Continuing Education Activity

Piebaldism is an autosomal dominant disorder of melanocyte migration and development characterized by isolated congenital leukoderma (white skin) and poliosis (white hair) in a distinct ventral midline pattern. This activity outlines the pathophysiology, evaluation, and treatment of piebaldism and reviews the role of the interprofessional team in evaluating, treating, and managing patients with this condition.

Objectives:

• Identify the etiology of piebaldism.
• Review the history, physical, and evaluation of piebaldism.
• Outline the treatment and management options available for piebaldism.
• Describe interprofessional team strategies for improving care coordination and communication to advance the care of piebaldism and improve outcomes.

Introduction

Piebaldism is an autosomal dominant disorder affecting melanocyte migration and development characterized by isolated congenital leukoderma (white skin) and poliosis (white hair) in a distinct ventral midline pattern. The most common cause of piebaldism is a mutation in the KIT proto-oncogene. However, researchers have identified other mutations.[1] This mutation leads to abnormal melanocyte migration from the neural crest leading to leukoderma affecting the central forehead, central frontal scalp, mid-portion of the extremities, and central anterior trunk. Poliosis affecting a lock of hair just above the forehead is the most common finding in this disease. Histopathologic examination of the affected areas reveals an absence of melanocytes in the epidermis and hair follicles. If the diagnosis of piebaldism is suspected, a careful examination should take place to exclude overlapping syndromes with extra-cutaneous manifestations, such as Waardenburg syndrome.[1] Although benign and isolated to the skin, piebaldism can be socially disabling for affected individuals. Treatment is targeted to improve cosmesis, including skin grafting, cell transplantation, camouflage techniques, and the use of hair dye for poliosis.[2]

Etiology

Piebaldism is an autosomal dominant disorder with incomplete penetrance and variable expressivity of melanocyte migration. Inherited and de novo mutations in the KIT proto-oncogene and SNAI2 gene have been implicated. The clinical manifestations are present at birth.

Epidemiology

Piebaldism is a rare inherited disorder with an estimated incidence of less than 1 in 20000 individuals.[3] Both males and females are affected equally. There is no known racial predilection.

Pathophysiology

The most common cause of piebaldism is a mutation in the KIT proto-oncogene. During embryogenesis, the KIT ligand produced within a dermatomyotome binds to the KIT receptor (a tyrosine kinase receptor) on melanoblasts and melanocytes, allowing for survival and migration along a given dermatomyotome. Mutations in KIT within the 4q12 locus lead to abnormal melanocyte migration and the absence of melanocytes in the ventral midline of the epidermis. This absence leads to the characteristic central leukoderma and poliosis seen in piebaldism.[4] The site of mutation within the KIT gene correlates with the phenotypic severity of the disease.[5] Additionally, mutations in SNAI2 within the 8q11.21 locus, a transcription regressor of KIT and E-cadherin important in maintaining melanoblast homeostasis, have also been implicated in cases of piebaldism.[3]

Histopathology

Although the diagnosis is possible with physical examination and family history alone, a biopsy can help in equivocal cases. Histopathologic examination of affected tissue will reveal the absence of melanocytes within the epidermis and hair follicles. Areas of hyperpigmentation surrounding the areas of depigmentation show a normal number of melanocytes. Unlike vitiligo, there will be no inflammatory infiltrate within the affected dermis.

History and Physical

Leukoderma and poliosis will be present at birth in a characteristic ventral midline pattern. The most common finding is a white forelock in a triangular shape, which is present in up to 90% of cases of piebaldism (poliosis circumscripta).[6] The medial eyebrows and eyelashes may also be affected. The classic distribution of the well-circumscribed depigmented macules and patches includes the central forehead, anterior torso, and mid-portion of the extremities. Areas of hyperpigmentation may be present within or bordering the areas of depigmentation. Piebaldism is notable for the absence of extracutaneous manifestations.

Evaluation

The phenotypic findings of piebaldism will be apparent at birth. Despite incomplete penetrance and variable expressivity, detailed family history is useful to establish an inherited genetic cause. During the postnatal period, careful physical examination, including ophthalmic examination and neurologic examination, can help distinguish piebaldism from syndromic causes of leukoderma, such as Waardenburg syndrome and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, Hirschsprung disease (PCWH). Although Waardenburg syndrome may have a similar phenotypic appearance to piebaldism, there will also be extracutaneous features, such as congenital deafness and heterochromia. Concomitant Hirschsprung disease is concerning for PCWH. Wood's lamp examination is useful to distinguish between piebaldism and nevus anemicus and nevus depigmentosus.[7] A biopsy, including the full thickness of the epidermis, can be helpful in equivocal cases.

Treatment / Management

Although the depigmented areas of piebaldism are benign and stable, the appearance can be socially and psychologically debilitating for some patients. Treatment is challenging and focuses on improving cosmesis. Although temporary, cosmetic camouflage (make-up) and hair dye can improve quality of life.[1] The depigmented areas have been successfully treated using dermabrasion and split-skin grafting, autologous melanocyte transplantation, epidermal sheet grafting, and autologous cell suspension transplantation after superficial full surface ablation.[8][9][10][11] Due to the absence of the photoprotective effects of epidermal melanin, patients with piebaldism should receive education on proper sun protection of depigmented areas of the skin, including sunscreen and protective clothing.

Differential Diagnosis

The differential diagnosis for piebaldism includes genodermatoses with defects in melanocyte development. Unlike piebaldism, these genodermatoses have associated extra-cutaneous manifestations and include:[1]

• Waardenburg syndrome (Types 1-4)
• Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH)
• Tietz syndrome

The differential diagnosis also includes the following disorders of hypopigmentation and/or melanocyte destruction:[1]

• Vitiligo
• Nevus anemicus
• Nevus depigmentosus
• Tuberous sclerosis 
• Hypomelanosis of Ito
• Chromosome 4q12q21 deletions

Prognosis

Individuals with piebaldism will present at birth with stable leukoderma and poliosis. Unlike vitiligo, these areas of depigmentation do not progress after birth. However, reports exist of rare cases of spontaneous repigmentation.[3]

Complications

Isolated piebaldism has no known complications.

Deterrence and Patient Education

Upon making the diagnosis of isolated piebaldism, family members require reassurance that this is a benign condition that is unlikely to progress. Due to the absence of the photoprotective effects of epidermal melanin, patients with piebaldism should receive education on proper sun protection of depigmented areas of the skin, including sunscreen and photoprotective clothing.

Pearls and Other Issues

• Piebaldism is a disorder of melanocyte migration and development
• A white forelock is present in approximately 90% of cases
• It is crucial to rule out associated syndromes at birth (e.g., Waardenburg)
• Treatment options include camouflage techniques, hair dyes, skin grafting, and cell transplantation

Enhancing Healthcare Team Outcomes

The management of piebaldism at birth requires an interprofessional team approach, including providers from dermatology, pediatrics, gastroenterology, and genetics. The reason for this approach is that this disorder is rare and acquired at birth. Secondly, it has features that mimic many other skin disorders, and often, an exhaustive workup is required. When the condition presents at birth or soon after, the patient should obtain a referral by the primary care provider to a dermatologist.

The first step is accurately diagnosing piebaldism as either isolated or part of a syndrome with extracutaneous manifestations. 

A dermatologist can help in the initial diagnostic workup to determine the cause (Wood's lamp evaluation, biopsy), the extent of lesions, and the presence of extracutaneous manifestations. Upon making the diagnosis of isolated piebaldism, family members need reassurance that this is a benign condition that is unlikely to progress. Affected individuals may experience significant social disability during childhood, adolescence, and adulthood. In these cases, referral to a mental health professional is a prudent course, and they can report back to the team on the results of therapy. Some patients may need cognitive behavior therapy. For the skin lesion, treatment to improve cosmesis can be sought with a dermatologist or plastic surgeon. 

Due to the absence of the photoprotective effects of epidermal melanin, patients with piebaldism should receive education from the pharmacist, nurse, or primary care provider on proper sun protection of depigmented areas of the skin, including sunscreen and protective clothing.

All members of the interprofessional team need to keep each other informed and up to date on their activities. While piebaldism is a benign condition, it does not obviate the health care team from collaborative activity. The education of the family must be coordinated by clinicians. [Level 5]