Hodgkin's Lymphoma as a Cause of Fever of Unknown Origin in HIV Infection

Abstract

The risk of Hodgkin's lymphoma is increased in HIV-infected patients. In these patients Hodgkin's lymphoma is an aggressive disease with poor clinical outcome. Complete remission and survival rates are far below that reported in HIV-uninfected population. Since the widespread use of highly active antiretroviral therapy, malignancies are the major cause of mortality in HIV-infected patients. We report a case of a 29-year-old HIV-positive male who presented with fever of unknown origin, pancytopenia, and hemophagocytic syndrome. The diagnosis of Hodgkin's lymphoma with bone marrow involvement was made on bone marrow biopsy, 5 months after the onset of fever. The patient was treated with chemotherapy and achieved a complete remission. Relapse occurred 28 months later and he died 31 months after initial diagnosis. Prolonged fever is frequently observed in HIV-infected patients and could represent a diagnostic challenge. Infectious diseases are the most common causes, however lymphomas are the third most common cause of fever of unknown origin in HIV disease. This case illustrates the difficulties in accurately diagnosing Hodgkin's lymphoma in patients presenting with prolonged, unexplained fever, and emphasizes the use of bone marrow biopsy to confirm Hodgkin's lymphoma, particularly if cytopenia and hemophagocytic syndrome are present.

Haemophagocytic lymphohistiocytosis in human immunodeficiency virus: a systematic review of literature

“…Of these, a total of seven patients were virologically suppressed at the time of diagnosis of HLH. A total of 26 patients were treated with steroids, while etoposide was used in only four patients (6)(7)(8)8,(11)(12)(13)(14)16,18,20,23,24,27,(30)(31)(32)(33)(34)(35)(36)(37)41,44). Death was reported in 21 patients (6,(12)(13)(14)(15)20,27,29,31,(36)(37)(38)(39)(40)(41)44).…”

“…A total of 26 patients were treated with steroids, while etoposide was used in only four patients (6)(7)(8)8,(11)(12)(13)(14)16,18,20,23,24,27,(30)(31)(32)(33)(34)(35)(36)(37)41,44). Death was reported in 21 patients (6,(12)(13)(14)(15)20,27,29,31,(36)(37)(38)(39)(40)(41)44). Steroids, when given as a part of HLH management, was associated with increased mortality (p = 0.048).…”

Haemophagocytic lymphohistiocytosis complicating Hodgkin's lymphoma in an HIV-positive individual

“…As HIV patients survive longer with highly active antiretroviral therapy, malignancies such as lymphoma are being diagnosed more frequently, and therefore cases of HLH may also increase. 1 Consequently, it is a condition which we must remain aware of, and investigate fully in those patients with appropriate clinical features, regardless of the stage of their HIV infection.…”

“…A subsequent inguinal lymph node biopsy confirmed a diagnosis of Epstein Barr virus (EBV)-positive Hodgkin's lymphoma, lymphocyte-depleted variant – a subtype that is more commonly seen in the HIV-positive population. 1 Staging investigations confirmed Stage IIB Hodgkin's disease with significant pelvic lymphadenopathy. The haematology team felt that the combination of pancytopenia, non-specific changes on bone marrow examination and raised ferritin could indicate underlying haemophagocytic lymphohistiocytosis (HLH), and were keen to investigate this further.…”

Management of pyrexia of unknown origin in HIV-positive patients

“…4–12 Occult malignancies, although much less common than infections, are an important, consistent and at times coexistent cause of PUO in reported case series: most frequently lymphoma (Hodgkin's or non-Hodgkin's lymphoma), which may be complicated by haemophagocytic syndrome. 13,14 As in HIV-negative patients, bacterial infections including occult collections, dental sepsis and syphilis 15 should be considered as well as drug reactions, 16 autoimmune conditions such as thyrioditis 17 or collagen vascular diseases. 18 Case reports of less frequently occurring infections, for example Babesiosis, demonstrate the importance of a through travel history.…”