Waldenström’s disease, also known as Waldenstrom’s macroglobulinemia, belongs to the leukemias, or more precisely to the lymphomas. The slowly progressive disease is rather rare and mostly affects elderly patients; patients younger than 40 years are affected only in exceptional cases.
What is Waldenström’s disease?
Waldenström’s macroglobulinemia is a malignant disease of the white blood cells named after the Swedish physician Jan Waldenström. The latter first described the disease in the 1940s. Waldenström’s disease is characterized by an uncontrolled proliferation of B lymphocytes, which belong to the white blood cells, the leukocytes. This results in a large number of functionally impaired B lymphocytes. B lymphocytes play an important role in immune defense. They are responsible for the production of antibodies, the so-called immunoglobulins. The disturbed B lymphocytes in Waldenström’s disease produce one of these immunoglobulins, immunoglobulin M (IgM), in large quantities. However, this IgM produced by the degenerated cells is functionless. In this case, one speaks of a paraprotein and, in the case of the increased occurrence of paraproteins in the blood, of a paraproteinemia. B lymphocytes, like most other blood cells, are produced in the bone marrow. However, because abnormally large numbers of B lymphocytes are produced in Waldenström’s disease, they infiltrate the bone marrow and displace the stem cells from which the other blood cells are formed. However, the degenerate B lymphocytes may also infiltrate other organs such as the spleen, lymph nodes, or liver.
Causes
Waldenström disease is a rare disorder. It occurs about once per 100,000 population per year in Germany. Most patients are over 60 years of age at diagnosis; only rarely is Waldenström disease diagnosed in patients younger than 40 years. As with most forms of leukemia, the cause of Waldenström’s macroglobulinemia is still unclear. However, various triggering factors are being discussed. Scientists assume that various chemicals, including benzene in particular, can lead to disturbances in blood formation. The same applies to cytostatic drugs. It is not uncommon for tumor patients to develop leukemia after treatment with cytostatic drugs. A similar situation is observed with ionizing radiation. In medicine, ionizing radiation is used, for example, in X-rays or radiation therapy in cancer treatment. Viruses are also suspected of playing an important role in the development of leukemias and tumors. Hepatitis B and C viruses, human papillomaviruses and the Epstein-Barr virus are particularly worthy of mention here. A genetic predisposition and psychogenic factors are also discussed as triggers or causes of leukemias.
Symptoms, complaints, and signs
Waldenström disease often goes undetected and is usually an incidental diagnosis during routine blood tests. Symptoms of the disease are caused by infiltration of the bone marrow and organs on the one hand and paraproteinemia on the other. Infiltration of the bone marrow severely limits the production of other blood cells. The lack of red blood cells leads to anemia with the typical anemia symptoms such as severe fatigue, pallor, chills, concentration problems, headaches or dizziness. Platelets are also no longer produced in sufficient quantities. Thrombocytes are blood platelets and an important part of blood clotting. If there are too few platelets in the blood, there is an increased tendency to bleed, as in Waldenström’s disease. This is manifested, for example, in frequent nosebleeds or the increased occurrence of bruises. In Waldenström’s disease, immunoglobulins are produced, but they are non-functional. There is a lack of functioning antibodies. The result is an increased tendency to infection. About two thirds of all Waldenström’s disease patients complain of polyneuropathies, i.e. sensory disturbances such as tingling, burning, formication or lack of sensation, in the extremities. This is caused by the impaired immunoglobulins that are deposited in the nerves. The immunoglobulins may also cause liver swelling, lymph node swelling, or pinpoint skin hemorrhages. The overproduction of the paraproteins also thickens the blood so that it cannot flow as quickly.This manifests itself, among other things, in non-specific symptoms such as weakness, fatigue or loss of appetite. Vision or hearing loss can also be caused by this so-called hyperviscosity syndrome.
Diagnosis and course of the disease
Waldenström disease is diagnosed by various laboratory, genetic, and immunologic tests. In the laboratory, protein electrophoresis is used to detect abnormal and markedly elevated immunoglobulin M. A bone marrow aspiration is performed, and the bone marrow aspirate shows a marked increase in B lymphocytes. These lymphocytes also exhibit a specific genetic mutation. Imaging techniques such as computed tomography or magnetic resonance imaging are used to determine the extent of infiltration in the body. The disease progresses slowly without treatment. With treatment, the median survival time is 7.7 years, meaning that within that time from diagnosis, half of all patients have died.
Complications
In most cases, Waldenström disease is diagnosed only by incidental examination, so early treatment is usually not possible. In this case, the affected person suffers from severely pronounced anemia and, consequently, fatigue and pallor. The ability of the affected person to cope with stress is also significantly reduced by the symptoms, and fatigue occurs. Furthermore, the patients also suffer from concentration disorders and severe dizziness. Headaches occur, and children in particular can be impaired in their development by these complaints. The patient’s quality of life is significantly reduced by Waldenström’s disease. It is not uncommon for those affected to also suffer from nosebleeds and paralysis or other sensory disturbances. Skin bleeding or a loss of appetite can also occur and continue to restrict the daily life of the affected person. Unfortunately, a causal therapy for Waldenström’s disease is not possible. However, the symptoms can be relatively well limited with the help of medication. Complications do not occur and the course of the disease is always positive. Life expectancy is also not usually reduced or limited with successful treatment.
When should you go to the doctor?
A physician should be consulted if the feeling of illness persists or increases. If there is diffuse malaise, inner restlessness, or a loss of well-being, a visit to the doctor is advisable. Since the disease is usually only discovered by chance, special attention to physical changes and impairments in coping with everyday life is necessary. The risk group for Waldenström’s disease includes women aged 40 and older. They in particular should consult a doctor in case of irregularities or changes. If there are sleep disturbances, headaches or a decrease in mental as well as physical performance, there is cause for concern. If there are disturbances in concentration and attention, dizziness or vomiting, clarification of the symptoms is necessary. The formation of bruises or other skin changes, a sudden tendency to bleed, and irregularities in the menstrual cycle should be discussed with a physician. Fatigue, tiredness and rapid fatigue indicate health disorders and should be investigated. If the tendency to infections increases, there are sensory disturbances on the skin, a feeling of numbness or a tingling sensation on the body, a doctor is needed. A pale appearance, disturbances in blood circulation or changes in heart rhythm are cause for concern. If the symptoms persist unabated for several weeks, a physician should be consulted.
Treatment and therapy
Therapy is not given until the disease causes symptoms. The goal of therapy in Waldenström disease is not to cure the disease but to eliminate or relieve symptoms. This is referred to as a palliative therapy approach. A combination of cytostatics and cortisone is used. If a large number of IgM are present in the blood and thus impair the flow properties of the blood, plasmapheresis can also be performed. In this procedure, the blood plasma and thus also the paraproteins contained therein are exchanged with a plasmapheresis device.
Outlook and prognosis
If left untreated, Waldenström disease progresses slowly.Since there are too few functional leukocytes in the body, an antibody deficiency syndrome occurs, which is associated with immune deficiency and an increased risk of infection. With contemporary therapy, the average survival time is 7 to 8 years after initial diagnosis. However, some affected persons live for more than 20 years with a high quality of life. The individual prognosis depends on various factors. For example, the prognosis depends on the risk group to which the affected person belongs. In high-risk patients, the 5-year survival rate averages 36 percent, while in low-risk patients it is 87 percent. According to the prognosis index of the International Scoring System for Waldenström’s Macroglobulinemia (ISSWM), parameters with a negative impact on prognosis are an age over 65 years, a decreased hemoglobin value (below 11.5 g/dl), a severely decreased platelet count (below 100,000/µl), an increased monoclonal protein concentration (above 70 g/l), and an increased beta-2-microglobulin blood value (above 3 mg/l). In many affected individuals before the age of 65, the disease can be regressed in the long term with therapy. Finally, therapy is continuously being expanded and improved by new drugs (including tyrosine kinase inhibitors, rituximab). Therefore, experts believe that the prognosis will improve significantly in the future.
Prevention
Because the causes of Waldenström disease are still not sufficiently understood, there are also no preventive measures against the disease. To reduce the risk of developing the disease, contact with chemical pollutants such as benzene should be avoided. Superfluous exposure to radiation, for example through increased X-ray examinations, should also be avoided.
Aftercare
In most cases, the measures of follow-up care for Waldenström disease are relatively limited or are not even available to the affected person. Therefore, ideally, a physician should be consulted at the first symptoms and signs of the disease to avoid further discomfort or complications. A self-healing process is not possible. Since it is a genetic disease, the affected person should have a genetic test performed if he or she wishes to have children in order to prevent a recurrence of Waldenström’s disease. Affected individuals are usually dependent on long-term treatment, although a complete cure cannot be achieved. In their daily lives, patients are therefore also dependent on the support and help of their own family and friends and acquaintances. This can also prevent psychological complaints or depression. Not infrequently, in Waldenström’s disease, contact with other patients of the disease can also be very useful. This often leads to an exchange of information, which can facilitate the daily life of the affected person. Possibly, the disease limits the life expectancy of the affected person.
This is what you can do yourself
Waldenström’s disease is a very rare disease, which must first be medically clarified and treated. It may be possible to take action against the consequences that infiltration of the bone marrow has on your own. Those affected should also take measures to reduce the mental stress associated with the disease. Physical therapy or yoga can be performed to accompany medical physical therapy. Physical exercises help to strengthen the musculoskeletal system and relieve pain. In addition, however, sufficient rest and relaxation are also important. This is the only way to ensure that the complaints do not worsen. If the main symptoms are accompanied by hyperviscosity syndrome, drug treatment is necessary. The patient can support this by noting any side effects and interactions in a complaints diary and reporting the results to the doctor. Finally, therapeutic help must always be sought for Waldenström’s disease. For example, patients can visit a self-help group and talk to other sufferers. Patients can also find support and information in Internet forums or in specialist centers for corresponding diseases. All measures should be taken in consultation with the responsible orthopedist or internist.
