Altaf et al. Journal of Medical Case Reports 2012, 6:141 http://www.jmedicalcasereports.com/content/6/1/141 should be aggressively pursued if there is suspicion about the possible presence of a malignancy [12]. Defects in interleukin-2 inducible T-cell kinase gene (ITK) are being noticed in females with EBV-induced HLH, clinically resembling X-linked lymphoproliferative disorder [13]. Testing for ITK did not show any abnor- mality in the gene. Over 90% of patients with defects in the XIAP gene develop HLH, associated with and with- out EBV. These patients are also at risk for recurrent HLH [14]. X-linked recessive inheritance of XIAP, is rarely seen in females, unless there is skewed inactiva- tion of the wild type X chromosome. We have not com- pletely ruled out this rare possibility in our patient. HLH is a disorder with an evolving spectrum of presentation. So far, 70% of the patients with familial HLH have an identified genetic mutation; 30% of North American patients do not have identified mutations in any of the four relevant genes [15]. As more genetic associations are identified, we will learn more about genotype- phenotype correlations in this disorder. Our report highlights the spectrum of findings asso- ciated with EBV infections, and the clinical overlap be- tween EBV-driven HLH and EBV-driven lymphoma. The initial presentation was that of secondary HLH related to EBV infection, which was suspected due to persist- ently rising EBV titers and the possibility of a weakened T-cell system from the immunosuppressive therapy for Crohn’s disease. Our patient may have been in the pre- clinical stages of lymphoma triggered by EBV affecting the B-lymphocytes, and this transformation was possibly hastened by the presence of impaired T-cells and histio- cytes. The clinical distinction between EBV-related HLH and EBV-associated lymphoma is also important for management purposes. Our patient responded clinically to HLH therapy, but would have gone on to develop fur- ther complications of lymphoma if this had not been promptly recognized. After completion of the lymphoma therapy, our patient has been in complete remission. Due to a lack of evidence of a primary immune defi- ciency and excellent response to therapy, bone marrow transplantation was not considered. Vigilant follow-up with imaging at scheduled intervals will be required for a prolonged period of time. Conclusion HLH is a rare disorder, but potentially lethal if not diag- nosed and treated in a timely manner. Our case high- lights the importance of considering this diagnosis in critically ill patients who may not initially fulfill formal diagnostic criteria. Potential complications of this dis- order, including malignancy, should also be anticipated. In patients diagnosed with HLH, occult malignancies should be aggressively ruled out. Page 5 of 6 Consent Written informed consent was obtained from the patient for the publication of this case report and any accom- panying images. A copy of the written consent is avail- able for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Author details 1Division of Pediatric Hematology/Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st Street SW, Rochester MN 55905, USA. 2Division Pediatric Critical Care, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st Street SW, Rochester MN 55905, USA. 3Division of Pediatric Allergy and Immunology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st Street SW, Rochester MN 55905, USA. Authors’ contributions SA compiled and analyzed the patient’s data and wrote the initial draft. 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