Castleman disease is a very rare severe disease of the lymph glands that occurs in episodes. It was classified in 1954 by the US pathologist Benjamin Castleman. The disease occurs in two forms, one less severe and one very rarely severe with an unfavorable prognosis.
What is Castleman disease?
Castleman’s disease is a lymph gland disorder that also affects the surrounding tissues. The lymph nodes grow excessively and form tumors. Depending on whether one lymph node/group of lymph nodes or several single/multiple groups are affected, medicine differentiates Castleman’s disease into unicentric (localized) and multicentric forms. The probability of getting the disease is 1:100,000 (patients/year). Both sexes are affected. Patients with the severe form have an older age than those with unicentric Castleman’s disease. The latter presents with much fewer symptoms than the severe form, which is usually coupled with HIV and HHV-8 infection. People with HIV infection/AIDS have an increased risk of getting the lymphatic disease. In them, the prognosis is much less favorable.
Causes
The causes that lead to the localized form of the disease are currently still controversial. Scientists assume that malignant cells in the patient’s body are responsible for IL-6 and IL-10 overproduction in the lymph node. An inflammatory autoimmune disease, a viral infection other than human herpes virus 8 (HHV-8), or a genetic predisposition could also be triggers of the milder Castleman’s disease. In this case, different variants of the interleukin-6 receptor coexist, which can accordingly affect more cells. Since at least 60 percent of patients with the severe course of the disease also have an HHV-8 infection, they develop a viral interleukin that resembles human IL-6. Viral IL-6 is also the causative agent of the cytokine storms typical of the multicentric form of Castleman’s disease: it infects a high number of plasma cells, most of which are located in the vicinity of lymphoid follicles.
Symptoms, complaints, and signs
Generally, the disease is accompanied by great pain of the affected lymph nodes. In the simpler form of the disease, B symptoms include involuntary weight loss, fever, and night sweats. In addition, the patient is weak and tired, feels pain in the chest and abdomen – depending on which region is affected by the disease. Often, mild anemia is still detectable. Patients with the multi-centric form of the disease suffer from nausea, vomiting and loss of appetite in addition to the B symptoms and have an enlarged liver and spleen. In addition, there are breathing problems, a tendency to edema, severe protein deficiency, severe anemia, various types of inflammation, and massive thrombocytopenia (platelet deficiency). Also POEMS syndrome and – (co)caused by the HIV infection present at the same time – lymphadenopathy, Kaposi’s sarcoma and malignant lymphomas. Depending on the severity and extent of symptoms, death may result from multiorgan failure, severe infection, and lymphoma.
Diagnosis and disease progression
Castleman disease must be differentially diagnosed from lymphoma and other severe diseases. In particular, the severe form is often mistaken for lymphoma. Ultrasound and CT are used to narrow down the size of the affected area. Lymph gland tissue is removed and examined histologically. Blood drawn during an episode of disease shows elevated IL-6 and CRP levels. The milder form of lymph gland disease does not show as pronounced symptoms and milder episodes. CRP levels are lower than in severe Castleman’s disease. Multicentric Castleman’s disease can vary greatly in course. Some patients are stable for years, while in others the disease progresses rapidly until it becomes life-threatening. Between relapses, the patient experiences periods of good health, normal CRP levels, and even regression of the affected lymph gland tissue. However, the longer the sufferer lives with the disease, the more frequent the relapses and the higher his or her risk of developing malignant lymphoma.
Complications
Castleman disease causes the patient to experience severe symptoms.As a rule, severe weight loss occurs and patients also suffer from fever or night sweats. Furthermore, it is not uncommon to experience pain in the stomach or abdomen, so that the patient’s quality of life is significantly reduced by this disease. Castleman’s disease also causes vomiting and nausea in the patient, with loss of appetite also occurring. The liver and spleen enlarge, which can also cause pain in the affected regions. Due to the anemia, the affected person is tired and fatigued. The patient’s ability to cope with stress also drops significantly as a result of this disease. Without treatment, Castleman’s disease leads to organ failure and ultimately to the death of the patient. The patient’s immune system is also weakened by the disease, making it easier for infections or inflammations to occur. Surgery can usually be performed to treat the symptoms. Furthermore, patients are not infrequently dependent on radiation therapy. Whether this will result in a completely positive course of the disease cannot generally be predicted. It is also possible that life expectancy is reduced by Castleman disease.
When should you see a doctor?
If there are problems at the lymph nodes, Castleman disease could be behind it. It is recommended to see a doctor immediately if such problems occur. He or she can decide whether unicentric or multicentric Castleman’s disease is behind it, or another condition affecting the lymphatic system. This relatively rare disease is accompanied by non-specific symptoms. Nonetheless, if prolonged, these often cannot be explained by lymph node swelling or fever due to the common cold. Persistently painful lymph nodes and associated organ enlargement also indicated that something might be wrong. Castleman’s disease usually occurs in episodes. This is also a signal that the cause of the swollen lymph glands needs to be looked for. The visit to the doctor should not be delayed for a long time in case of any suspicion of a serious disease. The determination of Castleman’s disease requires extensive diagnostics. First, other diseases must be ruled out. These include, for example, infections, autoimmune diseases or tumors. If only one lymph node is affected, it can be surgically removed. However, this is not possible in multicentric Castleman’s disease. Here, the therapeutic range is outlined by chemotherapy, radiation or targeted multimodal therapeutic approaches. In this context, the prognosis for Castleman disease is much worse, especially when serious immunodeficiencies such as AIDS are present.
Treatment and therapy
In unicentric Castleman disease, there is a good chance of cure if the affected person has the abnormally enlarged lymph node surgically removed. It is then rare for the disease to recur. If surgery is not possible, radiation therapy can be performed. The use of monoclonal antibodies against human IL-6 (siltuximab) shows good treatment success. In the multi-centric form, the prospect of successful treatment is much lower. This is due to the broad spectrum of effects that interleukins 6 and 10 have on the lymph gland cells, but also to the fact that most patients with the severe form are also infected with HIV and HHV-8 and have to take additional medication against these diseases (side effects, interactions, greater weakening of the body). In addition, the diseased lymph nodes cannot be surgically removed because they are located in several places in the body. In most cases, medical therapy is multi-pronged: in anti-inflammatory therapy, corticosteroids are administered. With the help of the monoclonal antibody Rituximab (either with or without taking cytostatic drugs), the cytokine-producing interleukins 6 and 10 are contained and their signaling pathways are blocked at the same time. Symptoms are treated with specific drugs (antiviral against HHV-8, anti-retroviral against HIV).
Outlook and prognosis
The specific prognosis for Castleman disease depends on the form present, the course, and the treatment method chosen. In addition, general health and the presence of other diseases are important.The unicentric form of Castleman’s disease has a very favorable prognosis if the affected lymph node is completely removed surgically or treated beforehand by radiation therapy. The overall survival rate for those affected with this form of the disease is 90 percent. A five-year disease-free survival rate is seen in more than 80 percent of patients. Within ten years, less than five percent die from unicentric Castleman’s disease. Slightly worse prognoses are seen in patients treated with chemotherapy. No concrete statements can yet be made regarding a prognosis for the multicentric form of Castleman’s disease due to the diverse course of the disease and the small number of cases. In general, the outlook is much worse than for patients with the unicentric form. After standard therapy consisting of treatment with glucocorticoids and chemotherapy, more than 50 percent of those affected relapse within three years. Patients who also have HIV have a particularly poor prognosis. Disease-free survival for them after three years is 25 percent. On average, patients died 14 months after diagnosis.
Prevention
Prevention of Castleman disease is not possible unless infection with HHV-8, HIV, etc. is avoided in advance.
Follow-up care
Aftercare of Castleman disease mainly refers to the possible preventive measures. It also includes the treatment of emotional distress. Patients need trusted support from family members and friends. After the completion of the initial therapy, physical exercise helps to strengthen the organism. The efforts should remain in the light to moderate range. In this way, they strengthen the immune system and improve the health prognosis. Suitable sports include endurance sports or water gymnastics. Respiratory therapy can also help optimize well-being. In addition, a diet that is as healthy as possible is helpful. The Mediterranean diet in particular has proven to be beneficial to health. For the recovery process, it makes sense to get help from a doctor or nutritionist. Of course, regular check-ups with the doctor in charge must also be kept. In this way, any complications can be detected at an early stage. If necessary, the doctor will initiate special measures to prevent the condition from worsening. Direct prevention of the disease is currently not possible. Patients can only strengthen protective measures against HIV infection. Psychological care can also have a positive effect on well-being.
Here’s what you can do yourself
When Castleman’s disease is diagnosed, it sometimes places a great emotional burden on those affected. The most important self-help measure is to talk with friends, family members, and other affected individuals. Physical activity is recommended during initial therapy and after completion of treatment. Light to moderate exercise is considered to be extremely effective in improving the prognosis of cancer. Suitable sports include endurance sports, strengthening gymnastics or water therapy. Breathing exercises, yoga, Tai Chi, aerobics and pelvic floor exercises are also suitable. To compensate for this, rest and relaxation are also important. In Castleman’s disease, a healthy diet is also essential. A Mediterranean diet in particular is considered an important building block for well-being and recovery. Those affected are best advised to talk to a nutritionist or the doctor in charge. After therapy, the body should be carefully monitored. If signs of recurrence appear or other complications arise, the doctor should be informed. In case of doubt, the nearest hospital must be visited with the complaints, so that the necessary measures can be taken immediately in case of serious complications, which can occur especially in the first months after completion of the therapy.
