Hemosiderosis

BackgroundThere is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.MethodsHere, we used an optimised liver T2* sequence calibrated against 50 liver biopsy samples on 25 patients with transfusional haemosiderosis using ordinary least squares linear regression, and assessed the method reproducibility in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman plots. Using mixed model linear regression we compared the new T2*-LIC with R2-LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and examined method agreement using Bland-Altman approach.ResultsStrong linear correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC = 31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC (Ferriscan) technique in 92 scans, we observed a close relationship between the two methods for values up to 10 mg/g dw, however the method agreement was poor.ConclusionsNew calibration of T2* against liver biopsy estimates LIC in a reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due to poor agreement, both methods should be used separately to diagnose or rule out liver iron overload in patients with increased ferritin.

BackgroundIdiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. Classically, diagnosis is based on a triad including hemoptysis, diffuse parenchymal infiltrates on chest X-rays, and iron-deficiency anemia. We present the French pediatric cohort of IPH collected through the French Reference Center for Rare Lung Diseases (RespiRare®, http://www.respirare.fr).MethodsSince 2008, a national network/web-linked RespiRare® database has been set up in 12 French pediatric respiratory centres. It is structured as a medical recording tool with extended disease-specific datasets containing clinical information relevant to all forms of rare lung diseases including IPH.ResultsWe identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0] yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16, 64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n = 11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung biopsy (6/25). In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%). All the patients were initially treated by corticosteroids. In 13 cases, immunosuppressants were introduced due to corticoresistance and/or major side effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage.ConclusionThe present cohort provides substantial information on clinical expression and outcomes of pediatric IPH. Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors.

BackgroundT2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T.MethodsA total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*.ResultsAssociation between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (R (2) = 0.954, p ConclusionHeart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*.

BackgroundIdiopathic pulmonary hemosiderosis (IPH) is a rare interstitial lung disease. Glucocorticosteroids and hydroxychloroquine are the most commonly used treatments. Although neuropsychiatric side effects related to hydroxychloroquine use are seen in adult cases, only one paediatric patient has been reported in the literature.Case presentationWe report a case of a 6-year-old girl with IPH, who developed neuropsychiatric symptoms, including restlessness, confusion and myoclonic movements, after the therapeutic use of hydroxychloroquine.ConclusionWith increasing knowledge and experience of interstitial lung disease, the use of hydroxychloroquine treatment is increasing. It is important to remember that hydroxychloroquine is a central nervous system stimulant, and neuropsychiatric side effects may be seen in children. This report highlights the importance of recognising potential neuropsychiatric side effects in paediatric patients using hydroxychloroquine, especially when combined with corticosteroids or other risk factors.