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REFERENCES

  • The etiology of lymphadenopathy includes viral and bacterial infections, neoplasms, inflammatory diseases, autoimmune disorders, and inherited metabolic storage diseases1
  • Liver diseases cause increased vascular pressure, leading to an increase in spleen size; neoplastic cells cause infiltration of the spleen; and infections lead to increased numbers of reticuloendothelial cells in the spleen2
  • Cytokine storms are characterized by perpetual activation of lymphocytes and macrophages, resulting in the secretion of large quantities of multiple cytokines3
  • Cytokine storms may lead to systemic inflammation, multicentric lymphadenopathy, cytopenia, and potentially fatal multiple organ dysfunction3
  • According to the National Heart, Lung, and Blood Institute (part of the National Institutes of Health), a normal platelet count in adults ranges from 150,000 to 450,000 platelets per microliter of blood4
  • A systematic review determined that the reference interval (2.5th to 97.5th percentiles) for serum creatinine was 0.72 mg/dL to 1.18 mg/dL for men compared with 0.55 mg/dL to 1.02 mg/dL for women5 
  • One of the key mediators of cytokine storms is interleukin-6 (IL-6), which is a cytokine that regulates inflammation, immune responses, and hematopoiesis6
  • List of autoimmune diseases7,14: systemic sclerosis, autoimmune lymphoproliferative syndrome, psoriatic arthritis, giant cell arteritis, adult-onset Still disease, systemic lupus erythematosus, Takayasu arteritis, malignancy-associated hemophagocytic lymphohistiocytosis
  • List of malignancies7,8,15: multiple myeloma, hepatocellular carcinoma, non-Hodgkin lymphoma, autoimmune lymphoproliferative syndrome, human herpesvirus-8 (HHV-8) infection, HIV(+) and/or HHV-8(+) multicentric Castleman disease, malignancy-associated hemophagocytic lymphohistiocytosis
  • List of infectious diseases7,16:  HHV-8 infection, acute Epstein-Barr virus, acute HIV, HIV(+) and/or HHV-8(+) multicentric Castleman disease
  • This disease has an average mortality rate of 2.6 years post index diagnosis17
  • A rare disease that is typically driven by IL-6 dysregulation3,7,18
  • Excisional biopsy is strongly recommended and may be the only definitive way to confirm diagnosis7
  • If untreated, could lead to malignancies and organ failure17
  • Idiopathic multicentric Castleman disease (iMCD) is a rare disease that can mimic autoimmune, malignant, and inflammatory conditions. Clinical presentation of iMCD can range from mild constitutional symptoms like fatigue to more severe symptoms like fever or organomegaly7,19-21
  • About 20% of patients with iMCD, as in this case, present with an intense inflammatory syndrome characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis or renal dysfunction, and organomegaly (TAFRO)18,19
  • iMCD can only be confirmed by an excisional biopsy of an affected lymph node7
  • While some anticancer or arthritis medicines are used for iMCD, only one targeted therapy neutralizes IL-6 and is approved by the FDA22,23
  • Siltuximab (SYLVANT®) is recommended by the National Comprehensive Cancer Network® (NCCN®) as a preferred treatment option for iMCD for plasmacytic/mixed histology. Siltuximab also continues to be the first-line therapy recommended by the Castleman Disease Collaborative Network (CDCN) guidelines with Category 1 evidence, regardless of histopathologic subtype22,24
References
  1. Freeman AM, Matto P. Adenopathy. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
  2. Chapman J, Bansai P, Goyal A, Azevedo AM. Splenomegaly. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
  3. England J, Abdulla A, Biggs CM, et al. Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes. Blood Rev. 2020;100707. doi: 10.1016/j.blre.2020.100707.
  4. National Heart, Lung, and Blood Institute. Thrombocytopenia. https://www.nhlbi.nih.gov/health-topics/thrombocytopenia. Accessed September 28, 2020.
  5. Cerrioti F, Boyd JC, Klein G; IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). Reference intervals for serum creatinine concentrations: assessments of available data for global application. Clin Chem. 2008;54(3):559-566.
  6. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295.
  7. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.
  8. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16:335-345.
  9. American Autoimmune Related Diseases Association, Inc. Ankylosing spondylitis. https://www.aarda.org/diseaseinfo/ankylosing-spondylitis/. Accessed September 28, 2020.
  10. Marks DJB, Rahman FZ, Sewell GW, Segal AW. Crohn’s disease: an immune deficiency state. Clin Rev Allergy Immunol. 2010;38(1):20-31.
  11. Scleroderma Foundation. What is scleroderma? https://www.scleroderma.org/site/SPageNavigator/patients_whatis.html#.X3H76pNKjlw. Accessed September 28, 2020.
  12. Arthritis Foundation. Giant cell arteritis. https://www.arthritis.org/diseases/giant-cell-arteritis#:~:text=Giant%20cell%20arteritis%20(GCA)-%2C,commonly%20associated%20with%20polymyalgia%20rheumatica. Accessed September 28, 2020.
  13. American College of Rheumatology. Takayasu’s arteritis. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Takayasus-Arteritis#:~:text=Takayasu's%20arteritis%2C%20also%20called%20TAK,in%20the%20walls%20of%20arteries. Accessed September 28, 2020.
  14. National Institute of Neurological Disorders and Stroke. Neuromyelitis optics information page. https://www.ninds.nih.gov/Disorders/All-Disorders/Neuromyelitis-Optica-Information-Page. Accessed September 28, 2020.
  15. Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity. 2019;50:1007-1023.
  16. Wilson JG, Simpson LJ, Ferreira AM, et al. Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight. 2020;5(17):e140289.
  17. Mukherjee S, Martin R, Sande B, et al. A longitudinal population level analysis of healthcare resource utilization, comorbidity, and survival in idiopathic multicentric Castleman disease patients. Blood. 2020:136(suppl 1):11.
  18. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330.
  19. Liu AY, Nabel CS, Finkelman BS, et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol. 2016:3(4):e163-e175. 
  20. Cheson BC, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano Classification. J Clin Oncol. 2014;32:3059-3067.
  21. Parekh BS, Ou CY, Fonjungo PN, et al. Diagnosis of human immunodeficiency virus infection. Clin Microbiol Rev. 2019;32:e00064-18.
  22. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed September 30, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  23. SYLVANT® [package insert]. Hertfordshire, UK: EUSA Pharma UK Ltd; 2019.
  24. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124.