Brown macules on a depigmented skin patch

HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Vesicular eruption in an ICU patient and Oral hyperpigmentation. Then take the post-test here. Piebaldism is a rare, autosomal...

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HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Vesicular eruption in an ICU patient and Oral hyperpigmentation. Then take the post-test here.

Piebaldism is a rare, autosomal dominant genodermatosis resulting from defective melanoblast migration. The estimated incidence in Caucasians is 1 in 40,000.¹ Although piebaldism can occur in any ethnicity, epidemiologic data in other races is lacking. Males and females are equally affected, which is expected in all disorders with autosomal dominant inheritance.

Piebaldism results from mutations in the KIT proto-oncogene, located on chromosome 4q11-12.1 KIT encodes the tyrosine kinase transmembrane receptor found on the surface of melanocytes, which binds steel factor. A functioning KITreceptor is required for the normal development and transport of melanocytes. The phenotype is variable depending on the location or type of mutation.

For example, a milder phenotype may be seen when mutations occur in the ligand-binding region, whereas a more severe phenotype may be seen when mutations occur in the tyrosine kinase receptor region of the receptor.² A variety of mutations have been reported including point mutations, deletions, splice mutations, and insertions in the KIT gene.^3,4

This mutation affects the development of melanocytes, both before melanoblast migration from the neural crest and postnatally, preventing melanoblast migration from the dorsally located neural crest cells (neck to posterior end) to the ventral surface of the body (forehead, abdomen, pre-tibial legs). Recently, a heterozygous deletion of SNAI2 gene has also been reported to cause piebaldism.¹ SNAI2 gene also encodes a transcription factor necessary for normal melanocyte development.¹ 

Clinically, piebaldism presents at birth with depigmented patches on the anterior midline body. The most common locations are the central anterior trunk, the mid-extremities, the central forehead, and the midline frontal scalp characterized by the white forelock.¹ A white forelock is seen in 80% to 90% of persons with piebaldism, and is triangular or diamond-shaped.¹ 

The skin underlying the forelock is completely amelanotic. The forelock may extend as far posteriorly as the vertex and as far anteriorly as the root of the nose, although extension to the nose has been rarely reported.¹ Poliosis (white hairs) of the eyebrows and eyelashes is common.¹ 

A distinctive feature of piebaldism is the presence of normally pigmented and hyperpigmented macules within the depigmented patches.² These macules may range in diameter from a few millimeters to several centimeters.¹ The depigmented areas are irregularly shaped, well-circumscribed, and milk-white in color.¹ 

Both the white forelock and the areas of leukoderma are present at birth and remain static over time. The exceptions to the relatively static nature of these lesions are the rare reports of spontaneous repigmentation, especially after injury.² 

The diagnosis of piebaldism is made clinically. However, if a skin biopsy is performed, the most notable finding is the complete absence of melanocytes in the depigmented area.² T

he histopathologic findings of the hyperpigmented macules are notable for an increased number of melanosomes in melanocytes and keratinocytes.¹ Electron microscopy also demonstrates the absence of melanocytes.¹ Gene mutation analysis is available but is not routinely performed as the clinical findings are relatively diagnostic.

Although the clinical findings of piebaldism are unique, the differential diagnosis of this condition includes vitiligo, halo nevus, and other genodermatoses with poliosis. Vitiligo is a common, acquired, automimmune condition resulting in depigmented macules and patches. 

Piebaldism often can be readily distinguished from vitiligo because of the presence of hyperpigmented and normally pigmented macules within areas of leukoderma in piebaldism. However, when vitiligo repigments, it begins from stem cells within the hair follicle, such that round, skin-colored macules develop within the patch of vitiligo in a follicular distribution. 

Features helpful in distinguishing repigmenting vitiligo from piebaldism are the time of onset, the natural history, and the location of the depigmented lesions. The depigmented patches of piebaldism are always present at birth, whereas vitiligo develops any time from shortly after birth to late adulthood.¹ 

The areas of leukoderma in piebaldism are stable, with no growth or development of new lesions. In contrast, depigmented areas in vitiligo enlarge with time, and it is common for patients to develop new areas of involvement. 

Lastly, due to the pattern of melanoblast migration in utero, the leukodermic areas of piebaldism are restricted to the anterior midline body, most commonly the midline frontal scalp, abdomen, and pre-tibial legs. In contrast, vitiligo has no such restriction and can appear anywhere on the body, with predilection for the face, dorsal hands, nipples, axillae, umbilicus, and the sacral, inguinal, and anogenital regions.¹ 

Rarely, piebaldism presents with only the white forelock. For an isolated circumscribed area of poliosis, the differential diagnosis includes halo nevus, vitiligo, and alopecia areata. The onset at birth and midline frontal location of the white forelock helps distinguish piebaldism from these other acquired conditions. In addition, alopecia areata will be preceded by a circumscribed area of complete hair loss preceding the onset of poliosis.

Many other syndromes can present with a circumscribed area of poliosis; however these syndromes have systemic findings, whereas piebaldism is restricted to skin and hair involvement. Like piebaldism, Waardenburg syndrome can also present with a white forelock on the midline frontal scalp. 

However, patients with Waardenburg syndrome will also present with any combination of the following features: congenital deafness, partial or total heterochromia iridis, medial eyebrow hyperplasia, and broad nasal root.¹ Similarly, Vogt-Koyanagi-Harada syndrome, Alezzandrini syndrome, white forelock with osteopathia striata, and white forelock with multiple malformations will present with various ophthalmologic, neurologic, skeletal, and cardiopulmonary findings, which piebaldism lacks.

As piebaldism is restricted to the skin and hair, the prognosis is excellent. Patients must be educated regarding good sun protection and sun avoidance to prevent sunburns in affected areas. Interventions are only necessary if patients are distressed by their cosmetic appearance. 

As no effective therapies exist, self-tanners and camouflage makeup (i.e., Dermablend or Covermark) are first-line treatments.⁵ There have been reports of autografts of normal skin into amelanotic areas, but this is not a readily available treatment option and requires multiple procedures.¹

The patient and his family were already aware of the diagnosis as other family members had the same genetic condition. However, a genetics referral was placed for counseling purposes.  

Audrey Chan, MD is a third-year dermatology resident at Baylor College of Medicine in Houston.

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HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Vesicular eruption in an ICU patient and Oral hyperpigmentation. Then take the post-test here.

References

1. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:922-923.
2. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011:861-862.
3. Agarwal S, Ojha A. Piebaldism: a brief report and review of the literature. Indian Dermatol Online J. 2012;3(2):144-147. Available at http://www.idoj.in/temp/IndianDermatolOnlineJ32144-7589397_210453.pdf; accessed April 15, 2014.
4. Richards KA, Fukai K, Oiso N, Paller AS. A novel KIT mutation results in piebaldism with progressive depigmentation. J Am Acad Dermatol. 2001;44(2):288-292.
5. Suga, Y, Ikejima A, Matsuba, S, Ogawa H. Medical pearl: DHA application for camouflaging segmental vitiligo and piebald lesions. J Am Acad Dermatol. 2002;47(3):436-438.