Introduction

Hemophagocytic lymphohistiocytosis (HLH) was first described by Farquhar and Claireaux in 1952 as familial hemophagocytic reticulocytosis [1]. Although frequently seen among the pediatric population, HLH can affect all ages [2,3]. The HLH-2004 trial redefined the diagnostic criteria for HLH, however definitive therapy may be initiated early on if there is a high degree of clinical suspicion, as the diagnostic criteria may oftentimes be too stringent [4]. Although we have well established treatment protocols, the mortality remains high, this could be due to morbidity associated with the disease, triggering factor and due to delay in diagnosis, which is often a limiting factor [5].

Case Description

We report a case-series of four patients diagnosed with HLH at a community center within a one-year time frame. First patient was a 63-y/o man admitted for hypoxic respiratory failure due to Covid-19, due to persistent fever & worsening bicytopenia, & high H-score, bone marrow biopsy was performed, consistent with HLH in setting of Covid-19 & CMV viremia. The patient received Dexamethasone & IVIG but died before starting Etoposide due to MSSA bacteremia. Second patient was a 42-y/o man admitted to MICU for septic shock, due to pancytopenia & elevated H-score, bone marrow biopsy revealed HLH in the setting of Hodgkin's lymphoma due to EBV infection. The patient was started on the HLH-94 regimen with Etoposide, Dexamethasone, & intrathecal methotrexate but died from septic shock before a bone marrow transplant could be performed. Third patient was a 57-y/o man admitted for pyrexia of unknown origin, an exclusionary diagnosis of idiopathic HLH was made after extensive work up. The patient was treated with the HLH-94 regimen, including Etoposide & intrathecal methotrexate/hydrocortisone. Due to worsening mental status, imaging revealed a hyperdense mass with obstructive hydrocephalus, consistent with primary CNS lymphoma. The patient continued treatment but succumbed to septic shock & was placed on comfort measures per family wishes. Fourth patient was a 62 y/o female who was admitted for unintentional weight loss and symptomatic anemia. Due to high H-score, patient underwent a bone marrow biopsy which was consistent with Plasmablastic lymphoma, which also noted on EGD biopsies, started on daily dexamethasone & bi-weekly etoposide, transferred to higher center for bone marrow transplant.

Discussion

HLH is triggered by various pathologies such as infectious diseases, malignancies, autoimmune diseases, & transplantation [6]. HLH has poor prognosis with a median survival of 2 months if left untreated. The H-score was developed to estimate an individual's risk of reactive hemophagocytic syndrome. An H-score of 169 corresponds to 93% sensitivity, 86% specificity, & accurate classification of 90% of the patients. Lymphoma-associated hemophagocytic syndrome (LAHS) is a specific subgroup of HLH which is associated with worse outcomes than benign disease-associated HLH. Both CD25 values (>5000U/mL) and CD25/Serum ferritin ratio (≥2) are associated with a high positive predictive value (PPV) for LAHS. When combined the PPV increases to >95%.

Conclusion

In community-based hospitals, it is essential to use H-score & CD-25/serum ferritin ratio tools to screen & prognostic this rare but fatal disease to allow for prompt and aggressive therapies, identification of possible unknown malignancy and early transfer to higher care centers.

References

  1. Farquhar JW, Clarieaux AE. Familial haemophagocytic reticulosis. Arch Dis Child. 1952 Dec;27(136):519-25.

  2. Janka GE, Lehmberg K. Hemophagocytic syndromes–an update. Blood Rev. 2014 Jul;28(4):135-42.

  3. Zhou M, Li L, Zhang Q, Ma S, Sun J, Zhu L, Lu D, Zhu J, Zhou D, Zheng Y, Yang X, Xie M, Zhu M, Ye X, Xie W. Clinical features and outcomes in secondary adult hemophagocytic lymphohistiocytosis. QJM. 2018 Jan 1;111(1):23-31.

  4. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31.

  5. Otrock ZK, Daver N, Kantarjian HM, Eby CS. Diagnostic Challenges of Hemophagocytic Lymphohistiocytosis. Clin Lymphoma Myeloma Leuk. 2017 Jul;17S:S105-S110.

  6. Esteban YM, de Jong JLO, Tesher MS. An Overview of Hemophagocytic Lymphohistiocytosis. Pediatr Ann. 2017 Aug 1;46(8):e309-e313.

Disclosures

No relevant conflicts of interest to declare.

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2024
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