2012年 · 第50卷第11期

The child was born in January 1992. Due to subcutaneous nodular ulcer for 10 years, intermittent fever, short stature, polydipsia and polyuria for 8 years, aggravated with fever for half a month, he was admitted to our hospital in September 2006. Multiple consultations in the Department of Internal Medicine after admission: according to clinical manifestations, past history, admission physical examination height of 100 cm, combined with imaging, laboratory and lymph node and skin biopsy pathological histological data, it was diagnosed with Langerhans cell histiocytosis (LCH) grade III, Han-Xu-Ke disease involving lymph nodes and skin ulcers complicated by staphylococcus aureus septic shock, adrenal crisis secondary to chronic pituitary insufficiency, and dwarfism. After comprehensive treatment with methylprednisolone combined with anti-infection, blood pressure was controlled at 100/80 mm Hg (1 mm Hg =0.133 kPa) and blood glucose was controlled at 6 mmol/L, and he was transferred to the hematology department of another hospital. It was considered that the child with poor physique was not suitable for combined chemotherapy for the time being, and continued to fight infection and control blood pressure and blood glucose. Methylprednisolone was changed to prednisone 20 mg/d, 12.5 mg at 8 am and 7.5 mg at afternoon. After 4 weeks, the symptoms were relieved and changed to 2 mg/d for maintenance. However, multiple skin ulcers did not heal, and combined chemotherapy was considered. The parents of the children gave up treatment and were discharged due to financial difficulties. Due to skin ulcer, pus and high fever, he returned to our hospital for treatment. General internal medicine consultation: Add thalidomide 25 mg/d twice a day for 4 weeks orally. After 10 days of treatment, the skin ulcer healed and the condition was relieved and changed to 25 mg/d. Discharge of dwarfism due to abandonment of alternative treatment due to financial difficulties. Because the child's poor physique was caused by cold and high fever, adrenal crisis was induced again. According to the routine diagnosis and treatment in other hospitals, blood pressure and blood sugar recovered, but it was found that the original skin healed and ulcers appeared again. Biopsy confirmed the recurrence of LCH. Thalidomide 25 mg/d was restored twice, and the skin ulcer healed after 10 days of treatment, and then changed to 25 mg/d for half a year. The condition was relieved, and the short-term efficacy was satisfactory. The short-term efficacy of this case was first reported when the child was 14 years old^[1]。

The child was a girl, 3 years and 9 months old. He was admitted to hospital in May 2011 due to fever for more than 70 days. More than 70 days before admission, there was fever without obvious trigger, and the body temperature was about 38 ℃. The interval of fever peaks was unknown. After oral antipyretic drugs, the body temperature could drop to normal. There was no rash, bleeding spots, oral ulcer, hair loss, joint redness and swelling and limited movement, no chills, chills, convulsions, cough, expectoration, frequent urination, urgency, painful urination, nausea, vomiting, diarrhea, hematemesis, hematochezia and other discomfort. Considering "acute upper respiratory tract infection", intermittent anti-infective treatment (specific medication unknown) for nearly 1 month, the child's fever gradually worsened, the highest body temperature was 39.5℃, the daily fever peak was 3 to 4 times, and mild claudication, unwillingness to walk, and no obvious joint swelling and pain. More than 40 days before admission, he went to another hospital and was diagnosed as "juvenile idiopathic arthritis (systemic type)". After intravenous infusion of methylprednisolone 320 mg/d, his body temperature dropped to normal. After 4 days of intravenous infusion of methylprednisolone, it was changed to prednisone acetate 10 mg orally 3 times a day. The child's body temperature was normal, and then oral glucocorticoid treatment was continued. Three days before admission, the child had fever again, with the highest body temperature of 39.0 ℃. He was seen in another hospital, and the blood test routine: white blood cell (WBC) 17.32×10⁹/L, lymphocytes 0.50, neutrophils 0.44, hemoglobin (HGB) 59 g/L, platelets (PLT) 147×10⁹/L; Blood biochemistry: Liver and kidney function, electrolytes and myocardial enzymes were roughly normal. For further diagnosis and treatment, he was referred to the specialized outpatient clinic of children's rheumatology in our hospital, and was admitted to the hospital with "anemia and fever to be examined".

congenital neutropenia (CN) is a heterogeneous group of diseases characterized by a decrease in the absolute value of neutrophils in the peripheral blood circulation.^[1]It is first reported that it can be autosomal recessive, dominant and X-linked recessive inheritance or sporadic. The definition of CN is still controversial. Strictly speaking, it only includes diseases with hematological manifestations, such as severe congenital neutropenia (SCN); CN in the broad sense includes some congenital diseases with neutropenia, and may have other systems or immunological abnormalities other than the blood system, such as Shwachman-Diamond syndrome (SDS). CN contains a large number of diseases, but most of them share the following common manifestations: decreased absolute neutrophils in peripheral blood, recurrent severe bacterial infections, stagnation of bone marrow granulocyte development at the early/mesomyelocytic stage and high risk of conversion to leukemia and myelodysplastic syndrome (MDS). In the past ten years, the pathogenic genes of some CN patients have been discovered one after another. The pathogenesis of the main CN pathogenic genes is summarized as follows.

patent ductus arteriosus (PDA) is the most common cardiovascular abnormality in newborns and one of the common complications in premature infants. It can induce and promote various complications such as congestive heart failure, pulmonary edema and pulmonary hemorrhage, chronic pulmonary disease, intracranial hemorrhage and necrotizing enterocolitis^[1]Increased mortality^[2]。 The incidence of PDA in ultra-low birth weight infants with gestational age less than 29 weeks or body weight less than 1000 g is approximately 70%^[3]。 Therefore, timely closure of ductus arteriosus can help improve hypoxia, control heart failure, and reduce premature mortality. However, there are still some controversies in the treatment timing, method selection, drug dosage and treatment course of patent ductus arteriosus in premature infants at present. This article reviews the progress of PDA treatment in premature infants, so as to better carry out relevant research and clinical application in China.

In 1994, Dutch scientists first reported brain folate deficiency^[1]In recent years, the research on its etiology, clinical phenotype, diagnosis and treatment methods at home and abroad has gradually matured. The results of peripheral blood folate metabolism in children with cerebral folate deficiency can be normal or decreased^[2]Due to the deficiency of 5-methyltetrahydrofolate in cerebrospinal fluid, it triggers a series of neuropsychiatric symptoms. The clinical and laboratory research progress of cerebral folate deficiency is reviewed.

hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is currently divided into two categories: primary and secondary. Among them, primary HLH can be divided into two categories: one is those with obvious familial genetic predisposition, called familial HLH (familial hemophagocytic lymphohistiocytosis, FHL); The second is primary immunodeficiency disease-related HLH. Secondary diseases are often secondary to viruses, protozoa, fungi, bacteria, autoimmune diseases, malignant tumors, etc. However, whether primary or secondary HLH, its etiology and pathogenesis are complex, the early symptoms are atypical, and the diagnosis is difficult. It is often easily confused with infectious diseases due to persistent fever. However, the disease progresses rapidly, and many children die quickly (within hours or days) due to untimely medical treatment or unclear diagnosis. Because of its low incidence, it was recognized late (first reported in 1952^[1]), and it is a clinical syndrome caused by multiple factors. In the past, there were no clinical diagnosis and treatment recommendations or guidelines published in China. However, the incidence types and conditions of HLH among ethnic groups are not exactly the same, and the international HLH-2004 diagnosis and treatment recommendations may not be completely suitable for China's national conditions. The Hematology Group of Pediatrics Branch of Chinese Medical Association drafted and formulated the "Suggestions for the Diagnosis and Treatment of Hemophagocytic Lymphohistiocytosis in Chinese Children" (hereinafter referred to as "Suggestions") for the reference of pediatric clinicians in China. Due to the complexity of the disease itself, the diversity of clinical manifestations, the imperfection of diagnostic indicators, especially the complexity of genetic diagnosis and the low success rate of treatment, clinicians have many confusions in the process of diagnosis and treatment, and medical staff from different units have different understanding levels of the disease, and there are many inconsistencies in diagnosis and treatment opinions. The purpose of this article is to make some necessary explanations on the possible problems and controversies on the basis of "suggestions", so as to provide reference for the rational diagnosis and treatment of HLH in clinical practice.

With the development of socioeconomy and the improvement of medical and health conditions, the spectrum of childhood diseases has also changed. Malignant tumor is no longer rare, and it has become one of the main causes of death in children in China^[1]。 Overall, the diagnosis and treatment level and prognosis of childhood malignant tumors have been significantly improved, but the "paraneoplastic syndrome" caused by them^[2,3]And therapeutic measures such as radiotherapy and chemotherapy can directly or indirectly involve the kidney, causing acute kidney injury (AKI) or chronic kidney disease (CKD)^[4,5]； As a result, its pathophysiology and clinical manifestations are complex and diverse, resulting in difficulties in diagnosis and treatment. In order to improve the outcome and quality of life of cancer patients, cancer centres in developed countries have established "multidisciplinary care teams", of which nephrologists are an essential member^[5]。 In rare cases, malignant tumors can also be acute renal failure, glomerulopathy, nephromegaly^[6]See nephrology department for first manifestation^[7]Nephrologists tend to ignore the primary tumor and delay diagnosis and treatment. The malignant tumors involving the kidney in childhood and common related problems are introduced as follows.

Dr. Wang Yuxin(450000 Department of Pediatrics, 153 Hospital of the People's Liberation Army, Zhengzhou) Q:

hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a group of hyperproliferation of activated lymphocytes and histiocytes but immune failure, causing hyperinflammatory response in multiple organs. The main clinical characteristics of HLH are fever, hepatosplenomegaly, liver function impairment, cytopenia and histiocyte hemophagy (mainly seen in bone marrow, liver and spleen and lymph nodes), with acute onset, rapid progression and high mortality. At present, it is believed that the main pathogenesis lies in the low function of NK cells and cytotoxic T lymphocytes (CTL), which cannot effectively eliminate virus or other antigens in time and continuously stimulate and activate immune cells, resulting in the proliferation of lymphocytes and histiocytes and the massive release of various cytokines (the so-called "cytokine storm"), resulting in high inflammatory response of multiple organs and tissue damage^[1,2,3]。

In 1968, scholars at Harvard Medical School put forward the concept of "irreversible coma" on the basis of a large amount of evidence^[1]And formally put forward the definition of brain death, which makes an important supplement to the traditional definition of death after cardiopulmonary failure, which becomes the "Harvard standard" for judging brain death: (1) non-susceptibility and non-responsiveness; (2) no movement or breathing; (3) non-reflection; (4) The electroencephalogram was straight. The above four tests should be repeated 24 h after the first examination, and no change can be judged as brain death. In fact, the future brain death standards or guidelines are based on the "Harvard standards" formulated and continuously improved.