A case control study of 12 patients with hemophagocytic lymphohiscytosis in adult-onset Still's disease

Abstract

Objective To analyze the clinical features of patients with hemophagocytic lymphohiscytosis(HLH)in adult-onset Still's disease(AOSD). Methods We retrospectively reviewed the clinical data of patients with AOSD complicated with HLH in Peking Union Medical College Hospital from August 2012 to September 2014, and we conducted a case-control study from the cohort of AOSD patients seen during the same period. Data were analyzed by using t-test or Mann-Whitney test and χ2 test(Fisher exact test). The treatments and outcomes of AOSD with HLH were also retrospectively analyzed. Results Twelve AOSD with HLH patients were included, and the prevalence of HLH in AOSD patients was 13%(12/96). Twelve AOSD with HLH patients were all female. The age at HLH onset was 19.7-52.3(33±12)years, usually during the 1-48(20±24)months following AOSD onset. HLH was associated with the activation of AOSD(n=9)and virus infection(n=3). Disseminated intravascular coagulation and shock were more frequently observed in patients with HLH than those without. The neutrophil count [3.14(0~21.98)×109/L vs 12.46(1.28 ~57.42)×109/L, Z= -4.309, P<0.01], hemoglobin levels [(81 ±27)g/L vs(107±21)g/L, t=3.815, P<0.01], platelet count [48(8~199)× 109/L vs 316(81 ~1 016)×109/L, Z=-5.351, P<0.01], fibrinogen levels [(1.3±0.6)g/L vs(5.0±2.1)g/L, t=12.987, P<0.01]were all lower in the group of HLH patients compared with the non-HLH patients, while the serum ALT [338(18~5 290)U/L vs 56(9~3 227)U/L, Z=-3.097, P=0.002]; AST [352(35~15 964)U/L vs 50(10~ 4 147)U/L, Z=-4.083, P=0.000]; LDH [2 074(381~18 815)U/L vs 518(91~2 131)U/L, Z=-3.855, P=0.000]and ferritin levels [16 990(6 321~59 952)U/L vs 2 092(118~44 169)U/L, Z=-4.708, P=0.000]were higher in the group of HLH patients compared with the non-HLH patients. After treated with large dose glucocortico-steroids, combined with immunosuppressants, intravenous immunoglobulin(IVIG)and treating underlying infections, 11 patients recovered, 1 patient died. Conclusion HLH usually occurs at the early course of AOSD. Infection and activation of AOSD are potential triggers of HLH. HLH should be considered when AOSD patients manifested with cytopenia, progressive elevation of ALT, AST serum LDH or ferritin levels, hypofi-brinogenemia, DIC and shock. Large dose glucocorticosteroids combined with immunosuppressants and IVIG may improve the outcome of HLH, while anti-infection therapy is necessary for patients complicated with active infection. Key words: Still's disease, adult-onset; Lymphohistiocytosis, hemophagocytic; Glucocorticoids