Viral infections associated with haemophagocytic syndrome

Abstract

Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T cell/NK cell dysregulation causes an aberrant cytokine release, resulting in proliferation/activation of histiocytes with subsequent haemophagocytosis. Histiocytic infiltration of the reticuloendothelial system results in hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading to multiple organ dysfunctions. Common clinical features include high fevers despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms, coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be either primary, i.e. due to an underlying genetic defect or secondary, associated with malignancies, autoimmune diseases (also called macrophage activation syndrome) or infections. Infectious triggers are most commonly due to viral infections mainly of the herpes group, with EBV being the most common cause. HPS can be fatal if untreated. Early recognition of the clinical presentation and laboratory abnormalities associated with HPS and prompt initiation of treatment can be life saving. HPS triggered by viral infections generally does not respond to specific antiviral therapy but may be treated with immunosuppressive/immunomodulatory agents and, in refractory cases, with bone marrow transplantation.

Macrophage activation syndrome

“…Wtórne formy HLH (secondary HLH -sHLH) rozwijają się w następstwie aktywacji immunologicznej wywołanej przez zakażenie (infection-associated HLH -I-HLH), chorobę autoimmunologiczną (autoimmune-associated HLH -A-HLH) lub nowotwór (malignancy-associated HLH -M-HLH) [2,7,10].…”

“…Także zakażenia wirusem cytomegalii (CMV), opryszczki (HSV), ospy wietrznej i półpaśca (VZV), wirusem HIV, wirusem grypy mogą prowadzić do rozwoju I-HLH [7,10]. Wszystkie uogólnione zakażenia bakteryjne (Escherichia coli, Salmonella), grzybicze (Aspergillus) oraz pasożytnicze (np.…”

“…przez limfocyty i komórki NK białka -perforyny [2,17], które po wbudowaniu do błony komórkowej tworzy kanał przepuszczający do komórki jony sodu i wodę, co powoduje lizę osmotyczną komórek docelowych [4,10]. Na skutek zmniejszonej ekspresji perforyn na limfocytach Tc i komórkach NK, nieprawidłowej ekspresji granzymy B (proteaza serynowa indukująca apoptozę) oraz małej aktywności NK (stwierdzane np.…”

Rare cause of fever in a patient with ulcerative colitis

“…Common laboratory findings are high bilirubin levels, elevated serum transaminases, elevated prothrombin, and partial thromboplastin times. 4 The main diagnostic problem is that initially HLH masquerades as a normal infection and too little attention is paid to the severity of symptoms. When a patient presents with prolonged fever unresponsive to antibiotics, hepatosplenomegaly, and cytopenias, HLH as a differential diagnosis should be considered.…”

“…This distinction is not categorical, as primary HLH can occur late in life and may be triggered by infections. 4 Without treatment, the uncontrolled hyperinflammation leads to sustained neutropenia with opportunistic infections or even to cerebral dysfunction. It is a life-threatening condition which may be difficult to distinguish from severe sepsis.…”