Castleman Disease (CD) (BJH 2017) 

HHV8 Infection

IL-6 pathway

Data used in these notes based on Oskenhendle case series of >200 patients

Further updates in 2026 from a Castleman’s webinar

 

Epidemiology

Any age group from adolescents to elderly

Male > Female

Estimated ~1500 cases per year in UK

Pathophysiology 

Multicentric CD characterised by episodic inflammatory symptoms & reactive lymphadenopathy

Chaotic in behavior & life-threatening with MOF 2o to excess IL-6 & other cytokines (inc. VGEF)

HHV8 infection appears to drive majority of cases. HIV also significant.

The excess IL-6 is viral in origin in HHV8 MCD, and human in iMCD

History of Medicine: 1954 Castleman et al; 1989 IL-6 identified as key driver; 1994 HHV8 identified as a cause

 

Classification

 

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TAFRO = Thrombocytopenia, Anasarca, BM fibrosis, Renal dysfunction & Organomegaly

IPL-type iMCD = Idiopathic Lymphadenopathy w/ Polyclonal Hyperimmunoglobulinaemia

 

Aggressiveness of disease

HIV neg HHV8 MCD > HIV pos HHV8 MCD > iMCD

 

Histology

UCD                – hyaline vascular morphology

HHV8 MCD     – large plasmablastic HHV8+ cells

iMCD               – plasmacytic morphology with polyclonal proliferation

 

Diagnostic Pathway

 

  1. Exclude diagnosis that present CD-like histopathology

    • E.g. HL, NHL, POEMS, Plasmacytoma, AI (SLE, Sjogrens, IgG4 disease)

  2. Stage the disease – UCD includes multiple LN within a single station

  3. Immunohistochemistry for HHV8

  4. Context of HIV infection

 

UCD

Median age 35, M = F

Asymptomatic or mildly symptomatic

Severe complications rare but included:

  • paraneoplastic pemphigus, polyneuropathy, failure to thrive, BOOP, AIHA

 

Normal FBC

2 yr OS 98%

 

Mx: Surgical resection (<10% relapse), Radiothwerapy, W&W, Steroids, Tocilizumab, Rituximab

iMCD

Median age 47, M > F

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Associations: Consanguinous parents, Hep C, IBD

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

2 yr OS 100%

 

TAFRO - thrombocytopenia, anasarca, fever, reticular marrow fibrosis, organomegaly

TAFRO-like presentations of iMCD have a poorer prognosis and worse response to treatment

IPL-type - Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinaemia

IPL-type typically thrombocytosis, hypergammaglobulinaemia and less severe oedema

Mx: Steroids (50% response), Siltuximab/Tociliz (100% response), Ritux (60% response), Etoposide, W&W

HIV negative, HHV8 positive MCD

Median age 65

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Haemophagocytic syndrome, Kaposi sarcoma

Associations: Consanguinous parents, Hep B/C, thymoma, MSM, immunosuppressant usage

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

75% DAT +, 40% MGUS

2 yr OS 89%

 

Mx: Etoposide, Rituximab, Steroids, Siltuximab/Tocilizumab

HIV positive, HHV8 positive MCD

Median age 41

Fever, splenomegaly, oedema, effusions, resp symptoms, renal impairment

Haemophagocytic syndrome, Kaposi sarcoma

 

Anaemia, Thrombocytosis/penia, Raised CRP, Low Albumin, Raised Ig’s

75% DAT +, 40% MGUS

2 yr OS 77% (not statistically different to HIV- patients)

 

Mx: Etoposide, Combination Chemo, Steroids, Rituximab, Siltuximab/Tocilizumab

Siltuximab

Anti-IL6 monoclonal antibody

NICE approved in 2023 (Tocilizumab is not as of 2026)

Lancet Oncology 2014: HIV-/HHV8- MCD. 76 patients. Siltuximab vs placebo + best supportive care

SE: Rash, itching, oedema, weight gain, infection