Clinical features and risk factors for recurrence of idiopathic pulmonary hemosiderosis in children.

BACKGROUND: This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. METHODS: Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. RESULTS: A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107-16.356) tended to experience disease recurrence (p = 0.01). CONCLUSIONS: Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. TRIAL REGISTRATION: This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Transfusional hemosiderosis in childhood cancer patients and survivors.

BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

Giant thigh hemosiderotic/aneurysmal dermatofibroma: Case report with radiologic-pathologic correlation.

Hemosiderotic/aneurysmal variant of dermatofibroma (DF) is infrequent and may be misdiagnosed with malignant lesions. We report the case of a giant (7.6cm) subcutaneous hemosiderotic/aneurysmal DF (H/ADF) of the thigh in a 53-year-old female patient. Internal arterial and venous hypervascularity was seen by spectral Doppler ultrasound. Magnetic resonance image showed a discrete homogeneous hypointense in T1-weighted images (WI) and T2-WI mass, with hyperintense areas in fat-suppressed T2-WI. The histology revealed a monotonous fusocelular proliferation without atypia, positive for CD163, factor XIIIa and CD10. Widely distributed hemosiderin pigment and two blood-filled pseudovascular spaces lacking endothelial lining were present. H/ADF was diagnosed. The mass was removed but surgical margins were affected. The patient did not present local relapse or distant metastasis. H/ADF are unusual cutaneous soft tissue tumours that can be clinically, radiologically and histopathologically confused with malignant lesions such as melanomas, vascular lesions or sarcomas, especially in giant cases.

Idiopathic pulmonary haemosiderosis.

In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.

Central Nervous System Siderosis Associated with Multiple Cerebral Aneurysms: Literature Review and Description of an Additional Case.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. METHODS: A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. RESULTS: A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. CONCLUSIONS: Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment.

Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

An Adult Case of Idiopathic Pulmonary Hemosiderosis Associated with Pulmonary Fibrosis and Emphysematous Change.

A 48-year-old woman was admitted to our hospital with acute respiratory failure. Chest computed tomography showed ground-glass opacity and patchy emphysematous lesions in both lungs. Corticosteroid therapy was effective; however, the disease worsened with the tapering of corticosteroids. Bronchoalveolar lavage revealed hemosiderin-laden macrophages, and video-assisted thoracic surgery showed diffuse interstitial fibrosis with diffuse alveolar hemorrhage (DAH). There was no evidence of vasculitis nor autoimmune diseases. This patient was diagnosed with idiopathic pulmonary hemosiderosis (IPH) that progressed to end-stage pulmonary fibrosis despite treatment. Autopsy demonstrated DAH with pulmonary fibrosis and emphysematous change, suggesting IPH-related pulmonary lesions.

Relationship between bone marrow iron load and liver iron concentration in dialysis-associated haemosiderosis.

BACKGROUND: Iron overload due to the excessive use of parenteral iron in haemodialysis is now an increasingly recognised clinical issue. Before erythropoiesis-stimulating agents (ESA) were introduced, a specific feature of patients treated by dialysis and having iron overload was that iron levels in the bone marrow were paradoxically low in most of them, despite severe hepatosplenic siderosis. Whether or not this paradox persists in the actual ESA era was unknown until recently, when an autopsy study in 21 patients treated by haemodialysis revealed similarities between liver and bone marrow iron content. The aim of this study was to further explore these recent findings in a cohort of alive patients on dialysis and to analyse the determinants of iron bone marrow. METHODS: Liver iron concentration (LIC) and vertebral T2∗ (a surrogate marker of bone marrow iron) were analysed retrospectively in 152 alive patients on dialysis (38.8% female) of whom 47.4% had iron overload by quantitative magnetic resonance imaging (MRI). FINDINGS: Vertebral T2∗ differed significantly between patients classified according to liver iron content at MRI: those with mild or moderate and severe liver iron overload had increased vertebral iron content at R2∗ relaxometry MRI (mild: vertebral T2∗ = 9.9 ms (4-24.8); moderate and severe: vertebral T2∗ = 8.5 ms (4.9-22.8)) when compared to patients with normal LIC (vertebral T2∗ = 13.2 ms (6.6-30.5) (p < 0.0001 Kruskal-Wallis test)). INTERPRETATION: The paradoxical discrepancy between bone marrow and liver iron-storage compartments observed in the pre-ESA era has disappeared today, as shown by a recent autopsy study and the present study in a cohort of alive patients treated by dialysis. FUNDING: None.

Idiopathic pulmonary haemosiderosis misdiagnosed as haemolytic anaemia: a case report.

Idiopathic pulmonary haemosiderosis is a rare disease primarily affecting children. The condition is characterized by widespread bleeding from alveolar capillaries, resulting in symptoms such as haemoptysis, shortness of breath and iron deficiency anaemia. However, it is not a specific disease and sometimes can manifest solely as anaemia, which may be easily overlooked and misdiagnosed. The purpose of this case report was to describe a 1-year-old boy who exhibited haemolytic anaemia as the only symptom of idiopathic pulmonary haemosiderosis, with the intention of offering clinical insights into the precise diagnosis and subsequent management of this rare and easily misdiagnosed disease. Clinicians should keep idiopathic pulmonary haemosiderosis in mind when evaluating children with haemolytic anaemia and promptly initiate testing and treatment to prevent misdiagnosis and improve outcomes.

Idiopathic Pulmonary Haemosiderosis: An Unusual Case Of Anaemia With Pulmonary Involvement.

Idiopathic pulmonary haemosiderosis is a rare disorder, with recurrent life-threatening alveolar haemorrhages and chronic lung parenchymal changes. It is associated with a triad of haemoptysis, iron deficiency anaemia, and diffuse pulmonary infiltrates. Although most cases are idiopathic, secondary haemosiderosis linked to known diseases has also been observed. Most of the cases remain undiagnosed because the disease is very low on the list of differentials. There is no specified age for the disease. The present study reports on an adolescent female patient who presented with microcytic anaemia and bilateral lung infiltrates to the National Institute of Child Health (NICH), Karachi, a tertiary care hospital. She was diagnosed with Idiopathic pulmonary haemosiderosis after ruling out other possibilities.

Hemosiderotic Xanthelasmas. A New Clinicopathological Variant of Xanthelasma Palpebrarum or a Localized Variant of Xanthosiderohistiocytosis of the Eyelids?

ABSTRACT: Xanthelasma palpebrarum represent the most common subtype of cutaneous plane xanthomas. Xanthosiderohistiocytosis is considered a rare variant of xanthoma disseminatum, with only 4 cases reported to date. We report the case of a man with progressive pigmented lesions on the 4 eyelids that could correspond to hemosiderotic xanthelasmas or a localized variant of xanthosiderohistiocytosis.

Leflunomide Is Safe and Effective for the Induction and Maintenance of Idiopathic Pulmonary Hemosiderosis Remission.

Objective: The present study was aimed to investigate the efficacy of leflunomide in idiopathic pulmonary hemosiderosis (IPH) disease control and glucocorticoid attenuation. Methods: The efficacy of leflunomide was determined based on disease control, safety, and glucocorticoid attenuation. Result: A total of 46 children with IPH were included in the present study. Of these 31 patients had been unsuccessfully treated with glucocorticoids before admission at our hospital and did not achieve complete remission; the other 15 patients had not previously received steroids. Leflunomide combined with glucocorticoid was administered to all patients, and all were followed up for a median duration of 3 years. The average hemoglobin level significantly increased and the median minimum steroid dose was significantly decreased after leflunomide administration. Conclusion: Leflunomide safely and effectively induced and maintained IPH remission and decreased IPH relapse and glucocorticoid dose.

Axillary Cutaneous Hemosiderosis in a Patient With Hyperhidrosis, After Intravenous Iron Infusion.

ABSTRACT: Hemosiderosis consists of an iron deposit in tissues, which does not cause organic damage to them. However, in the case of the skin, being an organ exposed to sight, siderosis can produce a brownish coloration that is aesthetically discomforting for the individual. Most cutaneous sideroses are because of venous insufficiency with hemorrhagic extravasation. There is also a group secondary to iron extravasation in the injection site of the transfusion. However, there are very few cases in which an intravenous injection of an iron preparation has produced diffuse siderosis in extensive areas of the skin. We present the case of a 31-year-old woman with hyperhidrosis, who was transfused as a result of postpartum hemorrhage and, shortly after receiving an intravenous iron infusion, developed extensive hyperpigmentation in both axillae.

Hemosiderosis in chronic dialysis patients: Monitoring the response to deferasirox by quantitative hepatic magnetic resonance imaging.

INTRODUCTION: Hemosiderosis of chronic dialysis has always been a frequent phenomenon in dialysis; formerly related to blood transfusions before the advent of Erythropoiesis Stimulating Agents (ESA), it is currently in connection with the use of massive doses of injectable iron, to ensure the full therapeutic efficacy of ESA. Few studies have looked at the therapeutic aspect of iron chelators in the dialysis population. METHODS: We followed 31 dialysis patients treated for secondary hemosiderosis with deferasirox (DFX) at the dose 10 mg/kg/day, by hepatic MRI from September 2017 to September 2021, in order to evaluate the efficacy of iron chelators on the reduction of liver iron concentration (LIC). The diagnosis of hemosiderosis was carried for a value of the LIC > 50 µmol/g of dry liver. RESULTS: Chelation resulted in a significant reduction in liver iron burden as measured by liver MRI: (201.4 ± 179.9 vs. 122.6 ± 154.3 µmol/g liver) (p = 0.000) and in mean ferritin level: (2058.8 ± 2004.9 vs. 644.2 ± 456.6 ng/mL) (p = 0.002). A gain of 1.1 g/dL in mean hemoglobin level: (10.5 ± 1.6 vs. 11.6 ± 2.0 g/dL) (p = 0.006). A significant increase in mean albumin level: (43 ± 5.5 to 46.2 ± 6.1 g/L) (p = 0.04). The therapeutic response was clearly influenced by the cause of overload, longer in polytransfused patients (p = 0.023) and the degree of overload assessed by MRI (p = 0.003) and ferritin level (p = 0.04). CONCLUSION: DFX, prescribed at a dose of 10 mg/kg/day, resulted in a significant reduction in hepatic iron burden as measured by liver MRI and ferritin. The therapeutic response was clearly influenced by blood transfusions and the degree of iron overload.

Bronchoalveolar lavage hemosiderosis in lightly active or sedentary horses.

BACKGROUND: Hemosiderophages in bronchoalveolar lavage fluid (BALF) are commonly ascribed to exercise-induced pulmonary hemorrhage (EIPH). Little information exists regarding the presence of these cells in horses that perform light or no work and that are referred for respiratory problems. OBJECTIVES: Evaluate the presence of hemosiderophages in BALF of horses suspected of respiratory disease without history of or risk factors for EIPH and determine predictors of hemosiderophages in BALF in this population. METHODS: Observational retrospective cross-sectional study using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Bronchoalveolar lavage fluid cytology reports of 353 horses evaluated for respiratory disease between 2012 and 2022 at the Cummings School for Veterinary Medicine were reviewed retrospectively. Horses with a history or likelihood of having performed past strenuous exercise were removed, and the remaining 91 horses were divided into hemosiderin-positive (HSD-POS) and hemosiderin-negative groups based on Perls' Prussian blue staining. Potential predictors for the presence of hemosiderophages in BALF (history, clinical evaluation, baseline lung function, airway reactivity, BALF cytology, and hemosiderin score) were compared between the 2 groups, using univariate and multivariate analyses. RESULTS: Horses with a diagnosis of severe equine asthma (sEA; odds ratio, 11.1; 95% confidence interval, 3.2-38.5; P < .001) were significantly more likely to be HSD-POS than horses with mild-to-moderate equine asthma. CONCLUSIONS AND CLINICAL IMPORTANCE: Hemosiderophages were found in the BALF cytology in a subset of horses that perform light or no work and presented for respiratory signs; these cells were found more frequently in horses with sEA. The link between hemosiderophages and sEA highlights previously unstudied pathology associated with this common disease.

Idiopathic pulmonary hemosiderosis and stroke secondary to protein C deficiency in a child with Down syndrome: a case report.

BACKGROUND: Patients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare. CASE PRESENTATION: We report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency. CONCLUSION: Idiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.

Unusual neuroimaging findings in spontaneous intracranial hypotension.

PURPOSE: The most common neuroimaging manifestations of patients suffering from spontaneous intracranial hypotension (SIH) include subdural fluid collections, enhancement of the pachymeninges, engorgement of venous structures, pituitary hyperemia, sagging of the brainstem, and cerebellar hemosiderosis. However, infrequently patients may present with separate neuroradiological findings which could be easily mistaken for other pathology. METHODS: We describe patients who presented with unique neuroimaging findings who were eventually found to have a spinal CSF leak or venous fistula. Relevant clinical history and neuroradiology findings are presented, and a relevant review of the literature is provided. RESULTS: We present six patients with a proven CSF leak or fistula who presented with dural venous sinus thrombosis, compressive ischemic injury, spinal hemosiderosis, subarachnoid hemorrhage, pial vascular engorgement, calvarial hyperostosis, and spinal dural calcifications. CONCLUSION: Radiologists should be familiar with atypical neuroimaging manifestations of SIH in order to avoid misdiagnosis and guide the clinical trajectory of the patient towards accurate diagnosis and eventual cure.