haemophagocytic lymphohistiocytosis- the most fatal ... · lessons learnt in a 17 year old with...
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Lessons learnt in a 17 year old with fever of unknown origin – Haemophagocytic lymphohistiocytosis- the most fatal outcome of EBV infection.
World congress on infectious diseases , London 2015
Dr Hajir Ibraheim, Princess Royal University Hospital, London
Lessons learnt in a 17 year old with PUO: Haemophagocytic lymphohistiocytosis- the most fatal outcome of EBV infection.
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Aims
Present a case of EBV-HLH
Describe the diagnosis and treatment of EBV-HLH
Reflect on lessons learnt
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The case P/C:
-17 year female
-4 day hx of fevers, sore throat, vomiting
PMH:
IgG subclass deficiency
Bronchiectasis
Viral meningitis
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Findings On examination:
Tachycardic
Febrile- 39 C
CVS: NAD
Chest: clear
Abdomen: no organomegaly
Petechial rash on uvula
No lymphadenopathy
Initial Ix
ECG: normal
CXR: NAD
Hb WCC Plts CRP ALP AST EBV
121 1.4 86 32 300 326 Monospot + 53000 copies
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Timeline
D2 ?infectious mononucleosis + bacterial
-US-NAD
-abx started
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D2 ?EBV + bacterial
-US-NAD
-abx started
D8 ?EBV hepatitis?CMV
-pancytopenic, persistent fevers, worsening LFT’s
-septic screen negative
-antivirals started
-abx escalated
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EBV load vs symptoms Persistent fevers
Worsening LFT’s
Clinically deteriorating
Reducing EBV viral load
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D2 ?EBV + bacterial
-US-NAD
-abx started
D8 ?EBV hepatitis?CMV
-pancytopenic, persistent fevers, worsening LFT’s
-septic screen negative
-antivirals started
-abx escalated
D10?cause
-rash
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D2 ?EBV + bacterial
-US-NAD
-abx started
D8 ?EBV hepatitis?CMV
-pancytopenic, persistent fevers, worsening LFT’s
-septic screen negative
-antivirals started
-abx escalated
D10?cause
-rash
D16 ?HLH
-bone marrow biopsy
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D16 Bone marrow aspirate
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D2 ?EBV + bacterial
-US-NAD
-abx started
D8 ?EBV hepatitis?CMV
-pancytopenic, persistent fevers, worsening LFT’s
-septic screen negative
-antivirals started
-abx escalated
D10?cause
-rash
D16 ?HLH
-bone marrow biopsy
D18-
?EBV-HLH ?lymphoma HLH
-MRI: sig hepatosplenomegaly- no lymphoma
-genetic studies sent
-high dose steroid started
-Transfer specialist unit
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EBV
Infectious mononucleosis
Chronic active EBV
Viral meningitis, encephalitis
Hepatitis
Lymphoma
Nasopharyngeal
Smooth muscle tumour EBV-HLH
GBS, transverse myelitis, MS
Neurological
Malignancy
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EBV-HLH HLH can be 10 (familial) or 20 (malignancy, viral)
Rare and aggressive syndrome
Excessive activation of T cells, NK cells + Macrophages cytokine storm
Cause haemophagocytosis, cellular damage and organ dysfunction
Most typical findings are fever, cytopenias, deranged liver function & hepatosplenomegaly
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Diagnosis 1) Molecular diagnosis consistent with HLH
Or
2) Fulfills at least 5 of the criteria
in the table
Criteria Did our patient have?
Fever
Splenomegaly
Cytopenias
Hypertriglyceridemia +/- hypofibrinogenemia
Haemophagocytosis in BM, spleen or lymph nodes
Hyperferritinemia
Low or absent NK cell cytotoxicity
N/A
Elevated sCD25 levels N/A
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Differentials?
ΔΔ
Sepsis/SIRS
Rheumatological
e.g Stills
Haematological e.g. lymphoma
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Complications
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Treatment
Early diagnosis
Steroids
Immuno-
chemoRx
Hematopoetic stem cell transplant
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Antiviral therapy?
In 1980’s Sullivan et al- successful Rx of x2 cases EBV-HLH with 10 days acyclovir
No concrete evidence for role of acyclovir
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Key lessons
1
• EBV-HLH mimics other inflammatory/infectious conditions
• Should be prompted by signs of unexplained fever, cytopenia, splenomegaly and deranged liver function.t
2
•S
• HLH is the most fatal complication of EBV.
• High mortality rate due to delayed diagnosis.
• Supporting text
3
•Sup
• Rx includes steroids,immuno chemotherapy, stem cell transplant.
• Early involvement of haematologists is paramount.