This is the third part of our series about the condition based on our patient booklet “Fast Facts for Patients: Waldenström Macroglobulinemia”. This article addresses some of the possible effects of Waldenström macroglobulinemia (WM).

 

The effects of WM vary from person to person. You may experience some or none of these effects.

Effects of Waldenström macroglobulinemia

Anti-MAG Neuropathy

IgM paraproteins may mistakenly target tissues and organs in the body. In anti-MAG (myelin-associated glycoprotein) neuropathy, the IgM paraprotein damages the axons of nerves (neurons) or the myelin that insulates them. This can lead to numbness or tingling in the hands and feet or problems with balance if the nerve damage is in the limbs (peripheral neuropathy).

It is important to mention any of these symptoms to your doctor, especially if they are getting worse over time.

You may need tests to examine your nervous system in more detail: a scan of your brain or spinal cord, a lumbar puncture to look for signs of inflammation, nerve conduction studies to see how well your nerves are conducting electrical impulses or perhaps a nerve biopsy (under a local anesthetic).

Anti-MAG neuropathy

Hyperviscosity Syndrome

As the graph shows, once blood IgM paraprotein levels increase past a certain point, the blood becomes much thicker or more viscous. This is called hyperviscosity syndrome.

Hyperviscosity syndrome

Symptoms include bleeding from the nose and mouth, headaches, blurred or loss of vision and dizziness. These symptoms are more likely to occur if your IgM level is over 40 g/L. Your doctor will recommend treatment if you have symptoms.

A test for blood thickness (serum or plasma viscosity) can be done in specialist laboratories.

Bing–Neel Syndrome

Very occasionally, LPL cells build up in the central nervous system (CNS), resulting in Bing–Neel syndrome. The symptoms are varied, but may include headaches, seizures, weakness of the facial or limb muscles, double vision, personality change and memory loss. Special tests such as brain scans and sampling of the cerebrospinal fluid by a lumbar puncture are needed to identify the cells. This rare complication can be treated if recognized promptly but requires special treatments.

Cold Agglutinin Disease

Cold temperatures may trigger IgM to act as a bridge between red blood cells, causing them to stick together in the cooler parts of the body, such as the hands and feet, the tip of the nose and the ear lobes. This is called agglutination and the condition is called cold agglutinin disease (CAD).

The affected areas have poor blood circulation, especially when it is cold: color changes and ulcers may develop as the skin breaks down. CAD also results in the breakdown of red blood cells (hemolytic anemia) due to activation of a part of the immune system called complement. This can cause bouts of fatigue and breathlessness and may cause the urine to become very dark from time to time, especially when conditions are cooler.

Cold agglutinin disease

Cryoglobulinemia

Cryoglobulinemia is different from CAD in that IgM molecules stick to each other when circulating in cooler parts of the body, such as the hands and feet, the tip of the nose or the ear lobes. This can cause poor circulation in these areas, color changes like Raynaud’s phenomenon or ulcers.

Cryoglobulinemia and Rynaud's phenomenon

A similar process can affect the joints, kidneys, skin and nerves, causing damage to these tissues. If you notice problematic cold intolerance, it is worth asking your doctor about cryoglobulinemia. Diagnosis requires a test in which the blood sample needs to be kept warm until it reaches the laboratory for analysis.

Amyloidosis

In amyloidosis, fragments of the IgM change and form an abnormal protein called AL amyloid. This can be deposited in various tissues and organs, causing them to function less well. The heart, spleen, lymph nodes, nerves, gastrointestinal tract, vocal cords and kidneys can be affected to varying degrees in different people.

Amyloidosis

Tell your doctor if you experience breathlessness, dizziness when standing up, low blood pressure, new intolerance of blood pressure medication, diarrhea, weight loss or symptoms of peripheral neuropathy (such as numbness, tingling or pain in your hands or feet).

AL amyloid usually builds up gradually, which often delays its detection. Tests may include blood tests to assess heart function (NT-proBNP test), urine tests to look for excess protein leakage (nephrotic syndrome), echocardiography (a type of ultrasound scan that looks at the heart and nearby blood vessels) and/or tissue biopsy (the tissue is then examined using a stain called Congo Red, which shows the build-up of amyloid deposits). In the UK, a SAP scan may be performed at the National Amyloidosis Centre in London. Serum amyloid P component (SAP) is a normal protein in the blood that binds to amyloid deposits.

Your doctor must suspect amyloidosis is a possible diagnosis for these tests to be carried out, so it is important to report the symptoms mentioned above and ask about amyloidosis.

Transformation to Aggressive Non-Hodgkin Lymphoma

In a small number of people, WM develops into an aggressive non-Hodgkin lymphoma in a process called high-grade transformation. Transformation means that LPL cells develop the biological characteristics of diffuse large B-cell lymphoma (DLBCL). This is usually accompanied by rapidly noticeable changes, such as new swellings, sweats and weight loss.

A tissue biopsy is needed to confirm transformation. Treatment requires intensive chemotherapy with or without stem cell transplantation or newer therapies.

 

Information based on Fast Facts for Patients: Waldenström Macroglobulinemia (Karger, 2022).

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