About iMCD

Castleman Disease (CD) is a collection of rare inflammatory blood disorders in which lymphocytes, a type of white blood cell, are over produced leading to enlarged lymph nodes.¹ CD can affect a person regardless of their age, gender, or race.^1,2,4 It is classified into distinct clinical subtypes based on the number of enlarged lymph node regions, histopathological features, and clinical presentation.^1-3 All types of CD may be symptomatic, progressive, and require treatment.^{1, 5} Idiopathic multicentric CD (iMCD) is a subset of CD involving multiple groups of enlarged lymph nodes in people who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.^5,6 Each year, between 3-4 people among every million in the general population are estimated to be diagnosed with iMCD.² This rare, difficult-to-diagnose condition can have serious and potentially life threatening consequences.^5-7

Symptoms: iMCD can present with a variety of symptoms and laboratory abnormalities that can be mistaken for other mimicking diseases.⁵ Patients often have serious comorbidities and may have multiple organ dysfunction or failure.^6,7

Common clinical signs and symptoms of iMCD may include: ^6-9

• Enlarged lymph nodes (multiple regions)
• Flu like symptoms: Night sweats, fever, weight loss, fatigue and weakness
• Laboratory findings: Anemia, elevated C- reactive protein, low albumin levels, elevated ESR, IL-6 and VEGF, high immunoglobulin levels
• Organ dysfunction: Enlarged liver or spleen, renal dysfunction
• Skin lesions
• Edema
• Respiratory symptoms, excess build-up of fluids in the lung

Diagnosis

iMCD diagnosis requires histopathological and clinical assessment for major, minor, and exclusion criteria as outlined by the diagnostic guidelines.⁶ Diagnosing iMCD is challenging due to lack of unique biomarkers and overlapping symptoms with infectious, immune, and malignant diseases. Diagnostic delays among patients with CD contribute to an overall increase in the burden of disease and an increase in morbidity and mortality for these patients.^10-11

Causes

iMCD pathology is poorly understood and the exact cause is unknown. The disease pathology is associated with a hyperinflammatory state and most likely to be driven by cytokines, specifically, interleukin-6 (IL-6). ^11-12

IL-6 is a cytokine that activates an inflammatory cascade across many tissues and organs.^12-13 Most signs and symptoms of iMCD have been linked to IL-6, and overproduction of IL-6 is a key proposed driver of iMCD, however, the cause of increased IL-6 in iMCD is currently unknown.^12-15