Winning Abstracts from the 2015 Medical Student Abstract Competition: Diffuse lymphadenopathy and weight loss of unknown etiology: A case of HLH in the outpatient setting
First Author: Abdul-Razaq Adeniyi, Sidney Kimmel Medical College, Thomas Jefferson University, Class of 2015
Hemaphagocytic lymphcytosis (HLH) is characterized by progressive histiocytic proliferation of non-malignant lymphocytes and macrophages. Excessive proliferation of these cells is the result of unchecked immune cell activation which leads to abnormal inflammation and tissue destruction. There is generally impaired regulatory activity of natural killer cells and cytotoxic lymphocytes leading to excessive activation of macrophages with abnormal cytokine release. The disease has both sporadic and familial presentations. Familial or primary HLH is a heritable disorder that is associated with 1 of 5 identified gene abnormalities, and symptoms usually present within the first few months of life. Sporadic or secondary HLH is often triggered by activation of the immune system during infections, autoimmune disorders, or other inflammatory states and can present at any age.
A 32 year old African American female presented to the outpatient adult medicine office of Wilmington Hospital complaining of 2 weeks of intermittent left leg and hand cramping with associated numbness. The symptoms were not triggered by any specific activities and were the latest symptoms in a presentation that included 3 months of persistent high grade fevers, chills, night sweats, fatigue, progressively worsening dyspnea on exertion, abdominal distention, poor appetite with associated nausea and vomiting, and a 25 pound weight loss. She was also concerned about worsening "yellowing of her eyes" over the last 2 months. Her physical exam was significant for scleral icterus, hepatomegaly and inguinal lymphadenopathy. She presented to the emergency room 2 months ago with similar symptoms and left neck swelling. At that point, imaging, including a PET scan, had demonstrated diffuse bulky lymphadenopathy and hepatosplenomegaly. Blood cultures were negative and viral assays ruled out HIV, CMV, EBV and hepatitis. She underwent a cervical lymph node biopsy and bone marrow biopsy that was consistent with lymphohistiocytic proliferation but negative for lymphoma. Repeat viral assays remained negative and she was subsequently referred to infectious disease for further workup. The diagnosis of HLH was made soon after.
HLH, though rare, should be strongly considered in presentations of diffuse lymphyadenopathy and weight loss as demonstrated by this case. The presentation is similar to more frequently considered etiologies such as HIV and B-cell lymphomas, and as a result is often not considered until much later in the diagnostic work up. Delayed diagnosis significantly increases the risk of mortality as prompt induction of immunotherapy is essential for survival. Earlier consideration of this disease entity during the work up phase might facilitate prompter treatment and eliminate unnecessary repeat testing.