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Acta Dermato-venereologica Jun 2019Erythropoietic protoporphyria is caused by a partial deficiency of ferrochelatase, which is the last enzyme in the heme biosynthesis pathway. In a typical erythropoietic... (Review)
Review
Erythropoietic protoporphyria is caused by a partial deficiency of ferrochelatase, which is the last enzyme in the heme biosynthesis pathway. In a typical erythropoietic protoporphyria, photosensitivity initially appears, following the first exposure to the sun in early infancy or childhood. Erythropoietic protoporphyria has been reported worldwide, but there is a regional variation in its epidemiology. Approximately 20% of the Japanese patients were recognized to have symptoms of erythropoietic protoporphyria after 10 years of age. Physicians occasionally encounter Japanese patients with erythropoietic protoporphyria, mild symptoms and no FECH gene mutations. The homozygous IVS3-48C polymorphism may cause a mild phenotype of the erythropoietic protoporphyria via a slight increase in protoporphyrin. The frequency of the homozygous IVS3-48C polymorphism in the Japanese population is higher than that observed in European countries. Japanese type of erythropoietic protopor-phyria shows a characteristic phenotype of the late onset and mild symptoms compared to the Caucasian erythropoietic protoporphyria. This review describes the characteristics of erythropoietic protoporphyria in Japanese patients.
Topics: Age of Onset; Anemia; Cholelithiasis; Europe; Ferrochelatase; Homozygote; Humans; Japan; Liver Diseases; Mutation; North America; Phenotype; Polymorphism, Genetic; Prevalence; Protoporphyria, Erythropoietic
PubMed: 30938825
DOI: 10.2340/00015555-3184 -
Photodiagnosis and Photodynamic Therapy Jun 2022Erythropoietic protoporphyria (EPP) is caused by deficiency of the enzyme converting protoporphyrin IX (PpIX) into heme resulting in accumulation of PpIX; leading to... (Review)
Review
BACKGROUND
Erythropoietic protoporphyria (EPP) is caused by deficiency of the enzyme converting protoporphyrin IX (PpIX) into heme resulting in accumulation of PpIX; leading to photosensitivity and liver toxicity. Cimetidine might inhibit δ-aminolevulinic acid synthase influencing the heme biosynthesis. We present cases with EPP treated with cimetidine at our department, and a literature review.
METHODS
Systematic searches were performed to identify literature describing EPP patients treated with cimetidine. On that ground we treated EPP patients with cimetidine through spring and summer in 2020 and 2021 at our department. Their erythrocyte PpIX level and standard blood and liver parameters were collected before and during 4 months of treatment. Using a questionnaire, patients were asked about change in photosensitivity, side effects, and whether they would like to resume treatment in the spring of 2022.
RESULTS
Literature searches identified 9 patients treated with cimetidine. Four were outpatients reporting decreased photosensitivity. At our department 18 outpatients started treatment. Fifteen used oral cimetidine daily for 4 months or more providing a significant decrease in erythrocyte PpIX with a median of 20% (range: -18% to 53%) after 4 months. Eleven of the 15 patients reported a decrease in photosensitivity during treatment, 3 patients were unsure, and 1 patient experienced unchanged photosensitivity. Only mild side effects were reported. Fourteen patients requested to resume treatment in the spring of 2022.
CONCLUSIONS
These cases suggest that cimetidine can lower erythrocyte PpIX in patients with EPP.
Topics: Cimetidine; Ferrochelatase; Heme; Humans; Photochemotherapy; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins
PubMed: 35245673
DOI: 10.1016/j.pdpdt.2022.102793 -
Journal of Cutaneous Medicine and... 2022
Topics: Humans; Protoporphyria, Erythropoietic
PubMed: 33945342
DOI: 10.1177/12034754211016295 -
MMW Fortschritte Der Medizin Feb 2022
Review
Topics: Burns; Humans; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Skin
PubMed: 35146708
DOI: 10.1007/s15006-022-0702-9 -
Experimental Dermatology Jul 2023Severe skin pain when exposed to long wave ultraviolet radiation or visible light is the main symptom of erythropoietic protoporphyria (EPP). Treatment options for EPP... (Review)
Review
Severe skin pain when exposed to long wave ultraviolet radiation or visible light is the main symptom of erythropoietic protoporphyria (EPP). Treatment options for EPP are inadequate and new treatments are needed but hampered by the lack of valid efficacy outcomes. Phototesting with well-defined illumination of the skin can be performed reliably. We aimed to provide an overview of phototest procedures used to evaluate EPP treatments. Systematic searches of Embase, MEDLINE and the Cochrane Library were performed. Searches identified 11 studies using photosensitivity as efficacy outcome. The studies used eight different phototest protocols. Illuminations were performed with a filtered high-pressure mercury arc, or a xenon arc lamp equipped with monochromator or filters. Some used broadband, others narrowband illumination. In all protocols phototests were performed on the hands or the back. Endpoints were minimal dose required to induce either first symptom of discomfort, erythema, urticaria or intolerable pain. Other endpoints were change in erythema intensity or diameter of any type of flare after exposure compared to before. In conclusion, protocols displayed extensive variability in illumination set-up and evaluation of phototest reactions. Implementation of a standardized phototest method will allow more consistent and reliable outcome evaluation in future therapeutic research of protoporphyric photosensitivity.
Topics: Humans; Protoporphyria, Erythropoietic; Ultraviolet Rays; Photosensitivity Disorders; Skin; Erythema
PubMed: 37052136
DOI: 10.1111/exd.14809 -
Orphanet Journal of Rare Diseases Sep 2009Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and... (Review)
Review
Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients.
Topics: Ferrochelatase; Humans; Photosensitivity Disorders; Protoporphyria, Erythropoietic
PubMed: 19744342
DOI: 10.1186/1750-1172-4-19 -
The New England Journal of Medicine Aug 2017
Review
Topics: Female; Heme; Hemin; Humans; Male; Phlebotomy; Porphobilinogen; Porphyria Cutanea Tarda; Porphyria, Acute Intermittent; Porphyrins; Prognosis; Protoporphyria, Erythropoietic; RNA, Small Interfering; Sunlight; Symptom Assessment
PubMed: 28854095
DOI: 10.1056/NEJMra1608634 -
Hematology, Transfusion and Cell Therapy 2018Hemoglobin is an essential biological component of human physiology and its production in red blood cells relies upon proper biosynthesis of heme and globin protein.... (Review)
Review
Hemoglobin is an essential biological component of human physiology and its production in red blood cells relies upon proper biosynthesis of heme and globin protein. Disruption in the synthesis of these precursors accounts for a number of human blood disorders found in patients. Mutations in genes encoding heme biosynthesis enzymes are associated with a broad class of metabolic disorders called porphyrias. In particular, one subtype - erythropoietic protoporphyria - is caused by the accumulation of protoporphyrin IX. Erythropoietic protoporphyria patients suffer from photosensitivity and a higher risk of liver failure, which is the principle cause of morbidity and mortality. Approximately 90% of these patients carry loss-of-function mutations in the enzyme ferrochelatase (), while 5% of cases are associated with activating mutations in the C-terminus of . Recent work has begun to uncover novel mechanisms of heme regulation that may account for the remaining 5% of cases with previously unknown genetic basis. One erythropoietic protoporphyria family has been identified with inherited mutations in the AAA+ protease ClpXP that regulates activity. In this review article, recent findings on the role of ClpXP as both an activating unfoldase and degrading protease and its impact on heme synthesis will be discussed. This review will also highlight the role of ClpX dysfunction in erythropoietic protoporphyria.
PubMed: 30057992
DOI: 10.1016/j.htct.2018.03.001 -
The Journal of Pediatrics Nov 2018Erythropoietic protoporphyria is a photodermatosis presenting in childhood with severe pain on sun exposure. The diagnosis is often delayed because of the lack of... (Review)
Review
Erythropoietic protoporphyria is a photodermatosis presenting in childhood with severe pain on sun exposure. The diagnosis is often delayed because of the lack of awareness among pediatricians. We describe the diagnostic odyssey of 2 children presenting with symptoms of erythropoietic protoporphyria and report results of a survey of 129 affected individuals.
Topics: Child, Preschool; Delayed Diagnosis; Diagnosis, Differential; Female; Humans; Hypersensitivity; Male; Photosensitivity Disorders; Prognosis; Protective Clothing; Protoporphyria, Erythropoietic; Recurrence; Risk Assessment; Severity of Illness Index; Sunlight
PubMed: 30041937
DOI: 10.1016/j.jpeds.2018.06.001 -
Photodermatology, Photoimmunology &... Jun 2003
Review
Topics: Humans; Porphyria, Erythropoietic
PubMed: 12914599
DOI: 10.1034/j.1600-0781.2002.00009.x