A sixty-two year old woman presented with altered mental status, acute right-sided weakness, hypoglycemia, and acute-on-chronic kidney disease. Physical exam was also significant for lower extremity edema. A head CT demonstrated left parietal meningioma. Her symptoms resolved, but her hospital course was complicated by worsening pulmonary hypertension, diastolic dysfunction and progression of her chronic kidney disease to end stage renal disease. Other laboratory abnormalities included anemia, elevated inflammatory markers, and hypoalbuminemia. Chest and abdominal CT showed extensive lymphadenopathy, prompting lymph node biopsy. HIV, RPR, ANA and HHV-8 were negative. Histologic examination of the biopsy showed features of multicentric Castleman disease, plasma cell variant. IL-6 was elevated, consistent with Castleman. Once she was medically stable, she began therapy with Siltuximab.
Discussion:
Castleman disease, or angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder. It is thought to be caused by dysregulation and increased amounts of IL-6 leading to B-cell proliferation, increased levels of vascular endothelial growth factor, and a subsequent increase in angiogenesis. The disease is classified as either unicentric or multicentric and can be further classified histologically as the hyaline-vascular or plasma cell variant, with some cases of mixed type variant.
Unicentric Castleman disease (UCD) is usually benign, localized and may be found incidentally on imaging or present with painless lymphadenopathy. Multicentric Castleman disease (MCD) is usually more aggressive and systemic. The disease is associated with HIV and HHV-8 and typically presents with generalized symptoms including fever, night sweats, weight loss, and fatigue. Other clinical features seen in MCD include hepatosplenomegaly, diffuse lymphadenopathy, pleural/pericardial effusions, ascites, lower extremity edema, anemia, hypoalbuminemia, hypergammaglobulinemia, and elevated inflammatory markers. Ultimately, MCD can cause organ failure and death. Survival rates for MCD from a systematic review published in 2011 which included 416 patients with MCD demonstrated a 45.7% 3-year disease free survival (DFS) in HIV-negative, HHV-8 unknown patients and 27.8% DFS in HIV-positive patients.
The diagnosis of Castleman disease is suggested by histological examination of a lymph node biopsy. Though it remains a diagnosis of exclusion, it must be differentiated from variants of lymphoma, rheumatoid arthritis, syphilis, and autoimmune disorders including Lupus. Thus, these other diseases should be ruled out with further laboratory and clinical evaluation. All patients with Castleman disease should be tested for HIV and HHV-8.
The treatment for UCD involves surgical resection when possible. Radiation therapy can also be used in addition to surgery when complete resection is not possible, or for patient’s that are not surgical candidates. The treatment for MCD, which has not been well studied, includes glucocorticoids, chemotherapy, monoclonal antibody therapy and antiviral therapy for patients that have HIV and HHV-8.
Conclusions:
Castleman disease is a rare, but potentially fatal disease that can present with painless lymphadenopathy alone or in combination with systemic symptoms and multi-organ failure. Excisional biopsy is required and the disease must be distinguished from lymphoma, infectious and autoimmune diseases.