What is Nevus of Ota and Ito?

Nevus of Ota is a harmless condition that causes increased pigment in certain areas of the skin, mainly on the face, where the trigeminal nerve is. This nerve has two parts – the ophthalmic and maxillary, which are most often affected in this condition. The hyperpigmentation or darkening, can also affect the eye. This condition is also referred to as ocular dermal melanosis.

This condition results in a characteristic gray-blue discoloration due to trapped pigment cells, called melanocytes. This usually occurs on one side of the face, leading to changes in the color of the conjunctiva (the clear layer of tissue lining the inside of the eyelid and the white part of the eyeball), the sclera (the white part of the eye), and the skin on the same side of the face. In these cases, there is a higher risk of developing uveal melanoma, a type of eye cancer, and glaucoma, a condition that damages the optic nerve of the eye. Some individuals may also have a change in the color of the roof of their mouth, known as the palate.

Nevus of Ito is a condition very similar to Nevus of Ota, with the key difference being the areas of the skin that are affected. It was first mentioned by Minor Ota in 1954. For Nevus of Ito, the nerve territory that is affected involves the nerves on the side of the arm and shoulder, as well as the posterior supraclavicular nerves, which are close to the collarbone. Both of these conditions have similar causes and development.

What Causes Nevus of Ota and Ito?

While we’re not totally sure why melanoma occurs, several theories have been put forward. One is that the cells that give color to the skin, called melanocytes, don’t move correctly from the nerve cells to the skin’s bottom layer during development. Another theory is that it might be linked to previous radiation treatment, exposure to radiation, or hormone-related factors.

Specific genes, called BRAF and NRAS, connected to a protein pathway in cells known as the MAP kinase, could have something to do with it. There might also be mutations in a protein called GNAQ, which causes the protein to be always turned on and might contribute to the disease.

During embryo development, certain color-giving cells migrate to the skin and a part of the eye known as the uvea. This may result in the unique bluish-gray color often seen in melanoma.

Additionally, certain genetic factors, such as the loss of one copy of chromosome 3 and gaining an extra copy of the long arm of chromosome 8q, can make melanoma in the eye (uveal melanoma) worse and increase the risk of a poor outcome.

Risk Factors and Frequency for Nevus of Ota and Ito

The condition predominantly affects Asians, with about 0.014% to 0.034% of this population being affected. It most often becomes evident at birth, but can also appear during puberty or pregnancy due to the influence of hormones. Women are more likely to be affected than men, with a ratio of 5:1. The condition is more prevalent in people of Asian and African descent as compared to whites. However, whites run a greater risk of developing malignant melanoma, a type of skin cancer.

Similarly, Nevus of Ito is usually observed during infancy or adolescence. This condition is more common in Asian communities and people with darker skin tones. Sometimes, Nevus of Ota is found to occur along with Nevus of Ito.

Nevus of Ota in a 3-year-old female: pigmentation of the eyelid skin and sclera

Signs and Symptoms of Nevus of Ota and Ito

Nevus of Ota is a condition that typically doesn’t cause any symptoms, even though it can in rare cases cause loss of sensation. This condition is identified by a blue-tinted pigmentation developing along the path of the ophthalmic (eye) and maxillary (jaw) divisions of the trigeminal nerve. Nevus of Ota normally just affects one side of the face but can sometimes affect both. The skin changes involved can appear as flat, brown, slate-blue, or grey-black spots or patches. The spots might merge together, don’t produce hair, and have blurred edges. The pigmentation can also spread to areas beyond the skin like the eyes, mouth, and the inside of the nose.

A comprehensive eye exam should be carried out, comprising of tests for seeing sharpness, inner eye pressure measurement, examination of the front of the eye through a device called a slit-lamp, and examination of the back of the eye using another instrument known as an indirect ophthalmoscope. The examination will also look out for pigmentation in the conjunctiva (the clear layer on the front of the eye) and episclera (a thin layer covering the sclera), which are easily observed during a slit-lamp examination. The angle where the cornea and iris meet should be examined for evidence of pigmentation in the trabecular meshwork (a mesh-like channel for draining fluid from inside the eye). An examination of the rear outer region of the retina should also be performed to ensure there isn’t a malignant growth or melanoma there. The appearance of the optic nerve needs to be documented. Finally, an oral examination should be done to check for any lesions in the mouth.

Nevus of Ota can be classified into four types according to Tanino’s system:

Type I (mild): Involvement of a few areas including periocular, zygomatic (cheek bone) region, forehead, or nose.
Type II (moderate): Similar to Type I, but with greater severity.
Type III (intensive): Involving the periocular areas, nose, and scalp.
Type IV: Involvement of both sides of the face.

The main difference between Nevus of Ota and Nevus of Ito lies in the regions they affect, with Nevus of Ito not having any association with eye complications. Additionally, the intensity of pigmentation for both conditions can vary due to factors such as menstruation, tiredness, or the weather. Usually, the pigmentation gets darker after puberty and becomes permanent without any spontaneous reduction or fading over time.

Testing for Nevus of Ota and Ito

The Nevus of Ota and Ito conditions can’t be confirmed by a specific diagnostic test. These conditions are mainly identified by a careful physical check-up and reviewing your medical history. A special skin test, called dermatoscopy, is typically used. It should show a bluish to dark grey, evenly spread skin pigment.

If the skin above the colored area starts to form an open wound, or if the color starts to change or bumps develop, a skin biopsy might be required. This is a procedure where a small sample of the unusual skin is taken to study closer under a microscope.

Lighter Nevus variants typically appear on cheeks, while deeper variants affect the areas around the eyes, the temples, and the forehead. Because these conditions can potentially cause issues with the eyes, it’s important to have your eyes checked by an eye doctor once a year.

Treatment Options for Nevus of Ota and Ito

When it comes to eye diseases like uveal melanomas, several tests are needed to determine if you have the condition. These tests can include vision tests, examining the pressure inside your eye, closely looking at your eye with a slit lamp, and dilating your pupil to check the back of your eye. Depending on the size and location of the melanoma, treatments can vary. These may include surgery to remove the melanoma, radiation therapy, heat therapy applied to the eye (known as transpupillary thermotherapy), or even removing the eye entirely (known as enucleation).

If the disease affects the skin, treatment is often necessary for cosmetic reasons, or if the disease has turned malignant (cancerous). The type of treatment then depends on how big and serious the disease is. For smaller cases, a surgical technique called Mohs micrographic surgery can be used. This involves removing the lesions and reconstructing the tissues around your eye. For more severe cases or when the disease has spread, treatment might include surgical excision combined with either radiotherapy, heat therapy applied to the eye, or chemotherapy.

Lasers can also be used to improve the appearance of skin lesions by destroying the problem cells (melanocytes). One such technique, pulsed Q-switched laser surgery, is effective for conditions like nevi of Ota and Ito. It targets the problem cells using a combination of heat and mechanical destruction to reduce pigmentation. Other treatments for cosmetic improvement can include chemical peels, dermabrasion (a type of skin resurfacing), electrocautery (using electric current to destroy tissue), or cryotherapy (freezing the tissue).

The diagnosis of nevus of Ota and Ito, certain types of skin conditions, can be made by examining the characteristics of the skin and the specific areas that are affected. When diagnosing these conditions, doctors also need to differentiate them from other skin disorders, which could include:

Mongolian spots: Usually, these appear in the lower back and buttock area and rarely on the face. They typically disappear on their own by the time a child is between 3 to 6 years old.
Acquired bilateral nevus of Ota-like macules (ABNOM), or Sun’s nevus: The sclera (white part of the eye) and oral mucosa (lining of the mouth) are not affected by this condition.
Melanoma metastasis: This is a form of skin cancer.
Ecchymoses: These are discolorations of the skin resulting from bleeding underneath, typically due to bruising.
Vascular malformations: These are abnormalities of the blood vessels.
Drug-induced hyperpigmentation: This is a skin darkening caused by certain medications such as minocycline, amiodarone, and gold.
Melasma: This typically happens with pregnancy.
Oral melanotic macule: This condition usually appears as a small, dark spot on the roof of the mouth and does not involve the sclera.

What to expect with Nevus of Ota and Ito

Most of the time, a particular type of medical condition called malignant degeneration is exceptional. This means the outlook is usually positive. Patients often seek treatment because of changes in the coloring of the white part of the eye (the sclera) or the colored part just around the pupil (the iris). In rare cases, it might be linked to a type of eye tumor called a cavernous hemangioma located on the optic disc, the area where the optic nerve connects to the eye.

However, there’s a 10.3% chance of developing an eye condition known as glaucoma, and 1 out of 400 patients may develop a type of skin cancer called malignant melanoma. That’s why there is a need for an annual eye check-up with an ophthalmologist. These checks include measuring the pressure inside your eyes and examining the inside of your eye using a special magnifying lens called an indirect ophthalmoscope.

If there are concerns about changes indicating malignant transformation, a skin biopsy (taking a small sample of skin for testing) will be suggested. Continued eye care follow-up is essential for patients with increased pressure inside the eye.

In general, these lesions are usually harmless and the outlook remains excellent with or without treatment. Therefore, it is recommended to have yearly screenings by an eye specialist and skin specialist to rule out the possibility of glaucoma and malignant melanoma.

Possible Complications When Diagnosed with Nevus of Ota and Ito

The biggest concern with nevi of Ota and Ito primarily revolves around their appearance. With nevus of Ota, it’s not uncommon for the eye’s sclera to be affected, which can lead to complications like heightened pressure within the eye and glaucoma. There’s also a risk of malignant melanoma, a serious skin cancer that can occur primarily on the skin, but can also impact the meninges (membranes that envelop the brain and spinal cord) and areas of the eye.

Potential Concerns:

Cosmetic issues
Effects on the eye’s sclera
Increased intraocular pressure
Glaucoma
Malignant melanoma, affecting skin, meninges, and ocular areas

Preventing Nevus of Ota and Ito

People who have a condition called nevus of Ota and Ito, which appears as a gray-blue coloring around the eye area, should know that these are harmless growths. The chances of these spots turning into cancer are very low. However, it’s always a good idea to see a doctor if there’s any change in the size or shape of the growths. Regular check-ups with an eye doctor are also recommended, as they can measure the pressure inside your eyes to ensure everything is normal.