Guidelines that can help diagnose iMCD

In order to diagnose a patient with idiopathic multicentric Castleman disease (iMCD), you must ensure they meet both Major Criteria and at least 2 of the 11 Minor Criteria, including ≥1 laboratory abnormality, and rule out diseases in the Exclusion Criteria.1

Major Criteria (need both)

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Histology consistent with Castleman disease (CD)

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≥2 enlarged lymph node groups

Minor Criteria (need ≥2, with ≥1 laboratory criterion)

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Clinical abnormality

  • Constitutional symptoms
  • Large spleen and/or liver
  • Fluid accumulation
  • Violaceous papules
  • Lymphocytic Interstitial pneumonitis
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Laboratory abnormality

  • Elevated C-reactive protein
  • Anemia
  • Thrombocytopenia
  • Hypergammaglobulinemia
  • Hypoalbuminemia
  • Renal dysfunction

Exclusion Criteria

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Exclude diseases that iMCD can mimic, such as autoimmune, malignant, and infectious diseases.

You can download a detailed, print-ready version of the Castleman Disease Collaborative Network diagnostic criteria, which includes a checklist that can help you during the diagnostic process.

DOWNLOAD
Pull down to reveal core biopsy
Graphic showing needle core biopsy, also known as incisional biopsy, may not be enough to confirm idiopathic multicentric Castleman disease.
Graphic showing needle core biopsy, also known as incisional biopsy, may not be enough to confirm idiopathic multicentric Castleman disease.
biopsy details
Regressed Germinal Center
biopsy detail #1
Regressed Germinal Center
biopsy detail
Regressed Germinal Center

An excisional biopsy ensures pathologic confirmation

A lymph node biopsy is necessary to confirm the diagnosis of iMCD.1 There are two types of biopsies2:

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Incisional (Core) Biopsy

Only extracts a small part of the enlarged lymph node

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Excisional Biopsy

The enlarged lymph node is removed completely

The hallmarks of iMCD may be missed in an incisional biopsy,3 as shown in the image. The ideal way to diagnosis iMCD is with an excisional biopsy.4

The iMCD diagnostic journey may involve multiple specialists

For a patient who potentially has iMCD, the diagnostic journey may start at their primary care physician’s (PCP’s) office or at a hospital. Initially, doctors may suspect infectious, autoimmune, or malignant disorders, and patients may then be referred to other specialists.

If all other conditions have been ruled out, then doctors may perform an excisional biopsy, which may be the most effective way to diagnose this condition.1,4

Potential patient journey

This patient journey is not a complete representation of all the
doctors a patient may see in their journey to diagnosis.

Potential patient journey - Sylvant
Physician diagnose icon Sylvant

A physician cannot diagnose iMCD without the help of a pathologist.1

References: 1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657. 2. Early detection, diagnosis, and staging of Castleman disease: tests for Castleman disease. American Cancer Society. https://www.cancer.org/content/dam/CRC/PDF/Public/8596.00.pdf. Revised February 2, 2018. Accessed August 15, 2022. 3. Allin D, David S, Jacob A, Mir N, Giles A, Gibbins N. Use of core biopsy in diagnosing cervical lymphadenopathy: a viable alternative to surgical excisional biopsy of lymph nodes? Ann R Coll Surg Engl. 2017;99(3):242-244. 4. Gaurin GE, da Costa Dourado CM. Castleman disease. Medscape. https://emedicine.medscape.com/article/2219018-overview. Updated November 24, 2021. Accessed August 15, 2022. 5. Infectious disease. American College of Physicians. https://www.acponline.org/about-acp/about-internal-medicine/subspecialties-of-internal-medicine/infectious-disease. Accessed August 15, 2022. 6. Rheumatologist. Dorland's Medical Dictionary Online. https://www.dorlandsonline.com/dorland/definition?id=43710. Accessed August 15, 2022. 7. Pathology. Dorland's Medical Dictionary Online. https://www.dorlandsonline.com/dorland/definition?id=37219. Accessed August 15, 2022. 8. Pathologist. Dorland's Medical Dictionary Online. https://www.dorlandsonline.com/dorland/definition?id=37218&searchterm=pathologist. Accessed August 15, 2022.

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SYLVANT® (siltuximab) for injection

INDICATIONS AND USAGE

SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

SYLVANT® (siltuximab) for injection

INDICATIONS AND USAGE

SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.

Concurrent Active Severe Infections: Do not administer SYLVANT to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute Phase reactants such as C-reactive protein (CRP). Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.

Vaccinations: Do not administer live vaccines to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.

Infusion Related Reactions and Hypersensitivity: Stop the infusion of SYLVANT if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT.

Stop the infusion if the patient develops a mild to moderate infusion reaction. If the reaction resolves, the SYLVANT infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions.

Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.

Gastrointestinal (GI) Perforation: Gastrointestinal (GI) perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.

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

Cytochrome P450 Substrates: Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).

Pregnancy and Lactation: SYLVANT may cause embryo-fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. Advise females not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.

Dosing and Administration: Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases, Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Before prescribing SYLVANT, please read the full Prescribing Information.

For your idiopathic multicentric Castleman disease (iMCD) Patients Taking SYLVANT® (siltuximab)

R.A.R.E.® can help

  • Co-pay assistance
  • Benefit investigations
  • Prior Authorization and Appeals Support:
    Phone: 1-855-299-8844
    Fax: 1-888-223-1746

One on one support

Helga will call enrolled patients to help:

  • Educate and answer questions about iMCD and SYLVANT
  • Help with access to SYLVANT medication
  • Connect them with other iMCD educational resources
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