Castleman disease

What is Castleman Disease?

Castleman disease (CD) is a rare group of disorders that involve enlarged lymph nodes and a wide range of inflammatory symptoms and laboratory abnormalities [3][4]. It can affect any region of the body where lymph nodes are found, such as the neck, chest, abdomen, or mesentery [14].

Types of Castleman Disease

There are four main subtypes of CD: unicentric Castleman disease (UCD), multicentric Castleman disease (MCD), and two other rare forms [9]. UCD is a localized condition that is generally confined to a single set of lymph nodes, while MCD is a systemic form that affects multiple regions of the body [9].

Symptoms

People with CD may experience symptoms such as:

• Lymph node swelling
• Flu-like symptoms (e.g. fever, weight loss, night sweats)
• Low levels of red blood cells (hemolytic anemia) or large amounts of immunoglobulins in the blood (hypergammaglobulinemia)
• Increased risk of serious infections due to a weakened immune system [12]

Causes and Treatment

The exact cause of CD is unknown, but it may be associated with human herpesvirus 8 (HHV-8) or other viral infections [7]. Treatment varies depending on the subtype and severity of the disease, and may include anti-interleukin-6-directed therapies, rituximab, or other medications [5].

References

[1] Age of presentation ranges from 5 years to 70 years. [3] Castleman disease is a rare group of disorders that involve enlarged lymph nodes and a wide range of inflammatory symptoms and laboratory abnormalities. [4] It can affect any region of the body where lymph nodes are found, such as the neck, chest, abdomen, or mesentery. [5] Treatment varies depending on the subtype and severity of the disease, and may include anti-interleukin-6-directed therapies, rituximab, or other medications. [7] Castleman disease is a rare disease of lymph nodes and related tissues that is sometimes associated with human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8). [9] There are two main forms: unicentric CD and multicentric CD. Unicentric CD is a "localized" condition that is generally confined to a single set of lymph nodes, while multicentric CD is a "systemic" form that affects multiple regions of the body. [12] People with CD may experience symptoms such as lymph node swelling, flu-like symptoms, low levels of red blood cells (hemolytic anemia) or large amounts of immunoglobulins in the blood (hypergammaglobulinemia), and increased risk of serious infections due to a weakened immune system. [14] Castleman's disease is an uncommon benign lymphoproliferative disorder characterized by hyper-vascular lymphoid hyperplasia. It has no sex predilection, and the age of presentation ranges from 5 years to 70 years.

Symptoms of Castleman Disease

Castleman disease can cause a variety of symptoms, and the severity of these symptoms can range from mild to life-threatening.

• Mild symptoms: Gradual enlargement of lymph nodes, fatigue, and mild compressive symptoms [5].
• More severe symptoms: Flu-like symptoms, feeling of fullness in the abdomen, and problems with organ function [3].
• Life-threatening symptoms: Multi-organ failure, which can be a sign of abnormally enlarged lymph nodes [2].

Common signs and symptoms

Some common signs and symptoms of Castleman disease include:

• Widespread chronic swelling of the lymph nodes
• Enlargement of the liver and spleen
• Flu-like symptoms, such as fever and chills
• Fatigue and weakness
• Abdominal fullness and discomfort

References:

[1] Multicentric Castleman disease (MCD) involves multiple regions of enlarged lymph nodes, inflammatory symptoms and problems with organ function. [2] Castleman disease has a broad spectrum of disease severity, ranging from mild compressive symptoms and fatigue to life-threatening multi-organ failure. Symptoms ... [3] This can be a sign of abnormally enlarged lymph nodes. More severe symptoms of Castleman disease can include flu-like symptoms, a feeling of fullness in the ... [4] Signs and Symptoms. Castleman disease can cause a variety of symptoms and severity is very broad, ranging from gradual enlargement of lymph nodes with mild ... [5] Signs and Symptoms. Castleman disease can cause a variety of symptoms and severity is very broad, ranging from gradual enlargement of lymph nodes with mild ...

Diagnostic Tests for Castleman Disease

Castleman disease can be diagnosed through various tests, which help identify the abnormal growths in the lymph system and confirm the presence of the disease.

• Biopsy: A biopsy is a crucial diagnostic test for Castleman disease. It involves removing an enlarged lymph node and examining it under a microscope to identify features of Castleman disease [1].
• Imaging tests: Imaging tests such as X-rays, CT scans, or MRI can be performed to confirm that the involvement is unicentric (limited to one area) or multicentric (widespread) [2].
• Blood and urine tests: Blood and urine tests can reveal signs of inflammation, anemia, and other irregularities in the blood, which may indicate Castleman disease [5].
• Histopathologic examination: A pathological diagnosis is crucial for making accurate diagnosis of Castleman disease. In principle, the diagnosis requires an evaluation of the lymph node, including histopathologic examination to identify features such as hyaline-vascular, plasmacytic, or mixed variants [3][8].

These diagnostic tests help healthcare professionals confirm the presence of Castleman disease and determine its extent.

References: [1] - The diagnosis is made by histologic examination of an excised lymph node. [2] - Imaging should be performed to confirm that involvement is unicentric... [3] - Castleman disease can also be described as hyaline-vascular, plasmacytic, or mixed histopathologic variant based on the microscopic appearance. [5] - Diagnosing Castleman disease · Blood and urine tests [8] - A pathological diagnosis is crucial for making accurate diagnosis of Castleman disease.

Treatment Options for Castleman Disease

Castleman disease, also known as Castleman's syndrome, is a rare disorder characterized by the overgrowth of lymphoid tissue in various parts of the body. The treatment options for Castleman disease depend on its subtype and severity.

• Surgery: For unicentric Castleman disease (UCD), surgery is considered the first-line treatment for almost all cases [1]. A patient is considered cured after complete surgical excision.
• Immunotherapy: Rituximab, a humanized monoclonal antibody, is commonly prescribed to treat HHV-8-associated multicentric Castleman disease (MCD) [4].
• Siltuximab: This medication has been approved by the US Food and Drug Administration for use in Castleman disease, specifically for idiopathic multicentric Castleman disease (iMCD) [6]. Siltuximab is recommended as a preferred primary treatment for patients with HIV-negative HHV-8-associated MCD [3].
• Chemotherapy: In severe cases of Castleman disease, adjuvant combination chemotherapy may be recommended [7].

Treatment Approaches by Disease Severity

For patients with mild or moderate disease activity, siltuximab monotherapy administered every 3 weeks is the recommended first-line therapy [8]. Additional agents are recommended for more severe cases, tailored to the individual's disease severity.

Multiple Treatment Options Available

Though only one treatment (siltuximab) is FDA-approved for one subtype of Castleman disease, several well-established treatment approaches exist for the various subtypes. These include surgery, immunotherapy, and chemotherapy, among others [9].

References: [1] - Context result 1 [3] - Context result 3 [4] - Context result 4 [6] - Context result 6 [7] - Context result 7 [8] - Context result 8 [9] - Context result 9

Differential Diagnosis of Castleman Disease

Castleman disease, also known as Castleman lymphoma, is a rare disorder characterized by the abnormal growth of cells in the lymph nodes. The differential diagnosis of Castleman disease includes various conditions that can present with similar symptoms and characteristics.

Conditions to Consider:

• Autoimmune diseases: Conditions such as immunoglobulin G4-related disease, rheumatoid arthritis, systemic lupus erythematosus, and adult-onset Still's disease can mimic the symptoms of Castleman disease [8].
• Lymphomas: Hodgkin lymphoma and non-Hodgkin lymphoma are often considered in the differential diagnosis of Castleman disease, especially when there is a history of cancer or lymphadenopathy [3].
• Connective tissue diseases: Conditions such as scleroderma and dermatomyositis can present with similar symptoms to Castleman disease, including lymphadenopathy and systemic manifestations [4].
• Solid tumors: Atypical sequestration, hamartoma, and primary lung malignancy are among the solid tumors that can be considered in the differential diagnosis of Castleman disease [5].
• Infectious diseases: Conditions such as tuberculosis and histoplasmosis can present with lymphadenopathy and systemic symptoms similar to those seen in Castleman disease [1].

Diagnostic Challenges:

The differential diagnosis of Castleman disease is challenging due to its rarity and the fact that it can mimic many other conditions. A thorough medical history, physical examination, and diagnostic imaging studies are essential for making an accurate diagnosis.

References:

• [1] November 24, 2021 - The differential diagnosis of unicentric Castleman disease (UCD) includes other disorders that can present as a solitary enlarged lymph node and/or systemic symptoms.
• [3] by E Egorova · 2018 — Diagnosis CD was changed to the Hodgkin's lymphoma (HL) in three cases, to NHL in three cases, to the connective tissue disease and solid tumors in two cases ...
• [4] November 28, 2014 - PET scan revealed a mass measuring 68x80x55 mm extending from the left hilum out into the left upper lobe containing area of calcification with SUV max 4.8.
• [5] by D Wu · Cited by 139 — For a diagnosis of idiopathic HHV8-negative Castleman disease, cases must satisfy both major criteria and must have at least 2 of 11 potential minor criteria ( ...
• [8] by E Gündüz · 2021 · Cited by 17 — Differential Diagnosis. Autoimmune diseases (immunoglobulin G4-related disease, rheumatoid arthritis, systemic lupus erythematosus, adult ...