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Castleman Disease: The Confounding Role of Immune Dysregulation in the Setting of Chronic Disease

Authors

Aydin Zahedivash; The University of Texas at Austin Dell Medical School< Jessica Chambers, MD; Department of Internal Medicine, The University of Texas at Austin Dell Medical School, Beth Miller, MD, MACP; Department of Internal Medicine, The University of Texas at Austin Dell Medical School

Introduction

Multicentric Castleman Disease (MCD) is a systemic disease characterized by angiofollicular lymph node hyperplasia often associated with human herpes virus 8 (HHV8) and human immunodeficiency virus (HIV). We demonstrate a case of idiopathic MCD and hypothesize that the etiology may be due to immune dysregulation triggered by uncontrolled diabetes mellitus rather than the common viral coinfections.

Case Presentation

A 33-year-old man with history of hypertension, asthma, and uncontrolled type 2 diabetes mellitus presented with wheezing for 1 month with only mild improvement when using his albuterol inhaler. He reported night sweats and productive cough with brown and green sputum and occasional bloody streaks for one month accompanied by a 100-pound weight loss over the past year. He denied tobacco use, sick contacts, recent viral illness, and recent travel. He is a carpenter by trade and has no pets. The physical examination showed vital signs that were within normal limits, moderate expiratory wheezing throughout lung fields, and painless submental, bilateral submandibular, bilateral femoral, bilateral axillary, and left epitrochlear lymphadenopathies, averaging 2-3 cm in size with no hepatosplenomegaly. A chest x-ray showed bilateral reticulonodular infiltrates, but no consolidation. Routine bacterial, AFB, and fungal cultures were negative as were HHV8 and HIV viral serologies. Glucose level on admission was 685 mg/dL and his HbA1C was greater than 14%.

The patient had significant improvement in his wheezing after receiving an empiric course with azithromycin-ceftriaxone and was able to walk for 5-10 minutes without shortness of breath. However, physical exam revealed only a mild regression of the diffuse lymphadenopathy and chest x-ray showed only mild regression of the bilateral reticulonodular infiltrates. The patient underwent a femoral lymph node biopsy given the persistent lymphadenopathy and radiological findings. Pathology results revealed Castleman Disease, vascular/hyaline type.

Discussion

This patient's case demonstrates an unusual presentation of MCD, considering the younger age of diagnosis and the absence of the common viral coinfections present in over 50% of cases. Cases of MCD without HHV8 and HIV coinfection are generally deemed to be idiopathic [1][2]. In addition to its association with HHV8 and HIV however, MCD has been associated more broadly with immune dysregulation [1][2]. Pertinent to this patient, it has been seen that hyperglycemia can alter various aspects of the immune response, in some cases interrupting antigen recognition pathways which can lead to a proinflammatory state [3], predisposing to MCD [1][2]. Additionally, the increased angiogenesis in chronic states of hyperglycemia further predisposes patients to MCD. This patient's young age in conjunction with uncontrolled blood glucose levels point to a possible link between MCD and the immune system dysregulation seen in uncontrolled diabetes mellitus, providing motivation for further investigation of the association in patients with a younger age at diagnosis.

References

[1] Fajgenbaum, D. C., van Rhee, F., & Nabel, C. S. (2014). HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood, blood-2013.

[2] Bianchi, M. M., Narváez, J., Santo, P., Ríos-Rodriguez, V., de la Fuente, D., Roig-Vilaseca, D., & Nolla, J. M. (2009). Multicentric Castleman's disease mimicking adult-onset Still's disease. Joint Bone Spine, 76(3), 304-307.

[3] Ilyas, R., Wallis, R., Soilleux, E. J., Townsend, P., Zehnder, D., Tan, B. K., ... & Mitchell, D. A. (2011). High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus. Immunobiology, 216(1), 126-131.

Back to the December 2019 issue of ACP IMpact