Home About us Editorial board Ahead of print Current issue Archives Instructions Submit article Search Subscribe Contacts Login
  • Users Online: 408
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 33-38

Role of oral corticosteroids, methotrexate, and azathioprine in patients with unstable vitiligo: A comparative study


Department of Dermatology, Venereology and Leprosy, Government Medical College, Amritsar, Punjab, India

Date of Submission17-Jan-2020
Date of Decision15-Aug-2020
Date of Acceptance11-Jan-2021
Date of Web Publication16-May-2022

Correspondence Address:
Dr. Tejinder Kaur
Professor and Head, C-12, Medical College Campus, Government Medical College, Circular Road, Amritsar, Punjab 143001
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational.Pigmentinternational_

Rights and Permissions
  Abstract 


Background: There are several medical and surgical interventions for vitiligo but still the search for a definite cure is going on. The first goal of the therapy is to make the disease stable by preventing the appearance of new lesions. Drugs like oral corticosteroids, methotrexate, and azathioprine have been found effective in this phase. Objective: To compare the efficacy of oral corticosteroids, methotrexate, and azathioprine in patients with unstable vitiligo. Materials and Methods: It was a retrospective data analysis of 319 vitiligo patients, out of which 52 patients with unstable vitiligo who have received treatment in the form of 0.5 mg/kg oral corticosteroids on 2 consecutive days per week, 0.3 mg/kg methotrexate per week, and 1 to 1.5 mg/kg azathioprine daily were selected and were evaluated for the effect of drug for 12weeks. Results: There was no statistically significant difference in the appearance of new lesions in all 3 groups; however, methotrexate showed the early effect which plateaus after a few weeks whereas steroids as well as azathioprine showed a gradual and consistent effect. Conclusion: Methotrexate, steroids, and azathioprine all arrest the disease activity in vitiligo. Methotrexate can be used to arrest disease activity in fast-spreading vitiligo. Azathioprine can be used in patients with active vitiligo, wherever steroids are contraindicated.


Keywords: Azathioprine, corticosteroids, methotrexate,vitiligo


How to cite this article:
Mittal N, Kaur T. Role of oral corticosteroids, methotrexate, and azathioprine in patients with unstable vitiligo: A comparative study. Pigment Int 2022;9:33-8

How to cite this URL:
Mittal N, Kaur T. Role of oral corticosteroids, methotrexate, and azathioprine in patients with unstable vitiligo: A comparative study. Pigment Int [serial online] 2022 [cited 2022 Jul 1];9:33-8. Available from: https://www.pigmentinternational.com/text.asp?2022/9/1/33/345297




  Introduction Top


Vitiligo is an acquired condition resulting from the progressive loss of melanocytes characterized by milkywhite well-defined macules and patches.[1] The worldwide prevalence of vitiligo is around 0.5% to 1% equally affecting both sexes.[2]

Although vitiligo has a benign course, it can severely affect a patient's relationships, social life, as well as mental health leading to anxiety and/or depression.[3]

Vitiligo has complex pathogenesis, with various theories hypothesized; however, the cause remains unknown. The autoimmune hypothesis is currently the best supported followed by oxidative stress theory which states that the accumulation of Reactive Oxygen Species (ROS), mainly H2O2 leads to apoptosis of melanocytes by disrupting mitochondria.[4]

Keratinocytes play a major role in the regulation of proliferation and differentiation of melanocytes via cytokines. Abnormalities in keratinocytes result in passive melanocyte death.[5]

Other theories include melanocytorrhagy, decreased survival of melanocyte, High mobility group box protein 1 (HMGB-1) DNA binding protein, homocysteine, and vitamin D deficiency.[4]

According to convergence theory, various factors such as stress, accumulation of toxic compounds, infection, autoimmunity, mutations, cellular environment changes, defect in melanocyte migration, and proliferation all play a role in varying proportions in the etiopathogenesis of vitiligo.[6]

The primary objective is always to arrest the disease activity followed by repigmentation. There are limited options for the treating practitioner and their choice depends on the extent and site of disease, age, and motivation of the patient.[3]


  Materials and methods Top


It was a retrospective data analysiswhich included 319 vitiligo patients attending vitiligo clinic of our department from January 2018 to January 2019 and patients were evaluated asper followinginclusionandexclusioncriteria asgivenbelow:

Inclusion criteria: Patients with unstable vitiligo, with either sex or age.

Exclusion criteria:
  1. Stable vitiligo patients
  2. Leukoderma secondary to other causes
  3. Pregnancy/lactation
  4. Active bacterial/viral infection
  5. Bleeding diathesis
  6. Patients with severe hepatic, renal, or other systemic disorder
  7. Immunosuppression
  8. Alcohol abuse
  9. Aphakia or cataract
  10. Patients on other immunosuppressants and phototherapy
  11. Patients who did not complete 4 weekly follow-up for 12 weeks were excluded.


Fifty-two patients who fulfilled the above criteria were selected and divided into three groups based on the treatment they received as:

Group 1 patients received corticosteroid oral minipulse (OMP) therapy in the form of 0.5 mg/kg taken on consecutive days in a week.

Group 2 patients received methotrexate in the form of 0.3 to 0.5 mg/kg per week, folic acid 5mg was given 5 days per day excluding day of methotrexate.

Group 3 patients received azathioprine in the form of 1 to 1.5 mg/kg daily.

Assessment was done by Vitiligo Area Scoring Index (VASI) and Vitiligo Disease Activity Score (VIDA) and effect of three drugs on activity of disease was compared at 4 weekly intervals for 12 weeks.

RESULTS

In this study, out of 52 patients, 30 patients in Group 1, 12 patients in Group 2, and 10 patients in Group 3 completed the study and were included in the final analysis.

The mean age in the study was 21.65±15.72 with the mean age in male being 20.31±13.17 and in females being 22.10±18.45. Mean duration of disease (in years) was found to be 3.25±3.99 with a mean duration of disease being 3.39±4.14 in males and 3.81±4.47 in females which is statistically insignificant (P = 0.33) as shown in [Table 1]. There were 20 males and 32 females as shown in [Figure 1]. There was no statistically significant difference among three groups in comparison to age, gender, and duration of disease.
Table 1: Demographic characteristics of the study population

Click here to view
Figure 1: Pie Chart showing Sex Distribution in the study population

Click here to view


Majority of patients, 16 patients (30.7%), were asymptomatic, 29 (50.7%) patients had cosmetic disfigurement, whereas seven patients (13.5%) complained of itching.

Onset of vitiligo patch was seen most commonly in the lower limb in 16 patients (30.77%) followed by head and trunk, both accounting for 8 patients (15.38%) suggesting a possible role of Koebner phenomenon.

Precipitating factors such as trauma was observed in two patients (3.85%), itching in two patients (3.85%), and after burn in one patient (1.92%) whereas no precipitating factor could be found in 47 patients (90.38%). History of contact leukoderma was present in two patients (3.13%) to bindi and shoes which later progressed to involve a distant area whereas rest of patients had no history of contact.

Average body surface area (BSA), VISA, and VIDA at the start of study was found to be 6.57±8.96, 5.44±8.18, and 3.17±1.17, respectively, as shown in [Figure 2].
Figure 2: Bar Diagram depicting a comparison of average BSA, VASI, and VIDA in the males and females (P-value 0.53, statistically insignificant). BSA, body surface area; VASI, vitiligo area scoring index; VIDA, vitiligo disease activity score

Click here to view


The most common type of vitiligo observed was nonsegmental vitiligo in 41 patients (78.85%) followed by vitiligo vulgaris in four patients (7.69%) as shown in [Figure 3].
Figure 3: Bar Graph showing a comparison of the prevalence of different types of vitiligo in males and females of our study NSV was the commonest type present in 78.85% of patients. NSV, non-segmental vitiligo

Click here to view


Disease activity

At the end of the study, patients in all three groups had a reduction in disease activity as shown by a decrease in VASI score on follow-ups as shown in [Figure 4].
Figure 4: Bar Diagram depicting a comparison of decline in VASI among Steroid, Azathioprine and Methotrexate group on monthly followups. Methotrexate has the steepest slope in the start which plateaus subsequently, however, both steroids and azathioprine have downgrading slope

Click here to view


Mean difference in VASI on subsequent follow-ups showed although all three drugs are effective in arresting disease activity but methotrexate has early effect whereas both steroids and azathioprine have a gradual and consistent effect as shown in [Table 2].
Table 2: Comparison of mean difference of VASI with baseline score after application of different medications

Click here to view



  Discussion Top


As vitiligo affects the social life of the person as well as their family, it needs to be controlled vigorously. However, response to treatment may vary depending on various factors such as duration of disease, skin type, and location of lesions such as recent onset lesion in fair skin on head, neck, and trunk will respond better than otherwise. Controlling the disease activity is as important as to induce repigmentation.

Search for the definitive cure of vitiligo is going on for decades. Different approaches, such as ultraviolet (UV) light, psoralens, corticosteroids, and surgical procedures, have been used in the treatment of generalized vitiligo.

Various studies have demonstrated the efficacy of topically applied corticosteroids in inducing repigmentation in localized areas of vitiligo; however, long-term use results in the development of skin atrophy and telangiectasia. Although it is difficult to apply in widespread vitiligo, it is still being preferred in pediatric patients with vitiligo.[7]

Although systemic corticosteroids were found to be efficacious in treatmentof widespread vitiligo, significant side effects were reported on their long-term use, for example, obesity, moon face, osteoporosis, and lens opacities, one of such study being done by Imamura and Tagami.[8]

To decrease side effects, intravenous pulsed administration of high-dose glucocorticosteroids was done. In a study by Seiter et al.,[9] 14 vitiligo patients were administered methylprednisolone 8 mg/kg Intravenous (IV) on 3 consecutive days. In which 85% showed cessation of disease progression. Repigmentation was observed in 71%.

Still better than that, to improve compliance and avoid invasive treatment, OMP corticosteroids were tried as in a study by Pasricha and Khaitan,[10] who administered oral dexamethasone 5 mg/day on 2 consecutive days weekly and a study by Kanwar et al.[12] who administered oral dexamethasone 2.5 mg/day on 2 consecutive days weekly showed arrest of disease activity in 89% and 91.8% patients, respectively, within 1 to 3 months of treatment initiation without any significant side effects.

OMP with betamethasone/dexamethasone is hence an effective alternative to arrest the disease progression in vitiligo. It also induces simultaneous repigmentation along with arresting disease activity.[7]

Our study results are consistent with the above studies with arrest of disease activity and repigmentation seen in 84.9% patients on OMP corticosteroids with minor side effects like weight gain, propensity to acquire infection in minority of them.

In lieu of searching for a better option for treatment of vitiligo, a number of drugs were tried. Following the case report by Sandra et al.,[11] in which a patient with longstanding rheumatoid arthritis with recently developed progressive vitiligo lesions responded well to a weekly oral dose of methotrexate 7.5 mg with improvement of arthritis and arrest of vitiligo activity along with considerable repigmentation at 3 months of follow-up.

Since then, the role of this antimetabolite and antifolate drug is being explored in vitiligo. It is being used in the treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortion successfully for years. It results in a decreased number of T-cells capable of Tumor Necrosis Factor (TNF) alpha production, whereas the number of T-cells producing Interleukin (IL)-10 after polyclonal activation increased. Methotrexate possibly suppresses TNF alpha-induced Nuclear Factor-kappa beta (NF-kB) activation.[12]

Further studies were conducted to confirm the effect of methotrexate in progressive vitiligo. One such study was conducted by Al Ghamdi and Khurrum[13] who studied the patients with more than 6% body surface area affected and who took treatment in the form of 25 mg/week with folic acid 5mg daily except the day on which methotrexate was taken. However, clinical and photographic assessment revealed no change in vitiligo lesions.

In this regard, a randomized, open-label trial of methotrexate was conducted by Singh et al.[14] in which methotrexate 10 mg weekly was compared with OMP steroid therapy in 52 patients with unstable vitiligo, and no difference in effectiveness between the two treatment modalities in halting the spread of depigmentation was found.

In our study, arrest of disease activity was achieved in first few weeks following ingestion of methotrexate in majority of patients with 89% patients showing inactivity of disease and repigmentation further confirming the effectiveness of drug; however, few patients (10%) complained of nausea and varicella was reported in one patient.

In patients in whom steroids were contraindicated or not tolerated, azathioprine was tried. Azathioprine is an immunomodulator used in the treatment of a variety of autoimmune diseases including pemphigus vulgaris, bullous pemphigoid, dermatomyositis, and Systemic Lupus Erythematosus (SLE). As compared with other cellular immunosuppressive agents, azathioprine is safe, costeffective, and more available and can be used without any side effects.[15]

Role of azathioprine is still in the research phase. Only one study has been conducted which showed that triple therapy of azathioprine in combination with prednisolone plus ultraviolet radiation in vitiligo was more likely to achieve 75% of skin repigmentation 4 months after treatment.[16]

Azathioprine, in our study, was found to be efficacious similar to corticosteroids with cessation of disease activity and repigmentation in 87.4% patients with lymphopenia noted in one patient, and hyperlipidemia in one patient. These results are similar to the results of other studies though only few studies are available on this drug.


  Conclusion Top


Although all three drugs are equally effective in controlling disease activity, methotrexate has early onset of action; however, the effect is nonprogressive after a few weeks hence it can be used to arrest disease activity in fastspreading vitiligo. Whereas, both steroids and azathioprine showed gradual and consistent effect in controlling the disease activity. Azathioprine can be used in patients with active vitiligo, wherever steroids are contraindicated.

The small sample size is one of the limitations of this study. A better conclusion could be obtained by studying a larger population. The long-term controlled studies with blinded assessment of a larger cohort are required to augment the findings of our study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bologna J, Pawelek JM. Biology of hypopigmentation. J Am Acad Dermatol 1988;19:217‘55.  Back to cited text no. 1
    
2.
Taieb A, Picardo M. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res 2007;20:27‘35.  Back to cited text no. 2
    
3.
Nordlund JJ, Halder RM, Grimes P. Management of vitiligo. Dermatol Clin 1993;11:27‘33.  Back to cited text no. 3
    
4.
Arora AK, Kumaran MS. Pathogenesis of vitiligo: an update. Pigment Int 2017;4:65‘77.  Back to cited text no. 4
    
5.
Lee AY. Role of keratinocytes in the development of vitiligo. Ann Dermatol 2012;24(2):115‘25.  Back to cited text no. 5
    
6.
Le Poole IC, Das PK, Van Den Wijngaard RM, Bos JD, Westerhof W. Review of the etiopathomechanism of vitiligo: a convergence theory.Exp Dermatol 1993;2:145‘53.  Back to cited text no. 6
    
7.
Kanwar AJ, Dhar S, Dawn G. Oral minipulse therapy in vitiligo. Dermatology 1995;190:251‘2.  Back to cited text no. 7
    
8.
Imamura S, Tagami H. Treatment of vitiligo with oral corticosteroids. Dermatologica 1976;153:179‘85.  Back to cited text no. 8
    
9.
Seiter S, Ugurel S, Pföhler C, Tilgen W, Reinhold U. Successful treatment of progressive vitiligo with high-dose intravenous methylprednisolone ‘pulse’ therapy. Dermatology 1999;199:261‘2.  Back to cited text no. 9
    
10.
Pasricha JS, Khaitan BK. Oral mini-pulse therapy with betamethasone in vitiligo patients having an extensive or fast-spreading disease. Int J Dermatol 1993;32:753‘7.  Back to cited text no. 10
    
11.
Sandra A, Pai S, Shenoi SD. Unstable vitiligo responding to methotrexate. Indian J Dermatol Venereol Leprol 1998;64:309.  Back to cited text no. 11
    
12.
Kanwar AJ, Mahajan R, Parsad D. Low-dose oral mini-pulse dexamethasone therapy in progressive unstable vitiligo. J Cutan Med Surg 2013;17:259‘68.  Back to cited text no. 12
    
13.
Al Ghamdi K, Khurrum H. Methotrexate for the treatment of generalized vitiligo. Saudi Pharm J 2013;21:423‘4.  Back to cited text no. 13
    
14.
Singh H, Kumaran MS, Bains A, Parsad D. A randomized comparative study of oral corticosteroid minipulse and low-dose oral methotrexate in the treatment of unstable vitiligo. Dermatology 2015;231:286‘90.  Back to cited text no. 14
    
15.
Goldstein E, Haberman HF, Menon IA, Pawloski D. Non-psoralen treatment of vitiligo. Part II. Less commonly used and experimental therapies. Int J Dermatol 1992;31:314‘9.  Back to cited text no. 15
    
16.
Radmanesh M, Sedi K. The efficacy of combined PUVA and low-dose azathioprine for early and enhanced repigmentation in vitiligo patients. J Dermatol Treat 2006;17:151‘3.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Figure 4], [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and me...
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed432    
    Printed6    
    Emailed0    
    PDF Downloaded35    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]