The Castleman Criteria
A novel ruleset may give hope to iMCD patients who remain undiagnosed
When your symptoms belong to a rare illness, such as Castleman disease (a lymph node disorder), the diagnostic outlook is bleak. Idiopathic multicentric Castleman disease (iMCD) is a life-threatening subtype that affects multiple lymph nodes. With no established diagnostic protocol in place, sufferers may remain undiagnosed – or misdiagnosed with lymphoma or autoimmune disorders – for years. To offer a solution, a multinational team of investigators banded together to pioneer a set of identification criteria (1).
Major Criteria
| Histopathological features consistent with iMCD on excisional lymph node biopsy |
| Enlarged (≥1 cm) lymph nodes in two or more lymph node stations |
Minor Criteria
| Clinical | Laboratory |
| Constitutional symptoms | Elevated C-reactive protein |
| Hepatosplenomegaly | Anemia |
| Edema or effusions | Hypoalbuminemia |
| Eruptive cherry hemangiomatosis or violaceous papules | Thrombocytopenia or thrombocytosis |
| Renal dysfunction | |
| Lymphocytic interstitial pneumonitis | Polyclonal hypergammaglobulinemia |
Table 1. Major and minor criteria for the diagnosis of iMCD.
The journey began with a review of 244 clinical cases and 88 lymph node biopsies from iMCD patients. Fifteen months of investigation yielded a set of major and minor criteria for diagnosis (see Table 1). To confirm iMCD, patients must exhibit at least two major and two minor criteria, including at least one abnormal laboratory result.
Next, the investigators used their criteria to retrospectively diagnose patients from a clinical trial of siltuximab, a therapeutic tested on iMCD patients. Trial participants who did not meet the criteria had no response to the drug, while those who did had a 43 percent response rate.
The outcome seems to show the effectiveness of the criteria, but that doesn’t mean the job is done. Using ACCELERATE, a research platform that collates iMCD clinical data, the researchers aim to keep fine-tuning their method. But even in this early stage, the investigators believe their Castleman criteria could help turn the tide in the fight against iMCD.
- DC Fajgenbaum et al., “International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease”, Blood, [Epub ahead of print] (2017). PMID: 28087540.
My fascination with science, gaming, and writing led to my studying biology at university, while simultaneously working as an online games journalist. After university, I travelled across Europe, working on a novel and developing a game, before finding my way to Texere. As Associate Editor, I’m evolving my loves of science and writing, while continuing to pursue my passion for gaming and creative writing in a personal capacity.
