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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 -
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 -
Biomedicine & Pharmacotherapy =... Feb 2023Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to... (Review)
Review
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to review the clinical evidence of efficacy and safety of skin photosensitivity treatments in individuals with EPP or XLP. We systematically searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov. A total of 40 studies with data on 18 treatment modalities were included. Comprehensive treatment safety data were obtained from the European Medicines Agency and the United States Food and Drug Administration. The studies used different outcome measures to evaluate the sensitivity without a generally accepted method to assess treatment effect on skin photosensitivity. Of the included studies, 13 were controlled trials. Gathered, the trials showed moderate positive effect of inorganic sunscreen application and subcutaneous implant of afamelanotide and no effect of organic sunscreen application, or oral treatment with beta-carotene, cysteine, N-acetylcysteine, vitamin C, or warfarin. Studies without control groups suggested treatment effect of foundation cream, dihydroxyacetone/lawsone cream, narrow-band ultraviolet B phototherapy, erythrocyte transfusion, extracorporeal erythrocyte photodynamic therapy, or oral treatment with zinc sulphate, terfenadine, cimetidine, or canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP or XLP carries a high risk of bias since experienced photosensitivity varies with both weather conditions, exposure pattern, and pigmentation. Controlled trials of promising treatment options are important although challenging in this small patient population.
Topics: United States; Humans; Protoporphyria, Erythropoietic; Sunscreening Agents; Photosensitivity Disorders; Genetic Diseases, X-Linked; Protoporphyrins
PubMed: 36525819
DOI: 10.1016/j.biopha.2022.114132 -
Photodermatology, Photoimmunology &... Sep 2021Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at... (Review)
Review
BACKGROUND
Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at any age, even during adulthood, and is associated with hematological disorders. A third, less-studied type of EPP is also inherited but appears later in life (during adulthood).
PURPOSE
To evaluate the characteristics of inherited genetic late-onset (IGLO) EPP.
METHODS
A systematic comprehensive search of the literature was conducted using PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases. Studies describing patients with IGLO EPP were included. Additionally, we present an index case of a patient, treated at our clinic in whom inherited genetic EPP was diagnosed at age 21 years.
RESULTS
The search yielded 1514 citations. Five publications were eligible for review. Along with our case, 7 patients (4 males) were included in the analysis. Mean age at disease onset was 34.2 years (range 18-69, median 30). Most patients presented with mild pruritus and rash in a photosensitive distribution. Mean level of free erythrocyte protoporphyrin IX (FEP) was 8.6 μmol/L. A mutant ferrochelatase gene (FECH) in trans to a hypomorphic FECH allele was found in 3 of the 4 patients who underwent genetic testing.
CONCLUSION
We describe the distinct features of IGLO EPP. This work emphasizes that a diagnosis of inherited genetic EPP should not be ruled out in adults with new-onset photosensitive manifestations.
Topics: Adolescent; Adult; Aged; Alleles; Child, Preschool; Ferrochelatase; Humans; Male; Middle Aged; Mutation; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Young Adult
PubMed: 33556208
DOI: 10.1111/phpp.12667 -
Photodermatology, Photoimmunology &... Jan 2020Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported;...
BACKGROUND
Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce.
PURPOSE
To evaluate the characteristics of acquired EPP.
METHODS
A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS).
RESULTS
We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 μg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients.
CONCLUSION
We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria.
Topics: Adult; Aged; Azacitidine; Chromosomes, Human, Pair 18; Erythrocytes; Female; Ferrochelatase; Genetic Loci; Humans; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins; beta Carotene
PubMed: 31374130
DOI: 10.1111/phpp.12501 -
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