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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 17-21

A comprehensive review on vitiligo and its pharmacotherapy: Recent trends and future challenges


1 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Asha 31982, Saudi Arabia
2 Postgraduate Student, Collage of Pharmacy, Jazan University, Saudi Arabia
3 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Asha 31982; Professor, Department of Pharmaceutics, Vidya Siri College of Pharmacy, Bengaluru, Karnataka, India, Saudi Arabia

Date of Submission09-Dec-2020
Date of Acceptance11-Dec-2020
Date of Web Publication21-Jan-2021

Correspondence Address:
Ms. Asmaa Moafa
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmo.ijmo_15_20

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  Abstract 


Approximately 1% of population in the world is affected by an intriguing skin depigmentation disorder, vitiligo. Typically, a vitiligo lesions are seen as white milky, nonscaly patches with separate edges. Vitiligo is caused by a selective loss of epidermal melanocytes. In vitiligo, there is impaired melanocyte regeneration and/or multiplication. Although the proportion of the population affected by this disease is very low, the disease is associated with a lot of social stigmas. This defect has an important effect on the life of the patient and still a persistent load.

Keywords: Depigmentation, epidemiology and dermatology, vitiligo


How to cite this article:
Moafa A, Khalawi F, Sreeharsha N. A comprehensive review on vitiligo and its pharmacotherapy: Recent trends and future challenges. Int J Med Oral Res 2021;6:17-21

How to cite this URL:
Moafa A, Khalawi F, Sreeharsha N. A comprehensive review on vitiligo and its pharmacotherapy: Recent trends and future challenges. Int J Med Oral Res [serial online] 2021 [cited 2021 Oct 20];6:17-21. Available from: http://www.ijmorweb.com/text.asp?2021/6/1/17/307581




  Different Types of Vitiligo Conditions Top


Segmental type vitiligo (SV) has a characteristic unilateral distribution. The findings suggest that this type of vitiligo is due to nonautoimmune factors and shows a quick stabilization. However, few cases to further progression of later stages have been reported.[1] In general, an early of vitiligo is seen in cases of SV compared with nonsegmental vitiligo. SV has been further classified based on the occurrence of lesions on the body parts.[1]

Face segmental type vitiligo

This classification was determined by differentiating the spread lesion figure in 257 Korean patients with SV on the face and was further subdivided into six subtypes as type 1a, 1b, 2, 3, 4, and 5. The most frequent subset is Type 1a, which is usually seen in the large section of the face at the left halve. Type 1a initiates on the right halve of the midline on the brow, leading to the core of the brow, further spreading horizontally and descending, which looks like a reversed V-shaped pattern. Type 1b is located on the left or right side of the forehead with frequent signs of poliosis. Type 2 lesions look like an arch pattern initiating from the otic region down to the midline region of the philtrum. In category 3, pigmentation is removed and initiates at one side of the bottom lip extend descending and somewhat laterally at neck direction. Category 4 firmly mimics category 1, but does not cross the central line (not same as type 1a) and is exclusively located on the right halve of the face. Finally, category 5 includes the right orbital zone, which can be seen as spreading to the temporal area.

Trunk segmental type vitiligo

Again, this subset is further subclassified as Type 1–6. In category I, II, and III, the top part of the trunk is affected, whereas in category IV and V, the central section of the trunk is affected and the bottom section of the trunk is affected in category VI. The most common SV is Type 3, which is seen as “trigon shape,” which can be noticed on the top trunk in opposition to the central line of the top thorax.


  Nonsegmental Vitiligo Top


The most common form of vitiligo is characterized by symmetrical and two-sided white spots. These macules have a typical tendency for symmetrical distribution. NSV lesions are typically disperse regular above the whole body or bilateral scattered in an acrofacial design.[2] Contrary to SV, in NSV, hairs of the body usually do not undergo depigmentation, although there is a possibility of hair depigmentation with disease progression.[3] The NSV includes many variants.

Generalized vitiligo

This most common form of vitiligo with characteristic milky-white spots presents on numerous pieces of the body, always in a symmetrical design. The most common initiation point of the disease is usually fingers, hands, and face. Pigmentation removal of scars is the most common indicator of Koebner's phenomenon (i.e., initiation of the diseases due to mechanical forces such as friction or usual pressure by wearing cloth or everyday tasks).[4] Koebner's phenomenon is thought to be responsible for the onset of so-termed isomorphic pigmentation-removed lesions.[3]

Acrofacial vitiligo

In acrofacial vitiligo, depigmentation is often located on the face, head, hands, and feet. A characteristic is the depigmentation of the distant finger and facial cavities. Later, it can proceed to more body parts as well and causes the typical generalized vitiligo. This type of vitiligo is further recurrent in late-onset cases like in adulthood.

Universal vitiligo or vitiligo universalis

A rare type of vitiligo is the most extensive form of the vitiligo that is usually seen in adulthood. Universal vitiligo corresponds to all pigmentation removal of the skin.[3] As the name suggests, “Universalis” means when pigmentation removal is effectively throughout the body (80%–90% of body skin), few pigmentations can be remains available i.n., hair partially spared. This diagnosis can be challenging in an individual with fair skin, while in the individual with dark skin, it can be easily diagnosed.

Apart from these classes of vitiligo, some other subsets also exist, namely, mixed vitiligo, bilateral segmental vitiligo, multisegmental vitiligo, focal vitiligo, mucosal vitiligo, and contact or occupational vitiligo.

The presence of segmental vitiligo and nonsegmental vitiligo simultaneously in a patient has been called mixed vitiligo, and in case the two SV lesions are in attendance on both body sides, it is termed as bilateral segmental vitiligo. If 2 clear segments on the same side are attending, it can be termed multi segmental vitiligo.[1] While, Focal vitiligo is an the presence of a little, isolated hypopigmented lesion, that neither fits into a typical segmental dispensation, nor does it evolves into NSV even after a duration of 1 or 2 years. Mucosal vitiligo typically mention to the include of the oral and/or genital mucosa.[3]


  Existing Pharmacotherapy for Vitiligo Top


Vitiligo is a complex autoimmune disease that affects an individual physically by causing skin disfiguration and ocular and auditory anomalies. A personalized approach is required for the management of vitiligo along with due consideration to several factors (vitiligo time periods, effect, skin type, area, gender, age, included areas, social life, and cultural influences). It has been observed that some regions, such as the face, always respond well to medicine while other body parts, namely, hands and feet remain unaffected. To date, there is no therapeutic remedy for vitiligo; however, current pharmacotherapeutic approaches can lead to significant improvement of vitiligo lesions.

The pharmacotherapy for the management of vitiligo intents to achieve the following three goals [Figure 1]:
Figure 1: Existing pharmacotherapy for the management of vitiligo

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  • Ceasing vitiligo development
  • Allowing complete natural coloring of lesional regions
  • Preventing recurrence.



  Ceasing the Disease Progression Top


Systemic corticosteroids

Systemic corticosteroids have been shown to quickly stop spreading disease and to make a natural color. Oral prednisolone in low doses (0.3 mg/kg) to be taken every day for 2 months along with a large dose of methylprednisolone (8 mg/kg) taken intravenously for consecutive 3 days. In addition, this regime has resulted in the induction of some repigmentation in almost 70% of the cases as well. Oral mini pulse of betamethasone or dexamethasone at a dose of 5 mg, two times a week, on consecutive 2 days for 3–6 months has also resulted in cessation of the disease progression. However, the cases of repigmentation in this therapy have been low. However side effects, namely increased weight, insomnia, acne, agitation, menstrual disturbance, and high blood pressure, can occur.[5]

Minocycline

Minocycline has anti-inflammatory, immunomodulatory, and free radical scavenging properties that encouraged the clinicians to use it in the management of vitiligo. 100 mg every day of minocycline has been found to halt the progression of vitiligo.[5]

Narrowband ultraviolet B

Two times a week, treatment with narrowband ultraviolet B (NB-UVB) has been found to be efficient to stop disease development and also has the major advantage of supporting more effective natural color of disease lesions.[5] In addition, melanocyte differentiation and melanin production are also induced by NB-UVB. The first-line therapy for extensive, progressive vitiligo is NB-UVB. This therapy has been found to be safe and can be administered safely to children and pregnant or lactating females. The therapy should be gradually optimized, with an aggressive approach. The initiation of the therapy is done at a low and safe dose of 200 mJ, administered twice or thrice a week with an increment of 10% to 20% of dose. The appearance of the symptomatic-free, light-pink erythema of the skin, which lasts for 24 h, is considered to be the optimal dose, and thereafter, therapy is continued at the same dose till erythema disappears.


  Repigmentation of Lesional Areas Top


Topical corticosteroids

Topical steroids are useful for little, localized regions, and sill one of the gold standard therapies for vitiligo. Children, in particular patients with dark skin with lesions on the face, respond to topical steroids more improved than old age patient, fair skin patients. Local side effects of cream steroids include atrophy, striae, telangiectases, perioral dermatitis, and glaucoma (when used around the eyes).[6] When choosing a cream corticosteroid, the site of the lesion and age of the patient need to be taken into consideration. Potent corticosteroids can be used for treating lesions on the body, whereas topical corticosteroids with less potency should be selected for the face, neck, and intertriginous regions and lesions in children. Daily or two times a day used with “days off” in a cyclic pattern is the possible regimens (e.g., 1-week use, then 1 week without for, 6 months, or application for 5 days followed by 2 days without).[7]

Topical calcineurin inhibitors

Creams calcineurin inhibitors (tacrolimus 0.03%/0.1% and pimecrolimus 1%) have been shown to be safe and effective in children's vitiligo, especially on the head and neck, in patients with the disease for <5 years, on intertriginous and genital skin, in facial segmental disease, in dark-skinned patients, on lesions on the head and neck (especially segmental facial type), and in patients with a Fitzpatrick skin type of 3–4. Children are nine times as likely as adults to get a good response. They are less effective in acral lesions and adults. Avoidance of application over atypical pigmented lesions is recommended.[6] Two times daily use is required for effective results. Topical calcineurin inhibitors are deemed to be the first-line therapy for facial vitiligo of childhood by the Vitiligo European Task Force.[6]

Topical Vitamin D

Calcipotriene is a Vitamin D analogous that is not effective for vitiligo individually, but is assistant helpful when taken with creams corticosteroids (e.g., betamethasone) for facial and body vitiligo in childhood or NB-UVB.[6]

Phototherapy is a beneficial therapeutic option for widespread vitiligo, especially in pediatric patients. Efficacy in childhood is two-fold, with stabilization of vitiligo being the first endpoint, which is achieved in 80% of children, and natural color being the secondary endpoint for children with generalized vitiligo.[6]

Apart from the above, few general points are to be taken care of in the management of vitiligo-

  • Avoiding Koebnerizing factors (friction, trauma) may help reduce the activation factors that progress new pigmentation removal
  • Good sun protection with sunscreens or clothing prevents sunburn on pigmented removal regions[8]
  • Diet rich in Vitamin B12, Vitamin B9, Vitamin C, Vitamin D, Vitamin E, and zinc enhances the effect of the therapy for vitiligo. Oral herbal supplements of Phyllanthus emblica fruit extract, Ginkgo biloba, Polypodium leucotomos, Piperine, Green tea, and epigallocatechin-3-gallate also help improve the effectiveness of vitiligo therapy.[9]


Potential emerging pharmacotherapy for vitiligo: Future research is now focused on three principle approaches:

Decreasing stress on melanocytes

This approach has been based on the fact that in vitiligo patients, elevated reactive oxygen species (ROS) levels and reduced levels of catalase enzyme in the epidermis lesional skin of vitiligo patients have been observed. Thus, using anti-oxidants or any agent that can reduce the ROS level seems to be a potential candidate for the management of vitiligo.[10] Pseudocatalase is one such drug, which has been evaluated in the past in combination with phototherapy. Topical treatment with pesudocatalase cream results in decreased ROS levels.[11],[12] Some clinical studies have been reported, wherein phototherapy along with a supplement (antioxidant or ROS reducing agent) has been found to promising. G. biloba[13],[14] and P. leucotomos with NB-UVB[15] are some of the phytopharmaceuticals which have been proved to be effective in the management of disease. Various antioxidants, namely, α-lipoic acid, Vitamin C, Vitamin E, and polyunsaturated fatty acids with and without phototherapy, have also been proven to be effective in vitiligo.[16]

Regulation of the autoimmune response

Immunomodulators are being explored to treat skin disorders, especially in conditions that involve the interplay of various immune factors. It has been reported that stressed melanocytes in vitiligo releases heat shock protein, HSP70i, thereby stimulating an innate inflammatory response in the skin.[17] Found that mutated protein, HSP70i, exhibited low immunogenicity and seems to induce tolerance, thereby averting the initiation of the disease. Antibodies and small-molecule inhibitors that can target interferon-γ, CXCL10, and the CXCL10 receptor, CXCR3, are being explored for the management of vitiligo and are under clinical evaluation.[18] Janus kinase (JAK)-STAT inhibitors are other important targets that are being explored for vitiligo. Oral tofacitinib, JAK 1/3 inhibitor, has been reported to provide a therapeutic effect in a generalized vitiligo patient. Tofacitinib has been approved by the Food and Drug Administration (FDA) for rheumatoid arthritis.[19] Another JAK inhibitor, Ruxolitinib, which has JAK 1/2 selectivity, and is FDA approved for the treatment of myelofibrosis and polycythemia vera, has been found to induce repigmentation.[20],[21] However, oral consumption of these immunosuppressants makes a patient more prone to a number of other diseases and side effects. Thereby, scientists now intend to develop topical formulations of these immunosuppressants.[21] Interestingly, it has been found that inhibition of HMG-CoA reductase correspondingly inhibits the function of STAT1. These findings have prompted the evaluation of statins, namely, atorvastatin and simvastatin in the management of vitiligo.[22]

Stimulating melanocyte regeneration

Α-melanocyte-stimulating hormone (α-MSH) is a hormone that is essential for the synthesis of melanin. Afamelanotide, an analog of α-MSH, is also being explored clinically for vitiligo. Patients with generalized vitiligo were administered a subcutaneous implant of afamelanotide along NB-UVB. It was found that a combination of NB-UVB and afamelanotide resulted in quicker and augmented total repigmentation compared to photo-monotherapy of NB-UVB.[23] This is one of the most promising potential candidates for vitiligo treatment. Defective WNT signaling is the hallmark for vitiligo. WNT signaling is a critical step in the differentiation of melanocyte during its synthesis. Ex vivo studies suggest it to be a potential target for vitiligo therapy.[24] The use of selective sunscreens is a very interesting approach that is being explored for vitiligo. In a small clinical trial, subjects were topical administered a 1% dimethicone formulation. Dimethicone is known to selectively block sunlight below 300 nm wavelength, thereby allowing nbUVB range (~311–312 nm) to penetrate and exert its therapeutic effect. However, large clinical trials need to be conducted to establish the effect of selective sunscreens [Table 1].
Table 1: Different pharmacotherapy for the management of vitiligo

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  Conclusion Top


Vitiligo is a complex chronic disease with an interplay of inflammatory-immune-activation-driven factors, without a conclusive treatment at present. Vitiligo is associated with a social stigma and affects the quality of the life of the patient immensely. The current pharmacotherapy, which involves the usage of drugs alone or in combination with phototherapy, has been able to either halt or reduce the disease progression and to a certain extent in promoting depigmentation. However, most of these approaches can result in a relapse of the disease. Hence, exploring novel targets for treating vitiligo becomes pertinent. Many new targets and drug candidates are under clinical trials and some of the candidates have shown promising results. This has increased the hope of developing a therapeutic candidate for vitiligo that can treat the disease completely. For this to achieve large, multicentered clinical trials for these drug candidates need to be carried out.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
van Geel N, Speeckaert R. Segmental vitiligo. Dermatol Clin 2017;35:145-50.  Back to cited text no. 1
    
2.
Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet 2015;386:74-84.  Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
Boniface K, Seneschal J, Picardo M, Taïeb A. Vitiligo: Focus on clinical aspects, immunopathogenesis, and therapy. Clin Rev Allergy Immunol 2018;54:52-67.  Back to cited text no. 4
    
5.
Passeron T. Medical and maintenance treatments for vitiligo. Dermatol Clin 2017;35:163-70.  Back to cited text no. 5
    
6.
Van Driessche F, Silverberg N. Current management of pediatric vitiligo. Paediatr Drugs 2015;17:303-13.  Back to cited text no. 6
    
7.
Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE, Vitiligo Working Group. Current and emerging treatments for vitiligo. J Am Acad Dermatol 2017;77:17-29.  Back to cited text no. 7
    
8.
Speeckaert R, van Geel N. Vitiligo: An update on pathophysiology and treatment options. Am J Clin Dermatol 2017;18:733-44.  Back to cited text no. 8
    
9.
Grimes PE, Nashawati R. The role of diet and supplements in vitiligo management. Dermatol Clin 2017;35:235-43.  Back to cited text no. 9
    
10.
Schallreuter KU, Wood JM, Lemke KR, Levenig C. Treatment of vitiligo with a topical application of pseudocatalase and calcium in combination with short-term UVB exposure: A case study on 33 patients. Dermatology 1995;190:223-9.  Back to cited text no. 10
    
11.
Patel DC, Evans AV, Hawk JL. Topical pseudocatalase mousse and narrowband UVB phototherapy is not effective for vitiligo: An open, single-centre study. Clin Exp Dermatol 2002;27:641-4.  Back to cited text no. 11
    
12.
BakisMs.Petsoglou S, Le Guay J, Wittal R. A randomized, double-blinded, placebo-controlled trial of pseudocatalase cream and narrowband ultraviolet B in the treatment of vitiligo. Br J Dermatol 2009;161:910-7.  Back to cited text no. 12
    
13.
Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of vitilgo vulgaris: An open label pilot clinical trial. BMC Complement Altern Med 2011;11:21.  Back to cited text no. 13
    
14.
Parsad D, Pandhi R, Juneja A. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol 2003;28:285-7.  Back to cited text no. 14
    
15.
Middelkamp-Hup M, Bos J, Rius-Diaz F, Gonzalez S, Westerhof W. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: A randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol 2007;21:942-50.  Back to cited text no. 15
    
16.
Dell'Anna M, Mastrofrancesco A, Sala R, Venturini M, Ottaviani M, Vidolin A, et al. Antioxidants and narrow band-UVB in the treatment of vitiligo: A double-blind placebo controlled trial. Clin Exp Dermatol 2007;32:631-6.  Back to cited text no. 16
    
17.
Mosenson JA, Zloza A, Klarquist J, Barfuss AJ, Guevara-Patino JA, Poole IC. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res 2012;25:88-98.  Back to cited text no. 17
    
18.
Rashighi M, Harris JE. Interfering with the IFN-γ/CXCL10 pathway to develop new targeted treatments for vitiligo. Ann Transl Med 2015;3:343.  Back to cited text no. 18
    
19.
Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: A pathogenesis-directed therapy. JAMA Dermatol 2015;151:1110-2.  Back to cited text no. 19
    
20.
Mesa RA, Yasothan U, Kirkpatrick P. Ruxolitinib. Nature Publishing Group; 2012.  Back to cited text no. 20
    
21.
Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB, et al. Ruxolitinib cream for treatment of vitiligo: A randomised, controlled, phase 2 trial. Lancet 2020;396:110-20.  Back to cited text no. 21
    
22.
Zar AR, Malik A, Mahmood A, Naseer QA, Yumei L. Pathogenesis and the emerging therapy of virtiligo. Arch Clin Biomed Res 2019;3:361-73.  Back to cited text no. 22
    
23.
Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M, Haddican M, et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: A randomized multicenter trial. JAMA Dermatol 2015;151:42-50.  Back to cited text no. 23
    
24.
Harris JE. Melanocyte regeneration in vitiligo requires WNT beneath their wings. J Invest Dermatol 2015;135:2921-3.  Back to cited text no. 24
    


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