Reactive haemophagocytic syndrome in children with inflammatory disorders.A retrospective study of 24 patients

Background. The reactive haemophagocytic syndrome (RHS) is a little-known l ife-threatening complication of rheumatic diseases in children. It reflects the extreme vulnerability of these patients. especially those with systemi c-onset juvenile chronic arthritis (JCA). This immunohaematological process may be triggered by events such as herpes virus infection and non-steroida l anti-inflammatory drug therapy. Treatment has not been standardized. Methods. We characterized this unusual disorder and determined its incidenc e by carrying out a retrospective study of patients identified over a 10-yr period in French paediatric units. Results, Twenty-four cases (nine males, 15 females) were studied. Eighteen had typical systemic-onset JCA, two had polyarthritis, two had lupus and tw o had unclassifiable disorders, Clinical features at diagnosis included hig h spiking fever (24 patients), enlargement of the liver and spleen (14), ha emorrhagic diathesis (six), pulmonary involvement (12) and neurological abn ormalities (coma or seizures) (12). RHS was the first manifestation of syst emic disease in three cases. Admission to intensive care was required in te n cases. Hypofibrinogenaemia, elevated liver enzymes and hypertriglyceridae mia were found consistently. Phagocytic histiocytes were found in 14 of 17 bone marrow smears. RHS was presumed to have been precipitated by infection in 11 cases (four Epstein-Barr virus, three varicella-zoster virus, one pa rvovirus B19. one Coxsackie virus, one Salmonella, one Pneumocystis carinii ) and by the introduction of medication in three cases (Salazopyrin plus me thotrexate; morniflumate, aspirin). Macrophage activation was indicated by high levels of monokines in the serum of two patients. Twenty patients had only one episode. three had an early relapse and one patient had two relaps es. The treatment regimen was tailored to each child as the clinical course was variable, There was no response to intravenous immunoglobulins, which were used in four cases. Intravenous steroids at doses ranging from convent ional to pulse methylprednisolone induced remission in 15 of 21 episodes wh en used alone as the first-line treatment. Cyclosporin A was consistently a nd rapidly effective. both when used as second-line therapy in all seven of the episodes in which steroids failed and in all five patients who receive d it as their first-line treatment, This supports a central role of T lymph ocytes in the haemophagocytic syndrome. Two patients died. One patient with lupus died of congestive fulminant heart failure after 4 days, despite tre atment with intravenous steroids and immunoglobulins, and one patient with systemic-onset JCA died from multiorgan failure despite aggressive therapy with pulsed steroids and etoposide. Conclusions. RHS may be a more common complication of systemic disease in c hildhood than previously thought. This life-threatening complication should be diagnosed promptly, as it calls for the immediate withdrawal of potenti ally triggering medications, anti-infective therapy when relevant. and urge nt immunosuppressive treatment, measures that are very often effective. Cyc losporin A may be the drug of choice.