Adult-onset dyschromatoses

Authors


  • Conflict of interest: none declared.

Dr Vasanop Vachiramon, Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University. 270 Rama VI Road, Rajthevi, Bangkok 10400, Thailand
E-mail: vasanop@gmail.com

Summary

The dyschromatoses are a group of pigmentary disorders characterized clinically by mixed and often guttate hypopigmentend and hyperpigmented lesions. There are many conditions that present with dyschromatosis, including genodermatoses, inflammatory skin diseases, infections, drug and chemical use, and nutritional disorders. Some conditions have extracutaneous features. In this article, we describe the dyschromatoses with typical onset in adulthood. Most diseases in this group are acquired conditions. To organize the various acquired dyschromatoses, we have categorized them into those with a history of chemical exposure, drug exposure or dermatological procedures, and those without a history of such exposure. In contrast to the genetic dyschromatoses, some acquired dyschromatoses are preventable and treatable. We hope this review will serve as a guide for dermatologists to the recognition and treatment of these conditions.

Introduction

Most adult-onset dyschromatoses are acquired (Table 1). Further differentiation can be made on the basis of history (e.g. drugs, chemicals and physical agent exposure) and clinical findings (e.g. distribution, associated dermatological and systemic involvement) (Fig. 1). Skin biopsy is useful in some cases [e.g. lupus erythematosus (LE), systemic sclerosis (SS)]. Laboratory investigation [e.g. antinuclear antibody, screening tests for syphilis (serum VDRL, Treponema pallidum haemagglutination, fluorescent treponemal antibody absorbed tests)] may be helpful when LE or secondary syphilis is suspected.

Table 1.   Differential diagnosis of adult-onset dyschromatoses.
Dyschromatoses secondary to chemicals, drugs, and physical agents
 Chronic arsenic toxicity
 Contact leucomelanosis
 Drug-induced photoleucomelanodermatitis
 Psolaren ultraviolet A photochemotherapy
Inflammatory skin disease & postinflammatory pigmentary alterations
 Cutaneous lupus erythematosus
 Systemic sclerosis
Infection
 Pinta (tertiary stage)
 Syphilitic leucomelanoderma
Miscellaneous conditions
 Acquired brachial cutaneous dyschromatosis
 Dyschromic amyloidosis
 Vagabond leucomelanoderma
Figure 1.

 Approach to dyschromatosis with typical onset in adulthood. PUVA, psoralen ultraviolet A.

Dyschromatoses secondary to chemicals, drugs and physical agents

Chemicals

There are many chemicals that cause contact leucomelanosis, including monobenzyl ether of hydroquinone, monomethyl ether of hydroquinone,1 phenyl–phenol compound,2 diphenylcyclopropenone,3 synthetic detergents,4 and betel leaf (Piper betel).5 These compounds diffuse into melanosomes of the pigment cells where they are oxidized by tyrosinase to produce free radicals which cause lipid peroxidation of cell membrane, resulting in melanocyte destruction.1

Monobenzyl ether of hydroquinone was used to treat acquired hyperpigmentation in the past. However, the side-effects include irritation, local sensitization, local and distant depigmentation, and leucomelanoderma. Van de Steen et al.3 reported hyperpigmentation with islands of hypopigmentation at the contact site and at remote sites in 4 out of 243 patients treated with topical diphenylcyclopropenone for alopecia areata. A preceding eczematous lesion was not present in all patients. The dyschromatosis appeared 4–14 months after the start of treatment, and remained unchanged during the follow-up period of 3–10 months. Patients with darker skin are at higher risk of developing this side-effect.

Contact leucomelanosis caused by betel leaves was described initially in Taiwanese patients who used steamed betel leaves as a home remedy to treat facial hyperpigmentation. This condition is characterized by hyperpigmentation interspersed with confetti-like hypopigmentation at the contact site (Fig. 2a,b). The condition can be divided into three stages. The first stage is the immediate bleaching stage, when irritant reaction is usually obvious. Most patients report a transient stinging sensation lasting a few minutes, and erythema lasting up to 2 days. The second stage consists of prominent hyperpigmentation, which develops after overexposure to sunlight. The third stage is characterized by confetti-like hypopigmentation induced by chemicals in the betel leaves such as phenol, catechol and benzene derivatives, which cause inhibition of melanin synthesis or melanocytotoxicity. Histopathological findings of the hyperpigmented area are basal hyperpigmentation and pigmentary incontinence in the dermis, whereas in hypopigmented spots, there is absence of melanocytes but presence of some melanophages in the dermis.5

Figure 2.

 Contact leucomelanosis due to betel leaf (Piper betel): (a) hyperpigmentation interspersed with confetti-like hypopigmentation on the face of a middle-aged woman who used steamed betel leaves to treat melasma (photo courtesy of Dr P. Wattanakrai). (b) Betel leaf.

Drug-induced photoleucomelanodermatitis is described as the combination of hyperpigmentation and depigmentation after transient photosensitivity in sun-exposed areas during periods of long-term ingestion of drugs. Causative agents include thiazide,6 meticrane,7 tetracycline and afloqualone.8 The clinical features include a pruritic erythematous rash in sun-exposed areas during the acute phase, and multiple depigmented spots on the background of hyperpigmentation in sun-exposed areas in the later stages. Histopathological examination of early lesions reveals spongiosis, basal liquefaction, perivascular lymphocytic infiltration, and upper dermal oedema. In the later stages, hyperpigmented lesions reveal basal hyperpigmentation and pigmentary incontinence, whereas depigmented lesions reveal epidermal atrophy and no basal pigmentation. Photopatch and oral-challenge tests are positive.8

Chronic arsenic toxicity is due to long-term exposure to arsenic compounds. The main sources of exposure are occupational exposure, ingestion of contaminated water, and use of drugs containing arsenic (e.g. Fowler, Pearson or Donovan solution, Asiatic pills, and traditional Chinese remedies). The onset of the clinical features is 6 months to > 10 years after exposure. Mucocutaneous features include skin hyperpigmentation, dyschromatosis, transverse white lines of the fingernails (Mees lines), palmoplantar hyperkeratosis, Bowen disease, basal cell carcinoma and squamous cell carcinoma, in both sun-exposed and unexposed areas (Fig. 3a). There are many patterns of pigmentary changes, including diffuse darkening of the palm or the entire body, and spotted melanosis on the chest, back or limbs. Oral mucosal involvement (diffuse, patchy or spotted melanosis) can include the tongue, gums or lips. Leucomelanosis is described as diffuse hyperpigmentation with superimposed guttate hypopigmented macules on the limbs, trunk and back, which have been described as resembling raindrops on a dusty road (Fig. 3b). This pigmentary change, although not present in all patients,9 tends to be permanent.

Figure 3.

 Chronic arsenic toxicity: (a) diffuse hyperpigmentation with superimposed guttate hypopigmented macules on the back resembling ‘raindrops on a dusty road’; (b) multiple hyperkeratotic papules on the palm. The white asterisk indicates a biopsy-proven squamous cell carcinoma.

Dyschromic skin changes have been reported after psoralen ultraviolet A (PUVA) therapy, in up to 2.3% of treated patients.10 The changes usually occur after 2–3 years of PUVA therapy.11 The condition is characterized by multiple irregular hyperpigmented macules admixed with hypo- and depigmented macules in areas that had been overdosed and exhibited marked erythema during the treatment phase. Histopathologically, the number of melanocytes is increased in hyperpigmented lesions, but decreased or normal in hypopigmented lesions. Melanocytes are larger than normal in both hyper- and hypopigmented areas.10,11

Inflammatory skin diseases and postinflammatory pigmentary alterations

Dyschromic skin changes are commonly seen in discoid LE. Hypopigmentation and depigmentation result from the vacuolar alteration with destruction of melanocytes in the basal layer of epidermis. The healed lesions are atrophic and depigmented, and may be surrounded by a rim of hyperpigmentation (Fig. 4). Histopathological examination of a depigmented lesion may show only postinflammatory pigmentary changes. However, the evidence of LE (e.g. basement-membrane thickening, hyperkeratosis, cellular infiltration and epidermal atrophy) may be seen.12

Figure 4.

 Healed lesions of discoid lupus erythematosus: atrophic, depigmented lesions surrounded by rim of hyperpigmentation.

In SS, there are many patterns of pigmentary change. The commonest is focal depigmentation with perifollicular hyperpigmentation or ‘salt and pepper’ pigmentation, which has been reported in up to 30% of cases (Fig. 5). It usually occurs over trauma-prone areas including the shins, elbows and dorsa of the hands. The pigmentation can occur in both sclerotic and nonsclerotic areas, and spontaneous resolution can occur.13,14 In addition, unusual hyperpigmented streaks over blood vessels on a background of depigmented skin on the legs have been reported.15

Figure 5.

 Dychromic change in systemic sclerosis: depigmentation with perifollicular hyperpigmentation (salt and pepper pigmentation).

Infection

Pinta is a contagious, nonvenereal disease caused by Treponema carateum. This disease affects predominantly poor, malnourished infants, children and adolescents who live in semi-arid, warm climate areas.16 The disease is transmitted between children before they are sexually active. Transmission occurs through direct contact with a cutaneous or mucous membrane lesion of an infected person.17 Pinta exclusively affects the skin. There are three clinical stages. The primary and secondary stage is characterized by erythematous papules and plaques. Dyschromic changes are typically seen in tertiary stage pinta, which takes 2–10 years to develop, and is characterized by symmetrical well-defined hyperchromic, hypochromic, achromic or dyschromic areas. More than one colour may be present in the same patient, resulting in a mottled appearance. Hyperchromic spots occur preferentially in sun-exposed skin areas, and hypochromic spots in unexposed areas. Histopathological findings in the late lesion include irregular acanthosis or epidermal atrophy. Lymphocytic infiltrate and melanophages may be present in the dermis. Treponemes may be seen in the epidermis by silver stain or immunofluorescent techniques.17 The treatment of choice is penicillin; primary and secondary lesions disappear 4–12 months after treatment. The pigmentary changes in tertiary pinta usually persist.

Pigmentary lesions may also be present in secondary syphilis. Multiple hypopigmented macules superimposed on hyperpigmented, reticulate patches (syphilitic leucomelanoderma) are characteristic. These pigmentary changes usually develop 6 months after the onset of the primary disease, are localized to the sides of the neck, chest and back, and are more common in women.18 Histological examination of a leucodermal lesion reveals T. pallidium around vessels and inside nerve fibres, and the mechanism responsible for hypopigmentation is possibly partial inhibition of the melanin transfer.19,20

Miscellaneous conditions

Acquired brachial cutaneous dyschromatosis is common in women with Fitzpatrick skin types III–IV in their fifth or sixth decades of life.21 It is characterized by asymptomatic grey-brown patches with an irregular geographical border, and superimposed multiple hypopigmented and slightly atrophic macules (Fig. 6). It is usually seen bilaterally on the dorsa of the forearms. The histopathological findings of the hyperpigmented lesion include epidermal atrophy, basal hyperpigmentation, solar elastosis and superficial telangiectasia, whereas in hypopigmented macules, epidermal atrophy and decrease in melanin in the basal layer of the epidermis are found. Association with poikiloderma of Civatte has been found in 45% of cases.

Figure 6.

 Acquired brachial cutaneous dyschromatosis: irregular brown patch with multiple atrophic hypopigmented macules on the extensor surface of the forearm.

Vagabond leucomelanoderma is characterized by multiple hypopigmented macules on a background of diffuse hyperpigmentation, especially on the neck, shoulder, axillae, wrists, groin and inner thighs. It is found in older people with alcoholism and malnutrition combined with poor hygiene and heavy infestation with lice and/or scabies; such patients are usually homeless. This condition most likely represents a combination of many disorders, and is improved with change in lifestyle.22

Treatment

Adult-onset dyschromatoses generally have a better treatment outcome than those in children, whose pigmentary disorders are mostly inherited. Some acquired diseases can improve once the cause is corrected. For those with an associated inflammatory component, anti-inflammatory medication (e.g. topical and systemic corticosteroids, topical calcineurin inhibitors) may be used. For some conditions (e.g. secondary syphilis, vagabond leucomelanoderma), treatment of the underlying cause may help reverse the pigmentary change. Autologous noncultured melanocyte grafting has been used successfully to treat the hypopigmented component of stable depigmented discoid LE.23,24

Photoprotection, including sun avoidance and the use of broad-spectrum sunscreen on large hypopigmented areas, is recommended. Hypopigmented lesions are more susceptible to sun damage, and hyperpigmented lesions will be more obvious after sun exposure because of the colour contrast between surrounding normal and hypopigmented skin. Camouflage using cosmetic or permanent makeup (cosmetic tattoos) can be used to cover the lesions. Possible risks and complications include infections, allergic reactions, scarring, and dissatisfaction with the colour and shape.25

Conclusion

Dyschromatoses in adults are usually acquired. History and physical examination (e.g. history of drug, chemical and physical agent exposure, the distribution of lesions, and associated dermatological and systemic involvement) are the most important tools for the diagnosis.

We hope this article will serve as a guide to the approach to adult patients presenting with a mixture of hypo- and hyperpigmented lesions. Histological examination of the skin and laboratory tests are useful in some instances, such as in SS and cutaneous LE.

Learning points

  • • Adult-onset dyschromatoses can be differentiated by history of exposure to drugs, chemicals and physical agents, characteristics and distribution of the lesions, and associated systemic involvement.
  • • Histopathological examination of hypo- and hyperpigmented lesions and laboratory investigation may be helpful in some cases.
  • • The prognosis of adult-onset dyschromatoses is usually benign, except in LE, SS and chronic arsenic toxicity, which can have systemic involvement.
  • • Dyschromatoses in adults generally have a better treatment outcome than in children, whose pigmentary disorders are mostly inherited. Some acquired diseases can improve once the cause is corrected.

Acknowledgements

We thank Drs P. Suchonwanit and S. Kanokrungsee for their help in the preparation of the illustrations.

CPD questions

Learning objectives

The purpose of these questions is to identify a practical approach to adult-onset dyschromatosis, based on the aetiology, distribution, and associated dermatological and systemic findings.

Question 1

Which one of the following agents has been reported as a cause of dyschromatosis?

a) Betel leaf

b) Diphenylcyclopropenone

c) Psoralen and ultraviolet A

d) Monobenzyl ether of hydroquinone

e) All of the above

Question 2

Which one of the following medications has been reported as a cause of photoleucomelanodermatitis?

a) Thiazide

b) Imatinib

c) Cyclophosphamide

d) Hydroxychloroquine

e) All of the above

Question 3

Which one of the following diseases has pigmentary changes characterized by focal depigmentation with perifollicular hyperpigmentation on trauma-prone areas?

a) Systemic sclerosis

b) Dyschromic amyloidosis

c) Syphilitic leucomelanoderma

d) Drug-induced dyschromatosis

e) Vagabond leucomelanoderma

Question 4

A 28-year-old woman with dark skin presents with a 4-week history of multiple hypopigmented macules superimposed on hyperpigmented, reticulate patches on the sides of the neck. Which of the following investigations is the most appropriate?

a) Patch test

b) Skin biopsy

c) Serum VDRL

d) Serum arsenic level

e) Serum antinuclear antibody

Question 5

Which of the following conditions is most commonly associated with acquired brachial cutaneous dyschromatosis?

a) Vitiligo

b) Skin thickening

c) Acanthosis nigricans

d) Poikiloderma of Civattte

e) Palmoplantar keratoderma

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