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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 121-125

Comparative study of safety and efficacy of oral betamethasone pulse therapy and azathioprine in vitiligo


Department of Dermatology, S. Nijalingappa Medical College, Bagalkote, Karnataka, India

Date of Web Publication15-Jul-2019

Correspondence Address:
Mahajabeen Madarkar
Department of Dermatology, S. Nijalingappa Medical College, Bagalkote, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_13_18

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  Abstract 


Background: Vitiligo is a common skin disorder causing depigmented macules that can impair a patient's quality of life. There are number of treatment modalities are available but at the present, there are no studies compairing betamethasone pulse therapy versus azathioprine daily therapy in treatment of vitiligo. Objectives: To compare the safety and efficacy of Azathioprine daily and Betamethasone pulse therapy in the treatment of in vitiligo. Materials and Methods: We included two vitiligo patient groups. namely group A and group B Patients of group A were given oral Azathioprine to be given 50mg twice daily and those of second group B, Betamethasone were given as a single oral dose of 5 mg on two consecutive days per week. Therapy in both groups was given for a total of 6months with follow up at 1, 3 and 6th month. Clinical photographs were taken at each visit. Side-effects if any were noted. Results were calculated with help of VASI score (vitiligo area severity index). Results: At the baseline: The patients to group A (SD 3.81± 2.3) and of group B (SD 3.76± 2.28) were having depigmented patches (P = 0.90). At the first follow up: Although there was significant improvement with perifollicular repigmentation started in both groups but the patients are of group B (SD 3.38±2.06) were showing slower response as compared to oral group A (SD 3.70± 2.28). At the second follow up: Remarkable improvement is seen in both groups compared (P = 0.17). At the third follow up: Significant improvement is seen in both groups compared (P = 0.09). Conclusions: Azathioprine and betamethasone pulse therapy are equally effective in treatment of vitiligo.

Keywords: Azathioprine, betamethasone, vitiligo


How to cite this article:
Madarkar M, Ankad BS, Manjula R. Comparative study of safety and efficacy of oral betamethasone pulse therapy and azathioprine in vitiligo. Clin Dermatol Rev 2019;3:121-5

How to cite this URL:
Madarkar M, Ankad BS, Manjula R. Comparative study of safety and efficacy of oral betamethasone pulse therapy and azathioprine in vitiligo. Clin Dermatol Rev [serial online] 2019 [cited 2019 Nov 11];3:121-5. Available from: http://www.cdriadvlkn.org/text.asp?2019/3/2/121/262768




  Introduction Top


Vitiligo is an acquired depigmenting disorder of multifactor origin affecting 0.5%–2% of the world population, with no sex predilection.[1] Vitiligo is characterized by macules and patches of depigmented skin. It occurs in localized, generalized, or segmental patterns. It can run a rapidly progressive course or remain stable.[2] It has a tremendous untoward effect on individual's outlook.[3] Hence, it warrants early and effective treatment. With the appropriate management, many patients can minimize disease progression, attain regimentation, and achieve cosmetically pleasing results.

There are numerous treatment modalities aimed at regimentation. The medical modalities of therapy include corticosteroids (both topical and systemic), immunomodulators, phototherapy (narrowband ultraviolet B [NBUVB]) and photochemotherapy (PUVA/PUVAsol), levamisole, calcipotriol, psuedocatalase, and placental extract.[1]

There are no studies showing a comparison of the effectiveness of azathioprine and betamethasone pulse therapy in the treatment of vitiligo.

Hence, the study aims at comparing the safety and efficacy of azathioprine and betamethasone pulse therapy in the treatment of progressive nonsegmental vitiligo.

Objectives

The objective of this study was

  1. To compare the efficacy of azathioprine daily and betamethasone pulse therapy in the treatment of in vitiligo
  2. To evaluate the adverse effects associated with the above-mentioned drugs.



  Materials and Methods Top


The study was conducted in one of the tertiary care centers of South India. It was a comparative study. The duration of the study was 6 months. Participants with clinical signs of vitiligo were included in the study. Informed written consent was taken from the patients. Ethical clearance was obtained from the Institutional Ethical Committee.

Patients were randomly divided into two equal groups, namely Group A and Group B. Patients of Group A were given betamethasone as a single oral dose of 5 mg on 2 consecutive days per week and those of the second Group B were given oral azathioprine 50 mg twice daily. Therapy in both groups was given for a total of 6 months with follow-up at 1st, 3rd, and 6th months. Clinical photographs were taken at each visit. Side effects if any were noted. Complete hemogram and liver function test were done once in 3 months.

Results were calculated with the help of vitiligo area severity index (VASI) score.

The percentage of vitiligo involvement is calculated regarding hand units. One hand unit (which encompasses the palm plus the volar surface of all digits) is approximately equivalent to 1% of the total body surface area. The degree of pigmentation is estimated to the nearest of one of the following percentages: 100% – complete depigmentation, no pigment is present; 90% – specks of pigment present; 75% – depigmented area exceeds the pigmented area; 50% – pigmented and depigmented areas are equal; 25% – pigmented area exceeds depigmented area; and 10% – only specks of depigmentation present.

The VASI for each body region is determined by the product of the area of vitiligo in hand units and the extent of depigmentation within each hand unit measured patch.[4]

Total body VASI = S All body sites (Hand Units) × (Residual depigmentation)

Statistical analysis was done using SPSS software, version 19 SPSS statistics for windows, (Version 19.0. Armonk, NY: IBM Corp.,) and Chi-square test and Student t-test for qualitative and quantitative data, respectively.

Inclusion criteria

  1. Patients with clinical signs of vitiligo
  2. Patients who have not taken any treatment for vitiligo during the last 6 months
  3. When body surface area >10% involved
  4. Patients with age more than 10 years
  5. Patients willing to participate in the study.


Exclusion criteria

  • Patients with segmental and mucosal vitiligo
  • Patients who are on different treatment modalities
  • Patients with age <10 years
  • Pregnancy and lactation
  • Patients with secondary pyoderma superseded in vitiligo
  • Patients not willing to participate in the study
  • Patients receiving topical or systemic therapy for vitiligo were given a wash-off period of 2 weeks before enrolling them into the study.



  Results Top


A total of 144 patients were recruited. There were 72 patients in each group, namely Group A and Group B, which were allocated by random allocation.

In Group A, the most common age group involved was 21–30 years, out of which 12 males and 11 females were there. In Group B, the most common age group involved was also 21–30 years, in which there were 10 males and 10 females [Figure 1].
Figure 1: Age distribution

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Forty-one patients (56.9%) in Group A were having progressive vitiligo whereas 39 patients (54.2%) in Group B were having progressive vitiligo [Figure 2].
Figure 2: Nature of disease

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Most of the patients in both the groups had taken treatment prior. Fifty-five patients (76.4%) in Group A and 57 patients (79.2%) in Group B had taken treatment prior.

Distribution of vitiligo in majority of cases was of generalized type in both the groups. In Group A, 42 patients (58.3%) were of generalized type of vitiligo, and in Group B, 39 patients (54.2%) were of generalized type of vitiligo.

Treatment outcome

At the end of the study period, the results were as follows: we compared the average repigmentation of patches with VASI score.

At the baseline

The patients of Group A (3.81 ± 2.3) and of Group B (3.76 ± 2.28) were having depigmented patches (P = 0.90) [Figure 3].
Figure 3: Comparative efficacy of Groups A and B with standard deviation

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At the first follow-up

Although there was a significant improvement with perifollicular repigmentation started in both groups, the patients of Group B (3.38 ± 2.06) were showing slower response as compared to oral Group A (3.70 ± 2.28) (P = 0.39) [Figure 3].

At the second follow-up

The extent of repigmentation varied in different patients and even in different lesions in the same patient. Remarkable improvement is seen in both the groups (P = 0.17) [Figure 3].

At the third follow-up

Remarkable improvement is seen in both the groups (P = 0.09) [Figure 3].

Seven patients (9.7%) of Group A and six patients (8.3%) of Group B showed nausea as side effect.

Five patients (6.9%) of Group A and three patients (4.2%) of Group B were having vomiting.

Twelve patients (16.7%) of Group A and one patient (1.4%) of Group B were having anemia.


  Discussion Top


Vitiligo is a disorder with great psychosocial implications, and its pathogenesis still eludes us. Although various treatment modalities were proposed for vitiligo, none is being uniformly effective.

Although vitiligo affects both sexes equally,[5] most of the studies[6],[7] show a female preponderance. The cause of female preponderance in our study is probably because of a greater cosmetic awareness among females and also social stigma associated with it.

In this study, in Group A, the most common age group involved was 21–30 years, out of which 12 males and 11 females were there. In Group B, the most common age group involved was also 21–30 years, in which 10 were male and 10 were female. In this study, slight female preponderance was seen.

In 1967, oral corticosteroids were used for the first time in vitiligo. Triamcinolone orally was found to have a synergistic effect with methoxypsoralen as compared to methoxypsoralen alone. In the year 1976, a mixture of prednisolone, betamethasone, paramethasone acetate, and methylprednisolone given orally was effective in producing satisfactory repigmentation in one-third of patients studied, thus confirming the efficacy of corticosteroids in vitiligo.[8]

Pulse therapy refers to the intermittent administration of large (suprapharmacological) doses to enhance the therapeutic effect and reduce the side effects of a particular drug. Oral minipulse (OMP) of moderate doses of betamethasone has been pioneered in India by Pasricha et al.[9]

OMP has stronger beneficial effects and fewer side effects, as it is administered twice weekly.

This treatment is so effective that the new lesions stop appearing within the first 1–2 months and the existing lesions start regimenting after 2 months.

In a research by Majid et al., 400 children with progressive vitiligo received oral methyl prednisolone (0.8 mg/kg with a maximum dose of 32 mg) on 2 consecutive days per week for 6 months. The progression of the disease was halted in more than 90% of the children, and moderate repigmentation was seen in 65.5% of the patients.[10]

In our present study, OMP therapy showed remarkable improvement in VASI [Figure 4], [Figure 5], [Figure 6], [Figure 7] score in each follow-up (3.8 ± 2.3).
Figure 4: At baseline of Group A patient

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Figure 5: At 1-month follow-up of Group A patient

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Figure 6: At 3-month follow-up of Group A patient

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Figure 7: At 6-month follow-up of Group A patient

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Azathioprine is an imidazole derivative of 6-mercaptopurine (6-MP) used as an immunosuppressant. It is a steroid-sparing agent, thereby reducing the toxicity associated with high dosage and prolonged usage of corticosteroids.[11]

Azathioprine is used in dermatological conditions such as atopic dermatitis,[12] psoriasis,[13] and lichen planus.[14]

In this study, azathioprine has shown good efficacy, better compliance, and reduced costs of treatment (3.76 ± 2.28) [Figure 8], [Figure 9], [Figure 10], [Figure 11].
Figure 8: At baseline of Group B patients

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Figure 9: At 1-month Group B follow-up

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Figure 10: At 3-month Group B follow-up

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Figure 11: At 6-month Group B follow-up

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There were negligible side effects such as nausea, vomiting, and anemia in patients of azathioprine group.


  Conclusion Top


Azathioprine and betamethasone pulse therapy are equally effective in the treatment of vitiligo. Azathioprine is helpful in halting progression and induces repigmentation with minimal side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Taieb A, Picardo M, editors. Epidemiology, definitions and classification. In: Vitiligo. Berlin, Heidelberg: Springer; 2010. p. 13-24.  Back to cited text no. 1
    
2.
Behl PN, Aggarwal A, Srivastava G. Vitiligo. In: Behl PN, Srivastava G, editors. Practice of Dermatology. 9th ed. New Delhi: CBS Publishers; 2003. p. 238-41.  Back to cited text no. 2
    
3.
Hautmann G, Panconesi E. Vitiligo: A psychologically influenced and influencing disease. Clin Dermatol 1997;15:879-90.  Back to cited text no. 3
    
4.
Komen L, da Graça V, Wolkerstorfer A, de Rie MA, Terwee CB, van der Veen JP, et al. Vitiligo area scoring index and vitiligo European task force assessment: Reliable and responsive instruments to measure the degree of depigmentation in vitiligo. Br J Dermatol 2015;172:437-43.  Back to cited text no. 4
    
5.
Sarin RC, Ajit SK. A clinical study of vitiligo. Indian J Dermatol Venereol Leprol 1977;43:311-4.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Howitz J, Brodthagen H, Schwartz M, Thomsen K. Prevalence of vitiligo. Epidemiological survey on the isle of Bornholm, Denmark. Arch Dermatol 1977;113:47-52.  Back to cited text no. 6
    
7.
Bor S, Feiwel M, Chanarin I. Vitiligo and its aetiological relationship to organ-specific autoimmune disease. Br J Dermatol 1969;81:83-8.  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.
Pasricha JS, Seetharam KA, Dashore A. Evaluation of five different regimes for the treatment of vitiligo. Indian J Dermatol Venereol Leprol 1989;55:18-21.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Majid I, Masood Q, Hassan I, Khan D, Chisti M. Childhood vitiligo: Response to methylprednisolone oral minipulse therapy and topical fluticasone combination. Indian J Dermatol 2009;54:124-7.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Chan GL, Canafax DM, Johnson CA. The therapeutic use of azathioprine in renal transplantation. Pharmacotherapy 1987;7:165-77.  Back to cited text no. 11
    
12.
Gunnar S, Johansson O, Juhlin L. Immunoglobulin E in “healed” atopic dermatitis and after treatment with corticosteroids and azathioprine. Br J Dermatol 1970;82:10-3.  Back to cited text no. 12
    
13.
Hacker SM, Ramos-Caro FA, Ford MJ, Flowers FP. Azathioprine: A forgotten alternative for treatment of severe psoriasis. Int J Dermatol 1992;31:873-4.  Back to cited text no. 13
    
14.
Klein LR, Callen JP. Azathioprine: Effective steroid-sparing therapy for generalized lichen planus. South Med J 1992;85:198-201.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]



 

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