Presentations and outcomes of familial hemophagocytic lymphohistiocytosis in the pediatric intensive care units (PICUs)

Fahad Alsohime; Mohamad-Hani Temsah; Rawan M Alotaibi; Reham M Alhalabi; Sarah AlEnezy; Aly Abdelrahman Yousef; Abdullah Mohammed Alzaydi; Hussam Sameer Inany; Ayman Al-Eyadhy; Mohammed Almazyad; Ali Alharbi; Abdulaziz Abdullah Alsoqati; Abdurahman Andijani; Mohammed Abu Ghazal; Kamal El Masri; Maher Doussouki; Raheel Farooq Butt; Saleh Alshehri; Mohammed Alsatrawi; Jaramia Macarambon; Gamal M Hasan; Abdulrahman Alsultan

doi:10.3389/fped.2023.1152409

Presentations and outcomes of familial hemophagocytic lymphohistiocytosis in the pediatric intensive care units (PICUs)

Front Pediatr. 2023 Apr 18:11:1152409. doi: 10.3389/fped.2023.1152409. eCollection 2023.

Authors

Fahad Alsohime^{1

2}, Mohamad-Hani Temsah^{1

2

3}, Rawan M Alotaibi⁴, Reham M Alhalabi⁴, Sarah AlEnezy⁴, Aly Abdelrahman Yousef^{5

6}, Abdullah Mohammed Alzaydi⁵, Hussam Sameer Inany⁵, Ayman Al-Eyadhy^{1

2}, Mohammed Almazyad^{1

2}, Ali Alharbi⁷, Abdulaziz Abdullah Alsoqati⁷, Abdurahman Andijani⁷, Mohammed Abu Ghazal⁷, Kamal El Masri⁸, Maher Doussouki⁹, Raheel Farooq Butt¹⁰, Saleh Alshehri¹⁰, Mohammed Alsatrawi^{1

2}, Jaramia Macarambon¹, Gamal M Hasan^{11

12}, Abdulrahman Alsultan^{1

13}

Affiliations

¹ Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
² Pediatric Intensive Care Unit, Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia.
³ Prince Abdullah bin Khaled Coeliac Disease Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁴ College of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia.
⁵ Division of Pediatric Critical Care, Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
⁶ Department of Pediatrics, Faculty of Medicine, Helwan University, Cairo, Egypt.
⁷ Pediatric Critical Care Division, Specialized Children Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
⁸ Pediatric Intensive Care Unit, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
⁹ Pediatric Hematology & Oncology Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
¹⁰ Pediatric Critical Care Division, King Saud Medical City, Riyadh, Saudi Arabia.
¹¹ Pediatric Department, Assiut Faculty of Medicine, Assiut University, Assiut, Egypt.
¹² Pediatric Department, Pediatric Intensive Care Unit, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
¹³ Oncology Center, King Saud University Medical City, Riyadh, Saudi Arabia.

Abstract

Objectives: We aimed to describe Familial Hemophagocytic Lymphohistiocytosis (F-HLH) patients' clinical features, intensive care courses, and outcomes.

Methods: Multi-center retrospective cohort study of pediatric patients diagnosed with F-HLH from 2015 to 2020 in five tertiary centers in Saudi Arabia. Patients were classified as F-HLH based on their genetic confirmation of known mutation or on their clinical criteria, which include a constellation of abnormalities, early disease onset, recurrent HLH in the absence of other causes, or a family history of HLH.

Results: Fifty-eight patients (28 male, 30 female), with a mean age of 21.0 ± 33.9 months, were included. The most common principal diagnosis was hematological or immune dysfunction (39.7%), followed by cardiovascular dysfunction in 13 (22.4%) patients. Fever was the most common clinical presentation in 27.6%, followed by convulsions (13.8%) and bleeding (13.8%). There were 20 patients (34.5%) who had splenomegaly, and more than 70% of patients had hyperferritinemia >500 mg/dl, hypertriglyceridemia >150 mg/dl and hemophagocytosis in bone marrow biopsy. Compared to deceased patients 18 (31%), survivors had significantly lower PT (p = 041), bilirubin level of <34.2 mmol/L (p = 0.042), higher serum triglyceride level (p = 0.036), and lesser bleeding within the initial 6 h of admission (p = 0.004). Risk factors for mortality included requirements of higher levels of hemodynamic (61.1% vs. 17.5%, p = 0.001) and respiratory (88.9% vs. 37.5%, p < 0.001) support, and positive fungal cultures (p = 0.046).

Conclusions: Familial HLH still represents a challenge in the pediatric critical care setting. Earlier diagnosis and prompt initiation of appropriate treatment could improve F-HLH survival.

Keywords: F-HLH: familial hemophagocytic lymphohistiocytosis; S-HLH: secondary hemophagocytic lymphohistiocytosis; clinical features; hemophagocytic syndrome; intensive care; pediatrics.

© 2023 Alsohime, Temsah, Alotaibi, Alhalabi, AlEnezy, Yousef, Alzaydi, Inany, Al-Eyadhy, Almazyad, Alharbi, Alsoqati, Andijani, Ghazal, Masri, Doussouki, Butt, Alshehri, Alsatrawi, Macarambon, Hasan and Alsultan.