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Melanoma Associated with the Use of Melanotan-II
Abstract
Background:
Unlicensed use of melanotan-II (MT-II) to promote skin pigmentation has become prevalent amongst young people attending fitness centres. We present a case where the melanocyte stimulation of MT-II in combination with the use of sun tanning beds coincided with cutaneous melanoma.
Observation:
A 20-year-old woman with Fitzpatrick skin type II was referred to a dermatology clinic. Clinical examination revealed a suspicious black melanocytic lesion in her left gluteal region. Furthermore, her skin was universally intensely pigmented. The melanocytic lesion was excised, and histology confirmed the diagnosis of melanoma. Three months prior to the excision the patient had conducted a 3- to 4-week course of self-injections with MT-II, intending an augmentation of sunbed tanning.
Conclusions and relevance:
This observation brings attention to the potential risks related to the use of the cyclic α-melanocyte-stimulating hormone analogue MT-II. There are several hazardous aspects of the possible widespread use of MT-II. As the drug is unlicensed and incompletely tested, the extent and types of adverse effects are unknown. Clinicians are advised to be aware of the problem, and counsel their at-risk patients regarding the potential hazards related to the use of MT-II.
... Of the reports which collected information on sourcing routes, thirteen patients sourced their Melanotan I/II product online (Devlin & Pomerleau, 2012; Langan, Ramlogan, Jamieson, & Rhodes, 2009; Nelson, Bryant, & Aks, 2012; Ong & Bowling, 2012; Shelley et al., 2009; Sivyer, 2012; Wijnands-Kleukers, Vries, Meulenbelt, & Van Riel, 2014 ) with one patient sourcing from a " cosmetic physician " (Paurobally, El Hayderi, Richert, Andre, & Nikkels, 2011) and one other from a 'beautician' (Reid, Fitzgerald, Fabre, & Kirby, 2013). From the clinical case presentations reviewed, Melanotan II is most commonly reported by patients as the injected substance (Cardones et al., 2009; Cousen, Colven, & Helbling, 2009; Devlin & Pomerleau, 2012; Fjellhuagan Hjuler & Lorentzen, 2014; Hueso-Gabriel, Mahiques Santos, Terrádez Mas, & Santonja López, Harms, J., Lautenshlager, S., Minder, C. E and Minder, E.I. ...
... High risk tanning behaviours. Of the reports which collected information on use of artificial UV light to enhance the tanning outcome, eleven patients reported use of sunbeds (Ellis, Kirkham, & Seukeran, 2009, Cousen, Colver, & Helbing, 2009 Fjellhuagan Hjuler & Lorentzen, 2014; Hueso-Gabriel et al., 2012; Langan et al., 2009; Ong & Bowling, 2012; Paurobally, Jason, Dezfoulian, & Nikkels, 2011; Schulze et al., 2013; Shelley et al., 2009; Sivyer, 2012). In the remainder of cases, whether the patient had used artificial UV light or not was not described. ...
... Chronic effects. Of adverse effects experienced, most prevalent amongst clinical case presentation reports are eruptive new naevi and darkening/enlargement of existing naevi (Burian & Burian, 2013; Cardones et al., 2009; Cousen, Colven and Helbling, 2009; Ellis, Kirkham, & Seukeran, 2009; Ferrándiz-Pulido et al., 2011; Fjellhuagan Hjuler & Lorentzen, 2014; Hueso-Gabriel et al., 2012; Langan et al., 2009; Ong & Bowling, 2012; Reid et al., 2013; Schulze et al., 2013; Shelley et al., 2009; Sivyer, 2012;, Jason, et al., 2011). In all melanoma cases, concurrent sunbed use was disclosed by the patient. ...
tAim: Socio-cultural emphasis on having a tan has led to blackmarket diversion of synthetic-tanningproducts Melanotan I and II. This review of literature on clinical outcomes of Melanotan I and II aims topresent extant literature on synthetic-tanning and its range of effects.Methods: A review was conducted according to The Critical Appraisal Skills Programme (CASP). A databasesearch was conducted to identify relevant publications. Clinical trials and clinical case presentationsrelating to melanotan use were included. Publications not in English and with a lack of specificity to thetopic were excluded.Results: The review yielded eighteen clinical trials and twenty-one clinical case presentations. Side effectsobserved include nausea, darkening of existing naevi and yawning. Systemic toxidrome and melanomahave also been evidenced. Potential harms include bloodborne virus, infection and contaminated andmislabelled products. Shortcomings in clinical reporting have limited determinations of causality indiagnoses.Conclusion: Side effects observed in clinical trials are largely minor. Long-term health outcomes are asyet undocumented. Much of the harms related to melanotan use are associated with online sourcing ofunregulated products. A systematic approach to clinical case reporting is needed in melanotan associatedadverse health outcomes. The counterfeit PIEDs market and polypharming practices amongst users mustbe considered in reports of harm.Implications: This review makes recommendations to inform enhanced clinical responses, and has under-scored the need for future Internet and clinical research to investigate prevalence and user profiling, andto map health outcomes in melanotan users.
... All individuals had other risk factors such as fair skin, excess sun exposure/tanning bed use and/or family history of melanoma. 125,[127][128][129][130] A 20-year-old woman with Fitzpatrick skin type II and a history of tanning bed use was diagnosed with melanoma on her left gluteal region 3 months after a 3-week course of self-administered melanotan II treatment. 129 In one report of a 23-year-old White woman with red hair and a familial history of melanoma, three melanoma lesions were identified on the back, abdomen and right arm following 3 years of self-administered melanotan II treatment. ...
... 125,[127][128][129][130] A 20-year-old woman with Fitzpatrick skin type II and a history of tanning bed use was diagnosed with melanoma on her left gluteal region 3 months after a 3-week course of self-administered melanotan II treatment. 129 In one report of a 23-year-old White woman with red hair and a familial history of melanoma, three melanoma lesions were identified on the back, abdomen and right arm following 3 years of self-administered melanotan II treatment. Genetic testing revealed heterozygous gene variants in MC1R and CDKN2A, a high-risk melanoma-associated gene. ...
The melanocortin‐1 receptor (MC1R) is a G protein‐coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss‐of‐function MC1R variants suppress G protein‐coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α–melanocortin‐stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV‐protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high‐risk individuals.
... Among the cutaneous complications that have been reported, are melanocytic changes and darkening of existing naevi and eruption of new naevi with dysplastic changes [21,22], [26][27][28], [31][32][33]35] and melanoma were reported from α -MSH analogue in its two forms Melanotan I and II [23,25,30,34]. (table 1). ...
... Case report Cardones and Grichnik (2009) 27 Emergence of new naevi and darkening of existing naevi, male 25 Sivyer (2012) 28 Growth and darkening of existing naevi, female Mang et al. (2012) 29 Pigmented Spitz naevus, male 24 Ong and Bowling (2012) 30 melanoma in situ, Female 23 Burian and Burian (2013) 31 Eruptive naevi, 2 females Reid et al. (2013) 32 Emergence of new naevi and darkening of existing naevi, female 33 years old Schulze et al. (2014) 33 Eruptive naevi Hjuler and Lorentzen (2014) 34 Melanoma, female 20 years old Al Abadie and Sharara (2024) 35 Eruptive naevi, new dysplastic naevi, female 28 years old Table 1: Reports of eruptive naevi and Melanoma in relation to Melanotan use α-MSH and its analogues are mitogenic for human melanocytes, with direct stimulatory and immunoregulatory activities on melanocytes [36]. ...
Self enhancement products have become increasingly popular options to achieve tanning in the pursuit of darker complexion. This practice is relatively popular among both men and women for aesthetic purposes.
Melanotan-I and melanotan-II are synthetic alpha-melanocyte stimulating hormone (α-MSH) analogues that stimulate tanning, which are available in two forms, injectable and nasal spray, and can be purchased via online portals and media outlets. The health consequences of these products range from minor to acute and chronic clinical outcomes. Sunless tanning products are alternatively, perceived as “healthy alternatives” to sunbathing, however, no consistent data on their safety is standardized.
... α-Melanocyte-stimulating hormone is a derivative of the precursor proopiomelanocortin, an agonist on the melanocortin-1 receptor that promotes formation of eumelanin. 1,3 Eumelanin then provides pigmentation to the skin. 3 Apart from its use for tanning, melanotan II has been reported to increase sexual function and aid in weight loss. 1 Melanotan II is not approved by the US Food and Drug Administration; however, injectable formulations can be obtained illegally on the Internet as well as at some tanning salons and beauty parlors. ...
... 1,3 Eumelanin then provides pigmentation to the skin. 3 Apart from its use for tanning, melanotan II has been reported to increase sexual function and aid in weight loss. 1 Melanotan II is not approved by the US Food and Drug Administration; however, injectable formulations can be obtained illegally on the Internet as well as at some tanning salons and beauty parlors. 4 Although injectable forms of melanotan II have been used for years to artificially increase skin pigmentation, the newly hyped nasal tanning sprays are drawing the attention of consumers. ...
... Additionally, studies have shown that the metabolite of MT II known as bremelanotide (PT-141), is effective in treating Female Sexual Desire Disorder. Despite some studies touting safety of the melanotan family of peptides, there are now increasing case reports of eruptive nevi, dysplastic nevi and melanoma in-situ associated with even short term melanotan peptide use [2][3][4][5][6][7][8][9]. ...
Injectable synthetic melanotropic peptides may be used to enhance tanning, improve erectile function and treat female hypoactive sexual desire disorder (FSDD). The peptides, Melanotan I (MT 1) and Melanotan II (MT II) have been touted as sunless tanning agents, with the potential to decrease harmful effects of UV damage. Most recently, bremelanotide (PT141), an active metabolite of MTII, has been FDA approved for the treatment of FSDD. Numerous case reports of melanoma, eruptive nevi and atypical nevi appearing after initiation of melanotropic peptides therapy have been reported. To date, most of these cases have involved unregulated melanotan. This often called into question the dosing and purity of the peptide. We report a case of melanoma in-situ diagnosed four weeks after initiation of MTII use from a regulated compounding pharmacy. Clinicians must be aware of increasing melanotropic peptide use and screen patients accordingly given its unknown carcinogenesis risk.
... Some concerns were raised regarding possible carcinogenic effects of afamelanotide, especially the potential increased risk for the development of melanoma [75]. These concerns were raised due to the illegal commercial use of Melanotan, the socalled 'Barbie drug' which was associated with melanoma [76]. However, the increased risk of melanoma in Melanotan users, who use it for tanning and exhibit sun-seeking behavior, can probably be explained by more UV exposure. ...
Introduction
In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life (QoL). Afamelanotide is the first effective approved medical treatment for EPP, acting on melanocortin-1 receptors. This article aims to review afamelanotide.
Areas covered
: This review summarizes the chemical properties, pharmacokinetics, safety, preclinical and clinical data on afamelanotide in EPP,and post-marketing surveillance. PubMed search, manufacturers’ websites and relevant articles used for approval by authorities were used for the literature search.
Expert opinion
Afamelanotide is an α-melanocyte stimulating hormone analogue. It can activate eumelanogenesis without exposure to UV radiation. Clinical studies in EPP showed that afamelanotide treatment significantly increased exposure to sunlight and QoL. In our clinical experience afamelanotide treatment is much more effective in clinical practice than demonstrated in clinical trials and should be made available for all EPP patients meeting inclusion-criteria. The 60-day interval period was not based on effectiveness studies, and therefor for some of the patients the maximum of four implants per year with the 60-day interval is insufficient. Afamelanotide is well tolerated; common adverse events were headache, fatigue and nausea.
... Secondly, it is possible to chart similar instances of diffusion by examining the growth of melanotan II, a relatively new drug with properties that mimic the effects of exposure to the sun, whilst also reportedly inducing penile erections and increasing sexual desire and weight loss (Hadley & Dorr, 2006). While much of the concerns regarding melanotan II has centred around its injection by naïve users (Van Hout & McVeigh, 2019), even with the development and promotion of a nasal formulation, there remains evidence of adverse consequences, such as renal infarction and systemic toxicity (Peters, Hadimeri, Wahlberg & Afghahi, 2020) (Nelson, Bryant & Aks, 2013) and most commonly changes to the skin such as the development of melanoma (Hjuler & Lorentzen, 2014;Paurobally, Jason, Dezfoulian & Nikkels, 2011). Competitive bodybuilders who sought all-over tans to help enhance the esthetic of their muscular definitions were early adopters of this drug, yet its use rapidly filtered down to other AAS users and was observed among service users of needle and syringe programmes in the United Kingdom (Evans-Brown, Dawson, Chandler & McVeigh, 2009). ...
There is heightened recognition of the public health implications of anabolic androgenic steroids (AAS) for the use of image and performance enhancement; with increasing evidence of their long-term negative health impacts, the hazards associated with their administration (often via injection), and the variability and unpredictability of their contents. In order to optimise the effects of these drugs, together with strict dietary and training regimes, AAS users typically supplement their use with an expansive and continually evolving range of ancillary drugs. The discovery and subsequent adoption of these drugs by the broader AAS user population is largely dependent upon a minority of social influencers within the bodybuilding community.
Pioneering enhanced bodybuilders who self-experiment with a diverse range of image and performance enhancing drugs (IPEDs) and ancillary drugs have been the forerunners in the development of an underground user-led literature, online discussion forums, and were early adopters of internet-facilitated drug markets. Yet the impact of their self-experimentations extends well beyond the enhanced bodybuilding community, particularly in their use of ancillary drugs.
Most significantly has been their role in the diffusion of various enhancement and psychoactive drugs to the wider population. Using the theoretical framework of the ‘diffusion of innovation’ we consider the role that pioneering enhanced bodybuilders have played in the diffusion of various enhancement and psychoactive drugs to the wider population through a focus on three substances: dinitrophenol (DNP), melanotan II and gamma-hydroxybtyrate (GHB). With an increasing range of drugs used by bodybuilders, coupled with an expansion in the use of online forums and online platforms to purchase pharmacological and new psychoactive drugs, we anticipate this trend of diffusion amongst the wider population will continue to flourish. Therefore, we highlight the need for policy makers to monitor emergent trends, not only in the general AAS population but particularly amongst enhanced bodybuilders.
... Melanoma was reported in five cases. One patient developed melanoma in relation to eczematous dermatitis [22], whereas two cases developed melanoma in correlation with usage of melanotan (however, the two latter cases had melanoma in preexisting nevi) [23,24]. A fourth case was seen in association with cutaneous mastocytosis, but the timeframe/correlation to the development of EMN was very uncertain [25]. ...
Eruptive melanocytic nevi (EMN) is a phenomenon characterized by the sudden onset of nevi. Our objective was to compile all published reports of EMN to identify possible precipitating factors and to evaluate the clinical appearance and course. We conducted a systematic bibliographic search and selected 93 articles, representing 179 patients with EMN. The suspected causes were skin and other diseases (50%); immunosuppressive agents, chemotherapy or melanotan (41%); and miscellaneous, including idiopathic (9%). The clinical manifestations could largely be divided into two categories: EMN associated with skin diseases were frequently few in number (fewer than ten nevi), large, and localized to the site of previous skin disease, whereas those due to other causes presented most often with multiple small widespread nevi. In general, EMN seem to persist unchanged after their appearance, but development over several years or fading has also been reported. Overall, 16% of the cases had at least one histologically confirmed dysplastic nevus. Five cases of associated melanoma were reported. We conclude that the clinical appearance of EMN may differ according to the suggested triggering factor. Based on the clinical distinction, we propose a new subclassification of EMN: (1) widespread eruptive nevi (WEN), with numerous small nevi, triggered by, for example, drugs and internal diseases, and (2) Köbner-like eruptive nevi, often with big and few nevi, associated with skin diseases and most often localized at the site of previous skin disease/trauma. The nature of the data precluded assessment of risk of malignant transformation.
... These compounds have been patented and clinical trials have been carried out to study their effects to promote skin tanning and to improve sexual function in male and females (Hadley & Dorr 2006). However, potential risks to develop melanoma related to the use of unlicensed MTII have been reported (Hjuler & Lorentzen 2014). Nevertheless, the first round of melanocortin receptor agonists have been the starting point to synthesize many other agonists and antagonists with elevated selectivity toward MC4R and MC3R (Hruby 2016, Ericson et al. 2017. ...
The initial discovery that ob/ob mice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) expressed by MC4R neurons to the paraventricular nucleus (PVN). Conversely, in the 'starved state' activity of agouti-related neuropeptide (AgRP) and of neuropeptide Y (NPY)-expressing neurons is increased by decreased levels of circulating leptin and insulin and by the orexigenic hormone ghrelin to promote food intake. This initial understanding of the melanocortin pathway has recently been implemented by the description of the complex neuronal circuit that controls the activity of POMC, AgRP/NPY and MC4R neurons and downstream signaling by these neurons. This review summarizes the progress done on the melanocortin pathway and describes how obesity alters this pathway to disrupt energy homeostasis. We also describe progress on how leptin and insulin receptors signal in POMC neurons, how MC4R signals and how altered expression and traffic of MC4R change the acute signaling and desensitization properties of the receptor. We also describe how the discovery of the melanocortin pathway has led to the use of melanocortin agonists to treat obesity derived from genetic disorders.
... In the scientific literature, several adverse effects of Melanotan® have been reported, such as cutaneous hyperpigmentation, melanocytic naevus, and even melanoma [5][6][7][8][9][10][11]. ...
... As a caveat, illegal internet-distributed chemical agents are sold for lifestyle and tanning purposes under false pretences using the false name of afamelanotide, or its previous names and, in the medical literature, serious conditions associated with the use of these compounds have been described [64][65][66][67][68][69][70]. As we did not observe any of the pathologies reported from these illegally-distributed compounds, and after having implanted more than 1000 implants of the genuine afamelanotide drug, we assume that the reported adverse effects of the illegal compounds are elicited by toxic additives or impurities that may be contained in those preparations, besides some kind of a-MSH-like peptides. ...
Afamelanotide, the first α-melanocyte-stimulating hormone (MSH) analogue, synthesized in 1980, was broadly investigated in all aspects of pigmentation because its activity and stability were higher than the natural hormone. Afamelanotide binds to the melanocortin-1 receptor (MC1R), and MC1R signaling increases melanin synthesis, induces antioxidant activities, enhances DNA repair processes and modulates inflammation. The loss-of-function variants of the MC1R present in fair-skinned Caucasians are less effectively activated by the natural hormone. Afamelanotide was the first α-MSH analogue to be applied to human volunteers. Ten daily doses of between 0.08 and 0.21 mg/kg in saline injected subcutaneously resulted in long-lasting skin pigmentation and enabled basic pharmacokinetics. Subcutaneous application had full bioavailability, but neither oral nor transdermal application resulted in measurable plasma concentrations or pigmentation response. Two trials in human volunteers showed that neither MC1R variants nor fair skin reduced the afamelanotide-induced increase in skin pigmentation. A controlled-release formulation optimizes administration in man and is effective at a lower dose than the daily saline injections. Promising therapeutic results were published in polymorphic light eruption, erythropoietic protoporphyria (EPP), solar urticaria, Hailey–Hailey disease and vitiligo. In 2014, afamelanotide was approved by the European Medicines Agency for the prevention of phototoxicity in adult patients with EPP. No late effects were reported in volunteers 25 years after the first exposure or after continuous long-term application of up to 8 years in EPP patients, and an immunogenic potential has been excluded. Generally, adverse effects were benign in all trials.
... [15] Data on the harm associated with melanotan II, when used in the general population, are limited, but a growing number of individual case reports of adverse reactions from the use of products claiming to contain melanotan II links this exogenous hormone to changes in pre-existing moles (stimulation of dysplastic naevi or malignant melanoma). [16][17][18][19] This information, along with accounts by users of melanotan II shared on the Internet, reports in the media, seizures by custom authorities, and observations of online shops, [10] suggest that these drugs have gained popularity over the years. In fact, the increasing demand for these drugs accounts for their presence on the illicit market. ...
An increasing range of drugs that are being used to enhance the body have recently become available on the illicit market. Many of these products contain pharmacologically active substances that are untested or banned (after being licensed as a medicinal product) and they are widely subject to adulteration and misbranding.
Eruptive melanocytic nevi (EMN) have been reported in the setting of immunosuppression, chemotherapy, and bullous skin disease, including less commonly, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This case report presents a 4‐year‐old girl who developed agminated EMN and nail changes after TEN. A systematic review of the literature supports clinically appropriate follow‐up of EMN, as there is no reports of malignancy in EMN following SJS/TEN, nor reports of pediatric melanoma arising within EMN of any etiology. Further study of the possible correlation of nail changes with the development of EMN and better characterization of the dermoscopic features of EMN could improve monitoring and care of these patients.
Endocrine disorders can exert major effects on the human skin, leading to different signs and symptoms, including skin dryness, hair loss or excessive hair growth, pruritus, pigmentary changes and hyperhidrosis. This chapter reviews these changes and provides a practical approach to patients with suspected underlying endocrinological disorders. The chapter also discusses the latest findings showing that the skin serves as a complex (neuro‐) endocrine organ by itself, and thus possesses important practical implications for future dermatological therapy.
Given that the skin is a major target organ of numerous hormones for which it expresses functional receptors, it is not surprising that excessive or insufficient systemic levels of these hormones induce clinically relevant cutaneous responses. These can manifest as general skin symptoms and signs such as pruritus, skin dryness, seborrhoea, hair loss, hypertrichosis, hirsutism, hyperhidrosis and/or hyperpigmentation, any of which prompts consideration of an underlying endocrine disease. In addition, characteristic skin lesions such as palmar erythema, gingival hyperpigmentation, stretch marks (striae distensae), acanthosis nigricans, pretibial myxoedema, necrobiosis lipoidica, melasma and acneform eruptions provide invaluable diagnostic clues to the possibility of unrecognized endocrine disease. More recently, the field has been revolutionized by the recognition that human skin is also a major endocrine and neuroendocrine organ which produces and/or metabolizes not only all classes of steroid hormones but also multiple peptide (neuro‐) hormones, neuropeptides and neurotransmitters. These impact profoundly on skin physiology and pathology at multiple levels, ranging from skin barrier function and neurogenic skin inflammation via wound healing to cutaneous stress responses. This has important implications for future dermatological therapy.
Background:
Melanotan II (MT II) is a synthetic analogue of α-melanocyte-stimulating hormone that, via interaction with the melanocortin 1 receptor, induces skin hyperpigmentation. The unregulated acquisition of MT II injections via the internet and other outlets has become popular over the last decades in order to exploit its properties for use as a tanning agent. Due to the covert nature of MT II use, it is difficult to assess the extent of its use among the general population and to characterise any associated side effects.
Objectives:
The aim of this study was to qualitatively examine MT II use, as portrayed on online forums, and to explore the motivations for its use and side effect profile.
Methods:
Data were extracted retrospectively from UK and Ireland online chatrooms and forums from January 2016 to October 2017. Inclusion criteria were active MT II chatrooms and forums considered to be within the public domain. An inductive thematic analysis identified themes within discussion threads.
Results:
A total of 623 discussion entries were extracted; 205 participants contributed to these entries. Emergent themes included motivation for MT II use, misinformation in the context of using an unregulated product, product preparation and administration, dosing regimens, sunbed use, side effects and concerning practices associated with MT II use.
Conclusion:
Motivations for MT II use included the pursuit of a tanned appearance, often in anticipation of sun holidays and fitness/body building competitions. Clinicians should be aware not only of the potential risks in relation to pigmented skin lesions, but also remain cognisant of the other medical hazards associated with the use of this substance, namely transmission of infectious diseases, use of potentially contaminated products, polypharmacy, and sunbed exposure.
An original approach is proposed for creating the molecularly imprinted polymer and the carrier of protein molecules. Specifically, a thermally and chemically stable branched N-vinylpyrrolidone copolymer was used as the model of an imprint biomolecule and the porogen in the three-dimensional radical copolymerization of N-vinylpyrrolidone and triethylene glycol dimethacrylate. Removal of the branched copolymer left cavities available for binding biomolecules to the copolymer matrix due to its mesoporous structure.
Background
UV radiation is a proven cause of skin cancer. Use of sunbeds has been shown to provide an attributable risk.
Objective
To evaluate the proportion of regular sunbed use in Germany based on large‐scale population‐based surveys over 15 years.
Methods
Skin cancer screenings by dermatologists were conducted between 2001 and 2015 in more than 500 German companies, including a clinical examination and interviews on the risk behavior related to sunburns and sunbeds.
Results
Among 155,679 persons included regular sunbed use significantly declined from 11.0% in 2001 to 1.6% in 2015 (p < 0.001). There were significantly higher rates of sunbed use in women (12.5% / 2.0%) versus men (7.3% / 1.3%; p < 0.001), in younger persons and in participants with darker skin (type II and III) versus fair skin (type I). Individuals with sunburns in childhood were significantly more often sunbed users (5.1% vs. 4.6%; p = 0.002). A remarkable decline of sunbed use was observed after 2009 (7.0% in 2001–2008 and 2.2% in 2009–2015). This reduction occurred in the time of a legal ban of sunbed use for minors but also with the start of the national skin cancer screening program.
Conclusion
Use of sunbeds in the German adult population has dropped by more than 85% in the past decade. Primary prevention, including the large public awareness following the legal ban of sunbed use for young people and the effects of the statutory skin cancer screening program may have contributed to this.
This article is protected by copyright. All rights reserved.
Recently, the unregulated use of untested synthetic alpha-melanocyte-stimulating hormone (α-MSH) analogues, commonly known as melanotan I and II, appears to have increased. These analogues are primarily used for their tan-stimulating effects. Dermatologists see many patients in their clinic who tan. This review provides an overview of the risks of the unregulated use of these substances. Other topics discussed here include the history and safety of afamelanotide, which is the only α-MSH analogue that is approved for use in a limited number of medical indications. Although afamelanotide has been thoroughly tested and deemed safe, illegal melanotans are likely risky for several reasons. There are questions regarding the preparation, administration, and dosage of these substances. In addition to these general risks, increasing numbers of case reports indicate that the unregulated use of both melanotan I and II is associated with cutaneous complications, particularly melanocytic changes in existing moles and newly emerging (dysplastic) nevi. Four case reports have described melanomas emerging from existing moles either during or shortly after the use of melanotan. Although conclusive evidence linking these phenomena is lacking, publications have stressed the importance of awareness that melanotan is a part of a 'tanning culture' in certain subpopulations. Multiple national health organizations have issued safety warnings regarding the use of melanotan I and II.
Introduction: The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown.
Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications.
Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports. Prevalence of this phenomenon is likely to be underestimated, thus reporting should be encouraged in order to better define the actual significance and related clinical implications. The development of multiple melanocytic nevi during immunosuppressive treatments highlights the importance of immune system integrity in the regulation of nevi growth. The observation of eruptive nevi as an unexpected effect of targeted therapies for specific types of cancer, including melanoma, provided intriguing hints to understand the mechanisms underlying this paradoxical event. The synergistic role of additional triggers in the occurrence of drug-induced eruptive nevi has not been explored and may be an interesting area of research.
Excessive exposure to solar radiation brings up two types of deleterious effects. Short term, the leading clinical effect is erythema, which includes swelling and redness, inflammation, and burning sensation. Long term, the predominant effect is photoaging, characterized by skin deterioration, susceptibility to develop skin cancer, and dramatic cosmetic consequences. Erythema is mainly caused by shorter wavelength UV photons that damage tissue, cell, and DNA alike. Photoaging is due to the transformative effect of longer wavelength and low-energy radiation, which causes oxidative damage, activates matrix metalloproteinases, and promotes DNA mutation. Conventional sunscreens protect against UV-induced erythema and photoaging. Broad-spectrum sunscreens are particularly useful to inhibit epidermal gene modifications like mutations on p53 gene, generation of thymine dimers, and induction of apoptosis or to minimize enzymatic damage to the dermal matrix (Seite et al., Photodermatol Photoimmunol Photomed 16(4):147–155, 2000; Moyal, Eur J Dermatol 8(3):209–211, 1998; van der Pols et al., Am J Epidemiol 163(11):982–988, 2006; Al Mahroos et al., Arch Dermatol 138(11):1480–1485, 2002; Bernerd et al., Photochem Photobiol 71(3):314–320, 2000).
New agents with photoprotective capabilities, some of them following oral or subcutaneous administration, have been recently developed. These prevent, ameliorate, or even repair solar-induced skin damage. Furthermore, chemoprevention via nontoxic agents, especially botanical antioxidants, constitutes a plausible strategy for prevention of acute and chronic photodamage including photocarcinogenesis.
In this chapter, we describe the state-of-the-art status of non-topical forms of photoprotective agents and substances with photoprotective properties. Evaluation of these agents in terms of photoprotection will also be discussed.
Injecting use of image and performance-enhancing drugs (IPED) in the general population is a public health concern. A wide and varied range of IPED are now easily accessible to all through the online market. A comprehensive literature review was undertaken according to Critical Appraisal Skills Programme (CASP) guidelines for systematic review, to identify the relevant literature. No date restrictions were placed on the database search in the case of human growth hormone melanotan I and II, and oil and cosmetic injectables. In the case of anabolic androgenic steroids search dates were restricted to January 2014–2015. Publications not in English and with a lack of specificity to the topic were excluded. The review yielded 133 relevant quantitative and qualitative papers, clinical trials, clinical case presentations and editorials/reports. Findings were examined/reviewed under emergent themes which identified/measured extent of use, user profiling, sourcing, product endorsement, risk behaviours and health outcomes in users. Motivation for IPED use may be grounded in appearance, pursuit of health and youth, and body image disturbance. IPED users can practice moderated use, with pathological use linked to high-risk behaviours, which may be normalised within IPED communities. Many IPED trajectories and pathways of use are not scientifically documented. Much of this information may be available online in IPED specific discussion forums, an underutilised setting for research, where uncensored discourse takes place among users. This review underscores the need for future internet and clinical research to investigate prevalence and patterns of injecting use, and to map health outcomes in IPED users. This paper provides community-based clinical practice and health promotion services with a detailed examination and analysis of the injecting use of IPED, highlighting the patterns of this public health issue. It serves to disseminate updated publication information to health and social policy makers and those in health service practice who are involved in harm reduction intervention.
Background:
Ultraviolet radiation (UVR) from the sun and solaria has addictive properties that may develop into dependence. In mice, UVR addiction was connected to β-endorphin (β-END) formed in the skin after UVR exposure. In humans, the formation of β-END in skin keratinocytes has not been confirmed in vivo.
Objective:
To determine with immunohistochemistry if sub-erythematous narrow-band UV-B (NB-UV-B) exposures stimulate p53 mediated expression of pro-opiomelanocortin (POMC), β-END and α-melanocyte stimulating hormone (α-MSH) in human skin keratinocytes in vivo.
Methods:
Within 12 healthy volunteers, 7 received a single 1 standard erythema dose (SED) of NB-UV-B on their whole body, and 5 volunteers received a cumulative dose of 3 SED delivered on two subsequent days i.e., 1+2 SED. Skin biopsies were taken immediately before the first exposure and at 24h from the last UV-B exposure to assess p53, β-END, POMC, and α-MSH expression.
Results:
Nuclear p53 expression increased in all samples taken at 24h after NB-UV-B exposure. UV-B irradiation also increased epidermal β-END expression in 11 out of 12 samples taken at 24h after UV-B exposure. The brownish staining was localized in the cytoplasm of keratinocytes and around the nuclei, being more pronounced in the basal cell layers. POMC and α-MSH staining showed no obvious meaningful increase since only one section of each showed any change compared with basal levels.
Conclusions:
Our study is the first to show that UV-B exposures increase β-END expression in epidermal keratinocytes of human skin in vivo, which could be the link to proposed UVR addiction.
Is unlicensed, unregulated, and potentially harmfulIn 2002 the media reported that the demand for synthetic melanocortin analogues melanotan I and melanotan II (melanotans) was likely to increase in the general population.1 This was mainly because of their ability to tan the skin, and—in the case of melanotan II—induce penile erections and increase sexual desire.2 In 2008, several workers at needle and syringe programmes in the United Kingdom contacted the substance use team at the Centre for Public Health, Liverpool, for information on “melanotan” after their clients reported injecting these drugs. Over the next year around 30 needle and syringe programmes in England and Wales and several drug workers and drug and alcohol action team commissioners have sought our advice in relation to the use of these drugs within the general population. The prevalence of the use of these drugs is unknown. Even though the drugs are unlicensed they are easily available through online shops (including, until recently, eBay.co.uk) and are also sold and administered in tanning salons, beauty parlours, and hairdressers (personal communication …
Few prospective studies have analyzed solar and artificial (solarium) UV exposure and melanoma risk. We investigated these associations in a Norwegian-Swedish cohort study and addressed effect modification by age, pigmentary characteristics, and nevi.
The cohort included women ages 30 to 50 years at enrollment from 1991 to 1992. Host factors and exposure to sun and solariums in life decades were collected by questionnaire at enrollment. Relative risks (RR) with 95% confidence intervals (CI) were estimated by Poisson regression.
Among 106,366 women with complete follow-up through 2005, 412 melanoma cases were diagnosed. Hair color and large, asymmetric nevi on the legs were strongly associated with melanoma risk (P(trend) < 0.001), and the RR for > or =2 nevi increased from brown/black to blond/yellow to red-haired women (RRs, 1.72, 3.30, and 4.95, respectively; P(interaction) = 0.18). Melanoma risk increased significantly with the number of sunburns and bathing vacations in the first three age decades (P(trend) < or = 0.04) and solarium use at ages 30 to 39 and 40 to 49 years [RRs for solarium use > or =1 time/mo 1.49 (95% CI, 1.11-2.00) and 1.61 (95% CI 1.10-2.35), respectively; P(trend) < or = 0.02]. Risk of melanoma associated with sunburns, bathing vacations, and solarium use increased with accumulating exposure across additional decades of life.
Melanoma risk seems to continue to increase with accumulating intermittent sun exposure and solarium use in early adulthood. Apparently, super-multiplicative joint effects of nevi and hair color identify people with red hair and multiple nevi as a very high risk group and suggest important gene-gene interactions involving MC1R in melanoma etiology.
alpha-Melanocyte-stimulating hormone (alpha-MSH) reversibly darkens frog skins by stimulating melanosome movement (dispersion) within melanophores. Heat-alkali treatment of alpha-MSH results in prolonged biological activity of the hormone. Quantitative gas chromatographic analysis of the hydrolyzed heat-alkali-treated peptide revealed partial racemization particularly at the 4(methionine) and 7(phenylalanine) positions. [Nle4]-alpha-MSH, a synthetic analogue of alpha-MSH, reversibly darkens frog skins and also exhibits prolonged activity after heat-alkali treatment. Synthesis of [Nle4, D-Phe7]-alpha-MSH provided an analogue with prolonged biological activity identical to that observed with heat-alkali-treated alpha-MSH or [Nle4]-alpha-MSH. [Nle4, D-Phe7]-alpha-MSH was resistant to enzymatic degradation by serum enzymes. In addition, this peptide exhibited dramatically increased biological activity as determined by frog skin bioassay, activation of mouse melanoma adenylate cyclase, and stimulation of mouse melanoma cell tyrosinase activity. This Nle4, D-Phe7 synthetic analogue of alpha-MSH is a very porent melanotropin, 26 times as potent as alpha-MSH in the adenylate cyclase assay. The resistance of the peptide to enzymatic degradation and its extraordinarily potent and prolonged biological activity should make this analogue of alpha-MSH an important molecular probe for studying the melanotropin receptors of both normal and abnormal (melanoma) melanocytes.
Ein 24-jähriger Patient injizierte sich aus kosmetischen Gründen regelmäßig ein aus dem Internet bezogenes Präparat mit α-MSH (α-Melanozyten-stimulierendes Hormon)-ähnlicher Wirkung subkutan (Melanotan II). Die Veränderung der melanozytären Nävi wurde während der Injektionen mittels sequenzieller Videodermatoskopie dokumentiert. Unter der Injektion von Melanotan zeigten sich dermatoskopische Veränderungen, die eine Diagnose eines Melanoms erschwerten.
Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH.
We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation.
We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.
Introduction:
Melanotan products are currently purchased over the Internet and are designed to induce melanogenesis to create sunless tanning as well are used as sexual stimulants. We report a novel case of systemic toxicity with sympathomimetic excess and rhabdomyolysis after use of Melanotan II.
Case report:
A 39 year-old Caucasian male injected subcutaneously 6 mg of Melanotan II purchased over the Internet in an attempt to darken his skin during wintertime. This dose was six times the recommended starting dose per the patient. In the emergency department two hours post injection, he complained of diffuse body aches, sweating, and a sensation of anxiety. Vital signs included BP 151/85 mmHg, HR 130 bpm that peaked at 146 bpm, and temperature of 97.8°F. Physical exam demonstrated a restless and anxious appearing male with mydriasis, diaphoresis, tachycardia, and diffuse muscle tremors. Pertinent laboratory values were creatinine 2.25 mg/dL, CPK 1760 IU/L, troponin 0.23 ng/mL, WBC 19.1 k/μL. Urinalysis demonstrated 3 + blood with red cell casts but 0-2 RBC/hpf. Qualitative urine drug screen was negative for metabolites of cocaine and amphetamines but positive for opiates. The patient received benzodiazepines for agitation and anxiety and had improvement in his symptoms. He was admitted to the ICU and during hospitalization his CPK elevated to 17773 IU/L 12 hours later. He continued to receive intravenous fluids with sodium bicarbonate for rhabdomyolysis and his CPK decreased to 2622 IU/L with improvement of creatinine to 1.23 mg/dL upon discharge from the ICU after 3 days. The substance, which he injected, was analyzed via mass spectrometry and was confirmed to be Melanotan II when compared with an industry purchased standard sample.
Discussion:
Melanotan products are purchased via the Internet and have three main formulations (Melanotan I, Melanotan II, and bremelanotide). Melanotan I increases melanogenesis and eumelanin content to produce sunless tanning. Melanotan II also increases skin pigmentation but also produces spontaneous penile erections and sexual stimulation. Bremelanotide is a variation of Melanotan II that is specifically designed for sexual stimulation. This unique case highlights the potential of systemic toxicity with sympathomimetic excess, rhabdomyolysis, and renal dysfunction from Melanotan II use.
Conclusion:
Melanotan II use resulted in systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis, and renal dysfunction.
Melanotan is a synthetic analogue of alpha melanocyte stimulating hormone (a-MSH) that stimulates melanogenesis. It is sold on the internet and tanning salons as a quick 'tanning jab'. We report a patient who developed multiple new onset atypical naevi within one week of receiving two Melanotan injections. This case highlights the potential risk of Melanotan in stimulating dysplastic naevi or possibly malignant melanoma.
A pilot phase I study was conducted with a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH). The lactam-bridged molecule, called Melanotan-II (MT-II), has the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH2 (MT-II) and has superpotent melanotropic activity in vitro. A single-blind, alternating day (saline or MT-II), placebo-controlled trial was conducted in 3 normal male volunteers at the starting dose of 0.01 mg/kg of MT-II. Subcutaneous injections of MT-II or saline were given daily (Monday-Friday) for 2 consecutive weeks. Two subjects were escalated by 0.005 mg/kg increments to 0.03 mg/kg and one to 0.025 mg/kg. The 0.03 mg/kg dose produced Grade II somnolence and fatigue in one of two subjects (WHO standards). Mild nausea, not requiring antiemetic treatment, was reported at most MT-II dose levels. A stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose. Two subjects had increased pigmentation in the face, upper body and buttock, as measured by quantitative reflectance and by visual perception 1 week after MT-II dosing ended. These results demonstrate that MT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection. The recommended single MT-II dose for future Phase I studies is 0.025 mg/kg/day.
Alpha-melanocyte stimulating hormone (alpha-MSH) arises from the proteolytic cleavage of proopiomelanocortin (POMC) and is the most potent naturally occurring melanotropic peptide. The biological effects of alpha-MSH are mediated via melanocortin receptors (MCRs), which are expressed in virtually every cutaneous cell type. alpha-MSH has pleiotrophic functions including the modulation of a wide range of inflammatory stimuli such as proinflammatory cytokines, adhesion molecules and inflammatory transcription factors. All of the former would be consistent with a cytoprotective role for this hormone in protecting skin cells from exogenous stress, as would occur following UV exposure or exposure to agents inducing inflammation or oxidative stress. In addition to actions on normal skin cells it also modulates both cutaneous and uveal melanoma cell behavior. With respect to melanoma, alpha-MSH is intriguing as studies have shown that while alpha-MSH has the potential to retard metastatic spread (by reducing cell migration and invasion) it is also capable of reducing the ability of the immune system to detect tumor cells (by down regulating adhesion molecules that would normally assist in immune cell interaction with melanoma cells). This review considers the evolving biology of alpha-MSH and discusses its role in man that extend far beyond pigmentation of skin melanocytes, suggesting that the detoxifying role of alpha-MSH in inducing melanogenesis is only one aspect of the stress-coping role of this hormone. Indeed melanoma cells may owe at least some of their success to the 'protective' role of alpha-MSH.
The melanocortins (MCs) are a family of multifunctional peptidergic hormones. Several superpotent, prolonged acting, enzymatically resistant, MC analogs have been designed and synthesized to help clarify the nature and role of MCs and their receptors (MCRs) in physiological functions. Two of these analogs, a linear peptide, melanotan I, and a cyclic truncated peptide, melanotan II (MTI and MTII, respectively) have been patented and tested clinically for studies on tanning of the skin (MTI) and for diagnosis and treatment of male erectile dysfunction (MTII). A new MTII analog, PT-141 (Palatin Technologies) has initial phase I/II trials and is scheduled to enter pivotal stage III clinical trials leading to commercialization. MTI may provide a therapeutic tan with the potential to lower the risk of skin cancer. PT-141 may improve sexual functionality in both males and females.