Hyperpigmentation - treatment, symptoms and cause of Hyperpigmentation

Disorders of hypopigmentation are classified as either diffuse or localized. The classic example of diffuse hypopigmentation is oculocutaneous albinism (OCA). The most common forms are due to mutations in the tyrosinase gene (type I) or the P gene (type II); patients with type IA OCA have a total lack of enzyme activity. At birth, different forms of OCA can appear similar - white hair, gray-blue eyes, and pink-white skin. However, the patients with no tyrosinase activity maintain this phenotype, whereas those with decreased activity or P gene mutations will acquire some pigmentation of the eyes, hair, and skin as they age. The degree of pigment formation is also a function of racial background, and the pigmentary dilution is readily apparent when patients are compared to their first-degree relatives.

The ocular findings in OCA correlate with the degree of hypopigmentation and include decreased visual acuity, nystagmus, photophobia, and monocular vision. 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.

The differential diagnosis of localized hypomelanosis includes the following primary cutaneous disorders: idiopathic guttate hypomelanosis, postinflammatory hypopigmentation, tinea (pityriasis) versicolor, vitiligo, chemical leukoderma, nevus depigmentosus, and piebaldism. In this group of diseases, the areas of involvement are macules or patches with a decrease or absence of pigmentation. 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 vitiligo¾Vogt-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. The 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.

There are two systemic disorders that may have the cutaneous findings of piebaldism. They are Hirschsprung's disease and Waardenburg's syndrome. A possible explanation for both disorders is an abnormal embryonic migration or survival of two neural crest-derived elements, one of them being melanocytes and the other myenteric ganglion cells (Hirschsprung's disease) or auditory nerve cells (Waardenburg's syndrome). The latter syndrome is characterized by congenital sensorineural hearing loss, dystopia canthorum (lateral displacement of the inner canthi but normal interpupillary distance), heterochromic irises, and a broad nasal root, in addition to the piebaldism. Patients with Waardenburg's syndrome have been shown to have mutations in two genes that encode DNA-binding proteins, PAX-3 and MITF, while patients with Hirschsprung's disease and white spotting have mutations in one of three genes¾endothelin 3, endothelin B receptor, and SOX-10.

In tuberous sclerosis, the earliest cutaneous sign is an ash leaf spot. These lesions are often present at birth and are usually multiple; however, detection may require Wood's lamp examination, especially in fair-skinned individuals. The pigment within them is reduced but not absent. The average size is 1 to 3 cm, and the common shapes are polygonal and lance-ovate. Examination of the patient for additional cutaneous signs such as adenoma sebaceum (multiple angiofibromas of the face), ungual and gingival fibromas, fibrous plaques of the forehead, and connective tissue nevi (shagreen patches) is recommended. It is important to remember that an ash leaf spot on the scalp will result in poliosis, which is a circumscribed patch of gray-white hair. Internal manifestations include seizures, mental retardation, central nervous system (CNS) and retinal hamartomas, renal angiomyolipomas, and cardiac rhabdomyomas. The latter can be detected in up to 60% of children (<18 years) with tuberous sclerosis by echocardiography.

Nevus depigmentosus is a stable, well-circumscribed hypomelanosis that is present at birth. There is usually a single circular or rectangular lesion, but occasionally the nevus has a dermatomal or whorled pattern. It is important to distinguish this more common entity from ash leaf spots especially when there are multiple lesions. In hypomelanosis of Ito, swirls and streaks of hypopigmentation run parallel to one another in a pattern that resembles a marble cake. Lesions may progress or regress with time, and in up to a third of patients, associated abnormalities are found including in the musculoskeletal system (asymmetry), the CNS (seizures and mental retardation), and the eyes (strabismus and hypertelorism). Chromosomal mosaicism has been detected in these patients; this lends support to the hypothesis that the pattern is the result of the migration of two clones of primordial melanocytes, each with a different pigment potential.

Localized areas of decreased pigmentation are commonly seen as a result of cutaneous inflammation and have been observed in the skin overlying active lesions of sarcoidosis as well as in CTCL. Cutaneous infections also present as disorders of hypopigmentation, and in tuberculoid leprosy there are a few asymmetric patches of hypomelanosis that have associated anesthesia, anhidrosis, and alopecia. Biopsy specimens of the palpable border show dermal granulomas that lack Mycobacterium leprae organisms.