Essential Mixed Cryoglobulinemia

What is Essential Mixed Cryoglobulinemia?

Essential mixed cryoglobulinemia is a rare disorder in which cryoglobulins, immune proteins that clump below normal body temperature and dissolve again when warmed, build up in the blood and deposit in small and medium blood vessels. This can injure the vessel walls and damage organs.^[1] "Mixed" means the clumps contain more than one kind of antibody. "Essential" is the older term used when no cause is found, which applies to about 10 percent of mixed cases. Most mixed cryoglobulinemia is linked to an infection or autoimmune disease, so the diagnosis calls for a careful search for a cause.^{[1, 2]}

For a condition like this, we ask that you are under a physician's care for it and that your treating team knows you are receiving complementary care.

Common symptoms

Symptoms depend on which organs are affected. Mild disease may cause purple spots on the skin (purpura), tiredness and joint pain, while more severe disease can cause skin ulcers, nerve damage and kidney involvement.^{[1, 2]}

• Purpura, rashes and slow-healing skin ulcers, most often on the legs
• Joint pain, especially in the hands and feet
• Numbness, tingling or weakness from nerve involvement (neuropathy)
• Fingers and toes that turn white or blue in the cold (Raynaud's phenomenon)
• Blood or protein in the urine, which can signal kidney inflammation^[3]
• Fatigue, fever and weight loss

Causes and risk factors

Mixed cryoglobulinemia is most often associated with hepatitis C infection. Other associations include hepatitis B, HIV, autoimmune diseases such as lupus and Sjögren syndrome, and disorders of B cells (a type of white blood cell).^{[1, 2]} In the United States, autoimmune diseases are now considered the most common cause, because hepatitis C treatment has reduced how often it occurs.^[3]

How it is diagnosed and treated conventionally

Diagnosis is based on symptoms, a blood test for cryoglobulins that requires careful sample handling, and tests for complement levels, kidney function and an underlying infection or disease. Biopsy of skin or kidney is sometimes needed.^[1]

Treatment depends on the cause and severity and is managed by specialists. Mixed cryoglobulinemia linked to hepatitis C or hepatitis B needs antiviral treatment. Severe vasculitis may be treated with corticosteroids, immune-modulating drugs, anti-CD20 antibodies such as rituximab, and plasma exchange. A multidisciplinary approach is considered essential.^[2] Because cold triggers the precipitation, keeping warm is a standard self-care measure.^[1]

Why Essential Mixed Cryoglobulinemia calls for a whole-person approach

Cryoglobulinemia affects several systems at once, so no single therapy addresses it. The immune and vascular process is treated by physicians, while pain, fatigue, circulation problems in the hands and feet, and the strain of living with a long-term illness all deserve attention too.

Supportive care does not remove cryoglobulins or treat vasculitis. The areas below are where symptom-level help may be possible.

Joint and musculoskeletal pain

Joint pain (arthralgia) is a common feature of the illness.^[1] Acupuncture has been studied for several chronic pain conditions, which is the closest evidence available.^[4]

Nerve symptoms

Numbness, tingling and weakness come from vasculitis affecting the nerves.^[2] Any new or worsening nerve symptoms need medical review before any complementary care.

Cold-sensitive circulation

Reduced blood flow to the fingers and toes in the cold can be part of the picture. Studies exist for Raynaud's phenomenon in general, covered below.

Fatigue and stress

Tiredness (asthenia) is among the symptoms of milder disease.^[2] Long-term illness, medicines such as steroids, and uncertainty all add to stress and poor sleep.

Acupuncture as supportive care in Essential Mixed Cryoglobulinemia

What the research shows

No clinical trials of acupuncture for cryoglobulinemia were found, so there is no evidence that it affects the disease. The evidence below is for symptoms in other conditions.

An individual patient data meta-analysis of 39 trials with about 20,800 patients found acupuncture reduced chronic musculoskeletal pain, osteoarthritis pain, headache and shoulder pain more than sham or no acupuncture, with effects lasting over a year.^[4] Cryoglobulinemia was not among those conditions. For fatigue, an overview of 51 systematic reviews in cancer reported benefit but rated most of them low or very low in quality, and a review of 16 trials in chronic fatigue syndrome found low-certainty evidence favoring acupuncture over sham.^{[5, 6]} In neuropathy caused by chemotherapy, a network meta-analysis of 33 trials suggested acupuncture-related treatments improved symptoms and pain, though that is a different cause of nerve damage from vasculitis.^[7]

For Raynaud's phenomenon, a 2009 review found only two acupuncture trials and called the literature inconclusive.^[8]

How acupuncture may work

We know of no research on how acupuncture might act in cryoglobulinemia, and we do not claim it influences the immune process or the vessels. Any benefit for pain or fatigue is a symptom-level effect.

What treatment involves

Treatment uses fine, sterile, single-use needles placed at selected points, usually left in for about 20 to 40 minutes, over a short course of visits with reassessment. Needles are not placed through ulcerated or inflamed skin.

Serious problems are rare. In prospective studies, about 9 in 100 patients had a minor reaction such as brief bleeding, soreness or redness at a needle site, and serious events occurred in about 1 in 10,000 patients.^[9] A meta-analysis of observational studies found a higher rate of hepatitis C infection among people who had received acupuncture, which is why single-use sterile needles matter, particularly for people who may have hepatitis C or whose immune system is suppressed.^[10] Tell the practitioner first about skin ulcers, bleeding problems, blood thinners, immune-suppressing medicines, pregnancy, or a pacemaker (relevant to electroacupuncture). Keep the room and your hands and feet warm during treatment.

Ayurvedic medicine as supportive care in Essential Mixed Cryoglobulinemia

The Ayurvedic view

Ayurveda has no counterpart to cryoglobulinemia. Practitioners may describe purpura, joint pain and cold-sensitive circulation in terms of disturbed rakta (blood tissue) with Pitta and Vata, and cold-triggered symptoms as Vata. These are traditional categories, not diagnoses.

Therapies that may be used

Supportive options include warm, regular, easily digested meals, a steady daily routine, keeping warm, restful sleep habits, and gentle breathing and relaxation practices. Gentle warm oil massage may be used on intact skin. Individually prescribed herbs may be used only with great caution because they can interact with medicines.^[11]

Panchakarma, the traditional cleansing program, is not appropriate during pregnancy, acute illness or frailty. It is also not suited to active vasculitis, kidney involvement, skin ulcers, low strength, or use of immune-suppressing drugs. An herbal preparation applied to the skin (transdermal medication therapy) may be considered on intact skin only.

What the research shows

We found no clinical trials of Ayurvedic treatment for cryoglobulinemia or for vasculitis, so there is no evidence that it helps.

Product quality is a particular concern for people with kidney or liver involvement. In one study, about one fifth of Ayurvedic medicines bought online contained detectable lead, mercury or arsenic.^[12]

Herbal medicine as supportive care in Essential Mixed Cryoglobulinemia

Herbs and formulas that have been studied

No clinical trials of herbal medicine for cryoglobulinemia were found. Since hepatitis C is a common trigger, we looked at herbs for that infection. Herbs tested include silymarin (milk thistle), oxymatrine, and several Chinese herbal mixtures. For Raynaud's phenomenon, Chinese formulas such as Danggui Sini Tang and Buyang Huanwu Tang have been tested in small trials.^{[13, 14, 15]}

What the research shows

The evidence is weak and does not apply directly. A Cochrane review of 13 trials of medicinal herbs for hepatitis C found no firm evidence of benefit, and adverse events were reported with herbs.^[13] A Cochrane review of milk thistle in alcohol-related or viral liver disease found that it did not seem to significantly influence the course of disease in high-quality trials.^[14] A meta-analysis of 8 trials in primary Raynaud's phenomenon found Chinese herbal medicine may help but called the benefit inconclusive, because the trials were of generally poor quality, compared against drugs, and did not report attack frequency or adverse events.^[15] Primary Raynaud's is a separate condition from the Raynaud's phenomenon that occurs with vasculitis.

Antiviral treatment, not herbs, is the established approach for hepatitis-related cryoglobulinemia.^[2]

Safety and herb-drug interactions

Herbs can interact with medicines. A review describes bleeding when warfarin is combined with danshen, ginkgo or garlic, and lowered ciclosporin levels with St. John's wort, which led to organ rejection in some cases.^[11] People with cryoglobulinemia often take corticosteroids, immune-suppressing drugs or antivirals, so every herb must be reviewed against your complete medicine list and agreed by your physicians.

Herbal and dietary supplements are a recognized cause of liver injury, which matters when hepatitis or liver-affecting medicines are involved.^[16] Tell us if you are pregnant or breastfeeding, have liver or kidney disease, or have surgery planned. Herbs should come from tested sources and are prescribed individually.

Translating traditional medicine into modern biological language

This section is interpretation, not equivalence. Chinese medicine may describe cold-sensitive, purple or blue fingers and joint pain as cold congealing in the channels with blood stasis. In biomedical terms the closest parallel is the blood vessel injury and impaired flow caused by cryoglobulins precipitating in cold, which is described in modern medicine as vasculitis.^[1]

Ayurveda's disturbed rakta or Pitta and Vata likewise has no established biological match. No study has shown that a qi pattern or dosha corresponds to cryoglobulin levels or vessel inflammation.

How this care fits with your medical care

Supportive care here is complementary. Stay under the care of your physicians, which may include a rheumatologist, hematologist, nephrologist or infectious disease specialist, and keep taking prescribed medicines. Do not stop or change antivirals, steroids, rituximab or any other treatment without your physician. We do not diagnose or manage cryoglobulinemia, and we do not prescribe or adjust drugs.

Please bring your diagnosis, recent blood and kidney test results, your hepatitis status if known, a list of all medicines and supplements, and any notes about skin ulcers or nerve symptoms.

When to seek urgent medical care

Cryoglobulinemia can flare and cause serious organ damage, so new symptoms should be reported promptly.

• New or spreading skin ulcers, black or blue skin, or very painful fingers or toes that do not warm up
• Blood in the urine, foamy urine, a sharp drop in urine, or new swelling of the legs or face
• New weakness, numbness that spreads, or difficulty walking
• Sudden shortness of breath, coughing blood, or chest pain
• Severe headache, confusion, or vision changes
• Fever with a flare of symptoms while taking immune-suppressing medicine

If you have any of these, call 911 or go to the nearest emergency department.