to break ou tin a sweat a couple of hours after taking prednisone.
  3. Insomnia. For me, this is the most annoying side-effect, particularly at higher doses. It is hard to sleep. I wind up taking melatonin at night and it seems to help a bit.
  4. Neurological Effects. This tends to happen to me at higher doses (greater than 40 mg/day) In particular, sudden bouts of shaky hands. This can be severe, and you should talk to your doctor if you develop odd neurological effects from using prednisone.
  5. cataracts. Your chances of developing cataracts are greatly increased if you are on prednisone.
  6. osteoporosis Bone loss is a big problem with prednisone, especially at higher doses and long term use. This can be corrected for to an extent with medication.
  7. Immunosuppression After you have been on prednisone for a while, it will begin to suppress your immune system. You need to be more careful of opportunistic infections.
  • There are more, the list is long, but these are the more common side effects of prednisone use.
  • In general, side effects will be worse at higher doses and may get worse with chronic use over time.
  • Everybody is a little different, and some people will experience more or fewer side effects.
  • It is a good idea to go to the drug manufacturers web site for the fact sheet for prednisone and read it.
  • The essence of all of this is that prednisone can be a wonder drug in terms of getting fast relief from a flaring autoimmune disorder, but is not really a good drug to be on long term unless there is no other option.
  • It basically ages your body rapidly, and you become progressively weaker in time, and there is a looming toxicity that increases with long term use.
  • It is a good idea to not stay on it any longer than you must.

Author’s Personal Note:   I have a long-standing love-hate thing relationship with prednisone.  I love what prednisone does for me, but I hate what prednisone does to me.  As a “rescue” medication it is the bomb!  I’m glad to have it as a tool to use.

 

Cold Soaked? Seven Ways to Warm Up.

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When it comes to cold weather, if you have cryoglobulinemia, less exposure to cold is best. For many people with type I cryo, their reaction to cold can be immediate and very strong, so great care must be taken to minimize cold exposure. For those of us with type II and type III cryoglobulins it often takes a little longer for us to react to cold, but we still do.. and it often does not matter which type you have when you can eventually reach a point where it seems that any temperature is equally “bad”.

For me, my first clue that I have overexposed myself to cold is usually a mild petichial rash, or raynauds, or levido reticularis on my extremities… usually on my hands or feet. Another clue is that I might suddenly find myself experiencing symptoms of rheumatoid arthritis, particularly stiff and sore knees. At this point ,I know I have done myself harm, and that I need to act right away to recover.

Everyone is a little different.. you are going to have to try some of these ideas to decide what works for you.

This is how I cope with it;

1) GET INDOORS AND WARM UP RIGHT AWAY! For me, I usually do not react to cold instantly, and reacting to cold seems to be the result of the total dose of cold over time. So I need to avoid getting deeply chilled and to warm up fast when I do.

2) sometimes it is a good idea to lay down , and get horizontal , to keep cryoglobulins from pooling in your legs and buttocks after long periods of sitting or standing. Sometimes an hour or so of getting horizontal with my feet elevated a little is helpful for me and will reduce pain and swelling in my feet/legs a bit..

3) If you are sitting, elevate your feet, and use a heated foot pad. This often makes me feel a lot more comfortable, reduces pain in stiff and sore feet and ankles, reduces swelling in my feet and lower legs a bit, and seems to help reduce skin damage from lesions and ulcers a little.
If you have sensorimotor neuropathy, your sense of pain might not be all too accurate, so be careful when using a heat pad to keep your feet warm.

4) If you can, get up and move around once in a while. If you just sit or stay in bed, and you are of the type who has rheumatoid arthritis , or symptoms like RA, staying immobile can be a bad idea. If you feel up to it, get up and move around once in a while to keep your joints limber… usually arthralgia will improve once you start moving around a bit in the morning. It is almost always worse in the AM, but often improves in an hour or two. Sometimes in the evening things can suddenly turn worse. You sort of need to learn when it is a good idea to stop and rest and when it is a good idea to push ahead against all odds.

5) If you are the type who develops palpable purpura or necrotic skin lesions rather easily, you might find it helpful to avoid clothing that puts pressure on your skin, such as tight-fitting socks and pants. I have learned the hard way that sometimes I am better off with no socks on my feet and fewer lesions than with socks and more lesions… I also found that at these times I can easily develop lesions on my skin by simply abrading the skin or by just bumping into things… so be careful and adjust your clothing and your behavior to your needs.

6) if you suddenly find yourself headed into a major flare you might need to call your doctor. For some of us a flare is mostly just discomfort, and for others of us it can be life threatening, so be alert to your condition and act on it early.

7) and lastly, STAY WARM!, dress in layers, use a heat pad to keep your feet warm! Keep your core body temperature up to reduce the possibility of cryoglobulins affecting internal organs.

B Cell and Cryo

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It has been speculated that B cells are living too long due to apoptosis failing, as they age past their pre-programmed expiration date they start producing cryoglobulins. It is very likely more complex than this, but failed apoptosis (programmed cell death) is one cause for B cell proliferation. However it is unclear if the failure is in the message sent to the B cells to die or if they are ignoring it. One clue is that in the case for HEPC patients is that cryoglobulins will frequently contain fragments of HEPC RNA. Cryoglobulins do appear to function as an immune system component, but they basically trap targeted antigens by snaring then in their spider-web-ish structure and ripping them apart under electrostatic tension. It is sort of like the Borg in Star Trek. They tear things apart and incorporate them into their molecular structure. The down side is that cryoglobulins behave a bit like both antigens and antibodies which results in a runaway immune system when the immune system basically attacks itself. I tend to interpret the cryoglobulins as the immune systems last desperate effort to rid itself on a source of long standing inflammation. This is not entirely true but it helps me to visualize it. Also, one thing that I suspect may be true is that in cases of non-HEPC cryo, one may benefit from keeping the immune system suppressed long enough, and deep enough to sometimes be effectively “cured”, or at least permanently in remission. This is also speculative, but the fact that stem cell transplants often “cure” cryo strongly suggests that something along this line is going on.