Case Presentation: A 44-year-old female with rheumatoid arthritis, recently started on methotrexate and infliximab presented to hospital on two occasions, one month apart, with fever, malaise, night sweats and abdominal discomfort. On both occasions she was hypotensive and pancytopenic (initial WBC 2.04 K/UL, Hbg 6.2 g/dL and Plt 131 K/UL). Both admissions were also characterized by sporadic episodes of bradycardia and hypothermia. She was treated for septic shock with vasopressors and empiric antibiotics and was successfully discharged after the first admission but a recurrence in her symptoms prompted her return to hospital. Infectious disease workup done during her hospitalizations included negative blood cultures, CMV, EBV and parvovirus titres, cryptococcal antigen, QuantiFERON gold, HIV and viral hepatitis testing were also negative. Peripheral blood smear and flow cytometry done during the initial admission showed no evidence of leukemia or lymphoma. Initial CT imaging showed moderate splenomegaly and retroperitoneal, iliac and inguinal lymphadenopathy; all of which enlarged on repeat imaging during her second admission, along with interval development of cervical, axillary and mediastinal lymphadenopathy. Despite a course of empiric antibiotics, she remained febrile with episodes of bradycardia and hypothermia. This prompted evaluation for non-infectious etiologies. A bone marrow biopsy revealed a partial replacement of bone marrow by classical Hodgkin lymphoma (cHL) with marked granulomatous reaction. She was started on glucocorticoids for symptomatic relief prior to initiation of systemic chemoimmunotherapy with brentuximab, doxorubicin, vinblastine, and dacarbazine with resolution of her pancytopenia, dysautonomia, and constitutional symptoms.
Discussion: HL is a B-cell neoplasm, in which malignant Hodgkin/Reed-Sternberg (HRS) cells are admixed with a heterogeneous population of non-neoplastic inflammatory cells. It represents about 9000 new cases and 1000 deaths in US annually. Prompt identification and initiation of appropriate therapy is essential to improve outcomes. The clinical presentation of cHL can be quite variable, but typically includes painless lymph node enlargement as well as “B-symptoms” such as fever, night sweats and weight loss. A rare sepsis-like syndrome has been described in a few cases of advanced cHL (Mangla, et al. Hematol Rep 2014). Our patient presented with recurrent episodes of SIRS and dysautonomia that persisted despite antibiotics and negative infectious workup. Two proposed mechanisms include: a complex interaction between cytokines released by malignant cells and mediators of vasodilation and HL-induced autonomic dysfunction as part of a paraneoplastic syndrome.
Conclusions: SIRS is a common clinical syndrome amongst hospitalized patients. While it is often related to an infection, it is paramount for hospital providers to consider malignancy as a potential cause when no clear infectious source is found. Furthermore, our case highlights the autonomic dysfunction that is uncommonly seen with advanced HL. This will result in fewer delays in diagnosis and timely initiation of lifesaving, curative intent treatments.