Disorders of Pigmentation

Disorders of Pigmentation

Normal pigmentation of the skin is due to melanin, whose role is that of a light barrier. It is synthesised by melanocytes which are distributed among the basal cells of the epidermis and in the hair matrix. These melanocytes are embryologically derived from the neural crest and they inject melanin into adjacent keratinocytes through dendritic processes. The depth of colour of the skin is genetically determined, yet the number of melanocytes in white or negro skin is the same, the difference in pigmentation resulting partly from greater activity of the melanocytes. In negroes the melanosomes are longer and arranged singly in keratinocytes while in Caucasians melanosomes occur in membrane- bounded complexes of three or more.

Disorders of Pigmentation

Melanin is derived from tyrosine which is manufactured in the body from the essential amino-acid phenylalanine. Tyrosine is first converted to dihydroxyphenylalanine (DOPA) which is then converted to dopaquinone and then to melanin. The stage of conversion of tyrosine to DOPA is dependent on the copper-containing enzyme tyrosinase and in the reaction dopa itself acts as a catalyst. The enzyme tyrosinase is inhibited by a compound containing sulphydryl groups.

Melanogenesis and melanin pigmentation is influenced by genetic and hormonal factors as well as physical and chemical agents. Melanocyte stimulating hormone (MSH) is produced by the anterior pituitary and both α MSH and β MSH produce darkening of the skin in man. Adrenocorticotrophic hormone (ACTH), oestrogens and progesterone may also affect the melanocyte and produce increased pigmentation.

Melanins range in colour from brown to black, called eumelanins; yellow and red pigments, phaeomelanins, are chemically distinct and formed by combination of dopa-quinone and cysteine.

Lack or loss of pigment

Albinism. This is an inborn error of metabolism which occurs in all races and is inherited as an autosomal recessive. Pigment is lacking in skin, hair, iris and retina due to a defect in the biosynthesis of tyrosinase.

Phenylketonuria. Another autosomal recessively inherited error of metabolism in which there is a block in the conversion of phenylalanine to tyrosine. The high blood level of phenylalanine can lead to competitive inhibition of the enzyme tyrosinase. The patients have fair skin, fair hair and blue eyes. Elimination of phenylalanine from the diet or oral administration of tyrosine partially restores colour to the hair.

Vitiligo is a condition of unknown aetiology which affects about 1 per cent of the population. Depigmented patches appear in the skin, which retains its normal texture. The failure of melanin pigmentation which occurs in these areas is due to a reduction in the number or complete absence of normal melanocytes.

Vitiligo may begin at any age but more commonly before the age of 20. About one-third of the subjects can trace it in another member of their family and it is seen in association with the organ-specific autoimmune diseases of the thyroid, pernicious anaemia, diabetes mellitus and also alopecia areata in a significant number of cases. In a few patients the onset is associated with physical or mental stress. The disorder has periods of quiescence and progression that are unpredictable and ultimately large areas of the skin can be affected, in only 10-20 per cent of cases does some spontaneous repigmentation occur.

Treatment. The treatment which was first described as having any definite effect was the use of psoralen compounds. 8-Methoxypsoralen (Methoxsalen) has been given in a dose of 10-20 mg twice daily or trimethylpsoralen in a dose of 15 to 30 mg daily during the summer. In countries where natural sunlight is a reliable commodity the patient is exposed to an increasing dose 2 hours after an oral dose and good results are reported. The use of other sources of UVL such as ‘Blacklite’ give disappointing results in our experience. Only about 30 per cent of patients so treated achieve any repigmentation. Recently developed patches are more likely to respond and there is a better response on areas of the body, limbs and face than on the backs of hands. Complete repigmentation only occurs in the minority of cases and increased pigmentation of the normal skin makes the condition even more obtrusive in the rest. There is increasing evidence that prolonged application of the stronger fluorinated steroids such as clobetasol propionate (Dermovate) to the depigmented patches can restore pigmentation in some cases even without additional exposure to ultra-violet light. In white patients satisfactory cosmetic results can be achieved by advising the patient to avoid exposure to sunshine, which increases pigmentation of the normal skin and by disguising the white patches with a cosmetic covering cream or dihydroxyacetone paint.

Endocrine disorders

Decreased pigmentation occurs in hypopituitarism and in acromegaly to a lack of MSH and is also seen in eunuchs.

Occupational depigmentation

Tyrosinase is inhibited by an antioxidant in rubber (monobenzyl ether of hydroquinone) as the result tf which the wearing of rubber gloves has caused depigmentation of the hands in negroes. Phenolic compounds contained in germicidal disinfectants have also caused vitiligo-like depigmentation among workers exposed to them.

Post-inflammatory

In conditions in which the epidermal cells are proliferating rapidly, such as psoriasis, there is a failure in the transport of melanin granules causing depigmentation in healed areas. Similar depigmentation occurs after eczema in the Negro. Increase in the horny layer may also screen the skin from the tanning effects of ultra-violet light, producing depigmented macules in tinea versicolor and also in the mild patchy, scaly dermatitis which may be produced on the faces of children by the effects of strong soap or cold winds. The latter condition heals with the avoidance of soap and the application of hydrocortisone or lanolin ointment.

Partial depigmentation occurs in the macular lesions of leprosy (q.v.).

Increased pigmentation

Sunlight is thought to inhibit the sulphydryl groups in tyrosinase inhibitor, freeing tyrosine and increasing pigmentation of the skin. The effects of sunlight are increased by photosensitisers of which industrial exposure to tar provides the most striking picture of pigmentation on the light exposed areas. A similar industrial pigmentation is sometimes produced by mineral oils used as coolants in engineering.

Endocrine disorders

Increased production of MSH occurs in pregnancy causing darkening of the nipples, genitalia and linea alba; also chloasma, a patchy pigmentation of the face especially marked on the temples. The endocrine changes produced by the contracepive pill also give rise to chloasma. Production of MSH is probably regulated by other hormones, in particular by hydrocortisone, so that damage to the adrenals by Addison’s disease leads to release of MSH and causes generalised pigmentation, most marked on the axilla, nipples, genitalia but also present on the buccal mucosa.

Increased production of ACTH or MSH in Cushing’s syndrome also causes generalised pigmentation. Similarly increased production tf MSH may cause pigmentation in hyperthyroidism and chronic liver disease.

Inflammation

Increase in pigmentation commonly follows inflammation of the skin and here again the mechanism is thought to be inactivation of the sulphydryl groups. This is more likely to occur in those who are racially pigmented. A biopsy of the hypermelanotic areas reveals pigment in macrophages lying in the papillary dermis.

Melanoderma

Patchy pigmentation of the face is occasionally complained of by women and may produce different patterns affecting the forehead and cheeks or mainly the peribuccal area. Reticulate patterns can be formed by the pigment and sometimes it is accompanied by telangiectasia. In such cases light sensitisation has usually been provoked by oil of bergamot which contains as the sensitising agent 5-methoxypsoralen. Oil of bergamot is widely used in the perfume industry and has commonly been applied in a face cream. More obvious pigmentation provoked by this perfume can be seen when scent runs down the side of the neck and produces a pigment streak.

Treatment. Such patients should be advised to stop using all perfumed cosmetics and avoid exposure to sunlight. It may take many months for the pigmentation to fade. The inhibiting effect on melanin formation of hydroquinone has been used to hasten the paling of such areas of pigmentation. It is applied in 2 per cent concentration in a cream base, but is liable to produce dermatitis.

Drugs. Inorganic arsenic used to be administered for a variety of illnesses including psoriasis and dermatitis herpetiformis and there still exist patients whose skin is pigmented from its use. Characteristically there are scattered macules of depigmentation giving the ‘raindrop’ appearance. Inactivation of sulphydryl groups by arsenic causes the pigmentation.

Chlorpromazine causes a slatey grey pigmentation of the skin in those who have been on the drug for a long time. The pigment is probably a dechlorinated chlorpromazine polymer which is bound to melanin.

Non-melanin pigmentation

Argyria due to deposition of silver salts in the skin produces a slate grey pigmentation which is still seen in silversmiths.
Haemochromatosis is a rare disorder of iron metabolism in which diabetes is found. Iron salts and melanin are responsible for the patient’s bronze colour.