Clinical features and outcomes in secondary adult hemophagocytic lymphohistiocytosis
Min ZhouL LiQ ZhangShanshan MaJianai SunLixia ZhuDebin LuJingjing ZhuDe ZhouYunquan ZhengYang XiangMixue XieMingkun ZhuX YeWanzhuo Xie
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Abstract:
Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by an infrequent but immune-mediated life-threatening disease, with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality and challenging diagnosis. The purpose of this study was to improve the recognition and understanding of HLH. Retrospective observational cross-sectional study. Data were collected for all cases of adult patients diagnosed with HLH in a large cohort managed at a single medical center from January 2011 to December 2015. The median age was 52 years (range 18–90 years) and 123 (60.0%) were male. Over 95% patients manifested fever, hyperferritinemia and elevated lactate dehydrogenase. Underlying triggers of HLH were as follows: 119 (58.0%) malignancies, 83 (40.5%) infections, 14 (6.8%) unknown triggers and 14 (6.8%) autoimmune disorders. The median overall survival was 55 days. And elderly patients (age ≥60 years) had a markedly worse survival compared with young patients (age <60 years) (median overall survival 24 days vs. 159 days, respectively; P <0.001). In a multivariable analysis, platelet <40 × 109/l (HR = 2.534; 95% CI 1.152–5.573; P = 0.021), PT prolonged >3 s (HR = 1.909; 95% CI 1.127–3.234; P = 0.016) and malignancy (HR = 1.614; 95% CI 1.008–2.582; P = 0.046) were correlated with poor survival. HLH adult patients had very complex clinical manifestations as well as underlying diseases. Patients with PLT <40 ×109/l, PT prolonged >3 s and malignancy had inferior survival. It is of great importance to improve our understanding of this syndrome.Keywords:
Hemophagocytic Lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH), is an uncommon, life-threatening hyperinflammatory syndrome caused by severe hypercytokinemia with excessive activation of lymphocytes and macrophages due to a highly stimulated but ineffective immune process. We report a case of Hemophagocytic Lymphohistiocytosis in a 15 year old boy presenting with fever, lymphadenopathy and pancytopenia due to infection caused by Klebsiella Pneumoniae and Acinetobacter.
Hemophagocytic Lymphohistiocytosis
Macrophage Activation Syndrome
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Hemophagocytic lymphohistiocytosis is a syndrome of pathologic immune activation that shares similar clinical and laboratory phenotypes with severe sepsis. Recent studies led to better recognition of hemophagocytic lymphohistiocytosis by clinicians, but no consensus exists on the criteria for high-risk patients.We retrospectively reviewed the medical records of patients diagnosed with hemophagocytic lymphohistiocytosis to analyze the risk factors associated with poor outcome.Pediatric intensive care and hematology units of three tertiary hospitals in Turkey.Fifty-two children with hemophagocytic lymphohistiocytosis.None.There were a total of 52 children meeting the diagnostic criteria of Histiocytic Society. Of them, 28 (54%) had a primary hemophagocytic lymphohistiocytosis. Mutation studies were performed in 18 of 28 patients (65%). Fourteen of them had PRF1, STX11, STXBP2, and UNC13D mutations, and four had Rab27a and LYST mutations. The remaining 24 patients (46%) were defined as having secondary hemophagocytic lymphohistiocytosis. Twenty-one of them had infection-associated hemophagocytic lymphohistiocytosis, and three had lysinuric protein intolerance. The mortality rate was significantly higher in primary hemophagocytic lymphohistiocytosis (64%) than in secondary hemophagocytic lymphohistiocytosis (16%) (p < 0.05). There were no significant differences for survival rate between hemophagocytic lymphohistiocytosis 94 (44%) and hemophagocytic lymphohistiocytosis 2004 (64%) protocols (p > 0.05). Age below 2 years, hyperferritinemia, thrombocytopenia, high disseminated intravascular coagulation score at diagnosis, and no clinical response at 2 weeks of treatment were independent prognostic factors for poor prognosis.Our data suggest that disseminated intravascular coagulation score greater than or equal to 5 can be used in the definition of high-risk patients. Early recognition of poor risk factors has important prognostic and therapeutic implications.
Hemophagocytic Lymphohistiocytosis
Hemophagocytosis
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Objective: To describe a case of adult onset, secondary hemophagocytic lymphohistiocytosis (HLH), with neurological manifestations. Background: HLH is a rare immune disorder, most often observed in children, involving macrophage hyperactivation and subsequent systemic inflammation. In adults, secondary HLH can be seen with infection, malignancy and autoimmune disorders. Design/Methods: Case report Results: A 69 year old male with a 40 pound weight loss over the previous four months was transferred from an outside hospital for further evaluation of a 1 week history of fever, as high as 103 Fahrenheit, fatigue, chills and productive cough. Papular skin lesions that developed into ulcerative areas were noted, skin biopsy was consistent with pyoderma gangrenosum. He was treated for community acquired pneumonia with a suspected myelodysplastic syndrome based on profound anemia (Hgb 7.5) and thrombocytopenia (platelets 10,000). Bone marrow biopsy and peripheral blood analysis demonstrated aberrant increased myeloblasts along with hemophagocytosis. Ferritinemia with >36,000 ng/ml was present. The patient’s neurologic examination was generally non focal, however, over the course of treatment he became lethargic. Subsequent brain MRI showed focal areas of restricted diffusion. The patient rapidly deteriorated with CNS, pulmonary, renal, dermatologic and hematologic involvement. He expired despite a regimen of etoposide and dexamethasone. Secondary hemophagocytic lymphohistiocytosis was diagnosed based on biopsy findings, elevated ferritin, fever and cytopenias. Conclusions: Secondary HLH is rare condition with a broad and variable presentation. In this case, the patient became encephalopathic with abnormalities on brain MRI, rapid decline and death. The restricted diffusion observed on MRI is consistent with thrombotic infarction, but whether from hypercoagulable state or inflammatory vasculopathy could not be determined. Thrombocytopenia and renal failure are significant barriers to diagnostic work up. Increased awareness and study of HLH is required to promote earlier treatment and ultimately better outcomes. Disclosure: Dr. Edwards has nothing to disclose. Dr. Shulman has nothing to disclose. Dr. Taylor has nothing to disclose.
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Diagnosis of hemophagocytic lymphohistiocytosis is a challenge in Nepal because of limited resources and the high prevalence of tropical febrile illness mimicking hemophagocytic lymphohistiocytosis. We retrospectively reviewed medical records of 21 patients who were diagnosed with hemophagocytic lymphohistiocytosis from 2010 to 2015 at a single center in Nepal. Two patients had a mutation in their perforin gene and underwent successful haploidentical stem cell transplantation. Marrow hemophagocytosis was found only in 57% of the patients. Five patients had hematological malignancy and were treated with disease-specific chemotherapy. Seven patients developed hemophagocytic lymphohistiocytosis secondary to an infection, including visceral leishmaniasis, scrub typhus, and Epstein Barr virus. EBV-associated hemophagocytic lymphohistiocytosis was refractory to hemophagocytic lymphohistiocytosis 94 protocol, including the addition of rituximab. Malignancy and infection-associated hemophagocytic lymphohistiocytosis was more common. The most common clinical presentations included fever, splenomegaly, hyponatremia, liver function derangement, hyperfibrinogenemia, hyperferritinemia, and cytopenia. With a mortality of 29% in our study cohort, hemophagocytic lymphohistiocytosis should be considered a lethal disease, and clinicians should maintain a high index of suspicion to diagnose this disease. Keywords: Hemophagocytic lymphohistiocytosis; infection; malignancy.
Hemophagocytic Lymphohistiocytosis
Hemophagocytosis
Cytopenia
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Hemophagocytic lymphohistiocytosis is a rare hematologic disorder caused by dysregulated immune activation and carries a high rate of mortality. It is categorized broadly into Primary (Familial ) and secondary types. The recent classification of histiocytoses by Histiocytic society has placed Hemophagocytic lymphohistiocytosis in the “H” group. Greater awareness of Familial hemophagocytic lymphohistiocytosis is required among clinicians and pathologists for early diagnosis and a better survival. Here we report a case of Familial hemophagocytic lymphohistiocytosis correlating with clinical history, family history, bone marrow findings and genetic tests.
Hemophagocytic Lymphohistiocytosis
Hematopathology
Hemophagocytosis
Immune Dysregulation
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BACKGROUND Children with hemophagocytic lymphohistiocytosis require rapid diagnosis for timely treatment. However, diagnostic delays may arise in settings with limited clinical resources. To address this issue, a simplified rule for diagnosing hemophagocytic lymphohistiocytosis has recently been proposed. We retrospectively applied this diagnostic rule in 2 infants to evaluate its generalizability to non-European children. CASE REPORT We present 2 cases of hemophagocytic lymphohistiocytosis, involving an Asian neonate with secondary hemophagocytic lymphohistiocytosis subsequent to echovirus infection and an African infant with familial hemophagocytic lymphohistiocytosis caused by PRF1 mutation. Limitations on time and clinical resources prevented tissue biopsy and measurement of natural killer cell activity in either case at our center. The Asian case did not meet HLH-2004 criteria, but both cases met a rapid diagnostic rule on admission to our center. Both cases were transported to a tertiary center and diagnosed with hemophagocytic lymphohistiocytosis based on HLH-2004 criteria. Although treatment suppressed disease activity, the Asian neonate died of multiple-organ failure at age 6 months. The African infant remains in remission after allogenic cord blood stem cell transplantation. CONCLUSIONS A simplified diagnostic rule for hemophagocytic lymphohistiocytosis may be useful for early diagnosis of hemophagocytic lymphohistiocytosis in Asian and African children, especially in resource-limited clinical settings. Further investigation is required to elucidate whether early diagnosis with a simplified diagnostic rule improves treatment outcomes for children with hemophagocytic lymphohistiocytosis.
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We report a case of hemophagocytic lymphohistiocytosis associated with acute myeloid leukemia. The usual etiologies of hemophagocytic lymphohistiocytosis were absent. Hemophagocytic lymphohistiocytosis secondary to acute myeloid leukemia is rare and deserves the attention of clinicians. Hemophagocytic lymphohistiocytosis may be masked by the tumour process, often making the diagnosis difficult.
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Etiology
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