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INSIDE Patterns of hypopigmentary disorders

Circumscribed hyperpigmentary disorders

Facial

Diffuse or systemic causes of hyperpigmentation

Reticulate and mottled hyperpigmentary disorders

Medication- induced hyperpigmentation Overview of pigmentary disorders

DISORDERS of pigmentation are a common presentation in derma- tology and general practice. The aesthetic appearance of either hyper- the authors pigmentation or , especially in the visible parts of the , can have major psychosocial implications. Although it is more of a cosmetic problem, a disorder of pigmentation can occasionally be associated with an underlying systemic disorder. It is therefore important to recognise the causes of Disorders of Dr Deepani Rathnayake pigmentary disorders to achieve the consultant dermatologist, Base best treatment outcome. Hospital Dambulla, Sri Lanka. This article discusses pigmentary disorders in general including the underlying pathological mecha- pigmentation nisms and management. It then looks at individual hyperpigmentary and hypopigmentary conditions in more detail. — Part 1: The single most important sub- stance determining human skin col- Professor Rod Sinclair our is the pigment . Other director and head, , compounds that may contribute to Epworth Hospital, Melbourne, the skin colour include carotenoids Hyperpigmentation Victoria. and haemoglobin. Melanin is produced by melano- cytes during melanogenesis. This This is the first of a two-part series on disorders of pigmentation. In Part 1, we discuss the nature of pigmentary occurs within , which disorders and then focus on hyperpigmentary disorders. In Part 2, we cover hypopigmentary disorders. are small membrane-bound pack- ages. When melanosomes become are found in the skin or , tyrosinase. produce several genes, such as the genes for full of melanin, they move along hair follicles, eye, nervous system, two types of melanin that give the the MSH cell surface receptor and Copyright © 2014 the arms of melanocytes and are leptomeninges and the inner ear. skin its colour. The most com- the melanosomal P-protein. These Australian Doctor All rights reserved. No part of this transferred to the . Melanocytes in the skin and other mon form of melanin is eumela- genes can regulate the variability of publication may be reproduced, One supplies melanin to body sites have a common embryo- nin, which gives a brown-black the skin colour in humans by mainly distributed, or transmitted in any about 36 keratinocytes. People have logical origin from the neural crest. colour and is more abundant in regulating the level and activities form or by any means without the same number of melanocytes but They migrate from here into these people with dark skin. Pheomela- of enzymes involved in the mela- the prior written permission of the publisher. their skin colour is determined by different body sites. nin gives a red-yellow colour to the nin biosynthesis, mostly the enzyme For permission requests, email: the amount and types of melanin the The production of melanin is skin. Both the amount and type of tyrosinase. [email protected] melanocytes produce. Melanocytes mainly regulated by the enzyme melanin produced is controlled by cont’d next page

www.australiandoctor.com.au 11 April 2014 | Australian Doctor | 29 How To Treat – Disorders of pigmentation — Part 1: Hyperpigmentation

from previous page mentation. A detailed drug history Formal counselling from a mental Pathogenesis Table 1: Wood’s lamp features in pigmentary disorders may help to determine if the hyper- health professional may be help- Disorders of pigmentation can be Condition Features pigmentation is caused by a photo- ful. Education about the disorder due to a variety of genetic and Pityriasis versicolor Yellowish-white or copper-orange fluorescence toxic or allergic reaction, or from and treatment options should be acquired causes. This is because fixed drug eruptions. fully provided so that the patients Bright areas with sharp borders, varying in there are many genes involved in can form realistic expectations and location and extent the different stages of melanin pro- Dermatoscope and Wood’s lamp participate in making important duction and transport abnormali- Patches; characteristic ash-leaf shape The dermatoscope and Wood’s decisions about their medical care. ties may arise from any of these Hypomelanosis of Ito Whorled or streaked patterns. lamp can assist the clinician in Patient support groups are helpful. stages. In , for exam- Erythrasma Shows coral red fluorescence diagnosing certain diseases. Table Cosmetic camouflage is an option ple, melanocyte migration from 1 shows clinical features that may in some patients, especially on vis- Pigments in the outer epidermal layer of the skin the neural crest is defective. Other be detected under a Wood’s lamp ible parts of the body. are accentuated while the colour of the deeper abnormalities may occur in the in a variety of pigmentary disor- dermal pigments is decreased formation of melanocytes and mel- ders. Dermatoscopy is a very use- Minimising sun exposure anosomes, or during the secretion ful tool in differentiating a benign Patients who have depigmented of melanosomes to keratinocytes. tory disorders, or be secondary to be diagnosed clinically. A detailed melanocytic naevus, pigmented or hypopigmented skin should Certain pigmentary disorders such chemicals or drugs. Increased pig- history and examination is impor- seborrhoeic from a malignant minimise sun exposure and use a as may mentation similarly can be induced tant and often gives clues to the . Histological diagnosis that provides protec- also be associated with visual and by many factors such as UV radia- underlying cause. A lesion present- will be required in some cases. tion from both UVA and UVB neurological defects, owing to tion, drugs, and ing from birth may be a naevus or light. Tanning makes the contrast the defects’ common embryologi- hormonal factors. Abnormalities a genetic disorder. A family history General principles of between normal and depigmented cal origin and migration from the in the other pigment compounds of a similar disease also favours a management skin more noticeable. Sunscreen neural crest. such as carotenoids and haemo- genetic disorder. Diffuse types of While mostly benign, both hyper- helps prevent tanning and also Acquired conditions of pigment globin may also result in certain pigmentary changes may be due pigmented and hypopigmented helps protect from and loss can arise from melanocyte pigmentary disorders. to metabolic, hormonal or nutri- lesions, such as vitiligo or facial long-term damage. Moreover, destruction. This may be due to tional causes. A preceding or melasma, can profoundly affect a hyperpigmentary disorders such as an underlying autoimmune disor- Diagnosis injury to the skin suggests post- patient’s emotional and psycho- melasma and can deterio- der such as vitiligo, or inflamma- Many pigmentary disorders can inflammatory hyper- or hypopig- logical wellbeing and self-esteem. rate with sun exposure.

Patterns of hyperpigmentary disorders

DISORDERS of hyperpigmen- 2). Certain conditions such as pigmentation (figure 1). Because tion need special attention. There hyperpigmented lesion. However, tation may be localised (ie, cir- poikilodermatous disorders cause of their cosmetic significance, is no set algorithm or specific figure 2 will help the clinician in cumscribed) or diffuse (table reticulate and mottled type of facial and periorbital pigmenta- way to approach a patient with a approaching a patient.

Figure 1: Hyperpigmented lesion in left anterior chest and upper arm Localised Diffuse Mottled or Blaschkoid in a patient • Drug induced reticulate • Pigmentary with mycosis • Associated pigmentation mosaicism fungoides. with systemic • Linear epidermal disease naevi

Genetic disorders Acquired • Dermatopathia Congenital Acquired • Poikiloderma of pigmentosa reticularis Civatte •  •  ab igne • Dowling–Degos • Poikilodermatous disease disorders (eg, Table 2: Patterns of hyperpigmentary disorders • Galli–Galli disease Circumscribed Freckles, lentigines, melanocytic naevi, melasma, acanthosis • Kitamura and ) nigricans, post-inflammatory, fixed , café-au- acropigmentation • Confluent lait macules, mastocytosis, pityriasis versicolor and reticulate Diffuse Drug-related, endocrinopathies, haemochromatosis, HIV papillomatosis • Livedoid vasculopathy Reticulate and , , genetic reticulate Epidermal Dermal Epidermal Dermal • Graft-vs-host disease mottled pigmentary disorders, poikilodermatous disorders (eg, • Café au lait • Naevus • Freckles • Melasma (dermal) • Post-kala azar dermal mycosis fungoides and dermatomyositis), confluent and macules of Ota • Lentigines • Post inflammatory leishmaniasis reticulate papillomatosis, livedoid vasculopathy, graft-vs- • Melanocytic • Blue • Melasma • Hyperpigmentation • Systemic sclerosis host disease, post-kala azar dermal leishmaniasis, systemic naevi naevus (epidermal) • Ashy dermatosis sclerosis Blaschkoid Pigmentary mosaicism, incontinentia pigment Figure 2: A simple clinical approach to a hyperpigmented lesion.

Circumscribed hyperpigmentary disorders

Freckles condition, some patients may be Lentigines Table 3: Syndromes and genetic diseases associated with FRECKLES are small flat brown distressed by their appearance and Lentigines are small, brown to hyperpigmentation circular spots arising on the face seek treatment. Sun protection black-coloured macular melanoses. and other sun-exposed areas. They is essential in managing this con- They have several points of differ- Freckles Xeroderma pigmentosum usually fade in winter with less sun dition if treatment is requested. ence to freckles: there is an increased Neurofibromatosis exposure and as the keratinocytes There are several safe and effective number of melanocytes in lentigi- Lentigines Peutz–Jeghers syndrome are replaced with new cells. They methods that are available to help nes, lentigines are darker, persist Leopard syndrome are most often seen in fair skinned, lighten or reduce the appearance throughout the year, and do not Carney complex red-haired people. Genetic tendency of freckles. Treatment options darken on exposure to sunlight. Xeroderma pigmentosum and sun exposure can predispose include bleaching or fading creams There are several types of lentigines, to development of freckles. Freck- (table 4), light application of liq- as listed in the box below. Multiple Café au lait macules Neurofibromatosis les represent an increase in the uid nitrogen, laser treatment and lentigines can occur in association McCune–Albright syndrome amount of melanin, not an increase chemical peels. Frequently, mul- with an underlying genodermatosis Fanconi anaemia in the total number of melanocytes. tiple or a combination of treat- (table 3). Tuberous sclerosis Increased tendency to develop freck- ments may be required for the best Reticulate pigmentation Dermatopathia pigmentosa reticularis les is seen in genetic disorders such results. Preventive photoprotec- Café au lait macules Dyskeratosis congenita as xeroderma pigmentosum. Axil- tion starting in early childhood Café au lait spots are macules Dowling–Degos disease lary freckles are a feature in neurofi- is important because freckles can varying from light brown to dark Galli–Galli disease bromatosis (table 3). easily recur with repeated UV brown with smooth or irregular Kitamura acropigmentation While freckles are a harmless exposure. borders. While having a few small

30 | Australian Doctor | 11 April 2014 www.australiandoctor.com.au lesions may be normal, a greater size and number can point towards Table 4: Depigmenting agents an underlying genetic disorder. The Name and preparation Clinical considerations Mechanism of action Side effects most commonly associated systemic Hydroquinone 2% and standard Most effective inhibitors of melanogenesis acts by Irritation disorder is neurofibromatosis type 1 4% preparations Most commonly used inhibiting tyrosinase* Phototoxic reactions with secondary (figure 3). Other syndromes assoc- Apply twice daily in the affected area post-inflammatory hyperpigmentation iated with café au lait spots are listed Should discontinue if no response Irreversible exogenous ochronosis in table 3. after eight weeks The café au lait macules them- Tretinoin Contraindicated in pregnancy Acts by increasing turnover and thus Skin irritation selves do not require medical 0.025-0.1% Should apply only in the night limiting the transfer of melanosomes to keratinocytes care. Pigment laser (Q-switched Takes more than 12 weeks to see a Paradoxical hyperpigmentation Nd:YAG) offers clearance in about response Burning, stinging, erythema, dryness 50% of cases when cosmetic treat- and scaling ment is requested. Discussion about Retinoid leads to the possible post-treatment compli- hyperpigmentation cations should occur prior to treat- ment. The complications include Azelaic acid Superior to 2% hydroquinone Weak competitive inhibitor of tyrosinase in vitro* Skin irritation transient hyperpigmentation and 20% cream Will not lighten skin with normally Has an antiproliferative and cytotoxic effect on No phototoxic or photoallergic reactions hypopigmentation, slight scarring, functioning melanocytes melanocytes have been reported permanent hyperpigmentation and Apply twice daily Seems to target only hyperactive melanocytes recurrence. (thus will not lighten skin with normally functioning melanocytes) Post-inflammatory Kojic acid — in A fungal metabolic product that inhibits the Irritant hyperpigmentation concentrations of 1-4% catecholase activity of tyrosinase* Post-inflammatory hyperpigmenta- Ascorbic acid Twice daily application Has antioxidant properties and reduces tion is a frequent fol- 10-15% serum or cream Takes 8-12 weeks to see a response melanogenesis lowing various cutaneous disorders. These cutaneous disorders may be Niacinamide Suppresses the transfer of melanosomes to the infections (eg, tinea), dermatitis, drug epidermal keratinocytes reactions and inflammatory skin dis- Soy Acts by reducing melanin transfer from melanocytes orders (eg, ). Epidermal to keratinocytes post-inflammatory hyperpigmenta- Arbutin Inhibits melanin synthesis by inhibition of tyrosinase tion appears light-brown to black activity* whereas deeper dermal pigmenta- Paper mulberry Inhibits melanin synthesis by inhibition of tyrosinase tion has a grey to bluish appearance. activity A variety of topical agents have Isolated from a plant extract been used to treat epidermal post- inflammatory hyperpigmentation, Liquorice extract Inhibits tyrosinase activity of melanocytes without with varying degrees of success. cytotoxicity These agents include hydroquinone, Topical steroids Monotherapy is not recommended Cause skin lightening as a result of reduced cell Skin with prolonged use tretinoin cream, corticosteroids, Has synergistic effects with, and turnover and reducing production of melanocyte- glycolic acid (GA) and azelaic acid used for the reduction of irritation stimulating hormone by reducing production of (table 4). A combination of topical from, other products like tretinoin precursor steroid hormones creams and gels, chemical peels and Hydroxy acids Acts by epidermal remodelling and accelerated Skin irritation may be necessary and is desquamation only effective for epidermal hyper- * Tyrosinase is the rate-limiting, essential enzyme in the biosynthesis of the skin pigment melanin; reduction of this enzyme leads to decreased production of melanin pigmentation. Laser treatment may be able to address dermal pigment deposition. Broad-spectrum sun- Types of lentigines Figure 3: Café au lait macules seen screens should be combined with Simple lentigines any treatment regimen. on the • Very common condition of a patient with Melasma • Benign, isolated pigmented macules neurofibromatosis type 1. Note the Melasma presents as bilateral sym- • Seen in any part of the body including palms and soles on metric hyperpigmented macules • Independent of UV exposure left of chin. commonly in the cheeks, the upper lip, the chin and the forehead (fig- • Usually do not need any treatment ure 4). The most significant cause Solar lentigines of melasma is exposure to sunlight. • Small, discrete, irregularly shaped and uniformly brown macules Female hormones also play a role and appearance of melasma can be • Typically seen in sun-exposed areas together with other features of chronic associated with pregnancy and con- sun damage traceptive pills. There is a known PUVA lentigines genetic predisposition to melasma. • Relatively large macular pigmentation Melasma can be epidermal, der- • Develop as a complication of long-term PUVA ( + UVA) therapy mal or mixed. Epidermal melasma has well-defined borders and is dark • May be a marker of increased future development of melanoma and non- Figure 4: Melasma brown in colour. Dermal melasma melanoma skin in a middle- is the common type with ill-defined Ink spot lentigines aged woman, showing the borders and is bluish in colour. The • Densely pigmented, relatively smaller macules mixed type has a combination of classic bilateral • Often alarm both the patient and the doctor because of their clinical clinical features (see table 5). hyperpigmented resemblance to melanoma macules on the Melasma can be difficult to treat cheeks and other and can be recurrent. There are parts of the face. several treatment modalities; these shown to work faster. mal and epidermal pigmentation. As should always be combined with Superficial chemical peels with they are selective of the target, there adequate sun protection. As shown glycolic acid, trichloroacetic acid is minimal damage to the surround- in table 5, epidermal melasma (TCA), tretinoin or are ing tissue. Repeated treatments are has a good response to treatment being used to treat melasma in resist- necessary to achieve a desirable out- while dermal melasma has a poor ant cases. Three steps are involved come. response. in treating with chemical peels: care- Fractional laser is a non-invasive Topical hydroquinone 2-4% ful patient selection, proper priming treatment that uses a device to cream twice a day with a sunscreen and post-procedural care (see box, deliver a laser beam divided into remains the first-line treatment. next page). thousands of microscopic treatment There are several other topical medi- Lasers that selectively target the zones that target a fraction of the pigmentation, hypopigmentation bleaching creams and post-proce- cations used in melasma that are hyperpigmentation in the correct skin at a time. This laser treatment and scarring are potential com- dure sun protection is necessary listed in table 4. A combination of depth can be used in resistant cases works at both the epidermal and plications. Patients with darker to minimise complications. Oral topical treatments (‘Triple Combi- but with caution. Highly pigment- dermal layers of the skin. Fractional skin should be treated with cau- tranexamic acid may be effec- nation Cream’) with hydroquinone selective short pulsed Q-switched lasers are FDA approved and have tion as even slight inflammation tive for some patients, but further 4%, tretinoin 0.05%, and fluo- lasers that target the melanosomes made lasers safer, especially for may worsen the hyperpigmenta- studies are needed. cinolone acetonide 0.01% has been are used in the treatment of both der- darker-skinned patients. Hyper- tion. Prior treatment with topical cont’d page 34

www.australiandoctor.com.au 11 April 2014 | Australian Doctor | 31 How To Treat – Disorders of pigmentation — Part 1: Hyperpigmentation

from page 31 Ashy dermatosis (erythema Table 5: Melasma categorised by depth of pigmentation and Three steps of a chemical peel dyschromicum perstans) ease of treatment Step 1. Patient selection and counselling Erythema dyschromicum perstans, Melasma type by Description Relative response to 1. Discussion with the patient should include: also called lichen planus pigmen- depth of pigmentation treatment • The procedure and the expected outcome tosis, causes ashy discolouration Epidermal Well-defined borders Good • Possibility of unexpected complications like increased pigmentation, of skin and is therefore also known Dark brown in colour hypopigmentation as ‘ashy dermatosis’. Ashy derma- Becomes prominent tosis is an asymptomatic eruption with Wood’s lamp • That treatment needs to be maintained of oval, polycyclic, or irregularly examination 2. Take care in approach to patients with unrealistic expectations, active shaped, grey-blue hyperpigmented Dermal Ill-defined borders Poor skin infections (HSV), keloidal tendency, uncooperative or non-compliant macules on the trunk, the arms, the Bluish in colour patients (careless about sun protection or maintaining treatment) face, and the (figure 5). There Become less obvious Step 2. Skin preparation or priming (start 2-4 weeks before chemical peel) are no systemic symptoms or asso- with the Wood’s lamp 1. Treat the pigmentation with 2-4% hydroquinone ciations. There are close similari- examination ties with lichen planus although 2. Start a mild peeling agent like 0.025% retinoids, 6-12% glycolic acid Mixed Combined features Partial the exact relationship is not clear. 3. Start a sunscreen and avoid sun exposure The disease is more common in Asian and Latin American people. Figure 5: Ashy 4. Stop the peeling agent three days before the peel Different treatments have been dermatosis on the Step 3. Post-procedure care* tried but ashy dermatosis is usually face of a middle- aged woman. 1. Maintain adequate sun protection resistant to treatment. Clofazimine 2. Do not pick, scrub or peel off the skin has shown satisfactory results in some patients. Other treatments 3. Gentle wash and cleanse such as dapsone, potent steroids 4. Start the maintenance treatment when skin returns to normal and bleaching creams have not *Proper post-procedural care is mandatory in achieving good results and in shown satisfactory results. preventing complications

Acanthosis nigricans causes Types of acanthosis nigricans increased pigmentation with a soft -associated acanthosis nigricans velvety appearance on the sides of • Most common type the neck, in the axillae and groin. • Also called pseudo-acanthosis nigricans There is also often an increased pigmentation of mucosal surfaces. • May be a marker for higher needs in obese women The mechanism responsible for periumbilical region and inter- • May be an early marker for in paediatric patients the pigmentation is unknown, but gluteal fold are less commonly Syndromic acanthosis nigricans increased melanocytes-stimulating involved in erythrasma. hormone activity is suspected. There Excessive sweating/hyperhi- • HAIR-AN syndrome: hyperandrogenism (HA), (IR), and are several types of acanthosis nigri- drosis, obesity, mellitus, acanthosis nigricans (AN) cans (see box, right). warm climate and poor hygiene • Polycystic ovarian syndrome The aim of treatment is to correct can predispose to the disease. • Uncontrolled diabetes mellitus the underlying disease. This may Erythrasma can be confused with • Ovarian hyperandrogenism involve multidisciplinary evaluation. acanthosis nigricans (which has a Treatment of the lesions of acan- velvety texture and ill defined bor- Acral acanthosis nigricans thosis nigricans is for cosmetic rea- ders), (which shows • Hyperkeratotic velvety lesions sons only. Topical medications that more erythema and fissuring at • Found over the dorsal aspects of the hands and feet, with knuckle have been effective include kerato- skin creases and shows satellite hyperpigmentation lytics (eg, topical tretinoin 0.05%, around the lesion), psoria- • Seen in otherwise healthy African-American individuals ammonium lactate 12% cream, or a sis (which has more pinkish well- combination of the two) and triple- defined lesions), and Drug-induced acanthosis nigricans combination depigmenting cream (which shows an active scaly edge). • Examples include nicotinic acid, systemic corticosteroids, oral (tretinoin 0.05%, hydroquinone Wood’s lamp examination of contraceptives, fusidic acid 4%, fluocinolone acetonide 0.01%) erythrasma lesions reveals coral- Figure 6: Hyperpigmentation due to Malignant acanthosis nigricans nightly with daily sunscreen. erythrasma in the right armpit. red fluorescence of lesions and is a helpful bedside test. • Examples include gastric adenocarcinoma, Wilms tumour, osteogenic Erythrasma Oral erythromycin 250mg sarcoma Erythrasma is a chronic superficial demarcated, uniform, brown-red four times daily for two weeks is • May present as lesions that arise rapidly, are more extensive, and in atypical infection of the intertriginous areas macular patches located over the the treatment of choice. Topical locations of the skin caused by Corynebacte- inner thighs, crural region, scro- fusidic acid or miconazole twice • May be associated with (thickened velvety palms that have the rium minutissimum. The typical tum and toe webs (figure 6). daily for 2-4 weeks are also help- appearance of stomach lining of beef, pork or sheep) appearance of erythrasma is well- The axillae, submammary area, ful. Facial hyperpigmentation

FACIAL hyperpigmentation is one Causes of facial include skin-lightening creams, the most common cosmetic com- A B hypermelanosis chemical peels, intense pulsed light, plaints and requires special consid- Q-switched ruby laser, autologous eration. The presentation may be Genetic fat transplantation, combinations either diffuse or patchy. The causes • Freckles of fat grafting and blepharoplasty, may be multifactorial (see box, • Lentigines and fillers. However, none have pro- right), including genetic factors, sun- vided a satisfactory treatment. • Naevus of Ota light, cosmetics and hormonal fact- Figure 7: A: Streaky ors. hyperpigmentation due to • Pigmentary demarcation lines Naevus of Ota on the right • Xeroderma pigmentosum Naevus of Ota is a hamartoma of Periorbital hyperpigmentation elbow and forearm. B: Streaky Acquired dermal melanocytes presenting as Dark circles around the eyes or peri- hyperpigmentation on the forehead a blue or grey patch on the face, orbital hyperpigmentation can cause and nose due to phytophotodermatitis • Melasma within the distribution of the oph- much psychological distress to the following a herbal extract application • Riehl’s thalmic and maxillary branches of on scalp and hair. patient. Even though the condition is Images courtesy of Dr Nayani Madarasingha. • Poikiloderma of Civatte the trigeminal nerve. The naevus usually benign, it can be very resist- the inner aspect of the lower eye- hyperpigmentation may be second- can be unilateral or bilateral, and, • Berloque dermatitis ant to treatment. It is a common lids, with prominent capillaries or ary to contact or . in addition to skin, it may involve condition and often familial. There . Bluish discolouration Shadow effects due to an overhang- • Hori’s naevus ocular and oral mucosal surfaces are most likely multiple causative of the lower eyelid can be seen as a ing tarsal muscle, eyebags or a deep • Actinic lichen planus (figure 9). factors involved, including epider- result of visible blue veins. Constitu- tear trough can cause dark eye circles • Seborrhoeic melanosis Cosmetic camouflage makeup can mal hypermelanosis, dermal mela- tional type can present with a curved more commonly seen with ageing. minimise the disfiguring facial pig- • Phytophotodermatitis (figure 7) nosis, increased vasculature, and band of brownish to black hyper- Dry skin, hormonal disturbances, mentation. Other topical therapy is normal anatomic variants. pigmentation with a velvety texture nutritional deficiencies and other •  maligna of no value. Pulsed Q-switched laser, The vascular type can present with and often involving the upper eye- chronic illnesses can also contribute. Q-switched ruby, Q-switched alex- erythema predominantly involving lids (figure 8). Post-inflammatory Treatments that have been tried andrite, and Q-switched Nd:YAG

34 | Australian Doctor | 11 April 2014 www.australiandoctor.com.au lasers have shown good results. Figure 8: Periorbital Figure 9: Naevus of Ota, Naevus of Ota can be associated hyperpigmentation of seen here prominently with increased intraocular pressure the constitutional type on the right forehead and and ophthalmic referral is necessary. showing curved bands face and smaller on the of brownish to black left temporal area. Hori’s naevus hyperpigmentation with a Hori’s naevus is an acquired bilat- velvety texture. eral naevus of Ota-like multiple brown-grey to brown-blue mac- ules, in the malar region of the face. It is differentiated from the naevus of Ota by the later age of onset and lack of conjunctival, mucosal and tympanic membrane contact dermatitis that results ity reaction. Standard patch test brown, reticulate pigmentation avoiding sun exposure and the involvement. Lasers are the most in basal cell damage and pig- series, cosmetic series, fragrance with atrophy of the skin and telan- proper use of sunscreens is most commonly used treatment for ment incontinence. Many cases series, and patient’s personal prod- giectasia that occurs on the lateral important. this condition and achieve good are preceded by mild erythema, ucts can be used depending on the cheeks and sides of the neck. It is results. oedema and pruritus, followed by suspected allergens. seen more commonly in middle- Berloque dermatitis a diffuse-to-reticulated pattern of aged women. Photosensitising Berloque dermatitis has drop-like Riehl’s melanosis hyperpigmentation. Other management measures chemicals in perfumes or cosmet- or streak-like hyperpigmentation (melanodermatitis toxica) Complete avoidance of the sus- ics together with chronic sun on the face or neck that arises from Riehl’s melanosis is caused by fre- Photo-patch testing pected allergen is necessary, leading exposure have been implicated in the application of perfumes and quent and repeated contact with Patch testing and photo-patch test- to a gradual improvement. Topical the pathogenesis of poikiloderma subsequently being exposed to the small amounts of sensitising aller- ing will help in making a diagno- creams containing 2-4% hydroqui- of Civatte. Hormonal changes sun. The principal management is gens in cosmetics at a concentra- sis. A photo-patch test is similar none twice daily for 4-8 weeks com- related to menopause or low oes- discontinuation of the offending tion that is too low to produce to a skin patch test except that the bined with tretinoin may hasten the trogen levels may also be a causa- substance and/or limiting the use typical eczematous dermatitis. allergens are applied on the skin in resolution of the hyperpigmentation. tive factor. the perfumes to covered areas. A However, the repeated contact duplicate. One set is exposed to a There is no specific medical short course of topical corticoster- over time and repeated sun expo- small dose of radiation Poikiloderma of Civatte treatment for poikiloderma of Civ- oids may help if there is inflamma- sure causes cumulative allergic (UVA) to detect a photosensitiv- Poikiloderma of Civatte is a reddish- atte. Educating the patient about tion and discomfort.

Diffuse or systemic causes of hyperpigmentation

DIFFUSE hyperpigmentation may in skin creases. The beds and son’s disease as part of a multiglan- mentation owing to the deposition cally found with carcinoma of the be due to an underlying systemic the oral mucosa may also become dular deficiency syndrome. of haemosiderin. In , lung. The pigmentation occurs disease (eg, Addison’s disease, hyperpigmented. The hyperpig- hyperpigmentation is generalised, because of the melanocyte-stim- hyperthyroidism, haemochroma- mentation is caused by an increased Other systemic conditions but there is accentuation of the ulating hormone-like activity of tosis) or it may be a side effect of activity of the melanocyte-stimu- Hyperthyroidism causes a pattern brown colour on the dorsal surface polypeptides produced by such medication use. lating hormone and adrenocorti- of hyperpigmentation similar to of the arms and hands. Occasion- tumours. Generalised melanosis cotropic hormone, both of which that in Addison’s disease, especially ally, vitiligo-like hypopigmentation may also be seen with advanced, Addison’s disease are capable of stimulating pigment in patients with darker complex- will be interspersed within areas of widespread melanoma, in which In Addison’s disease, hyperpigmen- production. Vitiligo, which is also ions. Haemochromatosis, a disor- darkened skin. case the colour is due to the pig- tation occurs over the entire body an autoimmune disorder, can be der of iron storage and deposition, Hyperpigmentation associated mented compounds produced with accentuation in old and associated in patients with Addi- can cause a slate-grey hyperpig- with malignancies is most classi- directly by the malignant cells.

Reticulate and mottled hyperpigmentary disorders

RETICULATE pigmentary disor- Figure 10: Confluent and ure 10). It usually develops between inflammatory skin disease charac- ders cause net-like patterns of cuta- reticulate papillomatosis the breasts and in the midline of the terised by pruritic, erythematous neous hyperpigmentation that are on the back showing red back, and gradually spreads over urticarial papules that are symmet- seen in both congenital and acquired and verrucous papular the breasts and abdomen. With rically localised on the trunk. The conditions (see tables 2 and 3). A lesions coalescing to form progression, the lesions acquire the lesions resolve, leaving reticulate plaques. formal diagnosis of any underlying characteristic reticulate appearance. pigmentation. Lesions in different disorder should be made because it This condition is commonly seen in stages are usually present together may be treatable and/or associated young females. at any one time; the condition has with malignancies and systemic dis- The treatment of choice for con- a waxing and waning course. Sev- eases. fluent and reticulate papillomatosis eral causative factors have been is minocycline 100-200mg per day implicated such as ethnic predispo- Erythema ab igne for weeks to months. Other anti- sition, environmental causes, sea- Erythema ab igne is characterised There may be an initial erythema term consequence. biotics that have been tried include sonal variation, mechanical stimuli by localised areas of reticulate ery- which then, with repeated exposure clarithromycin, erythromycin and and contact allergens. Different thema and hyperpigmentation that to heat, evolves into a non-blanch- Confluent and reticulate azithromycin. Isotretinoin, tacalcitol medications have been tried with result from chronic heat exposure ing dusky hyperpigmentation with papillomatosis and calcipotriol are useful topical variable results. Antihistamines (eg, heating pads, heating blanket, epidermal atrophy. The lesions of confluent and reticu- treatments. and steroids have been found to laptop computer). It is typically seen and bullae may be seen in the late late papillomatosis are red, verru- be ineffective while minocycline, in middle-aged or elderly patients, stage. Squamous cell carcinoma cous, minimally scaly papules, which Prurigo pigmentosa tetracycline and doxycycline have and is more common in women. may develop as a possible long- coalesce to form brown plaques (fig- Prurigo pigmentosa is a rare shown promising results.

Medication-induced hyperpigmentation

MANY drugs are known to cause Fixed drug eruptions Figure 11: Fixed drug sites following re-exposure to diffuse or localised hyperpigmenta- Fixed drug eruptions are com- eruption manifesting as a the same drug. Local symptoms tion. These are summarised in table mon and have some unique fea- with surrounding may include pruritus, burning, 6, see next page. tures. They are typically of acute hyperpigmentation. and pain. The initial eruption is onset and appear as annular, frequently located on the lip or Drug-induced pigmentation oedematous, reddish-brown to genitalia. The following features point to a violaceous macules or plaques. The common medications that drug-induced pigmentation: These erythematous patches may cause fixed drug eruptions • The increased pigmentation starts or plaques gradually fade with are analgesics, muscle relaxants, gradually after initiation and fades residual hyperpigmentation. The sedatives, anticonvulsants and when drug is discontinued. centre of the patch may blister or antibiotics. Patients should be • The hyperpigmentation shows become necrotic (figure 11). Their counselled on medication avoid- photo-aggregation. diagnostic hallmarks include ance and possible cross-reactions • Involvement of cartilage, mucosa, residual hyperpigmentation and to similar medications. nail and . recurrence at previously affected cont’d next page

www.australiandoctor.com.au 11 April 2014 | Australian Doctor | 35 How To Treat – Disorders of pigmentation — Part 1: Hyperpigmentation

from previous page Table 6: Medications that cause hyperpigmentation Conclusion Drug Description of hyperpigmentation PIGMENTATION disorders are Antimalarials Bluish-grey or purple pigmentation in the pretibial areas usually considered to be cosmetic in (eg, chloroquine, nature. However, it is important to hydroxychloroquine, recognise that they can cause psy- amodiaquine and chological distress to the patient. It quinacrine) is also important to remember that Chemotherapy Bleomycin causes a pigmented banding of the patient’s nails, generalised some hyperpigmentation disorders agents (eg, hypermelanosis to focal pigmentation of pressure points, linear or flagellated may be associated with an under- bleomycin, bands lying systemic disease or be caused 5-, 5-Fluorouracil causes photosensitivity reaction in sun-exposed skin, followed by a medication. A thorough his- adriamycin, by hyperpigmentation, hypermelanosis in the skin near infusion or portal tory and clinical examination is hydroxyurea) irradiation sites required, and investigations or Adriamycin causes pigmented patches in the oral mucosa and lateral aspect of specialist referrals should be made the tongue where appropriate. Hydroxyurea causes nail bed and/or lunula hyperpigmentation and tongue pigmentation Online resources Heavy metals (eg, Silver causes a generalised slate-grey pigmentation () that is most Figure 12: Violet-brown pigmentation in the face silver, gold, iron) accentuated in sun-exposed areas and often involves a patient’s nails, sclera developing from clofazimine in a patient treated for and mucous membranes . eMedicine Gold causes a blue-grey hyperpigmentation of sun-exposed skin, known as www.emedicine.com/derm/ DermNet NZ Iron causes a permanent blue-grey discolouration dermnetnz.org Tetracyclines Tetracyclines cause a brown discolouration of the teeth in children Minocycline causes blue-black discolouration localised to scars, blue- Further reading grey pigmentation on the extremities, and a generalised ‘muddy’ brown 1. Wolff K, et al. Fitzpatrick’s hyperpigmentation in sun-exposed skin Dermatology in General Medicine. 7th edn. McGraw-Hill Inc, New Amiodarone Blue-grey or violaceous pigmentation of sun-exposed skin and yellow-brown York, 2007. stippling of the cornea 2. James WD, et al. Andrews’ Diseases Antiretrovirals — Reversible dyspigmentation of the nails, brown mucocutaneous of The Skin: Clinical Dermatology. zidovudine hyperpigmentation 11th edn, Elsevier Inc., Edinburgh, Clofazimine Violet-brown or bluish cutaneous pigmentation most apparent in lesional skin 2011. (figure 12) 3. Burns T, et al. Rook’s Textbook of Dermatology. 8th edn, Wiley- Psychotropic drugs Slate or blue-grey pigmentation in sun-exposed areas of the skin Blackwell, Hoboken NJ, 2010.

Instructions Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. How to Treat Quiz We no longer accept quizzes by post or fax. Disorders of pigmentation — Part 1: The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. GO ONLINE TO COMPLETE THE QUIZ Hyperpigmentation— 11 April 2014 www.australiandoctor.com.au/education/how-to-treat

1. Which TWO statements are correct depigmented skin regarding the clinical features and a) Photo-patch testing helps the management regarding the pathophysiology of d) Sunscreen should be advised for both management of reticulate and mottled of Riehl’s melanosis by identifying the pigmentary disorders? hyperpigmentary and hypopigmentary hyperpigmentary disorders? causative agent to avoid a) Melanin, carotenoids and haemoglobin all disorders a) Confluent and reticulate papillomatosis b) The principal treatment for Berloque contribute to human skin colour usually forms between the breasts and on dermatitis is discontinuation of the offending b) Disorders affecting the enzyme tyrosinase 4. Which TWO statements are correct the back of young women substance may disrupt the production of melanin regarding the clinical features of b) Erythema ab igne is usually caused by c) Periorbital hyperpigmentation is readily c) Melanocyte numbers are never affected in circumscribed hyperpigmentary disorders? prolonged cold exposure treated with a chemical peel acquired conditions of pigment loss a) Melanocytic naevi, acanthosis nigricans c) Squamous cell carcinoma may develop d) Ophthalmology referral is essential for d) Darker skin colour is due to increasing and mastocytosis all have circumscribed as a long-term consequence of erythema patients with Hori’s naevus numbers of melanocytes hyperpigmented lesions ab igne b) Melasma presents as bilateral symmetric d) Prurigo pigmentosa may be effectively 9. Which TWO statements are correct 2. Which THREE statements are correct hyperpigmented macules treated with antihistamines and steroids regarding the clinical features of regarding clinical features associated with c) Lentigines, unlike freckles, darken on medication-induced hyperpigmentation? pigmentary disorder under Wood’s lamp exposure to sunlight 7. Which TWO statements are correct a) Drug-induced pigmentation usually fade examination? d) Freckles in the are a clinical feature of regarding the clinical features of facial when the drug is discontinued a) Pityriasis versicolor has a yellowish-white or fibromyalgia pigmentation? b) Drug-induced pigmentation usually occurs in copper-orange fluorescence a) Periorbital hyperpigmentation is never areas not exposed to the sun b) Vitiligo has increased sharpness of borders 5. Which TWO statements are correct familial nor due to contact dermatitis c) Fixed drug eruptions are usually gradual in c) Melasma has accentuated outer epidermal regarding the management of b) Naevus of Ota may be associated with onset layer pigmentation circumscribed hyperpigmentary disorders? increased intraocular pressure d) Common medications that may cause fixed d) Tuberous sclerosis has ovoid yellow patches a) Both epidermal and dermal melasma have a c) Riehl’s melanosis results from frequent drug eruptions include analgesics and good, curative response to treatment contact with sensitising allergens at a antibiotics 3. Which THREE statements are correct b) 50% of café au lait macules may clear with concentration that is too low to produce regarding the general management pigment laser typical eczematous dermatitis 10. Which THREE medical conditions principles of pigmentary disorders? c) Maintenance therapy is not required after a d) Poikiloderma of Civatte is a drop-like or may cause diffuse or systemic a) Formal counselling from a mental health successful chemical peel for melasma streak-like hyperpigmentation hyperpigmentation? professional may be helpful d) The primary aim of treatment of acanthosis a) Lung cancer b) Management of patient expectations nigricans is to correct the underlying disease 8. Which TWO statements are correct b) Addison’s disease is important regarding the management of facial c) Raynaud’s disease c) Tanning is a good strategy to improve 6. Which TWO statements are correct pigmentation? d) Hyperthyroidism

CPD QUIZ UPDATE The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2014-16 triennium. You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept how to treat Editor: Dr Steve Liang the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online. Email: [email protected]

Next week We conclude this series on disorders of pigmentation with a close examination of hypopigmentary disorders.

36 | Australian Doctor | 11 April 2014 www.australiandoctor.com.au