Angiofollicular lymph node hyperplasia is another name for Castleman disease. It is a rare problem of the lymph nodes, where the lymph node tissue grows too much and becomes enlarged. The growth is benign (not cancer) but can still cause serious symptoms because the immune system becomes over-active and releases many inflammatory proteins (cytokines). The disease can affect only one lymph node area (unicentric) or many lymph node areas at the same time (multicentric).Cancer.gov+2ScienceDirect+2
Angiofollicular lymph node hyperplasia is a lymphoproliferative disorder. This means the lymph node cells grow and multiply more than normal. The main cells involved are B-lymphocytes and plasma cells, which normally make antibodies. In this disease, the structure of the lymph node changes: the follicles (small round clusters of immune cells) are enlarged or shrunken, the mantle zones around them are thick, and there are many small blood vessels crossing the node. These changes can happen in one lymph node (usually in the chest or abdomen) or in many lymph nodes through the body, sometimes with liver, spleen, or bone marrow involvement. As the lymph nodes grow and the immune system becomes over-active, people can develop fever, weight loss, night sweats, swelling, and organ damage.ScienceDirect+2NCBI+2
Angiofollicular lymph node hyperplasia is another name for Castleman disease, a rare disorder where lymph node tissue grows in an abnormal but usually non-cancerous way. It can affect a single lymph node area (unicentric disease) or many lymph node areas and organs (multicentric disease). Unicentric disease often sits as one mass in the chest or abdomen and may cause few or no symptoms. Multicentric disease can cause fever, weight loss, night sweats, anemia, nerve problems, and organ damage, and it increases the risk of lymphoma. Mayo Clinic+3Cancer.gov+3PubMed+3
Doctors believe that excess immune activation and high levels of the inflammatory protein interleukin-6 (IL-6) are central in many patients, especially with idiopathic multicentric Castleman disease (iMCD). This overactive signaling drives inflammation, abnormal blood vessel growth, enlarged lymph nodes, and organ dysfunction. ScienceDirect+2FDA Access Data+2
Other names
Doctors use several different names for angiofollicular lymph node hyperplasia. The most common modern name is Castleman disease. Older or alternative names include giant lymph node hyperplasia, lymphoid hamartoma, and angiofollicular lymph node hyperplasia itself. All these names describe the same basic problem: a rare, non-cancerous overgrowth of B-cells and plasma cells in the lymph nodes, with many abnormal small blood vessels.PubMed+2Wikipedia+2
Types of angiofollicular lymph node hyperplasia
Doctors classify this disease in two main ways:
1. Clinical types (how many lymph nodes are involved)
Unicentric Castleman disease (UCD)
In unicentric disease, only one lymph node group (or one region) is affected. This is the most common form. Many people have no symptoms, and the enlarged node is found by chance on imaging for another problem. When symptoms are present, they are often mild. Surgery to remove the single abnormal lymph node can be curative in most cases.Cancer.gov+2NCBI+2Multicentric Castleman disease (MCD)
In multicentric disease, many lymph node regions are enlarged. The immune system is highly active and releases large amounts of cytokines, especially interleukin-6 (IL-6). This can cause fever, weight loss, night sweats, anemia, swelling, and organ problems. MCD is often more serious and needs systemic treatment, not just surgery. MCD can be further divided into:HHV-8–associated MCD (linked to human herpesvirus-8, often in people with HIV)
POEMS-associated MCD (occurring in people with POEMS syndrome)
Idiopathic MCD (iMCD), where no clear cause is found.ASH Publications+2Blood Research+2
2. Histologic (microscopic) types
When the lymph node is examined under the microscope, several patterns are seen:
Hyaline-vascular type
This is the most common pattern in unicentric disease. The follicles are small and “burned out,” the mantle zones around them are thick and layered (“onion skin”), and there are many small blood vessels with thick walls crossing the node (“lollipop” appearance). This type often causes few or no symptoms and is discovered incidentally.PMC+2njmonline.nl+2Plasma-cell type
In this pattern, the lymph node has large, active germinal centers and many plasma cells filling the spaces between follicles. This type is more often seen in multicentric disease and is more often associated with systemic symptoms like fever, anemia, and high inflammatory markers.PMC+2NCBI+2Mixed type
Some lymph nodes show features of both hyaline-vascular and plasma-cell patterns. These “mixed” nodes remind doctors that Castleman disease is a spectrum of changes rather than just one rigid pattern.Wikipedia+1Hypervascular / plasmablastic variants
Newer descriptions include hypervascular forms (especially in iMCD) and plasmablastic forms (often HHV-8–associated), where large abnormal plasmablasts are present. These are usually connected with more aggressive clinical disease and a stronger link to viral infection and cytokine storms.PMC+2CDCN+2
Causes and contributing factors
For this disease, one single cause is not known in most patients. Instead, doctors talk about possible triggers and risk factors that can lead to abnormal lymph node growth and immune over-activation.
1. Human herpesvirus-8 (HHV-8) infection
HHV-8 is a virus linked strongly to multicentric Castleman disease, especially in people who are HIV-positive. The virus can infect B-cells and produce a viral form of interleukin-6, which drives cell growth and inflammation. This viral activity is considered a direct cause of many HHV-8–associated MCD cases.ASH Publications+1
2. HIV infection
HIV itself does not cause Castleman disease, but it weakens the immune system and changes how it works. People with HIV have a higher chance of being infected with HHV-8 and of developing multicentric Castleman disease. In this setting, HIV and HHV-8 together create conditions for uncontrolled B-cell proliferation and cytokine release.Blood Research+2SciELO+2
3. Overproduction of interleukin-6 (IL-6)
IL-6 is a powerful cytokine that stimulates immune cells and the liver. In Castleman disease, IL-6 levels are often high. This overproduction can come from the patient’s own cells or from viruses like HHV-8. High IL-6 causes fever, weight loss, anemia, elevated CRP/ESR, and enlargement of lymph nodes and organs. It is a central mechanism in many forms of the disease.PMC+2Nature+2
4. Abnormal growth of B-cells and plasma cells
In Castleman disease, B-cells and plasma cells in lymph nodes can grow excessively, forming hyperplastic follicles and plasma-cell infiltrates. This growth is not quite cancer, but it is abnormal and uncontrolled compared to normal immune responses. This abnormal growth is a key pathologic cause of lymph node enlargement.PubMed+2ScienceDirect+2
5. Idiopathic immune dysregulation
In many patients with idiopathic multicentric Castleman disease, no virus or clear trigger is found. Doctors think that an internal problem in the immune system regulation leads to ongoing inflammation and cytokine release. This idiopathic immune dysregulation is treated as a cause when no other explanation is present.CDCN+2ASH Publications+2
6. POEMS syndrome–related plasma cell disorder
POEMS syndrome is a rare condition caused by an abnormal plasma cell clone that produces harmful proteins and cytokines. Some patients with POEMS also develop multicentric Castleman disease. In these cases, the plasma cell disorder and its cytokines are considered a driver of Castleman-type lymph node changes.Journal MC+2Bangladesh Journals Online+2
7. Genetic or somatic mutations in lymph node cells
Research suggests that some unicentric cases may be due to local genetic changes (somatic mutations) in lymph node cells, making them grow like a benign tumor. These changes are not fully mapped, but they may explain why a single node grows abnormally while others remain normal.CDCN+1
8. Chronic viral infections other than HHV-8
Other viruses such as Epstein–Barr virus (EBV) or cytomegalovirus (CMV) can strongly stimulate the immune system and B-cells. They are often seen in the differential diagnosis and may, in some patients, contribute to Castleman-like changes or coexist with Castleman disease.Blood Research+2JournalAgent+2
9. Autoimmune diseases
Conditions like systemic lupus erythematosus and rheumatoid arthritis can activate the immune system for long periods. Some patients with Castleman disease also have autoimmune conditions, and doctors think that chronic immune activation may contribute to the lymph node changes and cytokine imbalance in these cases.Blood Research+2ASH Publications+2
10. Chronic inflammatory states and cytokine storms
Any long-lasting inflammatory condition can lead to a “primed” immune system. In Castleman disease, this may develop into a chronic cytokine storm, especially in multicentric forms, with IL-6 and other cytokines driving further lymph node and organ changes.Nature+2NCBI+2
11. Immunosuppressive medication and transplant states
Patients who receive organ transplants or strong immunosuppressive drugs have altered immune control. In some cases, this setting is associated with HHV-8 infection and Castleman-like lymphoproliferative disorders. Here, the combination of viral infection and reduced immune surveillance can be a cause.SciELO+2Blood Research+2
12. Coexisting hematologic cancers or plasma cell neoplasms
Some Castleman cases occur with lymphoma or monoclonal plasma cell disorders. These cancers can produce cytokines or directly stimulate nearby lymph nodes, leading to Castleman-type changes. In such patients, the neoplasm is viewed as a causal or driving factor.PMC+2Cureus+2
13. Age and middle-adult life
Castleman disease can occur at any age, but many cases appear in young or middle-aged adults. Age itself is not a direct cause, but the immune system and exposure history at these ages may increase susceptibility compared with childhood.Wikipedia+1
14. Male sex in some subtypes
Several series report a slight male predominance, especially for certain multicentric forms. Sex hormones may influence immune responses and viral infections, though this is still under study. Thus, male sex can be considered a mild risk factor rather than a strong cause.Cureus+1
15. Family or genetic predisposition (rare)
Castleman disease is usually not inherited, but rare familial clusters have been described. These suggest that genetic background in immune regulation or cytokine pathways may act as a predisposing cause in a small number of cases.CDCN+1
16. Environmental or occupational immune triggers (suspected)
There are reports of Castleman disease occurring after long-term exposure to infections, toxins, or other triggers, but there is no single proven environmental cause. However, chronic antigen exposure is thought to contribute to ongoing immune activation and may play a role for some patients.ScienceDirect+2Blood Research+2
17. Disordered lymphangiogenesis and vascular growth
The “angio” part of the name reflects many abnormal blood vessels. Some researchers suggest that disordered growth of blood vessels and lymphatic vessels, driven by growth factors such as VEGF, contributes to the disease, especially in POEMS-related and hypervascular types.AJR Online+2CDCN+2
18. Hyaline-vascular microenvironment changes
In hyaline-vascular type disease, the structure of the follicle and surrounding tissue is altered in a specific way. The local microenvironment of stromal cells, follicular dendritic cells, and small vessels may create a “niche” that keeps the disease going. These local tissue changes may be both a result and a cause of continued lymph node hyperplasia.PMC+2njmonline.nl+2
19. Unknown (“true idiopathic”) causes
In many unicentric cases there is no virus, no autoimmune disease, and no cancer. These are called idiopathic. For these patients the exact cause remains unknown, but the lymph node behaves like a benign tumor with abnormal immune signaling.Wikipedia+2SpringerOpen+2
20. Interaction of multiple factors
Most experts believe that Castleman disease often results from a mix of factors: virus, host genetics, immune regulation, and environment. The interaction between these factors may tip the immune system into a chronic, self-sustaining inflammatory state, which then causes the lymph node hyperplasia seen in this condition.CDCN+2Nature+2
Common symptoms
Symptoms depend on whether the disease is unicentric or multicentric. Unicentric disease may cause no symptoms at all. Multicentric disease usually causes many systemic complaints.
1. Enlarged lymph node or lump
The most basic sign is a painless lump where a lymph node has enlarged. It may appear in the neck, underarm, mediastinum (chest), or abdomen. Sometimes this lump is found on imaging rather than by touch. Large nodes can press on nearby structures, causing cough, chest discomfort, or abdominal fullness.Cancer.gov+2Radiology Cases+2
2. Fever
Many patients, especially with multicentric disease, have recurrent or persistent fever. This is due to high levels of IL-6 and other inflammatory proteins. Fever often behaves like a flu-like illness and may come with chills and sweating.NCBI+2National Organization for Rare Disorders+2
3. Night sweats
Profuse night sweats that soak clothes or sheets are common. They indicate strong activation of the immune system and are part of the classic “B symptoms” seen in several lymphoproliferative disorders.Medscape+2Blood Research+2
4. Unintended weight loss
Patients may lose weight without trying. This happens because inflammatory cytokines reduce appetite and speed up the body’s metabolism. Prolonged weight loss can lead to muscle wasting and weakness.Cleveland Clinic+2National Organization for Rare Disorders+2
5. Fatigue and weakness
Severe tiredness is one of the most frequent complaints. Fatigue may be due to anemia, poor sleep from night sweats, chronic inflammation, or poor nutrition. Patients may feel exhausted even after small efforts.NCBI+2Cleveland Clinic+2
6. Loss of appetite, nausea, or vomiting
Many patients report reduced appetite, sometimes with nausea or vomiting. An enlarged abdominal node or spleen can also press on the stomach and intestines, making it uncomfortable to eat and contributing to weight loss.Cleveland Clinic+2National Organization for Rare Disorders+2
7. Abdominal pain or fullness
When lymph nodes in the abdomen or retroperitoneum are enlarged, people may feel pain, pressure, or fullness in the abdomen. The liver and spleen may also be enlarged and tender. This discomfort often leads to imaging and the discovery of the mass.AJR Online+2Radiology Cases+2
8. Enlarged liver (hepatomegaly)
The liver can become enlarged due to cytokine effects and infiltration. Patients may feel discomfort under the right rib cage, or the enlargement may be detected only on exam or imaging.NCBI+2National Organization for Rare Disorders+2
9. Enlarged spleen (splenomegaly)
An enlarged spleen is also common, especially in multicentric disease. Splenomegaly can cause left upper abdominal pain, a feeling of fullness, and sometimes low blood counts due to increased trapping of blood cells in the spleen.NCBI+2National Organization for Rare Disorders+2
10. Swelling of legs, feet, or abdomen (edema, anasarca, effusions)
Patients may develop swelling of the legs and feet, fluid in the abdomen (ascites), or fluid around the lungs or heart. This is due to low albumin, high cytokines, and sometimes heart or kidney involvement. In severe cases this is called anasarca.NCBI+2tsh.or.th+2
11. Shortness of breath and cough
If large lymph nodes press on the lungs or airways, or if there is fluid around the lungs, patients can have breathlessness and cough. Anemia can further worsen shortness of breath by reducing oxygen-carrying capacity.Medscape+2clinicalradiologyonline.net+2
12. Skin changes
Some people, especially those with POEMS-associated disease, develop skin changes such as darkening of the skin, thickening, or small vascular spots. Castleman disease can also be associated with paraneoplastic pemphigus, which presents with painful mouth ulcers and skin blisters.Journal MC+2JournalAgent+2
13. Peripheral neuropathy (numbness, tingling, weakness in limbs)
In POEMS-associated and some multicentric cases, patients develop nerve damage in the arms and legs. They may feel numbness, tingling, burning sensation, or weakness, making it hard to walk or hold objects. This neuropathy is due to underlying plasma cell disease and immune damage to nerves.Journal MC+2Bangladesh Journals Online+2
14. Frequent infections
Because the immune system is abnormal and blood counts may be low, some patients have repeated infections, such as pneumonia or skin infections. Anemia and low white blood cells can make infections more intense and slower to heal.NCBI+2National Organization for Rare Disorders+2
15. Symptoms of organ dysfunction (kidney, heart, lungs)
In advanced or severe multicentric disease, inflammation and low blood protein can affect kidney function, cause heart failure, or damage the lungs. Patients may notice reduced urine output, swelling, severe breathlessness, or chest discomfort. These signs indicate serious disease that needs urgent medical care.NCBI+2Medscape+2
Diagnostic tests
Diagnosis needs a combination of clinical evaluation, imaging, and especially lymph node biopsy. No single blood test alone can confirm the disease.NCBI+2CDCN+2
A. Physical examination (bedside)
1. General physical examination and vital signs
The doctor starts with a full exam and checks temperature, pulse, blood pressure, and breathing rate. They look for fever, rapid heart rate, and overall signs of illness such as pallor, sweating, or weight loss. These basic findings help show the level of systemic inflammation and guide further testing.BioMed Central+2Medscape+2
2. Palpation of lymph nodes
The doctor carefully feels (palpates) the lymph node regions in the neck, underarms, above the collarbone, and groin. They note the size, number, consistency, and tenderness of the nodes. In Castleman disease, nodes are usually enlarged, firm, and non-tender. Whether only one region or many regions are involved helps distinguish unicentric from multicentric disease.BioMed Central+2SciSpace+2
3. Abdominal examination for liver and spleen
The doctor feels and percusses the abdomen to look for enlarged liver and spleen. Hepatosplenomegaly is common in multicentric disease. This exam also looks for fluid in the abdomen (ascites) and tenderness due to large nodes or organ enlargement.E-Jyms+2tsh.or.th+2
4. Examination for edema and effusions
The legs and feet are checked for pitting edema, and the chest is listened to for reduced breath sounds that suggest fluid around the lungs. These findings suggest low albumin, heart or kidney involvement, or massive cytokine-driven fluid shifts, all of which are typical in severe multicentric Castleman disease.NCBI+2tsh.or.th+2
5. Skin and neurologic examination
The doctor looks for skin changes (dark patches, rashes, small hemangiomas) and performs a simple neurological exam to test sensation and strength in the limbs. These steps help detect associated conditions like POEMS syndrome or paraneoplastic pemphigus, which support the diagnosis of certain Castleman disease subtypes.Journal MC+2Bangladesh Journals Online+2
B. Manual tests and bedside assessments
6. Manual measurement of lymph node size and progression
Over time, the doctor measures lymph nodes by hand or with calipers and records their approximate size. Repeated examinations show whether the nodes are growing, shrinking, or stable. This is a simple but important manual test that helps monitor disease activity and response to treatment.clinicalradiologyonline.net+2ejradiology.com+2
7. Manual grading of edema and fluid overload
Using thumb pressure on the legs, the doctor grades pitting edema on a clinical scale (for example, +1 to +4). They may also estimate the amount of fluid in the abdomen. This manual grading helps assess how severe the body’s fluid overload is and whether it is improving with treatment.NCBI+2tsh.or.th+2
8. Performance status and functional tests
Simple bedside tests, such as observing how far a patient can walk, climb stairs, or perform daily tasks, give a performance status score. Poor performance status is common in advanced multicentric disease due to fatigue, anemia, and organ dysfunction, and it helps doctors judge disease severity and treatment tolerance.Cureus+2Blood Research+2
C. Laboratory and pathological tests
9. Complete blood count (CBC)
A CBC checks red cells, white cells, and platelets. In Castleman disease, common findings include anemia, high or low platelet counts, and sometimes leukocytosis. Anemia and platelet changes are part of the minor diagnostic criteria for idiopathic multicentric Castleman disease.NCBI+2Medscape+2
10. Inflammatory markers (ESR, CRP)
Tests such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often elevated because of strong inflammation and high IL-6 levels. These markers help show disease activity and are included in consensus diagnostic criteria for iMCD.ASH Publications+2SpringerOpen+2
11. Liver and kidney function tests
Blood tests for liver enzymes, bilirubin, albumin, creatinine, and urea check whether the liver and kidneys are affected. Low albumin, high liver enzymes, and kidney dysfunction are frequent in severe multicentric disease and form part of recommended laboratory assessments.NCBI+2Medscape+2
12. Serum protein electrophoresis and immunoglobulin levels
These tests look for polyclonal hypergammaglobulinemia (many kinds of antibodies) or monoclonal proteins. Polyclonal hypergammaglobulinemia is very common in multicentric disease, while a monoclonal spike may suggest an associated plasma cell neoplasm or POEMS syndrome.NCBI+2SpringerOpen+2
13. Viral serology (HHV-8, HIV, and others)
Tests for HHV-8 and HIV are essential, especially in multicentric disease, because HHV-8–positive MCD is a distinct form with specific treatment strategies. Doctors may also test for hepatitis viruses, EBV, or CMV to rule out other causes of lymphadenopathy and systemic inflammation.ASH Publications+2Blood Research+2
14. Interleukin-6 and other cytokine levels (if available)
In specialized centers, IL-6 levels and other cytokines can be measured. High IL-6 supports the diagnosis of Castleman disease and helps explain the systemic symptoms. These tests are not always required but can support treatment decisions, especially for anti-IL-6 drugs.CDCN+2Nature+2
15. Lymph node excisional biopsy with histopathology
This is the key diagnostic test. The whole lymph node (or a large part) is surgically removed and examined under a microscope. The pathologist looks for the typical Castleman features (hyaline-vascular or plasma-cell patterns, hypervascularity, mantle zone changes) and uses special stains, including tests for HHV-8. A biopsy is required to confirm Castleman disease and to exclude lymphoma and other conditions.NCBI+2CDCN+2
D. Electrodiagnostic tests
16. Nerve conduction studies and electromyography (EMG)
In patients with neuropathy (numbness, tingling, weakness), nerve conduction studies and EMG help measure how well the nerves conduct signals. In POEMS-associated Castleman disease, these tests show a demyelinating or axonal neuropathy. They help confirm that the nerve problems are real and guide further evaluation for plasma cell disorders.Journal MC+2Bangladesh Journals Online+2
17. Electrocardiogram (ECG) and possibly echocardiogram
An ECG checks the electrical activity of the heart. Some patients may have heart strain from anemia, high output states, or fluid overload. An echocardiogram may be done if there is concern for heart failure or fluid around the heart (pericardial effusion), which can occur in severe multicentric disease.NCBI+2tsh.or.th+2
E. Imaging tests
18. Chest X-ray
A chest X-ray is often the first imaging test. It may show widened mediastinum due to enlarged lymph nodes, or fluid around the lungs. This simple test can raise suspicion for a mediastinal mass that later proves to be Castleman disease.Radiology Cases+2tsh.or.th+2
19. Ultrasound of neck, chest, abdomen, or retroperitoneum
Ultrasound is a non-invasive way to look at lymph nodes and organs such as the liver and spleen. Enlarged lymph nodes appear as solid, usually homogeneous masses. Ultrasound can also detect ascites and guide needle biopsies, making it a useful first-line imaging tool.Radiology Cases+2Frontiers+2
20. CT and PET-CT scans
Computed tomography (CT) of the neck, chest, abdomen, and pelvis is central in evaluating Castleman disease. It shows the size, number, and location of enlarged lymph nodes and can suggest unicentric versus multicentric disease. Nodes often show strong enhancement after contrast injection. PET-CT uses a radioactive tracer to show metabolic activity. It helps distinguish Castleman disease from lymphoma, assess how active the disease is, and evaluate response to treatment.Mayo Clinic+2ejradiology.com+2
Non-pharmacological treatments
These approaches support medical treatment. They do not replace disease-specific drugs like siltuximab or chemotherapy.
1. Regular specialist follow-up and monitoring
Routine visits with a hematologist/oncologist or immunology specialist are one of the most important “non-drug” treatments. The doctor checks symptoms, lymph node size, blood counts, kidney and liver function, and inflammation markers such as CRP, ESR and IL-6, and can order scans when needed. This helps to catch relapse or progression early, adjust biologic or chemotherapy treatment, and prevent serious complications such as organ failure or lymphoma. Regular monitoring is also essential when using strong immune-targeting drugs, because they can cause infections, liver problems or low blood counts that must be detected and treated quickly. Mayo Clinic+2ScienceDirect+2
2. Individualized exercise and physical activity program
Gentle, regular exercise (for example walking, cycling on a stationary bike, or light strength training) can fight fatigue, protect muscles, and support heart and lung function. In people with Castleman disease, fatigue and weakness are common because of chronic inflammation, anemia, and low fitness. A supervised program, ideally designed by a physiotherapist, builds stamina step by step without over-exertion. Exercise also improves mood, sleep and quality of life, and can reduce some inflammation-related symptoms in chronic diseases in general, though it does not treat the lymph node disease itself. Mayo Clinic+1
3. Physiotherapy for pain, weakness and mobility
When enlarged nodes or organ enlargement cause pain, stiffness or nerve compression, physiotherapy can help maintain range of motion, improve posture, and strengthen supporting muscles. Techniques can include stretching, joint mobilization, gentle manual therapy and tailored home exercises. This may reduce pain, improve function and lower the risk of falls or joint contractures. Physiotherapy is especially helpful after surgery or intensive chemotherapy, when muscles may be weak and balance and coordination can be affected. ACS Journals+1
4. Occupational therapy and energy-conservation training
Occupational therapists teach practical strategies to manage daily tasks when patients feel tired or short of breath. They may suggest pacing activities, using assistive devices, arranging the home to reduce climbing and lifting, and using priority planning (doing the most important tasks when energy is highest). This “energy budgeting” can help patients with chronic Castleman disease keep independence, reduce frustration, and avoid over-exertion that worsens fatigue and pain. Mayo Clinic+1
5. Nutrition counseling for weight, anemia and organ health
Many patients lose weight or appetite, or have anemia and low protein because of chronic inflammation. A dietitian can create a meal plan rich in calories, high-quality protein, iron, folate, vitamin B12 and other nutrients that support red blood cell production and immune function, while protecting the liver and kidneys. For example, they may recommend frequent small meals, soft foods if swallowing is difficult, and limiting excess salt if there is fluid retention or heart failure risk. Nutrition does not cure Castleman disease, but it supports the body while strong medicines and procedures are used. Mayo Clinic+1
6. Infection-prevention behaviors
Multicentric Castleman disease and its treatments (steroids, chemotherapy, biologics) can weaken the immune system. Patients are often advised to wash hands frequently, avoid contact with sick people, use face masks in high-risk environments, maintain good oral hygiene, and keep skin clean and protected. They should promptly report fever, cough, urinary symptoms or new pain, because these can signal infection. Standard adult vaccines (such as influenza, COVID-19 and pneumococcal vaccines) may be recommended following guidelines, but timing must be coordinated with the treating team because some vaccines are contraindicated during intense immunosuppression. FDA Access Data+2FDA Access Data+2
7. Psychological counseling and cognitive-behavioural therapy (CBT)
Living with a rare, chronic and sometimes life-threatening disease can cause anxiety, depression, fear of relapse and social isolation. Psychological counseling or CBT can teach coping skills, challenge unhelpful thoughts, and build resilience. This may reduce distress, improve adherence to treatment plans, and support better sleep and relationships. Emotional support is especially important for younger patients or those facing aggressive multicentric disease and repeated hospital stays. Mayo Clinic+1
8. Patient education and self-management training
Clear information about the disease, its causes, typical symptoms and treatment options helps patients make informed decisions with their doctors. Education programs may cover how to monitor symptoms, how to read basic blood tests, what side effects to watch for with medications, and when to seek urgent care. In rare diseases like Castleman disease, education also empowers patients to advocate for themselves, seek second opinions when needed, and participate in registries or clinical trials. ASH Publications+2ScienceDirect+2
9. Peer support groups and patient organizations
Support groups, whether in person or online (for example through the Castleman Disease Collaborative Network), connect patients and families who share similar experiences. Hearing others’ stories can reduce feelings of isolation, provide practical tips for daily life, and help patients find experts and research opportunities. Peer support does not change the biology of the disease, but it strongly supports mental health and long-term coping. CDCN+1
10. Sleep hygiene and fatigue management
Good sleep is often disturbed by night sweats, pain, anxiety or steroid use. Sleep hygiene means keeping regular sleep and wake times, limiting caffeine in the afternoon, avoiding heavy meals before bed, creating a dark quiet bedroom, and limiting screens. Sometimes short naps are useful, but long daytime naps can make night-time insomnia worse. Better sleep can reduce fatigue, pain sensitivity and mood symptoms, which is important for overall quality of life in chronic inflammatory diseases. Mayo Clinic+1
11. Pain self-management strategies
Non-drug techniques such as heat packs, cold packs, gentle stretching, relaxation breathing, mindfulness, and distraction (music, reading, crafts) can help control mild to moderate pain from enlarged nodes, muscle aches or post-surgical discomfort. These methods are often used alongside prescribed pain medicines. They are low-risk, inexpensive, and give the patient an active role in managing symptoms, which can feel empowering. Medscape+1
12. Smoking cessation
If a patient smokes, stopping smoking significantly improves overall health, reduces infection risk, protects heart and blood vessels, and can improve surgical outcomes. Smoking is known to worsen immunity and reduce the body’s ability to cope with chronic inflammation and chemotherapy. Smoking cessation support may include counseling, nicotine replacement, and structured programs. Medscape+1
13. Alcohol moderation or avoidance
Alcohol stresses the liver, which may already be affected by Castleman disease, chronic inflammation, or hepatotoxic medicines such as methotrexate or some chemotherapy drugs. Limiting alcohol helps protect liver function and reduces the risk of interactions with medications. In some cases, doctors may advise complete avoidance, especially during active treatment. Medscape+1
14. Gentle yoga, tai chi or stretching programs
Slow, controlled movements and breathing techniques used in yoga or tai chi can improve flexibility, balance, and mental calm. These activities also provide a gentle cardiovascular workout without putting too much strain on joints or the heart. For many chronic inflammatory conditions, they have been associated with better fatigue, mood and sleep, although they are not specific treatments for Castleman disease itself. Medscape
15. Lymphedema and swelling management
Large lymph nodes or previous surgery/radiation can disrupt normal lymph drainage, leading to swollen limbs or tissues. Non-pharmacological care may include compression garments, manual lymph drainage massage from trained therapists, elevation of limbs, and skin care to prevent infection. This improves comfort, reduces heaviness and lowers the risk of cellulitis in the affected limb. ACS Journals+1
16. Workplace and school accommodations
Some patients need adjustments in work or school, such as flexible hours, possibility to work from home, lighter physical duties, or extra time for exams. Written documentation from the treating physician helps in negotiating these accommodations. These changes reduce stress, prevent physical over-load, and allow patients to stay engaged in meaningful activities. Mayo Clinic+1
17. Structured rehabilitation after surgery or intensive therapy
After major surgery to remove lymph node masses or after prolonged chemotherapy, structured rehab programs combine physiotherapy, occupational therapy, and sometimes speech or swallowing therapy. The aim is to restore strength, lung capacity, and daily living skills, and to prevent long-term loss of function. Rehab can be inpatient or outpatient, depending on the severity of illness. ACS Journals+2SpringerLink+2
18. Stress-reduction techniques and mindfulness
Chronic stress can worsen perception of pain, fatigue and mood symptoms. Mindfulness meditation, breathing exercises, progressive muscle relaxation, and guided imagery are simple tools patients can practice at home. These techniques do not change the disease process but can reduce anxiety, improve sleep, and help people feel more in control of their health. Medscape+1
19. Care coordination and case management
Because Castleman disease can involve many organs, patients may see hematologists, infectious disease specialists, rheumatologists, surgeons and other providers. Having one doctor or nurse coordinator who oversees the whole care plan reduces confusion about medicines, avoids duplicate tests, and ensures that important information is shared among all team members. This is critical in rare diseases where expertise may be spread across centers. ASH Publications+2ScienceDirect+2
20. Participation in registries and clinical trials
Joining a natural history registry or clinical trial (for example trials of sirolimus or other targeted drugs) helps researchers understand the disease and can give patients access to novel therapies under close monitoring. Data from such registries have already shaped modern treatment guidelines for idiopathic multicentric Castleman disease. SpringerLink+4CDCN+4PubMed+4
Drug treatments
Important: Dosages and schedules below are typical examples from labels or published studies for adults. They must be individualized by the treating physician, especially in Castleman disease where regimens differ by subtype (unicentric vs multicentric, idiopathic vs HHV-8 related, HIV status, organ function).
1. Siltuximab (SYLVANT) – anti-IL-6 monoclonal antibody
Siltuximab is the only FDA-approved drug specifically for idiopathic multicentric Castleman disease (iMCD) in HIV-negative and HHV-8-negative adults. It binds directly to interleukin-6 (IL-6) and neutralizes it, blocking the inflammatory cascade that drives fever, anemia, enlarged nodes and organ dysfunction. From FDA labeling, a common adult dose is 11 mg/kg by intravenous infusion every 3 weeks, continued as long as clinical benefit and tolerable safety are seen. The main purpose is to control symptoms, shrink nodes and improve lab tests. Common side effects include infusion reactions, infections, rash, pruritus, edema, and changes in liver tests or blood counts. CDCN+6FDA Access Data+6FDA Access Data+6
2. Tocilizumab (ACTEMRA and biosimilars) – IL-6 receptor blocker
Tocilizumab is an antibody that blocks the IL-6 receptor rather than IL-6 itself. Although it is FDA-approved for rheumatoid arthritis, giant cell arteritis, some juvenile arthritis and other conditions, it is widely used off-label in Castleman disease, especially when siltuximab is not available. Adult dosing in approved indications is often 162 mg subcutaneously weekly or every other week, or 8 mg/kg IV every 4 weeks, but in iMCD the exact regimen is decided by specialists. The purpose is similar to siltuximab: turning off IL-6–driven inflammation. Side effects include serious infections (TB, bacterial, fungal), liver enzyme elevations, lowered neutrophils and platelets, GI perforation risk, and infusion or injection reactions. LWW Journals+8FDA Access Data+8FDA Access Data+8
3. Rituximab (Rituxan and biosimilars) – anti-CD20 monoclonal antibody
Rituximab targets CD20 on B-cells. It is FDA-approved for lymphoma, chronic lymphocytic leukemia and some autoimmune diseases, and is commonly used off-label in Castleman disease, especially HHV-8–positive multicentric disease and some unicentric cases. Typical dosing in lymphoma is 375 mg/m² IV once weekly for 4 doses, sometimes repeated or combined with chemotherapy. The drug reduces B-cells that may harbor HHV-8 or drive antibody-mediated inflammation. Side effects include infusion reactions, infections, reactivation of hepatitis B, low immunoglobulins, and rare progressive multifocal leukoencephalopathy (PML). Wiley Online Library+5Mayo Clinic+5Wiley Online Library+5
4. Prednisone (and other systemic corticosteroids)
Prednisone is a corticosteroid that reduces inflammation by broadly suppressing immune activity and cytokine production. In Castleman disease it is used alone only in selected mild cases, and more commonly as a short-term adjunct with siltuximab, tocilizumab, rituximab or chemotherapy. Dosing varies widely, for example 0.5–1 mg/kg per day orally with a gradual taper. Steroids can rapidly relieve fever, night sweats and appetite loss, but long-term use causes many side effects: weight gain, mood changes, high blood pressure, diabetes, bone thinning, infection risk and muscle weakness. Medscape+3ASH Publications+3ScienceDirect+3
5. Cyclophosphamide
Cyclophosphamide is an alkylating chemotherapy drug used in regimens like CHOP or CVP for aggressive multicentric Castleman disease or when biologics are not effective or available. It cross-links DNA, stopping rapidly dividing cells, including abnormal lymphocytes. Dosing in CHOP is often 750 mg/m² IV on day 1 of a 21-day cycle combined with other agents. Side effects include low blood counts, nausea, hair loss, infertility, bladder irritation, and increased risk of infections and secondary malignancies. BioMed Central+4Medscape+4Dove Press+4
6. Doxorubicin
Doxorubicin is an anthracycline chemotherapy drug used in CHOP-like regimens. It intercalates into DNA and generates free radicals, killing rapidly dividing cells. In CHOP, a common adult dose is 50 mg/m² IV on day 1 every 21 days, combined with cyclophosphamide, vincristine and prednisone. It helps shrink bulky nodal or organ disease, but is limited by potential heart damage (cardiomyopathy), low blood counts, hair loss, nausea and mucositis. Lifetime cumulative doses are capped to reduce heart toxicity. BioMed Central+4Medscape+4Dove Press+4
7. Vincristine (or vinblastine)
Vincristine is a vinca alkaloid chemotherapy agent that disrupts microtubules and stops cell division. In CHOP, the typical adult dose is 1.4 mg/m² IV on day 1 (max 2 mg) every 21 days. It is used with other drugs to control multicentric disease. Side effects include peripheral neuropathy (numbness, tingling, weakness), constipation, jaw pain and hair loss, but less bone marrow suppression than some other agents. Vinblastine is a related drug sometimes used in alternative regimens. Dove Press+4Medscape+4Blood Research+4
8. Etoposide
Etoposide is a topoisomerase II inhibitor sometimes added to chemotherapy for very aggressive multicentric Castleman disease or overlapping hemophagocytic lymphohistiocytosis. It blocks DNA repair and replication in rapidly dividing cells. Dosing schemes vary, for example 100 mg/m² IV on days 1–3 in 21-day cycles, but must be personalized. Major adverse effects include profound neutropenia and risk of serious infection, hair loss, low platelets and rare secondary leukemias. BioMed Central+3Medscape+3e-Century Publishing+3
9. CVP or R-CVP regimen (cyclophosphamide, vincristine, prednisone ± rituximab)
CVP is a combination chemotherapy used in some patients with multicentric Castleman disease. Cyclophosphamide and vincristine attack rapidly dividing cells, while prednisone reduces inflammation; adding rituximab targets CD20-positive B-cells. A typical schedule is every 3 weeks for several cycles. The purpose is to control systemic disease when IL-6-directed therapy is not suitable or has failed. Toxicities are the combined side effects of each drug: neutropenia, infections, neuropathy, steroid-related problems, and GI side effects. PubMed+4ASH Publications+4Medscape+4
10. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
R-CHOP is a stronger regimen than CVP and is sometimes used in multicentric Castleman disease, especially when there is suspicion of overlapping lymphoma or very aggressive systemic disease. The combination attacks B-cells and other rapidly dividing cells from several angles. Cycles are usually given every 21 days, with the number of cycles based on response and tolerance. Benefits include strong tumor shrinkage; risks include severe neutropenia, infections, heart toxicity from doxorubicin, neuropathy and steroid-related complications. BioMed Central+4ASH Publications+4Medscape+4
11. Antiviral therapy (for HHV-8 or HIV)
In HHV-8–positive multicentric Castleman disease, controlling the virus is important. Antiviral drugs targeting HIV (HAART) and sometimes agents like ganciclovir or valganciclovir against HHV-8 may be used along with rituximab and chemotherapy. These drugs lower viral replication, reduce immune activation, and may improve survival. However, they can cause bone marrow suppression, kidney toxicity and other organ side effects, so dosing and combinations must be monitored by infectious disease specialists. Mayo Clinic+3PubMed+3Journal of Pediatrics+3
12. Lenalidomide
Lenalidomide is an oral immunomodulatory drug related to thalidomide. It has anti-inflammatory, anti-angiogenic and immune-modulating properties and can lower IL-6 levels. Case series suggest it may help in relapsed or refractory Castleman disease, sometimes combined with glucocorticoids or tocilizumab. Typical dosing patterns in reports are 10–25 mg orally once daily on days 1–21 of a 28-day cycle, but exact schedules vary. Side effects include neutropenia, thrombocytopenia, risk of blood clots, rash, diarrhea and fatigue. Strict pregnancy prevention measures are required. ResearchGate+6PubMed+6Taylor & Francis Online+6
13. Thalidomide
Thalidomide, an older immunomodulatory drug, has been used in some Castleman disease cases to reduce IL-6 and control symptoms. It interferes with blood vessel growth and modulates cytokine production. Doses vary but often range from 50–200 mg orally at bedtime, adjusted for tolerance. Because of serious risks such as birth defects, peripheral neuropathy, sedation and blood clots, it is now used less often than lenalidomide and only under strict safety programs. Dove Press+2Blood Research+2
14. Sirolimus (rapamycin)
Sirolimus is an oral mTOR inhibitor. Research has shown increased mTOR activation in iMCD, and recent case series and studies suggest sirolimus can be effective in refractory or relapsed iMCD after IL-6 inhibitors. Typical doses in studies are around 1–4 mg orally once daily, adjusted to maintain target blood levels and minimize toxicity. Sirolimus blocks mTOR signaling, which is involved in cell growth, metabolism and immune activation. Side effects include mouth ulcers, high cholesterol and triglycerides, low blood counts, delayed wound healing and increased infection risk. LWW Journals+4ASH Publications+4PubMed+4
15. Bortezomib
Bortezomib is a proteasome inhibitor used in multiple myeloma and some lymphomas. In Castleman disease, especially overlapping POEMS syndrome or plasma-cell–rich forms, bortezomib combined with rituximab and dexamethasone has shown benefit in some reports. Standard dosing is commonly 1.3 mg/m² IV or subcutaneously on days 1, 4, 8 and 11 of a 21-day cycle, but protocols vary. Side effects include peripheral neuropathy, low blood counts, shingles reactivation and GI upset. thejh.org+2EJCRIM+2
16. Anakinra (IL-1 receptor antagonist) – selected refractory cases
Anakinra blocks the interleukin-1 receptor and is used in various autoinflammatory diseases. In a few refractory Castleman disease cases, especially with high inflammatory cytokines, IL-1 blockade has been tried. Standard doses in other conditions are 100 mg subcutaneously daily in adults, but Castleman-specific dosing is individualized. Side effects include injection-site reactions, infections, neutropenia and elevated liver enzymes. Evidence is limited and it is generally reserved for very difficult cases guided by experts. ScienceDirect+2ScienceDirect+2
17. IVIG (intravenous immunoglobulin) – supportive therapy
IVIG is a pooled antibody product from donor plasma. In Castleman disease, it is not a primary disease-directed drug, but may be given to patients with very low immunoglobulin levels or recurrent infections, often due to rituximab or other immunosuppressive therapies. Doses differ, for example 0.4 g/kg daily for 5 days for some immune conditions or 0.4–1 g/kg every 3–4 weeks for replacement therapy. Side effects include headache, infusion reactions, kidney stress and rare blood clots. Wiley Online Library+1
18. Erythropoiesis-stimulating agents (ESAs) – epoetin alfa, darbepoetin
ESAs are not Castleman-specific but may be used to treat chronic anemia when iron and vitamins are adequate and inflammation or chemotherapy suppresses the marrow. They stimulate red blood cell production by acting like erythropoietin. Doses vary (for example, epoetin alfa 40,000 units subcutaneously weekly) and must be adjusted based on hemoglobin levels. Risks include blood clots, high blood pressure and, in cancer, possible effects on tumor outcomes; they are used cautiously and only when clearly indicated. Medscape+1
19. Growth-factor support (G-CSF, GM-CSF)
Granulocyte colony-stimulating factor (G-CSF, such as filgrastim) and GM-CSF are supportive drugs given to boost neutrophil counts after chemotherapy or with intense immunosuppression. They reduce the duration of neutropenia and lower infection risk but do not treat Castleman disease itself. Typical filgrastim dosing is 5 µg/kg/day subcutaneously after chemotherapy until neutrophils recover. Common side effects include bone pain and mild fever; rare effects include spleen enlargement and rupture. Medscape+2Blood Research+2
20. Standard symptomatic medications (antipyretics, analgesics, anticoagulants)
Many patients also receive supportive drugs such as acetaminophen for fever, non-opioid or opioid analgesics for pain, and anticoagulants if there is high risk of thrombosis due to inflammation, immobilization or use of immunomodulators like lenalidomide. Dosing follows general medical practice and must be individualized to kidney and liver function. These medicines help control discomfort and reduce complications but should be carefully coordinated with the main Castleman therapies to avoid interactions and organ toxicity. Mayo Clinic+2Medscape+2
Dietary molecular supplements
Supplements below are general immune- and health-supporting nutrients. There is no strong evidence that any supplement alone treats angiofollicular lymph node hyperplasia/Castleman disease. They should only be used under medical supervision, especially with liver or kidney issues and during chemotherapy.
1. Vitamin D
Vitamin D supports bone health, muscle function and immune regulation. Many patients with chronic illness and little sun exposure are deficient. Typical adult replacement doses range from 800–2000 IU daily, with higher short-term doses in severe deficiency as directed by a doctor. Vitamin D modulates innate and adaptive immunity and may help balance excessive inflammation. Taking too much can cause high calcium, kidney stones and confusion, so blood levels should be monitored. Medscape+1
2. Omega-3 fatty acids (EPA/DHA from fish oil)
Omega-3 fatty acids have anti-inflammatory effects by altering eicosanoid and cytokine production. Doses used in general inflammatory conditions usually range from 1–3 g of combined EPA/DHA per day, taken with meals. They may modestly improve triglycerides and systemic inflammation markers. Side effects can include fishy aftertaste, GI upset and, at high doses, increased bleeding risk, especially with anticoagulants or antiplatelet drugs, so coordination with the care team is important. Medscape+1
3. Curcumin (turmeric extract)
Curcumin is the active compound in turmeric and has been shown in laboratory and small clinical studies to have anti-inflammatory and antioxidant effects. Typical supplement doses in human studies range from 500–2000 mg per day of standardized extract, often split into two or three doses. It may reduce some inflammatory markers and joint pains, but bioavailability is variable. Curcumin can interact with blood thinners and may cause digestive upset; high doses should be avoided without medical advice. Medscape+1
4. Probiotics
Probiotic supplements contain live “good bacteria” that may support gut health and immune balance. In chronic illness, antibiotic use and poor diet can disturb the microbiome. Common products provide billions of colony-forming units (CFU) daily of Lactobacillus, Bifidobacterium or mixed strains. Probiotics may reduce antibiotic-associated diarrhea and modulate immune responses, though data are not specific to Castleman disease. In severely immunocompromised patients, rare bloodstream infections have been reported, so use should be discussed with the treating physician. Medscape+1
5. Iron (when deficient)
Chronic inflammation in Castleman disease often causes anemia. If tests show low iron stores (low ferritin and transferrin saturation) and other causes are excluded, oral or IV iron may be given. Oral doses are commonly 60–200 mg elemental iron daily, but regimens vary and recent guidelines often prefer lower, alternate-day dosing for tolerability. Iron supports hemoglobin production and energy. Excess iron can cause GI upset, constipation, and rarely iron overload, so therapy must be guided by lab tests and doctor oversight. Mayo Clinic+1
6. Vitamin B12
Vitamin B12 is needed for red blood cell formation and nerve function. Deficiency can worsen anemia and neuropathy, which may already be present due to disease or chemotherapy. Supplementation can be oral (for example 1000 µg daily) or intramuscular (for example 1000 µg weekly then monthly), depending on absorption. Side effects are usually minimal, but B12 should only be given when deficiency is documented or strongly suspected, and other causes of anemia evaluated. Medscape+1
7. Folate (folic acid)
Folate is another B-vitamin essential for red blood cell production. Some chemotherapy drugs or poor diet can lower folate levels. Typical supplement doses for deficiency are 1 mg daily, though diet rich in leafy greens also helps. Too much folic acid can mask B12 deficiency, so both vitamins should be checked. As with other nutrients, folate supports general health but does not specifically treat Castleman disease. Medscape+1
8. Coenzyme Q10 (CoQ10)
CoQ10 is an antioxidant involved in mitochondrial energy production. Some small studies in other conditions suggest it may help with fatigue and muscle function. Common supplement doses are 100–300 mg daily, divided with meals containing fat. Side effects are usually mild (GI discomfort, headache), but CoQ10 can interact with blood thinners like warfarin by affecting clotting factors, so close monitoring is needed. Evidence in Castleman disease is lacking; its use is purely supportive. Medscape+1
9. Selenium
Selenium is a trace mineral important for antioxidant enzymes and immune function. In areas with low dietary selenium, supplementation may be considered in small doses (for example 50–200 µg per day). Too much selenium can cause hair loss, brittle nails, and neurological symptoms, so it should not be taken in high doses without checking levels. Its role in Castleman disease is not proven; any use should be guided by blood tests and medical advice. Medscape+1
10. Multivitamin tailored to medical needs
Many patients benefit from a simple, once-daily multivitamin that provides recommended daily amounts of key vitamins and minerals, especially when appetite is poor. High-dose “megavitamin” products are generally not needed and can be harmful. A standard multivitamin supports general nutritional adequacy but is not a treatment for lymph node hyperplasia itself. Any product should be checked for interactions with chemotherapy or biologics. Medscape+1
Drugs for immune support / regenerative / stem-cell–related effects
Again, these are supportive or experimental tools in select patients, not primary curative treatments.
1. Filgrastim (G-CSF)
Filgrastim is a granulocyte colony-stimulating factor that boosts neutrophil production. Typical adult doses are 5 µg/kg/day subcutaneously after chemotherapy until neutrophils recover. Its function is to shorten the duration of neutropenia, reduce infection risk, and allow delivery of planned chemotherapy doses. Mechanistically, it stimulates bone marrow progenitors to mature into neutrophils. Side effects include bone pain, mild fever and very rarely spleen enlargement or rupture. Medscape+2Blood Research+2
2. Epoetin alfa (ESA)
Epoetin alfa is a synthetic erythropoietin analog that stimulates red blood cell production. It may be used when anemia is severe and other causes such as iron or B12 deficiency are corrected. Doses vary (for example 40,000 units subcutaneously weekly), with targets and duration defined by guidelines. Its function is regenerative for the red cell line, but it carries risks of blood clots, hypertension and possible effects on cancer outcomes, so it is used cautiously and under strict monitoring. Medscape+1
3. Romiplostim or eltrombopag (thrombopoietin receptor agonists)
In some patients with severe, persistent low platelets due to disease or treatment, thrombopoietin receptor agonists may be used to stimulate platelet production. Romiplostim is given as a weekly subcutaneous injection with doses titrated to platelet response, while eltrombopag is an oral drug with daily dosing. They act on the TPO receptor on megakaryocyte precursors to boost platelet output. Side effects include blood clots, liver enzyme elevations and, rarely, marrow fibrosis, so careful monitoring is essential. Medscape+1
4. Intravenous immunoglobulin (IVIG)
As noted above, IVIG supports humoral immunity when antibody levels are low. Its “regenerative” role is in replacing missing antibodies to help defend against infections. Typical replacement doses are 0.4–1 g/kg every 3–4 weeks. IVIG offers ready-made IgG antibodies from thousands of donors, but can cause headache, aseptic meningitis, kidney injury and rare thrombotic events, so infusion rate and hydration are important. Wiley Online Library+1
5. Plerixafor (stem cell mobilizer) – in stem cell transplantation settings
Plerixafor is a CXCR4 antagonist used together with G-CSF to mobilize hematopoietic stem cells from bone marrow into blood before autologous stem cell collection. While not a standard Castleman therapy, it may be used if high-dose chemotherapy with autologous stem cell transplant is chosen for very aggressive or refractory disease. Typical adult dosing is 0.24 mg/kg subcutaneously before apheresis sessions. Side effects include injection-site reactions, GI symptoms and rare splenic rupture. Medscape+1
6. Autologous or allogeneic hematopoietic stem cell transplantation (as a drug-procedure combination)
Although technically a procedure rather than a single “drug,” stem cell transplantation uses high-dose chemotherapy followed by infusion of hematopoietic stem cells (the “cellular drug”) to re-grow the bone marrow. It has been used in some cases of very aggressive multicentric Castleman disease or Castleman associated with other hematologic conditions. Conditioning regimens, cell doses and supportive drugs are highly individualized. Benefits may include long-term remission; risks include severe infections, graft-versus-host disease (for allogeneic transplant), organ toxicity and treatment-related mortality. Medscape+2Blood Research+2
Surgeries
1. Complete surgical excision of a unicentric lymph node mass
For unicentric Castleman disease, complete surgical removal of the affected lymph node mass is the gold-standard treatment. If the mass can be safely removed, surgery alone often cures the disease and gives excellent long-term survival. The surgeon carefully dissects and removes the node, often in the chest or abdomen. The purpose is both diagnostic (confirm the diagnosis on pathology) and therapeutic (remove the source of abnormal cytokine production). Risks depend on the location and include bleeding, infection and nerve or organ injury. ACS Journals+2SpringerLink+2
2. Excisional lymph node biopsy
Before any treatment is decided, an enlarged node is often removed entirely for detailed histopathology. This “excisional biopsy” is a smaller surgery, sometimes done as day-case. It allows pathologists to distinguish Castleman disease from lymphoma, infection or other causes. The purpose is accurate diagnosis; risks are small but include wound infection, bleeding and pain. PubMed+2Wikipedia+2
3. Debulking or partial resection of large masses
When a mass is very large or wrapped around vital structures (blood vessels, airways), complete removal may be unsafe. In such cases, surgeons may perform “debulking” to remove as much of the lesion as possible, then follow with medical therapy (rituximab, IL-6 inhibition, chemotherapy). The goal is to relieve compression symptoms (shortness of breath, pain) and improve response to drugs. Debulking carries higher risks due to the difficulty of the procedure. ACS Journals+2SpringerLink+2
4. Splenectomy (surgical removal of the spleen)
In some patients, the spleen is massively enlarged, causing pain, low blood counts or risk of rupture. Splenectomy removes this source of discomfort and may improve cytopenias. It also allows complete histologic evaluation of the spleen. However, removing the spleen permanently increases the risk of serious infections, especially from encapsulated bacteria, so vaccines and infection-prevention strategies are needed before and after surgery. Blood Research+2Mayo Clinic+2
5. Central venous access device placement
Patients receiving repeated intravenous biologics, chemotherapy or stem cell transplant often need a tunneled central venous catheter or implanted port. Placement is a minor surgical procedure done under local or general anesthesia. The purpose is to allow safe, repeated access to large veins for infusions and blood draws, reducing needle sticks and protecting small peripheral veins. Risks include line infection, clotting and mechanical complications, which are minimized with proper care. Medscape+1
Prevention strategies
Because the exact cause of idiopathic Castleman disease is unknown, we cannot fully prevent it. However, several strategies reduce complications and improve outcomes:
Early evaluation of persistent lymph node enlargement or systemic symptoms – Seek medical review if you have enlarged nodes, long-lasting fever, weight loss or night sweats for more than a few weeks. Early diagnosis allows earlier treatment and may prevent organ damage. Cancer.gov+1
Optimal control of HIV and HHV-8 infection – In people with HIV, strict adherence to antiretroviral therapy reduces the risk of HHV-8–related multicentric Castleman disease. PubMed+2Journal of Pediatrics+2
Vaccinations as recommended – Staying up to date with vaccines (influenza, COVID-19, pneumococcus, etc.) helps prevent serious infections, which can be more dangerous in immunosuppressed patients. Timing and types of vaccines should be agreed with the doctor. FDA Access Data+2FDA Access Data+2
Avoiding unnecessary immunosuppression – Long-term use of steroids or other immune-suppressing drugs for other conditions should be carefully reviewed, because they can worsen infection risk when Castleman disease is present. FDA Access Data+2FDA Access Data+2
Healthy lifestyle (diet, exercise, no smoking) – While lifestyle does not prevent Castleman disease itself, maintaining a healthy weight, regular activity, and avoiding tobacco and excess alcohol improves resilience against treatment side effects and infections. Mayo Clinic+1
Prompt treatment of infections – Early recognition and treatment of bacterial, viral or fungal infections lowers complications and may prevent worsening of inflammatory symptoms in multicentric disease. FDA Access Data+2FDA Access Data+2
Regular follow-up after remission – Even after successful therapy, regular clinical and laboratory follow-up helps detect relapse or evolution into lymphoma at an early stage. ASH Publications+2ScienceDirect+2
Monitoring for drug side effects – Blood tests and clinical checks during biologic therapy or chemotherapy help catch liver injury, cytopenias, or heart issues early, allowing dose adjustment or drug changes. Medscape+3FDA Access Data+3FDA Access Data+3
Genetic counseling or specialist review for complex syndromes – Some Castleman-like conditions appear in the context of syndromes such as POEMS. Early recognition and specialist referral can guide tailored treatment and monitoring. EJCRIM+1
Participation in expert centers and registries – Care at centers experienced in Castleman disease and participation in registries helps ensure up-to-date management and contributes to better prevention and treatment strategies for future patients. SpringerLink+3CDCN+3PubMed+3
When to see a doctor
You should see a doctor as soon as possible if you notice:
Enlarged lymph nodes (neck, armpit, groin, chest, abdomen) that last more than 3–4 weeks or keep growing.
Unexplained fever, night sweats or weight loss (sometimes called “B symptoms”).
Persistent fatigue, weakness, or shortness of breath, especially with evidence of anemia or low blood counts.
Swelling of the abdomen, legs or around the eyes, chest pain or trouble breathing that could indicate organ enlargement or fluid accumulation.
New severe pain, neurological symptoms (numbness, tingling, weakness), or confusion.
Any new or worsening symptoms if you already have a diagnosis of Castleman disease, including new fever, more swollen nodes, bleeding, or signs of infection during biologic or chemotherapy treatment. Medscape+3Cancer.gov+3Mayo Clinic+3
Seek emergency care if you have very high fever, severe shortness of breath, chest pain, sudden confusion, heavy bleeding, or signs of sepsis.
What to eat and what to avoid
There is no specific “Castleman diet”, but these simple rules support general health and treatment tolerance:
Eat plenty of fruits and vegetables – Aim for colorful plant foods (leafy greens, berries, carrots, tomatoes) to provide vitamins, minerals and antioxidants that support immunity and organ health. Medscape+1
Choose lean proteins – Include fish, poultry, eggs, beans, lentils and tofu to help maintain muscles and support repair, especially after surgery or chemotherapy. Protein is important when inflammation and catabolism are high. Medscape+1
Prefer whole grains over refined grains – Brown rice, whole-wheat bread and oats provide stable energy and fiber, which helps gut health, especially when on multiple medications. Medscape+1
Stay well hydrated – Water and clear fluids help kidney function, especially when taking drugs that can affect the kidneys. Limit sugary drinks. Medscape+1
Limit very salty and ultra-processed foods – Canned soups, chips, fast foods and processed meats can worsen fluid retention and blood pressure, which may already be affected by steroids or heart strain. Medscape+1
Avoid excessive alcohol – Alcohol can harm the liver and bone marrow and interact with many medications used in Castleman disease, so many patients are advised to avoid it entirely during active treatment. Medscape+1
Be cautious with raw or undercooked foods when immunosuppressed – Unpasteurized dairy, raw seafood and undercooked meats can carry infections. Neutropenic patients often follow food-safety guidance to lower infection risk. Medscape+1
Discuss herbal products with your doctor – Some herbs and “natural” remedies interact with chemotherapy or biologics (for example, St John’s wort with many drugs). Always check before starting any new product. Medscape+1
Adjust fiber and lactose based on symptoms – If diarrhea from treatment is a problem, very high-fiber foods or lactose-rich milk may need temporary reduction; if constipation is a problem, more fiber and fluid may help. A dietitian can guide this. Medscape+1
Use individualized nutrition plans in severe disease – Some patients may need high-calorie supplements or even tube feeding or parenteral nutrition in extreme cases. These should always be directed by specialists. Medscape+1
Frequently asked questions
1. Is angiofollicular lymph node hyperplasia a cancer?
No. It is usually described as a non-cancerous (benign) lymphoproliferative disorder, although it can behave in a serious way and increase the risk of later lymphoma. The lymph nodes grow abnormally, but not in the same malignant pattern as lymphoma. Blood Research+3Cancer.gov+3PubMed+3
2. What is the difference between unicentric and multicentric disease?
Unicentric disease involves a single lymph node region and often causes fewer symptoms; it is usually cured by surgical removal. Multicentric disease affects many node groups and sometimes organs, causing systemic symptoms like fever, weight loss and organ problems. It usually needs systemic medication such as siltuximab, tocilizumab, rituximab and/or chemotherapy. Mayo Clinic+3Cancer.gov+3PubMed+3
3. What causes angiofollicular lymph node hyperplasia?
The cause is not fully known. In some cases, especially in people with HIV, human herpesvirus-8 (HHV-8) infection is strongly linked to multicentric disease. In idiopathic cases, dysregulated immune signaling, especially high IL-6 and sometimes mTOR pathway activation, seems central. Genetics and other immune triggers may also play a role. Blood Research+3Mayo Clinic+3ScienceDirect+3
4. Is there a cure?
Unicentric disease is often cured by complete surgical excision. Multicentric disease is more chronic, but modern treatments (siltuximab and tocilizumab-based regimens, rituximab for HHV-8–positive disease, chemotherapy, sirolimus in refractory cases) can produce long-lasting remissions in many patients, especially when started early. PubMed+5ACS Journals+5SpringerLink+5
5. How is it diagnosed?
Diagnosis requires a combination of clinical evaluation, blood tests, imaging (CT, MRI or PET), and excisional lymph node biopsy with detailed histopathology. Other conditions like lymphoma and autoimmune diseases must be ruled out. Some patients also have bone marrow biopsy and detailed virology tests for HIV and HHV-8. Blood Research+3PubMed+3Wikipedia+3
6. Why is IL-6 such an important target?
IL-6 is a key inflammatory cytokine that drives fever, C-reactive protein elevation, anemia of chronic disease, fatigue and abnormal blood vessel growth in many Castleman patients. Blocking IL-6 (with siltuximab) or its receptor (with tocilizumab) directly attacks a central pathway in the disease rather than just treating symptoms. ASH Publications+4ScienceDirect+4FDA Access Data+4
7. How long do I need to stay on siltuximab or tocilizumab?
There is no single fixed answer. Many patients with idiopathic multicentric disease stay on anti-IL-6 therapy for years, with intervals adjusted based on response and tolerance. Some guidelines recommend continuing at least a year after complete remission and then considering careful spacing or tapering. Decisions should be made in partnership with a Castleman-experienced specialist. ASH Publications+3ASH Publications+3ScienceDirect+3
8. What are the main risks of biologic therapies like siltuximab and tocilizumab?
The main risks are infections (including serious bacterial, TB and opportunistic infections), changes in blood counts, liver enzyme elevations, infusion or injection reactions, and sometimes changes in cholesterol or GI perforation risk (more with tocilizumab). People need baseline screening (for example TB tests) and regular labs. FDA Access Data+6FDA Access Data+6FDA Access Data+6
9. Can Castleman disease turn into lymphoma?
Yes. Patients with multicentric disease, especially with chronic immune activation, have a higher risk of developing lymphoma over time compared with the general population. Regular follow-up, imaging and repeat biopsy of suspicious nodes help detect this early. Wiley Online Library+3Cancer.gov+3PubMed+3
10. Can lifestyle changes cure the disease?
No. Healthy diet, exercise, stress management and infection-prevention measures support general health and treatment tolerance, but they cannot replace medical treatments like surgery, biologics or chemotherapy. However, they may improve quality of life and reduce some complications. ScienceDirect+3Mayo Clinic+3Medscape+3
11. Are there new treatments being studied?
Yes. Ongoing research is exploring sirolimus and other mTOR inhibitors for IL-6-refractory disease, combinations of biologics and immunomodulatory drugs like lenalidomide, and more personalized treatment strategies guided by immune profiling. Clinical trials and registries are active in several countries. e-Century Publishing+4PubMed+4Wiley Online Library+4
12. Can children get Castleman disease?
Yes, although Castleman disease is rarer in children than adults. Pediatric cases require specialized care in experienced centers, and treatment often adapts adult regimens with age-appropriate dosing and careful monitoring for growth and development. Journal of Pediatrics+2Blood Research+2
13. What is the long-term outlook?
For unicentric disease treated surgically, long-term survival is excellent. For multicentric disease, prognosis has improved greatly with IL-6-targeted therapy and modern regimens, but it still depends on disease severity, organ involvement, response to treatment and comorbidities such as HIV. Early diagnosis and management at expert centers improve outcomes. e-Century Publishing+4ACS Journals+4SpringerLink+4
14. Can pregnancy be managed with Castleman disease?
Pregnancy in women with Castleman disease is complex and needs close coordination between hematology and obstetric teams. Some drugs (for example, lenalidomide, thalidomide, many chemotherapies) are not safe in pregnancy, while others may be used with caution. Planning pregnancy during stable disease and after discussion with specialists is very important. LWW Journals+4FDA Access Data+4FDA Access Data+4
15. Where can patients and doctors find reliable information and support?
Reliable sources include national cancer or hematology organizations, peer-reviewed journals, and dedicated groups such as the Castleman Disease Collaborative Network, which provide patient-friendly information, treatment guidelines and registry opportunities. Consultation with centers that have experience in Castleman disease is strongly recommended for complex cases. Wiley Online Library+3ASH Publications+3CDCN+3
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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: November 13, 2025.
