Secondary Hemophagocytic Lymphohistiocytosis in Adults: Experience from a Safety Net Hospital Serving an Underserved Population

Introduction:

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition, driven by an overactivation of the immune system, which causes inflammatory tissue damage potentially leading to organ failure and death. Secondary HLH in adults is a rare clinical entity and diagnosis often is delayed due to low index of clinical suspicion or limited availability of sophisticated testing. Therefore, evidence related to overall outcomes in underserved populations remains scarce.

Methods: After institutional review board approval, we retrospectively reviewed charts of patients 18 years or above, with a diagnosis of hemophagocytic lymphohistiocytosis at our institution between 2015-2021. Data on baseline characteristics, cause of HLH and overall outcomes were collected and analyzed. SAS v9.4 was used for statistical analysis.

Results: A total of 17 patients were included for the analysis. Majority patients were males (10/17, 58.8%) and mean age was 41.1 ± 17.1 years. Most patients lacked insurance coverage (12/17, 70.6%); in patients with insurance coverage, Medicaid was the most common primary payer (5/6, 83.3%). 8/17 (47.1%) patients were African Americans, similarly Caucasians (8/17, 47.1%), followed by Hispanics (1/17, 5.9%). Fever was noted to be the most common presentation (12/17, 70.6%), followed by abdominal pain, vomiting and cough which were present only in 3/17 (17.6%) patients. Splenomegaly/ hepatosplenomegaly was the most common finding on imaging (7/17, 41.2%). Laboratory investigations were consistent with with cytopenias (16/17, 94.1%) and transaminitis (13/17, 76.5%) in majority of the patients. Bone marrow biopsy was performed to aid in diagnosis in 8/17 (47.1%) patients, out of which, hemophagocytosis was noted only on 4/17 (23.5%). NK- cell activity was tested in 8/17 (47.1%) patients and was noted to be low. Soluble interleukin-2 receptor-alpha/CD25 was tested in 7/17 (41.2%) patients and ranged from 345-6,029 units/ml and was helpful in diagnosis (>2400 units/ml) only in 3/7 (42.9%) patients.

Underlying infection was the most common cause of HLH (8/17, 47.1%), out of which, majority had HIV (5/8, 62.5%). 4 out of 5 patients with HIV had disseminated histoplasmosis (80%). 4/17 (23.5%) patients were noted to have underlying rheumatologic disease; the cause of HLH was deemed to unknown in 4 patients (4/17, 23.5%)). One patient was diagnosed with an underlying malignancy, i.e., acute myeloid leukemia (1/17, 5.9%).

Majority patients were managed in intensive care unit setting (10/17, 58.8%). Patients managed in ICU setting had a lower median platelet count nadir than those managed on the floor (40,000 cells/cu. mm vs 52,000 cells/ cu. mm, p=0.04). However, no significant difference in the median platelet count, white blood cell count or median hemoglobin levels on presentation was noted between the two groups (p>0.05). Majority patients were managed with steroids alone (9/17, 52.9%), followed by steroids+steroid-sparing agents (4/17,23.5%), anti-fungal agents alone (2/17, 11.8%) and steroids+intravenous anti-globulin and anti-fungal agent (1/17, 5.9%). One patient (1/17, 5.9%) was only conservatively managed. Complete recovery was noted in majority of the patients (13/17, 76.5%), while 4/17 (23.5%) patients died during their hospital stay. 2 out of the 4 patients (50%) who died had underlying rheumatological disease, while the remaining two patients had acute myeloid leukemia and cellulitis respectively.

Conclusion: Majority of the cases of secondary HLH in our cohort of underserved adults were noted to be related to infectious causes. Contrary to existing literature, HIV was noted to be the predominant cause in these patients (as opposed to Epstein-Barr virus). HLH in patients with HIV should prompt investigation for underlying histoplasmosis. Patients with a lower platelet nadir appear to be at greater risk of escalation of level of care. HLH related to infections is associated with a relatively favorable outcome, which may explain the relatively lower overall mortality in our study population. Clinical presentation was widely non-specific, warranting a high index of suspicion for secondary HLH, to allow prompt diagnosis in these patients. Investigations such as bone marrow biopsy and interleukin-2 receptor-alpha/CD25 may not aid in diagnosis in many patients and may not be included in initial evaluation for HLH in resource-limited settings.

No relevant conflicts of interest to declare.