On 9th January 2021, NHS England published the UK Rare Disease Framework which aims to ensure that the lives of people living with rare diseases continues to improve by addressing the following issues: helping patients get a final diagnosis faster, increasing awareness of rare diseases among HCPs, better coordination of care and improving access to specialist care, treatment and drugs.

Castleman’s Disease (CD) is a heterogeneous group of lymphoproliferative disorders, characterised by lymph node enlargement with certain lymph node histopathological features, and a range of symptoms and clinical findings.

CD presents with vague symptoms that overlap with those of other autoimmune, malignant and infectious diseases.

CD is divided into two subtypes, based on the number of affected lymph nodes.

Unicentric CD (UCD) refers to localised lymphadenopathy in one lymph node site.

Multicentric CD (MCD) consists of multiple affected lymph node stations with a range of histopathology, accompanied by episodic systemic inflammation.
MCD is further classified into subgroups based on aetiology, HHV-8 positive MCD, POEMS associated MCD and idiopathic Multicentric Castleman’s Disease (iMCD).

iMCD is a rare, devasting disease that few clinicians will have come across in their daily practice.

Patients can experience symptoms of systemic inflammation that can interfere with their daily lives and, more seriously, significant organ damage due to the uncontrolled release of pro-inflammatory cytokines during a cytokine storm. Many of the symptoms associated with MCD, have been attributed to the excessive secretion of the cytokine interleukin-6 (IL-6).
Being able to identify signs of iMCD is important to allow prompt diagnosis and treatment.

No data exists which provides an accurate description of the number of patients with Castleman’s Disease in the UK. However based data from the USA it is estimated that there are approx. 160 patients living with iMCD in the UK.

The exact cause of iMCD is currently unknown, but there are three main hypotheses:
1. Pathogen Hypothesis
2. The autoimmune/auto-inflammatory hypothesis
3. The paraneoplastic hypothesis

Common symptoms iMCD patients may present with include:
1. Fever
2. Night Sweats
3. Weight Loss
4. Oedema
5. Anaemia
6. Lymphadenopathy
7. Kidney Dysfunction
8. Hepatosplenomegaly

Early diagnosis is essential to reducing mortality in iMCD patients, but diagnosis is often delayed because of the rarity of the disease and vague clinical symptoms. These symptoms can mimic other disease and there are currently no specific biomarkers for iMCD.

Patients suspected with Castleman’s Disease are referred and reviewed within the Specialist Integrated Haematological Malignancy Diagnostic Service (SIHMDS):
• Guy’s and St Thomas’ St Bartholomew’s
• Imperial College
• UCL
• Royal Marsden
• King’s College
• Bristol
• Southampton
• Leeds
• Sheffield
• Birmingham
• Nottingham
• Cardiff
• Manchester
• Newcastle
• Cambridge
• Oxford

The British Society of Haematology recently published guidelines*, in August 2021, to provide a framework for iMCD diagnosis, with a view to increasing the speed with which iMCD is recognised and diagnosed.

Diagnosis requires an interdisciplinary team of clinicians which include haematologists and pathologists, amongst others.

These guidelines detail diagnostic criteria that can be used to provide a definitive iMCD diagnosis and are composed of:
• Major criteria that must be fulfilled
• Minor criteria that must be partially fulfilled
(needs at least 2 of 11 criteria with at least 1 laboratory criterion)
• Exclusion criteria

Castleman’s Disease is a serious under diagnosed condition and there still remains a challenge in identifying and diagnosing CD patients correctly given the vague symptoms presented by CD patients. Disease awareness and education is key.

*The management of Castleman disease, British Society for Haematology
Oliver C. Lomas, Matthew Streetly, Guy Pratt, Jim Cavet, Daniel Royston, Stephen Schey,
Karthik Ramasamy and the British Society for Haematology (BSH) Committee

You can find EUSA Pharma on stand E54 at Oncology Professional Care, and see their session Malignancy of Unknown Origin (MUO), Lymphoma or Something Else? Demystifying the Diagnosis of Castleman Disease in the Early Diagnosis & Screening Theatre on 24 May at 13.45.