Diagnosing Multicentric Castleman’s Disease

Multicentric Castleman’s Disease Diagnosis
Multicentric Castleman’s Disease Diagnosis

Multicentric Castleman’s Disease – A lymphoproliferative disease

A rare disease with potentially serious consequences

  • Multicentric Castleman’s Disease (MCD) is a rare disease of lymph nodes and related tissues1
  • MCD is a serious disorder associated with problems such as fatigue,1-3 malaise,4,5 night sweats,1-5 peripheral sensory neuropathy,1,5 anorexia,1-3 and skin rashes1,3-5
  • While it is not a cancer1, it increases the risk of developing non-Hodgkin’s lymphoma1,2
  • A recent analysis of a US claims database estimated the incidence rate of MCD to be 5 to 6 per million person-years, which is equivalent to 1,100 to 1,300 Americans6

Overproduction of IL-6 plays an important role

  • Clinical evidence suggests that excess IL-6, an inflammatory regulating cytokine, plays an important role in the etiology of MCD2
  • Excess IL-6 leads to systemic inflammatory manifestations3
Multicentric Castleman’s Disease Diagnosis

Multicentric Castleman’s Disease Signs and Symptoms

Recognizing and diagnosing Multicentric Castleman’s Disease can be challenging

  • Typically, patients with MCD are in their 40s or 50s at the time of diagnosis3
  • To diagnose MCD, a lymph node biopsy is essential, ideally, the biopsy would be examined by a hematopathologist1
  • The signs and symptoms of MCD may resemble those seen in conditions such as lymphoma, HIV infection, chronic viral infections, rheumatoid arthritis, lupus, and Sjögren syndrome4

Multicentric Castleman’s Disease can cause a number of symptoms, which may include:

  • Enlarged lymph nodes (often in the neck, underarm, and groin areas), which can be seen or felt as lumps under the skin1,4
  • Enlarged liver, spleen, or other organs, which may been seen or felt as masses under either side of the rib cage1
  • Fever1,5
  • Weakness and tiredness (fatigue)1-3
  • Night sweats (that soak the sheets)1-5
  • Unintentional weight loss1-5
  • Loss of appetite1-3
  • Nausea and vomiting1
  • Numbness and tingling (neuropathy)1
  • Leg swelling (edema)1,3
  • Skin rashes1,3-5

The symptoms of MCD usually come on gradually.2 For some patients, however, the symptoms seem to begin after they have had some sort of viral infection.2

Multicentric Castleman’s Disease Diagnosis

Diagnosing Multicentric Castleman’s Disease

Because it resembles many other disorders, early identification of Multicentric Castleman’s Disease can be challenging.7 The lymph node abnormalities can resemble those in conditions such as chronic viral infections, rheumatoid arthritis, lupus, Sjögren syndrome, HIV infection, lymphoma, and drug sensitivity.4

A Multicentric Castleman’s Disease diagnosis involves a work-up to rule out other possible causes, and to identify histology and laboratory abnormalities that are characteristic of the disease.2

ANA anti-nuclear antibody
CBC complete blood count
CRP C-reactive protein
CT computed tomography
CT-PET computed tomography
– positron emission tomography
HHV-8 human herpesvirus-8
PCR polymerase chain reaction
VEGF vascular endothelial growth factor
WESR Westergren erythrocyte sedimentation rate 

SUGGESTED WORK-UP FOR MULTICENTRIC CASTLEMAN’S DISEASE3

Excisional lymph node biopsy

Pathology, exclude clonal malignancy

Virology

HIV and HHV-8 serology with quantitative PCR, if possible

Cytokines

IL-6, VEGF

Acute phase reactants

WESR, CRP, fibrinogen

General

CBC, renal and liver function

Immunology

ANA, others as indicated

Endocrine abnormalities

Thyroid function tests, others as indicated

Plasma cell dyscrasias

Immunoglobulins, urine and protein electrophoresis and immunofixation, light chains, bone marrow, 24-hour urine for protein qualification

Organ function

Echocardiogram, pulmonary function

Imaging

CT of neck, chest, abdomen, pelvis; CT-PET

Neurology

Nerve conduction as indicated

Contraindications

  • Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT®.

Adverse Reactions

  • The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

References

  1. Castleman’s Disease. American Cancer Society. http://www.cancer.org/cancer/castlemandisease/detailedguide/castleman-disease-what-is-castleman-disease. Accessed August 4, 2016.
  2. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and theapy. Clin Adv Hematol Oncol 2010;8(7):486-498.
  3. El-Osta HE, Kurzrock R. Castleman’s disease: from basic mechanisms to molecular therapeutics. Oncologist. 2011;16(4):497-511.
  4. Casper C. The ­aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol. 2005;129(1):3-17.
  5. Dispenzieri A, Gerta MA. Treatment of Castleman’s Disease. Curr Treat Opt Oncol. 2005;6:255-266.
  6. Mehra M; Cossrow N, Stellhorn R, et al. Use of a claims database to characterize and estimate the incidence of Castleman’s disease. Poster 4253. American Society of Hematology. Presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta, GA.
  7. Bonekamp D, Horton KM, Hruban RH, Fishman EK. Castleman disease: the great mimic. Radiographics. 2011;31(6):1793-1807.