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• Description
• In medical terms, by David Hellmann, M.D.

The name literally means “cold antibody in the blood”, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C infections. Hepatitis C is acquired by injection drug use (needle–sharing), tainted blood products, and (probably rarely), sexual transmission. Treatment of the underlying hepatitis may be an effective therapy for this type of vasculitis.

Pictured below is the hand from the same patient at different times. The image on the left is normal and the one on the right shows the patient in the midst of a flare of cryoglobuinemic vasculitis.

Pictured below is an electron micrograph of a kidney biopsy specimen from a patient with cryoglobulinemia.

In medical terms, by David Hellmann, M.D.

A discussion of Cryoglobulinemia written in medical terms by David Hellmann, M.D. (F.A.C.P.), Co-Director of the Johns Hopkins Vasculitis Center, for the Rheumatology Section of the Medical Knowledge Self-Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998). The American College of Physicians has given us permission to make this information available to patients contacting our Website.

Cryoglobulins are immunoglobulins that precipitate in the cold and disolve on rewarming. Three types of cryoglobulins are distinguished based on whether the cryoglboulin is monoclonal and has rheumatoid factor activity. Knowing the type usually allows the physician to predict the clinical features; alternatively knowing the clinical features allows one to deduce the type of cryoglobulin. Type I is a monoclonal antibody that does not have rheumatoid factor activity. Most commonly, type I is associated with lymphoma, Waldenström’s macroglobulinemia, and multiple myeloma. Because type I cryoglobulins do not easily activate complement, patients with type I are asymptomatic until the level of cryoglobulinemia is sufficiently high to cause hyperviscosity syndrome. Both types II and III are rheumatoid factors — antibodies that bind to the Fc fragment of IgG. Therefore, both types are called mixed cryoglobulins. In type II, the rheumatoid factor is monoclonal, whereas in type III it is polyclonal. Type II is associated with lymphoproliferative diseases, and both types can occur in patients with rheumatic diseases and chronic infections. Cryoglobulinemia is said to be essential when there is no identifiable underlying disease. Type II and III cryoglobulinemia frequently presents as vasculitis, most commonly with recurrentlower extremity purpura, glomerulonephritis, and peripheral neuropathy.

It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with anti–hepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.

Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms. Cryoglobulinemia with severe hyperviscosity syndrome requires plasmapheresis and chemotherapy of the underlying malignancy. Some patients with cryoglobulinemia suffer from mild, recurrent crops of lower extremity purpura that require no specific therapy. More extensive vasculitis associated with autoimmune diseases or essential cryoglobulinemia may respond to prednisone, cyclophosphamide, or both. The most effective treatment for cryoglobulinemia associated with hepatitis C has not yet been determined. Brief use of prednisone followed by 6 months of interferon alfa has produced clinical and liver function test improvement, but relapse of liver disease and vasculitis often occurs when interferon alfa is stopped.

What is methotrexate?

Methotrexate is an oral or injected drug used in the treatment of nearly every form of vasculitis. In fact, methotrexate is used in the treatment of most diseases seen by rheumatologists.

How does methotrexate work?

Methotrexate works by interfering with the replication of immune cells.

How is methotrexate given?

Methotrexate is always given once per week. It can be administered two ways: as pills taken by mouth, or as liquid that is injected subcutaneously. Patients who take methotrexate always need to take 1 mg folic acid by mouth every day to prevent side effects.

Side effects:

The side effects of methotrexate can be reduced by taking folic acid. Typical side effects can include hair thinning, oral ulcers, fatigue, nausea or diarrhea. We pay particular attention to liver function tests, renal function, and blood counts while using methotrexate. Patients taking methotrexate should not drink alcohol while using this medication.

All immunosuppressants require regular monitoring in the form of blood tests, in-person assessments, and prompt attention to any signs or symptoms of infection.

Advancing vasculitis research to improve diagnosis and treatment is critical for the care of our patients and important to the overall mission of our Center. We are successful in our mission only because of the combined efforts of all members of our Johns Hopkins Vasculitis Center team and their valuable contributions:

1. Dedicated physicians and research investigators
2. Generous patients who selflessly contribute their time and samples
3. Financial contributions to support vasculitis research

We welcome you to consider becoming a participant in one of our research studies related to vasculitis. Many studies involve little more than donating a blood sample during one of your appointments.

Often grateful patients, family members, and friends ask what they can do to support the work of the Johns Hopkins Vasculitis Center.  Financial support for medical research directly benefits our patients. For this reason, we have established the Discovery Fund for Vasculitis Research.

Although grants support some of our research and patient education projects, monetary gifts from individuals who realize the importance of these efforts play an essential role in maintaining the Johns Hopkins Vasculitis Center as a Center of Excellence.

We would like to share with you one such inspiring story:

Linda’s Loop – Linda Gray’s Family “hits the trail” in her honor 

We are happy to discuss research in progress with all current and potential donors. Please contact us at the Center directly to learn more about making a tax deductible contribution:

The Johns Hopkins Vasculitis Center

Bayview Medical Center
5501 Hopkins Bayview Circle
JHAAC, Room 1B.1A
Baltimore, Maryland  21224

Phone: 410-550-6825

Anna Dugan
Director of Development
Office: 443-571-7207
Email: adugan3@jh.edu

All information contained within the Johns Hopkins Vasculitis Center website is intended for educational purposes only. Visitors are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.

• What causes vasculitis?
• What is going to happen to me?
• Is vasculitis curable?
• Is vasculitis hereditary?
• Does diet affect vasculitis?
• Will my vasculitis return?
• How should I guard against the occurrence of a disease flare?
• Why do I have to have bloodwork checked frequently?

What causes vasculitis?

The causes of most forms of vasculitis remain unknown. Infections are strongly suspected of playing a role in in forms such as the association of hepatitis B (a virus) and polyarteritis nodosa, and hepatitis C (another virus) and cryoglobulinemic vasculitis. Bacterial infections have been suspected of playing a possible role in granulomatosis with polyangiitis (GPA, formerly known as Wegener’s) which is the reason that some patients with GPA that is limited to the upper respiratory tract are treated only with an antibiotic, Bactrim (trimethoprim/sulfamethoxazole). A general theory that applies to many types of vasculitis is that the disease results from the occurrence of a particular infection in a person whose genes (and other factors) make him/her susceptible to developing vasculitis.

What is going to happen to me?

The course of vasculitis is often difficult to predict. Some types of vasculitis may occur only once and do not return. Other types are prone to recurrences. For all patients with vasculitis, it is essential to be evaluated by physicians who are experienced in the treatment of these diseases. Vasculitis is treatable, and many patients achieve remissions through treatment. It is important to balance the types of medications necessary to control the disease and the risk of side effects that those medicines often bring. A primary aim of several ongoing new studies in vasculitis is to find drugs that help maintain remission.

Is vasculitis curable?

Most forms of vasculitis are treatable if detected early enough, before substantial organ damage has occurred. While often effective, however, the treatments remain imperfect and require improvement. Further research is needed in all forms of vasculitis. Greater knowledge of these diseases will lead to better treatments and, some day, to cures.

Will my children or other family members get it?

Vasculitis is not contagious. One cannot acquire vasculitis from contact with a vasculitis patient. In addition, despite the fact that genes probably play a role in susceptibility to some forms of vasculitis, it is unusual for vasculitis to occur in more than one member of the same family. Thus, vasculitis is not a heritable disorder. All of these points illustrate the fact that the causes of vasculitis are complex. In all likelihood, patients develop vasculitis because of the simultaneous occurrence of multiple risk factors, most of which remain poorly understood.

Does diet affect vasculitis?

This is one of the most commonly-asked questions by patients with vasculitis. All patients want to do whatever is within their power to help treat their disease. Unfortunately, there is presently no evidence that a person’s diet affects susceptibility to vasculitis, or that consuming or avoiding certain foods or beverages affects the course of the disease. In general, we advocate eating a balanced healthy diet rich in protein and vegetables. Avoidance of excessive empty calories, processed foods, and sugars may be very important, particularly in patients on steroids who are at risk for weight gain.

Will my vasculitis return?

After patients achieve remission from their vasculitis, it is logical for them to wonder if their disease will ever return. The answer, which is often difficult to give with certainty, depends in large part on the patient’s specific type of vasculitis. For example, some types of vasculitis, such as Henoch-Schönlein purpura (HSP) or vasculitis caused by a medication, are often self-limited and resolve on their own. Other forms of vasculitis (e.g., Buerger’s disease, a disease strongly associated with cigarette smoking) resolve with institution of the definitive treatment: smoking cessation.

However,  other forms of vasculitis behave less predictably and never come back in some patients but recur frequently in others. Granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), Takayasu arteritis, microscopic polyangiitis, and many other types of vasculitis fall into the category of diseases that have periods of quiescence and periods of flare. Disease flares in vasculitis can be mild (rash, minor joint pains) or severe (renal failure, skin ulcers). Flares may occur if medications are discontinued or dosage is lowered. Flare may occur in the context of infection. Often the reason for disease flare is unknown.

At the present time, the ability of doctors to predict who will suffer disease flares and who will maintain in long-term remissions (or be cured) needs refinement. Progress in this area will come through research.

How should I guard against the occurrence of a disease flare?

We believe that several points are worth keeping in mind:

First, the symptoms of flares are usually very similar those experienced at the onset of disease. If headaches signaled the beginning of giant cell arteritis, then the recurrence of headaches may indicate a disease flare. If leg ulcers began as painful red lumps on the leg the first time, then the return of painful red lumps may mean that vasculitis is back. Patients must become experts about their own manifestations of vasculitis so that they can recognize them immediately, consult their doctors, and begin appropriate treatment before serious damage occurs.

Second, we believe that patients truly know and understand their own bodies. It is important to discuss new or changing symptoms with your physicians. Together, patients and physicians can determine if new symptoms truly represent a vasculitis flare or if the cause is something equally as likely (medication side effect, infection, or other common medical issues).

Finally, because vasculitis treatments require careful monitoring by doctors, patients should discuss any changes in treatment with their physicians. Increasing or decreasing medications without consulting a physician may lead to trouble.

Why do I have to have bloodwork checked frequently?

Blood tests are helpful to monitor for the return of vasculitis by keeping a watchful eye on important parameters such as kidney function, liver tests, and markers of inflammation (ESR and CRP). Blood tests are also very important to ensure that medications are not causing any side effects such as liver irritation or low blood counts.

How often should my blood be checked?

This depends on the specific medicine or medicines that you take. Patients on cyclophosphamide (Cytoxan) should have their counts checked every week. Patients on most other kinds of medications used to treat vasculitis (Methotrexate, Azathioprine) usually only need to have their blood work checked monthly. If some laboratory tests are abnormal or nearly so, then more frequent monitoring may be required.

What type of tests do we check?

Regardless of the type of vasculitis and the exact type of medication that a patient takes, similar types of tests are monitored. These tests are:

1. a complete blood count;
2. tests of kidney function including a urinalysis; and
3. liver function tests.

The table below outlines the importance behind checking each of these tests.