Bullet Learning: Castleman's Disease

Unclear on Castleman's? Let's learn together in this bullet learning entry.

A rare entity with unknown etiology, Castleman’s Disease (CD) is a non-clonal lymphoproliferative disorder that primarily affects lymph nodes and features abundant proliferation of B cells and plasma cells in lymphoid organs.

Clinically, CD is classified as unicentric or multicentric, and pathologically it has 4 subtypes: hyaline vascular, plasma cell, mixed, and HHV-8 associated.

Current theories are that immune dysregulation, found in chronic inflammation or viral infection, underlies CD, and there is evidence that upregulation of the IL-6 pathway, through over-secretion of IL-6 or over-production of IL-6 receptor, is critical to the pathogenesis of CD.

Additionally, HIV is known to be associated with CD, especially the multicentric variant, and almost all cases of HIV-associated CD are HHV-8 positive. Non-HIV-associated CD, or idiopathic CD, features HHV-8 in ~50% of cases. 

First line therapy for the more common unicentric CD is surgical resection of the affected lymph node +/- IL-6 inhibition through Tocilizumab, a monoclonal antibody to the IL-6 receptor, or Siltuximab, a monoclonal antibody to IL-6.

Antiviral therapy against HHV-8 has also shown benefit, as have immunomodulatory treatments such as rituximab and interferon-alpha.

 References: 

Yoshizaki K, et al. The Role of Interleukin-6 in Castleman Disease. Hematol Oncol Clin North Am. 2018 Feb;32(1):23-36. doi: 10.1016/j.hoc.2017.09.003. PMID: 29157617.

Ehsan N, Zahra F. Castleman Disease. [Updated 2022 Nov 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576394/

Oksenhendler, E., et al. "The full spectrum of Castleman disease: 273 patients studied over 20 years." British journal of haematology 180.2 (2018): 206-216.

Fu, B., et al. Why tocilizumab could be an effective treatment for severe COVID-19?. J Transl Med 18, 164 (2020). https://doi.org/10.1186/s12967-020-02339-3