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Various immunodeficiencies Hyperinflammatory but inadequate immune response Clinical picture of HLH. Hemophagocytic lymphohistiocytosis (HLH) Clinical symptoms and findings - PowerPoint PPT Presentation
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Various immunodeficiencies
Hyperinflammatory but inadequate immune response
Clinical picture of HLH
Hemophagocytic lymphohistiocytosis (HLH) Clinical symptoms and findings
High fever, hepatosplenomegaly, pancytopenia Neurological symptoms, jaundice, edema, lymphadenopathy, rash
High triglycerides, low fibrinogen, coagulopathy high ferritin, transaminases, bilirubin, LDH CSF pleocytosis and/or elevated protein
Hemophagocytosis in BM or other organs
Phagocytosing macrophages in HLH
HLH Variable course of disease
Rapidly progressive leading to death within weeks
Transient improvements with unspecific therapies
Disappearance of symptoms without therapy
Disappearance of symptoms with immuno- suppressive/immunomodulatory drugs
HLH Classification
Genetic, primary HLH Acquired, secondary HLH FHLH - Perforin mutations (chr.10) Exogenous agents - infectious organisms, toxins - Chromosom 9 linkage (VAHS, IAHS)
- Unknown mutations HLH Endogenous products - tissue damage - radical stress - Immune deficiencies - metabolic products CHS Griscelli syndrome Rheumatic disorders XLP Malignancies SCID GJ 2002
Leishmaniase
„IAHS“ in Childhood (219 cases from the literature) 1979-1995
Organism Clinical outcome Dead Alive No data
EB Virus 121 72 27 22
Other viruses 28 11 13 4
Bacteria 11 2 9 0
Fungi 2 1 1 0
Protozoae 1 0 1 0 No organism 57 13 33 11
„IAHS“ in Childhood (219 cases from the literature)
(1979-1995)
Age Clinical outcome
Dead Alive No data
< 3 years: 77 40 26 11
> 3 years: 82 29 47 6
„Children“: 60 60 22 4
Total 219 103/198 95/198
(52%) (48%)
HLH Diagnostic criteria Histiocyte Society 1991 Clinical Fever > 38.5 Splenomegaly Laboratory Cytopenia of => 2/3 cell lines Hypertriglyceridemia and/or hypofibrinogenemia Histopathology Hemophagocytosis in bone marrow or spleen or liver or lymphnode
Strong supportive evidence are spinal fluid pleocytosis, liver histology resembling chronic persistent hepatitis, low natural killer cell activity
Diagnostic criteria
0 20 40 60 80 100
CNS protein
CNS cells >=5/ ul
Natrium < 130 mmol/ l
GPT > 50 U/ l
GOT > 50 U/ l
LDH > 400 U/ l
Triglycerides fasting >= 2mmol/ l
Fibrinogen < 1,5 g/ l
sCD 25 > 5000 U/ ml
NK cell activity negative ordecreased
Hemophagocytosis
Neutrophils < 1.0/ nl
Thrombocytes < 100/ nl
Hb < 90 g/ l
Cytopenia 1 cell line
Cytopenia 2 cell lines
Cytopenia 3 cell lines
Splenomegaly
Fever
Percent of cases
At initial presentation At diagnosis
HLH Immunological parameters
Hypercytokinemia (TNF, INF, IL 6, IL 8, IL 10),
Increased soluble CD 25 (interleukin 2 receptor -chain)
Increased soluble CD95-ligand
NK-cell activity below 5% lysis
CD2/CD86 positive cells in lymphocyte gate
Phagocytosing dendritic cells in culture
HLH Therapy Cytostatic and immunsuppressive/ immunomodulatory drugs: Corticosteroids, Cyclosporin A, Etoposide Immunoglobulins, Antithymocyte globulin Bone marrow transplantation
Prognosis In 20% no response to therapy After BMT 60-70% relapse-free survival
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