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Generalized vitiligo, phenylketonuria, and homocystinuria are other unusual causes of diffuse pigmentary dilution. In generalized vitiligo, melanocytes are not found in affected skin, whereas in OCA they are present but have decreased activity. Appropriate laboratory tests exclude the other disorders of metabolism.
Patients with vitiligo also have an increased incidence of several autoimmune disorders, including hypothyroidism, Graves' disease, pernicious anemia, Addison's disease, uveitis, alopecia areata, chronic mucocutaneous candidiasis, and the polyglandular autoimmune syndromes (types I and II). Diseases of the thyroid gland are the most frequently associated disorders, occurring in up to 30% of patients with vitiligo. Circulating autoantibodies are often found, and the most common ones are antithyroglobulin, antimicrosomal, and antiparietal cell antibodies.
There are three systemic diseases that should be considered in a patient with skin findings suggestive of vitiligo - Vogt-Koyanagi-Harada syndrome, scleroderma, and melanoma-associated leukoderma.
A history of aseptic meningitis, nontraumatic uveitis, tinnitus, hearing loss, and/or dysacousis points to the diagnosis of the Vogt-Koyanagi-Harada syndrome. In these patients, the face and scalp are the most common locations of pigment loss.
he vitiligo-like leukoderma seen in patients with scleroderma has a clinical resemblance to idiopathic vitiligo that has begun to repigment as a result of treatment; that is, perifollicular macules of normal pigmentation are seen within areas of depigmentation.
The basis of this leukoderma is unknown; there is no evidence of inflammation in areas of involvement, but it can resolve if the underlying connective tissue disease becomes inactive.
In contrast to idiopathic vitiligo, melanoma-associated leukoderma often begins on the trunk, and its appearance should prompt a search for metastatic disease. The possibility exists that the destruction of normal melanocytes is the result of an immune response against malignant melanocytes.
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