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AD_HTT_O25_032___FEB24_06 20/2/06 2:45 PM Page 25 How to treat w w w. a u s t r a l i a n d o c t o r. c o m . a u Pull-out section Earn CPD points on page 32 Complete How to Treat quizzes online (www.australiandoctor.com.au/cpd) or in every issue. inside Hyperpigmentation Hypopigmentation Vitiligo and rarer causes of depigmentation Case studies The author Disorders of DR ALEX CHAMBERLAIN, visiting dermatologist at The Alfred and Royal Children’s hospitals, and in private practice in Armadale, Caulfield and Hawthorn, Victoria. PIGMENTATION Background THE main determinant of skin colour across races is melanocyte activity, not density. Melanocytes, which are derived from the neural crest and scattered evenly across the basal layer of the epidermis and outer root sheath of the hair follicle, are principally responsible for melanin production. Originally synthesised from the amino acid tyrosine, melanin is transferred to neighbouring keratinocytes by long dendritic processes extending from each melanocyte. The organelles within melanocytes containing melanin are known as melanosomes. In dark skin, melano- does not imply that patients who don’t take NORVASC will have an MI. Before prescribing, please review Approved Product Information and PBS Information in the primary ad in this publication. Full Approved PI is available on request from Pfizer. Pfizer Australia Pty some size and number are much greater compared with in fair skin. The key factors that regulate melanin production include certain growth factors (basic fibroblast growth factor and endothelin-1), melanocyte-stimulating hormone and ultraviolet light. The key immunohistochemical stain for defining melanocytes within skin is S-100. Disorders of pigmentation are generally divided into those characterised by hyperpigmentation, hypopigmentation or depigmentation. Occasionally all three phases may be seen in the one disease process (eg, trichrome vitiligo). However, not all alterations in skin colour are due to disturbances in melanin. Cutaneous vascularity also contributes to skin colour, and other pigments such as carotene, haemosiderin and heavy metals may also affect skin colour. Occasionally accumulated dirt and grime on skin may masquerade as a pigmentary disturbance (terra firma forme dermatosis). While affected patients are seemingly unaware of the cause, the ‘dirty keratin’ is easily wiped clean with an alcohol wipe. When assessing pigmentary disorders the age of onset, presence of a preceding rash or insult, and pattern and distribution of pigment change can generally help define the precise diagnosis. Few bedside tools are required when assessing pigmentary disorders, except for a Wood’s lamp and a dermatoscope. The Wood’s lamp, which emits long-wave UV light (or black light), is particularly useful for accentuating epidermal pigment when used in a dark room. The dermatoscope, an illuminated hand-held magnifying tool, is equally invaluable in the assessment of melanocytic lesions such as lentigines, naevi and melanoma. †‘Ignorvasc’ ignorvasc † Ltd, ABN 50 008 422 348, 38–42 Wharf Road, West Ryde, NSW 2114. (amlodipine besylate/Pfizer) *Registered Trademark Pfizer Inc. 09/04 PFXNO5638 * www.australiandoctor.com.au 24 February 2006 | Australian Doctor | 25 AD_HTT_O25_032___FEB24_06 20/2/06 2:45 PM Page 26 How to treat – disorders of pigmentation Hyperpigmentation TABLE 1 summarises the causes of hyperpigmentation. Patterns of hyperpigmentation can include diffuse, circumscribed, reticulate and rippled forms (table 2). Figure 1: Café-au-lait macule. Café-au-lait macules Café-au-lait macules affect about 25% of the population. Their significance lies in their occasional association with a variety of multisystem genodermatoses (or genetic skin disorders). Generally, they are readily recognisable as well circumscribed, coffee-coloured macules that are usually present from birth. They vary in size, extending up to several centimetres in diameter (figure 1) and may be multiple in otherwise normal patients. Pigment laser (Qswitched Nd:YAG) offers clearance in about 50% of cases when cosmetic treatment is requested. These lesions may be associated with specific conditions such as: ■ Neurofibromatosis: patients with neurofibromatosis type 1 typically have six or more café-au-lait macules, axillary freckling and large numbers of neurofibromas. They are prone to CNS and other soft tissue malignancies (figure 2). ■ McCune-Albright syndrome: patients typically have a large segmental café-au-lait macule (with a jagged geographical border), underlying osseous dysplasia and various endocrine abnormalities such as thyroid disease and precocious puberty. ■ Tuberous sclerosis: these patients have café-au-lait macules associated with hypopigmentation (ashleaf, polygonal and confetti-shaped morphology), connective tissue naevi and various tumours (see under Hypopigmentation). They are at risk of seizures and mental retardation. Figure 2: Multiple café au lait macules in type 1 neurofibromatosis. Table 1: Causes of hyperpigmentation ■ Genetic — pigmentary mosaicism, incontinentia pigmenti, café-au-lait macules ■ Infective — pityriasis versicolor, HIV ■ Solar — poikiloderma of Civatte, melasma, lentigines ■ Metabolic — endocrinopathies, acanthosis nigricans, amyloid, haemochromatosis ■ Drugs — see table 5, page 28 ■ Physical — erythema ab igne ■ Neoplastic — melanoma, mastocytosis Table 2: Patterns of hyperpigmentation ■ Diffuse — drug-related, endocrinopathies, haemochromatosis, HIV, melanoma ■ Circumscribed — melasma, acanthosis nigricans, post-inflammatory, fixed drug eruption, café-au-lait macules, mastocytosis, diabetic dermopathy, pityriasis versicolor ■ Reticulate — poikiloderma of Civatte, erythema ab igne ■ Rippled — macular amyloid, lichen amyloidosis ■ Blaschkoid — pigmentary mosaicism, incontinentia pigmenti Common bleaching agents include 2-4% hydroquinone cream, (with or without 0.05% tretinoin) and 1% hydrocortisone. The major risk with higher-strength hydroquinone preparations is paradoxical and irreversible exogenous pigmentation known as ochronosis. Irritant and allergic contact dermatitis may also occur so it is advisable to test the product on a small area of skin (eg, behind the ear) before starting long-term therapy. Kojic acid, glycolic acid or azelaic acid preparations may also be of benefit. Superficial peels (50-70% glycolic acid or Jessner’s solution) may also be valuable in treating melasma in people with fairer skin, but laser has little therapeutic role and runs a significant risk of postinflammatory pigmentation. Poikiloderma of Civatte Agent Brand name HQ 2% salicylic acid 1.5% John Plunkett’s Superfade cream Poikiloderma refers to the combination of atrophy, telangiectasia, and reticulate hyper- and hypopigmentation. Poikiloderma of Civatte specifically refers to this appearance on the lateral aspects (figure 5) and ‘V’ of the neck, seen frequently in fairer-skinned people living in sunny climates. Photodynamic substances in fragrance may also play a role in the development of this condition. Treatment includes strict daily photoprotection, bleaching creams (table 4) for prominent hyperpigmentation, and multiple treatments with vascular laser or intense pulsed light for telangiectasia. HQ 3-5% in aqueous cream Compounded extemporaneously Pigmentary mosaicism HQ 5%/tretinoin 0.1%/HC 1% cream Compounded extemporaneously HQ 4-5% in tretinoin 0.025-0.05% Compounded with Retin-A, Stieva-A or Retrieve Lentiginoses Tretinoin 0.01% Retin-A gel Solar lentigines are small, discrete, irregularly shaped and uniformly brown macules, usually measuring 1cm or less in diameter (figure 3), that are often found on the upper back, forearms and hands of sundamaged Australians, particularly those who are fair-skinned. Unlike freckles (or ephelides) they are constant and do not fluctuate with sun exposure. They are often referred to by patients as age or liver spots but sun spots would be a more accurate term. An intensely black solar lentigo is referred to as an ink-spot lentigo and is no more dangerous than its lighter counterpart. Occasionally, large numbers of lentigines occur in association with an underlying genodermatosis such as PeutzJeghers syndrome, leopard syndrome, Carney complex or xeroderma pigmentosum (table 3). Solar lentigines may respond to light cryotherapy, topical tretinoin or pigment laser (Q-switched Nd:YAG). Tretinoin 0.025% Stieva-A cream Melasma Melasma (or chloasma) is a common acquired form of hyperpigmentation occurring symmetrically on sunexposed sites such as the forehead, bridge of the nose, upper lip and cheeks (figure 4). Women with darker skin are 26 | Australian Doctor | 24 February 2006 Table 3: Features of syndromic lentiginoses Peutz-Jeghers syndrome Perioral lentigines and GI polyposis with low malignant potential Figure 3: Biopsy-proven solar lentigo chest (a biopsy was performed because of the size and variegation in colour). Leopard syndrome Lentigines, ECG abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, growth retardation and deafness Carney complex Lentigines, blue naevi, ephelides and atrial myxomas Xeroderma pigmentosum Accelerated sun damage and aggressive skin cancers at a young age Table 4: Locally available depigmenting agents Figure 4: Melasma of the cheek. Figure 5: Poikiloderma of Civatte lateral neck. Figure 6: Naevoid pigmentary disorder. (Image courtesy of Dr Maureen Rogers, Children’s Hospital, Westmead, NSW.) Tretinoin 0.05% Stieva-A, Retin-A or Retrieve creams Tretinoin 0.1% Stieva-A forte cream Glycolic acid 10%/ HQ 2% Neostrata fading gel PHA 10%/HQ 2%/ kojic acid 3%/ licorice extract NeoCeuticals HQ skin lightening gel Azelaic acid 15% Finacea gel (Intendis) Azelaic acid 20% Skinoren cream (Schering) Arbutin 5%/ kojic acid 2% Skinceuticals Phyto+ Bearberry & licorice extracts with salicylic acid Naturopathica Fade-Away pigmentation lotion Ascorbic acid Cellex-C Fade Away gel Mulberry extract & ascorbic acid Neo Cosmetics whitening process cream HQ = hydroquinone; HC = hydrocortisone; PHA = polyhydroxy acids most prone and key aetiological factors include sunlight and oestrogens. Melasma is sometimes referred to as the ‘mask of pregnancy’. Treatment includes withdrawal of exogenous oestrogens (when possible), strict photoprotection and use of bleaching agents (table 4). Treatment is usually required for at least six months, and in most cases longer than 12 months. The condition may recur with further exposure to sun or oestrogen. www.australiandoctor.com.au Blaschko’s lines refer to a pattern assumed by many different naevoid and acquired skin diseases, probably determined by the migration of skin cells during embryogenesis. These are characterised by whorled patterning and a sharp midline cut-off (figure 6) and are different to dermatomes, Langer’s lines, Voigt’s lines and embryonic clefts. A variety of genetic defects (primarily chromosomal) account for the wide range of naevoid pigmentary disorders that manifest as blaschkoid hyperpigmentation, hypopigmentation or an admixture of both. At a cellular level two populations of cells existing within the skin (mosaicism) are responsible for the striking patterning in pigmentation. These disorders have previously been designated ‘linear and whorled hypermelanosis’ or ‘hypomelanosis of Ito’, but these terms are best avoided as they do not refer to any single entity. When the disturbance is widespread, associated ocular, neurological or skeletal abnormalities must be considered. However, in most patients there are no other abnormalities. Treatment of these bizarre pigmentary disorders is limited to cosmetic camouflage. Importantly, karyotyping of blood and skin, if necessary to detect mosaicism, is advocated in all patients presenting with blaschkoid pigmentary changes (either hyperpigmentation or hypopigmentation). cont’d page 28 AD_HTT_O25_032___FEB24_06 20/2/06 2:46 PM Page 28 How to treat – disorders of pigmentation from page 26 Incontinentia pigmenti Incontinentia pigmenti is an important genodermatosis with characteristic blaschkoid hyperpigmentation and ultimately hypopigmentation after preceding vesicular and verrucous phases. The inheritance of incontinentia pigmenti is X-linked dominant, with only females affected. The genetic basis is a mutation in the NEMO (nuclear factor-κβ essential modulator) gene. A range of other systems may be affected, including the dental, ocular, skeletal and neurological systems and the hair and nails, so multidisciplinary assessment is often required. Figure 7: Axillary acanthosis nigricans. (Image courtesy of Dr Adrian Mar, Monash Medical Centre, Clayton, Victoria.) Figure 8: Pretibial diabetic dermopathy. Hyperpigmentation due to metabolic disease Endocrine or metabolic disorders such as Addison’s disease, Cushing’s disease, acromegaly, carcinoid syndrome, hyperthyroidism and porphyria cutanea tarda can cause diffuse hyperpigmentation, with accentuation over flexures and pressure points. These conditions should be considered when there is no apparent drug cause. Other conditions causing hyperpigmentation include: ■ Haemochromatosis — a unique bronzed (brown-grey or sometimes blue-grey) appearance associated with glucose intolerance and iron overload. ■ Acanthosis nigricans, which is associated with insulin resistance and causes hyperpigmentation and thickened velvety skin (figure 7). It can be treated with weight loss, topical calcipotriol (Daivonex), metformin or ablative laser. ■ Paraneoplastic acanthosis nigricans — this occurs in GIT adenocarcinoma and should be considered in adults over 50 when hyperpigmentation is rapid and involves mucosal surfaces. ■ Diabetic dermopathy, which presents as pigmented atrophic plaques on the shins (figure 8) and is thought to be due to diabetic microangiopathy and repetitive trivial trauma. ■ Primary cutaneous amyloidosis, which has a unique rippled hyperpigmented appearance and is not associated with plasma cell dyscrasias. Lichen amyloidosis shares some similarities with lichen simplex and is seen most commonly on the shins of people of Asian descent (figure 9). Macular amyloid tends to affect the central back and is probably a response to rubbing and scratching. Drug Features Amiodarone Slate grey (blue-grey); face and sun-exposed skin Antimalarials Yellow-brown to blue-black; face, mucosae and legs Bleomycin Linear and flagellate; sites of scratching Carotene Yellow-orange; palmoplantar skin most conspicuous Chlorpromazine Slate grey; sun-exposed skin Chemotherapy Brown-grey; diffuse, including mucosae and nails Clofazamine Red-brown to purple; lesional skin most affected Dioxins Brown with associated chloracne; sun-exposed skin Heavy metals See ‘Drug-induced hyperpigmentation’, below Minocycline Brown-grey to blue-black; scars, mucosae and legs (figure 10) Oral contraceptive pill Melasma Phenytoin Melasma and acquired acromelanosis Psoralens Enhanced tanning in conjunction with UVA (PUVA) Thiazides Brown-grey; sun-exposed skin Zidovudine Blue-grey; diffuse, including mucosae and nails Figure 12: Erythema ab igne. (Image courtesy of department of dermatology, Alfred Hospital, Prahran, Victoria.) Figure 13: Urticaria pigmentosa. (Image courtesy of department of dermatology, Alfred Hospital, Prahran, Victoria.) Figure 9: Pretibial lichen amyloidosis. (Image courtesy of the department of dermatology, Alfred Hospital, Prahran, Victoria.) Response to bleaching agents takes time and patience: it is also prudent to treat a test area before committing to larger regions. Figure 10: Minocycline pigmentation lower limbs. (Image courtesy of department of dermatology, Alfred Hospital, Prahran, Victoria.) Figure 11: Fixed drug eruption. Drug-induced hyperpigmentation Skin hyperpigmentation is associated with a large number of drugs (table 5). It is primarily due to increased melanin concentration but 28 Table 5: Drugs causing pigmentation and specific features | Australian Doctor | 24 February 2006 may also be due to deposition of exogenous pigment. This type of photosensitivity, which is often blue-grey and on sun-exposed sites, occurs with amiodarone, phenothiazines, thiazides, certain cytotoxics and heavy metals. Resolution can occur after the drug is stopped but may take years. Pigment laser (Qswitched group, eg, Nd:YAG, Ruby, Alexandrite) may help in selected cases. Heavy metals can cause curious patterns of blue-grey pigmentation. Silver exposure (or argyria) can cause diffuse slate-grey pigmentation (particularly on sunexposed skin) with mucosal involvement. Lead exposure causes permanent mucosal (particularly ocular and gingival) and nail pigmentation. An unusual form of drugrelated pigmentation is the fixed drug eruption, which typically occurs within 24 hours of drug ingestion. The rash recurs and is usually seen on the hands, feet and around the mouth or on the glans penis. It is characterised by burning or itch followed by an oval inflammatory plaque that resolves, leaving pigmentation (figure 11). The plaques may multiply with further exposure to the drug. Possible triggers include antibiotics, NSAIDs, gold, codeine and the oral contraceptive pill. www.australiandoctor.com.au HIV/AIDS Diffuse Addisonian-like pigmentation of skin, mucosae and nails can occur in HIV infection, for unknown reasons. Erythema ab igne Erythema ab igne is a distinctive, reticular, telangiectatic pigmented dermatosis that occurs in response to chronic infrared radiation exposure. The most classic site of involvement is the lower legs (figure 12) or back. A typical patient will give a history of exposure to heat at close range from open fires, portable heaters under desks or hot water bottles. The clinician should consider hypothyroidism in patients with this condition, which may present as cold intolerance. The major differential diagnosis is livedo reticularis. Paraneoplastic hyperpigmentation Very rarely, patients with advanced metastatic melanoma develop diffuse bluegrey hyperpigmentation due to dermal melanin. Dark urine (melanogenuria) often coexists and is usually preterminal. Mastocytosis Mastocytosis is a reactive disorder of mast cells characterised by multisystem infiltration and a benign course in young patients. The most common subtype, urticaria pigmentosa, features widespread redbrown papules and plaques (figure 13) that urticate on rubbing (Darier’s sign), and may be mistaken for melanocytic naevi in adultonset mastocytosis. Patients often complain of pruritus, and an elevated serum tryptase level helps in reaching the diagnosis. Treatment is symptomatic using topical corticosteroids, antihistamines, oral sodium cromoglycate (Nalcrom), which is available through the Special Access Scheme, and phototherapy, but pigmentation often persists. More recently, imatinib (Glivec), a tyrosine kinase inhibitor, has shown promise in treatment of systemic mastocytosis. Post-inflammatory hyperpigmentation All severe inflammatory dermatoses are prone to leaving post-inflammatory hyperpigmentation or staining in people with darker skin. Antecedents include: ■ Acne. ■ Superficial burns. ■ Insect bites. ■ Contact dermatitis. ■ Lichen planus. ■ Discoid lupus erythematosus. Disorders featuring apoptotic damage at the dermoepidermal interface, such as lichen planus, are especially vulnerable to pigmentation. Although slow resolution over months to years is usual, some patients have persistent dermal pigmentation. If the pigment is epidermal (enhances under Wood’s lamp), bleaching agents, superficial peels and strict photoprotection may help. Dermal pigment sometimes responds to pigment laser but should only be considered in severe disabling cases because laser treatment may trigger further pigmentation. Treatment principles Treat any active skin or systemic disease first, then emphasise the importance of strict photoprotection with physical measures (shade and hats with a broad brim) plus broad-spectrum anti-UVA and UVB sunscreens applied frequently. Response to bleaching agents takes time and patience: it is also prudent to treat a test area before committing to larger regions. Superficial chemical peels benefit epidermal pigmentation, such as melasma and freckling. Pigment laser or intense pulsed light have a limited role in treating superficial pigment and pose the real risk of aggravating the problem. For many patients cosmetic camouflage is the most realistic treatment. Pityriasis versicolor See next section. AD_HTT_O25_032___FEB24_06 20/2/06 2:46 PM Page 29 Hypopigmentation HYPOPIGMENTATION generally occurs in a circumscribed fashion (unlike patterns of hyperpigmentation) and may be localised or widespread. Major causes include genetic, infective, inflammatory/autoimmune, solar, chemical, physical and neoplastic processes (table 6). Pityriasis alba Pityriasis alba is the most common cause of facial hypopigmentation presenting to the dermatologist. It is seen most often in prepubertal children and is especially noticeable in those with darker skin. The hypopigmentation of pityriasis alba is poorly defined and frequently lightly scaly and is thought to represent low-grade eczema. Erythema may occur in early lesions. The face is the most common site (figure 14) but it is occasionally seen on the trunk or limbs. Treatment (as for eczema) is with emollients and weak topical corticosteroids, such as 1% hydrocortisone ointment. Permanent resolution generally occurs after puberty. Table 6: Causes of hypopigmentation Genetic — tuberous sclerosis, pigmentary mosaicism, naevus depigmentosus ■ Infective — pityriasis versicolor, leprosy, syphilis ■ Inflammatory — pityriasis alba, lichen sclerosus, psoriasis, discoid lupus, sarcoidosis, pityriasis lichenoides chronica ■ Solar — idiopathic guttate hypomelanosis ■ Chemical — chemical leukoderma ■ Physical — cryotherapy, laser, ionising radiation ■ Neoplastic — cutaneous T-cell lymphoma ■ Figure 14: Pityriasis alba of the face. (Image courtesy of Dr David Orchard, Royal Children’s Hospital, Parkville, Victoria.) Tuberous sclerosis complex Figure 22: Scattered hypopigmentation and connective tissue naevi in tuberous sclerosis. (Image courtesy of Dr Adrian Mar, Monash Medical Centre, Clayton, Victoria.) Figure 15: Hyperpigmented pityriasis versicolor lower back. Figure 16: Hypopigmentation resulting from pityriasis versicolor. Figure 18: Idiopathic guttate hypomelanosis of the outer arm. (Image courtesy of Dr Adrian Mar, Monash Medical Centre, Clayton, Victoria.) Figure 23: Hypopigmentation in psoriasis. (Image courtesy of Dr Maureen Rogers, Children’s Hospital, Westmead, NSW.) Figure 19: Naevus depigmentosus. Figure 24: Hypopigmentation in pityriasis lichenoides chronica. (Image courtesy of Dr Maureen Rogers, Children’s Hospital, Westmead, NSW). Figure 20: Lichen sclerosus. Idiopathic guttate hypomelanosis Idiopathic guttate hypomelanosis is a very common finding on the limbs and especially the outer arms of Australian women (figure 18). It is most obvious in darker-skinned people, especially in older age. The principal lesion is a widely scattered, small hypopigmented macule that does not usually repigment. It can be thought of as a surrogate marker of chronic sun damage. Tanning may accentuate the contrast, and artificial tanning agents may be useful for camouflage. Naevus depigmentosus Naevus depigmentosus, or naevus achromicus, is a common pigmentary abnormality that occurs in more than 1% of the population and typically appears early in life as a solitary area of hypopigmentation with an irregular margin (figure 19). This pigmentary abnormality can also be considered a manifestation of mosaicism (see Pigmentary mosaicism, page 26). Naevus anaemicus, caused by a paucity of cutaneous vasculature, inhibitors, such as pimecrolimus (Elidel), have also been shown to have some effect in small case series. Circumcision should be considered in men and is often curative. The tuberous sclerosis complex is an autosomal dominant genodermatosis comprising hamartomas in the skin (figure 22), CNS, eyes, heart and kidneys. Recognising the various cutaneous features allows diagnosis at an early age, with earlier cosmetic treatment of the facial angiofibromas and screening for tumours. Hypopigmentation is characteristically either ash-leaf, polygonal or confetti-like in shape and the so called ‘ash-leaf macule’ is the earliest pigmentary finding. Fortunately the pigmentary changes are rarely cosmetically significant. Hypomelanosis of Ito Pityriasis versicolor Pityriasis versicolor is a common and often asymptomatic scaly eruption found on the upper trunk and shoulders. It is caused by the lipophilic yeast Malassezia furfur and infections are most common in summer or humid climates. When infection is active, the plaques are lightly scaly — best appreciated by stretching the skin. The colour of pityriasis versicolor is reddish-brown in fair skin (figure 15) and more hypopigmented in darker skin types (figure 16). In the latter, the rash usually resolves leaving hypopigmentation that persists for months. Skin scrapings of Malassezia furfur have a ‘spaghetti and meatballs’ appearance on potassium hydroxide examination (figure 17). Treatment includes topical antifungals as shampoos, foaming solutions or creams. Occasionally the infection may be difficult to clear with topical therapy alone and require combined treatment with oral antifungals such as ketoconazole (Nizoral). Figure 17: Malassezia furfur on KOH microscopy. Figure 21: Abdominal wall morphoea with central hypopigmentation. Hypomelanosis of Ito is another rare example of pigmentary mosaicism, appearing at birth or shortly afterwards. The term is probably best avoided because blaschkoid hypopigmentation occurs in a wide variety of genetic abnormalities (see Pigmentary mosaicism, page 26). Leprosy Leprosy, or Mycobacterium leprae infection, has a broad spectrum of clinical expressions, including hypopigmented macules, patches and plaques. This diagnosis should be considered is cases with unexplained nerve palsies or hypo-anaesthetic skin with lesions, especially patients from developing countries and particularly the Indian subcontinent. Psoriasis A white halo, known as Woronoff’s ring, may surround plaques of psoriasis, particularly after treatment with UV phototherapy or topical therapy. The ring is probably vascular rather than pigmentary in nature. Small-plaque psoriasis in darkskinned patients may be particularly hypopigmented (figure 23) and may masquerade as a primary pigmentary disorder. The white overlying scale (which enhances after scratching the plaques) is the key clue to the diagnosis. Pityriasis lichenoides chronica may also appear as a solitary pale patch but can be distinguished from naevus depigmentosus by compressing the edge with a glass slide (diascopy), which diminishes the demarcation between normal and lesional skin in the former. Naevus anaemicus also has a characteristically vague border, often with a surrounding blush of erythema. Under Wood’s lamp the distinction between hypopigmented and normal skin is accentuated in naevus depigmentosus but lost with naevus anaemicus. Distinguishing between theses two lesions allows a precise diagnosis for the patient, but there is no effective treatment for either. Lichen sclerosus Lichen sclerosus is a chronic inflammatory and possibly autoimmune www.australiandoctor.com.au dermatosis that affects anogenital (most often) and extra-genital skin, seen as porcelain-white and atrophic plaques with follicular plugging and occasional purpura. Genital lichen sclerosus is intensely pruritic and can lead to scarring and architectural distortion of the vulva in women or phimosis in men. Secondary squamous cell carcinoma occasionally complicates genital lichen sclerosus and justifies longterm monitoring. Extragenital lichen sclerosus is usually asymptomatic and can occur in a guttate form or coexist with localised scleroderma (morphoea) (figures 20, 21). Management of genital lichen sclerosus includes ultrapotent topical corticosteroids, which have been shown to improve symptoms and signs of the disease. Topical calcineurin Pityriasis lichenoides chronica is an inflammatory skin disorder that sometimes mimics psoriasis. The rash is known to be polymorphic and presents as crops of reddish-brown macules and papules with variable surface scaling, which resolve primarily with hypopigmentation (figure 24). The duration of the eruption is generally weeks to months. For symptomatic cases, treatment includes topical corticosteroids, antibiotics (erythromycin or tetracycline) or phototherapy. Progression to T-cell lymphoma has only been noted rarely. Chronic cutaneous lupus erythematosus Chronic cutaneous lupus includes discoid and subacute forms that both carry a small chance (5% and 15%, respectively) of progression to SLE. Discoid lupus is characterised by cont’d next page 24 February 2006 | Australian Doctor | 29 AD_HTT_O25_032___FEB24_06 20/2/06 2:46 PM Page 30 How to treat – disorders of pigmentation from previous page scaly erythematous plaques with follicular plugging, which ultimately resolve, leaving atrophy, scarring and a mix of hyper- and hypopigmentation (figure 25). The centre of the plaques is usually hypopigmented, with a margin of hyperpigmentation. Although the erythema and scaling respond to treatment (with photoprotection, topical steroids, antimalarials or methotrexate), hypopigmentation is often permanent. Figure 25: A. Hypopigmentation of the right cheek after treatment of discoid lupus erythematosus. B. Hypopigmentation of the hands resulting from subacute cutaneous lupus. (Images courtesy of Dr Adrian Mar, Monash Medical Centre, Clayton, Victoria.) B A Chemical leukoderma Physical factors Chemical leukoderma, or contact vitiligo, occurs without preceding inflammation. A large number of chemicals, including hydroquinone, monobenzyl ether of hydroquinone (MBEH), paratertiary butylphenol (PTBP), arsenic, mercurial compounds, azelaic acid and corticosteroids may be responsible. Phototherapy has limited treatment potential. Injury to melanocytes by cryotherapy, laser or radiotherapy often causes persistent hypopigmentation, so cryotherapy is a less suitable therapy in dark-skinned patients. The 1064nm Nd:YAG laser, which is deeply penetrating and less well absorbed by melanin, has less risk of dyspigmentation than other pigment lasers. Syphilis Sarcoidosis Sarcoidosis is a systemic disorder of unknown origin. About onethird of patients have cutaneous manifestations that can present in myriad ways ranging from yellowor red-brown papules, nodules or plaques to infiltrated scars, alopecia, erythroderma, ulcers and panniculitis. Hypopigmentation is an uncommon feature but there is likely to be a link to multisystem disease (most often pulmonary involvement, arthritis or cytopenias) when it does occur. Hypopigmentation may be seen rarely in secondary syphilis, and the diagnosis should be considered whenever a widespread scaly rash involves the palms. Other rare nonvenereal treponematoses such as pinta and yaws may also cause hypopigmentation. Cutaneous T-cell lymphoma Rarely, mycosis fungoides or cutaneous T-cell lymphoma may present as hypopigmented plaques. These are lightly scaly, atrophic and occur more often in darkskinned people. The poikilodermatous variant shows a mixture of hyper- and hypopigmentation (in addition to atrophy and telangiectasia). Vitiligo and rarer causes of depigmentation VITILIGO is an acquired and progressive disorder characterised by macular depigmentation or complete amelanosis, as distinct from disorders characterised by hypopigmentation or partial pigment loss (figure 26). It affects 1-2% of the general population and the cause is likely to be multifactorial and polygenic. In vitiligo, depigmentation is sharply circumscribed and may be induced by trauma to normal skin (the Koebner response). Sites of predilection include the face, axillae, nipples, groin, hands, feet and genitalia, although occasionally vitiligo may be localised in a segmental distribution. Whitening of hairs (leukotrichia, or poliosis) and follicular repigmentation are valuable clues to the diagnosis (figure 27). Vitiligo is frequently stable or slowly progressive over many years. Complete repigmentation is rarely observed. The disfigurement and psychological burden are often greatest in darker-skinned patients. Patients should be made aware of the rare association between vitiligo and diabetes or thyroid disease. Treatment of vitiligo is unpredictable and generally Figure 26: Extensive vitiligo over the trunk and limbs. topical immunomodulators in conjunction with sunscreens when treating exposed areas. Calcipotriol, a synthetic vitamin D analogue, has also been shown to have additional benefit in the treatment of vitiligo when combined with phototherapy (either narrow-band UVB or PUVA) or ultrapotent topical corticosteroids. Figure 27: Vitiligo with poliosis. Oculocutaneous albinism disappointing, although there have been advances in recent years. The benefits of cosmetic camouflage and protection from sunburn should be considered in all patients before the risks and benefits of active intervention are contemplated. Traditional treatments for vitiligo have included potent topical corticosteroids, psoralen phototherapy (PUVA) and depigmentation therapy in widespread cases (with topical 20% monobenzyl ether of hydroquinone). Newer treatments include topical immunomodulators, narrow-band UVB phototherapy (311nm), targeted phototherapy with the excimer laser (308nm) and calcipotriol (Daivonex) in conjunction with phototherapy. Narrow-band UVB phototherapy is probably the treatment of choice for widespread vitiligo — it offers equivalent efficacy to that of PUVA, with less toxicity. A typical course is often more than six months, as improvement is slow. Targeted phototherapy with the excimer laser is effective in treating localised areas of vitiligo by delivering high doses of light, and works well in combination with other topical agents such as tacrolimus or 8-methoxypsoralen (Oxsoralen lotion). The two topical immunomodulators are tacrolimus ointment (available in Europe and the US as Protopic but must be compounded in Australia) and pimecrolimus cream. These agents offer an advantage on the face and flexures as, unlike potent topical corticosteroids, they do not cause cutaneous atrophy when used long term. Because these agents are reasonably new there are no long-term safety data for their use in vitiligo. Clinicians should also be aware of black box warning labels issued by the US Food and Drug Administration in March 2005 for both agents due to concerns over increased frequency of skin cancer and lymphoma in animal studies and the small numbers of patients using the drugs. It is prudent therefore to use Oculocutaneous albinism refers to a group of inherited disorders characterised by abnormal melanin synthesis in the skin, hair and eyes. Type I is characterised by white hair and skin, blue-grey irides, nystagmus and reduced visual acuity. Skin and hair colour do not improve with age, and vision frequently worsens. These patients are at risk of solar keratoses and all forms of skin cancer, particularly squamous cell carcinoma and amelanotic melanoma. Type II is sometimes referred to as ‘partial albinism’ and is characterised by cream or pink skin, with cream to yellow hair. A variety of pigmented lesions, such as naevi, freckles and lentigines, develop with age and ocular problems are the same as for patients with type I. Types III and IV are far less common. Sun protection is clearly vital for these patients, as are regular dermatological surveillance and ophthalmological assessment. Piebaldism Piebaldism is a rare autosomal dominant genodermatosis characterised by a white forelock and vitiligo-like depigmentation. The genetic defect responsible for piebaldism is a mutation in the c-kit proto-oncogene on chromosome 4q. Piebaldism has a stable and chronic course, with changes evident from birth. The depigmented macules can be difficult to distinguish from vitiligo, but the presence of hyperpigmented islands within the white areas or normal skin are very suggestive of the disorder. The most characteristic sites of absent pigment are the anterior trunk and mid extremities. The hands and feet are usually spared, unlike some cases of vitiligo, and a skin biopsy demonstrates an absence of melanocytes. The mainstay of treatment is sun protection, cosmetic camouflage and possibly bleaching of the remaining skin with monobenzyl ether of hydroquinone. Author’s case study MISS M, 35, presented five years ago, unhappy because of dark brown pigmentation over her cheeks and forehead (figure 28). She tanned easily, was in good health and had been using the combined oral contraceptive pill since her mid-20s. Miss M was nulliparous but recognised a similar appearance in friends during pregnancy. The pigmentation was more noticeable in summer and she was already in the habit of applying a daily moisturiser with high-factor sunscreen. There was no history of preceding inflammation or rash before the pigmentation began and the patient had already inquired into the benefits of laser to improve her complexion. 30 | Australian Doctor | 24 February 2006 Figure 28: Melasma affecting the forehead. Comment Melasma, or chloasma, is a common diagnosis in women. Investigations are generally not required to confirm the diagnosis, provided the pigmentation is not felt to be post-inflammatory, such as that seen in acne or discoid lupus. Punctate melasma must be distinguished from solar lentigines (or solar freckling) but this is usually not difficult, as the latter have a moth-eaten border and are usually lighter. The importance of hormonal factors and solar exposure were explained to Miss M, and the type of sunscreen she used was checked: a combined anti-UVA and anti-UVB agent is most important to provide adequate protection. Because it was not convenient for her to change contraceptive measures www.australiandoctor.com.au she was treated with depigmenting agents but responded poorly to 5% hydroquinone cream and even hydroquionone-tretinoin combinations. Glycolic acid preparations, eg, Neostrata fading gel, were slightly more successful in lightening the pigment when used consistently over many months with strict photoprotection, but were even more successful in combination with superficial peels, courtesy of a local cosmetic dermatologist. Superficial peels with higher strengths of glycolic acid or trichloroacetic acid usually improve melasma but it must always be emphasised that even a short period of sun exposure (several days) can undo any improvements seen with months of bleaching agents. Online resources eMedicine — melasma: www.emedicine.com/derm/ topic260.htm n DermNet NZ — chloasma: dermnetnz.org/colour/ melasma.html n AD_HTT_O25_032___FEB24_06 20/2/06 2:46 PM Page 32 How to treat – disorders of pigmentation GP’s contribution Case study DR MARCIA MANNING Greenwich, NSW TR, a 50-year-old health professional, had been going through major conflict related to separation and divorce for the previous two years. She first noticed vulval itching and soreness about nine months ago and had treated herself twice with clotrimazole cream. Swabs grew Candida albicans and group B streptococcus. A single dose of fluconazole and a course of amoxycillin gave short-term respite. On examination about two months later, I suspected TR had vulval skin disease but a repeat swab grew group B streptococcus and a further attempt was made to eradicate this apparent pathogen. A few weeks later the vulva looked ‘soggy’ and there were distinct white areas and two small fissures. There were also several 5mm atrophic-looking ovoid patches on the skin over the inguinal ligaments, which on biopsy proved to be lichen sclerosus. A short course of Advantan ointment gave tremendous relief but the vulval pain recurred shortly after it was stopped, so several further brief courses were used. autoantibodies to extracellular matrix protein 1 (ECM1), a possible target antigen. Psychological stress is not known to trigger LS but may magnify symptoms. Infection may exacerbate LS but has never been substantiated as directly causal. Trauma is well known to exacerbate LS also, which can appear within surgical scars (Koebner phenomenon). A dermatologist also saw her because of continuing distress and prescribed a more intensive steroid regimen and regular review. By this time, TR had become severely distressed and anxious. She had also very tentatively started a new relationship, but was thinking that intercourse would be impossible. She was fearful of the amount of strong steroid she needed to control the symptoms and was also alarmed to discover she had already suffered some atrophy of the labia minora by the time all her symptoms had come under control. To add another layer of stress, a routine thyroid screen revealed mild hypothyroidism, although tests for thyroid auto-antibodies, antinuclear antibodies, DNA antibodies, C-reactive protein and extractable nuclear antigen were all negative. Questions for the author Is lichen sclerosus definitely autoimmune and does psychological distress trigger it, especially in someone at this age? (I have three other patients with this condition but they are much older). Are there other triggers? While the aetiology of lichen sclerosus (LS) is not entirely clear, evidence for an autoimmune basis is emerging. An association with certain HLA subtypes and other autoimmune diseases has been recognised for some time. More recently, studies have shown that most patients with LS have How to Treat Quiz INSTRUCTIONS Disorders of pigmentation — 24 February 2006 FAX BACK Photocopy form and fax to (02) 9422 2844 1. Which THREE factors are most likely to help in the diagnosis of conditions affecting pigmentation? ❏ a) Age of onset ❏ b) Sex ❏ c) Preceding rash ❏ d) Pigment distribution 2. Linda presents with her only child, Sophie, who is eight years old and has some large pigmented lesions consistent with café-au-lait macules. Which TWO features would be suggestive of underlying neurofibromatosis? ❏ a) More than six macules ❏ b) Axillary freckling ❏ c) Variable size ❏ d) Associated hair 3. Which TWO findings would make you consider McCune-Albright syndrome as the cause of a café-au-lait macule? ❏ a) A pathological fracture ❏ b) Precocious puberty ❏ c) A small regular lesion ❏ d) A positive family history of the condition 4. Geraldine, 37, complains of pigmentation affecting her face. If she has melasma, exposure to which THREE factors is most likely to be significant in causing her symptom? ❏ a) Perfume ❏ b) Oestrogen ❏ c) Sunlight ❏ d) Phenytoin 5. Which TWO of the following treatments are most likely to be beneficial? ❏ a) Narrow-band UVB therapy ❏ b) Hydroquinone plus tretinoin cream ❏ c) Azelaic acid cream or gel ❏ d) Laser 6. Geraldine sees you a year later after a visit to her son in Scotland. She has noticed a new rash on her back and legs. A ‘Yes’ response to which ONE question What would have helped to make the correct diagnosis more quickly? Should biopsy be considered in lichen simplex? Lichen sclerosus has a distinct appearance — generally with pallor, atrophy (wrinkled, shiny skin with telangiectasia) and ecchymoses, with or without fissures in a ‘figure of 8’ distribution over anogenital skin. The ivory white colour change is perhaps the most distinct feature. Lichen simplex, on the other hand (which is also pruritic), is distinguished by erythema, exaggerated skin markings and skin thickening rather than atrophy. Lichen simplex is more likely to occur in patients with a history of atopic dermatitis or exposure to irritants. When there is difficulty in distinguishing the entities clinically, a small punch biopsy will usually help to do so. How much does this disease usually affect sexual functioning? There is no doubt that lichen sclerosus affects psychosexual wellbeing. Dyspareunia may be a prominent symptom and both anxiety and loss of libido may stem from this. It has now been demonstrated that ultrapotent topical steroids will completely reverse the signs of the disease in about 20% of women, so this forms the cornerstone of treatment. When scarring is severe, surgery is occasionally of benefit. Washing with soap substitutes, avoiding irritants, and the use of lubricants (eg, Sylk or even vegetable oil) all help to allow more comfortable intercourse. Counselling and psychological support may also help women in coming to terms with this disease. The UK-based National Lichen Sclerosus Support Group web site can be found at www.lichensclerosus.org. Complete this quiz to earn 2 CPD points and/or 2 PDP points by marking the correct answer(s) with an X on this form. Fill in your contact details and return to us by fax or free post. FREE POST Australian Doctor Education Reply Paid 60416 Chatswood DC NSW 2067 would support a diagnosis of erythema ab igne? ❏ a) Does Geraldine also have a malar rash? ❏ b) Does she have joint pain? ❏ c) Has she had repeated exposure to a heater or open fire? ❏ d) Has she had palpitations, tremor and lost weight? 7. Nine-year-old Simone has had hypopigmented circumscribed patches on her face for six months. There is no scale or pruritus. Which ONE condition is the most likely cause? ❏ a) Naevus depigmentosus ❏ b) Lichen sclerosus ❏ c) Psoriasis ❏ d) Pityriasis alba 8. Which TWO characteristics would favour a diagnosis of vitiligo causing Simone’s lesions? ❏ a) Partial pigment loss only in the lesions ❏ b) History of lesions induced by skin trauma ONLINE www.australiandoctor.com.au/cpd/ for immediate feedback ❏ c) Whitening of hairs ❏ d) History of topical corticosteroid use 9. Maria, 62, was born in Greece. She complains of small pale spots on her arms and legs. If she has idiopathic guttate hypomelanosis, what advice can you give her (choose ONE)? ❏ a) Sun exposure will make the lesions less obvious ❏ b) The lesions are unlikely to repigment ❏ c) They will improve as she gets older ❏ d) Topical retinoids may lead to pigmentation 10. Maria returns six months later with new skin lesions. Which THREE characteristics would make you think she has pityriasis versicolor? ❏ a) Scaly rash on elbows and knees ❏ b) Lightly scaly plaques on the trunk ❏ c) Hypopigmentation persisting after treatment ❏ d) Onset during summer CONTACT DETAILS Dr: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phone: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E-mail: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RACGP QA & CPD No: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .and /or ACRRM membership No: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Address: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Postcode: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HOW TO TREAT Editor: Dr Lynn Buglar Co-ordinator: Julian McAllan Quiz: Dr Lynn Buglar The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Your CPD activity will be updated on your RACGP records every January, April, July and October. NEXT WEEK The next How to Treat tackles assessment, management and prevention of falls in the elderly. The authors are Dr Jacqueline Close, staff specialist in geriatric medicine at Prince of Wales Hospital, conjoint senior lecturer at the University of NSW, and senior research associate at the Prince of Wales Medical Research Institute, Randwick, Sydney, NSW; and Associate Professor Stephen Lord, NHMRC principal research fellow at the Prince of Wales Medical Research Institute. 32 | Australian Doctor | 24 February 2006 www.australiandoctor.com.au