Pigmentary Disorders In Children

BULLETIN FOR MEDICAL PRACTITIONERS

Dr Steven Thng Tien Guan

Adjunct Associate Consultant Dermatologist, National Skin Centre

Introduction

Pigmentary disorders are a common presentation to the dermatologist and in some cases, may be an indication of a more serious underlying systemic disease. Therefore, it is of utmost importance to develop a systemic approach to patients presenting with pigmentary disorders so as to come to an appropriate diagnosis and subsequent correct management.

Pigmentary disorders generally present as distinct problems of hypopigmentation or hyperpigmentation; although in some conditions, both hypo and hyperpigmented lesions occur together.

Disorders of hypopigmentation

The onset, distribution and pattern of lesions give valuable clues to the diagnosis.

>A. Present at birth/infancy

Hypopigmentation at birth or during infancy can be approached clinically based on the following groups: generalized hypopigmentation, localized, patterned hypopigmentation and localized, non-patterned hypopigmentation.

A-I. Generalized hypopigmentation

Oculocutaneous albinism

This group of disorders includes classic genodermatoses such as oculocutaneous albinism (OCA). Patients usually have a positive history of similar pigmentary disorders in the family. Patients with OCA have a pigmentary dilution of the hair, eyes and skin that is present at birth. The different types of oculocutaneous albinism, gene mutations as well as clinical manifestations are as summarized in Table 11.

In general, the more severe the pigmentary dilution, the more severe the ocular findings such as decreased visual acuity2. Other than visual acuity problems, a major complication of all forms of OCA is the development of cutaneous squamous cell carcinomas. Prompt diagnosis is important because early ophthalmological intervention and surgical correction of ocular abnormalities can be instituted. In addition, rigorous sun protection can be instituted at an early age to prevent development of cutaneous carcinomas.

A-II. Localized, patterned hypopigmentation

Hypomelanosis of Ito3

This neurocutaneous disorder is usually a sporadic condition although there have been some reports of autosomal dominance inheritance. This disorder is characterized by bilateral, symmetrical, hypopigmented macules in a whorled or streaked pattern, often following the lines of Blaschko. The trunks and extremities are usually involved. The disease is often associated with neurological, musculoskeletal and ocular abnormalities. These include seizures, mental retardation, developmental delays, macrocephaly, strabismus, nystagmus and hypertelorism among others.

Piebaldism

This is an autosomal dominant disorder characterized by congenital patches of depigmentation that lack melanocytes on histology. The characteristic features include a white forelock, depigmented triangular patch over the forehead and scalp and variable symmetrical patches on the trunk. The depigmented patches are usually on the ventral aspect and symmetrical and the primary pathology of this condition is from mutations of the kit protooncogene which codes for tyrosine kinase receptor. Mutation of the c-kit proto-oncogene causes a failure of migration and proliferation of melanocytes during melanogenesis4.

Waardenburg’s syndrome

This is autosomal dominant condition that presents with similar features as patients with piebaldism except that patients with Waardenburg’s syndrome also presents with heterochromia irides and dystopia canthorum (lateral displacement of inner canthus) and sensory-neural deafness. Treatment for this group of patients involves early detection of deafness and early intervention with hearing aids and specialized education.

A-III. Localized, non-patterned hypopigmentation

Naevus depigmentosus5

This uncommon congenital, nonhereditary, hypomelanotic lesion usually appears on the trunk as a unilateral, hypopigmented macular patch with irregular, serrated borders. The patch is off white in colour and on biopsy, there is a normal complement of melanocytes but a reduction in the number of melanosomes in melanocytes and keratinocytes.

Ash leaf spot (Figure 1)

This is designated as a tertiary feature in the diagnosis of tuberous sclerosis (TS). Not only are Ash leaf spots the earliest sign of tuberous sclerosis, they are also the most common cutaneous findings, seen in at least 87% of patients.

Naevus anaemicus

This is not a nevoid condition per se but rather, is an area of localized vasoconstriction. This condition can be easily differentiated with the above 2 conditions by simply blanching the ‘hypopigmented’ macules. The above 2 conditions are not blanchable while naevus anaemicus ‘disappears’ on pressure.
 

B. Onset during childhood

B-I. Autoimmune hypopigmentation

Vitiligo

Vitiligo is an autoimmune disorder characterized by ivory white patches secondary to immune destruction of the melanocytes. There are 2 main types of vitiligo:

Vitiligo vulgaris: this is the symmetrical generalized form of vitiligo developing in dorsa of hands, face, neck, trunk, umbilicus, genitalia and anus. This form of vitiligo can appear at sites of trauma or sunburn.

Segmental vitiligo: This variant of vitiligo is asymmetrical and usually confined to one nerve segment. This form of vitiligo is more common in children and is highly associated with autoimmune disorders and pre-mature greying.

The course of vitiligo is one of remission and exacerbation. Complete spontaneous remission is unusual and partial and temporary repigmentation has been reported in children for lesions less than 2 years of age6.

Localized patches of vitiligo can best be treated with topical steroids. A good response can be seen in 30-50% of the patients. Narrow-band UVB (NBUVB) therapy is an effective treatment modality for children with extensive vitiligo. Oral psoralen with UVA is not recommended for children with vitiligo as there is a long-term risk of skin carcinoma. Transplantation with autologous melanocytes can be performed in patients with stable vitiligo.

Vogt-Koyanagi-Harada syndrome7

This is a rare disorder characterized by bilateral uveitis, alopecia, vitiligo, deafness as well as meningeal irritation. It is therefore, of utmost importance to rule out this disease in patients presenting with vitiligo as the uveitis as well as meningeal irritation, if not recognized and treated early, will lead to permanent damage.

Alezzandrini syndrome

Patients with this condition presents similar to VKHS except that they have unilateral poliosis and vitiligo as opposed to VKHS.

B-II. Infectious hypomelanoses

The common causes of infectious hypomelanoses include tinea versicolor, leprosy and syphilis. Although tinea versicolor tends to affect adolescents, it can also occur in young children and even infants. Infection with Mycobacterium leprae will also present with hypopigmented macules and these macules are usually anaesthetic. Careful palpation of the cutaneous nerves might reveal thickened nerves confirming the diagnosis of Hansen’s disease. All cases of Hansen’s disease must be notified and referred to the appropriate centres for management.

B-III. Inflammatory hypomelanoses

These are common causes of hypomelanoses presenting in childhood. Pityriasis alba is a very common finding in prepubertal children with a personal or family history of atopy. Lesions commonly appear on the face, neck and arms and they consist of ill-defined, hypopigmented macules, a few centimetres in size with a white powdery scale. A skin scrape to rule out tinea versicolor is done in atypical cases and treatment is mild topical steroids like hydrocortisone. Other forms of post inflammatory hypopigmentation that might present in childhood include lichen sclerosus, pityriasis lichenoides, Darier’s disease etc.

B-IV. Others

Hypopigmented mycosis fungoides (Figure 2) is a common presentation of the disease in children. Patients usually present with hypopigmented macules and patches that might be scaly, and most commonly located over the trunk as well as the buttocks. Histological findings of epidermotropism of atypical lymphocytes confirm the disease. Other miscellaneous conditions that causes hypopigmentation in childhood includes sarcoidosis, leucoderma at sites of vaccination, cryosurgery for viral warts as well as topical medications like tretinoin and potent corticosteroids.

Disorders of hyperpigmentation

The pattern and characteristics of the hyperpigmentation give valuable clues as to its aetiology.

I. Generalised hyperpigmentation

Patients presenting with generalized hyperpigmentation usually have a more serious underlying systemic disorder. The major systemic disorders associated with generalized hyperpigmentation included endocrinopathies, nutritional diseases, autoimmune disorders as well as medications.

Endocrinopathies, like Addison’s disease, Nelson’s syndrome, Cushing’s syndrome, as well as metabolic disorders like haemochromatosis, Fanconi’s anaemia and Wilson’s disease all cause generalized hyperpigmentation. A detailed history and physical examination should point one to the possible diagnosis.

Several chemotherapeutic agents like cyclophosphamide, busulphan and hydroxyurea can produce diffuse hyperpigmentation too. Other drugs implicated included minocycline as well as chlorpromazine.

Diffuse hyperpigmentation is seen also in patients with nutritional deficiencies of several vitamins including folate, Vitamin B12 and niacin. Deficiency in niacin causes pellagra where the clinical picture is that of hyperpigmentation on sun exposed areas as well as upper chest. The hyperpigmentation accompanying kwashiorkor is different in that there is no relationship to sun and the skin is often fragile.

II. Reticulated hyper/hypo pigmentation

All the diseases discussed under this heading are rare and are usually genetic disorders.

Dyschromatosis universalis8

There are 2 variants of dyschromatosis universalis. A localized type known as reticulated acropigmentation of Dohi, which presents during infancy or childhood. Patients presents with bilateral symmetrical pinpoint hyper/hypo pigmentation on hands/feet and elbows. Palms and soles, mucous membranes, nails and hairs are usually spared. The second form of dyschromatosis universalis is the generalized type. This is inherited as an autosomal dominant condition and is found only in Asian families. It presents during infancy or early childhood with hyper and hypo pigmented macules all over body sparing face.

Incontinentia pigmenti

This is an X-linked dominant condition and therefore presents mainly in females. Patients goes through 4 stages and it is during the 3rd and 4th stage that patients may present with streaks and whorls of grey-brown pigmentation along the lines of Blaschko. Reticulated acropigmentation of Kitamura Patients present during the first decade of life with slightly depressed, well-demarcated, brown macules on dorsum of hands and feet that spread centripetally. Patients also have palmar and plantar pits.

Dyskeratosis congenita9

This group of patients usually presents at 4-10 years of age with a triad of reticulate hyperpigmentation and nail dystrophy and leukoplakia of the mucous membranes.

III. Velvety hyperpigmentation in flexural regions

There are 2 main conditions that presents with velvety hyperpigmentation along flexural regions. They are:

Acanthosis nigricans

There are 4 types. There is the familial type, an autosomal dominant condition which develops after puberty; acanthosis nigricans associated with endocrinopathy like insulin dependent diabetes and Cushing’s syndrome, acanthosis associated with obesity as well as acanthosis associated with malignancy.

Dowling-Degos disease

This presents like acanthosis nigricans with discrete brown/oval macules that coalesce and become lacelike, reticulated pattern. However, patients also have pitted acneiform scars in the perioral region with hyperkeratotic, comedo-like follicular papules on neck and axillae.

IV. Hyperpigmented brown macules

This is the commonest hyperpigmented group of disorders presenting in young children. Conditions that presents with hyperpigmented macules include Café-aulait macules (CALM), lentigenes, freckles, Becker’s naevus as well as mastocytosis.

Café-au-lait macules (CALM)10

CALMs are oval to round, light brown macules measuring about 0.5 to 20 cm in diameter. They appear at birth or shortly thereafter. They are present in 10-20% of normal population but it may be a sign of neurofibromatosis as 90% of patients with neurofibromatosis have multiple CALMs. According to Growe and Schull, the presence of six or more CALMs, >1.5cm in diameter in adults or >0.5 cm in prepubertal children is a presumptive sign of the presence of neurofibromatosis (Figure 3). Other syndromes that have a definite association with CALMs are McCune- Albright syndrome, Watson syndrome, Bloom’s syndrome etc.

Idiopathic CALMs can be treated with pigment laser with a success rate of about 50% but they recur in 50% of the cases that responded to laser treatment.

Lentigenes

Lentigenes are small, dark brown to black, oval macules usually of 1-2 cm in diameter. They usually appear in childhood and increase in number up to adulthood. Lesions can appear on any area and they are unaffected by sun exposure. Histologically, they have an increase in the number of melanocytes. Patients with multiple lentigenes may have an underlying syndrome and these include Leopard and Lamb syndrome, Peutz-Jeghers syndrome, centro-facial lentiginosis etc. Lentigenes can easily be treated with the pigment laser with good response.

Freckles

Freckles, or ephelides, are light brown macules usually less than 5mm in diameter. They appear between the ages of 2 to 4 years in fair-skinned individuals and are found mainly on face, shoulders and upper back. They get darker on sun exposure and freckles can be inherited as an autosomal dominant trait. They are also present in several disorders like xeroderma pigmentosum, progeria and neurofibromatosis. The numbers of melanocytes are normal.

Becker’s naevus

Becker’s naevi (Figure 4) represent localized hamartomas and are found mainly in the male population. There is usually a sudden onset of hyperpigmentation, during puberty, followed by a slow expansion phase and they are usually unilateral lesions found commonly on the shoulders and upper trunk. Partial lightening of the hyperpigmentation has been reported following treatment with Q-switched ruby or Nd:YAG lasers.

Mastocytosis

Mastocytosis, or urticaria pigmentosa, can present with hyperpigmented macules and papules, which may be confused with lentigenes, melanocytic naevi or even CALMs. Once the diagnosis of mastocytosis is considered, a positive Darier’s sign and the presence of an increased number of mast cells in the biopsy specimen quickly confirms the diagnosis.

V. Hyperpigmented bluish macules

The melanocytes found in these disorders are situated deeper into the dermis and as such, the lesions appear bluish black in colour. These lesions are usually nevoid and represents failure of migration of melanocytes into the epidermis. Conditions presenting with bluish pigmentation include Mongolian spot, Naevus of Ota and Naevus of Ito (found on the trunk). All these lesions may lighten with Q-switch Nd:YAG laser.

Conclusion

This short article covers the common disorders of pigmentation that may present during childhood. It can be seen that many of the pigmentary disorders have a more serious underlying systemic disease and as such, patients presenting with pigmentary disorders during childhood should be properly assessed before any plans are made to remove the pigmentary disorder whether it be by topicals, lasers or surgical means. 

References

1. Richard A. King. Albinsim. In: James J. Nordlund, Raymond E. Boissy, Vincent J. Hearing, Richard A. King, Jean-Paul Ortonne, eds. The Pigmentary System. Oxford. Oxford University Press, 1998: 553-569.
2. Jean L. Bolognia. Disorders of hypopigmentation and hyperpigmentation. In: Textbook of paediatric dermatology. Oxford University Press, 1999: 837-979.
3. Nelly Rubeiz, Abdul-Ghani Kibbi. Disorders of pigmentation in infants and children. Clinics in Dermatology; 2002: 20: 4-10.
4. Tomita Y. The molecular genetics of albinism and piebaldism. Arch Dermatol. 1994; 130:355-8.
5. Coupe RL. Unilateral systematized achromic naevus. Dermatologica 1967: 134: 19-35.
6. Cline DJ, Nordlund JJ. Vitiligo. In Greek KE, ed. Common problems in dermatology. Chicago; Year Book Medical Publishers, Inc, 1988: 421-30.
7. Westerhof W, Njoo D. Miscellaneous hypomelanoses. In: James J. Nordlund, Raymond E. Boissy, Vincent J. Hearing, Richard A. King, Jean-Paul Ortonne, eds. The Pigmentary System. Oxford. Oxford University Press, 1998: 672-677.
8. Rycroft RJG, Calnan CD, Wells RS. Universal dyschromatosis. Clin Exp Dermatol 1977; 2: 45-8.
9. Sirinavin C, Trowbridge AA. Dyskeratosis congenita: clinical features and genetic aspects. J Med Genetics 1975; 12: 339-54.
10. Growe FW, Schull WJ. Diagnostic importance of café au lait spot in neurofibromatosis. Arch Intern Med 1953; 91: 758.
     

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By National Skin Centre (Singapore)
Copyright (C) 1995 - National Skin Centre (Singapore)
 

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