2019 Research Forum

Mariam Abdelmisseh MD R3 1 , Gowri Rengenathan MD R2 1 , Alyssa Targovnik MS IV, Kyle Foster MS IV 1 , Amanda Brewster MS IV 1 , Everardo Cobos MD 1 1 Kern Medical Internal Medicine Department, Bakersfield, CA Hemophagocytic Lymphohistocytosis Induced by Pregnancy and Post-Partum Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare potentially fatal immunopathology resulting in overproduction of cytokines and unregulated proliferation of macrophages ultimately leading to multi-organ injury. This condition is often triggered by a primary genetic disorder (commonly seen in the pediatric population), or by secondary triggers including but not limited to malignancy, rheumatologic process, or viral infection. Here we present a case of a hemophagocytic lymphohistiocytosis precipitated by pregnancy and the postpartum state.

Discussion

Case Presentation:

Conclusions Previously documented triggers of HLH such as those stated above did not seem to play a role in this case. This created a significant challenge in properly diagnosing and treating our patient. Extensive literature search revealed that there are only 14 documented cases of HLH associated with pregnancy and the post-partum state. We hope this case raises awareness of the importance of proper diagnosis and treatment, as patients are able to have significant response rates with proper therapy and improve mortality References Henter, Jan-Inge, et al. Treatment of Hemophagocytic Lymphohistocytosis with HLH-94 Immunochemotherapy and Bone Marrow Transplantation. Blood, 1 Oct. 2002, Tierney, Lawrence M, et al. Case 10-2011 — A Woman with Fever, Confusion, Liver Failure, Anemia, and Thrombocytopenia.” New England Journal of Medicine , 31 Mar. 2011, Denimal, Damien, et al. Extreme hyperferritinemia in the setting of acute myeloid leukemia: a case report of hemophagocytic lymphohistocytosis. Biochemia Medica 2016:26(2):255-259

• Hemophagocytic lymphocytosis is an aggressive and life-threatening syndrome of excessive immune activation which results in multiorgan failure. There is a defective cytotoxic cell function coupled with unbridled macrophage activity leading to excessive cytokine production, subsequently leading to immune dysregulation, tissue damage and ultimately death from bacterial or fungal infection. • It is observed in children as a primary genetic disorder and as a acquired disorder in adults • Primary Genetic disorder: Autosomal Recessive, involving 16 potential loci • Acquired secondary to : Malignancy, Rheumatologic disorder, Viral Infection, Immunosuppression • The diagnosis of Hemophagocytic Lymphohistocytosis is based on clinical presentation and a set of laboratory parameters as proposed by the Histocyte Society in the pediatrics diagnostic guidelines, meeting at least 5 out 8 criteria. There is also H SCORE that can be calculated to estimate the probability of HLH. An H score >/= 250 indicates 99% probability of having HLH. However, an H score

Patient is a 28 year old G3P3 female, 22 days postpartum who presented to the ED with a month 1 month history of persistent pyrexia and shortness of breath. Initial labs were significant for anemia, thrombocytopenia, transaminitis, and apparent hepatic dysfunction. CT abdomen additionally revealed hepatosplenomegaly. Due to unknown source of symptoms, a full sepsis workup was performed, however no source of infection was able to be found. She was started on broad- spectrum antibiotic therapy however hepatic dysfunction continued to deteriorate. Bone marrow biopsy was performed to rule out hematologic malignancy, however results proved to be normal. Additionally, full infectious disease and rheumatologic workups were within normal limits. Further laboratory studies met diagnostic criteria of HLH as 5 of 8 criteria were met- in this particular case: elevated ferritin of 25074 ng/dL, elevated IL-2 of 16455, fever, hepatosplenomegaly, anemia, and thrombocytopenia. Subsequently, patient was started on corticosteroids and cyclosporine with resultant down-trending ferritin and IL-2 levels. Her hepatic function recovered with treatment as well

, Anna, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Advances 2017;1(26): 2529-2534

George, M R. Hemophagocytic lymphohistiocytosis:review of etiologies and management. Journal of Blood Medicine 2014:5 69- 86

• Our patient had 5 out 8 diagnostic criteria; he was febrile, had hepatosplenomegaly, had anemia, and thrombocytopenia, had hypertriglyceridemia and of course the ferritin of greater than 100,000. Our patient’s H score was 205 indicating 91% probability of having HLH. • It’s crucial to start treatment promptly to improve the overall survival rate • The principle of treatment is immune suppression to try to reduce the cytokine storm that is triggered in this condition. • Treatment depends on the etiology. In Familial HLH, there is HLH-94 protocol which consists of combined Chemotherapy and Immunotherapy, followed by BM transplantation if persistent and/or recurrent. The regimen includes etoposide, corticosteroids, cyclosporin A, and intrathecal Methotrexate if there is CNS disease.

Acknowledgements • DR. EVERARDO COBOS, MD, FACP- CHAIR OF MEDICINE • DR. SAMAN RATNAYAKE-INTERNAL MEDICINE

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