Expert Perspective: Diagnosis and Treatment of Castleman Disease
Bibliographic record
Abstract
Castleman disease (CD) is a major diagnostic challenge for rheumatologists. Unicentric CD (UCD) involves one enlarged lymph node region, whereas multicentric CD (MCD) involves multiple enlarged lymph node regions. Both UCD and MCD may exhibit a wide range of symptoms that overlap with other immune-mediated conditions. MCD can be associated with excessive cytokine production due to a plasma cell neoplasm (MCD-polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes) or uncontrolled human herpesvirus-8 infection (HHV-8) (HHV-8-positive MCD), but more than half of cases are idiopathic. Although they are all driven by excessive cytokines such as interleukin-6 (IL-6), patients with idiopathic MCD (iMCD) often present as a diagnostic mystery with heterogeneous symptomatology that can be classified into three subtypes. The three subtypes are iMCD-thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly (TAFRO); iMCD-idiopathic plasmacytic lymphadenopathy (IPL); and iMCD-not otherwise specified (NOS). Rapid onset cytokine storm with severe inflammation, anasarca, thrombocytopenia, and small volume lymphadenopathy, similar to hemophagocytic lymphohistiocytosis or sepsis, are the hallmarks of iMCD-TAFRO. Patients with iMCD-IPL present with subacute or chronic lymphadenopathy, anemia of inflammation, and polyclonal hypergammaglobulinemia, often with increased IgG4 in serum and lymph node tissue; these cases can be difficult to distinguish from IgG4-related disease and histiocyte disorders. Those who have iMCD not meeting criteria for TAFRO or IPL have iMCD-NOS, which often mimics indolent lymphoma or autoimmune conditions. Patients with autoimmune disease, lymphoma, and infections can experience Castleman-like changes in reactive lymph nodes, and thus histologic findings must be combined with clinical and laboratory findings to accurately diagnose iMCD. Broadly speaking, treatments for CD can be considered in three categories: immunomodulators such as glucocorticoids, cytokine inhibitors, and sirolimus; antilymphoma therapies such as rituximab, cytotoxic chemotherapy, and BTK inhibitors; and antimyeloma therapies such as thalidomide and bortezomib. The first-line therapy for all subtypes of iMCD is siltuximab, an IL-6 antagonist. Patients with refractory disease have numerous treatment options and consulting treatment guidelines as well as consultation with a center with expertise in CD are recommended.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.006 | 0.005 |
| Insufficient payload (model declined to judge) | 0.037 | 0.019 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".