. g n o s e m a s e h t g n i g n i s y g o o t a m r e D \211\210 y n o m r a h l \211\210 e c n a d r o c n o C LatinL & GreekG for dermatologists AlbaL=white (as in albino). CutisL=skin (subL=under, eg subcutaneous). DermaG \200\210e \200 =skin (intraL=within, hence intradermal=within the skin). EczemaG , from ekzein, to break out, boil over: ek, out; (zein=to boil). ErythemaG= redness (eg of the skin). ImpetereL = to attack (as in impetigo). IndurareL =to harden (as in induration). LichenL = tree moss; licheni \201 cation to dermat- ologist mea ns like Morocco leather, a condition caused by scratching ( \201 g 1). LivedoL livid (furi ous, red/blue); retic- ulumL = netL. Livedo reticularis, p588. Fig 1. Licheni \201 cation. LupusL=wolf. MaculaL=stain/spot (immaculate; without st - ain; macula peccati=the stain of original sin). Mens/mentemL=mind; nature; temper; men- tum=chin (submental=below the jaw). Muto (mutat)L=I (he) change(s)/mutate(s). PapillaL=nipple or teat (so papule; papilloma). P ilus/piliL=hair (hence fur coat; pelt)/hairs. PityriasisG=grain husk, scale; pityuron=bran. PsoriasisG=to have the itch (psora=itch; NB: psoriasis often does not itch). PurpuraL=purple (imperial) color; porphyra. G RoseaL=pink; akmeG=acne (summit; acme; pimple); 15 acne rosacea=pink pimples, p600). Seborrhoeic=making sebumL (suet, grease). Sen exL=old man. Tel G \200 telos=end+angeion=+vessel+ekstasis Fig 2. Purpura: on warfarin. Check her INR now! Is vitamin K needed? =extension, hence telangiectasia. TopicosG=surface (hence topography; creams are topical). VesicaL=purse, bladder ( \202 uid - \201 lled blister). VitellusL=spotted calf (vitiligo). So \200 try translating lupus pil um mutat, non mentem (the wolf can change his coat but not his nature); but it is unkind to think of dermatologists as wolves: think of them as leopards who can change their (and our ) spots. Possible causes of patterns of skin disease White lesions \200 Pityriasis versicolor: sup er \201 cial slightly scaly infection with the yeast Malassezia furfur; appears depigmente d on darker skins; \201\227: p598. \200 Pityriasis alba: post-eczema hypopigmentation, o ften on children \200\231s faces. \200 Vitiligo (vitellus is Latin for spotted calf ): wh ite patches hyperpigmented borders. Sunlight causes itch. Associations: Autoimmunity: pe rnicious an- aemia, thyroid or Addison \200\231s, DM, alopecia areata. \201\227: (unsatisf actory): try cos- metic camou \202 age, narrowband UVB PUVA (p595) 16 potent topical st eroids. 586 Ring-shaped lesions \200 Basal cell cancer (rodent ulcer; p590): pearly papule + central ulcer. \200 Tinea: active red scaly edge + central healing. \200 Granuloma annulare ( \201 g 1; 1cm ring on hand). \200 Erythema multiforme: target-like lesions, eg on extensor limb surfaces ( \201 g 2 p588). Fig 1. Granuloma annulare. Rarely, leprosy. Brown pigmented lesions Apart from sun-related freckles there are: \200 Lentigos: persistent brown macules, often larger than freckles ( \201 g 2). \200 Caf -a u-lait spots: faint brown macules; if >5, consider neuro \201 bromatosis. 17,18 \200 Seb orrhoeic keratoses/warts: benign greasy-brown warty lesions usually on Dr Jonathan Bowling. y g o o t a m r e D l the back, chest, and face; very common in the elderly. Chloasma (melasma) are brown patches especially on the face, related to pregnancy or Pill use. The condition may respond to topical azelaic acid. Systemic diseases: Addison \200\231s (palmar creases, oral mucosa, scars); haemo- chromatosis; porphyria cutanea tarda (+ skin fragility and blisters). Round, oval, or coin- shaped (discoid) lesions \200 Bowen \200\231s disease ( \201 g 7). \200 Discoid eczema ( \201 g 5 & p602): itchy, crusted/scaly eczema, worsened by heat. \200 Psoriasis: well -de \201 ned scaly red/pink plaques (p594). Distribution on exten- sor surfaces, scalp and natal cleft distinguishes it from discoid eczema (also, scales are thicker, get silvery on rubbing, and bleed on lifting). Pityriasis rosea: herald patch; oval red lesions with scaly edge, eg on trunk. \200 Eryth ema chronicum migrans ( \201 g 3). See p588. \200 Impetigo: well-de \201 ned red patche s, covered with honey-colored crust, \201 g 6. Linear lesions \200 K bner phenomenon: psoriasis, lichen planus. \200 Dermatitis artefacta: linear or bizarre-shaped lesions, in duced by patient. \200 Herpes zoster: polymorphous vesicles/pustules in dermatomal distri bution. \200 Scabies burrows ( \201 g 8, the mite is visible as a speck just above the r ed area). \200 Cutaneous larval migrans ( \201 g 4), eg from strongyloidiasis (OHCM p442 ). Subcutaneous nodules Rheumatoid nodules, rheumatic fever, PAN, xanthe- lasma, tuberous s clerosis, neuro \201 broma, sarcoidosis, granuloma annulare. Itch (pruritus) \200\207Itch can be very distressing. Skin will usually be scratched or rubbed and a number of secondar y skin signs are seen: excoriations (scratch marks); licheni \201 cation (skin thickening, \201 g 1 on p585); papules or nodules (lo- cal skin thickening). Causes: Dry (and older) skin tends to itch. Determine if there is a primary skin disease or is itch due to systemi c disease. \200 Itchy lesions: scabies (burrows in \201 nger-webs, wrists, groin, butto ck); urti- caria (transient wheals, dermatographism); atopic eczema ( \202 exural eruption , licheni \201 cation, \201 g 1 on p596); dermatitis herpetiformis (very itchy blisters on elbows, shoulders); lichen planus ( \202 at violet wrist papules). \200 In 22%, itch is caused by a systemic disease: 19 Fe \200\201 (koilonychia, pale); lym- phoma (nodes, he patosplenomegaly); hypo/hyperthyroidism; liver disease (jaundice, spider naevi); chronic re nal failure (dry sallow skin); malignancy (clubbing, masses); drugs. Do FBC, ESR, ferritin, LFT, U&E, glucose, TSH, CXR. Treatment: Treat any primary disease; bland emollients (eg Diprobase ) to soothe dry skin; emollient bath oils; sedative antihistamines at night. Lentigos are brown macules/patch- es. Some are premalignant. Fig 2: lentigo maligna (melano ma in situ) \200\224 precursor to invasive lentigo maligna melanoma. Typical patient: Cauca sian >40yrs. It develops in sun-damaged skin. It is \202 at, irregular, and variably pigm ented (darker areas may be in- vasive). Not all show ABCDE signs of malignancy.1 Use dermos copes2 biopsy in equivocal lesions. 20 Excision is best (>5mm margins); if impos- sible, try radiotherapy or topical 5% imiquimod \211\210 5/wk (typical time to clear: 9 wks; do repeated biopsy over the next years 21 to spot dangerously common occult recurrence). 22 587 y g o o t a m r e D l Fig 2. Lentigo maligna. Dr Suzannah Baron. Fig 3. Erythema chronicum migrans. Fig 4. Cutaneous larval migrans. Courtesy of Dr Jonathan Bowling. Courtesy of Dr Jonathan Bowling. Fig 5. Discoid/nummular eczema (p602). Fig 6. Impetigo (honey-colored crusts). Dr Jonathan Bowling (& \201 gs 7 & 8). Courtesy of Dr Samuel Da Silva. Fig 7. Bowen \200\231s disease. Fig 8. Scabies burrow (and mite, top). 1 A for asymmetry; B for border irregularity; C for color (non-uniform browns, blacks, reds , whites, or blues); D for diameter >6mm; E for evolving over time.23 2 The dermoscope is a battery-operated handheld microscope-like instrument using epiluminescence for evaluating pigmented skin lesions. It allows vision through the stratum corneum.24 Skin signs of systemic disease Diabetes Flexural candidiasis; necrobiosis lipoidica (waxy, shiny red/brown plaques, then atrophic/yellow, on shins. \200 : \200 \211\2103:1); follic ulitis; skin infections. Coeliac disease Dermatitis herpetiformis (very itchy/ \200\234burn ing \200\235 blisters on el- bows, scalp, shoulders, ankles). Treatment: long-term gluten-f ree diet. 25,26 It responds quickly to dapsone (50 \200\223200mg/day PO). SE: haemolysis, L FT \200\200, agranu- locytosis. CI: G6PD de \201 ciency. Small risk of lymphoma in chronic disease. 27 In \202 ammatory bowel disease \200 Erythema nodosum (tender ill-de \201 n ed sub- cutaneous nodules, eg on shins; other causes: sarcoidosis, drugs, TB, streps) \200 Pyoderma gangrenosum: recurring nodulo-pustular ulcers, 10cm wide, with tender red/blue overhanging necrotic edge, healing with cribriform (pitted) scars. Site: eg leg; abdomen; f ace. Other causes: autoimmune hepatitis; neo- plasia; Wegener \200\231s \202\223; myeloma. \200 : \200 >1 : 1. Rheumatoid arthritis (RA) Rheumatoid nodules; vasculitis (nodular pur pura, with ulcers). Systemic lupus erythematosus (SLE) OHCM p556. Facial butter \202 y ras h; pho- tosensitivity (face, dorsum of hands, V of neck); red scaly rash; diffuse alope- ci a. \201\231 : Autoantibodies; skin biopsy with immuno \202 uorescence. Erythema multiform e ( \201 g 2) Minor form: Target lesions, usually on extensor surfaces esp. of peripheries , palms, and soles. Major syndrome/toxic form: epidermal necrolysis, p601) associated with systemic upset, fever, severe mucosal involve- ment, including conjunctivae. Cause: Herpes simplex (70%);1 mycoplasma; viruses (minor form); drugs esp. sulfonamides, pen icillins (ma jor form). \201\227 : Treat the cause; supportive care, steroids (controversial; may \200 \200 mortality), other immunomodulators. 28 Major complica- tions: Strictures of mucous mem branes, eg with severe eye problems. 29 Erythema migrans ( \201 g 3 p587) We all need to b e good at this rash as it \200\231s the best way to diagnosis Lyme disease, as serology is diffi cult. \200\207 <50% give history of a tick bite. City and rural people have similar risk. A papule becomes a spreading red ring, lasting weeks to months. \201\227: 3wks PO do xycycline 100mg/12h, amoxicillin 500mg/8h, or cefuroxime. 30 Cutaneous vasculitis (capillar itis/venulitis/arteriolitis) Signs: Variable, eg palpable purpura, eg on legs; nodules; ulc ers; livedo reticularis. Causes: idio- pathic (often); thiazides; neoplasia; systemic vascu litis, eg polyarteritis nodosa (PAN), Henoch \200\223Sch nlein purpura (vasculitic rash on legs/buttocks arthral- gia, abdominal pain and glomerulonephritis); Wegener \200\231s \202\223 granulomatosis. Livedo reticularis ( \201 g 3) Non-blanching vague persistenting, red/blue zig-zags enclosing more normal skin, like diamond-shaped holes in a net, eg on le gs (reticulum is latin for net). Causes/triggers: cold, pregnancy; RA; SLE; lymph oma; PAN; TB; polymyositis; Raynaud \200\231s; Sneddon \200\231s cerebral infarction; (cryoglobulins ; sticky platelets; Ca2+ \200\200; intra-arterial injection; cholesterol emboli; homocystin uria). \200 : \200 >1:1 \201\227: Treat cause bath PUVA. 31 1 Erythema multiforme may be precipitated by orolabial and genital herpes recurrences and by recur- rences on buttoc ks and other sites. Episodes of erythema multiforme are not always associated with clinical herpetic recurrences. Herpes-associated erythema multiforme can be controlled by continuou s oral aciclovir; it is not prevented by aciclovir if a herpes simplex recurrence is presen t or just passed.32 588 y g o o t a m r e D l (Stevens \200\223Johnson Fig 2. Erythema multiforme. Fig 3. Livedo reticularis. Connective tissue and related diseases and the skin Lupus erythematosus (LE): 5 types of sk in change: 1) Chilblain LE: Cryoglob- ulin/cold agglutinin \200\223ve; \200\224: antimala rials, steroids, pentoxifylline, or dapsone. 33 2) Chronic cutaneous (discoid) LE: In \202 amed plaques + scarring atrophy; may respond to: \200\201sun exposure, topical steroid s, antimalarials (hydroxychloroquine). 3) Subacute cutaneous LE: Widespread, non-scarring r ound or psoriasis-like plaques in photodistribution. ANA or Ro/La +ve. 4) Acute systemic lu pus erythematosus (SLE): Speci \201 c malar induration forming butter \202 y rash or wide spread indurated erythema on upper trunk. 5) Non-speci \201 c cutaneous LE phenomenon: Vas culitis, alopecia, oral ulcers, palmar erythema, periungual erythema, Raynaud \200\231s phe nomenon. CREST: Scleroderma1/morphea with: calcinosis cutis; Raynaud \200\231s; oesopha- ge al dysmotility; sclerodactyly; telangiectasia. Typically anti-centromere +ve. Sarcoidosis ( Hypopigmented areas, waxy deposits; biopsy shows non-case- ating granulomata). Plaques are red/violet, indurated, and shiny, eg on face and extremities. They may become annular in sh ape and the center of the plaque may atrophy. If seen with telangiectasia, use the term ang iolupoid. Lupus pernio ( \201 g 1) (diagnostic of sarcoidosis): chronic sarcoid plaques eg on nose, ears, lips, and cheeks permanent scarring. Granulomatous in \201 l- tration o f nasal mucosa and respiratory tract may precede nasal septum destruction. Bulbous, sau- sa ge-shaped \201 ngers signify underlying bone cysts. \201\227: Alefacept (T-cell inhibito r) may be eff ective. 34 Darier \200\223Roussy subcutaneous nodules may be seen on arms and legs (typically non-tender). Fish-like ichthyosiform sarcoid presents as dark polygonal sc aly patches on the legs. 35 It may respond to ster- oids. 36 Verruciform (warty) lesions, e rythroderma, oral lesions, nail dystrophy, and scarring alopecia also occur. 37 Paraneoplas tic skin phenomena 38 If a tumor makes transforming growth factor (similar to epidermal gro wth factor and binds the same receptors) distant keratinocytes \202 ourish exces- sively, and a range of proliferative paraneoplastic signs erupt, eg sudden \202 ocks of seborrhe ic keratoses (Leser \200\223Tr lat sign), tripe palms (ridged velvety lesions), and \202 orid cutaneous papillomatosis and acanthosis ni- gricans \200\224symmetrical darkening and velvety skin thickening, most often of axillae, sides of the neck, and groin, seen with ga stric cancer and lymphoma (also: obesity; acromegaly, Cushing \200\231s, DM, and thyroid di sorders). 39 Pruritus (p586) may be paraneoplastic; others (all 6 are rare):2 1 Amyloidosis : Purpura ( \200\230raccoon eyes \200\231 if periorbital, \201 g 1 OHCM p364), macro- glo ssia; low-voltage ECG, nephrosis, carpal tunnel syndrome, neuropathy. Mal ignant associatio ns: myeloma, lymphoma, and endometrial cancer. 40 2 Paraneoplastic pemphigus: An autoimmune mucocutaneous disease as- sociated with lymphoproliferative disorders (eg leukemia); also melano- ma; mesenchymal sarcomas; BCC; bronchogenic carcinoma. 41 Signs: severe oral and co njunctival ulceration resembling Stevens \200\223Johnson \200\231s syndrome. 42 3 Dermatomy ositis: Heliotrope (red/purple) lids; periungual redness; Gottr- on \200\231s papules ( \202 at violet knuckle papules) from lung, breast, ovary, or colon ca. 4 Erythroderma (>50% of skin is too red) eg from lymphoreticular neoplasia. 5 Acquired ichthyosis: Dry scaly sk in; recent onset points to lymphoma or cancer; as one lost soul in denial said: \200\234Pa y no attention to the dry scales that discolor my skin, nor to the way my \202 esh wastes away. \200\235 Dante 589 y g o o t a m r e D l Fig 1. Lupus pernio of the nose. OTM/OUP. Purgatorio 6 Hypertrichosis lanuginosa (An increase in downy lanugo hair); associated with lung, bladd er, gallbladder, rectum, colon, uterus, and breast cancer. \200\200deposition of extracellular matrix in skin. 43 1 Connective tissue disease with chemokine-mediated 2 Ask the lab to characterize paraneopl astic antibodies (eg anti-Hu) from lung cancer (OHCM p539). Skin diagnoses not to miss Actinic (solar) keratoses (AK) ( \201 g 3) Pre-malignant crumbl y yellow-white scaly crusts occur on sun-exposed skin from dysplastic intra-epidermal proli f- eration of atypical keratinocytes. UK prevalence: If 40yrs old, 21%; if 70yrs old, 52%. Natural history: May regress/recur. \201\231 \201\231: Bowen \200\231s, psoriasis, seborrh oeic wart, BCC; if in doubt, biopsy. Treatment: See BOX. Prevention: Education; hats; sunsc reens \200\201dietary fat \200\224but enough vitamin A. 44 \200\22346 Basal cell carcin oma (BCC = rodent ulcer) Typical- ly, a pearly nodule with rolled telangiectatic edge on th e face. Metastases are very rare. It is locally destructive (esp. if multinodular). Lesions on the trunk can appear as red scaly plaques with raised smooth edge. Cause: UV exposure m ay induce mu- tations in TP53 tumor-suppressor gene. 47 \201\227: Exci- sion; radiotherapy if a big lesion, eg in the elderly. Cryo curettage can be used if non-critical site; 48 consider imiquimod if super \201 cial.49 Bowen \200\231s disease ( \201 g 4) Slow-growin g red scaly pla- que, eg on shin. Histology: Full-thickness dysplasia/car- cinoma in situ. May progress to squamous cell cancer (esp. if hyperkeratotic). \201\227: Cryo ( \200\2055s ec if on face); topi- cal \202 uorouracil (BOX); photodynamic therapy. 50 Leprosy ( \201 g 5) Rare; suspect in any hypopigmented anesthetic skin lesion. Leukoplakia (p607). Lentig os (p587) Melanoma (p592). Metastatic cancer Skin metastases are uncommon but well recogniz ed in association with carcinomas of breast ( \201 g 6), kidney, and lung. Non-Hodgkin \200\231s lymphoma and leukemia can also metastasize to the skin. Metastases are usually \201 rm, rather in \202 ammatory lesions; often on the scalp or trunk. Mycosis fungoides T he chief skin lymphoma (CD4 helper T-cell). 51 Well-de \201 ned red scaly patches or plaqu es on trunk/limbs. \201\231: Biopsy \201\227: Topical steroids, PUVA (p595; if early 52), electron-beam radiation. Leukaemic phase (Sezary syndrome) is associated with erythroderma and circulating Sezary cells, 53 and deletions on chromosome 10q. 54 5yr survival: 90%; mo st deaths are from sepsis. 55 Paget \200\231s disease of the nipple ( \201 g 7) An itchy, red, scaly, or crusted nipple, from intraductal breast cancer (with a mass in 50%). \201 \231: Biopsy. \201\231 \201\231: Eczema (but ec- zema is bilateral, non-deforming, and wax es and wanes), so \200\207always consider a biopsy in \200\234nipple eczema \200\235. Also consider ultrasound, mammography and sen- tinel node biopsy. Surgery: Mastectomy or le sser surgery radiotherapy. 56 \200\22358 Squamous cell cancer ( \201 g 2, the commonest skin cancer after BCC) A persistently ulcerated or crusted \201 rm irregular lesion ofte n on sun-exposed sites, eg ear; hand dorsum; bald scalp (here it may develop in a pre-exist ing AK, above). Also related to smoking (on lower lip), chronic in \202 ammation, eg venou s leg ulcers, and HPV (eg genital area or pe- riungual, like verrucas, p570). 59 \201\227: Excision. Topical imiquimod or 5FU if super \201 cial. 60 Metastases are rare, but are mo re frequent at some sites, eg the ears. Syphilis Isolated painless genital ulcers (1 chan - cre [ \201 g 8]). Pityriasis rosea-like copper-colored scaly rashes aff ecting trunk, li mbs, palms, and soles (2 syphilis). See OHCM p431. Are other sexually transmitted infecti ons present? 590 y g o o t a m r e D l Fig 1. BCC on the nose. Fig 2. Squamous cell ca. 591 We don \200\231t know which is best; but we do Options in actinic keratoses (AK) know which is cheapest: diclofenac gel. \200 Surgical excision and curettage: Excision of AKs is us ed only if invasive SCC is suspected or recurrent lesions are present. Curettage ( electro -surgery or cryotherapy) has very good cure rates. 61 \200 Cryotherapy: Warn that blister s may form afterwards; they may be burst, repeatedly, with a sterile needle; advise antisep tic cream to prevent infection aspirin for pain (adults). \200 Chemical peeling: It ca n be an alternative for treatment of extensive facial actinic keratoses. Recurrence rate is 25 \200\22335%. 61 \200 Photodynamic therapy: Application of a topical photosensitizer f ollowed by activation by a light source can give long-term prophylaxis for AKs and may \200\201 incidence of AK-related SCC. 61 \200 Fluorouracil (5FU) 5% cream once-daily, wit h this sequence of events: er ythema \200\203vesiculation \200\203erosion \200\203red, sore ulcers \200\203necrosis \200\203he al ing epi- thelialization. This in \202 ammatory resp onse is in pre-actinic lesions: healthy skin is less harmed. Using pulsed therapy (eg with gaps of a week or more) reduces this problem (if severe, 8-hourly Fucibet may help). y g o o t a m r e D l Diclofenac gel (3%) is eff ective (mechanism unknown); used twice daily for 2 months, it is well tolerated. 63,64 N=96 It may be tried on AK intruding on mucosa (eg from the lip \200 \231s vermilion). SE: dry skin; rash. 65 Expect \200\20675% near or com- plete clearance w ithin 90 days in \200\20675% of patients. 66 \200 Imiquimod 5% (3 \211\210weekly for 4wk s to lesions; assess after a 4wk treatment- free gap; repeat once if persisting; allow to s tay on site for 8h, then wash (soap & water). It augments cell mediated immunity by inducin g interferon- \200 . 67,68 SE: itch, \200\230burning \200\231, erythema, erosion, oedema, scabs, \200\231 \202 u-like symptoms. Fig 4. Bowen \200\231s disease. Fig 3. Solar keratosis. Fig 5. Leprosy. Fig 6. Breast cancer metastasis. Fig 8. Primary syphilis chancre. Fig 7. Paget \200\231s disease of nipple. Figs 3 \200\2238 courtesy of Dr Samuel da Silva: www.atlasdermatologico.com.br Moles and melanomas Malignant melanoma ( \201 g 1) \200 : \200 \211\2101 . 3:1. UK incid ence: \211 10:100,000/yr ( \200\200in the last 20yrs by 300% in \200 and 200% in \200 ). 5-yr survival is rising (now >80%). 4% have a family history of melanoma. Mortality: 1 .9:100,000/yr in UK. 69 Risk: UV exposure \200\200; sunburn, fair complexion, many common/d ysplastic moles, +ve family history, old age. 66% are related to BRAF mutations. 70 Early d iagnosis: \200\207Everyone should know what early melanomas look like, and know how to get help. Signs: Most arise in normal skin, a few in dysplas- tic naevi. All changing moles ar e suspect (esp. if edges irregular or color varies). Use a magnify- ing glass. \200\207Exc ise all new irregular black lesions however small 71 and all ABCDE lesions (opposite). \200 \200 : Benign melanocytic lesions; non-melanocytic pig mented lesions, eg seborrhoeic keratoses, common if >50yrs; they feel greasy, and look as if they are stuck on. Benign mo les tend to be <5mm across, with uniform color/shape, but melano- mas are often diff erent shades of brown, black, or blue. If melanomas incite in \202 ammation, pink- reds may appe ar. If immune response is active, areas of regression with dermal scarring appear as gray-w hite. 72,73 They may be nodular or \202 at. Unusual sites: Sole, eye, anus, vagina, palat e.etc Treatment: For any unusual, growing, or chang- ing pigmented lesion, excision biopsy must be considered (with a 1cm margin of normal skin around the lesion for every mm of dept h, up to Fig 1. Melanomas. Dr S Baron. 3cm (there is no evidence for wider excision), so don \200\231t do incisional biopsies for \200\230?melanoma \200\231. Prognosis depends on excision completeness and tumor depth ( \200\230Breslow thickness \200\231 is a major progn ostic sign). If <1mm thick, disease-free 5-yr survival is >75% (if >4mm it \200\231s 50%).1 Metastatic melanoma: Sentinel node mets \211\210 poorer prognosis. 74 Ask an onc- ologist to match molecular analysis of the tumor with the most appropriate agent,2 75 eg pegylated interferon alfa-2b, interleukin 2 cytotoxics 76 (10 \200\22330% respond) or ipilimumab (targets CTLA-4) dacarbazine. 77,78 Slip-slop-slap-seek-slide \200\230Slip on a shirt, slop on sunscreen,3 slap on a hat, seek shade, and slide on sunglasses \200\231 \200\224see BOX. Pigmented naevi/moles 3% of us have \211 2 pigmented naevi at birth and 20 \200\223 50 small naevi as teenagers. Numbers peak before 50yrs. By old age, they are relatively ra re. Most naevi are not pre-malignant. Lesions <5mm across with uniform color and outline do n \200\231t need histology unless they \200\231ve grown or changed. The benign halo naevus occurs most often on the back of young adults. The \200\230white \200\231 halo is not sini ster and results from loss of melanocytes by lymphocyte action. 79 When a prepubertal child \200\230has an obvious melanoma \200\231, the diagnosis may well be a benign Spitz (compo und) naevus with nests of See also SCC (p590) and MCC.4 spindle-shaped melanocytes. 80 592 y g o o t a m r e D l 1 TNM staging is complex; note that melanoma thickness and ulceration not level of invasion are used in the T category (except for T1); the number of metastatic nodes rather than gro ss dimensions is used in the N category; site of distant metastases and LDH \200\200 are us ed in the M category. Stage IIb is thick- ness \211 4mm, node \200\223ve for example; sta ge III is any primary tumor node +ve. 81 2 Various inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) yield high response rates in those harboring BRAF-V600E mutat ions. Mutations in C-kit respond to imatinib. 82 3 Sunsense products are good, eg Sunsens itive SPF50+ (said to be water-resistant for 4h). 4 Compared with melanoma, Merkel cell c ancer occurs in an older people, more often on head & neck, and in a higher %age of men (62 VS 57%). MCC metastasizes more. 10-yr survival is less (18 VS 61%). 83 593 Skin sensitivity to ultraviolet (UV) light We all have a genetic skin type which determines sensitivity to UV. . t e b r e t t e b Skin type Do you burn or tan? I II III IV V VI Those aff ected \200\234I always burn easily, but I never tan \200\235 Caucasians (many Celts) \200\234I always burn, but tan minimally \200\235 \200\234Sometimes I burn; I always tan \200\235 \200\234I rarely burn, and always tan well \200\235 \200\234I rarely burn, and always tan deeply \200\235 Dark-skinned eg Latin, Indian \200\234I never burn, but tan if very expose d \200\235 Black Africans Caucasians Caucasians Caucasians a s i y c a c o v d a - r e e p This helps predict individual susceptibility for development of skin cancers and manifestat ions of photo-ageing. While persons in groups I \200\223II are at highest risk, most skin c ancers cluster in type II & III people: type I people know from experience to stay out of t he sun. How to determine type: 84 \200 When you \201 rst go out in the sun each summer do you sunburn? \200 If so, do you always burn? Easily? Do you ever blister when you burn ? \200 Can you tan? Does it take a long time or do you tan easily? \200 Do you develop a deep tan or just a shade beyond your normal color? Ask about freckles and melanomas (self + family), and past sunbed and sunburn (esp. blistering). \200\234Do you use sun-screens and do skin selfexamina- tion (use mirrors or a friend for hard-to-see areas)? Are your job s/hobbies outdoor? Are you pregnant? \200\235 (expect mole darkening). Is hair red/blond? A re the eyes blue? Note number and type of all moles (examine all over). \200\207Don \200 \231t just diagnose today \200\231s melanoma: prevent tomorrow \200\231s by educat- ing all the family. 85 \200\207Avoid sunbeds and over-exposure (esp. around noon). \200\207Use p rotective clothing/sunscreens3 (may be less good). 86 We often ig- nore advice as sunlight feels good, and tans look good. This is why the fash- ion industry turns out to be a key co -educator. 87 Tailor advice to individual risk. \200\207Those at most risk bene \201 t fr om professional skin exam every 6 \200\2239 months. \200\234Would you like information abo ut harmful eff ects of sunlight? \200\235 When to refer ABCDE: Asymmetric lesions, Border i rregular, Color irreg- ularity, Diameter >6mm, or Evolving over time. Refer if \211 3 \200 \224or if there is a clear spontaneous change in any of A, B, C, or D \200\224or itching, p ain, or bleeding. Sunscreens3 and melanoma prevention The SPF (sun protection factor) indic ates how long an individual can be exposed to sunshine without burning, eg SPF8 means that an individual can stay out in the sun 8 times longer than the time it would normally take t hem to burn. Protection varies depending on skin type (and thickness of application, so SPF 50 \211\210 SPF15 unless plastered on thickly). SPF refers UVB. Many sunscreens contain UV A-block too, graded on a \200\230star-rating \200\231, which as yet, is not internationall y standardized. ; l i a f y g o o t a m r e D o t l d e e t n a r a u g t s o m l a s i e l p o e p g n u o y o t e c i v d a r u o o s \200 e s u o t n i a p a d n a e v i s n e p x e e r a Sunscreens protect by blocking light (eg titanium dioxide) or by absorb- ing light by photochemical reaction (eg benzophenones; cinnamates). 3 melanoma paradoxes: 1 Sunnier European countries have lower mela- noma mortality. 88 2 Occupational sun exposure is unrelated to melanoma risk. 89 3 Sun exposure \200\200 survival from melanoma. 90 Why? One of sunshine \200\231s best eff ects, apart from banishing British gloom, is to \200 \200vitamin D, which has antineoplastic eff ects ( \200\200cell diff erentiation & apoptosi s, and \200\201angiogenesis & metastases). 91 Early deaths from lack of UVB \211\210 22,0 00/yr for white Amer- icans: 92 much more than the 8000 deaths from melanoma. 93 This is du e to fewer deaths from bladder and lung cancer.et al Survival from cancers re \202 ects vi tamin D synthesis which in the UK is \205\223 that at the equator. 94 What does this mean ? Not \200\234Let \200\231s all go down to the beach for noon-time orgies of photosyn- the sis \200\235. Ask instead: \200\234How do we get the bene \201 t without the risk? \200 \235 Diet? Slip- So serum vitamin D levels of 70 \200\223100nmol/L might slop-slap-supple ments? be a reasonable target for melanoma patients (and for everyone else). 89 s t c u d o r p n o i t c e t o r p n u s d n a y x e s e r a s n a T Psoriasis Psoriasis is a chronic in \202 ammatory skin condition aff ecting 2% of Cauca- sians of any age, peaking in the 20s (type 1) and 50s (type 2). \200 : \200 \211\210 1 :1. There are 2 pathologies: epidermal proliferation (with abnormal diff erentiation) and T -cell driven in \202 ammatory in \201 ltration of the dermis and epidermis. TNF- \200 (t umor necrosis factor), activated T cells, macrophages, and dendritic cells play a central r ole in the pathogenesis of psoriasis. 95 In many, psoriasis is pre- ceded by a strep infect ion activating T cells (vaccination might be possible). 96 594 30% have a family member with psoriasis. HLA associations: HLA-CW6, HLA- B13, B17, DR7. If both parents have psoriasis, risk to off spring is 50%. Triggers: Stress, infections (esp. streps), skin trauma (K bner phenomenon), drugs (lith- ium, NSAIDs, \200 -blockers, anti malarials), alcohol, obesity, smoking, and climate. Signs ( \201 gs 1 \200\2234) Symmetric al well-de \201 ned red plaques with silvery scale on ext- ensor aspects of the elbows, kn ees, scalp, and sacrum. Flexures (axillae, groins, submammary areas, and umbilicus) also fr equently aff ected but lesions are non- scaly. Nail changes (in 50%): pitting, onycholysis (separation from nail-bed), thickening and subungual hyperkeratosis. Small plaques (guttate psoriasis) are seen in the young (especially if associated with concurrent streptococcal i nfection). Pustular variants (sterile) can aff ect the palms & soles. 97,98 General- ized ( erythrodermic) psoriasis (and generalized pustular psoriasis) may cause severe systemic ups et (fever, \200\200 WCC, dehydration) \200\224also triggered by rapid with- drawal of syst emic steroids. Other signs: K bner phenomenon (p584); Auspitz sign: pinpoint bleeding on s cale removal; pepper pot nail pitting; \200\230grease-spots \200\231. Systemic signs 7% de velop a seronegative arthropathy \200\2245 types: 1 Monoar- thritis or oligomonoarthritis 2 Psoriatic spondylitis 3 Asymmetrical polyarthri- tis 4 Arthritis mutilans (destructive) 5 Rheumatoid-like polyarthritis. Tests None is routine; histology: epidermal keratinocyte hyp erproliferation, parakeratosis intra-epidermal neutrophil microabscesses (of Munro). 99 \201 \201 Eczema; tinea (solitary or few lesions; asymmetrical; expanding); mycosis fung oides (asymmetric, less scaling, do biopsy); seborrhoeic dermatitis. Management Education i s vital; control, not cure, is realistic. Assess severity and proportion of skin aff ected. Find out what he/she \201 nds most distressing. Encourage a support group (Psoriasis Ass ociation) Remove triggers (above). If mild: Creams are mostly used, eg the vitamin D analog calcipotriol + betamethasone 0.05% (once daily Dovobet ;1 it \200\200quality of life). 1 00 Others: Tar: Messy (esp. ointments \200\224reserve for inpatient use); Alphosyl HC , tw ice daily, is cleaner). Dithranol: Available in creams for use in short-contact regimens (a p- ply carefully to aff ected skin; wash off after h): start at low concentrations (0.1%) ; increase as tolerated (eg 0.25%, 0.5%, 1%). SE: burning (avoid \202 exures); staining ( avoid on face). Tacalcitol may be applied once daily before going to bed (max 5g/day, and o nly up to two 12-week courses/yr). For \202 exural disease, topical steroid/antibiotic/an tifungal preparations can be useful (Trimovate ). Psoriatic arthropathy: 2 Consider etaner cept, in \202 iximab, 101 or methotrexate. 102 Moderate to severe psoriasis: Risk:bene \201 t ratio seems most favorable for Goeckerman PUVA (see BOX), followed by etanercept or adalimumab (BOX). 103 y g o o t a m r e D l Fig 1. Psoriasis aff ecting the nails. Courtesy of Dr J Bowling. \201\201 Recalcitrant psoriasis1 Be holistic! This is a biological as well as a social inj unction. 60% of patients with psoriasis are depressed. Cytokine levels correlate with depre ssion and TNF antagonists (below) directly reduce depressive symptoms in psoriasis. 104 Taz arotene (once daily topical retinoid): for mild/moderate psoriasis af- fecting <10% skin su rface. Avoid in pregnancy. Wash hands after use. Avoid contact with eyes, face, intertrigin ous areas, hair-covered scalp, in \202 amed skin; avoid exposure to UV light/PUVA etc. Don \200\231t use emollients or cosmetics within 1h of use. NB: clobetasol 0.05% cream was bet ter in one trial. 105 595 Phototherapy with a selective broadband ultraviolet (UV) source with lit- tle emission <290 nanometres is less photocarcinogenic than narrowband UVB; 106 avoid if history of photosen sitivity; most suitable for guttate/small plaque psoriasis. PUVA: UVA + oral/topical psoral en; suitable for extensive large plaque disease (oral psoralen) and localized psoriasis (to pical pso- ralen); limit total dose to 1000J/150 treatments to avoid undue skin ageing and risk of skin cancer (esp. squamous cell carcinoma); can be combined with oral retinoids (re -PUVA) to \200\201light dose needed to clear lesions. Goeckerman regimen: hospital day-bas ed \200\224 for 3 weeks with coal tar applied once or twice daily then washed off before t otal body UVB (then shower to wash off scales). Non-biologic oral drugs Severe psoriasis of ten needs oral drugs (get help). \200 Methotrexate 10 \200\22320mg/week PO; most useful i n elderly patients; avoid if \200\235 . s u o i g a t n o c m \200\231 I y g o o t a m r e D l s k n i h t e h t c e p x e young in view of long-term risk of hepatic \201 brosis. Monitor FBC & LFT. \200 Ciclosp orin: 2.5 \200\2235mg/kg/day PO; good, but SE bad (BP \200\200; renal dysfunction). \200 Acitretin: Oral retinoid; useful for moderate/severe disease; SE: teratogen- ic; dry skin a nd mucosae; \200\200lipids; glucose \200\200; \200\200LFT (reversible). Check lipids, glu cose, LFT at start, then every 2wks for 8wks, then every 12wks. In the UK, use is limited t o hospitals. Starting at 25 \200\22330mg/24h PO; typical mainte- nance: 25 \200\22350mg/day ; adjust according to response. Exclude pregnancy, and avoid donating blood for >1yr and pr egnancy until >2yrs after the last dose. \200 Hydroxycarbamide: 0.5 \200\2231.5g/24h PO. SE: marrow suppression. 107 Biological drugs inhibit T-cell activation and function, or neu tralize cyto- kines. They also can potentially \200\201 adverse systemic side eff ects bec ause of their high speci \201 city for pathogenic cells without aff ecting cells of other or- gans. 95 If psoriasis hasn \200\231t improved eg with ciclosporin, methotrexate and PUV A or these have had side eff ects, consider ustekinumab or etanercept (eg 25mg SC, twice we ekly for \211 24wks). 108 This tumor necrosis factor (TNF- \200 ) inhibitor can also help joints in psoriatic arthropathy (and \200\201radiographic pro- gression). 109 It is usuall y well tolerated. SE: vomiting, oesophagitis, cholecysti- tis, pancreatitis, GI bleeds, isc haemia, emboli, BP \200\200 \200\201, dyspnoea, demyelination, seizures. Specialist use on ly. Alternatives: in \202 iximab, adalimumab. \200 110 I e m t a g n i r a t s s p e e k e H : d e z i t a m g i t s l e e f I \200\234 Fig 2. Onycholysis. Nail pit- ting may also be present. Fig 4. Psoriasis of elbow. Fig 3. Plaques on hand. Figs 2, 3, & 4 Dr S Baron. 1 In stable plaque psoriasis, apply Dovobet to <30% of body surface for \211 4wks; max 1 5g/day or 100gwk; repeat if needed after \211 4wks. Avoid face, genitals and scalp. Dermov ate shampoo can help the scalp. 2 Psoriatic arthropathy may signify endothelial dysfuncti on and impaired coronary microcirculation, so consider a vigorous approach to controlling c ardiovascular risk factors. 111 Eczema (dermatitis) Acute eczema causes a rash with less scale and less demarcated than pso ria- sis. Eczema may be atopic, hypersensitive (type VI), or be caused by irritants or veno us stasis. See also discoid eczema (p602 & \201 g 5, p586). Diff erent types may co-exist . Ask about work, hobbies, and other exposures to allergens. Atopic eczema ( \201 g 1) Cau ses: Multifactorial: Genetic: A family history of atopy is common (70%); Overactive TH2 lym phocytes produce IL4 & IL5, stimulating IgE production. Infection: Staphs colonize lesions and toxins act as a superantigen. Allergens: \200\200IgE is common. RAST (radioallergo- so rbent testing) identi \201 es speci \201 c antigens, eg house dust mite or animal dander. Altered microbial exposure may have a role (probiotics improve this, see BOX). Diet: Some atopic chil- dren have food allergies, eg dairy products egg Fig 1. Atopic eczema. Dr S Baron which exacerbate eczema. Although infantile eczema is common ( 2% of UK infants), m ost grow out of it before 13yrs old. \201\227: \200 Management involves control, not cur e. Dry skin itches and is susceptible to irritants, so use emollients liberally, even when eczema is less active. They treat dryness and act as a barrier. Ditto for bath emollients, eg Oilatum or Aveeno (oat oils). Use soap substitutes such as emulsifying ointment. 596 y g o o t a m r e D l