|Year : 2016 | Volume
| Issue : 2 | Page : 72-76
Correlating melanin index to repigmentation potential: A novel prognostic tool in vitiligo
Puneet Bhargava, Chaitra Prakash, Siddhi Tiwari, Ridhima Lakhani
Department of Dermatology, Venereology and Leprosy, Sawai Man Singh Medical College and Attached Hospitals, Jaipur, Rajasthan, India
|Date of Web Publication||27-Dec-2016|
Dr. Puneet Bhargava
D-60, Mahesh Marg, Bapu Nagar, Jaipur - 302 015, Rajasthan
Source of Support: None, Conflict of Interest: None
Background: Vitiligo prevails to be a skin disease with endless possibilities but no promises. Despite substantial research in pathogenesis and therapeutic modalities, the literature is deplete with technologies to predict the probabilities for repigmentation with or without therapy in the common generalized vitiligo.
Aim: To correlate pretreatment melanin index in skin patches of nonsegmental vitiligo to probable extent of repigmentation following 6 months of monotherapy with a topical corticosteroid.
Methods: A prospective study was conducted including thirty patients of vitiligo and their melanin index (melanin value; pigmentation index) in representative skin lesion was determined using Mexameter® MX 18. Patients were studied under three groups (A, B, and C) based on the obtained melanin indices. The extent of repigmentation following 6 months of topical therapy with mometasone furoate 0.1% cream was correlated with pretreatment melanin indices.
Results: Repigmentation in Group C (mean melanin index >200) was significantly higher in terms of number of patients (P = 0.000) and area of patch coverage (P = 0.00) as against the other two groups with lower melanin indices.
Conclusion: Melanin index in depigmented lesions is a useful indicator in the management of nonsegmental vitiligo to predict the repigmentation and to choose the appropriate treatment option. Mexameter is a simple, noninvasive, low cost staging, and monitoring device to estimate the melanin reservoir in vitiligo.
Keywords: Melanin index, mexameter, prognosis, repigmentation, vitiligo
|How to cite this article:|
Bhargava P, Prakash C, Tiwari S, Lakhani R. Correlating melanin index to repigmentation potential: A novel prognostic tool in vitiligo. Pigment Int 2016;3:72-6
| Introduction|| |
Vitiligo is an acquired disorder of skin characterized by depigmented areas varying in number, form, and localization, which stem from melanocyte loss or dysfunction. Despite the classical idea of unsuccessful vitiligo treatments, recent advances in the knowledge of vitiligo’s pathogenesis have contributed to find better therapeutic options; so that, at present, many patients find a solution for depigmented skin.
For management of patients with vitiligo, the major emphasis has been on assessing the severity in terms of body surface area with apparent color loss in skin and hair. While this is essential, measuring the residual color in the depigmented areas could be an important clue in the treatment road map.
Medical and/or phototherapy is usually the first approach in vitiligo. However, the choice of surgery, which depends upon donor melanocytes is another option to reproduce color. Donor melanocytes may be required to initiate or hasten the process of repigmentation in those vitiliginous lesions where melanocytic reservoir is scanty or absent. Depigmentation of the remaining islands of colored skin should be chosen if the previously mentioned options are not adequate, and it must be reserved for cases where the vitiligo lesions cover most of the body surface with exhausting melanocytic niche. At last, camouflaging a vitiligo lesion could be considered when pigmentation and depigmentation are not realistic, or it may be applied hand in hand with both options considering the impact of the disease on the patient’s quality of life. Each vitiligo patient has a different story that demands a different therapeutic approach.,, Based on the factors that influence the density of functional melanocytes available for both “vertical” and “horizontal” migration, one should be able, after careful assessment, to make a prognosis for repigmentation and to plan medical and/or surgical treatment. Hence, the decision whether to “repigment,” “depigment,” or “camouflage” the lesions essentially depends on the melanocyte reservoir in these patients.
Vitiligo prevails to be a skin disease with “endless possibilities but no promises.” Although there is substantial research in pathogenesis and therapeutic modalities, the literature is deplete with technologies to predict the probabilities for repigmentation in the common generalized vitiligo, and hence, this study.
| Methods|| |
A prospective observational and descriptive study was designed to include thirty patients of vitiligo. The study was conducted at the Department of Dermatology, Sawai Man Singh Medical College and Attached Hospitals, Jaipur, India, from June 2014 to March 2015 after approval from the Institutional Ethics Committee. Patients included satisfied the following criteria: Age group 18–50 years, Fitzpatrick skin types IV–V, and stable nonsegmental vitiligo who were otherwise healthy and consent for the participation in the study. We preferred to include those patients with a clinically representative vitiliginous patch on the forearm to avoid the bias of anatomic site. The lesion selected for the study was photographed at baseline and after 6 months of treatment. Melanin index (melanin value; pigmentation index) of the vitiligo patch was assessed using Mexameter® MX 18 (Courage-Khazaka Electronic, Germany).
The mexameter is a noninvasive device to measure the components responsible for the color of the skin, mainly, the melanin and the hemoglobin (erythema). It uses the principle of light absorption and reflection by skin pigments. The probe of the Mexameter® MX 18 is scanned over the skin surface, which emits specific light wavelengths and receives the light reflected back by the skin. As the quantity of emitted and reflected light is recorded, the quantity of light absorbed by the skin can be calculated. The fraction of absorbed light corresponding to melanin-specific wavelength quantifies the melanin in the evaluated patch of vitiligo. The mexameter records the melanin index on a broad scale of 0–999.
The patch of interest in each patient was visually divided into four quadrants. The mean of readings taken from all four quadrants was recorded as the actual melanin index for that patch to avoid intralesional melanin variation. Patients were studied under three groups based on the melanin indices obtained (Group A: melanin index 0–100, Group B: melanin index 101–200, Group C: melanin index >200). All patients were prescribed to apply a firstline potent topical corticosteroid such as mometasone furoate 0.1% cream locally twice a day. They were instructed not to use other medications during the period of study. The lesion selected for study was photographed at baseline and after 6 months of treatment for the assessment of treatment outcome. The extent of repigmentation was measured by quartile grading scale. Each group was assigned a mean value of melanin indices obtained from all its patients. The number of patients showing different grades of repigmentation were charted under the respective groups. Data were analyzed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) and statistically significant value was measured using Chi-square test and P value.
| Results|| |
Out of the 30 patients included in the study, 22 were males and 8 were females. Sex distribution across the groups showed no statistical significance (χ2 = 4.432; P = 0.10). Groups were comparable according to age and duration of illness. The mean melanin indices obtained were 56, 132, and 256 in Group A, B, and C, respectively [Table 1]. Posttreatment results are depicted in the figure. All the patients in Group C (100%), 8 in Group B (80%), and only 1 (10%) in Group A showed repigmentation in patches at 6 months follow-up (χ2 = 15.83; P = 0.000). Repigmentation covering more than 25% of patch area was seen only in Group C (6 out of 10 patients; 60%) as against none in Group A and B (χ2 = 15; P = 0.00) [Figure 1]. Repigmentation covering more than 50% of patch area was also exclusively seen in a single patient belonging to Group C (χ2 = 2.069; P = 0.355). No patients showed repigmentation of more than 75% area.
|Table 1: Sex distribution, mean melanin indices, and extent of patch repigmentation across study groups|
Click here to view
|Figure 1: Extent of repigmentation (%) across study groups (Y-axis denotes number of patients)|
Click here to view
| Discussion|| |
Despite its many and overlapping clinical types, clinically vitiligo is often categorized as progressive (active), regressive or stable for the purpose of treatment and prognosis. The course of the disease is hard to predict in the individual patient; generally, it progresses slowly with varying periods of stability and spontaneous improvement.
The depigmentation process in vitiligo is thought to be a progressive and chronic disappearance of epidermal and/or follicular melanocytes caused by autoimmune, neural, and impaired redox mechanisms. Based on the recent findings supporting a chronic detachment and transepidermal loss of melanocytes in common generalized vitiligo, a new integrated theory is suggested proposing melanocytorrhagy as the primary defect underlying melanocyte loss., It is generally agreed that there are no longer functional melanocytes in vitiligo skin and that this loss of histochemically recognizable melanocytes is the result of their destruction. However, the absence of melanophages and significant inflammatory infiltrate in a long-standing lesion makes vitiligo - a disease of “crime with no cadaver.”,
Nevertheless, the possibility that melanocytes are still present in vitiligo skin but in an undifferentiated state without melanogenic activity has been proposed. The possibility that either inactive melanocytes with no identifiable melanosomes (electron microscopy) or dopa-negative melanocytes (histochemistry) remain in the white macules could not be ruled out. This consensus is in concordance with our observation that all the depigmented lesions studied showed a melanin index above zero.
Melanocytes synthesize and store melanin pigment within membrane-enclosed lysosome-related organelles called melanosomes. The beginning of melanin production takes place at Stage III of premelanosome, where pigment is deposited on protein fibrils. Upon complete melanization (Stage IV), these pigment orgenelles are transported to surrounding keratinocytes. By the virtue of high keratinocyte: Melanocyte ratio and rapid transportation of pigment vacuoles from melanocytes to keratinocytes with no accumulation within themselves, the pigment that one sees in skin by the naked eye is primarily within keratinocytes. Degree of skin pigmentation directly correlates with the amount of melanin in it. The decrease in skin pigmentation reflects the decrease of melanin content reflecting the inhibition of melanogenesis, as a secondary effect. An aberrant epidermal melanin unit with abnormal keratinocytes and defective intercellular adhesions is also described in vitiligo which prevents effective transfer of melanin to keratinocytes which in turn halts melanogenesis. This is often an undervalued pathology for depigmentation.
Repigmentation of vitiligo lesions either spontaneously or with treatment depends on the existence of residual melanocytes located in the interfollicular epidermis (horizontal migration), the outer root sheath of hair follicles, sebaceous, and eccrine glands (vertical migration).,,,, Multipotent stem cells with neural crest-like characteristics in the dermis (melanoblasts) are also able to home to the epidermis to differentiate into melanocytes. Melanin index in lesional vitiligo skin represents the residual dormant melanocytes in the epidermis and appendages or indirectly the melanocytic reservoir. Thus, the probability and extent of repigmentation is better in patients with higher melanin indices.
An attempt has been made to identify the residual melanin in vitiligo lesion based on their characteristics on naked eye examination. However, the degree of depigmentation of a patch is subject to observer variation and clinical loss of skin and/or hair color may not always indicate the absence of melanocytes. Several noninvasive devices including multispectral imaging devices have been developed which may quantify melanin more accurately such as the Chromameter®, the DermaSpectrometer®, the Mexameter,® and real-time in vivo confocal laser scanning microscopy., To the best of our knowledge, no studies have used these devices to prognosticate repigmentation in vitiligo. The current report is of a preliminary study which is first of its kind. Inclusion of larger sample sizes and different anatomic sites could add validity to this novel method. As mexameter can detect and quantify melanin in skin, its use is validated to measure the efficacy of depigmenting agents in hyperpigmented lesions., Based on the same principle, we used mexameter as a pigment detecting and quantifying device in depigmented lesions of vitiligo. In addition, correlation was done between pretreatment melanin content and degree of repigmentation following therapy. The results of our study were statistically significant in deriving conclusions. Since the occurrence of melanized keratinocytes, melanophages, and tumor cells in vitiligo lesion that can interfere with melanin index is rare, this can be conveniently used to estimate melanin content in the scenario.,,
| Conclusion|| |
Melanin index >100 in a vitiligo patch is a strong predictor of possibility of repigmentation either spontaneously or with therapy. Melanin index >200 is strong predictor of 25–50% repigmentation at 6 months of monotherapy with a potent topical corticosteroid. However, it does not show any significance in predicting >50% repigmentation and may require longer duration of study and/or with combined therapy.
While suggesting correlation between residual melanin and potential for repigmentaion by a quick and easy method, we conclude that mexameter is a simple, reliable, noninvasive, low cost disease staging, and monitoring device in nonsegmental vitiligo. Although melanin index in vitiligo is not an absolute parameter for disease prognosis, it can serve as an objective marker for probable outcome. Patients could be counseled better and discussed about the prognosis before and during treatment. Suitable surgical and camouflage options could be offered to the patients with low melanin indices. This work hopes to provide future directions for further research correlating residual melanin content and repigmentation with different treatment modalities, thereby advancing toward successful vitiligo management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ezzedine K, Lim HW, Suzuki T, Katayama I, Hamzavi I, Lan CC, et al.
Revised classification/nomenclature of vitiligo and related issues: The vitiligo global issues consensus conference. Pigment Cell Melanoma Res 2012;25:E1‑13.
Kwinter J, Pelletier J, Khambalia A, Pope E. High‑potency steroid use in children with vitiligo: A retrospective study. J Am Acad Dermatol 2007;56:236‑41.
Finamor DC, Sinigaglia‑Coimbra R, Neves LC, Gutierrez M, Silva JJ, Torres LD, et al.
A pilot study assessing the effect of prolonged administration of high daily doses of Vitamin D on the clinical course of vitiligo and psoriasis. Dermatoendocrinol 2013;5:222‑34.
Xie H, Zhou F, Liu L, Zhu G, Li Q, Li C, et al.
Vitiligo: How do oxidative stress‑induced autoantigens trigger autoimmunity? J Dermatol Sci 2016;81:3‑9.
Gauthier Y, Cario Andre M, Taïeb A. A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 2003;16:322‑32.
Cario‑André M, Pain C, Gauthier Y, Taïeb A. The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis. Pigment Cell Res 2007;20:385‑93.
Xiang W, Xu A, Xu J, Bi Z, Shang Y, Ren Q. In vivo
confocal laser scanning microscopy of hypopigmented macules: A preliminary comparison of confocal images in vitiligo, nevus depigmentosus and postinflammatory hypopigmentation. Lasers Med Sci 2010;25:551‑8.
Hann SK, Park YK, Lee KG, Choi EH, Im S. Epidermal changes in active vitiligo. J Dermatol 1992;19:217‑22.
Ortonne JP, Bose SK. Vitiligo: Where do we stand? Pigment Cell Res 1993;6:61‑72.
Cichorek M, Wachulska M, Stasiewicz A, Tyminska A. Skin melanocytes: Biology and development. Postepy Dermatol Alergol 2013;30:30‑41.
Yamashita T, Kuwahara T, González S, Takahashi M. Non‑invasive visualization of melanin and melanocytes by reflectance‑mode confocal microscopy. J Invest Dermatol 2005;124:235‑40.
Tobin DJ, Swanson NN, Pittelkow MR, Peters EM, Schallreuter KU. Melanocytes are not absent in lesional skin of long duration vitiligo. J Pathol 2000;191:407‑16.
Yu HS. Melanocyte destruction and repigmentation in vitiligo: A model for nerve cell damage and regrowth. J Biomed Sci 2002;9(6 Pt 2):564‑73.
Yamaguchi Y, Hearing VJ. Melanocytes and their diseases. Cold Spring Harb Perspect Med 2014;4. pii: A017046.
Grichnik JM, Ali WN, Burch JA, Byers JD, Garcia CA, Clark RE, et al.
KIT expression reveals a population of precursor melanocytes in human skin. J Invest Dermatol 1996;106:967‑71.
Okamoto N, Aoto T, Uhara H, Yamazaki S, Akutsu H, Umezawa A, et al.
A melanocyte - Melanoma precursor niche in sweat glands of volar skin. Pigment Cell Melanoma Res 2014;27:1039‑50.
Jang YH, Kim SL, Lee JS, Kwon KY, Lee SJ, Kim do W, et al.
Possible existence of melanocytes or melanoblasts in human sebaceous glands. Ann Dermatol 2014;26:469‑73.
Li L, Fukunaga‑Kalabis M, Yu H, Xu X, Kong J, Lee JT, et al.
Human dermal stem cells differentiate into functional epidermal melanocytes. J Cell Sci 2010;123(Pt 6):853‑60.
Benzekri L, Ezzedine K, Gauthier Y. Vitiligo potential repigmentation index: A simple clinical score that might predict the ability of vitiligo lesions to repigment under therapy. Br J Dermatol 2013;168:1143‑6.
Clarys P, Alewaeters K, Lambrecht R, Barel AO. Skin color measurements: Comparison between three instruments: The Chromameter(R), the DermaSpectrometer(R) and the Mexameter(R). Skin Res Technol 2000;6:230‑238.
Xiang W, Song X, Peng J, Xu A, Bi Z. Real‑time in vivo
confocal laser scanning microscopy of melanin‑containing cells: A promising diagnostic intervention. Microsc Res Tech 2015;78:1121‑7.
Chung JY, Lee JH, Lee JH. Topical tranexamic acid as an adjuvant treatment in melasma: Side‑by‑side comparison clinical study. J Dermatolog Treat 2015;4:1‑5.
Dobos G, Trojahn C, Lichterfeld A, D Alessandro B, Patwardhan SV, Canfield D, et al.
Quantifying dyspigmentation in facial skin ageing: An explorative study. Int J Cosmet Sci 2015;37:542‑9.
Cameli N, Abril E, Agozzino M, Mariano M. Clinical and instrumental evaluation of the efficacy of a new depigmenting agent containing a combination of a retinoid, a phenolic agent and an antioxidant for the treatment of solar lentigines. Dermatology 2015;230:360‑6.
Paradisi A, Tabolli S, Didona B, Sobrino L, Russo N, Abeni D. Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo. J Am Acad Dermatol 2014;71:1110‑6.