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Background: Chronic diseases are associated with a range of functional and psychosocial consequences that can adversely affect patients' quality of life (QoL). Haemochromatosis (HC) is a genetically heterogeneous disorder characterized by chronic iron overload that can ultimately lead to multiple organ dysfunction. Clinical diagnosis remains challenging due to the nonspecificity of symptoms and a lack of confirmatory genotyping in a substantial proportion of patients. Illness perception among HC patients has not been extensively investigated, lacking relevant information on how to improve their QoL., Methods: We present the results of the first worldwide survey conducted in nearly 1500 HC respondents, in which we collected essential demographic information and identified the aspects that concern HC patients the most., Results: Out of all the participants, 45.3% (n = 676) voiced their concern about physical and psychological consequences such as HC-related arthropathies, which can ultimately affect their social functioning. A similar proportion of patients (n = 635, 42.5%) also consider that better-informed doctors are key for improved HC disease management. Taking a patient-centred approach, we expose differences in patients' disease perspective by social and economic influences., Conclusions: We identify potential targets to improve patients' health-related QoL and reflect on strategic measures to foster gender equity in access to health resources. Finally, we make a call for a highly coordinated effort across a range of public policy areas to empower participants in the HC research process and design., Patient or Public Contribution: Nearly 1500 patients with hereditary HC responded to an anonymized online survey in which research and clinical priorities were addressed regarding this chronic and rare disease., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

While autoimmune antibodies or autoantibodies have been reported sporadically in adult patients with idiopathic pulmonary hemosiderosis (IPH), their true prevalence is unknown. The question as to whether any difference exists between antibody-positive and negative patients has not been explored. The primary objective of this paper was to assess the spectrum of autoantibody testing and its positivity rate. The other objectives included a comparative analysis of demographics, symptom onset, clinical manifestations, and differences in clinical outcomes between antibody-positive (cohort A) and negative (cohort B) patients. To that end, we conducted a retrospective review of the relevant published literature. Multiple databases were searched to retrieve studies published between 1990 and 2022. A total of 35 studies, involving 38 patients, were identified. Five of these patients had a positive autoantibody. Patients in cohort A were older and more likely to be male. The frequencies of testing for these antibodies were as follows: antineutrophil cytoplasmic antibody (ANCA): 37/38 (97.4%), antinuclear antibody (ANA): 31/38 (81.6%), and anti-glomerular basement membrane antibody (anti-GBM): 30/38 (78.9%); 5/38 (13.2%) patients tested positive for an autoantibody, and two of these patients were positive for ANA, two for antithyroid antibody, and one patient tested positive for ANCA, rheumatoid factor (RF), and granulocyte monocyte-colony stimulating factor (GM-CSF) antibody. There was no difference between the cohorts regarding their clinical presentations, recurrence risks, and survival. The occurrence of autoantibodies is uncommon in adult IPH patients. This is in contrast with the pediatric IPH patient population, where the prevalence is much higher (26.4% vs. 13.2%), and the antibodies are more diverse. Unlike pediatric patients, adult patients with autoantibodies do not necessarily have worse outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Saha et al.)

Idiopathic pulmonary hemosiderosis (IPH) causes diffuse alveolar hemorrhage (DAH) by a yet unknown mechanism. The coexistence of IPH and celiac disease (CD), also known as Lane-Hamilton syndrome (LHS), has been reported in both pediatric and adult patients. The objective of this study was to compare demographics, clinical and radiologic findings, treatment, and outcomes between adult patients with IPH and LHS. This is a systematic review of the literature. Multiple databases were searched using appropriate formulas to identify relevant articles. A total of 60 studies reporting 65 patients were included in the review. Forty-nine of these patients had IPH and 16 had LHS. The prevalence of anti-CD antibodies among tested patients was 13/22 (59%). The symptom onset and diagnosis of IPH occurred earlier in patients with LHS. The median delay in diagnosis was the same between the two groups (52 weeks). The classic triad was more likely to be present in patients with LHS. Only 20% of patients in the LHS cohort had any significant gastrointestinal (GI) symptoms at the time of IPH diagnosis. A gluten-free diet alone was effective in the majority of patients. Fewer patients in the LHS cohort received systemic corticosteroid than the IPH cohort. The recurrence and mortality in patients with LHS appear to be less than in the IPH cohort. The prevalence of CD is 25% in adult patients with IPH. Patients with LHS may have a milder course than patients without CD. Serologic testing for CD should be performed in all patients diagnosed with IPH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Saha et al.)

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH). Glucocorticosteroids (CS) represent the first line therapy for IPH. Although most patients respond to CS, steroid refractoriness is seen in an appreciable minority of patients. This paper reviews and evaluates the efficacy and safety profile of liposomal dexamethasone 21-palmitate (liposteroid) for the treatment of IPH. Medline, Embase and Web of Science biomedical databases were searched between 1980 and 2020 to identify papers describing patients with IPH, who were treated with liposteroid. A total of five articles were identified. Four in the form of case reports and one as a case series. A total of 12 pediatric patients (5 boys, 7 girls) were identified, with a median age of 2.3 years (range 0.5-8.6). Liposteroid therapy in intravenous doses ranging 0.06-0.1 mg/kg body weight appeared to be effective for both remission induction therapy, and maintenance therapy. There was no mortality among patients treated with liposteroid, either in the acute phase or during follow-up. The majority of patients for whom long-term follow-up data were available, were cured or in disease remission. No acute adverse events were reported, and long-term side effects were minimal and tolerable. Liposteroid represents a potential alternative or supplement to conventional CS therapy, as it appears to be more efficacious and associated with fewer side effects. Larger prospective, controlled trials are necessary to be able to define more precisely the therapeutic role of liposteroid in IPH.

Genetic hemochromatosis causes iron overload by excess absorption of dietary iron, due to a decreased expression of hepcidin. The objective was to elaborate dietary recommendations that can reduce intestinal iron absorption in hemochromatosis patients, based on our present knowledge of the iron contained in nutrients and the mechanisms of iron uptake. This is a narrative review. Literature search in PubMed and Google Scholar of papers dealing with iron absorption from the diet was conducted. Most important proposed dietary recommendations are: 1) Choose a varied vegetarian, semi-vegetarian or flexitarian diet. A "veggie-lacto-ovo-poultry-pescetarian" diet seems optimal. Avoid iron enriched foods and iron supplements. 2) Eat many vegetables and fruits, at least 600 g per day. Choose protein rich pulses and legumes (e.g., kidney- and soya beans). Fresh fruits should be eaten between meals. 3) Abstain from red meat from mammals and choose the lean, white meat from poultry. Avoid processed meat, offal and blood containing foods. Eat no more than 200 g meat from poultry per week. Choose fish, eggs, vegetables and protein rich legumes the other days. Eat fish two to four times a week as main course, 350 - 500 g fish per week, of which half should be fat fish. 4) Choose whole grain products in cereals and bread. Avoid iron enriched grains. Choose non-sourdough, yeast-fermented bread with at least 50% whole grain. 5) Choose vegetable oils, and low-fat dairy products. 6) Eat less sugar and salt. Choose whole foods and foods with minimal processing and none or little added sugar or salt. 7) Quench your thirst in water. Drink green- or black tea, coffee, or low-fat milk with the meals, alternatively water or non-alcoholic beer. Fruit juices must be consumed between meals. Abstain from alcoholic beverages. Drink soft drinks, non-alcoholic beer, or non-alcoholic wine instead. These advices are close to the official Danish dietary recommendations in 2021. In the management of hemochromatosis, dietary modifications that lower iron intake and decrease iron bioavailability may provide additional measures to reduce iron uptake from the foods and reduce the number of phlebotomies. However, there is a need for large, prospective, randomized studies that specifically evaluate the effect of dietary interventions., Competing Interests: The author declares to have no conflict of interest., (Copyright 2021, Milman.)

This paper briefly reviews the safety and efficacy of liposteroid in different inflammatory and non-inflammatory diseases. Corticosteroids (CS) are the first-line therapy in many inflammatory and autoimmune disorders. Although highly efficacious, long-term use of CS is limited due to the occurrence of significant side effects. Liposteroid, which is a liposomal formulation of dexamethasone palmitate, possess more potent anti-inflammatory and immunosuppressive properties compared to dexamethasone sodium phosphate. These two formulations have markedly different lipid solubility, resulting in different pharmacokinetic and pharmacodynamic properties. Liposteroid has been used with success in patients with rheumatoid arthritis, macrophage activation syndrome, and idiopathic pulmonary hemosiderosis. In addition, liposteroid has been used in some non-inflammatory diseases. Moreover, we conceive that liposteroid may have a beneficial effect in patients, who are critically ill due to COVID-19, and suffer from the macrophage activation syndrome.

The objective of this review was to assess whether dietary iron intake in men in Europe is in symphony with the dietary recommendations. A literature search of national dietary surveys reporting the intake of iron using PubMed, Google Scholar, National Nutrient Databases and previous literature on dietary reviews was performed. The subjects were men aged 18 - 70 years. A total of 39 national dietary surveys in 20 European countries in the period 1995 - 2016 were included. There were considerable differences between median/mean iron dietary intake in the 20 countries. Seven countries/regions, UK-Northern Ireland, UK-Wales, Sweden, Belgium, UK-Scotland, UK-England and Serbia reported median/mean iron intake ranging from 10.5 to 11.6 mg/day. Ten countries, Norway, Finland, Lithuania, Italy, Hungary, Portugal, The Netherlands, Denmark, Iceland and Austria reported iron intake from 12.0 to 13.5 mg/day. France, Germany, Ireland and Spain reported iron intake from 14.8 to 16.0 mg/day, while Poland and Slovakia reported the highest intake of 17.2 and 22.7 mg/day. In surveys from France and The Netherlands, intake of heme iron constituted 11% of total dietary iron intake. Nutrient density for iron, reported in five countries, varied from median 11.6 mg iron/10 MJ in Denmark to 16.0 in France. In all countries, the majority of men had a dietary iron intake markedly above a recommended intake of 9 mg/day. In Europe, 75-87% of men have a dietary iron intake above 9 mg/day. A high iron intake together with relatively high intakes of meat and alcohol contributes to a high iron status and a high frequency of body iron overload in many men. We need consensus on common European standardized dietary methods, uniform dietary reference values and uniform statistical methods to perform inter-country comparisons., Competing Interests: The author declares no conflict of interest., (Copyright 2020, Milman.)

Objective: To provide an overview of nutrients and compounds, which influence human intestinal iron absorption, thereby making a platform for elaboration of dietary recommendations that can reduce iron uptake in patients with genetic haemochromatosis., Design: Review. Setting . A literature search in PubMed and Google Scholar of papers dealing with iron absorption., Results: The most important promoters of iron absorption in foods are ascorbic acid, lactic acid (produced by fermentation), meat factors in animal meat, the presence of heme iron, and alcohol which stimulate iron uptake by inhibition of hepcidin expression. The most important inhibitors of iron uptake are phytic acid/phytates, polyphenols/tannins, proteins from soya beans, milk, eggs, and calcium. Oxalic acid/oxalate does not seem to influence iron uptake. Turmeric/curcumin may stimulate iron uptake through a decrease in hepcidin expression and inhibit uptake by complex formation with iron, but the net effect has not been clarified., Conclusions: In haemochromatosis, iron absorption is enhanced due to a decreased expression of hepcidin. Dietary modifications that lower iron intake and decrease iron bioavailability may provide additional measures to reduce iron uptake from the foods. This could stimulate the patients' active cooperation in the treatment of their disorder and reduce the number of phlebotomies., Competing Interests: The author declares no conflicts of interest., (Copyright © 2020 Nils Thorm Milman.)

Objective: Assessment of dietary iron intake in pregnant women in Europe., Design: Review. Setting . Literature search of dietary surveys reporting the intake of dietary iron using the PubMed and Google Scholar databases covering the years 1990-2019., Subjects: Healthy pregnant women., Results: 24 dietary surveys/studies in 14 European countries were included. Nine studies (38%) used Food Frequency Questionnaires, which yielded significantly higher iron intake than studies using Dietary Records. Results from Dietary Record studies in 11 countries showed that iron intake varied between 8.3-15.4 mg/day with an estimated "median" value of 10-11 mg/day. Spain, Bosnia, and Poland reported an intake of 8.3-10.1 mg/day, Croatia, England, Norway, and Finland an intake of 10.2-11.4 mg/day, and Germany, Portugal, Czech Republic, and Greece an intake of 12.2-15.4 mg/day. The recommended iron intake in the various countries varied from 14.8-30 mg/day. In all studies, 60-100% of the women had a dietary iron intake below the recommended intake., Conclusions: In Europe, the majority of pregnant women have a dietary iron intake, which is markedly below the recommended intake. This contributes to a low iron status in many pregnant women. Most guidelines do not advice routine iron supplements, while two guidelines (World Health Organization and Nordic Nutrition Recommendations) recommend routine iron supplementation during pregnancy. Within the European community, we need to reach consensus on the various guidelines and on the issue of iron supplementation. We should establish common European standardized dietary methods, uniform Dietary Reference Values, and uniform statistical methods in order to perform more reliable comparisons between studies in different countries., Competing Interests: The author declares that there are no conflicts of interest., (Copyright © 2020 Nils Thorm Milman.)

This paper outlines the Danish aspects of HFE -hemochromatosis, which is the most frequent genetic predisposition to iron overload in the five million ethnic Danes; more than 20,000 people are homozygous for the C282Y mutation and more than 500,000 people are compound heterozygous or heterozygous for the HFE -mutations. The disorder has a long preclinical stage with gradually increasing body iron overload and eventually 30% of men will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease and diabetes. Subsequently the disease may progress into irreversible arthritis, liver cirrhosis, cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective standard treatment is repeated phlebotomies, which in the preclinical and early clinical stages ensures a normal survival rate. Early detection of the genetic predisposition to the disorder is therefore important to reduce the overall burden of clinical disease. Population screening seems to be cost-effective and should be considered., Competing Interests: All the authors declare that they have no conflict of interest., (Copyright 2019, Milman et al.)

Objective: Assessment of dietary iron intake in women of reproductive age in Europe., Design: Review., Setting: Literature search of dietary surveys reporting intake of iron using PubMed, Internet browsers, and national nutrient databases in the period 1993-2015., Subjects: Women of reproductive age., Results: 49 dietary surveys/studies in 29 European countries were included. Belgium, Bosnia, Denmark, Hungary, Italy, Northern Ireland, Serbia, Scotland, Sweden, Switzerland, United Kingdom/England, and Wales reported a median/mean iron intake of 7.6-9.9 mg/day. Finland, Iceland, Ireland, the Netherlands, Norway, Poland, and Spain reported an intake of 10.0-10.7 mg/day. Austria, Estonia, France, and Russia reported an intake of 11.0-11.9 mg/day. Latvia and Germany reported an intake of 12.0-12.2 mg/day. Croatia, Lithuania, Portugal, and Slovakia reported an intake of 15.9-19.0 mg/day. The percentage of dietary iron consisting of heme iron, reported in 7 studies, varied from 4.3% in United Kingdom to 25% in Spain. Nutrient density for iron (mg iron/10 MJ, median/mean) varied from 11.8 in Sweden to 23.0 in Lithuania. The correlation between nutrient density and dietary iron was significant ( p =0.0006). In most countries, the majority of women had a dietary iron intake below 15 mg/day. In Belgium, Denmark, Hungary, and Sweden, 91-95% of women had an intake below 15 mg/day. In Ireland and Germany, 61-78% had an intake below 15 mg/day., Conclusions: In Europe, 61-97% of women have a dietary iron intake below 15 mg/day. This contributes to a low iron status in many women. We need common European standardized dietary methods, uniform dietary reference values, and uniform statistical methods to perform intercountry comparisons.