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Health condition · Clinically reviewed

Castleman disease, unicentric, multicentric and the IL-6 story.

A rare lymphoproliferative disorder with several faces. Surgery cures most unicentric cases. Multicentric disease is a specialist, cytokine-driven condition where IL-6 blockade has changed outcomes.

A radiographer guides a patient onto the bed of an advanced 3 Tesla MRI scanner in a London imaging suite

Why trust this guide

  • 01

    Clinically reviewed

    Written by our editorial team and reviewed by a UK haematology clinician before publication.

  • 02

    Sourced from guidance

    Checked against the Castleman Disease Collaborative Network, NCCN and peer-reviewed literature.

  • 03

    Current for 2026

    Reflects modern practice including siltuximab as first-line for idiopathic multicentric disease.

Key facts

Castleman disease at a glance.

The essentials, in plain English. What it is, the main subtypes, and the therapies that matter in current UK practice.

  • What it is

    A rare heterogeneous lymphoproliferative disorder, also called angiofollicular lymph node hyperplasia. Cytokine-driven, with IL-6 at the centre.

  • Unicentric (UCD)

    Single node or region. Usually young adults. Often asymptomatic. Surgical resection is curative in most cases.

  • Multicentric (MCD)

    Multiple nodal regions with systemic inflammation. Subtypes: HHV-8 associated, idiopathic (iMCD) and POEMS-associated.

  • iMCD and TAFRO

    Idiopathic MCD is HHV-8 and HIV negative. The TAFRO subtype adds thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly.

  • Histology

    Hyaline vascular pattern in around 90 percent of UCD. Plasma cell or mixed variants are more common in MCD.

  • First-line for iMCD

    Siltuximab, an anti-IL-6 monoclonal antibody, is the evidence-based standard per NCCN guidance.

Why this guide matters

A rare disease that needs a specialist path.

Castleman disease sits at the crossroads of haematology, oncology and immunology. The three points below shape everything else on this page.

  • Subtype guides treatment

    Unicentric, HHV-8 associated, idiopathic and POEMS-associated disease are treated very differently. Accurate subtyping is the whole ballgame.

  • IL-6 is the therapeutic target

    For idiopathic multicentric disease, siltuximab blocks the cytokine that drives inflammation. Outcomes have improved substantially.

  • MDT care changes outcomes

    Care under a haematology MDT with links to the CDCN gives access to evidence-based regimens, trials and specialist nursing.

How the diagnosis is made

From a suspicious node to a subtype and a plan.

The steps a UK haematology service will normally follow, in order, so you know what to expect and why each is important.

  1. 01

    Confirming

    Excisional lymph node biopsy

    Required for diagnosis. Histology plus immunohistochemistry including HHV-8 LANA, IL-6, CD138 and kappa/lambda light chains.

  2. 02

    Confirming

    HIV and HHV-8 testing

    Every patient. Splits multicentric disease into HHV-8 associated versus idiopathic and guides treatment.

  3. 03

    Confirming

    Inflammatory and marrow bloods

    FBC, LDH, IL-6, VEGF, CRP, ESR, immunoglobulins, serum electrophoresis and free light chains.

  4. 04

    Staging

    CT and PET-CT staging

    CT chest, abdomen and pelvis plus PET-CT to map nodal regions, measure lesions and stage the disease.

  5. 05

    Staging

    Subtype and CDCN criteria

    Histological subtyping and the Castleman Disease Collaborative Network criteria: two major plus at least two minor.

  6. 06

    Planning

    Exclude mimics

    Rule out lymphoma, POEMS syndrome, autoimmune disease, infection and IgG4-related disease before treatment.

  7. 07

    Planning

    Specialist MDT referral

    Haematology-led MDT with input from a specialist Castleman service and CDCN network expertise.

Typical timeline: biopsy to a treatment plan within a few weeks in a specialist service.

Symptoms

What Castleman disease actually looks like.

Unicentric disease is often silent. Multicentric disease is a systemic, cytokine-driven illness. The features below help you recognise both, and the flags that mean urgent review.

  • Lymphadenopathy

    Localised in unicentric disease. Generalised in multicentric disease, often bulky and progressive.

  • Fever and night sweats

    B-symptoms driven by IL-6 and acute phase response. A hallmark of multicentric disease.

  • Fatigue and weight loss

    Constitutional symptoms that track with cytokine activity and inflammatory burden.

  • Hepatosplenomegaly

    Enlargement of liver and spleen, common in multicentric disease and the TAFRO subtype.

  • Effusions and oedema

    Pleural effusions, ascites and anasarca, particularly prominent in TAFRO variant iMCD.

  • Rash and neuropathy

    Skin changes and peripheral neuropathy, sometimes overlapping with POEMS-associated disease.

  • Cytopenias and hypoalbuminaemia

    Anaemia, thrombocytopenia and low albumin. Polyclonal hypergammaglobulinaemia is typical.

  • Red flag - AL amyloidosis

    A recognised complication. New proteinuria, cardiac or neurological signs warrant urgent review.

Treatment

How Castleman disease is treated in the UK.

Surgery cures most unicentric disease. Multicentric disease is treated by subtype: rituximab-based therapy for HHV-8 disease, siltuximab first-line for idiopathic disease, and specific regimens for TAFRO and POEMS.

  • Surgical resection (UCD)

    The definitive treatment for unicentric disease. Complete excision is usually curative with an excellent prognosis.

  • Radiotherapy (UCD)

    An option when a unicentric lesion is unresectable due to location or comorbidity.

  • Siltuximab (iMCD first-line)

    Anti-IL-6 monoclonal antibody. Durable responses and the evidence-based standard for idiopathic multicentric disease per NCCN.

  • Tocilizumab

    Anti-IL-6 receptor antibody. A recognised alternative to siltuximab when access or tolerance is an issue.

  • Rituximab-based therapy (HHV-8)

    Rituximab, often with etoposide or liposomal doxorubicin, is the backbone for HHV-8 associated MCD. HAART is added for HIV.

  • Rituximab plus chemotherapy

    Rituximab with CHOP or CVP for severe or refractory iMCD not controlled with IL-6 blockade.

  • TAFRO regimens

    Combinations of corticosteroids, rituximab, cyclosporin and siltuximab for the TAFRO subtype of iMCD.

  • Corticosteroids and emerging

    Steroids support acute control. Bortezomib, IMiDs and JAK inhibitors are emerging options in relapsed disease.

Monitoring

Response is tracked with inflammatory markers (CRP, ESR), IL-6, FBC, LFTs and repeat imaging. Care is coordinated by a haematology MDT with input from a specialist Castleman service, the CDCN and a clinical nurse specialist.

What this guide is based on

The sources behind every claim on this page.

International specialist guidance and peer-reviewed consensus criteria, current at the time of last review.

Key references

Guidelines and standards we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your haematology team knows your history and imaging and can tell you which parts apply to you. If in doubt, contact your specialist nurse.

  • Castleman Disease Collaborative Network (CDCN). International diagnostic and treatment guidelines.

  • NCCN Guidelines. Castleman disease.

  • van Rhee F et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.

  • Fajgenbaum DC et al. HHV-8 negative, idiopathic multicentric Castleman disease consensus diagnostic criteria.

Red flags

When Castleman disease needs urgent attention.

Most patients are managed as outpatients under a haematology service. These are the situations that need same-day contact with your specialist team.

  • TAFRO flare

    Rapid onset thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Needs urgent inpatient haematology review.

  • AL amyloidosis

    New proteinuria, cardiac failure or unexplained neuropathy warrants urgent screening and specialist input.

  • Severe cytokine storm

    Marked fever, hypotension and multi-organ dysfunction driven by IL-6. Escalate for IL-6 blockade and supportive care.

  • Airway or vascular compression

    Bulky mediastinal or cervical disease pressing on airway or great vessels. Consider urgent imaging and surgical review.

  • HHV-8 with Kaposi sarcoma

    Concurrent Kaposi sarcoma in HIV positive patients needs coordinated oncology, haematology and HIV care.

  • Rapid effusion accumulation

    New pleural effusion, ascites or pericardial fluid needs drainage, cytology and prompt escalation.

  • Transformation to lymphoma

    Uncommon but recognised. Any change in nodal behaviour warrants repeat biopsy.

  • Neurological POEMS features

    Progressive peripheral neuropathy with organomegaly, endocrinopathy, M-protein and skin changes needs a POEMS workup.

  • Sepsis on immunosuppression

    Rituximab, chemotherapy and steroids increase infection risk. Any fever needs same-day assessment.

Living with it

A rare condition, with a growing evidence base.

Four things that make the biggest difference over the long haul: a specialist team, tracked markers, a named nurse and a patient community that understands the disease.

A quiet reminder

You are not meant to manage this alone.

Rare disease is a team sport. The right service, the right nurse and the right patient community shorten every difficult moment.

  1. 01 Team

    Stay under a specialist service

    Castleman disease is rare. Care is best coordinated by a haematology MDT with access to CDCN expertise.

  2. 02 Monitor

    Know your markers

    CRP, ESR, IL-6, immunoglobulins, FBC and LFTs are tracked over time. Rising markers can predict a flare.

  3. 03 Support

    Use a specialist nurse

    A clinical nurse specialist coordinates infusions, monitors side effects and is the fastest route back into the service.

  4. 04 Community

    Connect with the CDCN

    The Castleman Disease Collaborative Network offers patient resources, research updates and peer support.

Frequently asked

Everything we get asked about Castleman disease.

Quick answers on subtypes, diagnosis, siltuximab, prognosis and where to get specialist care.

  • What is Castleman disease?

    A rare lymphoproliferative disorder, also known as angiofollicular lymph node hyperplasia. It is heterogeneous and cytokine-driven, with interleukin-6 (IL-6) at the heart of inflammation, B-cell proliferation and the acute phase response.

  • What is the difference between unicentric and multicentric disease?

    Unicentric Castleman disease (UCD) affects a single node or region and is usually cured by surgical resection. Multicentric Castleman disease (MCD) affects multiple regions with systemic features and needs medical therapy, guided by whether it is HHV-8 associated, idiopathic (iMCD) or POEMS-associated.

  • What is idiopathic multicentric Castleman disease (iMCD)?

    iMCD is multicentric disease that is both HHV-8 negative and HIV negative. The TAFRO subtype adds thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly, and behaves more aggressively than the typical form.

  • Is Castleman disease a cancer?

    It is not a cancer in the traditional sense, but it is a lymphoproliferative disorder that can behave aggressively and can rarely transform into lymphoma. It is managed by haematology and oncology teams and treated with drugs used in blood cancer.

  • What is siltuximab and why is it first-line for iMCD?

    Siltuximab (Sylvant) is an anti-IL-6 monoclonal antibody that directly blocks the cytokine driving the disease. Randomised evidence shows durable responses and it is the evidence-based first-line therapy for iMCD in NCCN and CDCN guidance.

  • What is the prognosis?

    Unicentric disease has an excellent prognosis after resection. Multicentric disease outcomes depend on subtype: HHV-8 associated disease responds well to rituximab-based therapy, and iMCD outcomes have improved substantially with IL-6 blockade, though TAFRO variant remains more challenging.

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