Castleman’s disease is a very rare, serious disease of the lymph glands that occurs in episodes. It was classified by American pathologist Benjamin Castleman in 1954. The disease occurs in two forms, one less severe and one very rarely severe with an unfavorable prognosis.
What is Castleman’s disease?
Castleman ‘s disease is a disease of the lymph glands that also affects the surrounding tissue. The lymph nodes overgrow and form tumors. Depending on whether a lymph node/a group of lymph nodes or several individuals/several groups are affected, medicine distinguishes between the unicentric (localized) and the multicentric form of M. Castleman. See lawfaqs for Definitions of Hypophysitis.
The probability of getting the disease is 1:100,000 (patients/year). Both sexes are affected. Patients who develop the severe form are older than those with unicentric Castleman disease. The latter shows up with significantly 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 developing lymph gland disease. The prognosis for them is much worse.
The causes that lead to the localized form of the disease are currently still the subject of controversy. The scientists assume that malignant cells in the patient’s body are responsible for an overproduction of IL-6 and IL-10 in the lymph nodes. An inflammatory autoimmune disease, a viral infection other than human herpes virus 8 (HHV-8) or a genetic predisposition could also trigger the milder Castleman’s disease.
Different variants of the interleukin-6 receptor coexist in her, which can therefore 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 is similar to human IL-6.
Viral IL-6 is also the cause of the cytokine storms typical of the multi-centric form of Castleman’s disease: it infects a large number of plasma cells, which are mostly located in the vicinity of the lymphatic follicles.
Symptoms, Ailments & Signs
In general, the disease is accompanied by great pain in the affected lymph nodes. In the simpler form of the disease, the B symptoms are involuntary weight loss, fever and night sweats. Also, the patient is weak and tired, feels pain in the chest and abdomen – depending on which region is affected by the disease. Mild anemia is often detectable.
In addition to B symptoms, patients with the multicentric form of the disease suffer from nausea, vomiting and loss of appetite 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 the POEMS syndrome and – (partly) 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 can result from multiorgan failure, severe infection, and lymphoma.
Diagnosis & course of disease
Castleman’s disease must be differentiated from lymphoma and other serious diseases in the differential diagnosis. The severe form in particular is often mistaken for a lymphoma. Ultrasound and CT are used to narrow down the size of the affected area. Lymph gland tissue is removed and histologically examined. Blood drawn during a flare-up shows elevated IL-6 and CRP levels.
The milder form of the lymph gland disease shows less pronounced symptoms and milder flare-ups. The CRP value is lower than in severe Castleman disease. Multicentric Castleman’s disease can take a very different course. Some patients are stable for years, while in others the disease progresses rapidly until it becomes life-threatening.
Between the flare-ups, the patient experiences periods of well-being, normal CRP levels and even a regression of the affected lymph gland tissue. However, the longer people live with the disease, the more frequent flare-ups and the higher their risk of developing malignant lymphoma.
Castleman’s disease causes severe symptoms in the patient. Severe weight loss usually occurs and patients also suffer from fever or night sweats. Furthermore, it is not uncommon for pain in the stomach or abdomen to occur, so that the quality of life of the patient is significantly reduced by this disease.
Castleman’s disease also leads to vomiting and nausea in the patient, with loss of appetite. The liver and spleen enlarge, which can also cause pain in the affected areas. The anemia makes those affected tired and exhausted. The patient’s resilience also decreases significantly as a result of this disease.
If left untreated, Castleman’s disease leads to organ failure and eventually to the patient’s death. The patient’s immune system is also weakened by the disease, making it easier for infections or inflammation to occur. Surgery can usually be performed to treat the symptoms. Furthermore, the patients are often dependent on radiotherapy. It cannot generally be predicted whether the course of the disease will be completely positive. Life expectancy may also be reduced by Castleman’s disease.
When should you go to the doctor?
If there are problems in the lymph nodes, Castleman’s disease could be the cause. It is recommended to consult a doctor immediately in case of such problems. He can decide whether unicentric or multicentric Castleman’s disease is behind it, or another disease that affects the lymphatic system.
This relatively rare disease is associated with non-specific symptoms. Nevertheless, if they last longer, they often cannot be explained with swelling of the lymph nodes or fever caused by a cold. The persistently painful lymph nodes and the associated enlargement of organs also indicated that something could be wrong. Castleman’s disease usually occurs in episodes. This is also a signal that the cause of the swollen lymph glands must be sought.
A visit to the doctor should not be delayed if there is any suspicion of a serious illness. The diagnosis of Castleman’s disease requires extensive diagnostics. First, other diseases must be ruled out. These include, for example, infections, autoimmune diseases or tumorous events.
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 through chemotherapy, radiation or targeted, multimodal therapeutic approaches. The prognosis for Castleman’s disease is significantly worse, especially if there are serious immune deficiencies such as AIDS.
Treatment & Therapy
In the case of unicentric Castleman’s disease, there are good chances of recovery if the patient has the abnormally enlarged lymph nodes surgically removed. The disease then rarely recurs. If surgery is not possible, radiation therapy can be performed. The use of monoclonal antibodies against human IL-6 (siltuximab) shows good treatment success.
With the multi-centric form, the prospect of a successful treatment is much lower. On the one hand, this is due to the broad spectrum of effects that interleukins 6 and 10 have on the lymph gland cells, but on the other hand, it is also due to the fact that most patients with the severe form are also infected with HIV and HHV-8 at the same time and in addition Need to take medication for 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 parts of the body. Medicine usually treats in several ways: Corticosteroids are administered in anti-inflammatory therapy. With the help of the monoclonal antibody rituximab (either with or without taking cytostatics), the cytokine-producing interleukins 6 and 10 are contained and at the same time their signaling pathways are blocked. The symptoms are treated with special drugs (antivirals against HHV-8, anti-retrovirals against HIV).
Outlook & Forecast
The specific prognosis for Castleman’s disease depends on the present form, the course and the chosen treatment method. 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 surgically completely removed or previously treated with radiation therapy.
The overall survival rate for those affected with this form of the disease is 90 percent. A disease-free five-year survival rate is shown in over 80 percent of patients. Less than five percent die from unicentric Castleman disease within ten years. Patients treated with chemotherapy have a somewhat poorer prognosis.
Due to the diverse course of the disease and the small number of cases, no concrete statements can be made regarding a prognosis for the multicentric form of Castleman’s disease. In general, the outlook is much worse than in patients with the unicentric form. After the standard therapy consisting of treatment with glucocorticoids and chemotherapy, more than 50 percent of those affected suffer a relapse within three years.
Patients who also suffer from HIV have a particularly poor prognosis. Their disease-free survival rate after three years is 25 percent. On average, patients died 14 months after diagnosis.
Prevention of Castleman’s disease is not possible unless infection with HHV-8, HIV, etc. is avoided in advance.
The aftercare of Castleman’s disease relates primarily to the possible preventive measures. It also includes the treatment of mental stress. Patients need trusting support from family members and friends. After completing the first therapy, physical activity helps to strengthen the body.
Efforts should remain in the light to moderate range. They strengthen the immune system and improve the health prognosis. Endurance sports or water aerobics can be used as sports. Breathing therapy can also help to optimize well-being. Eating as healthy a diet as possible is also helpful. The Mediterranean diet in particular has proven to be health-promoting.
For the recovery process, it makes sense to get help from a doctor or nutritionist. Of course, the regular check-up appointments with the responsible doctor must also be observed. In this way, possible complications can be identified at an early stage. If necessary, the doctor initiates special measures to prevent the condition from deteriorating.
Direct prevention of the disease is currently not possible. Patients can only increase protective measures against HIV infection. Psychological support can also have a positive effect on well-being.
You can do that yourself
When Castleman’s disease is diagnosed, this sometimes represents a great emotional burden for those affected. The most important self-help measure is talking to friends, family and other affected people.
Physical activity is recommended during the initial therapy and after the end of the treatment. Light to moderate exertion is considered extremely effective in improving the prognosis of cancer. Suitable sports are, for example, endurance sports, strength gymnastics or water therapy. Breathing exercises, yoga, tai chi, aerobics and pelvic floor exercises are also available. As a balance to this, rest and rest are also important. A healthy diet is also essential for Castleman’s disease . Mediterranean food in particular is considered an important building block for well-being and recovery. It is best to talk to a nutritionist or the responsible doctor.
After therapy, the body should be carefully observed. If there are signs of a recurrence or other complications occur, the doctor must be informed. In case of doubt, the nearest hospital must be taken to the nearest hospital so that the necessary measures can be taken immediately in the event of serious complications, which can occur in the first few months after the end of the therapy.