Inflammatory Cytokines In Histiocytic Necrotic Lymphadenitis In Children

Part Ⅰ Clinical Characteristics of Histiocytic Necrotic Lymphadenitis in ChildrenObjective: Histiocytic necrotic lymphadenitis is also known as Kikuchi-Fujimoto disease(KFD).The clinical manifestations of this disease vary greatly,the laboratory examination lacks specificity.There are certain difficulties in clinical diagnosis,and some children may have serious complications such as macrophage activation syndrome(MAS).This study summarizes the clinical characteristics,laboratory indicators,treatment plans and prognosis of children with HNL to improve the early recognition,diagnosis of the disease by clinicians and improve the overall prognosis.Methods: The clinical data of children with HNL diagnosed by pathological biopsy of lymph nodes in Shenzhen Children’s Hospital from April 2015 to June 2022 were retrospectively analyzed.This disease characteristics of children with HNL were summarized by using a descriptive approach for the statistical analysis.Results: Among the 57 children,38 were male and 19 were female,the mean age was 9.2±3.2 years.The main clinical features included fever in 54cases(95.7%),lymph node enlargement in 53 cases(93.0%),rash in 15cases(26.3%),hepatomegaly in 20 cases(35.1%)and splenomegaly in 9cases(15.8%).Laboratory indicators showed that the number of white blood cells,neutrophils and lymphocytes decreased,the level of hemoglobin and albumin decreased,and ferritin,erythrocyte sedimentation rate and lactate dehydrogenase increased.25(62.5%)of the 40 children showed the phenomenon of phagocytosis of blood cells by bone marrow.A total of 50 children completed the autoantibody spectrum test,of which 10 were positive(20.0%),with antinuclear antibody positive(5 cases)being the most common.In terms of treatment effect,28 children were treated with glucocorticoids,including 18 patients treated with glucocorticoids alone and5 patients treated with high-dose methylprednisolone,8 patients were treated with intravenous immunoglobulin,and 27 patients were treated with antibiotics.All the above children improved after treatment,29 cases were relieved without treatment.Conclusions: Men are more common in children with HNL.Fever and/or lymph node enlargement can be the most common early manifestation or first symptom of the disease,and can also be combined with multiple organ function damage.Laboratory features include leukopenia,LDH,ESR and FER elevation.Half of the children are relieved by themselves.Receiving short-term glucocorticoid and IVIG treatment can quickly alleviate the condition of children with persistent or progressive symptoms,and the overall prognosis is good.Part Ⅱ Clinical Significance of Cytokine Spectrum Detection with Histiocytic Necrotic Lymphadenitis in ChildrenObjective: By studying the characteristics of serum inflammatory cytokine spectrum in children with HNL,it provides possible biological indicators for early diagnosis and differential diagnosis.Methods: The children with HNL diagnosed by pathological biopsy of lymph nodes and complete the inflammatory cytokine detection in Shenzhen Children’s Hospital from April 2015 to June 2022 was retrospectively collected.In the disease control group,Kawasaki disease(KD)and systemic juvenile idiopathic arthritis(s JIA)were selected.The children in the control group all met the following requirements at the same time: 1.When the fever caused by the activity of the primary disease itself was≥3 days,the serum cytokine test shall be performed;2.No other diseases,including immunodeficiency disease,chromosomal disease,tumor,severe trauma,acute infection and other rheumatic immune diseases,were involved in the improvement of cytokine detection;3.There is no special medication history such as chemotherapy drugs and immunosuppressants in the near future.Compare and analyze the differences of inflammatory cytokine levels in the three groups of diseases,and find out the Cut-off value that predicts the occurrence of HNL through the Receixer operating characterristic(ROC)curve of the subjects.Results:The level of serum IL-6 in HNL group increased slightly,but the increase was significantly lower than that in s JIA and KD groups(P<0.05)。Compared with the other two groups,the serum IFN-γ of HNL group level and The ratio of IFN-γ/ IL-6 increased significantly(P<0.001)After excluding the children with MAS,the subgroup analysis was performed on the children with simple HNL and s JIA,simple HNL and KD,respectively.The results showed that compared with s JIA or KD group,the increase of serum IL-6 level in HNL group was significantly reduced,and serum IFN-γ level and the ratio of IFN-γ/IL-6was significantly increased,and the difference was statistically significant(P<0.001).Through detecting of IL-6、IFN-γ and IFN-γ/IL-6 in children with HNL and s JIA by ROC curve,the area under curve(AUC)of IL-6、IFN-γ and IFN-γ/IL-6 were 0.920,0.996 and 1.000,and the Cut-off values were<47.72 pg/ml,>8.48 pg/ml and>0.45 respectively.The AUC of IFN-γ and IFN-γ/IL-6 in children with HNL and KD non-MAS groups were 0.976 and 0.998 respectively,and the Cut-off values were>8.56pg/ml and>0.45 respectively.Conclusions:When the child has fever of unknown cause,excluding acute infection、tumor and the combination of MAS or HLH,IFN-γ level(>8.56pg/m L)and IFN-γ/ IL-6 ratio(>0.45)can be used as an important biological indicator for the diagnosis and differential diagnosis of HNL.When IL-6>50.45pg/m L,the possibility of HNL is small,and s JIA and KD should be excluded first.