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Der Hautarzt; Zeitschrift Fur... Oct 2015Homogenous pigmentation can be induced by α-melanocyte-stimulating hormone (MSH) homologues. Cosmetically inacceptable pigmentation is mostly located on the face. (Review)
Review
BACKGROUND
Homogenous pigmentation can be induced by α-melanocyte-stimulating hormone (MSH) homologues. Cosmetically inacceptable pigmentation is mostly located on the face.
OBJECTIVES
Although afamelatonide is a prescription drug for the orphan disease erthropoetic protoporphyria, structurally related α-MSH derivatives are available via the internet. Preventive and therapeutical options are necessary for postinflammatory hyperpigmentation, melasma, and lentigines.
METHODS
Case reports address activation of dysplastic naevi by melanotan I. Wood's lamp is of some use in analyzing the level of hyperpigmentation. However, no guidelines have been established; thus, a summary of current studies is presented.
RESULTS
Melanotan I leads to the activation of dysplastic nevi. The gold standard for hyperpigmentation is triple therapy with hydrochinon, tretinoin, and steroids, which can cause irritation and lead to ochronosis in some individuals. Tyrosinase inhibitors, substances that increase the cell turnover, and plant derivatives are less efficient but more tolerable.
CONCLUSIONS
Melanotan I and bleaching creams, which may possibly contain mercury, are dangerous. Hyperpigmentation is best treated using a combination therapy that inhibits melanocyte activity and melanin synthesis, removes melanin, destroys melanin granules, and includes UV protection. Especially in Fitzpatrick skin types IV-VI, cryotherapy and laser are not the first line treatment options due to renewed posttreatment hyperpigmentation.
Topics: Combined Modality Therapy; Cosmetic Techniques; Evidence-Based Medicine; Facial Dermatoses; Humans; Immunosuppressive Agents; Keratolytic Agents; Monophenol Monooxygenase; Phototherapy; Pigmentation Disorders; Skin Lightening Preparations; Treatment Outcome
PubMed: 26315100
DOI: 10.1007/s00105-015-3671-4 -
Dermatologie (Heidelberg, Germany) Jun 2024Porphyrias are predominantly genetic metabolic disorders caused by dysregulation of specific enzymes in porphyrin-heme biosynthesis. The enzymatic dysfunction leads to... (Review)
Review
Porphyrias are predominantly genetic metabolic disorders caused by dysregulation of specific enzymes in porphyrin-heme biosynthesis. The enzymatic dysfunction leads to formation and excretion of intermediate metabolic products in the form of porphyrins and/or their precursors δ‑aminolevulinic acid and porphobilinogen, which have cyto- and tissue-toxic properties. Clinically, porphyrias are extremely diverse, with symptoms ranging from skin changes on light-exposed areas of the body to potentially life-threatening neurovisceral attacks. Biochemical tests in urine, blood and stool are used for diagnosis, which can be supplemented by molecular genetic analyses. Treatment of the various forms of porphyria is complex and often requires close interdisciplinary cooperation between different medical specialties.
PubMed: 38902527
DOI: 10.1007/s00105-024-05370-3 -
Gastroenterology Jan 2024
Topics: Humans; Protoporphyria, Erythropoietic; Photosensitivity Disorders; Abdominal Pain; Protoporphyrins
PubMed: 37579823
DOI: 10.1053/j.gastro.2023.07.028 -
Trends in Molecular Medicine Jun 2024Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic... (Review)
Review
Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic compound, protoporphyrin (PPIX), in red blood cells (RBCs). PPIX is responsible for painful cutaneous photosensitivity, which severely impairs quality of life. Hepatic elimination of PPIX increases the risk of cholestatic liver disease, requiring lifelong monitoring. Treatment options are scarce and mainly limited to supportive care such as protection from visible light. Here, we review the pathophysiology of protoporphyrias, their diagnosis, and current recommendations for medical care. We discuss new therapeutic strategies, some of which are currently undergoing clinical trials and are likely to radically alter the severity of the disease in the years to come.
PubMed: 38890030
DOI: 10.1016/j.molmed.2024.05.006 -
Blood Jun 2023Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by reduced expression of ferrochelatase, the enzyme that catalyzes the final step in heme...
Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by reduced expression of ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis. The resultant accumulation of protoporphyrin IX leads to severe, painful cutaneous photosensitivity, as well as potentially life-threatening liver disease in a small percentage of patients. X-linked protoporphyria (XLP) is clinically similar to EPP but results from increased activity of δ-aminolevulinic acid synthase 2, the first step in heme biosynthesis in the bone marrow, and also causes protoporphyrin accumulation. Although historically the management of EPP and XLP (collectively termed protoporphyria) centered around avoidance of sunlight, novel therapies have recently been approved or are in development, which will alter the therapeutic landscape for these conditions. We present 3 patient cases, highlighting key treatment considerations in patients with protoporphyria, including (1) approach to photosensitivity, (2) managing iron deficiency in protoporphyria, and (3) understanding hepatic failure in protoporphyria.
Topics: Humans; Protoporphyria, Erythropoietic; Ferrochelatase; Liver Diseases; Photosensitivity Disorders; Protoporphyrins; Heme
PubMed: 36898083
DOI: 10.1182/blood.2022018688 -
Metabolites Aug 2022Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At... (Review)
Review
Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme-the iron-chelated form of protoporphyrin IX-is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.
PubMed: 36144223
DOI: 10.3390/metabo12090819 -
Frontiers in Physiology 2022Partial deficiency of the last enzyme of the heme biosynthetic pathway, namely, ferrochelatase (FECH), is responsible for erythropoietic protoporphyria (EPP) in humans....
Partial deficiency of the last enzyme of the heme biosynthetic pathway, namely, ferrochelatase (FECH), is responsible for erythropoietic protoporphyria (EPP) in humans. This disorder is characterized by painful skin photosensitivity, due to excessive protoporphyrin IX (PPIX) production in erythrocytes. Although several papers report the presence of iron deficiency anemia in about 50% of EPP patients, there is still no a conclusive explanation of the why this occurs. In the present work, we explored hematological indices and iron status in 20 unrelated Italian EPP patients in order to propose a new hypothesis. Our data show that microcytosis is present in EPP patients also in the absence of anemia and iron deficiency with a link between PPIX accumulation and reduced MCV, probably indicating an indirect condition of heme deficiency. Patients studied had a downward shift of iron parameters due to increased hepcidin concentrations only in a state of repleted iron stores. Interestingly, hemoglobin synthesis was not limited by iron supply except in cases with further iron loss, in which concomitantly increased soluble transferrin (Tf) receptor (sTfR) levels were detected. The mechanisms involved in the iron uptake downregulation in EPP remain unclear, and the role of PPIX accumulation in microcytosis.
PubMed: 35309058
DOI: 10.3389/fphys.2022.841050 -
Diagnostics (Basel, Switzerland) May 2022The World Health Organization (WHO) describes "health" as a state of physical, mental, and social well-being and not merely the absence of disease or infirmity.... (Review)
Review
The World Health Organization (WHO) describes "health" as a state of physical, mental, and social well-being and not merely the absence of disease or infirmity. Therefore, a biopsychosocial approach should be considered as an integral part of patients' management. In this review, we summarize the available data starting from 1986 on the biological, psychological, and social aspects of porphyrias in order to provide a useful tool for clinicians about the missing knowledge within this field. Porphyrias are a group of rare metabolic disorders affecting the heme biosynthetic pathway and can be categorized into hepatic and erythropoietic. Here, a total of 20 articles reporting the psychological and the quality of life (QoL) data of porphyria patients affected by acute hepatic porphyrias (AHPs), Porphyria Cutanea Tarda (PCT), and Erythropoietic Protoporphyria (EPP) were analyzed. These 13 articles include reported quantitative methods using questionnaires, while the reaming articles employed qualitative descriptive approaches through direct interviews with patients by psychology professionals. We conclude that the use of questionnaires limits the complete description of all areas of a patient's life compared to a direct interview with specialists. However, only a combined use of these methods could be the best approach for the correct disorder management.
PubMed: 35626348
DOI: 10.3390/diagnostics12051193 -
American Journal of Clinical Dermatology Apr 2016Afamelanotide (SCENESSE(®)) is a synthetic α-melanocyte stimulating hormone analogue and first-in-class melanocortin-1 receptor agonist that is approved in the EU for... (Review)
Review
Afamelanotide (SCENESSE(®)) is a synthetic α-melanocyte stimulating hormone analogue and first-in-class melanocortin-1 receptor agonist that is approved in the EU for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). It is administered subcutaneously as a biodegradable, controlled-release implant containing 16 mg of afamelanotide. This article reviews the clinical efficacy and tolerability of afamelanotide in EPP and summarizes its pharmacological properties. In the phase III trial, CUV039, afamelanotide treatment improved light tolerance in patients with EPP. Compared with placebo, afamelanotide treatment enabled patients to spend more time in direct sunlight without pain and increased the time to the appearance of the first symptoms of phototoxicity provoked by a standardized light source. Afamelanotide was generally well tolerated in this trial, with no drug-related serious adverse events reported. Commonly occurring adverse reactions included headache and implant-site reactions. Efficacy and safety data from earlier phase III trials are consistent with those from the CUV039 trial. Afamelanotide, approved in the EU for the prevention of EPP phototoxicity, represents a useful addition to the management of the disorder.
Topics: Absorbable Implants; Adult; Clinical Trials, Phase III as Topic; Dermatitis, Phototoxic; Drug Implants; European Union; Headache; Humans; Protoporphyria, Erythropoietic; Receptor, Melanocortin, Type 1; Subcutaneous Absorption; Sunlight; Treatment Outcome; alpha-MSH
PubMed: 26979527
DOI: 10.1007/s40257-016-0184-6