Indian Journal of Dermatology
ORIGINAL ARTICLE
Year
: 2013  |  Volume : 58  |  Issue : 2  |  Page : 113--116

Relapse after methylprednisolone oral minipulse therapy in childhood vitiligo: A 12-month follow-up study


Imran Majid1, Saher Imran2,  
1 Department of Dermatology, Government Medical College Srinagar, India
2 CUTIS Skin and Laser Institute, Srinagar, Kashmir, India

Correspondence Address:
Imran Majid
CUTIS Skin and Laser Institute, Karanagar Chowk, Srinagar, Kashmir
India

Abstract

Background: Oral minipulse (OMP) therapy with methylprednisolone is presently one of the most common oral treatments used for progressive vitiligo in children. The treatment is usually given for a period of 6 months during which majority of patients are reported to go into remission. However, there are no follow-up studies to comment upon what happens to the disease after OMP therapy is withdrawn. Aim of the study: To document the incidence of relapse over a period of 1 year after OMP therapy is stopped in children with vitiligo. Materials and Methods: The study was conducted in 180 patients of childhood vitiligo (<15 years of age) who had been on OMP therapy with oral methylprednisolone for at least 6 months and who had achieved a complete remission of their disease during the treatment period. The enrolled patients were followed up for a period of 1 year and examined clinically for any sign of reactivation of their disease over either the old lesions or at any new area of the body. Results: Forty-two patients were lost and could not complete the follow-up period of 1 year. Out of the 138 patients available at the end of 1 year, relapse was observed in 48 patients (34.8%). Rest of 90 patients remained in remission over the follow-up period of 1 year. Relapse was more common in patients below 10 years of age (47.4%) as compared with older children (25.9%). Conclusion: Relapse after using methylprednisolone OMP therapy in children with vitiligo is quite common especially in younger age groups. Studies are needed to see whether these relapses could be avoided by giving the treatment for a period longer than 6 months.



How to cite this article:
Majid I, Imran S. Relapse after methylprednisolone oral minipulse therapy in childhood vitiligo: A 12-month follow-up study.Indian J Dermatol 2013;58:113-116


How to cite this URL:
Majid I, Imran S. Relapse after methylprednisolone oral minipulse therapy in childhood vitiligo: A 12-month follow-up study. Indian J Dermatol [serial online] 2013 [cited 2020 May 25 ];58:113-116
Available from: http://www.e-ijd.org/text.asp?2013/58/2/113/108040


Full Text

 Introduction



Vitiligo is one of the most common skin disorders with a worldwide distribution and an overall prevalence of about 1% in the world. [1] The onset of vitiligo is in childhood in majority of cases and it has been shown that in 80% of patients the disease starts before the age of 20 years. [2] This means that the majority of vitiligo patients presenting to any dermatologist for the first time belong to the childhood vitiligo group. And it is in this group that the treatment is the most difficult owing to the high incidence of adverse effects with any systemic treatment option in childhood. Vitiligo is always associated with tremendous psychological trauma in both children as well as in adults and this is even more pronounced in people with colored skin. [3],[4],[5] All these factors make the treatment of progressive childhood vitiligo a really challenging task.

Treatment options available to treat vitiligo in children are limited. On the topical front, corticosteroids, calcineurin inhibitors like tacrolimus and pimecrolimus, psoralens in solution or ointment base, and human placental extracts have been seen to be useful treatment options in childhood vitiligo. [6],[7],[8] However, children having progressive vitiligo usually need some form of systemic therapy to control their disease. Oral psoralens are generally not given in younger age groups because of their long-term adverse effect profile. [7] Oral corticosteroids have been used in vitiligo quite commonly in the past. [9],[10],[11] However, as the treatment has to be prolonged in a disease like vitiligo, this form of treatment is not without its risks. To overcome the risks of prolonged steroid therapy, at least partially, oral minipulse (OMP) therapy with betamethasone or methylprednisolone has been devised to control progressive vitiligo in children as well as in adults. In this form of treatment, oral corticosteroids are given on two consecutive days every week with a 5-days rest between the two minipulses. [12],[13],[14],[15] The dose of betamethasone that has been used in this form of therapy is 5 mg on each of the 2 days in adults [13] while as methylprednisolone is used in a dose of 0.8 mg/kg body weight (max 32 mg) on each day of the minipulse. [12] The treatment is thus continued in most cases for duration of 6 months after which the treatment is usually withdrawn. The treatment is advocated in patients with progressive patchy or generalized vitiligo and even in acrofacial vitiligo. Segmental vitiligo is usually not treated with this regimen because of its non-progressive nature and relative unresponsiveness to oral steroids or even to OMP. In addition to childhood and adult vitiligo, OMP therapy has been used in many other skin disorders as well. [16],[17],[18] However, there are a lot of questions that remain still unanswered about OMP therapy (OMP) in general and especially in vitiligo. How OMP treatment needs to be withdrawn, whether abruptly or gradually as is done in any prolonged steroid therapy has not been commented upon till date. And what happens to vitiligo that has gone into remission with OMP therapy after the treatment is withdrawn is also not known clearly. Similarly, is the duration of 6 months really enough for the disease to go into a permanent remission or is there a need to give the treatment for a more prolonged period especially in patients with a severe disease. All these questions are still unanswered as of today.

 Materials and Methods



This prospective study was conducted on 180 patients of childhood vitiligo who had received OMP therapy for a minimum period of 6 months at our center for progressive vitiligo. All patients below 15 years of age, who had gone into complete remission with OMP and had remained in remission throughout the duration of treatment, were enrolled for the follow-up study. Patients achieving partial remission only or showing brief periods of activity of the disease while on OMP were excluded from the present study. The percentage of body area involved by vitiligo, the extent of repigmentation achieved after treatment with OMP, any concomitant medical disorders as well as any complications arising out of OMP were noted down at the time of enrolment. Patients who had either stopped their OMP abruptly after 6 months or withdrawn the treatment gradually over 6-12 weeks after the completion of 6-month therapy were all enrolled for the study. Patients suffering from segmental vitiligo were excluded as OMP was not routinely used as a treatment option in this morphological type of vitiligo. After enrolment, patients were not offered any systemic therapy in the follow-up period and were prescribed only topical therapies if there were any residual lesions of vitiligo left. Topical therapies that were allowed in the follow-up period included topical psoralens and topical calcineurin inhibitors like tacrolimus or pimecrolimus.

Follow up of the patients was carried out every month for the first 3 months and then every 3 monthly for a total duration of 1 year. Additionally, the patients were also told to report anytime if they noticed any suspicious lesion of vitiligo or any depigmentation at the already involved sites. The patients were evaluated clinically as well as with repeated digital photographs and the points that were noted down at each follow-up visit included progression of any residual vitiligo lesions present, any negative change in the repigmentation achieved at the end of OMP therapy or any fresh lesion of vitiligo anywhere over the body. Patients going into relapse at any time in the follow-up period were offered alternative therapies if their disease was progressing fast.

 Results



Out of the 180 patients enrolled for the study, 42 could not complete the mandatory 1-year follow up and were thus dropped from the study analysis.

Of the rest of 138 patients who completed the follow-up period of 1 year we had 82 females and 56 males with a sex ratio of 1:1.5 (approx).

The mean age of the patients was 9.93 years with a standard deviation of 2.9 years. Patchy and generalized vitiligo was the most common type of vitiligo present, seen in 129 patients (93.5% of total) while acrofacial vitiligo was seen in 9 patients only (6.5%). Segmental vitiligo, as already stated, was not included in the study.

In 84 patients (61%) out of the total of 138, the OMP therapy had been withdrawn with a gradual reduction in dose of methylprednisolone every 2 weeks over a period of 6 to 12 weeks. However, in 54 patients (39%), OMP had been stopped abruptly after 6 months without any tapering in the dose.

The duration of vitiligo at the time of starting OMP therapy in the study patients ranged from a minimum of 1 month to a maximum of 6 years with a mean of 5.2 months.

The characteristics of patients and the type of vitiligo in different age groups are given in [Table 1].{Table 1}

Overall, relapse of vitiligo was seen in 48 patients out of the total of 138 (34.8%) over the follow-up period of 1 year [Table 2]. Out of these 48 relapses, 8 relapses occurred in the first 3 months and another 21 were seen in the next 3 months of follow up. Thus we had a total of 29 relapses in total in the first six months after discontinuation of OMP. In the next 6 months of follow up there were further 19 relapses, 15 in the 3 rd quarter and only 4 in the last quarter of the 1-year follow up. Thus, the maximum risk of relapse was observed between the 3 rd and 9 th month of the 1-year follow-up period.{Table 2}

Age of the patients was seen to have a correlation with the relapse rate. Out of the total of 138 patients who completed the follow up of 1 year, there were 57 patients below 10 years of age and among these patients, relapse was seen in 27 patients (47.4%). In the age group of 11-15 years there were 81 patients out of whom 21 developed a relapse of the disease (25.9%). The correlation of relapse rate with the age of the patient was tested for statistical significance by using SPSS software for Windows. We used Chi-square test and Fisher's exact test to get the statistical conclusions. The difference in the relapse rates between the two age groups was found to be statistically significant ( P < 0.008) [Figure 1].{Figure 1}

The relapse rate was correlated with the method of discontinuation of OMP therapy as well. In 84 patients who had withdrawn the OMP therapy gradually with tapering of the dose over a period of 6 to 12 weeks, relapse was seen in 27 (32.1%) patients. However, in 54 patients in whom OMP had been stopped abruptly after 6 months without any tapering in the dose, relapse occurred in 21 (38.8%) patients. The difference in the relapse rate between the two groups was, however, found to be statistically not significant ( P > 0.5).

Among the different morphological types of vitiligo, relapse was seen to be relatively more common in acrofacial vitiligo. Among 9 patients of acrofacial vitiligo, relapse was seen in 7 patients (77.8%). On the other hand, 41 patients (31.7%) out of a total of 129 with patchy and generalized vitiligo showed a relapse over 1-year follow up. However, due to a very small number of patients with acrofacial vitiligo, the difference in relapse rates between the two morphological types was not tested for any statistical significance.

 Discussion



Treatment of vitiligo is done on two fronts- one, to control the progression of the disease and the other, to cause a repigmentation of already developed lesions. Both of these fronts are almost equally important as a patient who is achieving some repigmentation but continues to have fresh lesions elsewhere will never be satisfied with the treatment offered. Similarly, a patient whose disease gets stabilized but the lesions persist without any repigmentation cannot be termed as 'cured'. OMP therapy with either betamethasone or methylprednisolone is basically used to cause a stabilization of disease process in vitiligo. And going by the studies available in world literature at present, this treatment seems to be effective on this front in the large majority of affected patients. [12],[13],[14],[15] However, what happens to vitiligo once OMP therapy is discontinued has never been documented upon till date.

Vitiligo is presumed to be an autoimmune disease and that is how steroids or even OMP therapy has a role in this disease. [19],[20],[21] However, as is expected with any disease of autoimmune origin, the disease may relapse anytime after going into remission with any of the treatment options offered to the patient. In fact, studies conducted on the stability of pigmentation in vitiligo with some other treatment options like Narrowband UVB (NBUVB) or Psoralens photochemotherapy have shown that majority of patients do show a relapse of the depigmenting process once the therapy is discontinued. [22],[23] Does this apply to OMP therapy as well-that is what we tried to see in this study.

The results of this study have clearly shown that there are fair chances of relapse in progressive vitiligo which gets stabilized with OMP therapy after the treatment is withdrawn. Relapse was seen in 34% of our patients in the follow-up period of 1 year-this means that on an overall basis about one in every three patients is likely to show a relapse after withdrawal of OMP therapy over 1 year. What happens beyond 1-year follow up is beyond the scope of the present study but it can be presumed that the percentage of patients going into relapse is likely to be more if the follow up is extended beyond this period.

Relapse in the first year of follow up can occur at any time but the maximum chance of seeing a relapse is between the 3 rd and 9 th month. Furthermore, what this study has shown is that relapse can occur irrespective of whether the treatment is stopped either abruptly after 6 months or gradually over a period of 1-3 months after completing 6 months of standard OMP therapy.

Patients belonging to younger age group show an increased propensity to develop a relapse than the older age groups. What we have observed in our study is that patients below 10 years of age have a worse prognosis as far as the relapse of vitiligo after stopping OMP therapy is concerned. The inference that can be drawn from this observation is that vitiligo that starts in younger age groups is inherently more severe or is more likely to recur after immunosuppressant therapy than that in older age groups. It is also a possibility that patients belonging to younger age groups may need either a more prolonged course or an increased dose of methylprednisolone per kg body weight as compared with older age groups for the disease to remain stable after the end of OMP therapy. This remains to be seen and can be elucidated with further scientific studies.

 Conclusion



While we can safely comment after conducting this study that relapse is likely to occur in about 34% patients over 1 year after we stop OMP therapy, what about the rest of 66%? Can their disease be termed as permanently stable after the follow-up period of 1 year? Probably not, as vitiligo is known to recur after years or even decades of inactivity. However we can safely say that the disease in this subgroup has definitely "stabilized" with OMP therapy. We certainly need more studies with more prolonged follow ups to comment upon the future of this 'stabilized' vitiligo. Similarly, we need studies with different dosage schedules or treatment durations of OMP therapy are needed to see whether the chances of relapse can be further minimized in childhood vitiligo.

 Acknowledgements



I would like to acknowledge the help of our colleague Dr Inam for the statistical help in this manuscript.

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