Hypopigmented Macules

Excerpt

Hypopigmented macules are one of the most common skin lesions encountered in clinical practice. The word hypopigmentation indicates decreased pigmentation, which means significantly reduced melanin compared to the normal skin. This should not be confused with the word depigmentation, which is an indicator of the complete absence of melanin due to the significant loss of melanocytes. Clinically, it is challenging to differentiate hypopigmented disorders from depigmented disorders.

It is important to understand the difference between these conditions since the treatment and prognosis often differ. Hypomelanosis is often benign, may be associated with the function of internal viscera, and rarely associated with malignancy. One of the frequent reasons to seek treatment is the cosmetic appearance, which can cause stress and social stigma (especially in dark-skinned people) in the patients. Repigmentation can be achieved in some cases by the right diagnosis and prompt treatment. A detailed history, clinical signs along with wood's lamp examination, and dermoscopy help in making the right diagnosis. Apart from these, a skin biopsy histopathological findings provide additional information to understand the underlying pathogenesis. This article briefly reviews the common disease conditions associated with hypopigmented macular lesions (size less than 0.5 cm) and patches (more than 0.5cm). A brief idea of the anatomy of the skin and the mechanism of skin pigmentation is important to understand the pathogenesis and histologic findings of hypopigmentation disorders.

Anatomy of the Skin- Skin is the largest organ in the body and is made up of three layers- epidermis, dermis, and hypodermis. The epidermis is again divided into five layers. They are Stratum basal (the deepest layer of the epidermis), S.spinosum, S.granulosum, S.lucidum, and S.corneum (most superficial layer of the epidermis; normally, cells in this layer do not contain any nuclei). Stratum lucidum is present only in the areas of thick skin (eg., palms of hand).

Mechanism of skin pigmentation- It is mainly regulated by keratinocytes and melanocytes present in the basal layer of the epidermis. Melanocytes are embryologically derived from neural crest cells, and their migration to skin and hair is regulated by various transcription factors and signaling pathways. Melanocytes produce a brown pigment - melanin, which protects the skin from potentially harmful UV radiation present in sunlight. Exposure to UV light could potentially cause defects in the DNA of keratinocytes. This leads to overexpression of the P53 gene resulting in increased transcription of the POMC gene (proopiomelanocortin), thereby increasing the synthesis of POMC protein. The POMC protein is cleaved into ACTH and alpha MSH. Alpha MSH binds to the G-protein receptor (MC1R) on melanocyte, activates adenyl cyclase, and mitogen-activated protein (MAP). In turn, this results in the production of eumelanin, tyrosinase, and tyrosinase-related protein. The tyrosinase enzyme converts tyrosine into DOPA and melanin.

Tyrosinase is the rate-limiting enzyme for melanogenesis. Melanin is then packed in melanosomes (lysosome-like organelles) and is transferred to keratinocytes through protease-activated receptors. As the skin ages, the keratinocytes move from the basal to superficial layer along with these ingested melanosomes, which give the brownish tint to the skin. There are two kinds of melanin- pheomelanin and eumelanin. Pheomelanin is predominant in fair-skinned people and eumelanin in dark-skinned people. Eumelanin protects the skin against UV radiation better than pheomelanin.