Haemophagocytic syndrome

From Ganfyd

A group of disorders, characterized by :

• persistent or intermittent fevers
• hepatosplenomegaly (often manifested initially as isolated splenomegaly)
• thrombocytopenia and anaemia that often evolve to severe pancytopenia
• coagulation abnormalities (in particular, hypofibrinogenemia)
• hepatic dysfunction

All in the absence of other causes of thrombocytopenia and hepatosplenomegaly. Other names are macrophage activation syndrome, haemophagocytic lymphohistiocytosis (HLH). Henter diagnostic criteria apply.

The common factor is the inability to kill infected target cells. The resulting sustained natural-killer-cell and cytotoxic T-cell activity leads via inflammatory cytokines to macrophage activation, dissemination, and organ infiltration. Haemophagocytosis in the marrow is not always evident at presentation so serial bone marrow examinations may be required. A spleen aspirate may be an alternative to marrow.

There are four categories:

1. A familial syndrome (perforin deficiency)
2. Haemophagocytic syndromes associated with infections (Epstein-Barr virus, cytomegalovirus, parvovirus B19, bacteria, fungi, mycobacteria, and parasites)
3. Associated with Juvenile idiopathic arthritis (ESR may be low, due to low fibrinogen cf underlying (JIA).
4. Associated with immunodeficiency states:
   • DiGeorge syndrome should be excluded by FISH
   • Lysinuric protein intolerance - hyperammonaemia is characteristic
   • Chediak-Higashi and Griscelli syndromes: the accelerated phases are both characterized by albinism - mutations in the LYST or RAB27A gene, respectively, will confirm the diagnosis.
   • X-linked lymphoproliferative disease (susceptibility to kill Epstein-Barr virus.

Treatment

HLH94 regimen then ciclosporin for control, bone marrow transplant for cure.