Castleman disease

Disease Description (Causes and Symptoms)

Castleman disease is a rare disease characterized by abnormal proliferation of lymph nodes (a lymphoproliferative disorder). The disease is primarily divided into the following two clinical types.

• Unicentric: Limited to one lymph node or a group of adjacent lymph nodes. It can usually be cured by complete resection of the single lesion.
• Multicentric (MCD): Accompanied by generalized lymph node enlargement and systemic symptoms. The prognosis varies, and immunosuppressive or anti-cytokine treatment is required.

Causes and pathophysiology:

• Excessive production of interleukin-6 (IL‑6) is an important pathogenic mechanism, causing systemic inflammation and proliferation of B cells/plasma cells.
• Human herpesvirus‑8 (HHV‑8, KSHV) infection plays a key role, particularly in HHV‑8-associated MCD (especially common in people with HIV infection).
• Histologic subtypes: hyaline-vascular, plasma cell, and mixed types.

Main symptoms:

• Asymptomatic or gradual lymph node enlargement
• Fever, generalized fatigue, weight loss, night sweats
• Anemia, hypoalbuminemia, hypergammaglobulinemia (increased levels of multiple immunoglobulins)
• Edema (related to hypoalbuminemia/nephrotic syndrome), proteinuria, hepatosplenomegaly, pleural effusion, etc.
• In severe cases, systemic inflammatory response and possible organ failure

Treatment Methods

Standard treatment (varies by type):

• Unicentric
  • Complete surgical resection: Therapeutic and diagnostic standard. Usually curative.
  • If surgery is not possible, low-dose radiation therapy may control the lesion.
• Multicentric
  • Anti-IL‑6 treatment: siltuximab (an anti‑IL‑6 antibody) has demonstrated efficacy for idiopathic MCD (iMCD). tocilizumab (an anti‑IL‑6 receptor antibody) is also used.
  • Rituximab (anti‑CD20): Used especially in HHV‑8-associated disease or when B-cell accumulation is prominent. Used alone or in combination with chemotherapy.
  • Chemotherapy (e.g., CHOP-based regimens): For severe/rapidly progressive MCD or when lymphoma is suspected.
  • Steroids: Used for symptom relief and bridge therapy.
  • HIV/HHV‑8-positive patients: Antiretroviral therapy (ART) is important; antiviral drugs (e.g., the ganciclovir class) may be considered in some cases.
  • Refractory/relapsed disease: Intensive treatment, such as autologous/allogeneic hematopoietic stem cell transplantation, may be considered.

Supportive care:

• Blood transfusions (anemia), immunoglobulin (low immune status), diuretics and albumin supplementation (edema/hypoalbuminemia), and treatment of nephrotic syndrome
• Infection prevention (vaccination recommended; live vaccines prohibited during immunosuppressive treatment)
• Regular blood tests and imaging follow-up

Precautions (including self-care):

• The risk of infection increases with immunosuppressive and biologic agent use — seek medical attention immediately if fever or respiratory symptoms occur.
• Vaccines (especially pneumococcal and influenza vaccines) are recommended, but avoid live vaccines during treatment.
• Long-term immunosuppression may increase the risk of developing malignant lymphoma, Kaposi sarcoma, and other conditions.

Checklist Before an Outpatient Visit (Including Sample Questions)

Items/documents that are helpful to prepare or submit:

• List of currently used medications (including prescription drugs, over-the-counter drugs, and supplements)
• Past medical history and surgical history, and HIV test results (if available)
• Recent blood test results (CBC, general chemistry, albumin, creatinine, liver function, immunoglobulins) and urinalysis (proteinuria)
• Existing imaging (CT, MRI, PET‑CT) and pathology (biopsy) reports
• Record of symptom changes: fever patterns, weight changes, night sweats, changes in lymph node size, and the timing and location of edema if it occurs

Examples of questions to record in advance for the doctor during an outpatient visit:

• When did the symptoms begin (date/pattern)?
• Have there been any recent changes in weight or worsening of symptoms such as fever or night sweats?
• Information about current medications and previous treatments (especially immunosuppressants/anticancer drugs)

General Examples of Questions to Ask the Doctor

• Is my disease type unicentric or multicentric? What is the histologic subtype?
• What are my treatment options, and what are the expected benefits and major side effects of each treatment?
• What tests do I need during treatment, and how often should they be performed (CBC, liver and kidney tests, imaging, etc.)?
• Which vaccines do you recommend to prevent infections? Are there any activities or medications I should avoid during immunosuppressive treatment?
• If I am planning a pregnancy or breastfeeding, what are the effects of treatment and the recommendations?

Examples of Disease-Specific Questions

• Are my HHV‑8 (or HIV) test results positive? How will the treatment plan change based on the results?
• Is the lesion amenable to complete surgical resection? If not, how much control do you expect to achieve with radiation or local treatment?