Updates in the Treatment of Cryoglobulinemic Vasculitis

Introduction

Vasculitis is a rare group of diseases that is marked by inflammation of blood vessels. The blood flow is restricted owing to the narrowing of the blood vessels. The vessel walls thicken and weaken over time, with a serious possibility of bursting open due to immense pressure. This phenomenon can lead to internal bleeding or hemorrhage and requires immediate medical intervention. Vasculitis may affect any organ or organ system of the body. The disease can be categorized into subtypes based on the size of the vessel involved, such as large vessel vasculitis, medium-vessel vasculitis, and small vessel vasculitis. Cryoglobulinemia is the type that belongs to small vessel vasculitis. This article overviews the symptoms and management of cryoglobulinemic vasculitis.

What Is Cryoglobulinemia?

Cryo = cold, globulin = proteins, emia = present in the blood.

Cryoglobulinemia as a whole is a typical disease that is characterized by the clumping of blood proteins when one is subject to low temperatures. The protein clumps block the flow of blood in vessels, thereby obstructing the smooth supply of blood to surrounding regions of the body. The resultant consequence involves damage to the skin, muscles, nerves, and organs. Kidneys are reported to be the most affected organs.

What Causes Cryoglobulinemic Vasculitis?

Vasculitis is termed an autoimmune disease. This involves the body’s natural defense system to work against the healthy living tissues of the body. There are no specific reasons for such abnormal immune responses in the body. However, many factors are considered responsible, such as family history or genetic make-up, administration of certain medications, exposure to specific infections, environmental factors including pollutants, habits like smoking, and immunological factors.

Although the cause of cryoglobulinemia is not certain, its incidence is reported in 90 percent of people with hepatitis C virus infection. It may also occur along with co-existing inflammatory diseases like systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis.

Who Is Affected by Cryoglobulinemic Vasculitis?

Cryoglobulinemia is an autoimmune disease that is highly prevalent in women compared to men. Out of every 4 people affected with cryoglobulinemia, only one identifies as male. The disease type is quite rare, presented in about one in every 100,000 people. The age of onset usually lies above 50 years of age. People affected with hepatitis C virus are more likely to present with cryoglobulinemic vasculitis compared to others. Secondary infections that may precipitate the development of this disease include hepatitis B, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus (HIV), and candidiasis.

What Are the Symptoms of Cryoglobulinemic Vasculitis?

Cryoglobulinemia may or may not present with any underlying symptoms. The presence of elevated cryoglobulin levels in blood is a reliable biomarker of the disease's activity. However, some patients may present with symptoms.

• Extreme fatigue, tiredness.

• Development of purplish-bluish rash under the skin.

• Raynaud’s phenomenon involves tingling sensations in the extremities of hands and feet.

• Numbness in limbs due to nerve involvement.

• Soreness of muscles.

• Joint aches and pains.

• Cold hands and feet.

• In severe cases, ulcers or gangrene of the limb involved may also develop.

• Involvement of the kidneys.

• Swelling of lymph nodes.

• Headaches or strokes in cases where brain damage is evident.

• Congestive heart failure may occur in rare cases where heat is impacted.

How to Diagnose Cryoglobulinemic Vasculitis?

The diagnosis of cryoglobulinemia can prove to be a little challenging for clinicians as the disease may also be present with no specific symptoms. The doctor orders a few tests to confirm the diagnosis.

1. Blood Tests: The clinician orders specific blood tests that may confirm the elevated levels of cryoglobulins present in blood.

2. Urine Analysis: Urine laboratory tests may be carried out to assess the presence of blood in urine. This indicates the severity of damage to kidneys, if present.

3. Imaging Studies: Several radiographs like chest X-rays, computed tomography (CT) scans of the heart or lungs, and angiograms showing images of arteries are taken to check for precipitation of proteins in blood vessels.

4. Electromyography Tests: They can be carried out to examine the nerve conduction process, especially in arms and legs.

5. Biopsy: Surgical excision of a tiny part of the suspected organ involved can be tested to confirm the damage caused by cryoglobulinemia.

Apart from the above methods, a thorough medical history and physical examination can aid the clinician in making a confirmed diagnosis of this rare atypical disease.

What Is the Treatment of Cryoglobulinemic Vasculitis?

The treatment of Cryoglobulinemia is highly individualized based on the severity of the disease, the organ or organ systems affected, and the type of symptoms it presents.

• For mild cases of cryoglobulinemic vasculitis, the doctor advises avoiding staying in cold regions and prescribes over-the-counter drugs to subside pain and inflammation. One can achieve good relief from pain upon following these minor changes.

• For moderate to severe cases, the treatment becomes a little complex. Several modes are adopted to improve the symptoms of the disease. These are discussed below.

1. Anti-Viral Therapy: Antiviral drugs are administered in patients with hepatitis C virus infection. HCV is, 90 percent of the time, the major contributor to the incidence of cryoglobulinemic vasculitis. Upon removal of HCV infection, the vasculitis also improves gradually. Reference to a hepatologist (liver specialist) is essential to obtain a fair prognosis.

2. Immunosuppressant Therapy: Vasculitis belongs to a rare group of diseases that are autoimmunity mediated. Immunosuppressive drugs aid in keeping the inflammatory response of the body’s defense system in check, thereby controlling the development of cryoglobulinemic vasculitis to a fair extent. Corticosteroids like Prednisone are widely utilized.

3. Biologic Drugs: Certain biologic drugs like Rituximab are administered to keep one’s inflammatory response in check. These drugs are reported to be effective in managing the symptoms of autoimmune disorders.

4. Plasmapheresis: A variety of blood disorders are treated by opting for plasmapheresis. This process involves the removal, return, or exchange of blood plasma and its components. It is generally carried out by performing centrifugation or filtration techniques. The clumps of blood proteins can be filtered using this method, thus re-initiating the proper flow of blood through the previously obstructed blood vessels. However, this technique is only utilized in severe life-threatening stages of the disease.

Conclusion

Cryoglobulinemia treatment must be prompt to achieve a good prognosis. The medications administered to treat the disease come bearing with it certain side effects like a weakened immune system, which may predispose one to acquiring severe infections that are otherwise preventable with a strong defense system. Therefore, the patients must be advised to get vaccinated before initiating immunosuppressive therapy for cryoglobulinemia. In cases of relapse, one must report to the doctor as early as possible.