eMedicine Specialties > Pediatrics: General Medicine > Dermatology

Hypomelanosis of Ito: Differential Diagnoses & Workup

Author: Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Coauthor(s): Marcio Sotero de Menezes, MD, Associate Professor, Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Seattle, University of Washington
Contributor Information and Disclosures

Updated: Sep 29, 2008

Differential Diagnoses

Tuberous Sclerosis

Other Problems to Be Considered

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.10

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.11 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 HI, 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 HI.

Nevus depigmentosus

Nevus depigmentosus is characterized by hypochromic lesions in streaks and whorls, which also follow the lines of Blaschko. The hypochromic lesions tend to be circumscribed and are present at birth, changing little thereafter. Systemic abnormalities are rare in nevus depigmentosus.

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 HI, 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 HI. 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 HI. The reader is referred to Rosman, 1987, for a review of the clinical picture of incontinentia pigmenti.12

Vitiligo

Segmental vitiligo may be a consideration.13,14

Workup

Laboratory Studies

  • Chromosomal analysis
    • Blood karyotyping is indicated, especially when systemic abnormalities are present.
    • Fibroblast karyotyping (sampling the dark and light skin) can reveal mosaicism but is not mandatory for diagnosis.

Imaging Studies

  • Neuroradiological abnormalities are reported in at least one third of the patients. Because many of the lesions are dysplastic or neuroblastic migration abnormalities, MRI is more useful than CT scanning.
    • Increase in the T2 signal of white matter is one of the most common findings. White matter abnormalities are somewhat predictive of a poor neurological outcome.
    • Neuroblast migration includes heterotopia, pachygyria, and polymicrogyria. Heterotopia may be observed at the level of the basal ganglia or as a periventricular band. Some of the dysplastic lesions may be localized, and hemimegalencephaly is also visualized.
    • Cerebral atrophy can be unilateral or generalized. Cases of cerebral hemiatrophy and porencephaly are often associated with a history of perinatal hypoxia or low birth weight.
  • Other rare imaging associations include the following:
    • Noncommunicating hydrocephalus
    • Megacisterna magna
    • Arteriovenous malformation
    • Cerebellar hypoplasia (hemispheres and vermis)
    • Brainstem hypoplasia
    • Brain tumors: MRI rarely reveals brain tumors; thus, patients occasionally have abnormal MRI findings but are neurologically healthy.
  • Brain imaging in patients with hypomelanosis of Ito (HI) and medically refractory epilepsy: The area that generates seizures (zone of ictal onset) should be found using a prolonged video-EEG, single-photon emission computed tomography (SPECT) or positron emission tomography (PET), and high-resolution MRI. If resective epilepsy surgery is a serious consideration after the preliminary tests are done (video-EEG, SPECT or PET) and the zone of ictal onset could not be determined, the patient may need to undergo invasive EEG monitoring with subdural grids or strips.
  • Other imaging tests
    • Musculoskeletal abnormalities often require radiography for proper quantification. A CT scan of the chest may be necessary when mediastinal tumors are investigated.
    • Abdominal ultrasonography may be required for diagnosis of genitourinary anomalies such as single kidney and urethral duplication.

Other Tests

  • In patients with seizures, an EEG is indicated to show focal discharges and slowing.
  • Most patients with cardiac anomalies require an ECG.
  • Perform a slit lamp examination in patients with ophthalmologic abnormalities.

Procedures

  • Biopsies of affected and nonaffected skin are sometimes indicated.
  • In select patients with cardiac anomalies, cardiac catheterization is recommended for proper diagnosis.

Histologic Findings

Dihydroxyphenylalanine (DOPA) staining of the skin may reveal decreased size and number of melanosomes in hypopigmented areas. The melanocytes may be smaller and fewer, and their dendrites are short and sparse. Melanin incontinence (ie, melanin is absent in the epidermis but present in the deeper dermis) is not observed in patients with HI. Histopathological alterations are not always typical; normal histology findings have been described in some cases. Neuropathological studies demonstrate polymicrogyria, disarray of cortical lamination, and heterotopic neurons in the white matter and giant cells.

Ultrastructural cutaneous studies may reveal normal-appearing basal and malpighian keratinocytes but a lack of melanosomes in the malpighian cells.6 Melanosomes are dramatically reduced in the basal keratinocytes and appear small, single, or clustered and surrounded by a membrane. Melanocytic degeneration may be evident, and dendritic melanocytes contain various stages of nonmelanized premelanosome (stage II), partially melanized premelanosome (stage III), and, rarely, stage IV melanosomes. Unmyelinated axons of nerve-containing melanosomes may be seen at the dermoepidermal junction. Abnormal nerve termination has been observed in close relationship with basal keratinocytes, degenerated melanocytes, premelanosomes, and Langerhans cells.

More on Hypomelanosis of Ito

Overview: Hypomelanosis of Ito
Differential Diagnoses & Workup: Hypomelanosis of Ito
Treatment & Medication: Hypomelanosis of Ito
Follow-up: Hypomelanosis of Ito
References
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References

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Further Reading

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Keywords

hypomelanosis of Ito, HI, hypomelanosis of Ito syndrome, HI syndrome, incontinentia pigmenti achromians, whirled hypochromic skin lesions, hypopigmented skin, hyperpigmented skin, neurocutaneous disease, seizures, mental retardation, whirled-marble lesions, hemimegalencephaly, lines of Blaschko, whorled nevoid hypermelanosis, nevus depigmentosus, persistent mongolian blue spots, nevus of Ota, nevus marmoratus, angiomatous nevi, soft fibroma, pilomatrixoma, aplasia cutis, atopic dermatitis, slow hair growth, diffuse alopecia, trichorrhexis, widow's peak, generalized hirsutism, facial hypertrichosis, low hairline, ungual hypoplasia, abnormal, generalized tonic-clonic seizures, Lennox-Gastaut syndrome, autism, hypotonia, pes valgus, genu valgus, brain tumors, macrocephaly, microcephaly, medulloblastoma, choroid plexus papilloma, ataxic gait, sensory neuropathy, chronic distal spinal muscular atrophy, torticollis, auditory conduction defect, hyperactivity, spina bifida occulta, visual field defects, polymicrogyria, disarray of cortical lamination, heterotopic neurons in the white matter, tessellated fundus, radial hypopigmented streaks, unilateral heterochromic iris, myopia, hyperopia, astigmatism, megalocornea, opaque corneas, scleral melanosis, strabismus, slow pupillary response, pupillary atrophy, pupillary irregularity, nonclosure of the upper eyelid, ptosis, symblepharon, optic atrophy, choroidal atrophy, microphthalmia, macrophthalmia, epicanthal folds, dacryostenosis, nystagmus, musculoskeletal abnormalities, arm and leg length discrepancy, scoliosis, finger atrophy, syndactyly, polydactyly, clinodactyly, bifid thumb, luxatio coxae, hypertelorism, coarse facies, cleft lip and palate, delayed fontanelle closure, asymmetry of the head, imperfect teeth implantation, partial anodontia, dental dysplasia, defective enamel, hamartomatous cuspids, ventricular septum defect, atrial septum defect, pulmonary artery stenosis, Tetralogy of Fallot, incomplete right bundle branch block, cardiomegaly, hypospadias, micropenis, single kidney, urethral duplication, cryptorchidism, precocious puberty, gynecomastia, asymmetrical breasts, nephritis, segmental dilation of the colon, diaphragmatic hernia, umbilical hernia, inguinal hernia, proteinuria, focal segmental glomerulosclerosis, end-stage renal disease

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Contributor Information and Disclosures

Author

Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Marcio Sotero de Menezes, MD, Associate Professor, Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Seattle, University of Washington
Marcio Sotero de Menezes, MD is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society
Disclosure: Nothing to disclose.

Medical Editor

Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center
Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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