Diagnostic challenges in adult hemophagocytic lymphohistiocytosis: A case series

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition marked by non-specific symptoms like fever, low blood cell counts, and problems in multiple organs. In adults, HLH is often secondary to infections, cancers, or autoimmune disorders. It is often misdiagnosed, which leads to [poor outcomes. We present four adult cases of HLH to illustrate the challenges in diagnosis and the effects of starting treatment early compared to delaying it. Case Presentations: Case 1: A 46-year-old male came in with neutropenic fever and markedly elevated ferritin levels (8210 ng/mL HLH was suspected on day 3, and dexamethasone was initiated. A bone marrow biopsy confirmed hemophagocytosis and by day 4, etoposide was given, resulting in significant clinical improvement. The patient later had a hematopoietic stem cell transplant but was lost to follow-up. Case 2: A 49-year-old male presented with pancytopenia, weight loss, and lymphadenopathy. Despite a ferritin level of 17,000 ng/mL, HLH was not initially suspected. The diagnosis was only confirmed upon identifying Hodgkin lymphoma and hemophagocytosis on bone marrow biopsy. The patient responded to steroids and chemotherapy at first, but his condition worsened due to HLH relapse. Despite reinitiating therapy, he succumbed on Day 10 after readmission. Case 3: A 53-year-old woman with respiratory failure and severe leukocytosis (>128,000 /µL) received a delayed diagnosis of HLH on day 6. This occurred despite high ferritin levels (17,035 ng/mL) and hemophagocytosis found on biopsy. After starting dexamethasone and etoposide, the patient quickly deteriorated and died by day 9. Case 4: A 38-year-old woman with recurrent infections came in with neutropenic fever, anemia, and high ferritin levels (>2000 ng/mL). HLH was suspected on day 3 after a bone marrow biopsy showed hemophagocytosis and atypical blasts. Even though dexamethasone was started on day 4, the patient worsened and died before etoposide could be given. Discussion: Diagnosing adult HLH is challenging due to vague clinical signs, overlapping symptoms with other illnesses, and a lack of awareness. Delayed recognition is closely linked to higher mortality rates. Quickly identifying the condition, using clinical tools like the HScore, and starting immunosuppressive therapy (such as dexamethasone and etoposide) early are vital for better survival rates. Strong clinical suspicion, prompt diagnostic tests, and swift treatment actions are key strategies to address the negative outcomes related to delayed diagnosis in adult HLH.