PEDIATRIC DERMATOLOGY Series Editor: Camila K. Janniger, MD Nevus of Ota in Children Smeeta Sinha, MD; Philip J. Cohen, MD; Robert A. Schwartz, MD, MPH Nevus of Ota, synonymously termed oculodermal seen most commonly in individuals of Japanese melanosis, is an uncommon dermal melanosis descent, and is less likely to present in individuals most commonly seen at birth in children of of Chinese or Korean descent, though individuals Japanese descent, though it can affect individu- descending from the Indian subcontinent, Africa, als of any age or ethnicity. The disease tends to and Europe also may be affected.7 In early sur- persist and extend locally, becoming increasingly veys of Japanese patients at dermatology clinics, prominent with age, puberty, and postmenopausal the incidence of nevus of Ota was determined to state. Treatment should begin early after diagno- be 0.4% (110/27,500).4 Cowan and Balistocky8 sis using multiple sessions of laser photother- calculated the incidence of oculodermal melano- molysis to avoid darkening and extension of the cytosis in black patients to be 0.016%. A study of lesion. Important associated disorders include 2914 Chinese children in Calgary, Alberta, Canada, ipsilateral glaucoma; intracranial melanocyto- reported an incidence of oculodermal melanocytosis sis; and rarely cutaneous, ocular, or intracranial of 0.034% (1/2914).9 melanoma. Recommendations are discussed for managing nevus of Ota in children. Clinical Manifestation Cutis. 2008;82:25-29. The typical nevus of Ota is a unilateral facial dis- coloration that is macular, speckled, and bluish gray or brown, with edges that blend with bordering skin evus of Ota is a rare disorder characterized (Figure).10 The dermatomal distribution of pigment by melanocytic pigmentation of the sclera characterizes this diagnosis in most cases. Typical Nand ipsilateral skin along the distribution locations (in order of decreasing frequency) include of the ophthalmic and maxillary branches of the the skin of the upper and lower eyelids, temples, fifth cranial nerve. Hulke1 is credited with first zygomatic region, and forehead.5,11 The area affected describing oculodermal melanosis (nevus of Ota) in usually lacks hair and is ordinarily unilateral, though 1861. In 1916, Pusey2 observed a Chinese student 5% of patients demonstrate bilateral pigmentation.10 affected by the disorder. In 1939, Japanese dermatol- The disease tends to persist and extend locally, ogy professor Masao Ota3 characterized and descrip- becoming increasingly prominent with age, puberty, tively named the disorder naevus fusco-caeruleus and postmenopausal state. Approximately 60% of ophthalmomaxillaris. Yoshida4 conducted a large sta- cases present at birth or shortly thereafter, with the tistical study of Japanese patients with nevus of Ota and further elaborated clinical aspects of the disease. In 1956, Fitzpatrick et al5 renamed the syndrome oculodermal melanocytosis. Nevus of Ota affects females approximately 5 times more often than males.6 It is known to affect individuals with darker-pigmented skin, is Accepted for publication September 6, 2007. From Dermatology and Pediatrics, New Jersey Medical School, Newark. The authors report no conflict of interest. Correspondence: Robert A. Schwartz, MD, MPH, Dermatology, New Jersey Medical School, 185 South Orange Ave, Newark, NJ A 12-year-old girl of sub-Saharan descent with nevus 07103 ([email protected]). of Ota. VOLUME 82, JULY 2008 25 Pediatric Dermatology remainder presenting at puberty.6,10 Patients have the leptomeninges more often than the dural and reported heightened pigmentation with fatigue, parenchymal tissues.13 Consequently, periodic der- menstruation, insomnia, environmental tempera- matologic evaluation is warranted in these patients, ture extremes, and cloudy weather.5,6,10,11 along with biopsy of rapidly changing nevi. Oculodermal melanocytosis is not known to fol- Another well-known complication associated low a recognizable inheritance pattern, though there with oculodermal melanocytosis is glaucoma in are cases of families with multiple members affected the ipsilateral eye, which has been described in by the condition.6 Other disorders that may be approximately 10% of patients.12,22 Glaucoma may associated with the nevus of Ota include the related be detected at birth or any age, is usually open nevus of Ito, telangiectatic nevi in phakomatosis angle,22,23 and typically is asymptomatic with gradual pigmentovascularis, nevus flammeus, and neurofi- loss of visual acuity. The pathophysiologic process bromatosis.11-13 Nevus of Ota has been associated leading to glaucoma in these patients is most likely with Sturge-Weber and Klippel-Trenaunay-Weber deposition of melanocytes within the trabecular syndromes; a neurodevelopmental error may be meshwork at the iridocorneal angle. common to all 3 disorders.14,15 Associated melanosis of the ipsilateral eye occurs Histopathology in approximately 2 of 3 cases of nevus of Ota. The Biopsy specimens of nevi show an epidermis with most commonly affected structure is the sclera, increased melanocytes but no activity at the dermoepi- though pigmentation of the ipsilateral iris, conjunc- dermal junction. Fusiform, bipolar, elongated, heavily tiva, retina, cornea, choroid, extraocular muscles, pigmented, dendritic melanocytes with extracellular and retrobulbar fat also have been described.11,16 sheaths are scattered at various levels within the upper Optic nerve involvement occurs in 1% to 4% of dermis and mid-dermis.10,24 These melanocytes do not patients.16 Ipsilateral sensorineural hearing loss also alter the overlying architecture of the skin, a charac- has been described. Pigmentation of other mucosal teristic that helps distinguish nevus of Ota from other surfaces of the head and neck may occur, involving dermal melanocytoses.25 Malignant change has the the nasal and oral mucosa, tympanic membrane, and histologic appearance of a malignant blue nevus. external auditory canal. Palatal pigmentation is rare and occurs most frequently in patients with bilateral Pathogenesis nevi of Ota.6,16 Patients with bilateral nevi of Ota Although the pathogenesis is not precisely known, often have extensive mongolian spots.6,7 it is generally believed that nevus of Ota represents Nevi of Ota have the potential to undergo a failed migration of melanocytes from the neural melanomatous change. Malignant degeneration crest to the dermoepidermal junction and subsequent occurred in 4.6% of reported cases of oculodermal arrest within the dermis.26 melanocytosis and was more frequent in light- Contrary to the spontaneous regression of mon- skinned patients.17-19 In one study, white individu- golian spots, most nevi of Ota do not improve als accounted for approximately 76% (36/47) of with age. The lesions may darken or extend during cases of malignant melanoma.18 The average age at puberty and in postmenopausal women. It is hypoth- diagnosis of melanoma is approximately 60 years,11 esized that these aberrant dermal melanocytes may though there is no known association between the be influenced hormonally by a mechanism within age of the nevus and development of melanoma. the hypothalamic-pituitary-ovarian axis.5,10 Malignant change occurs most frequently within the Nevi of Ota were originally classified based on choroid but may develop in the skin, orbit, menin- clinical descriptions of pigmentation: type I (small ges, and brain.11,17,19,20 The majority of these primary lesions), type II (moderately sized lesions), type III melanomas develop ipsilateral to the nevus.18 The (extensive lesions), and type IV (bilateral lesions).6 combination of nevus of Ota and meningeal mela- In 1991, nevi of Ota were histologically reclassified nocytoma also has been described.21 according to the location of melanocytes within the Cutaneous malignancy frequently manifests as dermis, including superficial, deep, diffuse, super- new or enlarging subcutaneous nodules, as opposed ficial dominant, and deep dominant types.27 This to the ABCD (asymmetry, border irregularity, color, newer classification is more relevant for predicting diameter) spectrum of changes typically seen in patient response to treatment because superficial melanoma, representing a malignant blue nevus melanocytes are most amenable to therapy. that did not arise at the dermoepidermal junction.17 Additionally, melanoma may develop in clinically Differential Diagnosis resolving nevi.12 Intracranial melanoma rarely occurs Nevus of Ota belongs to the family of circum- in patients with nevus of Ota, and these cases involve scribed dermal melanocytoses (Table), along with the 26 CUTIS® Pediatric Dermatology mongolian spot and cellular blue nevus, and may Treatment be misdiagnosed as an ectopic mongolian spot. Treatment for oculodermal melanocytosis has evolved Mongolian spots are homogeneously pigmented and greatly over the past 4 decades. Makeup may be characteristically contain melanocytes in the lower applied to cover and blend the lesion with the sur- half of the dermis, whereas the nevus of Ota is a rounding skin but offers only temporary improvement speckled, superficial, dermal melanocytosis.10,28,29 The in cosmesis and requires diligent daily application.33,34 face is an unusual location for a mongolian spot, Achievement of long-term depigmentation is the cur- which most commonly occurs in the sacrococcygeal rent goal of therapy. region. Additionally, mongolian spots lack malignant The 2 most effective treatment options are lasers potential and are not