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The Journal of Dermatology Apr 2023Erythropoietic protoporphyria (EPP) patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. However, there is...
Erythropoietic protoporphyria (EPP) patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. However, there is limited information on the psychosocial aspects of EPP. To investigate the clinical features and social aspects of living with EPP, before and during afamelanotide treatment in the Netherlands. A single-center prospective longitudinal study of adult patients with EPP attending the Erasmus MC Rotterdam. Patients completed questionnaires, comprising demographic, clinical and social details, including two generic (DS-14 and SF-36) and a disease specific (EPP-QoL) QoL questionnaires. 121 adult EPP patients were included. The educational level of EPP patients seemed higher compared to the Dutch population (36% vs. 30% high-education, 42% vs. 37% middle-education). At baseline 5% of the EPP patients were unemployed, none were unemployed during afamelanotide treatment. Full- and part-time employment rate increased from 59.5% to 69.9% on afamelanotide treatment (p > 0.05). EPP-QoL improved from 44% to 75% on afamelanotide treatment (p < 0.001). Type-D personality was present in 27.4% of patients; their social inhibition scores improved significantly on afamelanotide treatment (p = 0.019). EPP patients scored low on the social functioning domain (SF-36) compared to the Dutch population (74.4 ± 27.3 vs. 84.0 ± 22.4; respectively), and improved during afamelanotide treatment (84.3 ± 20.9, p = 0.001). EPP has a significant negative impact on social aspects, with less employment despite a higher education level. Afamelanotide treatment improves quality of life, social functioning and possibly employment rate. It is important to recognize the impact of EPP on social life, although, more research is needed.
Topics: Adult; Humans; Protoporphyria, Erythropoietic; Quality of Life; Prospective Studies; Longitudinal Studies; Netherlands; Pain
PubMed: 36579412
DOI: 10.1111/1346-8138.16690 -
Journal of Paediatrics and Child Health Feb 2019
Topics: Adolescent; Female; Foot; Hand; Humans; Pain; Protoporphyria, Erythropoietic
PubMed: 30288822
DOI: 10.1111/jpc.14244 -
Cellular and Molecular Biology... Feb 2009Erythropoietic protoporphyria (EPP) is a rare inherited disease characterized by dermal photosensitivity due to the accumulation of photosensitizer protoporphyrin IX. We... (Review)
Review
Erythropoietic protoporphyria (EPP) is a rare inherited disease characterized by dermal photosensitivity due to the accumulation of photosensitizer protoporphyrin IX. We performed a systematic database search on studies related to treatment of EPP. A total of 25 relevant studies were retrieved, 16 of them dealing with the application of beta-carotene. Two studies were found on each of the three substances, n-acetyl-cysteine (NAC), cysteine, and dihydroxyacetone/Lawson (henna). In addition, single studies on vitamin C, canthaxanthin and UVB treatment respectively, were located. The total number of patients in the 25 studies was 454, including 337 patients in the various beta-carotene trials. Most studies were published in the 1970's. Efficacy criteria were not standardized. Only 5 of the 25 studies were randomized and controlled trials; the rest were either open-label, uncontrolled studies or retrospective case reports. Four of the five well-designed studies suggested lack of efficacy of beta-carotene, NAC and vitamin C. The results of the beta-carotene studies were strongly contradictory and efficacy was inversely correlated with study quality. Our data confirm the opinion of experts in the field who are much more skeptical as to its efficacy than were early proponents of treatment with this agent. We conclude, that the available data are insufficient to prove efficacy of any treatments studied so far in EPP. We emphasize the necessity of high quality efficacy studies in porphyrias and in other rare diseases.
Topics: Ascorbic Acid; Clinical Trials as Topic; Cysteine; Humans; Protoporphyria, Erythropoietic; Treatment Outcome; beta Carotene
PubMed: 19268006
DOI: No ID Found -
Annals of Hematology Jul 2010
Topics: Aged; Humans; Male; Myelodysplastic Syndromes; Protoporphyria, Erythropoietic; Protoporphyrins; Sunlight; Vitamins; beta Carotene
PubMed: 19902211
DOI: 10.1007/s00277-009-0859-7 -
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 -
European Journal of Pediatrics Oct 2000Erythropoietic protoporphyria (EPP, MIM 177000) is an inherited disorder caused by a partial deficiency of ferrochelatase (FECH) which catalyses the chelation of iron... (Review)
Review
UNLABELLED
Erythropoietic protoporphyria (EPP, MIM 177000) is an inherited disorder caused by a partial deficiency of ferrochelatase (FECH) which catalyses the chelation of iron into protoporphyrin to form haem. The majority of EPP patients experience solely a painful photosensitivity whereas a small number of them develop liver complications due to the accumulation of excessive amount of protoporphyrin in the liver. EPP is considered to be an autosomal dominant disorder, however, with a low clinical penetrance. To date, a total of 65 different mutations have been identified in the FECH gene of EPP patients. Among the 89 EPP patients who carry a "null allele" mutation which results in the formation of a truncated protein, 18 of them developed EPP-related liver complications. None of the 16 missense mutations identified among 19 patients on the other hand, have been associated with liver disease (P = 0.038). The allelic constellation of an overt patient consists of a mutated FECH allele and a "low expressed" normal allele and that of an asymptomatic carrier, a combination of a mutated and a normally expressed FECH allele. The identification of the "low expressed" allele is facilitated by haplotype analysis using two single nucleotide polymorphisms, -251 A/G in the promoter region and IVS1-23C/T. At the current time when only partially effective therapies are available, the disclosures of both "null allele" and the "low expression" mechanisms will improve patient management.
CONCLUSION
While covering the important clinical aspect of erythropoietic protoporphyria, this article emphasises the latest achievements in the molecular genetics of the disorder.
Topics: Alleles; Ferrochelatase; Genetic Predisposition to Disease; Heterozygote; Humans; Liver Diseases; Lymphocytes; Mutation; Phenotype; Photosensitivity Disorders; Polymorphism, Genetic; Porphyria, Hepatoerythropoietic; Protoporphyria, Erythropoietic; Switzerland
PubMed: 11039124
DOI: 10.1007/s004310000494 -
Journal of the American Veterinary... Dec 2020A 6-month-old sexually intact male Clumber Spaniel was evaluated because of small stature, recurrent dermatitis of the head, and progressive pigmentary hepatopathy.
CASE DESCRIPTION
A 6-month-old sexually intact male Clumber Spaniel was evaluated because of small stature, recurrent dermatitis of the head, and progressive pigmentary hepatopathy.
CLINICAL FINDINGS
Clinicopathologic findings included nonanemic hypochromic microcytosis, hypocholesterolemia, persistently high serum liver enzyme activities, and anicteric hyperbilirubinemia. Histologic examination of liver biopsy specimens collected when the dog was 6 months and 2 years of age revealed expansion and bridging of portal tracts, occasional centrilobular parenchymal collapse, scattered lymphoplasmacytic infiltrates, and dark red to brown pigment within large aggregates of macrophages, engorged bile canaliculi, and hepatocytes. The pigment failed to stain for the presence of iron, copper, bile, and glycoprotein and, when examined with polarized microscopy, emitted a yellow to green birefringence with occasional Maltese cross configurations. Further analyses confirmed marked porphyrin accumulation in blood, urine, feces, and liver tissue; protoporphyrin accumulation in RBCs and liver tissue; and a signature porphyrin profile and fluorescence peak consistent with erythropoietic protoporphyria. Advanced protoporphyric hepatopathy was diagnosed. The chronic dermatopathy was presumed to reflect protoporphyric photosensitivity.
TREATMENT AND OUTCOME
Management was focused on avoiding conditions known to induce heme synthesis and catabolism, administrating ursodeoxycholic acid and antioxidants -adenosylmethionine and vitamin E, and avoiding sunlight exposure. At follow-up at 4 years of age, the dog was stable without evidence of jaundice but with probable persistent erythropoietic protoporphyria-related solar dermatopathy.
CLINICAL RELEVANCE
Clinical and histologic features of congenital erythropoietic protoporphyria and resultant protoporphyric hepatopathy, the diagnosis, and the successful management of a dog with these conditions over 4 years were described. Veterinarians should consider porphyric syndromes when unusual pigmentary hepatopathies are encountered.
Topics: Animals; Bile; Dog Diseases; Dogs; Liver; Liver Diseases; Male; Protoporphyria, Erythropoietic; Ursodeoxycholic Acid
PubMed: 33226294
DOI: 10.2460/javma.2020.257.11.1148 -
Journal of Photochemistry and... Sep 1991In erythropoietic protoporphyria, protoporphyrin overproduction occurs mainly in erythroid tissue. Protoporphyrin can be released from erythrocytes in the dark, but the... (Review)
Review
In erythropoietic protoporphyria, protoporphyrin overproduction occurs mainly in erythroid tissue. Protoporphyrin can be released from erythrocytes in the dark, but the release is greatly increased if the erythrocytes are exposed to small amounts of light. Protoporphyrin can be bound in plasma either to albumin or to low density or high density lipoprotein. The cutaneous symptoms in erythropoietic protoporphyria are primarily elicited by protoporphyrin-sensitized photodamage of endothelial cells due to the presence of protoporphyrin in lipid structures. Which structures are damaged first in endothelial cells is unknown. Endothelial cells probably accumulate protoporphyrin from albumin or lipoproteins present in the plasma. A direct transfer from the erythrocyte membrane to the endothelial cell membrane can also occur. The transfer processes are probably facilitated by light exposure. Degranulation of mast cells, invasion of neutrophils into interstitial tissue and complement activation seem to be of less importance than endothelial cell injury in the pathogenesis of erythropoietic protoporphyria. These processes may, however, participate in the final expression of the cutaneous symptoms. Uroporphyrin and coproporphyrin are hydrophilic and are probably unbound in plasma, although weak binding to plasma proteins cannot be excluded. In the hepatic porphyrias and in erythropoietic porphyria, the clinical symptoms are probably evoked by uroporphyrin and coproporphyrin present in the interstitial tissue. Very little is known about the primary targets of uroporphyrin and coproporphyrin photodamage in these disorders, but photodamage to intercellular structures probably represents the initial event. Activation of complement may contribute to the final expression of the cutaneous symptoms.
Topics: Endothelium, Vascular; Erythrocytes; Erythropoiesis; Humans; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins
PubMed: 1791486
DOI: 10.1016/1011-1344(91)80015-a -
Photodiagnosis and Photodynamic Therapy Mar 2023Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by light exposure. The patients have very limited treatment options. Sunless skin tanning with dihydroxyacetone (DHA) is now being investigated as a possible treatment modality of skin photosensitivity in EPP.
METHODS
We simulated the theoretical light protection factor provided by DHA application. In addition, we present 19 cases with EPP who were treated at our department with DHA weekly during spring and summer from 2018 to 2021 inclusive.
RESULTS
The protection factor against UVA and visible light was estimated to approximately two. Out of the 19 patients with EPP who were treated with DHA in 2018, 11 patients experienced a sustained good effect and continued to use the treatment on a weekly basis in the spring and summer of 2019, 2020, and 2021.
CONCLUSION AND PERSPECTIVES
Both the theoretical estimates and the uncontrolled study suggest that sunless tanning with DHA reduces photosensitivity in patients with EPP. Our hypothesis is that skin treated with DHA can tolerate twice the daylight dose compared to untreated skin before onset of skin symptoms. To validate this conclusion, we plan a randomized clinical trial to determine the effect of DHA application to reduce photosensitivity in patients with EPP under controlled clinical conditions. The study protocol for this trial is presented in the paper.
Topics: Humans; Protoporphyria, Erythropoietic; Dihydroxyacetone; Photochemotherapy; Photosensitizing Agents; Light; Photosensitivity Disorders
PubMed: 36690194
DOI: 10.1016/j.pdpdt.2023.103302 -
The Australasian Journal of Dermatology Nov 2019
Comparative Study
Topics: Adult; Aortic Valve Stenosis; Australia; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Pilot Projects; Postoperative Care; Protoporphyria, Erythropoietic; Retrospective Studies; Risk Assessment; Sampling Studies; Treatment Failure; Warfarin; Young Adult
PubMed: 30916386
DOI: 10.1111/ajd.13033