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Life (Basel, Switzerland) Apr 2024Porphyria denotes a heterogeneous group of metabolic disorders caused by anomalies in the biosynthesis of heme, a crucial component of hemoglobin and other vital...
Porphyria denotes a heterogeneous group of metabolic disorders caused by anomalies in the biosynthesis of heme, a crucial component of hemoglobin and other vital hemoproteins [...].
PubMed: 38792603
DOI: 10.3390/life14050581 -
International Journal of Environmental... May 2024The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY...
Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England.
The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY is a measure that combines the size of the clinical benefit of a treatment with the time the patient benefits from it, i.e., the time horizon. We wanted to know how consistently QALY gains are calculated at NICE. Therefore, we have analysed information on the time horizons used for the QALY calculations of the concluded evaluations conducted under the Highly Specialised Technologies programme for treatments of very rare diseases at NICE. For treatments with final guidance published by December 2023 ( = 29), a time horizon of median 97.5 years (range: 35 to 125 years) was used to calculate the QALY gains. For most QALY calculations, the accepted time horizon was longer than either the expected treatment duration or the estimated life expectancy. In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed.
Topics: Rare Diseases; Quality-Adjusted Life Years; Humans; England; Cost-Benefit Analysis; Decision Making; Time Factors
PubMed: 38791830
DOI: 10.3390/ijerph21050616 -
Postepy Dermatologii I Alergologii Apr 2024Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced... (Review)
Review
Afamelanotide is a synthetic alpha melanocyte stimulating hormone presenting a higher activity than natural hormones. Its main properties are related to the enhanced production of eumelanin by agonistically binding to the melanocortin-1 receptor. Since 2016 afamelanotide has been especially applied to treat cases of erythropoietic porphyria (EPP), where painful photosensitivity has been observed since early childhood. The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care.
PubMed: 38784937
DOI: 10.5114/ada.2024.138818 -
Seminars in Liver Disease May 2024Hepatic porphyrias are a group of metabolic disorders that are characterized by overproduction and accumulation of porphyrin precursors in the liver. These porphyrins...
Hepatic porphyrias are a group of metabolic disorders that are characterized by overproduction and accumulation of porphyrin precursors in the liver. These porphyrins cause neurologic symptoms as well as cutaneous photosensitivity, and in some cases patients can experience life-threatening acute neurovisceral attacks. This review describes the acute hepatic porphyrias in detail, including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, as well as the hepatic porphyrias with cutaneous manifestations such as porphyria cutanea tarda and hepatoerythropoietic porphyria. Each section will cover disease prevalence, clinical manifestations, and current therapies, including strategies to manage symptoms. Finally, we review new and emerging treatment modalities, including gene therapy through use of adeno-associated vectors and chaperone therapies such as lipid nanoparticle and small interfering RNA-based therapeutics.
PubMed: 38772406
DOI: 10.1055/s-0044-1787076 -
Liver International : Official Journal... May 2024We describe developments in understanding of the porphyrias associated with each step in the haem biosynthesis pathway and the role of individuals whose contributions... (Review)
Review
We describe developments in understanding of the porphyrias associated with each step in the haem biosynthesis pathway and the role of individuals whose contributions led to major advances over the past 150 years. The first case of erythropoietic porphyria was reported in 1870, and the first with acute porphyria in 1889. Photosensitisation by porphyrin was confirmed by Meyer-Betz, who self-injected haematoporphyrin. Günther classified porphyrias into haematoporphyria acuta, acuta toxica, congenita and chronica. This was revised by Waldenström into porphyria congenita, acuta and cutanea tarda, with the latter describing those with late-onset skin lesions. Waldenström was the first to recognise porphobilinogen's association with acute porphyria, although its structure was not solved until 1953. Hans Fischer was awarded the Nobel prize in 1930 for solving the structure of porphyrins and the synthesis of haemin. After 1945, research by several groups elucidated the pathway of haem biosynthesis and its negative feedback regulation by haem. By 1961, following the work of Watson, Schmid, Rimington, Goldberg, Dean, Magnus and others, aided by the availability of modern techniques of porphyrin separation, six of the porphyrias were identified and classified as erythropoietic or hepatic. The seventh, 5-aminolaevulinate dehydratase deficiency porphyria, was described by Doss in 1979. The discovery of increased hepatic 5-aminolaevulinate synthase activity in acute porphyria led to development of haematin as a treatment for acute attacks. By 2000, all the haem biosynthesis genes were cloned, sequenced and assigned to chromosomes and disease-specific mutations identified in all inherited porphyrias. These advances have allowed definitive family studies and development of new treatments.
PubMed: 38767598
DOI: 10.1111/liv.15960 -
Journal of the European Academy of... May 2024Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective... (Review)
Review
Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.
PubMed: 38752605
DOI: 10.1111/jdv.20098 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211 -
Clinica Chimica Acta; International... Jun 2024
Corrigendum to "The European biological variation study (EuBIVAS): Biological variation data for testosterone, follicle stimulating hormone, prolactin, luteinizing hormone and dehydroepiandrosterone sulfate in men" [Clin. Chim. Acta 555 (2024) 117806].
PubMed: 38729904
DOI: 10.1016/j.cca.2024.119720 -
Hematology, Transfusion and Cell Therapy Apr 2024
PubMed: 38719715
DOI: 10.1016/j.htct.2024.02.027 -
Liver International : Official Journal... May 2024Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease due to the deficient, but not absent, activity of uroporphyrinogen III synthase (UROS),... (Review)
Review
Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease due to the deficient, but not absent, activity of uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthesis pathway. Biallelic variants in the UROS gene result in decreased UROS enzymatic activity and the accumulation of non-physiologic Type I porphyrins in cells and fluids. Overproduced uroporphyrins in haematopoietic cells are released into the circulation and distributed to tissues, inducing primarily hematologic and dermatologic symptoms. The clinical manifestations vary in severity ranging from non-immune hydrops fetalis in utero to mild dermatologic manifestations in adults. Here, the biochemical, molecular and clinical features of CEP as well as current and new treatment options, including the rescue of UROS enzyme activity by chaperones, are presented.
PubMed: 38717058
DOI: 10.1111/liv.15958