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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

The dyschromatoses are a group of pigmentary disorders characterized clinically by mixed and often guttate hypopigmented 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. Poikiloderma (a combination of hypo- and hyperpigmentation with telangiectasia and atrophy) must be excluded. In this article, we describe the dyschromatoses typically presenting in infancy and childhood, most of which are genodermatoses. The approach we have taken in classifying them is based on organ involvement. We hope this article will serve as a guide for dermatologists to the recognition of these uncommon conditions.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

When paediatric patients present with mixed hypo- and hyperpigmented lesions, a number of possible differential diagnoses must be considered (Table 1). Most conditions are genetic in origin. They can generally be classified based on the extent of involvement (i.e. skin only, skin plus other ectodermal structures, and skin plus systemic involvement) (Fig. 1). The distribution of the lesions is also an important aid to the diagnosis. Acquired dyschromatoses (e.g. cutaneous lupus erythematosus, systemic sclerosis, tertiary pinta, contact leucomelanosis) may also be seen in children, but are more common in adults, and will be discussed in a separate article on adult-onset dyschromatoses.

Table 1.   Differential diagnosis of infancy and childhood dyschromatoses.
  1. *Also known as hereditary congenital hypopigmented and hyperpigmented macules.

Genodermatoses
 Dyschromatosis symmetrica hereditaria
 Dyschromatosis universalis hereditaria
 Dyschromatosis ptychotropica
 Xeroderma pigmentosum
 Dyskeratosis congenita
 Epidermolysis bullosa with mottled pigmentation
 Ziprkowski–Margolis syndrome
 Chédiak–Higashi syndrome
 Cutis tricolor
 Westerhof syndrome*
 Syndrome with ectodermal dysplasia
Inflammatory skin disease & postinflammatory pigmentary alterations
 Cutaneous lupus erythematosus
 Systemic sclerosis
Infection
 Pinta (tertiary stage)
Drug and chemical induced dyschromatosis
 Contact leucomelanosis
 Drug-induced photoleucomelanodermatitis
Nutritional disorders
 Kwashiorkor
Miscellaneous conditions
 Dyschromic amyloidosis
image

Figure 1.  Approach to dyschromatoses with typical onset in infancy and childhood. DSH, dyschromatosis symmetrica hereditaria; DKC, dyskeratosis congenita; DUH, dyschromatosis universalis hereditaria, EBS-MP, epidermolysis bullosa simplex with mottled pigmentation; XP, xeroderma pigmentosum.

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Infancy and childhood dyschromatoses

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

Dyschromatoses typically involving only the skin

Dyschromatosis symmetrica hereditaria (DSH, also known as acropigmentation of Dohi) is an autosomal dominant genodermatosis, characterized by multiple small hypo- and hyperpigmented macules of irregular size and shape, distributed symmetrically on the face and distal limbs, especially the dorsa of the hands and feet (Fig. 2a,b). The palms, soles and mucous membranes are spared. The lesions usually develop before the age of 6 years, and persist for life.1 Histopathological examination of the hypopigmented and hyperpigmented macules reveals basal hypomelanosis and hypermelanosis, respectively. The differential diagnosis for DSH includes acropigmentation of Kitamura, which is characterized by slightly depressed, pigmented reticular macules on the dorsal surface of the limbs, without hypopigmentation.

image

Figure 2.  Dyschromatosis symmetrica hereditaria: (a,b) multiple small hypo- and hyperpigmented macules with irregular sizes and shapes on the dorsal side of the hands and feet of a 22-year-old man who developed pigmentary changes from the age of 2 years.

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Dyschromatosis universalis hereditaria (DUH) is an autosomal dominant disorder, presenting within the first year of life.2 It is characterized by a mixture of pinpoint to pea-sized hypo- and hyperpigmented macules with irregular borders, distributed over the trunk, abdomen and limbs (Fig. 3). Hyperpigmented macules are seen on the face in about 50% of the cases, resembling ephelides. The mucous membranes, palms and soles may be involved.1 Histopathological findings include focal increase in the melanin content of the basal layer in hyperpigmented lesions, and decreased melanin content in hypopigmented lesions. Occasionally, pigmentary incontinence is present.3 DSH and DUH usually affect only the skin; however, they are rarely associated with neurological abnormalities.4–6

image

Figure 3.  Dyschromatosis universalis hereditaria: mixture of pinpoint to pea-sized hypo- and hyperpigmented macules with irregular border on the abdomen of an18-year-old man, who developed pigmentary changes from the age of 6 months.

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Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is an autosomal dominant genodermatosis characterized by intraepidermal blisters after minimal trauma, and palmoplantar hyperkeratosis, nail dystrophy and mottled pigmentation. The onset of skin blistering occurs at or shortly after birth, and appears as blisters, either generalized, or localized to the limbs.7 Reticulate hypo- and hyperpigmentation usually begin in infancy, commonly involve the limbs and trunk, and are not related to the areas with previous blister formation.7 In contrast to cases with other EBS-associated mutations, most cases of EBS-MP are associated with a missense mutation in the V1 domain of the keratin 5 gene.8 This domain has been suggested to play a role in melanosome transport, which may underlie the abnormal pigmentation in EBS-MP. Histopathological examination of a hyperpigmented macule shows epidermal atrophy and increased basal pigmentation, which is most prominent in the area of greatest epidermal atrophy. Basal vacuolation is seen, and scattered dyskeratotic cells are present. Pigmentary incontinence is present, and is most noticeable where epidermal pigmentation is the greatest.7 The occurrence of blisters decreases with age; however, the pigmentation may either fade or persist.7

Dyschromic amyloidosis is a rare variant of primary cutaneous amyloidosis, characterized by multiple guttate hypopigmented macules on the background of hyperpigmentation on the trunk and limbs (Fig. 4). It may be admixed with characteristic lesions of macular or lichen amyloidosis. It is presumed to be a familial disorder with autosomal recessive inheritance and typical onset before puberty.9 There is no systemic association. Histopathological examination of hyperpigmented and hypopigmented lesions reveals amorphous eosinophilic material (amyloid) in the papillary dermis, with pigmentary incontinence in the dermis.10

image

Figure 4.  Dyschromic amyloidosis: multiple guttate hypopigmented macules on a background of hyperpigmentation on the upper back of a 13-year-old girl.

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Dyschromatoses with ectodermal structure involvement (ectodermal dysplasia)

Ectodermal dysplasias (EDs) are a group of inherited disorders characterized by structural or functional abnormalities of two or more ectodermal structures. The most commonly described ectodermal dysplasias include hypohidrotic ED, hidrotic ED, ankyloblepharon–ectodermal dysplasia–clefting (AEC) syndrome, and ectrodactyly–ectodermal dysplasia–clefting (EEC) syndrome. Some EDs that have been described in case reports and series also had coexisting skin dyschromatosis (Table 2).11–15

Table 2.   Infancy and childhood dyschromatosis with ectodermal structures involvement.
ReferencesPatients, n (study population)Pigmentary changesOther features
Berlin114 (2 male, 2 female of a parents with consanguineous marriage)Generalized greyish-brown hyperpigmentation with multiple guttate hypopigmented maculesSparse eyebrows with absent lateral area; delayed dentition hypodontia; short stature; sexual underdevelopment
Siemens121 femaleDiffuse hyperpigmentation with guttate hypopigmentation on acral and flexural areasMultiple keratotic follicular papules; atrophic skin on dorsa of the hands and feet; pili torti; platonychia
Chiba and Miura132 (a mother and a son)Skin hyperpigmentation with multiple pinhole-sized hypomelanotic macules on dorsal aspect of the hands and forearmsScalp hypotrichosis; thumb hypoplasia
Lucky et al.142 (1 female, 1 male, unrelated family)Multiple hyperpigmented macules with scattered hypopigmented macules on both groins, axillae, and neckAlopecia; abnormal thumb; short stature; delayed bone age; juvenile-onset diabetes mellitus
Winter et al.154 (a mother and 3 sons)Skin hyperpigmentation with raindrop depigmentation on the groins, lower abdomen, and neckTransient urticarial-like reaction on the arms and hands; sparse scalp hair; single upper central incisor; hypoplastic thumbs; short stature

Dyschromatoses with systemic associations

Westerhof syndrome (hereditary congenital hypopigmented and hyperpigmented macules) is characterized by congenital multiple, discrete, well-defined, asymmetrical hypo- and hyperpigmented macules and patches, ranging from 10 to 150 mm in diameter.16 They occur on any part of the body, without mucosal involvement. Histopathological examination shows a decreased number of epidermal melanocytes in the hypopigmented macules, and an increased number in the hyperpigmented macules.17 According to the original report by Westerhof et al.,16 the most probable mode of inheritance is autosomal dominant. The skin lesions may be an isolated finding, or may be associated with systemic conditions (e.g. growth retardation and mental deficiency).16,17

Cutis tricolour is the term introduced by Happle et al. in 199718 to describe the coexistence of congenital hyper- and hypopigmented lesions in close proximity to each other on a background of normal skin. These dichotomous pigmentary lesions most likely represent a didymosis (twin spotting). The pattern of hypo- and hyperpigmentation may be multiple small macules, diffuse patches, or streaks along the lines of Blaschko.19,20 The typical distribution is on the trunk and arms. Histopathological examination of hypopigmented lesions shows a decreased number of epidermal melanocytes, whereas pigmentary incontinence is noted in hyperpigmented lesions.21 Cutis tricolour is occasionally associated with systemic conditions (e.g. dysmorphic features, neuropsychiatric and skeletal abnormalities, and ipsilateral breast hypoplasia).20–22

Dyschromatosis ptychotropica is characterized by mixed hypo- and hyperpigmentation with neurological abnormalities, which develops in infancy.23 The skin lesions are multiple, irregular, small, hypo- and hyperpigmented macules measuring 2–4 mm in diameter. They are initially noted on the neck, axillae and inguinal regions, and slowly progress to extensive dyschromic changes on the trunk and limbs, with pronounced involvement of the body folds (ptychotropism means affinity to the body folds). Histopathological examination of the hyperpigmented area reveals basal hyperpigmentation with normal distribution of melanocytes.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, pigmentary changes, premature skin ageing, and increased risk of skin cancer. The skin may appear normal at birth, but exposure to sunlight gradually produces diffuse erythema, drying, scaling, and freckle-like hyperpigmentation on the face, anterior ‘V’ of the chest, dorsa of the hands and feet, and other sun-exposed areas, resulting in either dyschromic change (Fig. 5a,b) or poikiloderma. Skin cancers including basal cell carcinoma, squamous cell carcinoma and malignant melanoma can occur during the first decade of life.24 Ocular complications and neurological complications have been found in 40% and 20% of patients, respectively.24

image

Figure 5.  Xeroderma pigmentosum: (a,b) Multiple freckle-like hyperpigmented macules admixed with hypopigmented macules on the face and anterior V of the neck.

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Dyskeratosis congenita (DKC) is an inherited bone-marrow failure syndrome characterized by a triad of reticulate skin hyperpigmentation, nail dystrophy and mucosal leucoplakia. The pattern of inheritance is heterogeneous, with X-linked recessive, autosomal dominant and autosomal recessive subtypes.25 The primary finding is reticulate hyperpigmentation on the face, neck, shoulders and trunk. The mean age of onset of skin pigmentation is 9, 4 and 7 years in the X-linked recessive, autosomal dominant and autosomal recessive types, respectively. Multiple hypopigmented macules may be admixed between areas of hyperpigmentation. Skin atrophy and telangiectasia are occasionally seen. Other findings include alopecia of the scalp, eyebrows and eyelashes; premature greying of the hair, hyperhidrosis; nail dystrophy; and mucosal leucoplakia. The histological findings described in the literature vary from case to case. Common findings include flattening of the rete ridges, hyperkeratosis, basal hyperpigmentation, and melanophages in the upper dermis. Bone-marrow failure usually occurs in the second decade of life. Patients are also at increased risk of developing cancer, including oropharyngeal, gastrointestinal or pancreatic carcinomas, leucoplakia, and Hodgkin disease.25

Ziprkowski–Margolis syndrome is a rare X-linked recessive genodermatosis characterized by diffuse pigmentary dilution of the skin and hair from birth, with sparing of the buttocks and genital region.26,27 Later, multiple hyperpigmented macules develop in a symmetrical distribution, giving a leopard-like appearance. Other findings include heterochromia irides and congenital deafness.

Chédiak–Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by diffuse pigmentary dilution, immunodeficiency, bleeding tendencies, neurological deficits, and the presence of abnormal large cytoplasmic granules in all nucleated cells. Diffuse pigmentary dilution of the skin and hair from infancy is a typical feature. In dark-skinned patients, multiple guttate hypopigmentation may occur on a background of diffuse hyperpigmentation in sun-exposed areas.28,29 Patients usually develop an accelerated lymphoproliferative phase in late childhood. The disease is often fatal, as a result of haemorrhage and infections.

Kwashiorkor refers to an inadequate protein intake with reasonable caloric (energy) intake. This condition is more prevalent in children between 6 months and 8 years of age. The clinical presentations include failure to thrive, oedema of the limbs, muscle wasting, swollen abdomen, and changes of the skin and hair. The skin changes are characterized by hypopigmentation in the nappy area, upper legs and lower abdomen. It is marked in dark-skinned patients, and may follow abrasion or ulceration. Skin hyperpigmentation resembling ‘enamel paint’ marks occurs as the disease progresses, usually over pressure areas such as the extensor surfaces of the arms and legs. The skin is dry and split, resulting in pale areas between the cracks, described as ‘crazy paving dermatosis’.30

Treatment

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

In general, treatment options for genetic dyschromatoses are limited. In kwashiorkor, all cutaneous lesions are reversible with adequate protein and caloric intake. Acitretin has been reported to be an effective treatment for dyschromic amyloidosis.31 Split-thickness autograft may improve cosmesis in some patients with DSH.32 In some conditions (e.g. XP), rigorous sun protection is required. Camouflage using cosmetic makeup may be the only option in certain conditions. The psychosocial implications of the disease are also important, as dyschromatoses often cause psychological trauma, especially in school-age children, and thus appropriate counselling is needed.

Conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

Dyschromatoses in infancy and childhood are usually inherited. The distribution of pigmentation, and the associated dermatological and systemic involvement, are key to the diagnosis. We hope this article will serve as a guide to management of dyschromatosis in paediatric patients, as this is a group of diseases with heterogeneous causes, for which histological examination is rarely diagnostic.

Learning points

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions
  • • 
    Infancy- and childhood-onset dyschromatosis is usually, but not always, genodermatosis.
  • • 
    Infancy- and childhood-onset dyschromatosis can be differentiated by the distribution of the lesions, and the associated hair, nail, tooth, eccrine and systemic abnormalities.
  • • 
    Histopathological examination of hypo- and hyperpigmented lesions is usually not diagnostic. Clinical findings are the key to the diagnosis.
  • • 
    The prognosis of infancy- and childhood-onset dyschromatosis with skin involvement only is benign. However, conditions with systemic association (e.g. SP, DKC, CHS) often have a worse prognosis.
  • • 
    Comprehensive examination, early diagnosis and appropriate referral are important.
  • • 
    Treatment of infancy- and childhood-onset dyschromatosis is often unsatisfactory. Camouflage may be the only appropriate option, and the psychosocial effects are also important.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

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

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

CPD questions

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

Learning objectives

The purpose of these questions is to identify a practical approach to dyschromatosis with an onset in infancy and childhood based on the distribution, associated dermatological and systemic findings, and distinguishing features of each condition.

Question 1

Which one of the following diseases is not classified as a dyschromatosis?

a) Westerhof syndrome

b) Xeroderma pigmentosum

c) Ziprkowski–Margolis syndrome

d) Reticulate acropigmentation of Dohi

e) Reticulate acropigmentation of Kitamura

Question 2

Which one of the following diseases has the typical distribution on the body fold?

a) Cutis tricolor

b) Dyskeratosis congenita

c) Dyschromatosis ptychotropica

d) Dyschromatosis universalis hereditaria

e) Dyschromatosis symmetrica hereditaria

Question 3

Which one of the following diseases is histologically characterized by epidermal atrophy on the hyperpigmented lesion?

a) Cutis tricolor

b) Dyschromatosis ptychotropica

c) Dyschromatosis universalis hereditaria

d) Dyschromatosis universalis hereditaria

e) Epidermolysis bullosa simplex with mottled pigmentation

Question 4

Which of the following malignancies has been reported in dyskeratosis congenita?

a) Hodgkin’s disease.

b) Pancreatic carcinoma

c) Oropharyngeal carcinoma

d) Gastrointestinal carcinoma

e) All of the above

Question 5

Which of the following complications should be kept under surveillance in patients with photosensitivity, dyschromic changes in sun-exposed areas and premature skin ageing?

a) Skin cancer

b) Systemic infection

c) Bleeding tendency

d) Carcinoma of leucoplakia

e) All of the above

Instructions for answering questions

  1. Top of page
  2. Summary
  3. Introduction
  4. Infancy and childhood dyschromatoses
  5. Treatment
  6. Conclusion
  7. Learning points
  8. Acknowledgements
  9. References
  10. CPD questions
  11. Instructions for answering questions

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