People with iMCD have enlarged lymph nodes in multiple regions and often have flu-like symptoms, abnormal findings on blood tests, and dysfunction of vital organs, such as the liver, kidneys, and bone marrow.

Patients with iMCD may experience enlarged lymph nodes in multiple lymph node regions; systemic symptoms (fever, night sweats, unintended weight loss, fatigue); enlargement of the liver and/or spleen; extravascular fluid accumulation in the extremities (edema), abdomen (ascites), or lining of the lungs (pleural effusion); lung symptoms such as cough and shortness of breath; and skin findings such as cherry hemangiomas.

[1] In cases where IL-6 does play a role, the underlying cause of elevated IL-6 levels and the cells responsible for producing IL-6 remain unknown.

[citation needed] iMCD is diagnosed according to evidence-based consensus diagnostic criteria, which require a thorough evaluation including patient history, physical exam, laboratory testing, radiologic imaging, and microscopic analysis (histology) of biopsied tissue from an enlarged lymph node.

[1] Patients may also have elevations of molecules involved in inflammation (cytokines), such as Interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF).

[4] Radiologic imaging will demonstrate enlarged lymph nodes in multiple regions, which are typically 18F-fluorodoxyglucose (FDG) avid on positron-emission tomography (PET).

[5] The microscopic appearance (histology) of biopsied tissue from an enlarged lymph node must demonstrate a constellation of features consistent with Castleman disease.

[citation needed] Staining with latency-associated nuclear antigen (LANA-1), a marker of HHV-8 infection, must be negative to diagnose iMCD.

[citation needed] Patients with iMCD are classified as having severe or non-severe disease based on the 5 criteria listed below.

[citation needed] Patients with iMCD are evaluated for treatment response based on changes in symptoms, sizes of involved lymph nodes, and laboratory testing.

[citation needed] Siltuximab, an IL-6 blocker, is the recommended treatment for all patients with non-severe iMCD regardless of measured IL-6 levels.

[citation needed] For patients with non-severe disease who fail to respond to siltuximab, tocilizumab, and rituximab, treatment recommendations are not well defined.

As an alternative, immunomodulators such as thalidomide, cyclosporine A, sirolimus, bortezomib, and anakinra are recommended due to their similar response rates and more favorable long term side effect profiles.

[citation needed] Recommended initial treatment for all patients with severe iMCD is high dose steroids combined with an anti-IL-6 agent such as siltuximab or tocilizumab, regardless of measured IL-6 levels.

For patients who immediately improve with this regimen, steroids may be slowly tapered, but the anti-IL-6 agent should be continued indefinitely due to the high relapse rate with withdrawal of treatment.

Patients with life-threatening disease, particularly those with TAFRO Syndrome, may require advanced measures such as breathing support with a mechanical ventilator or treatment with dialysis for kidney failure.

It is recommended that follow-up visits include evaluation of symptoms, physical examination, laboratory testing, and radiologic imaging.