OVERVIEW

What is Castleman disease?

Castleman disease (CD), also known as angiofollicular lymphoid hyperplasia or giant lymph node hyperplasia, is a chronic lymphoproliferative disorder first reported by Benjamin Castleman.

It is associated with human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8).

Patients may present with symptoms such as lymphadenopathy, fever, and weight loss; diagnosis typically requires histopathological examination.

Treatment often involves glucocorticoids, immunosuppressive therapy, and chemotherapy, with a poor prognosis. Untreated cases can be fatal.

What are the types of Castleman disease?

Castleman disease consists of two distinct types with markedly different prognoses: unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). Both types may develop malignancies, such as non-Hodgkin lymphoma.

Is Castleman disease common?

• Unicentric Castleman disease is rare, and there are no reliable estimates of its incidence. It typically affects younger adults, with a median age of onset around 35 years, and occurs equally in males and females.

• Patients with multicentric Castleman disease have a median age of onset between 50 and 65 years, with earlier onset in HIV-infected individuals. Approximately 50%–65% of cases occur in males.

SYMPTOMS

What are the symptoms of Castleman disease patients?

The clinical manifestations of unicentric and multicentric lymph node hyperplasia differ:

• Unicentric lymph node hyperplasia: Usually asymptomatic, often discovered during physical or imaging examinations when enlarged lymph nodes are found. Systemic symptoms such as fever, night sweats, and weight loss are limited to a small number of patients. Skin lesions like rashes, hemangiomas, and pemphigus may occur.

• Multicentric lymph node hyperplasia: Nearly all patients experience fever, with most exhibiting systemic symptoms like night sweats, weight loss, weakness, or fatigue. Lymphadenopathy is typically widespread and often accompanied by hepatosplenomegaly. Some patients may present with edema, body cavity effusions (manifesting as dyspnea, abdominal distension, increased abdominal girth, etc.), skin lesions (including rashes, hemangiomas, and pemphigus), and neurological changes.

CAUSES

What are the causes of Castleman disease?

Currently, little is known about the etiology and pathogenesis of Castleman disease. It is believed to be potentially associated with human immunodeficiency virus (HIV) and human herpesvirus 8 (HHV-8).

Both unicentric and multicentric lymphoproliferative disorders are linked to excessive release of interleukin-6 (IL-6) or related peptides, such as the IL-6 homolog encoded by the HHV-8 genome.

Multicentric lymphoproliferative disorder is more frequently associated with human herpesvirus 8 (HHV-8) infection, whereas unicentric lymphoproliferative disorder is less commonly related to HHV-8 infection or POEMS syndrome.

DIAGNOSIS

What tests are needed to diagnose Castleman's disease?

• Laboratory tests: Including complete blood count, erythrocyte sedimentation rate, lactate dehydrogenase (LDH), serum albumin, C-reactive protein, interleukin-6 (IL-6), immunofixation electrophoresis, etc., to determine the presence of anemia, thrombocytopenia, elevated erythrocyte sedimentation rate, hypoalbuminemia, increased C-reactive protein, elevated IL-6, and to rule out clonal plasma cell disorders. Serological tests for HIV and HHV-8 infections (also requiring venous blood samples) should also be performed.

• Imaging tests: Including CT, MRI, and PET-CT, which can indicate the presence of tissue masses, lymphadenopathy, or organ enlargement such as splenomegaly, and further clarify the nature of the masses or enlarged lymph nodes.

• If imaging suggests suspicious affected tissues and the patient's condition permits, a pathological examination via tissue biopsy can be performed. Castleman's disease requires pathological examination of affected tissues for definitive diagnosis. If the initial biopsy is inconclusive but clinical suspicion remains high, repeat biopsy may be necessary to confirm the diagnosis.

• During diagnosis, other conditions that may cause lymph node hyperplasia, such as rheumatoid arthritis, other connective tissue diseases, and HIV infection, should be ruled out.

TREATMENT

Which department should Castleman's disease patients visit?

This disease primarily manifests as lymphadenopathy of unknown origin, and patients are generally advised to visit the general surgery department.

How is Castleman's disease treated?

First, disease activity should be assessed through tests such as complete blood count, liver and kidney function with electrolytes, LDH, serum albumin, HHV-8/HIV serology, C-reactive protein, erythrocyte sedimentation rate, IL-6, VEGF, contrast-enhanced CT, and PET-CT. Additional evaluations should identify coexisting conditions that may influence treatment choices. Treatment varies depending on the classification.

Unicentric Castleman's disease (UCD):

• Complete surgical resection of the affected lymph node is curative and remains the gold standard for UCD. For large unresectable masses due to size or location, systemic therapy should be administered to achieve initial tumor reduction (similar to multicentric Castleman's disease treatment, discussed later), followed by surgical intervention.

• Systemic corticosteroids may alleviate symptoms but are not expected to shrink the tumor.

• Radiation therapy has also been used for UCD, but responses are limited. Patients with incompletely resected lesions still have a favorable prognosis, as residual masses may remain stable and asymptomatic for many years.

Multicentric Castleman's disease (MCD):

• There is no standard therapy. Treatment selection primarily depends on whether the patient is HIV/HHV-8 positive and the aggressiveness of the disease.

• Treatment options include: IL-6-directed therapy; anti-CD20 monoclonal antibody rituximab, with or without corticosteroids and/or cytotoxic chemotherapy;

• For HIV/HHV-8-positive patients, antiviral therapy with ganciclovir and ART.

• Surgical lymph node resection is ineffective for MCD.

• Splenectomy may temporarily improve symptoms in select patients.

The natural course of MCD varies:

• Indolent MCD may persist for months to years without progression.

• Rapidly progressive MCD can lead to death within weeks, particularly in HIV-infected individuals.

• Untreated MCD has a poor prognosis.

DIET & LIFESTYLE

What should Castleman disease patients pay attention to in daily life?

Regular outpatient follow-ups and tests such as blood routine, liver/kidney function, LDH, IL-6, and CT/PET-CT are required to monitor disease progression and adjust medications.

• For unicentric Castleman disease, patients without complications who have undergone surgery should maintain healthy habits with no specific restrictions.

• For multicentric Castleman disease, lifestyle adjustments should be based on disease status and medication. Prioritize rest, minimize external contact to prevent infections, and tailor activities to individual conditions.

PREVENTION

Can Castleman Disease Be Prevented?

Since the cause and pathogenesis of Castleman disease remain unclear, there is currently no reliable prevention method. It is important to avoid HIV/HHV-8 infection.

For patients already diagnosed with Castleman disease, especially those using glucocorticoids, immunomodulators (such as rituximab), or chemotherapy drugs, it is essential to avoid fatigue and crowded places to prevent infections.