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17 KOSMETISCHE MEDIZIN 6.14 DAS MELANOCORTIN-SYSTEM: DIE BEHANDLUNG MELANOZYTÄRER NÄVI The Melanocortin System: Medical Management of Congenital Melanotic Naevi NINIAN PECKITT 1 , JESPERANZA RAGUINDIN R.N. 2 INTRODUCTION Congenital melanocytic naevi (CMN) are proliferations of benign melanocytes that are present at birth or develop shortly after birth [1]. Other melanocytic naevi, but were not present at birth, are termed: congenital naevus-like naevi congenital type naevi tardive naevi. Naevi may also form from other skin cells eg vascular naevi. Some of these are also congenital. CLASSIFICATION OF CONGENITAL MELANOCYTIC NAEVI (CMN) CMN are usually classified by size. Small congenital melanocytic naevi are < 1.5 cm in diameter Medium congenital melanocytic naevi are 1.5–19.9 cm Giant congenital melanocytic naevi are 20 cm in diameter A modification of the above classification [2]: Small congenital melanocytic naevi are < 1.5 cm in diameter Medium congenital melanocytic naevi are 1.5–10 cm Large congenital melanocytic naevi are 11–20 cm Giant congenital naevi are further subdivided into: G1 (21–30 cm) G2 (31–40 cm) G3 (> 40 cm) Incidence CMN Small 1 : 100 births [1–3] Medium 1 : 1000 births [1] Giant 1 : 20, 000 live births [1–3] They occur in all races and ethnic groups, and males and fe- males are at equal risk. 1 Professor: European University College, Dubai, UAE Adjunct Associate Professor of Engineering Assisted Surgery, School of Engineering and Advanced Technology Massey University, New Zealand 2 Staff Nurse, Nicolas & Asp Clinics, Dubai, UAE KEYWORDS: process oriented aesthetics, paradigm change aesthet- ics, network theory, system theory SUMMARY Since its beginning exists a cross-fertilizing link between aesthetic medicine and other faculties. Aesthetics were responsible for the inte- gration of superficial treatment options of elder patients into anti- aging therapies, in contrary many other faculties have influenced the development of aesthetic medicine as well. Future developments will not change this cross-link. Since the beginning of the last century the model of science theory and philosophy is in a process of revolutionary changes caused by new findings in physics and biology, and nowadays this development has already touched medicine. These new findings cannot be explained by using the old model of science theory.Topic of this article will be the opportunities that can be offered to aesthetics by the new scientific paradigm. SCHLÜSSELWÖRTER: Prozessorientierte Ästhetik, Paradigmenwechsel Ästhetik, Netzwerktheorie, Systemtheorie ZUSAMMENFASSUNG Es hat schon immer einen befruchtenden Austausch zwischen der Ästhe- tik und den anderen Fachgruppen gegeben. Ästhetische Medizin war verantwortlich für die Einbeziehung des äußeren Erscheinungsbildes alter Menschen in die Anti Aging Medizin, die anderen Fachdisziplinen aber haben auch die Entwicklung der Ästhetik stark beeinflusst. Dies wird auch in Zukunft so bleiben. Seit Beginn des letzten Jahrhunderts ist die ganze Wissenschaftstheorie und -philosophie im Umbruch durch neue Erkenntnisse in der Physik und Biologie, die nicht mehr mit den herkömmlichen Erklärungsmodellen erfasst werden können, und diese Entwicklung hat die Medizin längst erreicht. Welche Möglichkeiten das neue Wissenschaftsparadigma der ästhetischen Medizin bietet, soll Gegenstand dieses Artikels sein.

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Page 1: Seiten aus KM6_2014_23_12-2

17KosmetisChe medizin 6.14

das melanoCortin-system: die BehandlUng melanozytÄrer nÄVi

the melanocortin System:medical management of Congenital

melanotic Naevininian PeCKitt1, JesPeranza ragUindin r.n.2

INtroDuCtIoN

Congenital melanocytic naevi (Cmn) are proliferations of benign melanocytes that are present at birth or develop shortly after birth [1].

other melanocytic naevi, but were not present at birth, are termed:• congenital naevus-like naevi• congenital type naevi• tardive naevi.

naevi may also form from other skin cells eg vascular naevi. some of these are also congenital.

ClaSSIFICatIoN oF CoNGENItal mElaNoCytIC NaEVI (CmN)

Cmn are usually classified by size. • small congenital melanocytic naevi are < 1.5 cm in diameter• medium congenital melanocytic naevi are 1.5–19.9 cm• giant congenital melanocytic naevi are ≥ 20 cm in diameter

a modification of the above classification [2]: • small congenital melanocytic naevi are < 1.5 cm in diameter• medium congenital melanocytic naevi are 1.5–10 cm• large congenital melanocytic naevi are 11–20 cm

giant congenital naevi are further subdivided into:• g1 (21–30 cm)• g2 (31–40 cm)• g3 (> 40 cm)

Incidence CmN• small 1 : 100 births [1–3]• medium 1 : 1000 births [1]• giant 1 : 20, 000 live births [1–3]they occur in all races and ethnic groups, and males and fe-males are at equal risk.

1 professor: European university College, Dubai, uaE

adjunct associate professor of Engineering assisted Surgery,

School of Engineering and advanced technology massey university,

New Zealand

2 Staff Nurse, Nicolas & asp Clinics, Dubai, uaE

Keywords: process oriented aesthetics, paradigm change aesthet-

ics, network theory, system theory

summary

Since its beginning exists a cross-fertilizing link between aesthetic

medicine and other faculties. aesthetics were responsible for the inte-

gration of superficial treatment options of elder patients into anti-

aging therapies, in contrary many other faculties have influenced the

development of aesthetic medicine as well. Future developments will

not change this cross-link. Since the beginning of the last century the

model of science theory and philosophy is in a process of revolutionary

changes caused by new findings in physics and biology, and nowadays

this development has already touched medicine. these new findings

cannot be explained by using the old model of science theory.topic of

this article will be the opportunities that can be offered to aesthetics

by the new scientific paradigm.

schlüsselwörter: prozessorientierte Ästhetik, paradigmenwechsel

Ästhetik, Netzwerktheorie, Systemtheorie

Zusammenfassung

Es hat schon immer einen befruchtenden austausch zwischen der Ästhe-

tik und den anderen Fachgruppen gegeben. Ästhetische medizin war

verantwortlich für die Einbeziehung des äußeren Erscheinungsbildes

alter menschen in die anti aging medizin, die anderen Fachdisziplinen

aber haben auch die Entwicklung der Ästhetik stark beeinflusst. Dies

wird auch in Zukunft so bleiben. Seit Beginn des letzten Jahrhunderts

ist die ganze Wissenschaftstheorie und -philosophie im umbruch durch

neue Erkenntnisse in der physik und Biologie, die nicht mehr mit den

herkömmlichen Erklärungsmodellen erfasst werden können, und diese

Entwicklung hat die medizin längst erreicht. Welche möglichkeiten das

neue Wissenschaftsparadigma der ästhetischen medizin bietet, soll

Gegenstand dieses artikels sein.

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macroscopic appearance • single or multi-shaded• round or oval shaped pigmented patches [2]. • hyertrichosis may be a feature• the surface may be slightly rough or bumpy.

Natural Historygrowth is usually proportionally with the child. as a rough guide, the likely adult size of a congenital naevus can be calculated as follows: • lower limbs: adult size is x 3.3 size at birth• Upper limbs/torso: adult size is x 2.8 size at birth• head: adult size is x 1.7 size at birthCongenital naevi may become smaller and thus less obvious. rarely some may even disappear. Particularly around puberty they become darker, raised, bumpy and hairy.

Symptomatology• Usually asymptomatic• Pruritis – especially larger lesions. • sebaceous and eccrine gland atrophy may contribute to skin dryness and itch. • skin erosion / ulceration of skin• skin fragility – weakening of dermal epidermal junction• Cosmesis – anxiety and impaired self image • increased risk of developing cutaneous melanoma, neurocutaneous melanoma and rarely other tumours.

aetiologygenetic abnormalities and melanocyte proliferation between the 5–24 weeks of gestation. if proliferation starts early in

development, giant and medium sized congenital melanocytic naevi are formed [1]. at the same time, smaller congenital mel-anocytic naevi are formed, after the melanoblasts have migrated from the neural crest to the skin [1]. in some cases, there are also overgrowth of hair-forming cells and epidermis, forming an or-ganoid naevus.

melaninmelanin is a broad term for a group of natural pigments found in most organisms (arachnids are one of the few groups in which it has not been detected). melanin is a two staged process: 1. oxidation of the amino acid tyrosine2. secondary polymerisation. the pigment is produced in a specialized group of cells known as melanocytes. there are three basic types of melanin:

molecular Biology [4]Proto-oncogenes c-met [4] and c-kit [5] have important roles in the development of melanocytes. hepatocyte growth factor, a cytokine that regulates the proliferation and migration of mel-anocytes, may also be important in the development of congen-ital melanocytic naevi [1]. c-met is a proto-oncogene that en-codes a protein, hepatocyte growth factor receptor (hgFr) [1, 2].this possesses tyrosine-kinase activity [3]. met proto-oncogene is translated into a trans-membrane met protein which is a re-ceptor for tyrosine kinase (rtK) through transphosphorylation. met is a trans-membrane receptor that is essential for embry-onic development and wound healing.

• hepatocyte growth factor (hgF) is the only known ligand of the met receptor.

taB. 1: ClaSSIFICatIoN oF CoNGENItal mElaNotoC NaEVI

Café-au-lait macule

speckled lentiginous naevus

satellite lesions

tardive naevi

garment naevi

halo phenomenon

• Inheritedflattanmark• Usuallyovalinshape• Multiplecafé-au-laitmaculesmaybeasignofneurofibromatosis

• Alsocallednaevusspilus• Darkspotsonaflattanbackground

• Smallermelanocyticlesions• Onperipheryofcentralcongenitalmelanocyticnaevus• Presentin>70%oflargecongenitalmelanocyticnaevi

• Naevithatappearafterbirth• Slowergrowthandlesssynthesisofmelaninthancongenitalnaevi[3]

• Namerelatestoanatomicallocationofnaevus• Bathingtrunknaeviinvolvecentralareasusuallycoveredbyabathingcostume• Coatsleeveneviinvolveanentirearmandproximalshoulder

• Affectssomecongenitalmelanocyticnaevi• Surroundingskinbecomeslighter• Centrallesionmayalsobecomelighterandsmaller• Duetoimmunedestructionofmelanocytes

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19KosmetisChe medizin 6.14

• met is normally expressed by cells of epithelial origin• expression of hgF is restricted to cells of mesenchymal origin. • Upon hgF stimulation, met induces several biological responses that collectively give rise to • a programme known as invasive growth.• abnormal met activation in cancer correlates with poor prognosis• aberrantly active met triggers tumour growth, angiogenesis, and facilitates metastasis. • met is deregulated in many types of human malignancies, including cancers of kidney, liver, stomach, breast, and brain.

normally, only stem cells and progenitor cells express met, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult. however, cancer stem cells are thought to hijack the abil-ity of normal stem cells to express met, and thus become the cause of cancer persistence and metastatic spread to other sites in the body. Various mutations in the met gene are associated with papillary renal carcinoma [4].

c-Kit [5]Proto-oncogene c-Kit or tyrosine-protein kinase Kit or Cd117, al-so known as mast/stem cell growth factor receptor (sCFr), is a protein that in humans is encoded by the Kit gene. hematopoiet-ic stem cells (hsC), multipotent progenitors (mPP), and common myeloid progenitors (CmP) express high levels of Cd117. in ad-dition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express Cd117. Cd117 is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. altered forms of this receptor may be associated with some types of cancer. Cd117 is a receptor tyrosine kinase type iii, which binds to stem cell factor. signal-ling through Cd117 plays a role in cell survival, proliferation, and differentiation. activating mutations in this gene are associated with gastrointestinal stromal tumors, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivat-ing mutations are associated with the genetic defect piebaldism. Cd117 is a proto-oncogene. overexpression or mutations of this protein can lead to cancer.

• seminomas• leukemia• melanoma • mast cell disease• gastrointestinal stromal tumors (gists)

the site of mutation determines the efficacy of immunotherapy:• imatinib, a Cd117 inhibitor, targets mutation in exon 11 (e.g. gists) • dasatinib and nilotinib targets mutation in exon 17 (e.g. seminomas and leukemia)

melancortin Drug Developmenton the basis of their prominent regulatory role in many of these functions, the development of melanocortin-based drugs is pres-ently in the developmental phase, for the treatment of skin cancer and other cutaneous disorders, including giant Cmn, obesity, ano-rexia nervosa, cachexia, erectile dysfunction, inflammatory diseas-es, pain, and nerve injury. antagonists and inverse agonists include:• mC1 selective agouti signalling peptide• mC4 • selective agouti-related peptide (inverse agonist at both mC3 and mC4)• hs-014• hs-024• mCl-0042• mCl-0129• mPB-10• shU-9119 (agonist at mC1 and mC5, antagonist at mC3 and mC4)

melanocortins and pigmentationactivation of mC1r by á-msh stimulates eumelanin synthe-sis. Conversely, antagonism of á-msh action by agouti favours phaeomelanin synthesis. mC1r has also been reported to be up-regulated by UV radiation.

melanocortin-1-receptor gene mC1rKinsler et al [7] have demonstrated an association with mel-anocortin-1-receptor gene (mC1r) – known to result in red hair,

taB. 2: tHE mElaNoCortIN SyStEm [6]

mC1r

mC2r

mC3r

mC4r

mC5r

potency of ligands

á-msh = aCth > â-msh > ã-msh

aCth

á-msh = â-msh = ã-msh = aCth

á-msh = aCth > â-msh > ã-msh

á-msh > aCth > â-msh > ã-msh

antagonists

agouti

agouti

agouti, agrP

agouti, agrP

primary Functions

Pigmentation, inflammation

steroidogenesis

energy homeostasis

energy homeostasis, erectile function

sebaceous gland secretion

mC1r = melanocortin receptor-1; msh = melanocyte-stimulating hormone; aCth = adrenocorticotropic hormone; agrP = agouti-related protein

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freckles, and pale skin, and Cutaneous melanotic naevus. Con-genital melanocytic nevi (Cmn) are pigmented birthmarks that affectupto80%of theskinsurfacearea.The increasedfre-quency of Cmn in families of severely affected individuals is suggestive of a predisposing germline genotype. Kinsler et al noted a high prevalence of red hair in affected families, and considered a role for mC1r in this condition. a cohort of 166 Cmn subjects underwent pigmentary phenotyping, with mC1r genotyping in 113. results were compared with a local control group of 60 unrelated children and with 300 UK children wit-hout Cmn. Cmn subjects had higher prevalences of red hair and a red-haired parent than local controls and had a higher rate of compound heterozygosity and homozygosity for mC1r vari-ants. the presence of a V92m or r allele (d84e, r151C, r160w, d294h) was associated with increasing size of the Cmn, imply-ing a growth-promoting effect of these alleles. Unexpectedly, the V92m and r151C alleles were also strongly associated with birth weight in the Cmn cohort, a finding confirmed in the con-trol group. the effect of germline mC1r genotype on develop-ment and severity of Cmn led us to investigate potential broa-der effects on growth, revealing a role for mC1r in normal fetal development.

the mC1r gene has more than 100 known variants. in this study, a third of children with Cmn had a first- or second-de-gree family history of any size of Cmn. small Cmn are very common, occurring in one in every 100 babies. these children had a higher instance of at least one mC1r allele than children without a family history of Cmn.

two specific variants, V92m and r151C are strongly associ-ated with increased birth weight, suggesting a previously unk-nown role for mC1r in normal foetal development. in children with Cmn, the presence of these and a few other alleles appear also to correlate with increased size of the Cmn.

red Hair [8]• Incidence1–2%• MorefrequentinNorthern/WesternEuropeancestory(2–6%)• autosomal recessive gene (Chromosome 16) with mutation in the mC1r Protein• Colour varies from burgundy to bright copper• related to high levels of pheomelanin and low levels of eumelanin• InScotlandandIreland40%and46%respectivelyare thought to carry the recessive red hair gene• during the spanish inquisition all redheads were identified as being Jewish• IntheUSAanestimated2–6%ofthepopulationare redheads (i.e. n = 6–18 million)the significance of red hair and fair skin is related to the ability to make Vitamin d under low light conditions.

Features of the mC1r recessive Gene• red hair• non-tanning skin (alleles for red hair and skin pigmentation are close to each other)• Freckles

• 80%ofredheadshaveanMC1Rgenevariant• Phenotypic expression of lighter skin and red hair are interrelated• mC1r is not the only gene for red hair production (hCl2 chromosome 4 may have role)

medical Implications• u.v sensitivity and cutaneous malignancy - basal cell carcinoma - squamous cell carcinoma - malignant melanoma• Pain tolerance and injury - redheads – different sensitivity to pain - more sensitive to thermal pain (naturally low Vitamin K levels) - redheads are less sensitive to pain from multiple modalities > noxious stimuli > electrically induced pain - redheads require greater amounts of anaesthetic - Female redheads require less pentazocine - Female redheads have greater response to pentazocine than men - Female redheads greater response to morphine-6-glucuronide

the increased tolerance to pain can be explained by a mutation in a hormone receptor which can respond to two hormones mel-anocyte stimulating hormone (msh) and endorphins. Both derive from the same precursor molecule Proopiomelanocortin (PomC) and are structurally similar. specifically redheads have a mutated mC1r gene that produces an altered receptor for msh on the mel-anocytes. Binding at this mutated receptor site results in the pro-duction of reddish pheomelain rather than eumelanin.mC1r also occurs in the brain where it is one of a large number of PomC re-ceptors apparently not only responding to msh but also to endor-phins. this explains the pain tolerance recorded in redheads.

Haemorrhagethere is little or no evidence to support the belief that patients with red hair have a higher incidence of haemorrhage or suffer other bleeding complications. But one study reports a higher in-cidence of bruising.

Neurocutaneous melanosis [1, 2]neurocutaneous melanocytosis is a rare syndrome defined by the proliferation of melanocytes in the central nervous system (brain and spinal cord) and the presence of a congenital melano-cytic naevus the majority of cases are associated with a giant congenital melanocytic naevus and satellite lesions.

Itisestimatedneurocutaneousmelanosisaffects5–10%ofpeople that have a giant congenital melanocytic naevus. how-ever it is likely that the majority of cases remain asymptoma-tic, and the true incidence remains unknown. the melanocytes in the brain and spinal cord may often be detected by an mri scan but the use of these scans is controversial, because the condition is not easily treatable.

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neurocutaneous melanocytosis may present with symptoms of raised intracranial pressure, such as headache, Vomiting, irritability, Focal cranial nerve signs, seizures, hydrocephalus (increased water around the brain), delayed development

DIaGNoSIS

is made on clinical appearance, dermoscopy – to reveal the pattern of pigmentation, symmetry and/or lack of symmetry and biopsy.

Dermoscopy Featuresdermoscopy is one of several non-invasive techniques which permit accurate clinical diagnosis of pigmented lesions. oil or alcohol solution is applied to the surface of the dermatoscope to improve the clarity of the magnified image and subsurface structures. dermoscopy is very helpful to distinguish melano-cytic versus non-melanocytic lesions, and pattern analysis can be employed to assist in differentiating benign from malignant melanocytic lesions. algorithms [9] and checklists, increase the diagnostic accuracy: • menzie‘s method• the seven-point method• pattern recognition• aBCd algorithm, have been shown to improve diagnostic accuracy

pathology Cmn usually larger than acquired naevi (those that appear after 2 years of age). the naevus cells often extend deeper into the dermis, fat layer, and deeper structures. they characteristically cluster around blood vessels, hair follicles, sebaceous and ec-crine glands, and other skin structures. Congenital naevus cells tend to involve collagen bundles in the deeper layers of the skin more than is the case in an acquired naevus [1, 2]

Endogenous antagonists to mC1r [6]Perhaps one of the most interesting aspects of the melanocor-tin system is that it has two endogenous antagonists, agouti* and agrP. these proteins are unique in that no inhibitory pro-teins have been identified for any of the seven-transmembrane receptor family. agouti and agrP are paracrine signalling mol-ecules, which are endogenous antagonists of the mCrs. agouti and agrP have the potential in vivo to regulate their respective mCrs, even in the absence of melanocortins.

* agouti refers to a hair colour pattern commonly seen in mam-mals, which is characterized by a subapical yellow band on an otherwise black or brown background.

dominant mutations of the agouti gene cause mice to develop yellow fur, obesity, insulin resistance, increased somatic growth, and a predisposition to tumour genesis. the normal role of agou-ti, however, is to act in conjunction with alpha-msh and mC1r to determine mammalian coat colour. agouti is produced by

taB. 3: DErmoSCopy

Criteria

Pigment network

dots/globules

Blue-white veil

Vascular structures

regression structure

milia-like cysts

Benign pigmented Naevi

• uniform• regularlymeshed• homogeneouspigment• thinningatperiphery

• regular• brownorblack

Usually absent

some – regular vascular pattern

Usually absent

some congenital / papillomatous melanocytic naevi

melanoma

• Black/brown/grey• thickenedandirregularnetwork• streaks• pseudopods

• Irregular• peripheralblack,brown, blue-grey (pepper-like)

Present, may have “ground glass” appearance

• Atypicalvascularpattern• linear/dottedvessels= neovascularization

Present, white scar-like areas or bluish-white areas

absent

Seborrheic Keratosis

• Network-likestructure• Ridgesandfurrows• Finger-likepattern• Moth-eatenborder

Comedo-like openings

absent

hairpin blood vessels

absent

Present

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the dermal papillae cell and acts on the adjacent melanocyte to block melanocortin action at mC1r. this interaction has a ma-jor effect on pigmentation. Pharmacologically, agouti is a high-affinity, competitive antagonist of the melanocortin peptides at mC1r and mC4r. in rodents, agouti is expressed only in skin. the human homolog of agouti, called agouti-signaling protein (asP), has a wider pattern of expression, including adipose tis-sue, testis, ovary, and heart and lower levels of expression in foreskin, kidney, and liver. at the present time, the physiological function(s) of asP in humans is unknown.

ancillary proteinsmahogany and syndecan-3 are proteins that modulate the activ-ity of agouti and agrP, respectively. mahogany is a single-pass transmembrane protein that is expressed primarily in brain, in-cluding the hypothalamus, and skin and is involved in mamma-lian coat colouration. syndecan-3 is a heparan sulphate proteo-glycan, a class of single-pass transmembrane molecules whose ectodomain is shed from the cell surface in response to defined stimuli. syndecans are molecules that bind extracellular ligands. overexpression in transgenic mice may be associated with obe-sity. Food deprivation increases hypothalamic syndecan-3 more than fourfold.

CmN – risk of melanoma the following characteristics of congenital melanocytic nae-vus are associated with the increased risk of development of melanoma: • large or giant size• axial or paravertebral location (crossing the spine)• multiple congenital satellite naevi• neurocutaneous melanosis• early childhood

the risk of melanoma:• SmallandmediumsizedCMN<1%

• Giantcongenitalnaevi(lifetimeestimatesare5–10%) - particularly in lesions that lie across the spine - or where there are multiple satellite lesions - melanoma-genesis may occur deep inside the naevus or within any neuromelanosis found in the brain and spinal cord - other tissues that contain melanocytes may also be a source of melanoma such as the gastrointestinal tract mucosa -In24%ofcases,theoriginofthemelanomacannotbe identified [2]

melanoma associated with congenital melanocytic naevi or neu-romelanosis can be very difficult to detect and treat. the risk of developmentofmelanomaisgreaterinearlychildhood;70%ofmelanomas associated with giant congenital melanocytic naevi are diagnosed by the age of ten years [1, 3]. rarely, other types of tumour may develop within giant congenital melanocytic nae-vi including benign tumours (lipomas, schwannomas) and other malignant tumours (including sarcomas).

regular follow-up • Close-up photographs• digital surveillance using dermoscopic images (mole mapping) • it is advisable to continue close observation in those at risk of neurocutaneous melanosis even after the primary lesion has been excised [3]

prognosis of melanoma associated with congenital melanocytic naevus • melanoma and giant Cmn have an unfavourable prognosis• melanoma arises in deeper origin of the tumour• more difficult to detect – later stage at presentation• deeper location also facilitates earlier blood / lymph spread• 24%ofmelanomasalreadymetastasedatdiagnosis

CmN – treatment• age of the subject• the lesion size• location and depth• risk of developing malignant change within the lesion

Giant CmNthe only definite indication for surgery in a giant congenital mel-anocytic naevus is when a melanoma develops within it.

Cosmetic Camouflage [10]makeup should be applied in the following sequence:• Foundation, preceded if required by Under-eye Concealers.• Corrections and improvements• Blushers• Powders• eye makeup• lip makeup

Fig. 1: the mEt protein

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makeup tuition Softwaremakeup software is become increasingly available. some is fair-ly basic permitting different hairstyles etc. sophisticated tuition software is also available which offer a colour analysis package and makeup advice.

Cosmetic Camouflagethere are 3 basic approaches to cosmetic camouflage: • Concealersthey often thicker and more opaque than regular foundation makeup, effectively covering healed incision lines from surgery, scars and/or bruises. they are usually available as creams with a variety of shades to match the natural colour of the skin and may be blended with colour correctors to achieve a good colour match. liquid colour-matched concealers also closely resemble normal skin. • Colour CorrectionColour correction is used to disguise the yellowish shade of a bruise or the overall redness from a burn they come in tints, purple corrector blended with concealer neutralises yellow skin tones and green corrector yields a brown tone to neutralise redness. • ContouringContouring corrects the irregular facial surface contours, cre-ating a dimension using light and shadow. dark colours make swellings or protrusions appear to recede, while light colours make surface depressions appear shallower.

to achieve contouring you need a highlighter, which is about 2 shades lighter than the concealer, and a contour shadow, which is about 2 shades darker. Powdered blush-type products are best suited for contouring. Camouflage makeup needs to be removed from your face and neck every night before bed. Because of their waterproof nature, an oily cleansing cream or lotion may be need-ed to wipe off the makeup followed by cleaning with soap and wa-ter or a normal facial cleansing routine. liquid camouflage prod-ucts and camouflage cosmetics used elsewhere on the body can be left on for 3 or 4 days before removing them and re-applying.

thin lizzythin lizzy Cosmetic Products may be purchased on line and are effective camouflage agents for the concealment of skin naevi, tattoos etc. a shade guide is available on line for colour match-ing the skin. the system comprises of three constituents:

1. Concealer Cream (waterproof beeswax formulation)• applied with Black Brush• linear strokes quick and thick application• dab with finger tips• allow to dry• reapply as required for concealment

2. mineral Foundation Powder sPF 15• apply with Pink Kabuki Brush• swiping rotation and Polishing movements for mineral application

• repeat to desired result• effect is to warm up and illuminate the skin

3. 6 : 1 Professional Powder• gentle application with fine Blue Brush• illuminates skin to produce a natural glow• Bronzing effect• giant Pigmented naevi

the risk of malignant transformation in giant Pigmented naevi estimatedatabout8%maybeanoverestimationofmalignantchange, which be difficult to spot if the area is depigmented e.g. with laser, chemical peel, or bleaching agents. excision, in ac-cordance with surgical aesthetic zone principles, does not nec-essarily produce excellent cosmesis, but is suggested to be the cosmetic treatment of choice. in this case, excellent cosmetic camouflage of the lesion has been achieved, and this case em-phasises the importance of a cosmetics education and tuition of the patient in the optimisation of facial aesthetics with cosmetic

Fig- 2: c-met pathway

• METactivationbyitsligandHGFinducesMETkinasecatalyticactivity

• ThistriggerstransphosphorylationofthetyrosinesTyr1234

and tyr 1235

• Signaltransducersinteracttogeneratetheinvasivegrowth

programme

directly

- Growth factor receptor-bound protein 2 (GrB2)

- the oncogene Src Homology 2 Domain (SHC)

- proto-oncogene tyrosine-protein kinase (SrC)

Indirectly

- GaB1 – a scaffolding protein and key coordinator of the cellular

responses to mEt

- GaB1 phosphorylation by mEt results in a sustained signal that

mediates most of the downstream signaling pathways [16]

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KosmetisChe medizin 6.14 ÜBErSICHtEN | rEVIEWS 24

products. the role of surgery as the primary treatment option therefore needs to be questioned and each case should be treat-ed on an individual basis.

Small congenital naevi if small congenital naevi are just growing at the same rate as the child, and are not changing in any other way, the usual practice is not to remove them until the child is old enough to co-operate with a local anaesthetic injection, usually around the age of 10 to 12 years. even then, removal is not essential.

prophylactic surgical removaltreatment decisions should be tailored to individual patients, taking into account lesion size, location, appearance and lep-tomeningeal involvement. small Cmn do not require prophylactic

removal; however, they should be evaluated closely for changes in lesion asymmetry, border, colour, and diameter. intermediate-sized Cmn may require prophylactic excision, especially if le-sions appear atypical.

Prophylactic removal should be considered before the teenage years because risk for malignant melanoma is high-er in postpubertal children. Prophylactic removal of large Cmn continues to be an area of controversy. Prophylactic surgical removal is performed if it is felt that there is a high risk that a melanoma may arise within the lesion. the following factors should be considered:

• Prophylactic excision of small lesions may be delayed until an age when the patient is old enough to make an informed choice • small or medium sized congenital melanocytic naevi are at a lower risk for developing malignant change, and such worrying change tends to occur later• irregular, lumpy or thick lesions or lesions that are difficult to clinically assess may have a lower threshold for consideration of surgical excision• 50%ofmelanomasdiagnosedinthosewithgiantcongenital melanocytic naevi occur at another site. therefore surgical excision of the lesion may not eliminate the risk of melanoma• large or giant melanocytic lesions may be too large to excise completely• large lesions may require a skin flap or graft to close the surgical defect • Cns imaging studies may be employed for all infants with largeCMN.Inonestudy,30%ofasymptomaticpatientswith large Cmn were found to have leptomeningeal melanosis, suggesting that the incidence of Cns involvement is high. In71%ofinfantswithabnormalMRIscans,theCMNcovered much of the spinal area and satellite nevi were seen on the scalp.

Complications of surgery Complications that may occur after surgery include graft or flap failure, infection, wound breakdown, bleeding or haematoma and hypertrophic or keloid scar.

otHEr trEatmENt optIoNS

Dermabrasion dermabrasion can allow partial removal of a large congenital naevus. however, deeper naevus cells may persist. dermabra-sion may lighten the colour of the naevus but may not reduce hair growth within it.

tangential (shave) excision tangential or shave excision uses a blade to remove the top lay-ers of the skin (epidermis and upper dermis). this may reduce the pigmentation but the lesion may not be completely removed. shave excision may result in significant scarring.

Fig. 3: Giant CmN Grade G2 – Cosmetic Camouflage – thin lizzy

System [10]. (acknowledgement: Wendy Nowell-usticke of thin lizzy

auckland, New Zealand for her contribution to the management of this

case via an Internet-based Joint management Clinic)

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25KosmetisChe medizin 6.14

Chemical peels Chemical peels using trichloroacetic acid or phenol may light-en the pigmentation of a superficial (surface) congenital naevus that is located in the upper layers of the skin

lasers laser treatment be considered if surgical intervention is not possible. they may result in lightening of the lesion. suitable devices include ruby Q-switched lasers and carbon dioxide re-surfacing lasers. techniques that result in partial removal of a congenital naevus can make the lesion more difficult to assess during long term surveillance.

CoNCluSIoNS

advances in the understanding molecular biology of genes espe-cially Proto–oncogenes c-met [4], c-kit [5] and the mC1r genes of the melanocortin peptides are catalysing the development of therapies targeting gene mutations. this heralds the develop-ment of melanocortin-based drugs for the treatment of skin can-cer and other cutaneous disorders, including giant Cmn, obesity, anorexia nervosa, cachexia, erectile dysfunction, inflammatory diseases, pain, and nerve injury. Currently Cosmetic camouflage offers an effective option for improvement of aesthetics whilst permitting the monitoring of lesions for malignant change.

address of Correspondence:ninian Peckitt, FrCs FFd rCs Fds rCs FaCCs

al zahra hospital

Po Box 124412

sheikh zayed road, al, Barsha 1

dubai Uae

references: 1. Viana aCl, gontijo B, Bittencourt FV. giant congenital melanocytic nevus.

an Bras dermatol. 2013; 88: 863-78.

2.eds. Bolognia J, Jorizzo J, schaffer J (2012) dermatology. 3rd ed. elsevier

saunders P 1871-6

3.Kovalyshyn i, Braun r, marghoob a (2009) Congenital melanocytic naevi.

aust J derm 50: 231-40.

4. c-met http://en.wikipedia.org/wiki/C-met

5. c-kit http://en.wikipedia.org/wiki/C-kit

6. gantz i, Fong tm (2003) the melanocortin system. am J Physiol endocri-

nol metab 284: e468-e474.

7. Kinsler Va, abu-amero s, Budd P et al. (2012) melanocortin-1-receptor

genotype is associated with severity of Cutaneous Phenotype in Congenital

melanocytic nevi: a role for mC1r in human Fetal development. J invest

dermatol (2012) 132: 2026–2032.

8. red hair http://en.wikipedia.org/wiki/red_hair

9. dermoscopy algorithms http://www.dermnetnz.org/doctors/dermoscopy-

course/algorithms.html#menz

10. Peckitt ns in: abφut Face. the Principles and Practice of Cosmetic

medicine and surgery. Currently in Press. austin macauley Publishers ltd.

london.