Etiology and clinical characteristics of fever of unknown origin in 357 pediatric patients / 中华儿科杂志

Objective: To explore the etiologies and clinical characteristics of fever of unknown origin (FUO) and to provide clues for early diagnosis of FUO. Methods: The data about etiology, age, sex, clinical course, length of hospital stays and the expression levels of inflammatory factors in fever phase of 357 pediatric inpatients who were diagnosed with FUO in Children's Hospital of Fudan University from 1 January 2016 to 31 December 2020 were collected and retrospectively analyzed. Participants were grouped into infectious disease, inflammatory disease, malignancy and others and according to the classification of diseases and also grouped into those aged<1 year, 1-<3 years,3-<6 years, 6-<12 years and 12-<18 years. Comparisons between groups were performed using the Mann-Whitney U test, Kruskal-Wallis H test and χ² test. Results: Among the 357 patients (217 males and 140 females). The age of onset was 3.9 (1.3, 9.2) years and visiting age was 5.1 (2.0, 9.3) years. The time-consuming of diagnosis was 94 (66, 213) days. The hospital stay was 8 (6, 14) days. The most frequently identified cause of FUO was infectious diseases (163 cases, 45.7%), followed by non-infectious inflammatory diseases (133 cases, 37.2%), malignancy (21 cases, 5.9%) and others (40 cases, 11.2%). The patients at younger age were more likely to be attacked by malignancy, oncologic diagnoses, and others, nevertheless patients at older age were more likely to be attacked by non-infectious inflammatory diseases oppositely (9.8 (3.6, 11.5) vs. 3.0 (1.2, 7.0), 2.3 (1.0, 5.2), 0.9 (0.5, 1.8) years, U=41.30, 15.94, 37.08, all P<0.01);106 (65%) patients were male, and 57 (35%) patients were female. This result indicated that boys were more susceptible to infectious diseases (χ²=14.73, P<0.01). Analysis of inflammatory factors in serum among 103 patients, interleukin (IL)-6 level in 40 infectious diseases patients (9 (2, 38) ng/L) was significantly lower than those of 6 tumor patients (89 (64, 599) ng/L) and 57 non-infectious inflammatory diseases patients (25 (8, 78) ng/L, U=51.05, 15.70, both P<0.05), no significant difference was observed in IL-2, IL-4, IL-10, tumor necrosis factor α and interferon among the groups (all P>0.05). The patients grouped into those aged 1-<3 years and 3-<6 years were more likely to be attacked by infectious diseases (51.3% (59/115) and 57.1% (40/70)), while patients grouped into those aged 6-<12 years and 12-<18 years were more likely to be attacked by non-infectious inflammatory diseases (55.6% (65/117) and 72.4% (21/29)). Conclusions: Infectious disease is still the main cause of FUO in children and the boys are more susceptible to infectious diseases. However, the morbidity of non-infectious inflammatory diseases increases to number 1 in FUO of children over 6 years of age.

Clinical features of 107 autoimmune hepatitis patients and 30 of them with AIH-primary biliary cirrhosis overlap syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>In order to provide a reliable basis for the diagnosis and treatment of autoimmune hepatitis (AIH) and its overlap syndrome, we investigated the clinical, immunological characteristics of and the therapeutic methods for AIH and AIH-primary biliary cirrhosis (PBC) overlap syndrome.</p><p><b>METHODS</b>One hundred seven patients (77 with AIH and 30 with AIH-PBC overlap syndrome) were enrolled in the study. Their clinical manifestations, serum liver function tests (LFTs) findings, serum immunoglobulins, liver histopathological changes and their responsiveness to the therapies were investigated.</p><p><b>RESULTS</b>The age distribution of AIH patients showed a single peak during their fifties and their main clinical manifestations were malaise, abdominal distension, anorexia and jaundice. Serum gamma globulin and IgG were significantly higher than their normal levels. 74% of the patients were positive for anti-nuclear antibody (ANA), 32% of the patients were positive for anti-smooth muscle antibody (AMA), and over 50% of the patients suffered from concurrent extrahepatic autoimmune diseases. The main histological changes in the liver biopsies were interface hepatitis (65%), lobular hepatitis and rosette formation of liver cells. Bridging necrosis was observed in severe AIH cases. In the AIH-PBC overlap syndrome patients, the levels of serum ALT, AST, GGT, ALP and incidences of ANA and AMA/AMA-M2 were all significantly higher than those of the AIH group. After treating AIH patients with prednisolone and azathioprine (Aza), complete response was seen in 42 cases (70%), sustained response was seen in 26 cases (43%). Sixteen cases had relapses after the withdrawal of the treatment or prednisolone dosage was reduced lower than 10 mg/d. The cases having normal serum ALT, AST, gamma-globulin and IgG levels after treatment were still responding to the reduced prednisolone dosage of 5-10 mg/d without azathioprine added. After combination with ursodeoxycholic acid (UDCA) treatment, the liver function tests (AST, ALT, TBil) of AIH-PBC overlap syndrome patients also significantly improved compared to those before the treatment (P<0.01).</p><p><b>CONCLUSION</b>AIH and AIH-PBC overlap syndrome are not rare in our clinics. Their diagnoses should be based on the clinical presentations, biochemical and immunological indices and liver histological changes. In AIH cases, once their AST, ALT, gamma-globulin and IgG levels return to normal, the prednisolone dosage can be maintained at 5-10 mg/d and Aza can even be withdrawn. Good improvement for patients with AIH-PBC overlap syndrome can be obtained with UDCA and immunosuppression treatment.</p>