Sekundäärinen HLH mainitaan COVID-19 komplikaatioissa

Kuten tiedetään primäärinenkin HLHJ on vaikeahoitoinen. HLH:n kaltaista oireyhtymää kuvattiin joksus lintuinfluenssan yhteydessä. 

Nyt se on ponnahtanut taas artikkeleissa ilmi COVID-19 komplikaatioissa. 

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av P Mehta - ‎Citerat av 59

16 mars 2020 - A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, ...

(PDF) Interleukin-6 Use in COVID-19 Pneumonia Related ...

www.researchgate.net › publication › 34026618...

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29 mars 2020 - Macrophage activation syndrome in COVID-19 pneumonia? Although pneumonitis 

 may occur, the classic MAS/sHLH picture in. sJIA and other ...

Relative Innate and Adaptive Immune Mechanisms in HLH Spectrum Pathology.

•   Immunodeficiency State (Primary HLH) Vs Immunocompetency State (MAS/sHLH.

•  COVID-19 Immunodeficiency State Vs Immunocompetency State.

 The HLH responses can occur in the setting of both immunodeficiency states and in immunocompetence settings and following adaptive immune system engineering (Panel A and B in blue). In humans with defects in NK and CD8+ T-cells, the inability to kill virally infected cells results in primary HLH with hyper-cytokinaemia that can't be cured with anti-cytokine strategies as genetic defect typically in perforin pathway machinery makes pathogen elimination impossible [58] (Panel A). 

In CAR-T cell therapy hyper proliferating engineered T-cells may drive MAS/sHLH that only lasts for the duration of the presence of detectable tumour antigen (Panel B).

 Similar mechanisms may occur in sJIA or autoimmune diseases, but this remains to be fully defined. This model is based on the immunological disease continuum modified for gain or loss of function in innate or adaptive immunity (Reference 43). 

When COVID-19 hyper-inflammatory or cytokine storm reactions are viewed through the lens of primary and secondary HLH, it is noteworthy that virally induced immunosuppression may play a key role (Panel C). 

Coronavirus family members including COVID-19 pneumonia is associated with robust interferon suppression, blood lymphopenia including NK cell abnormalities. Such scenarios likely drive macrophage infiltration and the "second wave" of non-type-1 interferon pathway cytokines including IL-6, IL-1, IL-18, INFγ, GM-CSF and others that lead to a blood hyper-cytokinaemic picture (Panel B).

It remains to be seen how many cases of COVID-19 related fatalities have mutations in genes associated with the primary HLH disorders and thus closely resemble primary HLH (Panel A).

 Based on persistent viral shedding from the respiratory tract during COVID-19 related disease, then an exaggerated immune response including IFN driven and T-cell driven responses that clears the virus but induces pulmonary immune system collateral damage and ARDS offers an explanation for the more typical MAS/sHLH phenotype. Viral clearance in the face of marked hyper-inflammation would be expected in the face of brisk anti-viral antigen responses.

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•  Mikä on HLH? Esimerkki.

Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment

Article (PDF Available) in Rheumatology (Oxford, England) 58(1) · February 2018 with 1,380 Reads 

DOI: 10.1093/rheumatology/key006

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which if not promptly treated, can lead rapidly to critical illness and death. HLH is termed macrophage activation syndrome (MAS) when associated with rheumatic disease (where it is best characterized in systemic JIA) and secondary HLH (sHLH) when associated with other triggers including malignancy and infection. MAS/sHLH is rare and coupled with its mimicry of other conditions, is underrecognized. These inherent challenges can lead to diagnostic and management challenges in multiple medical specialties including haematology, infectious diseases, critical care and rheumatology. In this review we highlight the pathogenesis of MAS/sHLH including its underlying triggers, key clinical features and diagnostic challenges, prognostic factors and current treatments in adults.