The term haemophagocytic lymphohistiocytosis (HLH) includes the disease that was previously known as familial erythrophagocytic lymphohistiocytosis and cases associated with infection, including virus associated haemophagocytic syndrome. The distinction was misleading; cases that are likely to have a genetic basis may not have a positive family history. Familial HLH can be triggered by infection, including infection with viruses.
Establish epidemiological data in the absence of other data from the United Kingdom (only one retrospective survey has been reported, from Sweden)
Improve awareness and diagnosis. Although there is no diagnostic test, the syndrome is fairly easy to recognise if clinicians are aware of it.
Advise on management. The advent of bone marrow transplantation has made this disease potentially curable. The study co-ordinators advised on diagnosis and current management based on an increasing number of patient histories and contact with reporting practitioners.
Research on aetiology and pathogenesis.
Haemophagocytosis in bone marrow, spleen, lymph nodes, or other sites without evidence of malignancy.
Note: Haemophagocytic activity may not always be seen at the time of presentation and serial aspirates over a period of time may be useful.
Exclusion criteria: previous immunosuppressive therapy, concurrent malignancy, and Langerhans cell histiocytosis.
Study duration: The study began in September 1991 and ended in August 1994.
Ninety reports were made during the three years of the survey, 54 of which have been confirmed as cases. Twenty-seven of the 90 were duplicates, 6 were reported in error or the diagnosis subsequently changed, and the diagnosis of two reported patients is not yet known. The annual incidence (18 reported cases a year) for the 36 month period was approximately 1.52 cases/million children/year. The incidence exceeds that obtained in a retrospective study in Sweden (1.2 cases/million children/year) by 27% but study design and population background are likely to explain the difference.
Most of the patients were treated using a protocol, which includes etoposide and prednisolone and more recently with dexamthasone according to a newly established international treatment protocol (HLH 1994). Cyclosporin A has been mostly used after the initial treatment intended to induce remission. Patients with severe disease who do not respond have been given antilymphocyte globulin. Severe involvement of the central nervous system at presentation seems to be a poor prognostic factor. Matched boned marrow transplantation (also recently with matched unrelated donors (MUD)) in remission has been successful in several patients.
This study has helped to establish a network of clinical and basic research. Studies are underway to identify the underlying genetic susceptibility in a subgroup of those patients and will be reported when completed.
No optimal treatment of HLH currently exists, but international collaboration has led to the development of diagnostic and treatment protocols, which are being evaluated prospectively. The study co-ordinator is Dr David Webb, who can be contacted at the Department of Paediatrics, Llandough Hospital, Llandough, Cardiff, South Glamorgan, (telephone 01222 711711). It is important to enrol as many patients as possible, especially with the aim of assessing the overall benefits of sibling and matched bone marrow transplantation from siblings and matched unrelated donors (MUD).
The investigators would like to thank the practitioners who reported the patients and readily provided further clinical information. We are especially grateful to those who provided samples for further immunological and genetic analysis.
The reporting system has been very successful (as judged by the number of duplicate reports). We ask all practitioners and paediatricians to continue reporting direct to the addresses below in order to enrol patients into the therapeutic study and to help with the continuing clinical and research analysis of this still unresolved disease.
Professor S Strobel, Institute of Child Health, 30 Guilford Street, London WC1N 1EH. Tel: 020 7242 9789 Fax: 020 7242 8437 Email: sstrobel@ich.bpmf.ac.uk