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 Table of Contents  
EDITORIAL
Year : 2014  |  Volume : 1  |  Issue : 1  |  Page : 5-7

Pigmentary disorders: An insight


Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication26-Jun-2014

Correspondence Address:
Sunil Dogra
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5847.135429

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How to cite this article:
Dogra S, Sarangal R. Pigmentary disorders: An insight. Pigment Int 2014;1:5-7

How to cite this URL:
Dogra S, Sarangal R. Pigmentary disorders: An insight. Pigment Int [serial online] 2014 [cited 2019 Sep 15];1:5-7. Available from: http://www.pigmentinternational.com/text.asp?2014/1/1/5/135429

The earth counts variegated collection of people with different skin colors. The skin color is one of the most obvious ways in which human races are defined and there are very few things, which are affronted discriminated against than the "discolored skin." In recent years, there have been tremendous strides in research related to biology of melanocytes, clinical aspects and treatment of pigmentary disorders. There are more than 4000 different known diseases of the skin. Many of these disorders are associated with a change in skin color.

The epidemiology of pigmentary disorders varies in different geographical areas of world, skin races and age groups. A study on dermatoses in childhood and adolescence from Northern India, describes 6.9% patients were suffering from pigmentary disorders [1] whereas studies from South India have reported frequency of hypopigmentary [2] and hyperpigmentary [3] disorders among children attending the general outpatient departments as 3.28 and 1.54 per 1000 children, respectively. In a study among the adult population, 10.8% of patients attending dermatology clinic at a hospital in Western India were reported to have pigmentary disorders. [4]

Overall, melasma is the most common pigmentary disorder in India and South-East Asia [5] with prevalence ranging from 0.25% to 4%, respectively. [5],[6],[7] This is followed by the vitiligo with its prevalence ranging between 0.25% and 2.5%. [6],[8] The common hyperpigmentary disorders seen in adults are melasma, Riehl's melanosis, idiopathic guttate and confluent hypermelanosis, postinflammatory melanosis, lichen amyloidosis, nevus of Ota, lichen planus. The common hypopigmentary disorders in adulthood are vitiligo, pityriasis versicolor, hypopigmented leprosy, nevus achromicus and albinism. [6] The most common hypopigmentary disorders described in childhood are pityriasis alba, vitiligo, leprosy, nevus de-pigmentosus and pityriasis versicolor, [2] whereas common hyperpigmentary disorders in this age group are cafe-au-lait macules, postinflammatory hyperpigmentation, congenital melanocytic nevi, pigmentary mosaicism, lichen planus and Mongolian spots. [3]

The constitutive pigmentation (phenotype) of skin, hair and eyes is due to genetic factors and depend primarily on the functions of melanocytes and the cellular interactions between epidermal-melanin unit. In human skin, melanocytes are localized at the dermo-epidermal junction in a characteristic regularly dispersed pattern. Each melanocyte at the basal layer of the epidermis is functionally connected to underlying fibroblasts in the dermis and to keratinocytes in the overlying epidermis. These three types of cells are highly interactive and communicate with each other via secreted factors and their receptors and via cell/cell contacts to regulate the function and phenotype of the skin. The genotypes of melanocytes determine the quantity and type of melanosomes that are transferred to surrounding keratinocytes. The keratinocytes also have some control over melanosomal transfer and this is by protease activated receptors-2, located on the surface of keratinocytes. These receptors alter the capacity of keratinocytes to ingest melanosomes. Besides the genetic make-up, the racial and ethnic differences in skin color depend upon other intrinsic and extrinsic factors (facultative pigmentation). These are endocrine factors such as estrogen, α-melanocyte-stimulating hormone, adrenocorticotropic hormone, paracrine and autocrine factors, the ultraviolet radiation (UV-R) exposure, vitamin D, all these factors enhance melanogenesis. [9] Eighty percent of the world's population consists of individuals with pigmented skin. Expression of this receptor is constitutively higher in darker skin and is also up regulated by UV-R. [9]

All disorders of pigmentation revolve around the pathologies either in melanocytes or in the process of melanisation. These pathologies can be inherited or acquired manifesting locally or diffuse. Disorders of pigmentation can result from abnormal migration of melanocytes from the neural crest to the skin during embryogenesis. Apart from it, impairment of melanosome transfer to the surrounding keratinocytes, an alteration in melanin synthesis and a defective degradation or removal of melanin may lead to abnormal skin pigmentation. Immunologic or toxic mediated destructions of melanocytes are also a cause for pigmentation disorders.

Ultraviolet-induced skin darkening involves an increase in the number of melanocytes as well as stimulation of melanin synthesis and melanocyte dendricity. [10],[11],[12] UV-R also causes peroxidation of lipids in cellular membranes, leading to generation of reactive oxygen species, which may stimulate melanocytes to produce excess melanin. [10],[11],[12] Beside above mentioned factors, various common drugs can stimulate skin hyperpigmentation such as certain antibiotics (sulfonamides and tetracyclines), diuretics, nonsteroidal anti-inflammatory drugs, pain relievers, some psychoactive medications, oral contraceptive pills, chloroquine, clofazimine and so on. [10] All these drugs stimulate melanogenesis and increase melanin content in large size melanocytes. Heavy metals can also elicit hyperpigmentation, which can arise after the extensive use of drugs containing arsenic, bismuth, gold, or silver. The metals are believed to act by binding and thereby inactivating sulfhydryl compounds in the skin that normally inhibit tyrosinase activity. Removal of this inhibition stimulates melanogenesis. [10]

On the other hand, etiopathogenesis of vitiligo is very complex and is not known fully, it include the susceptible genes, which influence the autoimmune response against melanocytes and melanogenesis, genetically abnormal melanocytes and environmental or physiological factors that activates genetic program for melanocyte destruction. [13],[14],[15] Both cellular and humoral immune responses have been implicated in the etiology of vitiligo. [14],[15] The inflammatory cells, which are commonly observed in the vicinity of vitiliginous lesions are CD4, CD8 T-cells and CD11-dendritic cells. Serum auto-antibodies against many melanocyte cytoplasmic antigens have been identified in vitiligo patients, which can cause antibody-dependent cellular cytotoxicity as well as complement-dependent cytotoxicity of cultured melanocytes. [15],[16]

In addition to genetically aberrant immune system, melanocytes in vitiligo are itself defective. Studies have demonstrated that the melanocytes in the skin of vitiligo patients can exhibit morphologic abnormalities, including enlargement, fragmentation, extracellular granular material, and dilated rough endoplasmic reticulum. [17]

Beside innate defect in the immune system and melanocytes itself, various extrinsic precipitating factors co-related with vitiligo are severe sunburn, pregnancy, physical and emotional stress/trauma, wounds or areas of microtrauma and so on. [13] Contact/occupational leukoderma is the most obvious example which correlates external precipitating factors (phenolic and catecholic compounds) with the onset of melanocyte destruction. [18]

Multiple inflammatory diseases, especially of the papulosquamous and vesiculobullous type, can cause postinflammatory hyperpigmentation and hypopigmentation. The actual pathogeneses of post-inflammatory hyperpigmentation and hypopigmentation remain unknown. Skin insult due to any intrinsic or extrinsic factors, ultimately lead to inflammation in skin layers, which may enhance melanogenesis or may destroy the melanocytes partially or completely leading hyperpigmentation or hypo-de-pigmented dermatoses. The postinflammatory hyperpigmentation at the cellular level is characterized by normal number of melanocytes that have increased melanin production. The arachidonate-derived inflammatory chemical mediators, especially leukotrienes such as LTC4 and LTD4, and thromboxanes such as TXB2 stimulate melanocytes. [10] Another important mediators in inflammation are nitric oxide (NO) and NO synthetase enzyme (NOS), which are found in melanocytes, keratinocytes and Langerhans cells. Following UV-R exposure, the controlled production of NO and NOS stimulates melanogenesis by activation transcription of tyrosinase enzyme but when released in excess amounts from langerhans cells it is melano-cytotoxic leading to melanocyte destruction causing hypo/de-pigmented skin lesions. [10],[19],[20] The other oxidative stress, which is related to de-pigmentation is a disruption of the biopterin metabolic pathway and network that induces reactive oxygen species (H 2 O 2 ). Generation of reactive oxygen species, initially causes lipid peroxidation and then induce apoptosis of melanocytes. [13],[21]

Treatment of pigmentation disorders are based on diagnosis, which sometimes allow a specific intervention, although cosmetically acceptable results are in general difficult to obtain. The management of hyperpigmentary disorders involves multi-factorial treatment approach, which includes photoprotection, topical and systemic lightening agents various procedures for re-calcitrant cases such as chemical peels, resurfacing and laser techniques. [22],[23]

In the management of stable vitiligo, gold standard is phototherapy for which various light sources are available like UVA, BB-UVB, NB-UVB, excimer laser. [24] Topical therapies like corticosteroids, topical calcineurin inhibitors, vitamin D analogues (calcipotriol, tacalcitrol) are useful as monotherapy or adjunctive to systemic treatment. [25] For progressive vitiligo, the aberrant immune responses are counteracted by systemic immunosuppressive like corticosteriods, steriod sparing immunosuppressants immunomodulating drugs like levamisole and oral antioxidants. Surgical modalities are reserved for stable, medical treatment resistant, and residual de-pigmented lesions. [26]

 
  References Top

1.Sharma S, Bassi R, Sodhi MK. Epidemiology of dermatoses in children and adolescents in Punjab, India. J Pak Assoc Dermatol 2012;22:224-9.  Back to cited text no. 1
    
2.Sori T, Nath AK, Thappa DM, Jaisankar TJ. Hypopigmentary disorders in children in South India. Indian J Dermatol 2011;56:546-9.  Back to cited text no. 2
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3.Sori T, Jaisankar TJ, Thappa DM, Nath AK. Hyperpigmentary disorders in children: A hospital-based study in a tertiary care center. Indian Dermatol Online J 2013;4:148-52.  Back to cited text no. 3
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4.Sayal SK, Das AL, Gupta CM. Pattern of skin diseases among civil population and armed forces personnel at Pune. Indian J Dermatol Venereol Leprol 1997;63:29-32.  Back to cited text no. 4
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5.Achar A, Rathi SK. Melasma: A clinico-epidemiological study of 312 cases. Indian J Dermatol 2011;56:380-2.  Back to cited text no. 5
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8.Singh S, Pandey U, Pandey SS. Epidemiological profile of vitiligo in Northern India. J App Pharm Sci 2011;1:211-4.  Back to cited text no. 8
    
9.Seiberg M. Keratinocyte-melanocyte interactions during melanosome transfer. Pigment Cell Res 2001;14:236-42.  Back to cited text no. 9
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10.Costin GE, Hearing VJ. Human skin pigmentation: Melanocytes modulate skin color in response to stress. FASEB J 2007;21:976-94.  Back to cited text no. 10
    
11.Nordlund JJ. The melanocyte and the epidermal melanin unit: An expanded concept. Dermatol Clin 2007;25:271-81, vii.  Back to cited text no. 11
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12.Archambault M, Yaar M, Gilchrest BA. Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation. J Invest Dermatol 1995;104:859-67.  Back to cited text no. 12
    
13.Boissy RE, Dell'Anna ML, Picardo M. On the pathophysiology of vitiligo: Possible treatment options. Indian J Dermatol Venereol Leprol 2012;78:24-9.  Back to cited text no. 13
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14.Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M, et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: Direct evidence of t cell-mediated vitiligo. J Exp Med 2000;192:1637-44.  Back to cited text no. 14
    
15.Kemp EH, Gavalas NG, Gawkrodger DJ, Weetman AP. Autoantibody responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun Rev 2007;6:138-42.  Back to cited text no. 15
    
16.Kemp EH, Wwwtman AP, Gawkrodger DG. Humoral immunity. In: Picardo M, Taieb A, editors. Berlin, Hedelberg: Springer-Verlag, Vitiligo; 2010. p. 248-56.  Back to cited text no. 16
    
17.Boissy RE. The intrinsic (genetic) theory for the cause of vitiligo. In: Hann SK, Nordlund JJ, editors. Vitiligo a Monograph on the Basic and Clinical Science. Oxford: Blackwell Science Ltd.; 2000. p. 123-8.  Back to cited text no. 17
    
18.Boissy RE, Manga P. On the etiology of contact/occupational vitiligo. Pigment Cell Res 2004;17:208-14.  Back to cited text no. 18
    
19.Sasaki M, Horikoshi T, Uchiwa H, Miyachi Y. Up-regulation of tyrosinase gene by nitric oxide in human melanocytes. Pigment Cell Res 2000;13:248-52.  Back to cited text no. 19
    
20.Iuga AO, Qureshi AA, Lerner EA. Nitric oxide is toxic to melanocytes in vitro. Pigment Cell Res 2004;17:302-6.  Back to cited text no. 20
    
21.Dell'Anna ML, Ottaviani M, Albanesi V, Vidolin AP, Leone G, Ferraro C, et al. Membrane lipid alterations as a possible basis for melanocyte degeneration in vitiligo. J Invest Dermatol 2007;127:1226-33.  Back to cited text no. 21
    
22.Sarkar R, Chugh S, Garg VK. Newer and upcoming therapies for melasma. Indian J Dermatol Venereol Leprol 2012;78:417-28.  Back to cited text no. 22
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23.Arora P, Sarkar R, Garg VK, Arya L. Lasers for treatment of melasma and post-inflammatory hyperpigmentation. J Cutan Aesthet Surg 2012;5:93-103.  Back to cited text no. 23
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24.Kanwar AJ, Dogra S, Parsad D, Kumar B. Narrow-band UVB for the treatment of vitiligo: An emerging effective and well-tolerated therapy. Int J Dermatol 2005;44:57-60.  Back to cited text no. 24
    
25.Kanwar AJ, Dogra S, Parsad D. Topical tacrolimus for treatment of childhood vitiligo in Asians. Clin Exp Dermatol 2004;29:589-92.  Back to cited text no. 25
    
26.Vinay K, Dogra S, Parsad D, Kanwar AJ, Kumar R, Minz RW, et al. Clinical and treatment characteristics determining therapeutic outcome in patients undergoing autologous non-cultured outer root sheath hair follicle cell suspension for treatment of stable vitiligo. J Eur Acad Dermatol Venereol 2014. [Epub ahead of print].  Back to cited text no. 26
    



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