Altaf et al. Journal of Medical Case Reports 2012, 6:141 http://www.jmedicalcasereports.com/content/6/1/141 recessive disorder in association with XIAP (X-linked in- hibitor of apoptosis protein, formerly BIRC4) mutations and X-linked lymphoproliferative disease. It usually mani- fests during infancy, but rare cases have been described in older children and adults [2]. The secondary or acquired form is caused by a variety of diseases including viral, bac- terial and protozoan infections, malignancies and macro- phage activation syndrome associated with autoimmune disorders [3]. Case presentation A 15-year-old Caucasian girl with Crohn’s disease, who was on immunosuppressive therapy with oral 6- mercaptopurine, presented with fevers and sore throat, six months after her diagnosis of inflammatory bowel disease. On examination, she had bilateral tonsillar hypertrophy with basilar exudate. Epstein-Barr virus (EBV) serologies showed the presence of viral capsid antigen immuno- globulin M, immunoglobulin G and positivity for EBV nu- clear antigen suggesting reactivation of the infection (Table 1). She went on to develop significant jaundice and liver function tests revealed elevated transaminases and direct hyperbilirubinemia (Table 2). An ultrasound of her liver did not show any obstructive pathology. The patient was hospitalized because of her persistent fevers along with jaundice, with the admitting diagnosis of EBV- induced cholestatic hepatitis. Serologies for hepatitis A, B and C, cytomegalovirus and human immunodeficiency virus (HIV) were negative. EBV copies continued to rise throughout the course of her illness, from 1,500 to 20,000 copies/mL. She continued to be febrile and developed se- vere respiratory distress and hypoxemia, requiring transfer to the pediatric Intensive Care Unit. A bone marrow biopsy and a diagnostic lumbar punc- ture were performed. Her cerebrospinal fluid showed evidence of pleocytosis. The bone marrow biopsy showed pancytopenia and increased lymphohistiocytic infiltrates with prominent hemophagocytosis (Figure 1). The significant inflammatory response with high fevers and pancytopenia was attributed to her being infected with EBV. A decision was made to administer one dose of rituximab and high dose immunoglobulins to control the exaggerated immune response. Table 1 Epstein-Barr virus serologies during the course of illness EBV nuclear antigen EBV viral capsid antigen Positive immunoglobulin G EBV viral capsid antigen Positive immunoglobulin M Diagnosis of HLH At completion of therapy Positive Negative Negative Negative Page 2 of 6 There was laboratory evidence of cytopenia, with results notable for falling neutrophil count, severe anemia and thrombocytopenia (Table 2). There was moderate elevation of ferritin and triglycerides. Her soluble CD25 (soluble interleukin-2 receptor) level was elevated at 39,322U/mL. (this information was not available at initial presentation). There was complete absence of CD16 and CD56 positive NK cells. NK cytotoxicity, porphyrin and granzyme testing could not be done with the initial presentation due to the absence of NK cells. Fibrinogen and coagulation studies remained within normal limits. Our patient was diagnosed with EBV-driven HLH as she fulfilled five of the eight required criteria for diagnosis, and she was started on chemotherapy with etoposide, dexamethasone and ciclos- porin based on HLH 2004 protocol. Testing was also done to rule out HIV and other immune deficiencies. Genetic testing was carried out to rule out PRF 1, UNC13D, STX11 and STXBP2 mutations as well as sig- naling lymphocytic activation molecule-associated protein expression (SLAM) on cytotoxic lymphocytes. Our patient had moderate cervical lymphadenopathy (2cm), which was attributed to her EBV viremia at the time of diagnosis of HLH. There was moderate splenomegaly on a computed tomography scan of her abdomen but no other significant lymphadenopathy was noted, hence the diagno- sis of lymphoma was not strongly considered. No further doses of rituximab were administered once HLH therapy was started. Her chemotherapeutic regimen included dexa- methasone, etoposide and ciclosporin. Our patient received eight weeks of therapy on this protocol. She responded to therapy and improved clinically. Table 2 Laboratory data at diagnosis of hemophagocytic lymphohistiocytosis and lymphoma Hemoglobin (g/dL) White blood cells (×109/L) Absolute neutrophil count (×109/L) Platelets (×109/L) Ferritin (mcg/L) Fibrinogen (mg/dl) Alanine transaminase (U/L) Total bilirubin (mg/dL) Direct bilirubin (mg/dL) Triglycerides (mg/dL) Epstein-Barr virus copies Soluble CD25 (U/mL) Aspartate transaminase (U/L) 8 to 43 Reference range 12 to 15.5 3.5 to 10.5 1.7 to 7.0 Diagnosis of HLH 7.7 0.3 0 150 to 450 17 11 to 307 4,485 200 to 430 309 7 to 45 0.1 to 1.0 0.0 to 0.3 - - 45 to 1105 39,322 146 264 6.5 4.4 341 20,500 1,500 Diagnosis of lymphoma 9.6 3.1 2.39 99 1,749 38 45 0.7 0.4 - - EBV: Epstein-Barr virus; HLH: hemophagocytic lymphohistiocytosis. HLH: hemophagocytic lymphohistiocytosis.