Haemochromatosis patients' research priorities: Towards an improved quality of life.

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.

Liposteroid Therapy for Idiopathic Pulmonary Hemosiderosis: A Scoping Review of the Literature.

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.

Short Review of Liposteroid: A Novel Targeted Glucocorticoid Preparation for Treatment of Autoimmune and Inflammatory Diseases.

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.

Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP).

OBJECTIVE: To compare the efficacy and safety of intravenous ferric carboxymaltose (FCM) with first-line oral ferrous sulfate (FS) in pregnant women with iron deficiency anemia (IDA). MATERIALS AND METHODS: Pregnant women (n=252; gestational weeks 16-33) with IDA were randomized 1:1 to FCM (1000-1500 mg iron) or FS (200 mg iron/day) for 12 weeks. The primary objective was to compare efficacy; secondary objectives included safety and quality of life. RESULTS: Hemoglobin (Hb) levels improved at comparable rates across both treatments; however, significantly more women achieved anemia correction with FCM vs. FS [Hb ≥11.0 g/dL; 84% vs. 70%; odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07, 3.97; P=0.031] and within a shorter time frame (median 3.4 vs. 4.3 weeks). FCM treatment significantly improved vitality (P=0.025) and social functioning (P=0.049) prior to delivery. Treatment-related adverse events were experienced by 14 (FCM; 11%) and 19 (FS; 15%) women, with markedly higher rates of gastrointestinal disorders reported with FS (16 women) than with FCM (3 women). Newborn characteristics were similar across treatments. CONCLUSIONS: During late-stage pregnancy, FCM may be a more appropriate option than first-line oral iron for rapid and effective anemia correction, with additional benefits for vitality and social functioning.

Supplementation during pregnancy: beliefs and science.

Pregnancy represents a challenge from a nutritional perspective, because micronutrient intake during the periconceptional period and in pregnancy affects fetal organ development and the mother's health. Inappropriate diet/nutrition in pregnancy can lead to numerous deficiencies including iron deficiency and may impair placental function and play a role in miscarriage, intrauterine growth restriction, preterm delivery, and preeclampsia. This article reviews the risks associated with nutrient deficiencies in pregnant women and presents an overview of recommendations for dietary supplementation in pregnancy, focusing on oral iron supplementation. Risk factor detection, including dietary patterns and comorbidities, is paramount in optimal pregnancy management. Dietary habits, which can lead to deficiencies (e.g., iron, folate, vitamin D, and calcium) and result in negative health consequences for the mother and fetus/newborn, need to be investigated. Prenatal care should be personalized, accounting for ethnicity, culture, education, information level about pregnancy, and dietary and physical habits. Clinicians should make a plan for appropriate supplementation and prophylaxis/treatment of nutritional and other needs, and consider adequate intake of calcium, iodine, vitamin D, folate, and iron. Among the available oral iron supplements, prolonged-released ferrous sulfate (ferrous sulfate-polymeric complex) presents the lowest incidence of overall and gastrointestinal adverse events, with positive implications for compliance.

Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial.

OBJECTIVE: To compare the effects of oral ferrous bisglycinate 25 mg iron/day vs. ferrous sulfate 50 mg iron/day in the prevention of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women. DESIGN: Randomized, double-blind, intention-to-treat study. SETTING: Antenatal care clinic. SAMPLE: 80 healthy ethnic Danish pregnant women. METHODS: Women were allocated to ferrous bisglycinate 25 mg elemental iron (Aminojern®) (n=40) or ferrous sulfate 50 mg elemental iron (n=40) from 15 to 19 weeks of gestation to delivery. Hematological status (hemoglobin, red blood cell indices) and iron status (plasma iron, plasma transferrin, plasma transferrin saturation, plasma ferritin) were measured at 15-19 weeks (baseline), 27-28 weeks and 36-37 weeks of gestation. MAIN OUTCOME MEASURES: Occurrence of ID (ferritin <15 µg/L) and IDA (ferritin <12 µg/L and hemoglobin <110 g/L). RESULTS: At inclusion, there were no significant differences between the bisglycinate and sulfate group concerning hematological status and iron status. The frequencies of ID and IDA were low and not significantly different in the two iron groups. The frequency of gastrointestinal complaints was lower in the bisglycinate than in the sulfate group (P=0.001). Newborns weight was slightly higher in the bisglycinate vs. the sulfate group (3601±517 g vs. 3395±426 g, P=0.09). CONCLUSIONS: In the prevention of ID and IDA, ferrous bisglycinate was not inferior to ferrous sulfate. Ferrous bisglycinate in a low dose of 25 mg iron/day appears to be adequate to prevent IDA in more than 95% of Danish women during pregnancy and postpartum.

Correction to: Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect.

[This corrects the article DOI: 10.14740/gr1206.].

Postpartum anemia II: prevention and treatment.

This review focuses on the prevention and treatment of anemia in women who have just given childbirth (postpartum anemia). The problem of anemia both prepartum and postpartum is far more prevalent in developing countries than in the Western societies. The conditions for mother and child in the postpartum, nursing, and lactation period should be as favorable as possible. Many young mothers have a troublesome life due to iron deficiency and iron deficiency anemia (IDA) causing a plethora of symptoms including fatigue, physical disability, cognitive problems, and psychiatric disorders. Routine screening for postpartum anemia should be considered as part of the national maternal health programs. Major causes of postpartum anemia are prepartum iron deficiency and IDA in combination with excessive blood losses at delivery. Postpartum anemia should be defined as a hemoglobin level of <110 g/l at 1 week postpartum and <120 g/l at 8 weeks postpartum. Bleeding exceeding normal blood losses of approximately 300 ml may lead to rapid depletion of body iron reserves and may, unless treated, elicit long-standing iron deficiency and IDA in the postpartum period. The prophylaxis of postpartum anemia should begin already in early pregnancy in order to ensure a good iron status prior to delivery. The most reliable way to obtain this goal is to give prophylactic oral ferrous iron supplements 30-50 mg daily from early pregnancy and take obstetric precautions in pregnancies at risk for complications. In the treatment of slight-to-moderate postpartum IDA, the first choice should be oral ferrous iron 100 to 200 mg daily; it is essential to analyze hemoglobin after approximately 2 weeks in order to check whether treatment works. In severe IDA, intravenous ferric iron in doses ranging from 800 to 1,500 mg should be considered as first choice. In a few women with severe anemia and blunted erythropoiesis due to infection and/or inflammation, additional recombinant human erythropoietin may be considered. Blood transfusion should be restricted to women who develop circulatory instability due to postpartum hemorrhage. National health authorities should establish guidelines to combat iron deficiency in pregnancy and postpartum in order to facilitate a prosperous future for both mothers and children in a continuing globalized world.

Differentiation of idiopathic pulmonary hemosiderosis from rheumatologic and autoimmune diseases causing diffuse alveolar hemorrhage: establishing a diagnostic approach.

This narrative review provides an overview of diffuse alveolar hemorrhage (DAH) associated with rheumatologic and autoimmune diseases and their differentiation from idiopathic pulmonary hemosiderosis (IPH). Relevant immunologic diseases associated with DAH are discussed, and a diagnostic flowchart is proposed to establish a "definitive" diagnosis of IPH within the spectrum of DAH. IPH is a rare cause of recurrent DAH both in children and adults. In adults, a definitive diagnosis of IPH requires a lung biopsy and histopathologic examination demonstrating intraalveolar hemorrhage, hemosiderin-laden macrophages, and a variable degree of fibrosis in the absence of both capillaritis and cellular inflammation. The presence of small vessel vasculitis points towards immunologic, well-differentiated, or sometimes undifferentiated rheumatologic diseases. However, it is essential to recognize that many rheumatologic diseases may in the initial phase present with DAH without any evidence of capillaritis, thus mimicking IPH. Although not definitely established, it is likely that immunologic processes are involved in IPH, and we, therefore, suggest the consideration of a more suitable term for the disease, e.g., "Immune-mediated Pulmonary Hemosiderosis" to acknowledge the aberrancy in the immune parameters and a positive response to immunosuppressive therapy.

Prevalence of autoantibodies in pediatric patients with idiopathic pulmonary hemosiderosis: a scoping review of the literature in the period 1980-2021.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology. Due to the frequent findings of autoimmune antibodies - autoantibodies, immunologic causation of the diffuse alveolar hemorrhage in IPH has been proposed, to assess the prevalence/frequency and type of autoantibodies in pediatric patients with IPH. In addition, the patient demographics, diagnostic modalities used to diagnose IPH, treatment, and outcomes were also evaluated. Scoping review: The PubMed, Medline, and Embase databases were searched with appropriate MeSH terms to identify relevant papers consistent with the defined inclusion criteria. Thirteen observational studies comprising a total of 352 pediatric patients were included in this review. The majority of subjects were girls 217 out of 352 (61.6%). The mean and median ages of patients ranged from 3.1-6.5 years to 2.3-7 years, respectively. In the 10 studies that specified the number of patients in their cohorts with either at least one positive autoantibody or no antibody, the overall prevalence of autoantibodies was 76 out of 288 patients (26.4%). The prevalence of specific antibodies was as follows: ANA, 20.3%; ANCA, 17%; anti-dsDNA, 9.1%; RF, 12%; anti-SMA, 23.2%; and celiac antibodies, 25.9%. Cow's milk protein allergy was present in 16.2% of the children. The significance of an association between IPH and the presence of autoantibodies has not been clarified. The autoantibodies could be suggestive of an overall immune dysregulation rather than causation. However, limited evidence based on a single study suggests that the presence of ANA may be associated with a higher risk of recurrence and worse outcomes. Further research, including prospective studies, will be crucial to explore a possible genetic linkage between vasculitides, systemic rheumatologic diseases, and IPH.

Comparative Analysis of Adult Patients With Idiopathic Pulmonary Hemosiderosis and Lane-Hamilton Syndrome: A Systematic Review of the Literature in the Period 1971-2022.

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.

The Spectrum of Autoantibodies in Adult Patients With Idiopathic Pulmonary Hemosiderosis: A Brief Review of the Literature.

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.

Postpartum anemia I: definition, prevalence, causes, and consequences.

This review provides a status on the definition, prevalence, causes, and consequences of anemia in women who have given childbirth, i.e., postpartum anemia. The diagnosis of iron deficiency anemia relies on a full blood count including hemoglobin, serum ferritin, and serum soluble transferrin receptor, which appear to be reliable indicators of anemia and iron status 1 week postpartum while serum transferrin saturation is an unreliable indicator several weeks after delivery. It is recommended that postpartum anemia should be defined by hemoglobin <110 g/L at 1 week postpartum and <120 g/L at 8 weeks postpartum. The major causes of postpartum anemia are prepartum anemia combined with acute bleeding anemia due blood losses at delivery. Normal peripartum blood losses are approximately 300 ml, but hemorrhage >500 ml occur in 5-6% of the women. In healthy women after normal delivery, the prevalence of anemia (hemoglobin <110 g/L) 1 week postpartum is 14% in iron-supplemented women and 24% in non-supplemented women. In consecutive series of European women, the prevalence of anemia 48 h after delivery is approximately 50%. In developing countries, the prevalence of postpartum anemia is in the range of 50-80%. Postpartum anemia is associated with an impaired quality of life, reduced cognitive abilities, emotional instability, and depression and constitutes a significant health problem in women of reproductive age.

Anemia--still a major health problem in many parts of the world!

Anemia is a major global health problem, especially in developing countries. This fundamental health issue still has not been solved and continues to exist affecting the health, quality of life, and working capacity in billions of people all over the world. This paper gives a review on the prevalence and major causes of anemia seen on a global scale. Most cases of anemia are due to iron deficiency, which often work in symphony with folate deficiency and/or vitamin B12 deficiency as well as with infections. More efforts should be dedicated to tackle this massive problem--we have the tools, and we know the ways. Iron fortification of appropriate food items combined with iron supplements in specific population groups has proven to be efficient. Initially, the efforts should be centered on the specific risk groups for iron deficiency anemia, i.e., young children, adolescent females, women of reproductive age, as well as pregnant women and postpartum lactating mothers.

Quantiferon test for tuberculosis screening in sarcoidosis patients.

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) inhibitors have been introduced in the treatment of refractory sarcoidosis. These biologics may reactivate latent tuberculosis infection (LTBI). Despite its known limitations, the tuberculin skin test (TST) is currently used for the diagnosis of LTBI in Danish sarcoidosis patients. We report the results of a screening using the interferon-gamma release assay (IGRA) QuantiFERON TB Gold (QFN) for the diagnosis of LTBI. We aimed to assess whether the QFN is reliable for diagnosing LTBI among sarcoidosis patients and if results are influenced by disease activity or immunosuppressive treatment. METHODS: A prospective study was performed from 2005 to 2007 among sarcoidosis patients who were candidates for TNF-α inhibitor treatment. Information on immunosuppressive treatment was obtained from the medical records. Disease activity was assessed by biochemistry, chest roentgenograms and pulmonary function tests. The predictive value of QFN results was evaluated by follow-up in the Danish National Tuberculosis Registry. RESULTS: A total of 44 sarcoidosis patients (22 men) with a median age of 39 y (range 25-59 y) were enrolled; 93% had a negative QFN test result and 7% had an indeterminate result. Forty-three percent had disease activity and 57% (n = 25) received immunosuppressive treatment. There was no significant difference in QFN interferon-γ response between subjects with or without disease activity (p > 0.4) and between treated vs non-treated patients (p > 0.5). At follow-up using the Danish tuberculosis registry, there was no occurrence of tuberculosis among study participants. CONCLUSIONS: The predictive value of the QFN seems good among Danish sarcoidosis patients and the results appear to be unaffected by sarcoidosis disease activity and immunosuppressive treatment.

Is sarcoidosis a rickettsiosis? An archival study.

BACKGROUND: Based on earlier research, Rickettsia helvetica could possibly be involved in the pathogenesis of sarcoidosis. Rickettsiae are transmitted to humans by a tick vector, Ixodes ricinus; this tick is highly prevalent in Northern Europe. We aimed to investigate the association between evidence of rickettsiae and sarcoidosis in histological samples. METHODS: We included formalin-fixed, paraffin-embedded mediastinal lymph node biopsies from 52 ethnic Danish patients with sarcoidosis and compared these with 50 biopsies from ethnic Danish patients with mediastinal lymphadenopathy of other causes. Samples were analysed for: (1) rickettsial DNA by real-time polymerase chain reaction (PCR) and (2) rickettsial rDNA (ribosomal DNA) by a specific fluorescence in situ hybridization technique (FISH). RESULTS: Rickettsia was not detected in biopsies by real-time PCR and/or FISH analyses. CONCLUSION: Our results do not support the hypothesis that Rickettsia is involved in the pathogenesis of sarcoidosis.

Iron in pregnancy: How do we secure an appropriate iron status in the mother and child?

Iron deficiency and iron deficiency anemia (IDA) during pregnancy are risk factors for preterm delivery, prematurity, and small for gestational age birth weight. Iron deficiency has a negative effect on intelligence and behavioral development in the infant. It is essential to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. The requirements for absorbed iron increase during pregnancy from ∼1.0 mg/day in the first trimester to 7.5 mg/day in the third trimester. More than 90% of Scandinavian women of reproductive age have a dietary iron intake below the recommended 15 mg/day. Among nonpregnant women of reproductive age, ∼40% have plasma ferritin ≤30 µg/l, i.e. an unfavorable iron status with respect to pregnancy. An adequate iron status during pregnancy implies body iron reserves ≥500 mg at conception, but only 15-20% of women have iron reserves of such a magnitude. Iron supplements during pregnancy reduce the prevalence of IDA. In Europe, IDA can be prevented by a general low-dose iron prophylaxis of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. In affluent societies, individual iron prophylaxis tailored by the ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are: ferritin >70 µg/l, no iron supplements; ferritin 31-70 µg/l, 30-40 mg ferrous iron per day, and ferritin ≤30 µg/l, 60-80 mg ferrous iron per day. In women with ferritin <15 µg/l, i.e. depleted iron reserves and possible IDA, therapeutic doses of 100 mg ferrous iron per day should be advised.

Vitamin D status during normal pregnancy and postpartum. A longitudinal study in 141 Danish women.

BACKGROUND/OBJECTIVES: To assess vitamin D status during normal pregnancy and in the postpartum lactation period. SUBJECTS/METHODS: The study comprised 141 healthy, ethnic Danish women with normal pregnancies, who were residents in Greater Copenhagen. Serum 25-hydroxy-vitamin D2+D3(25-OH-vitamin D) was measured at 18, 32 and 39 weeks' gestation and 8 weeks postpartum. RESULTS: There was a significant increase in 25-OH-vitamin D from 18 to 32 weeks' gestation (P=0.0001) followed by a significant decrease from 32 to 39 weeks (P=0.001) as well as from 39 weeks to 8 weeks postpartum (P<0.0001). At 18, 32, 39 weeks' gestation and 8 weeks postpartum, median 25-OH-vitamin D values were 77, 98, 91, and 73 nmol/L, respectively. During pregnancy and postpartum, none of the women displayed severe vitamin D deficiency (values <13 nmol/L). Between 1.4% and 4.3% of the participants displayed moderate vitamin D deficiency (values 13-24 nmol/L), 16-19% displayed vitamin D insufficiency (values 25-50 nmol/L), 77-84% had values >50 nmol/L and 0.7-2.8% had values >200 nmol/L. CONCLUSIONS: Low vitamin D status is frequent among pregnant Danish women, especially in late pregnancy and during lactation. Median dietary intake of vitamin D in women of reproductive age was 2.4 µg/day (10-90 percentile range=1.4-5.0). The recommendations for vitamin D supplementation prior to conception, during pregnancy and lactation should be reconsidered.

Managing Genetic Hemochromatosis: An Overview of Dietary Measures, Which May Reduce Intestinal Iron Absorption in Persons With Iron Overload.

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.

Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions.

This paper reviews the literature on the treatment modalities for idiopathic pulmonary hemosiderosis (IPH) used over the past 30 years, attempting to define treatment options that appear to be efficacious and safe, and in addition presents a treatment algorithm. IPH is an uncommon etiology of diffuse alveolar hemorrhage. IPH is a rare disease in adults and often associated with a significant temporal delay in diagnosis. Patients present with hemoptysis, radiographic chest abnormalities, and iron deficiency anemia. Although several pathogenetic hypotheses have been proposed, IPH appears to be an immunologic disease, possibly with a genetic component. Corticosteroid therapy represents the first line of treatment, including liposome-incorporated dexamethasone palmitate (liposteroid). Additional immunomodulatory/immunosuppressive medications have been used with varying success, especially in the setting of steroid-refractory disease. Cyclophosphamide, azathioprine, hydroxychloroquine, mycophenolate mofetil, and mesenchymal cell transplantation have been attempted to improve outcome and reduce side effects. Controlled studies are needed to assess the optimal combination of medications, which are effective to control the disease.