|Year : 2020 | Volume
| Issue : 1 | Page : 32-38
A randomized controlled study to compare the efficacy of methotrexate vs. oral minipulse (betamethasone) along with NBUVB in patients with vitiligo vulgaris
Ashish Deshmukh, Garima Khurana
Department of Skin and VD, MGM Medical College and Hospital, Aurangabad, Maharashtra, India
|Date of Submission||25-Feb-2019|
|Date of Decision||07-Apr-2019|
|Date of Acceptance||12-May-2019|
|Date of Web Publication||10-Jul-2020|
Department of Skin and VD, MGM Medical College and Hospital, Aurangabad, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Several different treatment modalities are available to treat vitiligo. One of them is topical corticosteroids but it has limitations if used for longer time. To overcome the side effects, we evaluated the efficacy of oral steroids in minipulse form along with antimetabolite methotrexate (MTX) and narrow-band ultraviolet B (NBUVB). Aim: This article aims to compare the efficacy of oral MTX with NBUVB vs. oral minipulse with betamethasone along with NBUVB in the patients of vitiligo vulgaris. Materials and Methods: A prospective study was conducted in 100 clinically diagnosed cases of vitiligo vulgaris; 50 of them were given NBUVB twice in a week along with MTX orally in a dose of 7.5 mg once weekly for 6 months. Remaining 50 were given NBUVB twice in a week along with betamethasone in a dose of 5 mg on two consecutive days per week for 6 months. The patients were assessed after every 2 weeks for 6 months. Blood pressure was checked regularly at each visit. Complete blood count, liver function tests, kidney function tests, blood sugar levels, and even ophthalmic examination was done at the end of 3 months. Repigmentation in the patients was assessed at the end of 6 months according to the Vitiligo European Task Force scoring system. Results: There was a significant reduction (P < 0.05) in depigmented area and staging with complete cessation of spreading of the vitiligo lesion after 6 months of therapy with MTX and NBUVB and also with another group taking oral minipulse betamethasone and NBUVB. Limitations: It was an open-labeled study. Conclusion: MTX along with NBUVB is equally an effective modality in controlling the progression of vitiligo vulgaris with minimal side effects, and hence MTX can be used as a steroid-sparing drug in patients with active vitiligo wherever corticosteroids are contraindicated.
Keywords: Melanocytes, methotrexate, NBUVB, steroids, vitiligo
|How to cite this article:|
Deshmukh A, Khurana G. A randomized controlled study to compare the efficacy of methotrexate vs. oral minipulse (betamethasone) along with NBUVB in patients with vitiligo vulgaris. Pigment Int 2020;7:32-8
|How to cite this URL:|
Deshmukh A, Khurana G. A randomized controlled study to compare the efficacy of methotrexate vs. oral minipulse (betamethasone) along with NBUVB in patients with vitiligo vulgaris. Pigment Int [serial online] 2020 [cited 2020 Nov 30];7:32-8. Available from: https://www.pigmentinternational.com/text.asp?2020/7/1/32/289332
| Introduction|| |
Vitiligo is a common, acquired, depigmentary disorder of the skin, mucous membrane, and hair resulting from destruction of functional melanocytes. It is characterized by well circumscribed asymptomatic depigmented/chalky white macules of different size and shapes with the tendency to increase in size centrifugally. It affects all the ethnic groups and has a worldwide occurrence of 0.3% to 1%. Adults and children of both sexes are equally affected although the greater number of reports among females is probably due to greater social consequences to women and girls affected by this condition.
Vitiligo is considered to be a multifactorial disorder. An assortment of hypothesis such as genetic, neural, biochemical, and autoimmune have been put forth to elucidate its etiopathological mechanism. Three major factors seem to be involved in the destruction of melanocytes in patients with vitiligo.
- Vitiligo patients inherit a set of three vitiligo genes that predispose them to destruction of melanocytes.
- The melanocytes in vitiligo patients differ from that of normal person. They are more sensitive to phenolic chemicals and require different, more fastidious culture conditions than those of normal individuals.
- Destruction of melanocytes occurs due to activation of vitiligo genes by environmental agents, which further leads to activation of autoimmunity and apoptosis of melanocytes.
Cellular mechanisms are as important as humoral mechanisms in destroying melanocytes. Biopsies from vitiligo lesions show mild mononuclear infiltrate in the margins of lesional skin in active vitiligo with or without basal vacuolization. Active lesions show increased numbers of CD4+ T cells and increased epidermal expression of intercellular adhesion molecule 1 (ICAM-1). Both the CD4+ and CD8+ T cells from perilesional and nonlesional skin in vitiligo show polarization toward the type 1 cytokine profile that parallels depigmentation. The melanocyte-specific cytotoxic T cells found in perilesional biopsies have the ability to infiltrate normal skin and destroy the melanocytes. Besides cytotoxic T cells, regulatory T cells (Tregs) also have a role in vitiligo. The Treg population is not decreased in the peripheral circulation; however, these Tregs are not able to settle in the skin and this defect seems to be crucial in the observed perpetual antimelanocyte reactivity in progressive disease.
Autoimmunity theory appears to be most plausible as of its association with autoimmune disorders. Among cutaneous associations, premature graying of hair, leukotrichia, halo nevus, and alopecia areata are frequently reported. Furthermore, psoriasis vulgaris may be confined to vitiligo patches. Among systemic association, hypothyroidism/hyperthyroidism, diabetes mellitus, and pernicious anemia,,,,,, have been regarded [Figure 1],[Figure 2],[Figure 3].
|Figure 1 Vitiligo patches over dorsum of both the hands (A) before treatment and (B) after treatment with MTX and narrow-band ultraviolet B.|
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|Figure 2 Vitiligo patches over right elbow (A) before treatment and (B) after treatment with MTX and narrow-band ultraviolet B.|
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|Figure 3 Vitiligo patches over both arms (A) before treatment and (B) after treatment with oral minipulse (OMP) betamethasone and narrow-band ultraviolet B.|
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On the basis of clinical observation, vitiligo may be classified according to the distribution of vitiligo lesions:
- Generalized − (a) vulgaris; (b) acrofacial; (c) universal.
- Localized − (a) focal; (b) segmental.
Current clinical recommendations for vitiligo, limited to only a few patches, include treatment with topical agents such as corticosteroids and calcineurin inhibitors and localized narrow-band ultraviolet B (NBUVB) phototherapy. For more extensive or spreading disease, whole-body NBUVB phototherapy is recommended. Phototherapy with topical or oral psoralen combined with UVA irradiation is also effective.
Oral minipulse (OMP) therapy with betamethasone has been shown to be effective without any major side effect. Pulse therapy is a type of systemic management in which large amounts of medications are administered to patients in short time and intervals (e.g., weekly) to get the stronger effects of medication sooner and avoid their long-term use.
Pulse steroid therapy was firstly used in a patient with renal allograft in 1969. OMP is a type of pulse steroid therapy that is given orally in intervals to patients. An immediate profound antiinflammatory effect is achieved and the toxicities seen with conventional high-dose oral therapy are low with no suppressive effect on the hypothalamic–pituitary axis., It is more comfortable for patients to comply with than daily systemic steroid therapy.
Corticosteroids suppress autoantibody formation and likely induce apoptosis of cytotoxic T cells. The autoimmune hypothesis still prevails in the pathogenesis of nonsegmental vitiligo, and the autoimmune process is not limited to the skin. In progressive disease, there is continuous assault on melanocytes. Topical corticosteroids, tacrolimus, or any other topical agent may suppress autoimmune dysfunction at the site of a vitiligo lesion, but these do not have any effect on the disease process per se.
Photochemotherapy and phototherapy stimulate melanocytes to cause repigmentation and have minimal immunomodulatory action on T lymphocytes, but may not halt the rapid destruction of melanocytes.
Systemic corticosteroids act not only on lesional immune activity, but also on the T cells in peripheral circulation. Besides modulating cell-mediated immunity, corticosteroids also suppress autoantibody formation. The serum of actively spreading vitiligo patients who received oral corticosteroids and showed improvement had a decrease in complement-mediated cytotoxicity by melanocyte antibodies.
Methotrexate (MTX) is an antimetabolite and antifolate drug. It is used in the treatment of carcinomas, autoimmune diseases, and ectopic pregnancy, and for the induction of medical termination of pregnancy. It acts by inhibiting the metabolism of folic acid. It is used as a treatment for some autoimmune diseases including psoriasis and psoriatic arthritis, Crohn’s disease, and rheumatoid arthritis. MTX possibly suppresses tumor necrosis factor-α-induced nuclear factor-κB activation.
| Materials and methods|| |
This was a prospective randomized controlled comparative study to compare the efficacy of MTX with OMP with betamethasone along with narrow-band ultraviolet B (NBUVB) in the patients of vitiligo vulgaris in patients attending Skin and VD OPD with the approval of the Institutional Ethical Committee. A total of 100 patients were enrolled for the study according to the inclusion criteria.
- All clinically confirmed cases of vitiligo vulgaris attending Skin and VD OPD of MGM Hospital, Aurangabad, Maharashtra, India.
- Patients of age group 18 to 60 years were included in the study.
- The patients with preexisting leukopenia (below 4000/mm3), thrombocytopenia (count below 1,00,000/μL), or significant anemia (hemoglobin below 6 g/dL).
- Pregnant and breast-feeding women.
- Patients with diabetes mellitus.
- Patients prone to develop photosensitivity reactions.
- Patients with active severe infections and immunodeficiency syndrome such as human immunodeficiency virus and tuberculosis.
Detailed history of each patient was noted in a documented proforma. Relevant investigations were performed and on the basis of the investigations, the assessment was made.The patients were randomly divided into two groups − A and B − by using computerized randomized tables [Table 1],[Table 2],[Table 3].
Group A patients were given NBUVB along with MTX orally in a dose of 7.5 mg once weekly for 6 months.
NBUVB was started with a dose of 300 mJ/cm2 twice in a week and the dose was increased stepwise depending upon the patient’s erythema response. After every 2 weeks, assessment was done that was continued for a period of 6 months.
Complete blood count, liver function tests, and kidney function tests were done after every 3 months to assess the side effects of the drug.
Group B patients were given NBUVB along with betamethasone in a dose of 5 mg on two consecutive days per week after food with ranitidine.
NBUVB was given to the patients starting with a dose of 300 mJ/cm2 twice in a week and the dose was increased stepwise depending upon the patient’s erythema response. Patients were assessed after every 2 weeks for 6 months.
Blood pressure was checked regularly at each visit. Blood sugar levels and ophthalmic examination was done at the end of 3 months. Serial photographs of the patients were taken before and after the study with name, date, and registration number to assess the outcomes of the study.
Repigmentation in the patients of vitiligo vulgaris following the treatment was assessed at the end of 6 months according to the Vitiligo European Task Force scoring system.
The Vitiligo European Task Force scoring system is a clinical assessment tool that combines analysis of the extent, grading of depigmentation, and progression. For the evaluation of the extent of depigmentation, the “rule of nine” was adopted from the already used Severity Scoring for Atopic Dermatitis (SCORAD) index for atopic eczema.
The “rule of nine” is used to calculate the affected area as a percentage of the whole body, by estimating the face and neck and the upper limbs, as 9% of the whole-body surface each, 18% for the lower limbs and anterior trunk each, and 1% each for genitals, each palm, and the back of each hand.
Data are statistically described in number of cases and percentages when appropriate. Chi-square test and analysis of variance method was used for statistical significance.
Statistical calculations were done using computer programs IBM SPSS (Statistical Package for Social Science, IBM Corp, Armonk, NY) version 20 for Microsoft Windows. Findings were considered significant with P value <0.05.
| Observations and results|| |
In our study, a total of 100 patients were included. Detailed history was taken and examination was done.
There was a significant reduction (P < 0.05) in depigmented area (51%) and staging (50%) with complete cessation of spreading of the vitiligo lesion after 6 months of therapy with MTX and NBUVB.
There was a significant reduction (P < 0.05) in depigmented area (43%) and staging (48%) with complete cessation of spreading of the vitiligo lesion after 6 months of therapy with OMP betamethasone and NBUVB.
The analysis of variance revealed that there was no significant difference in the repigmented area, staging, and spreading before and after the treatment between the MTX and betamethasone group [Graphs 1-3].
| Discussion|| |
The prevalence of vitiligo is high in India. The relative prevalence varies between 0.46% and 8.8%. The varying ethnic backgrounds of the population residing in different geographic regions with varying environmental conditions may contribute to the wide variation in the prevalence of vitiligo in India.
The treatment results were compared with other studies in terms of repigmentation, staging, and spreading. Our study revealed that there was a significant difference in the percentage area, staging, and spreading before and after the treatment in MTX as well as betamethasone group with use of NBUVB in both the groups.
In betamethasone group, the mean depigmented area before was 17.54% that reduced to 9.98% after the treatment, mean staging reduced to 3.04 from 5.90, and mean spreading reduced to −2.58 from 2.62 in all the patients of vitiligo after 6 months of treatment that was consistent with the other studies done by Pasricha and Khaitan and Radakovic-Fijan et al. Side effects were recorded in 3% of the patients that included edema only. None of the patients developed new vitiligo lesions during the course of therapy. Although mild-to-moderate side effects are common with long-term therapy of betamethasone, it was concluded that treatment with OMP of betamethasone once a week along with NBUVB is effective in arresting progression of vitiligo.In MTX group, the mean depigmented area before was 16.42% that reduced to 8.06% after the treatment, mean staging reduced to 2.92 from 5.84 and mean spreading reduced to −2.58 from 2.62 in all the patients of vitiligo after 6 months of treatment, which was consistent with the study conducted by Singh et al. and one of the study conducted in the Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA. None of the patients on therapy developed new vitiligo lesions. No side effects were seen in the 6 months of study in the patients receiving low-dose MTX weekly for 6 months.
Thus, it was concluded that MTX along with NBUVB is an effective modality in controlling the progression of vitiligo vulgaris. At the end of the study, it was demonstrated that patients in both the groups had a similar reduction in the vitiligo disease activity score in terms of percentage area, staging, and spreading score with minimal side effects. Betamethasone and MTX both are equally effective in controlling the disease activity of vitiligo along with NBUVB.
Thus, we conclude that MTX can be used in patients with active vitiligo wherever corticosteroids are contraindicated.
We acknowledge the limitations of our study, which was an open labeled. Halting the progression is also the limitation of study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]