Pediatric hemophagocytic lymphohistiocytosis: A rarely diagnosed entity in a developing country

Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is an exaggerated inflammatory reaction secondary to a host’s inadequate immune response causing a self-perpetuating loop of altered regulation. Signs and symptoms of HLH are compatible with other common diseases and are nonspecific. Underdiagnosis makes it difficult to estimate the real incidence of HLH, especially in developing countries. Methods Retrospective, descriptive study of pediatric patients admitted to a high-complexity institution in Cali, Colombia between 2012 and 2019 with HLH diagnosis. Medical history review to complete an electronic database and a secondary, descriptive analysis was carried out. The study was approved by the Institutional Ethics Committee. Results Twenty-one patients were included. 52.4 % of the population was male with a median age of 9.3 years [IQR (3.0-13.7 years)]. More than half of patients (66.6 %) had viral disease at diagnosis, the most frequent being Epstein-Barr Virus (EBV) (52.3 %) and dengue (14.3 %). Three patients had confirmed gene mutations (G6PC3, XIAP, and UNC13D). 95 % of the patients were treated with the HLH 2004 protocol, half of them received incomplete protocol with intravenous immunoglobulin (IVIG) and/or systemic steroids, while the other half received the complete protocol including etoposide and cyclosporine. More than three-fourths (76.2 %) required admission to an ICU with a median stay of 14 days [IQR (11–37 days)] and a median hospital stay of 30 days [IQR (18–93 days)]. 14.3 % (n = 3) of patients died. Conclusions HLH is a complex disease that requires multidisciplinary management with secondary HLH due to EBV infection being a common cause. There is increasing awareness of HLH diagnosis in developing countries such as Colombia which can offer earlier treatment options and better outcomes.

Successful use of emapalumab in refractory hemophagocytic lymphohistiocytosis in a child with Chédiak–Higashi syndrome: a case report

“…HLH can be familial with a clear genetic component (primary HLH), or can be an acquired disorder due to other conditions such as infections and malignancy (secondary HLH) [ 4 ]. HLH is primarily complicated by delays in diagnosis and treatment, predominately due to its nonspecific symptoms (fever, cytopenia, hepatosplenomegaly, and multisystem organ failure), and inadequate access to necessary specific laboratory and genetic testing [ 3 , 5 ].…”

Pediatric Hemophagocytic Lymphohistiocytosis: Formation of an Interdisciplinary HLH Working Group at a Single Institution

“…Recent literature stresses the importance of early inclusion of HLH in the differential diagnoses in an effort to prompt appropriate diagnosis and ultimately improve patient outcomes. 7,11 To address this issue, Cook Children's Medical Center (CCMC), in Fort Worth, Texas has recently developed an interdisciplinary HLH work group comprised of hematologists, oncologists, rheumatologists, infectious disease providers, hospitalists, and intensive care unit providers along with clinical pharmacists. Since its inception in July, 2019, this group has met every 3 months to discuss relevant topics and patient presentations in an effort to create a collective experience on a rare disorder.…”

“…When a cause can be identified, the most common etiologies of FUO include leukemia and lymphoma; less common etiologies include malignant histiocytosis, neuroblastoma, hepatoma, sarcoma, and atrial myxoma 4. On the other hand, HLH is an aggressive syndrome characterized by excessive activation of inflammatory cells, and it commonly presents with fever 6,7. According to a review of HLH cases in Texas pediatric hospitals, the incidence of HLH is 1 in 100,000 children 8.…”

“…Due to the rarity of histiocytic disorders and nonspecific symptoms, specialists are often consulted later in the disease process, requiring emergent decision-making with regard to treatment. Recent literature stresses the importance of early inclusion of HLH in the differential diagnoses in an effort to prompt appropriate diagnosis and ultimately improve patient outcomes 7,11. To address this issue, Cook Children’s Medical Center (CCMC), in Fort Worth, Texas has recently developed an interdisciplinary HLH work group comprised of hematologists, oncologists, rheumatologists, infectious disease providers, hospitalists, and intensive care unit providers along with clinical pharmacists.…”

“…4 On the other hand, HLH is an aggressive syndrome characterized by excessive activation of inflammatory cells, and it commonly presents with fever. 6,7 According to a review of HLH cases in Texas pediatric hospitals, the incidence of HLH is 1 in 100,000 children. 8 The signs and symptoms of HLH are often nonspecific and may correlate with other, more common conditions in the fields of infectious disease, rheumatology, and hematology/oncology.…”