Pediatric Hypomelanosis of Ito Differential Diagnoses

Updated: Aug 04, 2022
  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
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Diagnostic Considerations

Many other skin pigmentary abnormalities may be associated with systemic and neurological abnormalities. In tuberous sclerosis, the lesions are round, oval, or in the shape of an ash leaf and do not follow the lines of Blaschko. [24]  A novel mosaic neuroectodermal syndrome may resemble hypomelanosis of Ito. [25]  

Linear and whorled nevoid hypermelanosis

These conditions are characterized by brown pigmentation and hypopigmentation in streaks and whorls, which follow the lines of Blaschko. Because determining whether the darker or lighter skin color is the normal one is difficult, Sybert suggests that differentiating the dermatological features of linear and whorled nevoid hypermelanosis from the ones found in hypomelanosis of Ito (HI) is virtually impossible. [26] In patients with linear and whorled nevoid hypermelanosis, the lesions appear in infancy and gradually spread though the body. This feature is not helpful in the differentiation from hypomelanosis of Ito, in which skin lesions are present at birth in more than one half of patients. Linear and whorled nevoid hypermelanosis are not associated with systemic abnormalities, unlike in hypomelanosis of Ito.

Nevus depigmentosus

Nevus depigmentosus is characterized by hypochromic lesions in streaks and whorls, which also follow the lines of Blaschko. [27] The hypochromic lesions tend to be circumscribed and are present at birth, changing little thereafter. Systemic abnormalities are rare in nevus depigmentosus; it may rarely be seen together with eccrine angiomatous hamartoma and nevus spilus. [28]

Incontinentia pigmenti

Incontinentia pigmenti (IP) is a condition seen mostly in girls; thus, X-linked dominant transmission is postulated. Patients with IP frequently have systemic involvement, similar to the involvement in patients with hypomelanosis of Ito, including CNS manifestations. In patients with IP, cutaneous lesions undergo 3 stages, which may overlap.

The first phase is characterized by vesiculobullous lesions that appear in a linear array (with no dermatomal distribution) and are present from birth or develop in the first 2 weeks of life in 90% of patients. Vesicles are proximal in the limbs, are located in flexor surfaces, and contain eosinophils. This first phase may last days to months. Between the second and sixth week of life, the vesicles become pustular, verrucous, or keratotic, marking the second phase. In this phase, the lesions tend to be more distally and dorsally prominent in the limbs.

The second phase, during which hypopigmentation and skin atrophy develop, usually lasts for months.

During the third phase, hyperpigmentation of lesions is observed, peaking from 12-26 weeks of life. The dermatological appearance involves streaks, whorls, macules, and flecks. The color of the lesions is chocolate-brown or tan. Some patients are born with lesions already in the third phase. This phenomenon is thought to be caused by in utero onset of the inflammatory process.

The term incontinentia pigmenti is used because melanin is not observed in the epidermis but is present in the dermis, as if it had leaked or dropped into the deeper layer of the skin; thus, the epidermis is incontinent of melanin. This incontinence of melanin is not observed in the skin of patients with hypomelanosis of Ito. Alopecia may be observed in one third of patients with IP.

Neuropathologically, patients with IP may show neuroblast migration disturbances, such as polymicrogyria. Inflammatory and destructive alterations often accompany IP lesions, which is a pattern often missing in hypomelanosis of Ito. The reader is referred to Rosman, 1987, for a review of the clinical picture of incontinentia pigmenti. [29]

Voigt-Futcher pigmentary demarcation lines

Pigmentary demarcation lines are physiological abrupt transitions between hyperpigmented and lighter skin, a common finding dark-complexioned women and a substantial percentage of light-complexioned ones. [30]


Segmental vitiligo may be a consideration. [31, 32]

Pityriasis alba

Pityriasis alba, a localized hypopigmented disorder, has many existing clinical variants, some of which may require distinction from IP. [33]

Differential Diagnoses