Corticosteroid in Combination with Leflunomide and Mesenchymal Stem Cells for Treatment of Pediatric Idiopathic Pulmonary Hemosiderosis.

Background: This study evaluated the efficiency of corticosteroid, leflunomide and mesenchymal stem cells (MSCs) in the treatment of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods: Ten patients were included in the study. The diagnosis of IPH was based on clinical symptoms, laboratory examinations and pulmonary hemosiderosis. Induction therapy consisted of methylprednisolone pulse therapy, followed by prednisone plus leflunomide. Maintenance therapy consisted of low-dose prednisone, leflunomide and administration of MSCs. Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). Moreover, administration of MSCs induced an increase in the percentage of CD4+ CD25+ regulatory T cells but a decrease in the percentage of Th17 cells. Conclusion: Treatment with corticosteroid, leflunomide and MSCs for pediatric IPH was safe and effective.

Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient.

Idiopathic pulmonary haemosiderosis (IPH) is a rare disease characterized by alveolar capillary haemorrhage resulting in deposition and accumulation of haemosiderin in the lungs. Although its precise pathophysiology remains unclear, several hypotheses have been proposed to explain the aetiology of the disorder, including autoimmune, environmental, allergic, and genetic theories. IPH is typically diagnosed in childhood, usually before the age of 10 years; however, this entity may be encountered in older patients given the greater awareness of the diagnosis, availability and utilization of advanced imaging techniques, and improved treatment and survival. The classic presentation of IPH consists of the triad of haemoptysis, iron-deficiency anaemia, and pulmonary opacities on chest radiography. The diagnosis is usually confirmed via bronchoscopy with bronchoalveolar lavage (BAL), at which time haemosiderin-laden macrophages referred to as siderophages, considered pathognomonic for IPH, may be identified. However, lung biopsy may ultimately be necessary to exclude other disease processes. For children with IPH, the disease course is severe and the prognosis is poor. However, adults generally have a longer disease course with milder symptoms and the prognosis is more favourable. Specific imaging features, although non-specific in isolation, may be identified on thoracic imaging studies, principally chest radiography and CT, depending on the phase of disease (acute or chronic). Recognition of these findings is important to guide appropriate clinical management.

Extracorporeal life support for a 5-week-old infant with idiopathic pulmonary hemosiderosis.

UNLABELLED: Idiopathic pulmonary hemosiderosis is a rare disease defined by the triad of iron deficiency anemia, hemoptysis, and diffuse pulmonary infiltrates on chest radiograph. Idiopathic pulmonary hemosiderosis is known to cause dyspnea and, in some cases, acute onset of massive pulmonary hemorrhage which is traditionally treated with conventional mechanical ventilation or high-frequency oscillation in conjunction with immunosuppressive therapy. In this case report, we describe a 5-week-old infant presenting with hemoptysis, massive pulmonary hemorrhage, and significant hypercapnic respiratory failure. The patient failed conventional ventilation but responded well to extracorporeal life support that was initiated early in his course. Idiopathic pulmonary hemosiderosis was suspected in light of his response to high-dose steroids and was confirmed by subsequent lung biopsies. CONCLUSION: Patients with severe pulmonary hemorrhage secondary to idiopathic pulmonary hemosiderosis can be safely supported with extracorporeal life support when conventional therapies have been exhausted.

In vitro extraction of intra-corneal iron using reverse iontophoresis and vitamin C.

PURPOSE: The aim of this study was to optimize reverse iontophoretic (RI) extraction of ferric/ferrous ions from the cornea. METHODS: Group I consisted of the right eye corneas from 20 normal rabbits. Corneal blood staining was induced in 60 right eyes. The corneal depths from the endothelium to the epithelium layers were divided into three groups by slit-lamp examination: Group II, one-third corneal thickness; Group III, one-half corneal thickness; Group IV, full corneal thickness. RI was performed using vertical diffusion cells. The lower chamber was loaded with glutathione bicarbonate Ringer's buffer (GBR; pH 7.0) or vitamin C (12.5 mg/mL) and GBR (pH 7.0), while the upper chamber was filled with 1 mL GBR. Progress of corneal blood staining removal was evaluated. RESULTS: Application of 1.5 mA to the cornea increased flux by 1.72- and 2.19-fold in Groups III and IV, respectively, but not in Groups I or II, compared to the control. When vitamin C was included, we observed significant flux increases in the controls (1.5-, 2.06-, 2.60-, and 4.59-fold) for Groups I, II, III, and IV, and under RI conditions for Groups III and IV. Following RI, the corneal endothelia appeared similar to corneas from untreated control rabbits, while Draize scores were zero. CONCLUSIONS: These results suggested that extracellular ferric/ferrous ions could be extracted from the cornea in vitro by RI, and that vitamin C reduced Fe(3+) to Fe(2+) in the cornea and altered its permselectivity, thus increasing the RI contribution to iron extraction.

On myocardial siderosis and left ventricular dysfunction in hemochromatosis.

BACKGROUND: Chronically increased intestinal iron uptake in genetic hemochromatosis (HC) may cause organ failure. Whilst iron loading from blood transfusions may cause dilated cardiomyopathy in conditions such as thalassemia, the in-vivo prevalence of myocardial siderosis in HC is unclear, and its relation to left ventricular (LV) dysfunction is controversial. Most previous data on myocardial siderosis in HC has come from post-mortem studies. METHODS: Cardiovascular magnetic resonance (CMR) was performed at first presentation of 41 HC patients (58.9 ± 14.1 years) to measure myocardial iron and left ventricular (LV) ejection fraction (EF). RESULTS: In 31 patients (genetically confirmed HFE-HC), the HFE genotype was C282Y/C282Y (n = 30) and C282Y/H63D (n = 1). Patients with other genotypes (n = 10) were labeled genetically unconfirmed HC. Of the genetically confirmed HFE-HC patients, 6 (19%) had myocardial siderosis (T2* <20 ms). Of these, 5 (83%) had heart failure and reduced LVEF which was correlated to the severity of siderosis (R2 0.57, p = 0.049). Two patients had follow-up scans and both had marked improvements in T2* and LVEF following venesection. Myocardial siderosis was present in 6/18 (33%) of patients with presenting ferritin ≥ 1000 µg/L at diagnosis but in 0/13 (0%) patients with ferritin <1000 µg/L (p = 0.028). Overall however, the relation between myocardial siderosis and ferritin was weak (R2 0.20, p = 0.011). In the 10 genetically unconfirmed HC patients, 1 patient had mild myocardial siderosis but normal EF. Of all 31 patients, 4 had low LVEF from other identifiable causes without myocardial siderosis. CONCLUSION: Myocardial siderosis was present in 33% of newly presenting genetically confirmed HFE-HC patients with ferritin >1000 µg/L, and was the commonest cause of reduced LVEF. Heart failure due to myocardial siderosis was only found in these HFE-HC patients, and was reversible with venesection. Myocardial iron was normal in patients with other causes of LV dysfunction.

Updates in idiopathic pulmonary hemosiderosis in 2022: A state of the art review.

This manuscript reports the recent advances in idiopathic pulmonary hemosiderosis (IPH), a rare cause of diffuse alveolar hemorrhage in children and adults. This narrative review of the literature summarizes different aspects of IPH, including proposed pathogenesis, patient demographics, clinical and radiological characteristics, treatment, and prognosis. Additionally, the association between Celiac Disease (CD) and IPH is carefully evaluated. IPH is a frequently misdiagnosed disease. The delay in the diagnosis of IPH is often significant but fortunately, appears to have decreased in recent years. IPH in adults and children have distinct demographic preferences. The autoantibodies are common in IPH but with a definite difference between the adult and pediatric populations. The definitive diagnosis of IPH requires lung biopsy and careful exclusion of all competing diagnoses, even with lung biopsy showing bland pulmonary hemorrhage. The presence of nonspecific inflammatory cells or lymphoid aggregates may suggest a secondary immunologic phenomenon and needs careful evaluation and follow-up. A substantial number of patients suffer from coexisting CD, also known as Lane-Hamilton syndrome (LHS), and all patients with IPH need to be evaluated for LHS by serology. Although strict gluten free diet can manage the majority of patients with LHS, other patients generally require immunosuppressive therapy. The corticosteroids are the backbone of IPH therapy. Recently utilized experimental treatment options include mesenchymal stem cell transplant, liposteroid and bronchial artery embolization. The immunosuppression should be adjusted to achieve optimal disease control. Patients may progress to end-stage lung disease despite all measures, and lung transplantation may be the only viable option.

Superficial siderosis of the central nervous system: a rare cause of dementia with therapeutic consequences.

A 75-year-old patient was evaluated for dementia. His past medical history included an ischaemic cardiomyopathy treated with aspirin daily. His neurological examination showed mild ataxia syndrome and central deafness. The neuropsychological examination did not suggest Alzheimer's disease. No specific aetiology was found from biological investigations, but MRI scans revealed a superficial siderosis, which was further confirmed with CSF exams. This case highlights the interest of MRI with echo-gradient-T2 weighted sequences in patients investigated for memory disorders. Once the diagnosis is known, specific preventive measures have to be taken: searching for a treatable source of bleeding and the interruption of antiplatelet aggregation or anticoagulant treatments.

Child with idiopathic pulmonary hemosiderosis: a case report from Pakistan with multiple ethical and moral issues.

This report discusses the case of a young Pakistani child diagnosed with idiopathic pulmonary hemosiderosis (IPH). The key features of IPH were iron deficiency anemia and pulmonary symptoms due to recurrent pulmonary hemorrhages. The child showed complications of the disease process because of late diagnosis. Because various ethical and moral issues were associated with the diagnosis and management of IPH, this case provides insights about the care burden of health care professionals and a child's parents in a Pakistani pediatric setting. During the course of the child's treatment at one of the private tertiary care settings of Karachi, Pakistan, the key challenges were as follows: declaring the diagnosis to the parents, dealing with the request of the child's parents for withdrawal of ventilatory support and withholding treatment, deciding the code status of the child, and ensuring the quality of the child's life after discharge from the hospital. It was learned from this case report that shared decision making and open communication with the child's family enabled the pediatric health care professionals to determine what was in the best interest of the child, resulting in provision of effective palliative care to the child. Moreover, it was realized that early detection of the disease and availability of hospice care can facilitate palliative care of children diagnosed with IPH.

Clinical case of the month. Idiopathic pulmonary hemosiderosis presenting as a rare cause of iron deficiency anemia in a toddler--a diagnostic challenge.

Iron deficiency anemia is the most common cause of anemia in all age groups. Idiopathic pulmonary hemosiderosis is an extremely rare etiology of iron deficiency anemia seen predominantly in the pediatric population. Idiopathic pulmonary hemosiderosis is characterized by the triad of symptoms consisting of iron deficiency anemia, diffuse pulmonary infiltrates, and hemoptysis. The clinical presentation is extremely variable, and all three symptoms may not always be seen. Due to the rarity of the disease and the variability in clinical presentation, diagnosis is usually delayed. Early diagnosis and treatment with corticosteroids prevents further episodes of recurrent alveolar hemorrhage and improves the clinical outcome. Hence, a high index of suspicion is required for the diagnosis of this condition in young patients presenting with severe iron deficiency anemia and diffuse pulmonary infiltrates. We report a toddler with idiopathic pulmonary hemosiderosis whose initial clinical presentation was severe iron deficiency anemia.

Lane-Hamilton syndrome: case report and review of the literature.

We report a case of a three-and-a-half-year-old boy, who presented with poor general condition, stunted growth, had the presence of nail clubbing, persistent cough and frequent diarrhoea. Persistent iron deficiency anaemia without signs of haemolysis suggested Lane-Hamilton syndrome (LHS) which is or/is an extremely rare combination of idiopathic pulmonary haemosiderosis (IPH) and celiac disease (CD), although both diseases are immunologically mediated and the pathogenetic link between them is not clear. We have now 3 years of follow-up on gluten-free diet (GFD), resulting in a gradual recovery of the abnormal laboratory results in combination with an improving growth. Clinically, he is asymptomatic without any additional treatment. Our case illustrates that CD should be specifically looked for in patients with IPH, especially those in whom the severity of anaemia is disproportionate to the IPH symptoms. Both diseases may benefit from a GFD.

Hemolysis and acute kidney failure.

Deposits of iron and hemosiderosis in the kidney have been observed in diseases with intravascular hemolysis, including paroxysmal nocturnal hemoglobinuria, and valvular heart diseases and prosthetic heart valve implants. However, the decrease in kidney function associated with hemolysis caused by cardiac valvular disease or prostheses is less well recognized. We present a case of intravascular hemolysis after repair and banding of the mitral valve that resulted in massive renal tubular deposition of hemosiderin with decreased kidney function. We discuss the pathophysiologic process of both acute and chronic tubular injury from heme and heme proteins, including injury to organelles resulting in autophagic vacuoles containing damaged organelles, such as mitochondria. We conclude that tubular injury resulting from heme proteins should be considered as a cause of decreased kidney function in all patients with a cardiac valvular disease or prosthesis.

[Determinants for iron overload in patients with acute leukemias and aplastic anemia].

AIM: to reveal the determinants of the development of iron overload in patients with acute leukemias (AL) and aplastic anemia (AA). SUBJECTS AND METHODS: The investigation included 104 patients, including 64 with various types of AL, 31 with AA, and 9 with myelodysplastic syndromes (MDS). A group affiliation and an erythrocyte phenotype were determined from rhesus system antigens in all the patients and the HFE gene was studied to identify mutations. For control of siderosis, the authors determined serum iron (SI) by a colorimetric technique, by applying the kits of the AGAT firm (Russia), serum ferritin (SF) by an immunoradiometric method, by using the kits of Immunotech (Czechia). The volume of transfusion was estimated in the period of June 2007 to November 2009. RESULTS: There is evidence for a relationship between the higher level of SF and the number of transfusions. SF was 1046.1 microg/l in patients, H63D heterozygous carriers who had received less than 10 packed red blood cell transfusions and 2856 microg/l in those who had 20 transfusions (p < 0.005). HFE gene mutation carriage accelerates iron accumulation and is an additional risk factor for siderosis. In patients with transfusion chimeras and a rare phenotype in terms of rhesus antigens, packed red blood cell transfusion results in a much more increase in iron stores. CONCLUSION: The most important factor of iron overload acceleration is no specific choice of packed red blood cells for patients with rare combinations of red blood cell antigens and for those with artificially induced chimeras.

Pathological and Radiological Correlation in Prolonged Myeloperoxidase Anti-neutrophil Cytoplasmic Antibody-related Diffuse Alveolar Hemosiderosis.

A 60-year-old woman with a 20-year history of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis visited our hospital due to productive cough and a low-grade fever for several weeks. Thoracic computed tomography demonstrated scattered tiny nodules, patchy consolidation, ground glass opacities, and thickening interlobular septa. On video-assisted thoracic surgery, those abnormalities were found to correspond to the accumulation of hemosiderin-laden alveolar macrophages (AMs) in the alveolar spaces and alveolar septa due to MPO-ANCA vasculitis. The radiological findings persisted for a further two years, indicating the possibility of persistent vasculitis in the lung or evidence of incomplete clearance of hemosiderin-laden AMs.

[Chronic hepatitis B, hemosiderosis, and hepatic fibrosis in a renal graft recipient].

Chronic hepatitis B is a frequent concomitant disease in recipients of a renal graft that worsens results of kidney transplantation due to renal and extrarenal complications. Much rarer hemochromatosis either has genetic roots (hereditary hemochromatosis) or results from multiple blood transfusions and hemolysis during treatment by hemodialysis (secondary hemochromatosis). Combination of chronic hepatitis B and hemochromatosis increases the risk of chronic liver disease leading to cirrhosis and hepatocellular carcinoma. Success of antiviral therapy combined with massive phlebotomy is illustrated by a case of kidney transplantation to a patient with chronic hepatitis B of large duration and iron overload syndrome.

Pulmonary Hemorrhage in Children: Etiology, Clinical Profile and Outcome.

OBJECTIVE: To describe etiology, clinical profile, treatment and outcome of children with pulmonary hemorrhage. METHODS: A chart review of children with pulmonary hemorrhage attending Pediatric Pulmonology services of a tertiary care hospital in North-India was done. RESULTS: Data of 44 children (mean age 59.2 ± 32.1 mo; 28 boys) were included for the study. Possible idiopathic pulmonary hemosiderosis 16 (36.4%), post infectious complications 11 (25%), immune mediated disorders 8 (18.2%), cardiac and vascular disorders 7 (15.9%), and airway pathologies 2 (4.5%) were the etiologies of pulmonary hemorrhage. Treatment options like medications, bronchial artery embolization and surgical resections were offered according to the etiology. Children with idiopathic pulmonary hemosiderosis and those with immune mediated diseases were treated with systemic steroids and steroid sparing agents; the latter group took longer time to respond and had more relapses. CONCLUSIONS: Identification of main etiological categories of pulmonary hemorrhage in children could be useful to plan investigations and management of wide range of causes in more practical way.

Rare neonatal interstitial lung disease masquerading as pulmonary hemosiderosis.

A preterm 32-week neonate presented on the 14th day of life with respiratory distress and cyanosis. The respiratory distress worsened progressively, which was managed with continuous positive airway pressure support. The neonate had blood-tinged oral secretions on the 39th day of life, for which bronchoscopy was performed, whose findings were suggestive of pulmonary hemosiderosis. Lung biopsy confirmed the diagnosis of pulmonary interstitial glycogenosis with pulmonary arterial hypertension. The neonate was treated successfully with systemic corticosteroids and discharged home at 3 months of age.

Management of a parturient with an acute exacerbation of idiopathic pulmonary haemosiderosis and posterior spinal instrumentation.

Idiopathic pulmonary haemosiderosis (IPH) is a rare condition associated with diffuse alveolar haemorrhage and pulmonary fibrosis. We describe the anaesthetic management of a parturient with a history of posterior spinal fusion presenting with an acute exacerbation of IPH necessitating vaginal delivery at 34 weeks gestation. We used a spinal catheter for labour analgesia and bilevel positive airway pressure (BIPAP) ventilation to improve oxygenation during labour. An arterial line sited to allow frequent arterial blood gas sampling also facilitated continuous cardiac output monitoring. The use of a carefully titrated neuraxial block for analgesia, in conjunction with BIPAP, was associated with minimal haemodynamic and respiratory compromise during labour in this patient.

Bilirubin cholelithiasis and haemosiderosis in an anaemic pyruvate kinase-deficient Somali cat.

A Somali cat was presented with recurrent anorexia, lethargy, vomiting and icterus. A macrocytic-hypochromic, regenerative haemolytic anaemia was identified and hereditary pyruvate kinase deficiency was confirmed by means of breed-specific DNA mutation analysis. The case was complicated by the presence of markedly elevated serum liver enzyme activities, hyperbilirubinaemia, coagulopathy and ultrasonographic evidence of gall bladder choleliths and extrahepatic bile duct obstruction. The choleliths consisted of 100 per cent bilirubin, likely because of chronic haemolysis and haeme degradation. In conclusion, haemosiderosis and bilirubin cholelithiasis can be a consequence of chronic haemolysis in pyruvate kinase-deficient cats, as seen in human beings with a variety of chronic haemolytic disorders.

Aceruloplasminemia with Abnormal Compound Heterozygous Mutations Developed Neurological Dysfunction during Phlebotomy Therapy.

Aceruloplasminemia is an autosomal recessive inherited disorder caused by ceruloplasmin gene mutations. The loss of ferroxidase activity of ceruloplasmin due to gene mutations causes a disturbance in cellular iron transport. We herein describe a patient with aceruloplasminemia, who presented with diabetes mellitus that was treated by insulin injections, liver hemosiderosis treated by phlebotomy therapy, and neurological impairment. A genetic analysis of the ceruloplasmin gene revealed novel compound heterozygous mutations of c.1286_1290insTATAC in exon 7 and c.2185delC in exon 12. This abnormal compound heterozygote had typical clinical features similar to those observed in aceruloplasminemia patients with other gene mutations.