7 Key Signs and Symptoms of Castleman Disease You Should Know

Castleman disease, also known as Castleman’s disease or giant lymph node hyperplasia, is a rare disorder that affects the lymph nodes and related tissues throughout the body. This condition causes an overgrowth of cells in the lymphatic system, leading to enlarged lymph nodes and various systemic symptoms. There are two main types: unicentric Castleman disease (UCD), which affects a single lymph node region, and multicentric Castleman disease (MCD), which involves multiple lymph node regions and is generally more severe.

Understanding the symptoms of Castleman disease is crucial for early detection and appropriate medical intervention. The symptoms can vary significantly depending on the type and severity of the condition. While some people may experience only mild symptoms, others may develop serious complications that require immediate medical attention. Below, we explore the seven key symptoms associated with this rare condition.

1. Enlarged Lymph Nodes

The most characteristic symptom of Castleman disease is enlarged lymph nodes, which can occur in various parts of the body. In unicentric Castleman disease, typically only one lymph node region is affected, commonly in the chest, abdomen, or neck. These enlarged nodes may be discovered incidentally during imaging tests for other conditions, as they don’t always cause noticeable symptoms.

In multicentric Castleman disease, multiple lymph node regions throughout the body become enlarged simultaneously. You may notice:

• Visible or palpable lumps in the neck, armpit, or groin areas
• Swelling that may be painless or tender to touch
• Lymph nodes that feel firm or rubbery
• Progressive enlargement over time

The size of enlarged lymph nodes can range from a few centimeters to much larger masses that may compress nearby organs or blood vessels, potentially causing additional complications.

2. Persistent Fever and Night Sweats

Many people with Castleman disease, particularly the multicentric type, experience recurrent fevers that come and go without an obvious infection. These fevers are often accompanied by drenching night sweats that may require changing clothes or bedding during the night.

The fever associated with Castleman disease typically:

• Occurs intermittently rather than continuously
• May spike to high temperatures (above 101°F or 38.3°C)
• Doesn’t respond well to standard fever-reducing medications
• Often worsens during disease flares

These symptoms result from the overproduction of inflammatory proteins called cytokines, particularly interleukin-6 (IL-6), which affects the body’s temperature regulation system. The persistent nature of these symptoms can significantly impact daily activities and quality of life.

3. Severe Fatigue and Weakness

Extreme tiredness is one of the most debilitating symptoms of Castleman disease, particularly in the multicentric form. This isn’t ordinary tiredness that improves with rest; rather, it’s a profound exhaustion that can make even simple daily tasks feel overwhelming.

The fatigue associated with Castleman disease is characterized by:

• Persistent lack of energy that doesn’t improve with sleep
• Physical weakness affecting muscles throughout the body
• Difficulty concentrating or mental fog
• Reduced ability to perform routine activities
• Feeling exhausted after minimal exertion

This fatigue stems from multiple factors, including chronic inflammation, anemia (low red blood cell count), and the body’s constant immune system activation. The exhaustion can be so severe that it interferes with work, social activities, and overall quality of life.

4. Unintended Weight Loss and Loss of Appetite

Significant weight loss without trying is a common symptom, especially in multicentric Castleman disease. Many patients report losing 10% or more of their body weight over a relatively short period, often accompanied by a marked decrease in appetite.

This symptom manifests as:

• Gradual but steady weight loss despite normal eating habits
• Early satiety (feeling full quickly when eating)
• General disinterest in food
• Nausea that may worsen the appetite loss
• Muscle wasting in advanced cases

The weight loss occurs due to the hypermetabolic state caused by chronic inflammation, where the body burns more calories than usual. Additionally, elevated cytokine levels can suppress appetite and alter metabolism, contributing to progressive weight loss that can lead to malnutrition if left unmanaged.

5. Skin Rashes and Changes

Dermatological manifestations are frequently observed in patients with Castleman disease, particularly those with the multicentric variant. These skin changes can vary widely in appearance and may be among the first noticeable signs of the condition.

Common skin-related symptoms include:

• Red or purple skin lesions resembling Kaposi sarcoma
• Petechiae (small red or purple spots caused by bleeding under the skin)
• Generalized itching without visible rash
• Skin that appears pale due to anemia
• Violaceous (purple-colored) plaques or nodules

These skin changes result from various mechanisms, including inflammation, blood vessel abnormalities, and low platelet counts. The rashes may appear suddenly during disease flares and can be accompanied by other systemic symptoms. Some patients also develop edema (swelling) in the extremities, which may cause the skin to appear stretched or shiny.

6. Breathing Difficulties and Chest Discomfort

When enlarged lymph nodes develop in the chest cavity, they can cause respiratory symptoms that range from mild discomfort to severe breathing problems. This is particularly common in unicentric Castleman disease affecting the mediastinum (the central area of the chest).

Respiratory symptoms may include:

• Shortness of breath, especially with physical activity
• Persistent cough that doesn’t respond to typical treatments
• Chest pain or pressure sensation
• Difficulty taking deep breaths
• Wheezing or abnormal breathing sounds
• Sensation of fullness in the chest

Large lymph node masses in the chest can compress the airways, blood vessels, or lungs themselves, leading to these symptoms. In severe cases, compression of major blood vessels like the superior vena cava can cause additional complications such as facial swelling, neck vein distension, and upper body edema—a condition known as superior vena cava syndrome.

7. Abdominal Pain and Digestive Issues

Enlarged lymph nodes in the abdomen can cause various gastrointestinal symptoms that may initially be mistaken for other digestive disorders. These symptoms are particularly common when the disease affects lymph nodes in the mesentery (the tissue that attaches the intestines to the abdominal wall) or around other abdominal organs.

Abdominal symptoms associated with Castleman disease include:

• Diffuse or localized abdominal pain or discomfort
• Feeling of abdominal fullness or bloating
• Nausea and vomiting
• Changes in bowel habits (diarrhea or constipation)
• Enlarged liver (hepatomegaly) or spleen (splenomegaly)
• Fluid accumulation in the abdomen (ascites) in severe cases

The enlarged lymph nodes can press on nearby organs such as the stomach, intestines, liver, or spleen, causing discomfort and functional problems. An enlarged spleen, in particular, can contribute to additional symptoms such as feeling full quickly when eating, anemia, and low platelet counts.

Main Causes of Castleman Disease

The exact cause of Castleman disease remains incompletely understood, but researchers have identified several factors that contribute to its development:

Human Herpesvirus-8 (HHV-8) Infection: A significant proportion of multicentric Castleman disease cases, particularly in people with HIV, are associated with HHV-8 infection. This virus, also linked to Kaposi sarcoma, appears to trigger abnormal immune responses that lead to lymph node enlargement and excessive cytokine production.

Immune System Dysregulation: Castleman disease involves inappropriate activation of the immune system, leading to overproduction of inflammatory proteins, especially interleukin-6 (IL-6). This cytokine storm causes many of the systemic symptoms and complications associated with the disease.

Idiopathic (Unknown) Causes: In many cases, particularly unicentric Castleman disease, no specific trigger can be identified. These idiopathic cases suggest that genetic factors, environmental triggers, or yet-undiscovered infectious agents may play a role.

Associated Conditions: Castleman disease sometimes occurs alongside other conditions, including:

• HIV/AIDS infection
• POEMS syndrome (a rare blood disorder)
• Other autoimmune or inflammatory conditions
• Certain cancers, particularly lymphomas

Genetic Susceptibility: While Castleman disease is not directly inherited, some research suggests that genetic factors may influence susceptibility to developing the condition when exposed to certain triggers.

Frequently Asked Questions

Is Castleman disease a type of cancer?

Castleman disease is not cancer, but it is a lymphoproliferative disorder that causes abnormal growth of lymphatic tissue. However, people with Castleman disease, particularly the multicentric type, have an increased risk of developing lymphomas and other cancers. The condition shares some features with cancer, such as abnormal cell growth, but it responds to different treatment approaches.

How is Castleman disease diagnosed?

Diagnosis typically requires a combination of imaging studies (CT scans, PET scans, or MRI), blood tests showing elevated inflammatory markers, and most importantly, a lymph node biopsy. The biopsy allows pathologists to examine the tissue under a microscope and identify the characteristic features of Castleman disease, which include specific patterns of cell growth and blood vessel proliferation.

Can Castleman disease go away on its own?

Castleman disease does not resolve spontaneously and requires medical intervention. Unicentric Castleman disease can often be cured by surgical removal of the affected lymph node. Multicentric Castleman disease is more challenging and typically requires ongoing management, though it can sometimes go into remission with appropriate treatment.

Is Castleman disease contagious?

Castleman disease itself is not contagious and cannot be transmitted from person to person. However, the HHV-8 virus, which is associated with some cases of multicentric Castleman disease, can be transmitted through saliva, sexual contact, or blood. It’s important to note that most people infected with HHV-8 never develop Castleman disease.

What is the life expectancy for someone with Castleman disease?

Prognosis varies significantly depending on the type of Castleman disease. Unicentric Castleman disease generally has an excellent prognosis, with most patients being cured after surgical removal of the affected lymph node. Multicentric Castleman disease has a more variable outlook, depending on factors such as HIV status, HHV-8 infection, severity of symptoms, and response to treatment. With modern therapeutic approaches, many patients with MCD can achieve good disease control and maintain quality of life for many years.

Who is most at risk for developing Castleman disease?

Castleman disease is extremely rare and can affect people of any age, though it’s most commonly diagnosed in young adults. Risk factors include HIV infection, which significantly increases the risk of developing multicentric Castleman disease, and infection with HHV-8. The unicentric form appears to affect men and women equally, while the multicentric form is slightly more common in men. There is no clear racial or ethnic predisposition.

Can Castleman disease affect children?

Yes, although rare, Castleman disease can occur in children. The unicentric form is more common in pediatric cases than the multicentric form. Children typically present with an enlarged lymph node mass, often in the chest or abdomen, which may be discovered incidentally or cause symptoms due to compression of nearby structures. The prognosis for children with unicentric Castleman disease is generally excellent following surgical removal.

References:

• Mayo Clinic – Castleman Disease
• National Organization for Rare Disorders (NORD) – Castleman Disease
• National Cancer Institute – Castleman Disease
• Castleman Disease Collaborative Network
• StatPearls – Castleman Disease