Hemophagocytic lymphohistiocytosis induced by viral diseases is a well recognized entity. Severe forms of H5N1 influenza are known to be associated with symptoms very similar to a reactive hemophagocytic syndrome. We report a case of fulminant lymphohistiocytosis associated with the pandemic A (H1N1) variant.
A 42-year-old Caucasian woman developed a syndrome of fatal hemophagocytic lymphohistiocytosis shortly after H1N1 influenza. Initial symptoms of the viral disease were unusual, with acute abdominal involvement. Our patient's course was complicated by diffuse skin rash and ileal ischemia. Our patient died of refractory shock and multi-organ failure. Skin, ileum and colon histology was consistent with an acute apoptosis combined with an increased cellular regeneration.
Influenza may be complicated by severe forms of hemophagocytic lymphohistiocytosis. To ensure early recognition and treatment, physicians should be aware of the possible induction of the syndrome by the novel H1N1 variant. The rapid occurrence of a multi-organ involvement with evocative biological features of macrophage activation should alert clinicians.
Hemophagocytic lymphohistiocytosis is an immune-mediated syndrome that typically has a rapidly progressive course that can result in pancytopenia, coagulopathy, multi-system organ failure and death.
A 57-year-old Caucasian woman was referred in fulminant hemophagocytic lymphohistiocytosis, with fever, pancytopenia, splenomegaly, mental status changes and respiratory failure. She was found to have stage IV classical Hodgkin lymphoma, in addition to Epstein-Barr virus and cytomegalovirus viremia. Her presentation was preceded by a 3-year prodrome consisting of cytopenia and fever that were partially controlled by steroids and azathioprine.
Fulminant hemophagocytic lymphohistiocytosis may follow a prodromal phase that possesses features suggestive of a chronic form of hemophagocytic lymphohistiocytosis, but which may also resemble immune cytopenias of other causes. A diagnosis of hemophagocytic lymphohistiocytosis should be considered in the setting of chronic pancytopenia.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, fatal disorder of children, affecting predominantly the mononuclear phagocytic system. Previous reports indicate that Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) can also be fatal in many cases, although the prognosis for EBV-HLH is better than for the familial form of hemophagocytic lymphohistiocytosis. We treated four patients with EBV-HLH using immunochemotherapy including steroid, etoposide (VP-16), and cyclosporin, according to the HLH-94 protocol. All patients experienced persistent fever, cytopenia, and hypertriglyceridemia. Serological testing for EBV showed reactivated EBV infections in all patients. EBV DNA detected by PCR and EBV-encoded small RNA measured by in situ hybridization were confirmed in the patients' bone marrow specimens. Hemophagocytosis was shown in bone marrow aspirates and liver biopsy specimen. Complete remission was achieved in all patients after induction and continuation therapy for 4-10 months (median, 7 months) and was maintained for 15-27 months (median, 19 months) without the need for bone marrow transplantation. These results suggest that EBV-HLH can be effectively controlled by immunochemotherapy using the HLH-94 protocol.
Epstein-Barr Virus Infections; Hemophagocytic Lymphohistiocytosis; Histiocytosis, Non-Langerhans-Cell; Etoposide; Cyclosporine; HLH-94; Child
Hemophagocytic lymphohistiocytosis is a potentially fatal disease characterized by excessive macrophage and lymphocyte activity. Patients can be affected following immune activation after an oncologic, autoimmune or infectious trigger. An associated gene mutation may be found which impairs cytolytic lymphocyte function. We describe a pediatric case of hemophagocytic lymphohistiocytosis with a novel mutation of MUNC 13–4 whose diagnosis was confounded by concurrent immunosuppression. Clinical reassessment for hemophagocytic lymphohistiocytosis is necessary in persistently febrile patients with laboratory derangements in the setting of immunosuppressive agent exposure.
Hemophagocytic lymphohistiocytosis; MUNC 13–4; Macrophage activation syndrome
Hemophagocytic lymphohistiocytosis is characterized by multisystem inflammation, resulting from prolonged and intense activation of macrophages, histiocytes and CD8+ T-cells. Due to its variable presentation and non-specific findings, timely diagnosis can be challenging. This condition has been associated with malignancies, most commonly with lymphomas and leukemias of T-cell lineage. This case report represents the less commonly associated B-cell lymphomas. We also highlight the difficulties in managing hemophagocytosis with an evolving malignancy. This case report will add to the increasing literature on the diagnosis, complications and management of this complex disorder.
A 15-year-old Caucasian girl, previously diagnosed with Crohn’s disease and treated with 6-mercaptopurine, developed Epstein-Barr virus infection-driven hemophagocytic lymphohistiocytosis. The diagnosis was challenging due to her critical illness and the lack of enough features to fulfill diagnostic criteria at presentation (moderately elevated ferritin, normal coagulation profiles and normal triglycerides). While receiving therapy for hemophagocytic lymphohistiocytosis, she developed bulky cervical lymphadenopathy and was diagnosed with diffuse large B-cell lymphoma. Therapy for lymphoma was initiated and she tolerated the therapy well.
Hemophagocytic lymphohistiocytosis is a rare disorder, but potentially lethal if not diagnosed and treated in a timely manner. Our case highlights the importance of considering this diagnosis in critically ill patients who may not initially fulfill formal diagnostic criteria. In patients diagnosed with hemophagocytic lymphohistiocytosis, occult malignancies should be aggressively ruled out as they can manifest prior to the hemophagocytic lymphohistiocytosis diagnosis or appear during the treatment phase. An accurate diagnosis is also important because management of Epstein-Barr virus-driven hemophagocytic lymphohistiocytosis and Epstein-Barr virus-driven lymphoma differs due to the difference in pathophysiology and the involvement of different immune cell lines.
Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and pathologic findings of hemophagocytosis in the bone marrow and other tissues. HLH may be familial or associated with different types of infections, autoimmune disorders, or malignancies. Infection-associated HLH has been reported in various viral, bacterial, fungal, and parasitic infections, and case reports of parasitic infections implicated in HLH include rare cases from Plasmodium vivax infection, which occasionally affects both military personnel and civilians in Korea. We describe an unusual case of HLH resulting from Plasmodium vivax infection and review the literature. This case suggests that clinical suspicion of HLH is important when P. vivax infection is accompanied by cytopenias. Administration of antimalarial drugs may prevent irreversible end organ damage resulting from P. vivax-associated HLH.
Hemophagocytic lymphohistiocytosis; Plasmodium vivax
Patient: Male, 30
Final Diagnosis: Hemophagocytic lymphohistiocytosis (LHL)
Symptoms: Abdominal pain • fever • hypotension • pancytopenia
Specialty: Infectious Diseases
Hemophagocytic lymphohistiocytosis (HLH) is a result of dysregulated cellular response system. Primary HLH is an autosomal recessive disorder of childhood, with defects in cellular cytotoxicity. Secondary HLH is an acquired syndrome that presents in young adulthood secondary to a variety of inflammatory conditions: viral infections, rheumatologic conditions, or malignant processes. The inflammatory nature of certain conditions triggers a cytokine release in individuals who have abnormal T cell activation.
A 30-year-old Hispanic male presented with worsening abdominal pain for 5 months and was found to have fever, pancytopenia, and hypotension. Serial CT scans of the abdomen/pelvis showed splenomegaly but no abscesses, areas of infection, or masses. Infectious causes were considered but results of all cultures and tests were negative except for a high Epstein-Barr viral load. The patient deteriorated and required intubation on hospital day 28. Repeat bone marrow biopsy on day 32 suggested a diagnosis of hemophagocytic lymphohistiocytosis, although there was no evidence of hemophagocytosis within the bone marrow. The patient continued to deteriorate and was too unstable to receive treatment with chemotherapy. He died on hospital day 34.
This case highlights the importance of early consideration and treatment of secondary HLH in an individual presenting with progressive fever, hepatomegaly, and cytopenias.
EBV; EBV associated with hemophagocytic lymphohistiocytosis; hemophagocytic lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis (HLH) implies a benign generalized histiocytic proliferate with erythrophagocytosis and it includes familial hemophagocytic lymphohistiocytosis and secondary hemophgocytosis. Spinal fluid changes like mild to moderate pleocytosis (most of the cells are lymphocytes and macrophages) and sometimes hemophagocytosis are seen in primary HLH but are not reported in secondary HLH. Here we report a case of a previously healthy 10 months old male infant who was diagnosed as familial HLH with evidence of CSF hemophagocytosis. He was started on the HLH 2004 treatment protocol with no improvement. A second bone marrow aspiration revealed leshmania donovani antibodies and he was started on anti-leishmania treatment with dramatic response.To the best of our knowledge, this is the first case of secondary HLH with evidence of hemophagocytosis in cerebrospinal fluid.
Lymphohistiocytosis; hemophagocytic; Leishmaniasis; Cerebrospinal fluid; Case Report; Oman
Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow and other tissues. HLH may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently linked with Epstein-Barr (EBV) virus infection. Hyperproduction of cytokines, including interferon-gamma and tumor necrosis factor-alpha, by EBV- infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy, while hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.
Mycoplasma pneumoniae (Mp) sometimes causes immunological complications in children. We present a rare case of hemophagocytic syndrome (HPS) caused by Mp in a previously healthy 7-year-old Japanese girl. A chest radiograph obtained to evaluate the source of her fever showed infiltration in the lower right lung with mild splenomegaly. We could diagnose the patient with HPS on the basis of the hemophagocytic-lymphohistiocytosis- (HLH) 2004 criteria. She met the criteria for fever, splenomegaly, neutrophil count (<1,000/μL), platelet count (<10.0 × 104/μL), fasting triglyceride level (>265 mg/dL), and ferritin level (>500 ng/mL). Furthermore, a peripheral blood smear showed an increased number of monocytes/macrophages with erythrophagocytosis. Treatment with clarithromycin and prednisolone, which was initiated soon after the diagnosis, was successful. Mp infection might partly progress to HPS in certain conditions. Clinicians should be aware of HPS caused by Mp and start appropriate treatment as soon as possible if the disease is suspected.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-γ and TNFα is present in serum. In animal models of the disease, IFN-γ and TNF-α have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-γ, and TNF-α have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) resulting in an excess of free IL-18. Here we studied whether IL-18BP could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock-out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18BP treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-γ and TNF-α production by CD8+ T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18BP is beneficial in an animal model of HLH and in combination with anti-infectious therapy may be a promising strategy to treat HLH patients.
IL-18; IL-18 binding protein; natural killer cells; hemophagocytic lymphohistiocytosis; macrophage activation syndrome
Identify risk factors associated to mortality in pediatric patients with hemophagocytic lymphohistiocytosis.
Retrospective cross-sectional study of medical records with discharge diagnosis of Hemophagocytic syndrome/Hemophagocytic lymphohistiocytosis (ICD-10; D76.1/D76.2) from Jan2004-May2011 in a pediatric-tertiary-care-center. Descriptive and risk analysis were made on SPSS Statistics V17.0.
Thirty medical records were analyzed. Median-for-age: 2 years 8 months, (range: 2 months-to-15 years). Sex distribution: 14 girls (47%), 16 boys (53%). Median of symptoms duration: 1 month (range: 3 days-to-7 years). Reported symptoms and physical signs at hospital admission: fever n = 28 (93%), asthenia/adynamia n = 11 (37%), skin findings n = 10 (33%), epistaxis n = 5 (17%), gastrointestinal bleeding n = 4 (13%), hepatomegaly n = 27 (90%), splenomegaly n = 21 (70%), lymphadenopathies n = 14 (47%), paleness n = 14 (47%), purpura n = 5 (17%). Laboratory findings: anemia n = 29 (97%), LDH elevation n = 28 (93%), hypoalbuminemia n = 27 (90%), thrombocytopenia n = 26 (87%), hypertransaminasemia n = 25 (83%), haemophagocytosis n = 22 (73%), hypertrigliceridemia n = 21 (70%), hypofibrinogenemia n = 20 (67%), leucopenia n = 19 (63%), hyperferritinemia n = 15(50%). In 18 patients (60%) active infection was evident at hospital admission: pneumonia n = 9(50%), gastroenteritis n = 2 (11%), meningitis n = 1 (5%), others n = 6 (33%). Epstein-Barr virus infection was diagnosed in 7 patients (23%). All patients were treated according to HLH-2004 guidelines. Overall mortality 63% (n = 19), 9(47%) died from septic-shock, 7 (36%) haemorraghic-shock, and 1(5%) with acute liver failure. Differences between non-survivours and survivours by (x2): hypofibrinogenemia (53%versus 13%; P = 0.039), epistaxis (17% versus 0%; P = 0.023), evident clinical infection (47%versus 13%; P = 0.044), elevated LDH levels (63% versus 30%; P = 0.039), hemophagocytosis (57% versus 17%; P = 0.024). Risk factors associated to mortality: history of epistaxis (OR = 1.78, 95% CI, 1.26-2.52; P = 0.023), evident clinical infection at hospital admission (OR = 2.41, 95% CI, 1.08-5.8; P = 0.044). Normal levels of LDH showed diminished mortality risk (OR = 0.32, 95%, CI, 0.18-0.55; P = 0.039).
The present study describes the most common clinical, physical and laboratory findings in patients with haemophagocytic lymphohistiocytosis attended in our hospital. We were able to identify risk factors associated to mortality, and 1 protective factor.
The involvement of the central nervous system (CNS) in familial hemophagocytic lymphohistiocytosis (FHL) has known to be limited to the brain, brain stem, and cerebellum. Herein, we report an 11-year-old boy who presented with neurological symptoms and was diagnosed as FHL by molecular diagnosis. The hemophagocytic lesions in the CNS were shown to extend to the thoracal level of spinal cord which completely disappeared after the completion of hemophagocytic lymphohistiocytosis-2004 protocol.
Central nervous system; familial hemophagocytic lymphohistiocytosis; spinal cord involvement; UNC13D gene mutation
Hemophagocytic lymphohistiocytosis (HLH) in different ethnicities has been described in the literature, but few cases in patients of Chinese descent have been reported. Here, we describe the case of a Chinese neonate presenting with HLH carrying novel, compound heterozygous mutations of the UNC13D gene, including [c.2295_2298delGCAG, p.Glu765Aspfs*27] in exon 23, c.-250C>T, c.1+30G>A, c.279C>T, c.888G>C, c.18+36A>G, c.20-48T>C, c.1977C>T, c.2296C>T, c.24-46C>T, c.26-9_26-8insC, c.2599A>G, c.28+48C>T and c.3198A>G, some of which have not been reported in the literature. Cytokine profile analyses were performed in this patient, and the results were consistent with our previous findings in HLH patients. Cytokine profile monitoring may be helpful in differentiating among various clinical phases of HLH.
FHL; hemophagocytic lymphohistiocytosis; UNC13D; CD107a; cytokine monitoring
Background. Chronic granulomatous disease is a rare inherited disorder of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The clinical course of the disease is marked by recurrent infections, including Burkholderia cepacia complex infection. Case Report. Here we report the case of a 21-year-old male hospitalized for a Burkholderia cepacia complex pneumonia. Despite the broad spectrum antibiotic treatment, fever continued and patient's condition worsened. Anemia and thrombocytopenia developed together with hypofibrinogenemia. The patient died of multiple organ dysfunction 17 days after his admission. Autopsy revealed hemophagocytosis, suggesting the diagnosis of acquired hemophagocytic lymphohistiocytosis. DNA analysis showed a deletion in the p47phox gene, confirming the diagnosis of autosomal recessive chronic granulomatous disease. Discussion. In addition to chronic granulomatous disease, recent findings have demonstrated that Burkholderia cepacia complex can decrease activity of the NADPH oxidase. Interestingly, hemophagocytic lymphohistiocytosis is characterized by an impaired function of the T-cell mediated inflammation which is partly regulated by the NADPH oxidase. Physicians should therefore pay particular attention to this deadly association.
Stevens-Johnson syndrome (SJS) is a severe skin and mucosal bullous disease. When complicated with Hemophagocytic lymphohistiocytosis (HLH), the condition is especially life-threatening.
Here we report the case of a 4-year-old boy suffering from SJS with extensive erythema multiforme and bulla. Despite active intervention and supportive care, the boy experienced increased skin lesions and a higher fever. Meanwhile, decreases in white blood cell count and hemoglobin were observed. Hyperferritinemia, increased soluble CD25 level, decreased NK cell activity and hemophagocytosis in the boy’s bone marrow confirmed the diagnosis of HLH. After high-dose intravenous immunoglobulin and methylprednisone pulse therapy, the boy was discharged in good condition.
Simultaneous occurrence of HLH and SJS is very uncommon and the condition is life-threatening. Pancytopenia can be a precocious indicator and enables to start a prompt diagnosis and treatment.
Pancytopenia; Early diagnosis; Stevens-Johnson syndrome (SJS); Hemophagocytic lymphohistiocytosis (HLH)
Hemophagocytic lymphohistiocytosis (HLH) has been described in patients with advanced stages of human immunodeficiency virus (HIV) infection, but rarely occurs during the seroconversion stage of acute HIV infection. We report a case of acute HIV syndrome that presented with virus-associated HLH. The patient recovered spontaneously without any immunomodulating therapy. This case suggests that acute HIV infection should be included in the differential diagnosis of HLH and indicates that HLH associated with acute HIV infection can have a favorable outcome.
Acute human immunodeficiency virus syndrome; hemophagocytic lymphohistiocytosis
We report a case of Epstein-Barr virus (EBV) primo infection with the development of successive infectious mononucleosis, hemophagocytic lymphohistiocytosis, and B-cell lymphoproliferative disorder in a patient treated with azathioprine for Crohn's disease. This case report suggests that specific EBV-related clinical and virological management should be considered when treating a patient with inflammatory bowel disease with azathioprine.
Background. Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an “accelerated phase” characterized by hemophagocytic lymphohistiocytosis (HLH). The disease is caused by mutations in the CHS1/LYST gene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in the CHS1 gene: c.3622C > T (p.Q1208X) and c.11002G > T (p.E3668X). Conclusions. Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in the CHS1 gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS.
Perforin plays a key role in the cytotoxicity of natural killer and cytotoxic T cells. Genetic mutations in the perforin gene (PRF1) give rise to approximately 30% cases of familial hemophagocytic lymphohistiocytosis. A frequent polymorphism, A91V (C to T transition at position 272), may impair processing of perforin protein to the active form, and has been suggested to increase susceptibility to childhood acute lymphoblastic leukemia (ALL). To investigate the role of A91V in ALL, we genotyped 2272 children with de novo ALL registered on the Pediatric Oncology Group ALL Classification study P9900 and 655 normal controls. Allele frequencies in the controls showed a very low frequency of the variant allele in blacks, 0.7% compared to 4% in white controls. In light of this, analysis was restricted to a comparison of white cases and controls only. Overall genotype frequencies were similar in white ALL cases and normal white controls (P = 0.58), indicating that in contrast to the previous report, A91V polymorphism is not associated with increased risk of childhood ALL. PRF1 A91V frequency was significantly increased in children with BCR-ABL positive ALL (24 vs 8.5%; P = 0.0048); however, this observation includes a relatively small number of cases and needs further exploration.
perforin; polymorphism; acute lymphoblastic leukemia
We present a case of hemophagocytic lymphohistiocytosis (HLH) in a previously healthy 30-year-old woman. The patient presented with features consistent with HLH: persistent fever, neurological abnormalities, lymphadenopathy, anaemia, leucopoenia and markedly elevated serum lactate dehydrogenase and ferritin levels. Diagnosis was delayed for approximately 1 month beyond presentation. Once initiated on treatment, the patient rapidly improved and was discharged from the intensive care unit and subsequently sent home. Unfortunately, she succumbed to progressive HLH 5 months after her initial presentation. This case highlights key clinical features associated with HLH to help prevent late diagnosis as delayed treatment may lead to irreversible multi-organ failure and/or death.
Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare immune deficiency with defective cytotoxic function. The age at onset is usually young and the natural course is rapidly fatal if untreated. A later onset of the disease has been sporadically reported even in adolescents and adults. We report the results of our retrospective data collection of all cases diagnosed with FHL at an age of 18 years or older and enrolled in the Italian Registry of HLH. All cases were diagnosed with FHL based on evidence of genetic defect in one FHL-related gene. A total of 11 patients were diagnosed with FHL. They were 9 males and 2 females, from 10 unrelated families; their age ranged between 18 and 43 years (median, 23 years). Family history was unremarkable in eight families at the time of the diagnosis. Their genetic diagnoses are: FHL2 (n = 6), FHL3 (n = 2), FHL5 (n = 1), XLP1 (n = 2). Clinical, molecular and functional data are described. These data confirm that FHL may present beyond the pediatric age and up to the fifth decade. FHL2 due to perforin defect is the most frequently reported subtype. Adult specialists should consider FHL in the differential diagnosis of patients with cytopenia and liver or central nervous system disorders, especially when a lymphoproliferative disease is suspected but eventually not confirmed. FHL may turn to be fatal within a short time course even in adults. This risk, together with the continuous improvement in the transplant technique, especially in the area of transplant from matched unrelated donor, resulting in reduced treatment related mortality, might suggest a wider use of SCT in this population. Current diagnostic approach allows prompt identification of patients by flow-cytometry screening, then confirmed by the genetic study, and treatment with chemo-immunotherapy followed by stem cell transplantation.
To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH.
We conducted a retrospective study of all children who developed HLH over an 8 year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD.
20 cases of HLH occurred among children in Wisconsin during the study period. Five cases occurred in children with IBD. Common characteristics include: Crohn disease (CD), thiopurine administration, fever >5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia and elevated serum triglycerides and ferritin. Four patients had primary Epstein Bar Virus (EBV) infections. The incidence of HLH among all children in Wisconsin was 1.5/100,000 per year. The risk was more than 100 fold greater for children with CD (p< 0.00001).
Pediatric patients with CD are at increased risk for developing HLH; primary EBV infection and thiopurine administration may be risk factors.
inflammatory bowel disease; pediatrics; Epstein Bar Virus
Granulocyte transfusions may be useful for neutropenic pediatric patients with refractory bacterial or fungal infections. Many potential adverse sequelae associated with granulocyte transfusions are well recognized, including febrile reactions, fluid overload, alloimmunization, and lung injury. Other potential adverse sequelae, however, are less well known. This case report describes an infant with familial hemophagocytic lymphohistiocytosis (FHL) who developed polycythemia (hemoglobin 10 g/dL to 17.6 g/dL) following four daily transfusions of 20 ml/kg of apheresis collected, steroid stimulated donor granulocytes. Expanded knowledge of potential risks of transfused granulocytes will allow for rapid recognition of transfusion related complications, should they occur.
Transfusion; red blood cells; granulocytes; neutropenia
Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient’s ability to receive optimal chemotherapy.
Design and Methods
To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).
According to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01) and a higher mortality rate (47.4% vs. 30.2%, P<0.01) than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI.
AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.