Differential diagnosis and clinical course of autoimmune neutropenia in infancy: comparison with congenital neutropenia

Aim: Autoimmune neutropenia in infancy (AIN) is caused by granulocyte-specific autoantibodies. Clinical presentation and diagnosis have not been well studied, resulting in cumbersome diagnostic investigations and unnecessary treatment such as granulocyte colony-stimulating factor (G-CSF) therapy. Methods: Clinical, laboratory and immunological data of 18 infants with AIN were evaluated. Granulocyte-specific autoantibodies were detected by the direct granulocyte immunofluorescence test (D-GIFT), indirect granulocyte immunofluorescence test (I-GIFT) and immunoblotting. Results: The average age of onset and resolution of neutropenia in AIN was 7.4 ±3.4 mo (mean ±SD) and 20.4 ±4.9 mo, respectively. Sixteen of the 18 patients presented with mild infectious symptoms; the other 2 patients were detected by chance and presented with no infectious symptoms. D-GIFT was positive in all patients, and I-GIFT was positive in 17 of these 18 patients. Most patients showed preferential binding to neutrophils from NA(1 + 2-)-phenotyped donors by I-GIFT and immunoblotting. An antibiotic (sulfamethoxazole-trimethoprim) was given to 15 patients for prophylaxis. G-CSF was given to only one infectious patient.

Conclusion: A combination of diagnostic tests for the detection of granulocyte-specific autoantibodies was useful in diagnosing AIN, thus avoiding unnecessary investigations. Continuous treatment with G-CSF was not necessary for prophylaxis, even if neutrophil counts were extremely low.     

Autoimmune neutropenia and Hodgkin's disease: successful treatment with intravenous gammaglobulin

We describe a child with Hodgkin's disease (HD) who presented with profound neutropenia, secondary to an antineutrophil antibody. The patient responded to intravenous immunoglobulin (IVIG), with prompt and sustained improvement in total white blood cell count (WBC) and absolute neutrophil count (ANC). The literature pertaining to autoimmune cytopenias complicating HD is reviewed, as well as the role of IVIG in management of these disorders.     

Autoimmune neutropenia in children: analysis of 116 cases

To cite this article: Audrain M, Martin J, Fromont P, Prié N, Thomas C, Muller J‐Y. Autoimmune neutropenia in children: analysis of 116 cases. Pediatr Allergy Immunol 2011; 22 : 494–496. Diagnosis of autoimmune neutropenia (AIN) in infants is important, because it allows the exclusion of more severe forms of neutropenia that have an increased risk for leukemia. AIN is characterized by chronic neutropenia, which spontaneously resolves within several months to a few years, and mild infections. Diagnosis is confirmed by the presence of antibodies directed against neutrophil antigens. The human neutrophil antigen (HNA) system is a polymorphic system, which includes five antigen groups with different polymorphisms. In AIN, antibodies are mostly directed against HNA‐1 (or against a specific allele of HNA‐1) and HNA‐4. Here, we present a series of 116 infants with AIN. We observed that anti‐neutrophil antibodies were present in 60% cases; directed against HNA‐1a in 73% of cases. In addition, we showed there was a bias in the HNA allele distribution in these infants because the frequency of the HNA‐1a allele was greater in comparison with controls.     

How we approach: Severe congenital neutropenia and myelofibrosis due to mutations in VPS45

Mutations in the VPS45 gene lead to a severe primary immune deficiency characterized by severe congenital neutropenia and primary myelofibrosis, leading to overwhelming infection and early death. This condition is exceedingly rare with only 16 patients previously reported, including four with successful hematopoietic stem cell transplantation. We review the pathophysiology underlying this condition and detail our approach to treatment, particularly vis‐à‐vis bone marrow transplantation and the challenges of transplanting into a diseased bone marrow niche. We provide an update on the progress of our three previously reported patients, and two additional patients transplanted at our center.     

Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established.
Methods: Seventy-nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re-investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed.
Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection-induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti-inflammatory therapy was common in children with rhinovirus infection-induced wheezing in infancy ( n  = 13/19; P  = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n  = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them.
Conclusions: After early childhood wheezing requiring hospitalization, one-fourth of children will have decreased lung function and one-eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.     

Serum granulocyte colony-stimulating factor levels are not increased in patients with autoimmune neutropenia of infancy

OBJECTIVE: To assess the role of granulocyte colony-stimulating factor (G-CSF) in autoimmune neutropenia (AIN). DESIGN: Serum G-CSF levels were measured in 57 children with AIN. Two different G-CSF-dependent assays were used: a solid-phase "sandwich" enzyme-linked immunosorbent assay and a proliferation assay. Sera from healthy persons and from patients with severe congenital neutropenia were used for negative and positive controls. RESULTS: The median G-CSF level in healthy persons (n = 13) was low, 45.6 pg/mL (range <39 to 141 pg/mL). The median G-CSF level in patients with AIN (n = 57) was very similar, 45.5 pg/mL (range <39 to 2500 pg/mL). Forty-five (79%) of 57 patients with AIN had levels within the range of the control group. Seven (12%) had marginally increased G-CSF levels (141 to 400 pg/mL), and only 5 (9%) had levels higher than 400 pg/mL. The G-CSF levels measured by enzyme-linked immunosorbent assay correlated well with levels measured by the proliferation assay, thus demonstrating that antibodies present in patient sera did not affect the biologic activity of G-CSF. CONCLUSION: G-CSF production in AIN is not increased despite the low neutrophil count, similar to thrombopoietin in immune thrombocytopenic purpura.     

Latex agglutination test: An adjunct to the laboratory diagnosis of pyogenic bacterial meningitis

Gram stain, culture and latex agglutination test (LAT) of cerebrospinal flud were performed in 50 patients clinically diagnosed as suffering from pyogenic bacterial meningitus. Using all the three techniques, an aetiological diagnosis was made in 27 (54%).Neisseria meningitidis, Streptococcus pneumoniae and H. influenzae were the infecting organisms in 21 cases (44%). There were 12 additional cases in which LAT was the only clue to the diagnosis as compared to conventional techniques.Propionibacterium acnes was isolated from one case of anaerobic meningitis. It is concluded that LAT is an adjunct to conventional techniques in the diagnosis of pyogenic bacterial meningitis, where the latter tests fail.     

不同底物间接免疫荧光法检测细胞膜DNA抗体在儿童系统性红斑狼疮的临床价值研究

目的：比较两种细胞株为底物间接免疫荧光法( indirect immunofluorescence assay,IIF)检测细胞膜DNA( cell membrane DNA,cmDNA)抗体在儿童系统性红斑狼疮( juvenile systemic lupus erythema-tosus,JSLE)中的检测效果。评价cmDNA抗体单独及与核小体抗体( anti-nucleosome antibody,AnuA)、史密斯( Smith,Sm)抗体和双链DNA( double-stranded DNA,dsDNA)抗体联合检测对JSLE的诊断价值;探讨cmDNA抗体与临床特点的相关性。方法选取92例JSLE为研究对象,71例非JSLE风湿病患儿为对照组。留血清采用IIF分别观察培养的人B细胞株Raji、人早幼粒白血病细胞株HL60细胞膜的荧光图形;同时用IIF检测抗核抗体( antinuclear antibody,ANA);联合酶联免疫吸附法( enzyme-linked immuno sorbent assay,ELISA)和IIF检测dsDNA抗体;联合应用免疫双扩散法和免疫印迹法检测Sm抗体、ELISA法测定AnuA,收集同期临床资料。结果以两种细胞株为底物检测JSLE患儿血清cmDNA抗体,发现Raji细胞株较HL60细胞株更易复苏、荧光图形亮度更强,表达效果更好。 cmDNA抗体在JSLE组较对照组有更高的阳性率。以Raji细胞株为底物检测cmDNA抗体,cmDNA抗体的敏感性明显高于Sm抗体及dsDNA抗体(P<0．01),特异性与dsDNA抗体相似(P>0．05),但低于Sm抗体及AnuA(P<0．01)。 cmDNA抗体分别与dsDNA抗体、Sm抗体及AnuA联合检测在SLE诊断中的敏感性均明显高于单独检测( P<0．05)。cmDNA抗体与SLE疾病活动度评分无相关性( P=0．907)。结论 cmDNA抗体对儿童SLE诊断的敏感性高,特异性强,可能成为儿童SLE诊断的相对特异性抗体之一。 cmDNA抗体与dsDNA抗体、Sm抗体及AnuA联合检测可提高对儿童SLE诊断的敏感性。选择Raji细胞株为底物检测cmDNA抗体较HL60细胞株更有优势。     

Cushing's disease due to a giant pituitary adenoma in early infancy: CT and MRI features

We report the case of a 12-month-old girl presenting with diabetes insipidus and Cushing's disease. Brain magnetic resonance imaging (MRI) demonstrated a large tumour arising from the sella turcica, extending up to the foramen of Monro and invading the cavernous sinuses. Surgery was performed to remove the suprasellar part of the tumour, and histology revealed an adrenocorticotrophin (ACTH) secreting pituitary adenoma. This entity is very rare in this age group and the MRI features have not previously been described.     

Metabolic alkalosis due to the use of an oligoantigenic diet in infancy

A 7-month-old boy on an oligoantigenic diet because of multiple food intolerances presented with anorexia, failure to gain weight and severe hypochloremic metabolic alkalosis with hyperreninemia. Clinical symptoms and biochemical abnormalities disappeared after adequate dietary supplementation with potassium and sodium chloride. This case emphasizes that minimal daily mineral requirements must be provided in infant diets, and highlights the risk of nutritional deficiencies inherent in the prolonged use of oligoantigenic diets not adequately supplemented.