Acquired hypochromic and microcytic sideroblastic anaemia responsive to pyridoxine with low value of free erythrocyte protoporphyrin: a possible subgroup of idiopathic acquired sideroblastic anaemia (IASA)

Patients with idiopathic acquired sideroblastic anaemia (IASA) usually show macrocytic or normocytic anaemia and increased free erythrocyte protoporphyrin (FEP). The mean cell haemoglobin concentration is normal or slightly low. Here we report a pyridoxine-responsive IASA patient with microcytic and hypochromic anaemia and low FEL level; these features are usually seen in cases of hereditary sideroblastic anaemia. Microcytosis increased during therapy.
There may be a subgroup of IASA with microcytic and hypochromic anaemia, low normal FEP and some response to pyridoxine like hereditary sideroblastic anaemia.     

Diagnosing fibrotic lung disease: When is high‐resolution computed tomography sufficient to make a diagnosis of idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF), a progressive and fatal diffuse parenchymal lung disease, is defined pathologically by the pattern of usual interstitial pneumonia (UIP). Unfortunately, a surgical lung biopsy cannot be performed in all patients due to comorbidities that may significantly increase the morbidity and mortality of the procedure. High-resolution computed tomography (HRCT) has been put forth as a surrogate to recognize pathological UIP. The quality of the HRCT impacts the ability to make a diagnosis of UIP and varies based on the centre performing the study and patient factors. The evaluation of the HRCT includes assessing the distribution and predominance of key radiographical findings, such as honeycomb, septal thickening, traction bronchiectasis and ground glass attenuation lesions. The combination of the pattern and distribution is what leads to a diagnosis and associated confidence level. HRCT features of definite UIP (subpleural, basal predominant honeycomb with septal thickening, traction bronchiectasis and ground glass attenuation lesions) have a high specificity for the UIP pathological pattern. In such cases, surgical lung biopsy can be avoided. There are caveats to using the HRCT to diagnose IPF in isolation as a variety of chronic pulmonary interstitial diseases may progress to a UIP pattern. Referral centres with experience in diffuse parenchymal lung disease that have multidisciplinary teams encompassing clinicians, radiologists and pathologists have the highest level of agreement in diagnosing IPF.     

Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab

In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74 ± 5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75 ± 3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89 ± 3.9 U/L) was significantly higher than that in the active period (P < 0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment.     

Health related quality of life survey about children and adolescents with juvenile idiopathic arthritis

This study aimed to investigate the proxy-reported Health related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA). It was hypothesized that HRQOL would decrease with worsening disease and disability. Data were available in cross-sectional study on children and adolescents with JIA according to the ILAR criteria. Patient demographics, type of JIA, clinical determinants and laboratory parameters relating to JIA were obtained for each patient. Functional disability was assessed using the parent’s or children’s version of the child health assessment questionnaire (CHAQ). The HRQOL was evaluated using the juvenile arthritis quality of life questionnaire (JAQQ). These questionnaires were previously translated and validated in Moroccan children. A total of 80 participants were enrolled with mean age of 11 [6–17 years], and female predominance (59%). Many patients (42.5%) had oligoarticular subtype; 31.3% polyarticular subtypes and 26.2% systemic form. The mean global score of JAQQ was 2.6 ± 1.3 (1–6). Patients with persistant oligoarticular had better gross motor function (P < 0.0001), better fine motor function (P < 0.0001), less psychosocial impact (P = 0.001), and less symptoms (P = 0.001) in comparison with polyarticular and systemic subtypes. The HRQOL assessed by the JAQQ was worse in adolescent patients in comparison with children except for symptoms (P = 0.15). The gender (P = 0.95), age at onset of JIA (P = 0.81), and evolution duration (P = 0.34) were not correlated with global score of JAQQ. The diagnosis delay was significantly associated with decrease of HRQOL (P = 0.001). The decrease of HRQOL was correlated with disease activity [pain (VAS), painful and swollen joints, erythrocyte sedimentation rate (for P < 0.0001)], with disability index (CHAQ) (P = 0.001) and presence of hip involvement (P = 0.01). This study suggests that JIA can have a significant adverse effect on the HRQOL of moroccan patients, particularly adolescents with polyarticular and systemic subtypes. Disease duration, disability score (CHAQ) and pain were the strongest determinants of poorer HRQOL.     

A Case Report of Successful Treatment With Plasma Exchange for Hemophagocytic Syndrome Associated With Severe Systemic Juvenile Idiopathic Arthritis in an Infant Girl

Abstract: An infantile case of hemophagocytic syndrome (HPS) with systemic juvenile idiopathic arthritis (s-JIA), refractory to methylprednisolone pulse therapy and cyclosporine A administration, was successfully treated by plasma exchange. The patient was a one-year-old Japanese girl who had developed recurrent steroid-dependent signs, including fever, skin eruption, and hepatopathy, while in France, where she had been diagnosed as having s-JIA at eight months of age. As a high fever and rheumatoid rash were evident on arrival at our hospital, she was admitted and given intravenous methylprednisolone pulse therapy and cyclosporine A. She developed pancytopenia with a generalized clonic seizure, high fever, and liver dysfunction after her cytomegalovirus (CMV) titer became positive during the course of treatment; therefore, she was treated with ganciclovir. She was subsequently diagnosed as having HPS complicating s-JIA from the findings of a bone marrow aspirate. At this time, her blood examination data including a high level of C-reactive protein and hyperferritinemia, suggested that her s-JIA was very active, and the pancytopenia continued after her CMV titer became negative. Therefore, CMV infection against a background of active s-JIA could have triggered the HPS in this case. Because the HPS was resistant to an immunosuppressive regime of methylprednisolone pulse therapy and cyclosporine A, plasma exchange therapy was started. After three sessions of this therapy, the patient's symptoms and laboratory data were markedly improved. Our experience suggests that plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.     

T-bet、GATA-3在慢性特发性血小板减少性紫癜患者外周血中的表达及意义

目的进一步探讨慢性特发性血小板减少性紫癜（CITP）的发病机制。方法选择25例CITP患者（CITP组）及25例健康体检者（正常对照组）,采用ELISA法检测外周血Th细胞因子IFN-γ、IL-10表达;采用RT—PCR检测外周血淋巴细胞中转录因子T-bet、GATA-3mRNA表达。结果与正常对照组相比,CITP组IFN—γ表达显著升高、IL-10表达显著降低（P〈0．01）,T—betmRNA表达明显升高、GATA-3mRNA表达明显下降（P〈0．05）。结论T-bet、GATA-3表达异常在CITP发生、发展过程中发挥重要作用,可能机制为增强TM细胞功能、抑制Th2细胞功能。     

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynaud's phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.     

Direct and indirect action modes of acetylcholine in cholinergic urticaria

Cholinergic urticaria (CholU) manifests small, itchy and/or painful wheals occurring upon perspiration and mechanically involving acetylcholine (Ach). Although a considerable number of studies have been conducted, the pathomechanisms underlying perspiration-associated release of histamine remain to be elucidated. We have proposed that CholU can be categorized into two major subtypes: Ach-indirectly induced, sweat allergic type and Ach-directly induced, depressed sweating type. In the former type, Ach evokes perspiration, and some sweat antigen(s) leaking from the sweat ducts to the dermis may stimulate mast cells to release histamine. In this scenario, the ducts might be damaged or obstructed for sweat leakage, and patients frequently exhibit positive autologous sweat skin test, representing “sweat allergy (hypersensitivity)”. On the other hand, the latter Ach-mast cell directly interacting type, typically seen as “CholU with anhidrosis and/or hypohidrosis (CUAH)”, eccrine sweat gland epithelial cells lack cholinergic receptor M3 expression. The expression of cholinergic receptors is completely absent in the anhidrotic areas and only slightly expressed in the hypohidrotic areas. In the hypohidrotic area, where pinpoint wheal occurs, it is hypothesized that released Ach cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheal formation. Thus, sweat allergy is not a requirement in this depressed sweating type. Although some additional complications, such as angioedema, anaphylaxis, and cold urticaria, have been documented, these two types represent the modes of action of Ach in this enigmatic urticaria.     

Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®

BackgroundBird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research.MethodsWe executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients.ResultsThe levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85–91% and 73–80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48–61% and 73–80%, respectively.ConclusionsMeasurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.