-
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 -
The British Journal of Dermatology May 2020The photodermatoses affect large proportions of the population but their impact on quality of life (QoL) and psychological health has not been reviewed. Several tools... (Review)
Review
BACKGROUND
The photodermatoses affect large proportions of the population but their impact on quality of life (QoL) and psychological health has not been reviewed. Several tools are available to evaluate QoL and psychological impacts.
OBJECTIVES
To systematically review current literature to identify tools used to assess QoL and psychological impacts in patients with photodermatoses, and to summarize the reported findings.
METHODS
A systematic search of PubMed, OVID Medline, PsycInfo and CINAHL was performed for articles investigating QoL and/or psychological impact in patients with photodermatoses, published between 1960 and September 2018.
RESULTS
Twenty studies were included: 19 incorporated QoL assessment while three evaluated psychological morbidity. Six QoL tools were found to be used: Dermatology Life Quality Index (DLQI), Children's DLQI, Family DLQI, Skindex (16- and 29-item versions), Erythropoietic Protoporphyria Quality of Life (EPP-QoL) and EuroQol. Between 31% and 39% of photosensitive patients reported a very large impact on QoL (DLQI > 10). Employment and education, social and leisure activities, and clothing choices were particularly affected. Only one tool was specifically designed for a photodermatosis (EPP-QoL). Four tools were used to evaluate psychological impact: the Hospital Anxiety and Depression Scale, Fear of Negative Evaluation, brief COPE and Illness Perception Questionnaire-Revised. Levels of anxiety and depression were approximately double British population data. Patients with facial involvement, female gender and younger age at onset showed more psychological morbidity.
CONCLUSIONS
Several tools have been used to assess QoL in the photodermatoses, and confirm substantial impact on QoL. Development of specific, validated QoL measures would address their unique impacts. Research delineating their psychological comorbidity is sparse and requires further exploration. What's already known about this topic? The photodermatoses negatively impact quality of life (QoL) and cause psychological distress, but no reviews of this area appear in the literature. What does this study add? Few studies have explored the psychological and social impacts of the photodermatoses. There are no fully validated QoL tools specific to the photodermatoses. Around one-third of adult and child patients with photosensitivity experience very or extremely large impact on QoL, with particular effect on clothing choices, employment and social and leisure activities. Studies suggest anxiety and depression levels in these patients are around double those in the U.K. general population. More attention is required on these 'hidden' conditions.
Topics: Adult; Anxiety; Anxiety Disorders; Child; Female; Humans; Photosensitivity Disorders; Quality of Life; Surveys and Questionnaires
PubMed: 31278744
DOI: 10.1111/bjd.18326 -
Genes & Genomics 2017The main purpose of present review is to describe and organize autosomal recessive disorders (arachnomelia, syndactylism, osteopetrosis, dwarfism, crooked tail syndrome,... (Review)
Review
The main purpose of present review is to describe and organize autosomal recessive disorders (arachnomelia, syndactylism, osteopetrosis, dwarfism, crooked tail syndrome, muscular hyperplasia, glycogen storage disease, protoporphyria), which occur among beef cattle, and methods that can be applied to detect these defects. Prevalence of adverse alleles in beef breeds happens due to human activity-selections of favorable features, e.g. developed muscle tissue. Unfortunately, carriers of autosomal recessive diseases are often characterized by these attributes. Fast and effective identification of individuals, that may carry faulty genes, can prevent economical losses.
PubMed: 28458779
DOI: 10.1007/s13258-017-0525-8 -
Wideochirurgia I Inne Techniki... Jun 2022Erythropoietic protoporphyria is a hereditary defect in heme synthesis, causing protoporphyrin deposition and phototoxic reactions after exposure to light, especially at...
Erythropoietic protoporphyria is a hereditary defect in heme synthesis, causing protoporphyrin deposition and phototoxic reactions after exposure to light, especially at a wavelength of about 400 nm. Sensitivity to light may cause postoperative complications. Therefore, in open surgery protective filters are employed on surgical luminaires. The dangers of laparoscopy are little understood and the intensity of the light used can be high. To protect against phototoxic injury, we inserted an OG 530 filter in the video track. This filter blocks wavelengths below 470 nm. Three cholecystectomies and one sigmoidectomies were performed laparoscopically. The procedures were uneventful, and the patients suffered no adverse reactions, including phototoxic symptoms. The filter had a moderate influence on color perception and caused no significant restrictions on working conditions. We consider that it is appropriate to develop a relevant design to meet the suitable requirements for a durable filter holder in the laparoscopic video track.
PubMed: 35707342
DOI: 10.5114/wiitm.2022.115003 -
Molecular Genetics and Metabolism... Dec 2022The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports....
The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18 years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30 ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325 mg twice daily was administered for 12 months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12 months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8 years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3 months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study ( = 8; median relative difference: -0.21 (IQR: -0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP. Trial registration: NCT02979249.
PubMed: 36406817
DOI: 10.1016/j.ymgmr.2022.100939 -
Frontiers in Physiology 2022
PubMed: 36117690
DOI: 10.3389/fphys.2022.993287 -
The New England Journal of Medicine Jun 2023
Topics: Humans; Protoporphyria, Erythropoietic; Erythropoiesis
PubMed: 37379150
DOI: 10.1056/NEJMc2305601 -
The New England Journal of Medicine Jun 2023
Topics: Humans; Protoporphyria, Erythropoietic; Erythropoiesis
PubMed: 37379149
DOI: 10.1056/NEJMc2305601 -
The New England Journal of Medicine Jul 2015Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly reduced quality of life. We evaluated the safety and efficacy of an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease pain and improve quality of life.
METHODS
We conducted two multicenter, randomized, double-blind, placebo-controlled trials of subcutaneous implants containing 16 mg of afamelanotide. Patients in the European Union (74 patients) and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to receive a subcutaneous implant containing either afamelanotide or placebo every 60 days (a total of five implants in the European Union study and three in the U.S study). The type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded over the respective 180-day and 270-day study periods. Quality of life was assessed with the use of validated questionnaires. A subgroup of U.S. patients underwent photoprovocation testing. The primary efficacy end point was the number of hours of direct exposure to sunlight without pain.
RESULTS
In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug.
CONCLUSIONS
Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.).
Topics: Adult; Double-Blind Method; Drug Implants; Humans; Middle Aged; Pain; Protoporphyria, Erythropoietic; Sunlight; alpha-MSH
PubMed: 26132941
DOI: 10.1056/NEJMoa1411481 -
Expert Review of Clinical Pharmacology Feb 2021: In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients... (Review)
Review
: In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. Afamelanotide is the first effective approved medical treatment for EPP, acting on melanocortin-1 receptors. This article aims to review afamelanotide.: This review summarizes the chemical properties, pharmacokinetics, safety, preclinical and clinical data on afamelanotide in EPP, and post-marketing surveillance. PubMed search, manufacturers' websites, and relevant articles used for approval by authorities were used for the literature search.: Afamelanotide is an α-melanocyte-stimulating hormone analog. It can activate eumelanogenesis without exposure to UV radiation. Clinical studies in EPP showed that afamelanotide treatment significantly increased exposure to sunlight and QoL. In our clinical experience afamelanotide treatment is much more effective in clinical practice than demonstrated in clinical trials and should be made available for all EPP patients meeting inclusion criteria. The 60-day interval period was not based on effectiveness studies, and therefore for some of the patients the maximum of four implants per year with the 60-day interval is insufficient. Afamelanotide is well tolerated; common adverse events were headache, fatigue, and nausea.
Topics: Animals; Dermatitis, Phototoxic; Dermatologic Agents; Humans; Pain; Protoporphyria, Erythropoietic; Quality of Life; Sunlight; alpha-MSH
PubMed: 33507118
DOI: 10.1080/17512433.2021.1879638