Reactive hemophagocytic syndromes in children with rheumatic diseases

Reactive haemophagocytic syndrome (RHPS), also calledmacrophage activation syndrome (MAS), is a serious complicationof viral, rheumatic and malignant diseases, thought to be causedby the excessive activation of T lymphocytes and macrophages.MAS is characterized by polyorgan involvement with typical features:non-remitting fever, hepatic enlargement, considerable loweringof blood cell count and erythrocyte sedimentation rate (ESR),elevation of serum glutamic-oxaloacetic transaminase (SGOT),serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase(LDH) and serum ferritin level, with hypofibrinogenemia. Themost characteristic feature is the presence of well differentiatedmacrophages, revealing an active haemophagocytosis in the bonemarrow aspirate. Because of rapid progression and fatal prognosisof the disease, prompt and immediate therapeutic intervention isvery important. Although there is no standardized treatment, commonlyapplied glucocorticoids (GCS), and cyclosporine A (CsA) areused. The study was aimed to a general characteristics of pathogenicfactors, clinical picture, laboratory features and results oftreatment in 8 children with RHPS /MAS. Material and methods: The study included 8 children (5 girls and3 boys) aged 3 to 16 years (mean age was 10 years and 3 months)hospitalized in the Clinic of Pediatrics at IPCZD and in the Departmentof Pediatric Rheumatology at the Institute of Rheumatology in Warsaw. The analysis covered potential etiological factors, consideringthe basic disease, clinical symptoms (Table II), results oflaboratory tests (Table III), including immunological tests, appliedtherapy. In 4 patients, systemic-onset juvenile idiopathic arthritiswas accompanied by MAS, and in 2 patients it was the first manifestationof sJIA. In one patient, EBV infection was confirmed bythe polymerase chain reaction (case 1). In patient 3, PCR evaluationrevealed Cytomegalovirus (CMV) infection. Cytomegalovirus infectionwas also confirmed in case 4, however, simultaneously geneticas well as serological evaluation for Parvovirus B19 infectionrevealed positive results in this patient. In patient 5 CMV infectionand/or Toxocara canis infection could be a triggering factor forRHPS (Table I).In seven patients, haemophagocytosis was confirmed in bone marrowbiopsy. No response to GCS treatment, including pulse therapy,or IVIG therapy was observed. Remission was induced by treatmentwith CsA (Table IV). The diagnostic criteria for haemo phagocyticlymphohistiocytosis are presented in Table V.