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The British Journal of Dermatology Jun 2015
Topics: Dermatologic Agents; Female; Humans; Male; Protoporphyria, Erythropoietic; alpha-MSH
PubMed: 26036158
DOI: 10.1111/bjd.13769 -
Pharmacology & Therapeutics Aug 2023Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic... (Review)
Review
Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic protoporphyria and X-linked protoporphyria causes painful phototoxic reactions of the skin, which can significantly impact daily life. Endothelial cells in the skin have been proposed as the primary target for PPIX-induced phototoxicity through light-triggered generation of reactive oxygen species. Current approaches for the management of PPIX-induced phototoxicity include opaque clothing, sunscreens, phototherapy, blood therapy, antioxidants, bone marrow transplantation, and drugs that increase skin pigmentation. In this review, we discuss the present understanding of PPIX-induced phototoxicity including PPIX production and disposition, conditions that lead to PPIX accumulation, symptoms and individual differences, mechanisms, and therapeutics.
Topics: Humans; Endothelial Cells; Protoporphyrins; Protoporphyria, Erythropoietic; 5-Aminolevulinate Synthetase
PubMed: 37392940
DOI: 10.1016/j.pharmthera.2023.108487 -
Frontiers in Immunology 2021The homeostasis of tissues in a chronic disease is an essential function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it...
The homeostasis of tissues in a chronic disease is an essential function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells with a consequent aggravation of symptoms. The protoporphyria (PP) is a rare chronic disease that causes phototoxicity in visible light with local skin pain and general malaise. In order to establish if there is a systemic involvement of the CS during sun exposure, we designed a non-invasive method with a serum collection in winter and summer from 19 PP and 13 controls to detect the levels of CS protein: Properdin, Factor H (FH), and C5. Moreover, the global radiation data were collected from the regional agency of environmental protection (ARPA). The results show growing values for every protein in patients with PP, compared to control, in both seasons, in particular in summer compared to winter. To reinforce the evidence, we have estimated the personal exposure of patients based on the global radiation data. The main factors of the AP increased over the season, confirming the involvement of the AP in relation to light exposure. The systemic response could justify the general malaise of patients after long light exposure and can be exploited to elucidate new therapeutic approaches.
Topics: Adult; Biomarkers; Complement C5; Complement Factor H; Complement Pathway, Alternative; Complement System Proteins; Disease Susceptibility; Female; Humans; Male; Middle Aged; Properdin; Protoporphyria, Erythropoietic; Seasons; Sunlight
PubMed: 33664746
DOI: 10.3389/fimmu.2021.615620 -
Journal of the Royal Society of Medicine Aug 1995Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of... (Review)
Review
Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra-violet light causing tissue damage by release of free oxygen radicals, which manifests as photosensitivity. The majority of cases of erythropoietic protoporphyria present in childhood although sometimes symptoms are delayed until the second decade. We report here a case presenting in adulthood and discuss the risk of liver disease in the condition.
Topics: Adult; Humans; Liver Cirrhosis; Male; Photosensitivity Disorders; Porphyria, Hepatoerythropoietic
PubMed: 7562835
DOI: No ID Found -
[Clinicopathologic features of three cases of erythropoietic protoporphyria with liver involvement].Zhonghua Bing Li Xue Za Zhi = Chinese... Oct 2017To investigate the clinicopathologic features of the erythropoietic protoporphyria (EPP) with liver involvement. The clinical findings and hepatic biopsy of 3 cases of... (Review)
Review
To investigate the clinicopathologic features of the erythropoietic protoporphyria (EPP) with liver involvement. The clinical findings and hepatic biopsy of 3 cases of EPP diagnosed between July, 2011 to August, 2014 with liver involvement were reviewed, with relevant literature review. All patients presented with persistent and refractory abdominal pain, with obvious jaundice and deranged liver function. Imaging showed homogeneous hepatomegaly in all patients. Histologically, the hepatocytes were edematous, and contained numerous cytoplasmic globular brown pigments and bile pigments, which were also found in Kupffer cells, in the bile canaliculi and in some of dilated sinusoid. The pigments were of different sizes and showed uneven distribution. Some pigments showed bright red or yellow birefringence with a distinctive central maltese cross configuration on polarizing microscopy. Furthermore, some hepatocytes showed piecemeal necrosis and steatosis, the portal tracts were usually infiltrated by lymphocytes, with fibroplasia and biliary ductular reaction. There was no dilatation of intrahepatic bile ducts. Full understanding of the clinical and pathological features of EPP with liver involvement can help to recognize this small group of patients, and to offer proper effective treatments.
Topics: Bile Pigments; Hepatocytes; Humans; Kupffer Cells; Liver; Necrosis; Protoporphyria, Erythropoietic; Protoporphyrins
PubMed: 29050073
DOI: 10.3760/cma.j.issn.0529-5807.2017.10.009 -
The Australasian Journal of Dermatology Feb 2022Children with erythropoietic porphyria are generally under the care of paediatric dermatologists. When these children undergo major surgery, they are at risk of unusual...
Children with erythropoietic porphyria are generally under the care of paediatric dermatologists. When these children undergo major surgery, they are at risk of unusual complications due to their photosensitivity. Dermatologists may be consulted prior to surgery for advice. We describe a case of a child with erythropoietic porphyria undergoing open heart surgery, utilising an exchange transfusion alongside other strategies to minimise the risk of photosensitivity-induced haemolysis.
Topics: Cardiopulmonary Bypass; Child, Preschool; Exchange Transfusion, Whole Blood; Hemolysis; Humans; Lighting; Male; Photosensitivity Disorders; Protoporphyria, Erythropoietic
PubMed: 34817070
DOI: 10.1111/ajd.13751 -
Archives of Disease in Childhood Jan 2015
Topics: Child; Humans; Male; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins
PubMed: 25392202
DOI: 10.1136/archdischild-2014-307082 -
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 Opinion on Investigational Drugs Dec 2010Afamelanotide, an α-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated... (Review)
Review
IMPORTANCE OF THE FIELD
Afamelanotide, an α-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated with absolute sunlight-intolerance is discussed.
AREAS COVERED IN THIS REVIEW
The genetics and existing therapy of the inherited disease PP comprising both erythropoietic protoporphyria and X-linked dominant protoporphyria. The physiological and pharmacological actions of α-MSH and afamelanotide including receptor-mediated intracellular signaling and effects of receptor polymorphisms. Adverse effects and safety issues.
WHAT THE READER WILL GAIN
The clinical severity and the necessity for an effective therapy for the rare disease PP are illustrated by a short, up-to-date portrait. A condensed description of clinically important aspects of α-MSH signaling, physiological, pharmacological and safety issues of afamelanotide applied to humans and the rational for its potential efficacy in PP are given. The different trials of afamelanotide in PP and their most recent results are discussed.
TAKE HOME MESSAGE
Although early, results of the first trials of afamelanotide for PP are promising and the risk-safety profile appears favorable today. We expect afamelanotide and analogs thereof to be a prospective therapeutic tool in light-related skin diseases, and in future this drug class might prove effectiveness in other medical conditions.
Topics: Administration, Cutaneous; Animals; Clinical Trials as Topic; Dermatitis, Phototoxic; Humans; Protoporphyria, Erythropoietic; Skin; alpha-MSH
PubMed: 21073357
DOI: 10.1517/13543784.2010.535515 -
Digestive and Liver Disease : Official... Sep 2023
Topics: Humans; Protoporphyria, Erythropoietic; Liver
PubMed: 37100709
DOI: 10.1016/j.dld.2023.04.001