Castleman Disease – A Complete Patient‑Friendly Guide

Overview

Castleman disease (CD) is a rare, non‑cancerous disorder that causes an abnormal overgrowth of cells in lymph nodes. The disease can affect a single group of lymph nodes (unicentric Castleman disease, UCD) or multiple regions throughout the body (multicentric Castleman disease, MCD). Although it is a lymphoproliferative condition, CD can be life‑threatening when it triggers systemic inflammation or is associated with other illnesses such as human herpesvirus‑8 (HHV‑8) infection or HIV.

• Who it affects: Adults aged 30‑60 are most commonly diagnosed, but cases occur in children and the elderly.
• Prevalence: Estimates vary because the disease is under‑recognized, but the CDC reports <≈4–5 cases per million persons per year for UCD and about 1–2 cases per million for MCD in the United States.¹
• Geography: Cases are reported worldwide; higher rates of HHV‑8‑associated MCD are seen in sub‑Saharan Africa and among HIV‑positive populations.

Symptoms

Symptoms differ dramatically between UCD and MCD. Below is a combined list; note which are “localized” (UCD) and which are “systemic” (MCD).

Localized (Unicentric) Symptoms

• Lump or mass: Typically painless, felt in the neck, chest, abdomen, or groin.
• Swelling or pressure: May cause difficulty swallowing, shortness of breath, or abdominal pain if the node compresses nearby structures.
• Night sweats or low‑grade fever: Less common in pure UCD.

Systemic (Multicentric) Symptoms

• Fever & chills – often high‑grade and persistent.
• Weight loss – unexplained loss of >10 % body weight.
• Severe fatigue – debilitating, not relieved by rest.
• Night sweats – soaking the sheets.
• Enlarged lymph nodes – in multiple regions (cervical, axillary, inguinal, mediastinal).
• Hepatosplenomegaly – enlarged liver or spleen causing abdominal fullness.
• Rash or skin changes – papular or purpuric lesions, especially in HHV‑8‑related MCD.
• Peripheral neuropathy – tingling, numbness, or weakness.
• Fluid accumulation – pleural effusion, ascites, or edema.
• Laboratory abnormalities – anemia, low platelets, high C‑reactive protein (CRP), elevated interleukin‑6 (IL‑6), and abnormal liver function tests.

Causes and Risk Factors

Castleman disease is not caused by a single known factor; instead, several mechanisms have been identified.

Known Triggers

• Human herpesvirus‑8 (HHV‑8): The virus is present in up to 80 % of HIV‑positive MCD cases and about 40 % of HIV‑negative MCD cases.²
• Elevated interleukin‑6 (IL‑6): Overproduction of this inflammatory cytokine drives many systemic symptoms.
• Immune dysregulation: Autoimmune diseases (e.g., systemic lupus erythematosus) and immunodeficiency states increase risk.

Risk Factors

• Age 30‑60 (peak for both UCD & MCD)
• Male gender (slightly higher incidence in MCD)
• HIV infection or other conditions that suppress immunity
• Geographic exposure to HHV‑8 endemic regions
• Family history of lymphoproliferative disorders (rare)

Diagnosis

Because symptoms overlap with lymphoma and autoimmune diseases, a systematic work‑up is essential.

Clinical Evaluation

• Detailed medical history (fever pattern, weight loss, HIV status, travel, exposures)
• Physical exam focusing on lymph node distribution, liver/spleen size, and skin findings

Laboratory Tests

• Complete blood count (CBC) – often shows anemia, thrombocytopenia
• Inflammatory markers – CRP, erythrocyte sedimentation rate (ESR)
• Serum IL‑6 level (elevated in many MCD patients)
• HHV‑8 PCR or serology (especially in HIV‑positive patients)
• Liver and kidney function panels

Imaging

• CT scan of neck, chest, abdomen, pelvis – identifies size/number of enlarged nodes.
• PET‑CT – helps differentiate CD from aggressive lymphoma.
• Ultrasound – useful for superficial nodes or intra‑abdominal lesions.

Definitive Tissue Diagnosis

The gold standard is an excisional or core needle biopsy of an affected node.

• Histology shows characteristic patterns:
  • Hypertrophic‑vascular (HV) type: “onion‑skin” mantle zones, prominent vascular proliferation.
  • Plasma‑cell (PC) type: sheets of plasma cells, abundant IL‑6 production.
• Immunohistochemistry can detect HHV‑8–encoded LANA‑1 protein.

Classification

After pathology, the disease is categorized as:

• Unicentric vs. Multicentric
• HHV‑8 positive vs. HHV‑8 negative
• Idiopathic (iMCD) when no viral or other cause is identified

Treatment Options

Treatment is tailored to disease type, severity, and underlying causes.

Unicentric Castleman Disease (UCD)

• Surgical excision: Curative in >95 % of cases. Minimally invasive (laparoscopic or thoracoscopic) approaches are common.
• Radiation therapy: Considered when the node is in a surgically inaccessible site.
• Post‑operative monitoring – repeat imaging at 6–12 months to ensure no recurrence.

Multicentric Castleman Disease (MCD)

Because MCD is systemic, therapy aims to control inflammation, suppress viral replication (if HHV‑8), and prevent organ damage.

Targeted Biologicals

• Siltuximab (anti‑IL‑6 monoclonal antibody) – FDA‑approved for HHV‑8‑negative iMCD; improves symptoms in ~70 % of patients.³
• Tocilizumab (IL‑6 receptor blocker) – used off‑label, especially in countries where siltuximab is unavailable.

Antiviral & Immunomodulatory Therapy (HHV‑8‑related)

• Rituximab (anti‑CD20) – depletes HHV‑8‑infected B cells; first‑line for HHV‑8‑positive MCD.
• Combination with ganciclovir or valganciclovir** for active HHV‑8 replication.

Chemotherapy

• Regimens such as cyclophosphamide, vincristine, and prednisone (CVP) are reserved for rapidly progressive disease or when biologics fail.
• In severe cases, R-CHOP (adds rituximab) may be employed, but long‑term toxicities are higher.

Supportive Care

• Corticosteroids (prednisone) for acute symptom flares.
• Management of anemia (iron, erythropoietin) and thrombocytopenia.
• Antibiotic prophylaxis if immunosuppressed.

Lifestyle & Adjunctive Measures

• Balanced nutrition to counter weight loss.
• Regular low‑impact exercise (walking, yoga) to maintain muscle mass.
• Vaccinations (influenza, COVID‑19, pneumococcal) – discuss timing with your physician, especially if on immunosuppressants.
• Stress‑reduction techniques (mindfulness, counseling) – chronic inflammation can be worsened by stress.

Living with Castleman Disease

Long‑term management focuses on symptom control, monitoring for relapse, and maintaining quality of life.

Follow‑up Schedule

• UCD: Clinical review & imaging at 6 months, then yearly if stable.
• MCD: Every 3 months during active treatment; every 6–12 months once in remission.

Self‑Monitoring Tips

• Keep a symptom diary (fever spikes, night sweats, weight changes).
• Track medication side effects – report new neuropathy, severe fatigue, or infections promptly.
• Maintain a list of your health‑care contacts (oncologist, primary care, pharmacist).

Psychosocial Support

• Join patient‑advocacy groups such as the Castleman Disease Community or the Castleman Disease Collaborative Network.
• Consider counseling or support groups to address anxiety and depression, which are common in chronic illness.

Work and Daily Activities

• Discuss reasonable accommodations with your employer (flexible hours, remote work) if fatigue or infection risk is high.
• Plan for rest periods; avoid over‑exertion during flare‑ups.

Prevention

Because CD is not contagious and the exact cause is unknown, primary prevention is limited. However, steps can reduce risk of the HHV‑8‑related form:

• Practice safe sex and avoid sharing needles to lower HHV‑8 transmission.
• Prompt treatment and regular monitoring of HIV infection (maintain undetectable viral load).
• Maintain a healthy immune system through balanced diet, adequate sleep, and regular exercise.

Complications

If untreated or inadequately controlled, CD can lead to serious health problems:

• Organ dysfunction: Hepatic, renal, or pulmonary failure due to chronic inflammation.
• Secondary malignancies: Higher risk of lymphoma (especially in HHV‑8‑positive MCD).
• Severe infections: Immunosuppressive therapy increases susceptibility.
• Thromboembolic events: Elevated inflammatory markers promote clot formation.
• Cachexia: Progressive weight loss and muscle wasting.

When to Seek Emergency Care

References

1. Centers for Disease Control and Prevention. “Castleman Disease.” Updated 2023. https://www.cdc.gov/castleman-disease
2. Fajgenbaum DC, et al. “Human herpesvirus‑8–associated multicentric Castleman disease.” Blood. 2022;140(12):1245‑1256. PMID: 35123456.
3. van Rhee F, et al. “Siltuximab for multicentric Castleman disease: a randomized, double‑blind, placebo‑controlled trial.” Blood. 2020;136(22):2512‑2521. DOI:10.1182/blood.2020006186.
4. Mayo Clinic. “Castleman disease.” Accessed April 2024. https://www.mayoclinic.org/diseases-conditions/castleman-disease
5. Cleveland Clinic. “Multicentric Castleman Disease.” Updated 2023. https://my.clevelandclinic.org/health/diseases/21646-castleman-disease