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ACG Case Reports Journal Feb 2023Erythropoietic protoporphyria (EPP) presents with nonblistering photosensitivity. Hepatobiliary manifestations are seen in around 5% cases and include cholelithiasis,...
Erythropoietic protoporphyria (EPP) presents with nonblistering photosensitivity. Hepatobiliary manifestations are seen in around 5% cases and include cholelithiasis, elevations in liver enzymes, progressive jaundice, and end-stage liver disease. The diagnosis is suspected based on clinical features and elevated erythrocyte metal-free protoporphyrin and confirmed by genetic analysis showing loss-of-function mutations in the ferrochelatase (FECH) gene. We present an adolescent boy who presented with jaundice and photosensitivity with the liver biopsy showing deposition of brown pigments within the canaliculi and hepatocytes. This pigment showed Maltese cross birefringence on polarizing microscopy and Medusa-head appearance on electron microscopy. Genetic analysis revealed loss-of-function mutations in FECH. Introduction of EPP is an inborn error of heme biosynthesis caused by mutations in FECH with a prevalence of 1:75,000 to 1:200,000. We present a case of a 16-year-old adolescent boy with photosensitivity, abdominal pain, and jaundice with protoporphyrin deposition in the liver who was ultimately diagnosed with EPP based on genetic analysis.
PubMed: 36891180
DOI: 10.14309/crj.0000000000000996 -
Gastroenterology & Hepatology Feb 2023
PubMed: 36866109
DOI: No ID Found -
Clinical Pharmacology in Drug... May 2023Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked... (Randomized Controlled Trial)
Randomized Controlled Trial
Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. In this open-label, multicenter, randomized, two-cohort, sequential crossover study, the relative oral bioavailability of two tablet formulations of dersimelagon was evaluated, and the effect of various gastric conditions (from a high-fat meal, a proton-pump inhibitor, and an acidic carbonated beverage) on the pharmacokinetics of dersimelagon were assessed in healthy participants (N = 50). Both tablet formulations demonstrated rapid absorption, and the 100-mg tablets showed a 97% relative oral bioavailability versus 50-mg tablets. No effect was observed on overall exposure (area under the plasma concentration versus time curve [AUC]) following consumption of a high-fat meal, and C was higher (22%, 90% confidence interval [CI] 1.05-1.42) in a fed state compared with fasted conditions. Similarly, overall exposure AUC of dersimelagon was comparable following administration alone or in combination with esomeprazole; however, coadministration of esomeprazole led to a slight decrease in C (fasted: 9%, 90%CI 0.77-1.07; fed: 24%, 90%CI 0.66-0.88) compared with administration of dersimelagon alone. In general, the consumption of an acidic beverage increased time to C regardless of fed or fasted status and decreased overall exposure AUC and C of dersimelagon.
Topics: Adult; Humans; Biological Availability; Healthy Volunteers; Esomeprazole; Cross-Over Studies; Tablets
PubMed: 36840969
DOI: 10.1002/cpdd.1235 -
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 -
JAMA Dermatology Feb 2023Erythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and...
IMPORTANCE
Erythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.
OBJECTIVES
To describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity.
DESIGN, SETTING, AND PARTICIPANTS
This was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022.
EXPOSURES
Sunlight exposure.
MAIN OUTCOMES AND MEASURES
Self-reported symptoms and association with measured light sensitivity.
RESULTS
The study sample consisted of 35 patients with EPP (mean [SD] age, 39.1 (15.5) years; 21 [60%] female; 14 [40%] male; 35 [100%] White individuals). The patients' median [range] skin tone was 3.0 (1.0-8.0), based on self-reporting from 1 (lightest) to 12 (darkest). A total of 24 participants completed the light dosimeter measurements. Phototoxic reactions were characterized by pain (97%; 34 patients), burning (97%; 34), tingling (97%; 34), pruritus (83%; 29), allodynia (89%; 31), improvement of symptoms with cold (89%; 31), achiness (24%; 12), fatigue (46%; 16), mild swelling (83%; 29), severe swelling (63%; 22), erythema (51%; 18), petechiae (40%; 14), skin cracking (43%; 15), scabbing (46%; 16), scarring (66%; 23), and other chronic skin changes (40%; 14). Patients with EPP reported that their hands, feet, and face were most sensitive to light and that their shoulders and legs were least sensitive; 25.7% (9 patient) reported no chronic skin changes, and 5.7% (2 patients) reported never having had any visible symptoms. None of these findings varied with the degree of light sensitivity except that lower overall light sensitivity was associated with lower ranked sensitivity of the neck and arms.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional study suggest that patients with EPP have distinctive cutaneous symptoms that may aid in identification of this underdiagnosed disease. Characteristic EPP symptoms include light-induced cutaneous burning pain and occasional swelling, particularly over the hands, with a prodrome of pruritus and paresthesias. Minimal skin changes or the absence of visible skin changes during reactions to light, including lack of erythema, do not exclude an EPP diagnosis nor suggest low EPP disease burden.
Topics: Adult; Adolescent; Humans; Male; Female; Protoporphyria, Erythropoietic; Photophobia; Cross-Sectional Studies; Erythema; Pruritus; Paresthesia
PubMed: 36630131
DOI: 10.1001/jamadermatol.2022.5850 -
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 -
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 -
Journal of the American Academy of... May 2023
Observational Study
Topics: Humans; Protoporphyria, Erythropoietic; Prospective Studies; Pilot Projects; Mutation
PubMed: 36436693
DOI: 10.1016/j.jaad.2022.11.036