Diane Dike

Additional Therapies

• LAC (low antigen content) diet is a particular diet that can improve the clearance of circulating immune-complexes by restoring the activity of the reticulo-endothelial system which are cells that filter out and destroy bacteria, viruses and foreign substances and destroy worn out or damaged cells. This diet eliminates meat (except turkey), eggs, dairy, food additives, preservatives and all beverages except water. It is rich in fruits and vegetables.

• Vitamin D therapy can be added to traditional treatments because a deficiency in vitamin D has been linked to many of the underlying conditions usually associated with cryoglobulinemia.

• Omega 3 fatty acids such as fish oil has proven to be beneficial in treating inflammatory disorders by inhibiting arachidonic acid, an enzyme in the body or diet that causes inflammation.

• Regular exercise helps aid the body in keeping your immune system strong, muscles flexible and strong, improves the vascular system, helps joints, improves mental outlook and numerous other benefits.

• Massage therapy helps the circulatory system and endocrine system while boosting the immune response and reducing stress.

• Meditation. Yoga or personal faith helps to reduce stress and improve depression and general outlook.

• Medical Marijuana. Certain cannabinoid drugs have been approved by the US Food and Drug Administration (FDA) to relieve nausea, pain and vomiting and increase appetite in people with cancer and AIDS. Other marijuana extracts are still being tested. THC and marijuana are promoted to relieve pain, control nausea and vomiting, and stimulate appetite in people with cancer and AIDS. Some cryo patients have found it helpful in managing symptoms of cryo and it's related conditions. Remember we are are relaying information CVO members have experienced and research we've done over the years to try and understand this complicated disease. If you have any concerns or questions, please consult your doctor.

 

Plasmapheresis/Cryoflitration Symptoms of high blood viscosity (thickness) include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, headaches, vertigo, seizures and coma. Hyperviscosity syndrome may be caused by an increase in serum proteins or cells. Plasmapheresis can be used to decrease viscosity. During plasmapheresis, blood is initially taken out of the body through a needle or previously implanted catheter. Rapid removal of disease-causing autoantibodies from the circulation can be helpful to temper the disease. Plasma exchange offers a quick short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be suppressed, usually by the use of medications such as prednisone, cyclophosphamide, cyclosporine, mycophenolate mofetil, rituximab, Interferon or a mixture of these. Cryofiltration with plasmapheresis is placing the plasma in a refrigerater to chill until the cryoglobulins precipitate out of the plasma. The precipitated cryoglobulins are filtered out by the cryofilter. The filtered plasma is warmed, recombined with the blood cells, and returned in the patient's vein (1). We do not now of any medical professionals practicing this at this time.

 

Cryofibrinogenemia (CF) refers to thrombotic occlusive vascular disease resulting from the cold precipitation of cryofibrinogens. Cryofibrinogens are cryoproteins in anticoagulated blood or plasma that are composed of fibrinogens (a protein in the blood plasma that is essential for the coagulation of blood and is converted to fibrin by thrombin and ionized calcium, also called factor I) that reversibly precipitate in the cold. The clinical exam and course is similar to cryoglobulinemia with a mean onset age of 50-60 years. Cryofibrinogenemia can be idiopathic (primary) or associated with malignancy (particularly prostatic cancer), thromboembolic disease, oral contraceptive pills, hyperglycemia, diabetes, pregnancy, and pseudotumor cerebri. Skin lesions like in cryo patients include purpura, livedo and Raynaud's phenomenon. In severe cases, skin ulcerations or necrosis and gangrene can occur.

Complications

The illness is not predictable.

Kidney damage can be serious and result in failure.

Death usually occurs from heart disease, infection or brain hemorrhage. Because of the thickness of the blood, stroke, blood clots, and blood clots in the eye-leading to blindness can occur.

Vasculitis of the arteries can result in blockage leading to damage in the organs such as in the skin, kidneys and bleeding in the lungs.

Ulcerated sores can lead to gangrene because of a profound lack of blood flow especially to the extremities. The vessels shut down as if a tourniquet was applied.

 

The first line of treatment is staying warm-wear mittens, even to open the fridge! This is of utmost importance and a necessary preventative measure. Seems simple enough--well, if you are challenged in this way, it is not quite that easy. For instance, I lived in warm, sunny Florida; seems like that would be a good place to live in health and warmth. Well, try going into a grocery store, restaurant, or anywhere the air condition runs after being out in the heat. I need to wear full ski mountain gear to make it through a shopping experience in a cold store. Have you ever seen anyone in a grocery store in Florida with full ski gear on? You really stand out--get looks of judgment. People whisper, make fun and even say hurtful, insensitive comments. So you begin to think it is easier to just stay home.

 

Service Dog

But now that I have Gracie trained to stay in the snugli against my heart creating heat for me that I cannot, it is a whole new world! She helps me to participate in life more safely. She is more than a dog, she is a medical device of necessity. Because cryoglobulinemia is rare and each patient is unique in the way this disease presents itself, there is no standard treatment protocol.

 

Physicians will vary in how they choose to treat each patient based on lab findings and symptoms. In an effort to give education about treatments, we will speak in general overall terms and if you have any questions about how a treatment mentioned may pertain to your particular case, please consult your physician.

 

The main goal in treatment for cryoglobulinemia is to limit organ damage by reducing the amount of cryocrit, reducing damaging systemic inflammation and treat underlying conditions. Asymptomatic cyroglobulinemia typically requires careful monitoring rather than treatment. Mild to moderate symptoms might require anti-inflammatory treatment, immune suppression medicines or sometimes low dose chemotherapy regimens. Severe symptoms are treated with higher doses of the moderate symptom treatments, plasmapharesis, anti-viral treatment or monoclonal antibodies.

The purpose of cryo typing is to help diagnose possible underlying diseases or possible future developments. However, this is not an exact process and the underlying cause and future development of the disease can remain unknown. An assigned classification only groups the patient with people experiencing or likely to experience certain diseases or malignancies. Nonetheless, it is a useful tool because it helps direct the physician's path in determining the best protocol for each unique patient. If you haven't been typed yet, ask your doctor about it.

Diane Dike

Type III - POLYCLONAL mixed cryo

 

• 25-30% of the reported cases fall into Type III

• Has a polyclonal rheumatoid factor or systemic lupus connection

Types II and III, also known as the mixed cryoglobulinemias, associated with

• Chronic inflammatory states such as systemic lupus erythematosus (SLE), Sjögren syndrome, and hepatitis virus infections. 

 

Type II MIXED WITH ONE MONOCLONAL a mix of IgM and IgG proteins that resemble classic rheumatoid factor

• Referred to as mixed cryoglobulinemia

• 50-60% of the cases are grouped into Type II

• Has a monoclonal rheumatoid factor

• Associated with multiple myeloma, Waldenstrom's, hepatitis C, leukemia, lupus, rheumatoid arthritis, Sjogrens

Type I MONOCLONAL (pure) is the least common type

 • Is usually composed of a single monoclonal immunoglobulin (IgM, IgG, IgA, or Bence Jones protein)

• Often related to cancer of the blood or immune system

• 10-15% of the cases are grouped into Type I

• Usually does not have rheumatoid factor activity

• Cutaneous lesions of the head or neck or petechial, purpura, or ulcerated/infarcted lesions of the lip, mucosa membranes, or palate are common

• Associated with malignancies of the immune system: lymphoma, leukemia, Waldenstrom's macroglobulinemia and multiiple myeloma

• May result in hyperviscosity (inflammatory vasculitis/thickening) due to high levels of circulating monoclonal cryoglobulin, leading to obstruction of vessels.

Types of Cryoglobulinemia

The types of cryoglobulinemia are grouped into what's called Brouet's Classification based on immunoglobulin compositions. Once cryoglobulins are detected, the serum can be typed depending on the antibody produced

In Summary

Why join CVO? Due to its rarity, we need cryoglobulinemia sufferers to join CVO. When you do you gather with others to create a voice. The more we have, the louder we become. Our needs are great and our goals are high. CVO is working for you, your future and future generations. Also, please consider enrolling into the CoRDS registry because they help to connect researchers with patients. A primary challenge faced by patients, families, physicians, and researchers of the rare disease community is the overall lack of information and treatment protocol. We are better when we work together, CVO's slogan while putting the unity back into our community.

Clothing: see http://dynamics.org/~altenber/cryo/COLD_GEAR/

I (Diane) have most of the clothing listed on Dr. Altenberg's page. I even have battery operated heating gloves and boots.

 

Working Dogs: Nothing works as well as Gracie. She offers consistent heat. She helps to maintain a life saving homeostasis providing regular, consistent and necessary temperature regulation and feedback. She was trained to stay in a carrier against by body, specifically my core. I’ve trained her to be a constant alerting device to changes in body temperature which can result in loss of life or limb.

 

Complications: This very difficult disease and its unwelcome roommates includes symptoms associated with MS, Lupus or diabetes. Cryoglobulins are antibodies. It is not known why the abnormal proteins become solid and thicken (gel-like) at low temperatures. But, when they do, they can block blood vessels throughout the body leading to complications ranging from skin rashes to kidney failure to death..

Did you know... many people with cryoglobulinemia don’t look sick? 

* People with cryo can feel isolated, misunderstood, rejected and forgotten.

* People with cryo are more likely to improve their outlook and well-being with support, prayer, staying active and focusing on helping others.

* It can affect people of all ages?

* There is no cure for cryo unless, in some cases, when it is secondary to another disease. Overall, treatment is aimed at helping reduce symptoms.

* It is an autoimmune disease where the body attacks itself?

* It may affect many organs at the same time?

* It may take months to years to get a confirmed diagnosis?

* It is considered rare through out the world?

* Some patients have had fingers, toes or extremities amputated?

* A service dog can help cryo patients more safely participate in life!

Diane Dike Volunteers

The mean age of onset: 47 years. Ages range from 34-66 years. (5,11). Men were affected 2:1 in a one study (12).

Types II and III are associated with autoimmune diseases, chronic inflammatory, immunoproliferative, infectious diseases and renal and neurologic involvement is more frequent (6,7). Overall, cryo is associated with autoimmune and connective tissue diseases and conditions such as lymphoproliferative disorders but mostly known for association with hepatitis viral infections. Rare occurences with Epstein-Barr, syphilis, bacterial endocarditis, HIV and leprosy. Cryoglobulinemia may also be classified based on the underlying associated disease. 

Heritability of Cryoglobulinemia

http://www.biooncology.com/tumor-types/multiple-myeloma

The lifetime risk of multiple myeloma is 1 in 1591From

 

http://informahealthcare.com/doi/abs/10.3109/10428194.2011.639881

"While the etiology of multiple myeloma (MM) is largely unknown, evidence for an inherited genetic susceptibility is provided by the two-fold increased risk of the disease seen in first-degree relatives of cases of MM." Putting those together, since several at least two in our group have first-degree relatives that had myeloma, our lifetime risk would be 1 out of 796.

Cryoglobulin – Used to help detect the presence and relative quantity of cryoglobulins in the blood.

Rheumatoid Factor (RF) – Primarily used to help diagnose rheumatoid arthritis or Sjogren syndrome and to help distinguish them from other forms of arthritis or other conditions that cause similar symptoms.

Urinalysis (UA) – Used as a screening and/or diagnostic tool because it can help detect substances or cellular material in the urine associated with different metabolic and kidney disorders.

Urine Protein (24 hour Urine Protein) – Used to detect protein in the urine, to help evaluate and monitor kidney function, and to help detect and diagnose early kidney damage and disease.Information above was derived from http://labtestsonline.org.

Diagnosed with Cryo: Twenty-three years ago when I was diagnosed there was not much information available pertaining to living with, overcoming and managing cryoglobulinemia.

 

CVO is working hard to change that so no one has to feel as scared, lonely and confused as I did. 

 

Cryoglobuinemia is a painful systemic inflammatory blood clotting disease that intensifies when I get cold, stressed, experience a breeze, stand or sit with my feet hanging down.

CVO’s goals are to increase advocacy, awareness, education, research and support for cryoglobulinemic patients for the benefit of quicker diagnosis, better treatments, and some day a cure. Many cryoglobulinemia patients go without a diagnosis for years.

 

A diagnosis of cryoglobulinemia indicates the presence of cryoglobulins in the blood (abnormal forms of protein molecules that precipitate at cold temperatures). When exposed to cold, a cryo sufferer may experience impaired circulation, color changes in the skin and nails, hives, damage to the extremities, bleeding into the skin (purpura), and other issues listed below.

Eating can be difficult. Keep it simple: no ice in drinks, no frozen drinks or ice cream. Careful, some sauces and spices can cause a reactions, hurt during digestion or make cryo patients nauseated, induce colitis or tired of chewing. Supplement your diet and eat healthy. Twenty-four years later, I avoid going to the hospital since there is little that can be done, it's often too cold, they don't know what to do to help and I'd would rather suffer or work through a flare up at home.

 

References

1. Altenberg, Ph.D. Lee, Cryoglobulinemia Home Page, Updated December 10, 2002

2. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinemias. Lancet 2012; 379:348.

3. Wintrobe MM, Buell MV. Hyperproteinemia associated with multiple myeloma: with report of a case in which an extraordinary hyperproteinemia was associated with thrombosis of the retinal veins and symptoms suggesting Raynaud's disease. Bulletin of the Johns Hopkins Hospital 1933; 52:156.

4. LERNER AB, WATSON CJ. Studies of cryoglobulins; unusual purpura associated with the presence of a high concentration of cryoglobulin (cold precipitable serum globulin). Am J Med Sci 1947; 214:410.

5. Cohen SJ, Pittelkow MR, Su WPD. Cutaneous manifestations of cryoglobulinemia: Clinical and histopathologic study of seventy-two patients. J Am Acad Dermatol 1991;25:21-7.

6. Meltzer M, Franklin EC, Elias K, et al. Cryoglobulinemia: A clinical and laboratory study. Am J Med 1966;40:837-56.

7. Brouet JC, Clauvel JP, Danon F, et al. Biological and clinical significance of cryoglobulins. Am J Med 1974;57:775-88.

8. Marcellin P, Descamps, Martinot-Peignoux M, et al. Cryoglobulinemia with vasculitis associated with hepatitis virus infection. Gastroenterology 1993;104:272-7.

9. Burke E, Humphrey RL, Horn TD. Nonhealing ulcers on the lower extremities. Arch Dermatol 1997;133(7):909-14.

10. Doutre M. Hepatitis C Virus-related skin diseases. Arch Dermatol 1999;135:1401-3.

11. Gumber SC, Chopra S. Hepatitis C: A multifaceted disease: Review of extrahepatic manifestation. Ann Int Med 1995;123(8):615-20.

12. Daoud MS, el-Azhary RA, Gibson LE, et al. Chronic hepatitis C, cryoglobulinemia, and cutaneous necrotizing vasculitis. J Am Acad Dermatol 1996;34:219-23.

13. Pawlotsky J-M, Dhumeaux D, Bagot M. Hepatitis C virus in dermatology. Arch Dermatol 1995;131:1185-93.

14. Levey JM, Bjornsson B, Banner B, et al. Mixed cryoglobulinemia in chronic hepatitis C infection. Medicine 1994;73(1):53-67.

15. Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. N Engl J Med 1989;321(22):1502-5.

16. Smith JB, Shenefelt PD, Soto O, Valeriano J. Pyoderma gangrenosum in a patient with cryoglobulinemia and hepatitis C successfully treated with interferon alpha. J Am Acad Dermatol 1996;34(5 Pt 2):901-3.

17. Gorevic PD, Kassab HJ, Levo Y, et al. Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients. Am J Med 1980;69:287-303.

18. Ferri C, Zignego AL, Pileri SA (2002). "Cryoglobulins". J. Clin. Pathol. 55 (1): 4–13. doi:10.1136/jcp.55.1.4. PMC 1769573. PMID 11825916.

Treatment Protocols

Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms.

Management involves treatment of underlying disease and may include immunosuppression (prednisone and/or other cytotoxic agents, such as chemotherapy), interferon alfa (for hepatitis), and plasmapheresis (for progressive systemic involvement of vasculitis). Results of several studies suggest that treating the hepatitis C infection helps to eradicate the hepatitis C-associated cryoglobulinemia. Therefore, high doses of interferon alfa for longer treatment periods and antiviral drugs may be beneficial.

NSAIDS (Nonsteroidal anti-inflammatory drugs) such as Ibuprofen, Naproxen or Nabumetone can be prescribed to reduce inflammation, treat arthralgia and fatigue.

Immunosuppresants might be prescribed to suppress the immune response in those with underlying autoimmune diseases, vasculitis, organ involvement or skin manifestations. Drugs used for this might be Plaquenil (Hydroxychloroquine), Imuran (Azathioprine), or Cytoxan (cyclophosphamide).

Corticosteroid treatment such as Prednisone is used to treat more severe inflammation

• Interferon treatment called Pegylated interferon alfa (IFN-alfa) combined with ribavirin (antiviral) has proven effective in patients with underlying Hepatitis C, leukemia, and lymphomas.

Antivirals like ribavirin (Virazole) can be used to treat Hepatitis C patients who have cryoglobulinemia. Entacavir is an antiviral for those with Hepatitis B as well as cryoglobulinemia.

Chemotherapy agents such as Methotrexate, Velcade and Cytoxin (also an immunesuppressant drug) can be used to not only treatunderlying malignancies but also treat primary cryoglobulinemia as well.

Monoclonal antibody such as Rituximab can be used alone or in combination with other chemotherapy agents or steroids for treatment of malignancies, Hepatitis, lupus, underlying autoimmune diseases such as rheumatoid arthritis or maintenance for the symptoms of cryoglobulinemia.

Plasmapheresis is used to relieve symptoms of severe or uncontrolled cryoglobulinemia. This process removes whole blood from the body and separates plasma, which contains the cryocrit antibodies. The cells are then suspended and the plasma replaced. The blood is then returned to the body (12-17).

Cryoglobulinemia Blood Testing Details

"Cryoglobulins come out of solution below body temperature. Serum must be obtained from clotted blood maintained at body temperature, from time of withdrawal. If blood is kept at lower temperatures, the cryoprecipitate may centrifuge out with the blood clot." For a detailed description of testing, collection, processing and results please refer to our friend and bio-chemist Lee Altenberg, Ph.D. cryoglobulinemia website. *If the testing and or lab work is not done correctly it can give a false negative. Many labs do not follow proper procedure.

 

We have a volunteer lab technician on staff that can answer any questions you may have. Please visit Dr. Altenberg's website to review and print out proper procedure.

 

Labs

Each cryoglobulinemia patient is very unique as to the variety of conditions they present. Due to this fact, we are listing the most common labs typically ordered.

• CBC with Differential and Platelet (CBC) – This is a test is often used as a broad screening test to determine an individual’s general health status.

• Comprehensive Metabolic Panel (CMP) – These tests give your doctor important information about the current status of your kidneys, liver and electrolyte and acid/base balance as well as your blood sugar and blood proteins.

• Sedimentation Rate (Sed Rate, ESR) – This test is ordered to help detect conditions associated with acute and chronic inflammation, including infections, cancers, and autoimmune diseases.

• C-Reactive Protein (CRP) – A non-specific test to detect inflammation if there is a high suspicion of tissue injury or infection somewhere in the body, but the test cannot tell where the inflammation is or what condition is causing it.

• Antinuclear Antibody (ANA) – Used to help screen for autoimmune disorders and is most often used as one of the tests to diagnose systemic lupus erythematosis (SLE).

Hepatitis C antibody (anti-HCV) – Used to detect and diagnose and infection and/or monitor the treatment of hepatitis C virus.

Serum Protein Electropheresis (SPEP) – Used to identify the presence of abnormal proteins, to identify the absence of normal proteins, and to determine when different groups of proteins are present in unusually high or low amounts.

Anti-dsDNA – Used in support of a diagnosis of systemic lupus erythematosus (SLE) and distinguishes it from other autoimmune disorders.

ENA Panel – Usually ordered following a positive ANA test in people who have clinical signs of an autoimmune disorder. The 4-test ENA Panel is used to help diagnose mixed connective tissue disease, systemic lupus erythematosus, and Sjogrens syndrome. The 6-test ENA can also help identify scleroderma and polymyositis.

Bone Marrow Aspiration and Biopsy – Provides information about the status of and capability for blood cell production.

HIV Testing - There are a number of tests that are used to find out whether a person is infected with HIV. These include the HIV antibody test, p24 antigen test and PCR test. There are other types of HIV testing, which are used once a person has been diagnosed with the virus. These include the CD4 test and the viral load test.

Cryo=cold; globu=clot; nemia=blood. 
Cryoglobulinemia
is a medical condition caused by abnormal immunoglobulins (blood proteins), called cryoglobulins. Cryoglobulin means "cold antibody in the blood."
 

The blood turns into a thick jelly like substance, straining the heart and damaging vessels. Extremities can become heavy, swell, sore, throb, itchy, with burning hives, swelling and pain while leading to agony, confusion and heartbreak. Proteins deposit in small and medium-sized blood vessels, which can lead to restricted blood flow to joints, muscles, and organs. I had ulcerated, pitted sores for over three years that wouldn't heal no matter what we tried until I gave in to staying safe and warm in bed, giving up my careers and preventing flare ups at all cost (see "Living with Cryo" website page for 20 lifesaving prevention ideas).

 

Cryoglobulinemia is a rare autoimmune disorder that affects twice as many women as men, usually not apparent until middle age. I was one of the youngest cases. The acute onset started at the tender age of 23 but it took almost three years of thinking I was allergic to living and lots of tests, doctor appointments, hospital stays... to figure out what I had. One of the reasons it took so long is because it is rare and requires a special blood test (Diane Dike, Ph.D.).

 

Vasculitis: (the hurting disease) Vascu=vessel, litis=inflammation.

Vasculitis refers to inflammation of the blood vessel that includes the veins, arteries and capillaries. Vasculitis causes changes in the walls of blood vessels, including thickening, weakening, narrowing and scarring. The cause, a very rare condition may include diseases of: the immune system, certain cells in the bone marrow (monoclonal gammopathy of undetermined significance-MGUS or its malignant form, multiple myeloma), and some infectious diseases.

 

Diagnosis of cryoglobulinemia depends on the presence of cryoglobulins in the blood and then searching for a possible underlying cause. The first cryoprecipitation phenomenon has been attributed to Wintrobe and Buell, who in 1933 described a patient with signs and symptoms of hyperviscosity associated with multiple myeloma. In 1947, the “cold precipitable serum globulin” was assigned the term “cryoglobulin”.

 

Cryoglobulinemia is the presence of these abnormal proteins in the blood. These abnormal proteins become thick or gel-like when exposed to cold temperatures and stress. Cryoglobulinemia as a form of vasculitis can cause damage and inflammation of the blood vessels, that includes the veins, arteries and capillaries, throughout the body. The appearance of precipitated cryoglobulins and various cryo patients flare ups are illustrated on our picture page.

What is Cryoglobulinemia?