Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome

ABSTRACT

Background

Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations.

Research designand methods

We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children’s Hospital,Cairo, Egypt.

Results

Median age at diagnosis was 19 months (range 2–180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity.

Conclusions

This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

KEYWORDS:

• Hemophagocytic lymphohistiocytosis
• diagnostic criteria
• genetic variants
• treatment outcome
• UNCD
• Mortality

Abbreviations

CHS	=	Chediak-Higashi syndrome
FHLH	=	familial hemophagocytic lymphohistiocytosis
GS	=	Griscelli syndrome
HLH	=	Hemophagocytic lymphohistiocytosis
HPS	=	Hermansky-Pudlak syndrome
HSCT	=	Hematopoeietic stem cell transplantation
LCH	=	Langerhans cell histiocytosis
PRF	=	Perforin
SAP	=	Signaling lymphocytic activation moleculeassociated protein
STX	=	Syntaxin
XIAP	=	X linked inhibitor of apoptosis protein
XLP	=	X-linked lymphoproliferative

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

AA Tantawy contributed to project administration. NHK Elsherif contributed to conceptualization, methodology, investigation, and writing the original draft. SM Elsayed contributed to data curation, and reviewing and editing the writing. HGA Ali contributed to the methodology, investigation, formal analysis, and writing the original draft. SM Makkeyah contributed to the investigation, resources, and review and editing the writing. HIE Elsantiel contributed to the investigation and the resources. G de Saint Basile contributed to the methodology, investigation, and review and editing the writing. IA Ragab contributed to the conceptualization, methodology, and review and editing the writing.

Ethical approval

The study was approved by the local ethics committee of the Paediatrics Department, Faculty of Medicine, Ain Shams University.

Patient consent

Patient`s legal guardians consented before reviewing the medical records and signed consent for genetic testing.

Acknowledgments

We are grateful to Nathalie Lambert and Virginie Grandin for their technical assistance in genetic screening.

Data availability statement

Raw data was generated at Ain Shams University, Faculty of Medicine, Pediatric Hematology-Oncology Unit. Derived data supporting the findings of this study is available from the corresponding author IA Ragab on request.

Additional information

Funding

The molecular studies were supported by funding from INSERM [Institut National de la Santé et de la Recherche Médicale] and from the association LHF espoir [Lymphohistiocytose Famililale Espoir].