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Surgery and Cosmetics

Systemic Corticosteroids in the Treatment of Progressive Unstable Vitiligo

Adriana Rodriguez, Amit G. Pandya, MD

Monday, September 01, 2014

Vitiligo, an acquired, idiopathic, chronic pigmentary disorder of the skin causing hypo and depigmented macules, causes significant psychosocial stress in affected patients.1 The etiology of vitiligo is thought to be autoimmune and has been studied in animals and humans.2,3 An inflammatory infiltrate of T cells appears to be an important factor in causing lesions to appear and expand.2,4 Multiple agents to reduce inflammation have been used over the years, including corticosteroids and calcineurin inhibitors.5 Even systemic corticosteroids have been used to halt the spread of vitiligo and induce repigmentation in a few reports.6 What is the evidence of their efficacy?

Prior to embarking on a discussion of systemic corticosteroids for vitiligo, one must pause and ask: Is it ethical and appropriate to use systemic agents with significant side effects for a disease that only causes pigmentary changes? What if there is a serious side effect? Controversy exists regarding the safety and efficacy of systemic corticosteroids for vitiligo and they are not currently considered a conventional treatment for this disease.7 Clearly this is a situation in which the benefit: risk ratio must be evaluated carefully.

Pulse therapy refers to the administration of supra-pharmacologic doses of drugs in an intermittent manner to enhance the therapeutic effect and reduce the side effects of a particular drug.6,8 Oral minipulse (OMP) therapy using arbitrary doses of betamethasone, dexamethasone or methylprednisolone have been successfully employed since 1989 to arrest the activity of vitiligo (Table 1); however, the optimal agent is still not clear. A regimen of dexamethasone, 5 mg/day for 2 consecutive days per week (half dose in children), is frequently used in reports of OMP therapy (Figures 1 and 2).5,6 Although stabilization of disease is the desired outcome, there have been reports of repigmentation as well.5

 

Table 1. Oral minipulse therapy

Steroid

Dose

n

Arrest of progression

Time required for effect

Side effects

Betamethasone + 0.01% fluticasone ointment9

5 mg/day for 2 days per week; children <11 years were given half dose

40

89%

1-3 months

Overall: 25%

Weight gain (5%), mild headache (5%), transitory weakness (5%), bad taste (7.5%)

Dexamethasone10

5 mg/day for 2 days per week; children <16 years were given half dose

32

44%

15 weeks

Not reported

Dexamethasone11

10 mg/day for 2 days per week

29

88%

18 weeks

Overall: 69%

Weight gain (31%), insomnia (24%), acne (17%), agitation (17%)

Methylprednisolone12

0.8 mg/kg (max 32 mg/day) for 2 days per week

343

90%

N/A

Weight gain (16.6%), gastric irritation (5.2%), tinea capitis and/or corporis (4.6%), acne (3.2%)

Dexamethasone8

5 mg/day for 2 days per week; children <11 years were given half dose

444

92%

10-16 weeks

Overall: 9.2%

Weight gain (7%), gastric upset (3.5%), acneiform eruptions (1.5%), weakness and lethargy (1%)

 

 

Figure 1

Figure 1. Vitiligo of the face and neck prior to treatment

 

Figure 2

Figure 2. Vitiligo of the face and neck after 10 months of oral dexamethasone 4 mg on 2 consecutive days per week showing stabilization of disease but minimal repigmentation

 

The wide array of side effects from systemic corticosteroids are well known to all physicians.13 Fortunately, most side effects from corticosteroids in OMP studies for vitiligo were minimal or reversed with discontinuation of the corticosteroid (Table 1).5

 

A perspective

It appears that systemic corticosteroids are effective in stopping the progression of vitiligo in most patients and may also lead to repigmentation with longer use, but they have a significant potential to cause side effects. What is the clinician to do? In medical school we are taught 'primum non nocere', a Latin phrase meaning 'first, do no harm'. In other words, in the best interest of the patient, it is sometimes better to give a less toxic treatment or to do nothing at all rather than doing something that would bring the patient harm. So in an otherwise healthy patient who only has lack of pigmentation as a chief complaint, is it right to treat with a systemic agent that may cause harm?

To examine this further, it is important to remember we are also called to adhere to the principle of beneficence, or the duty of healthcare providers to be of a benefit to the patient, as well as to take positive steps to prevent and to remove harm from the patient. What if the patient is undergoing severe depression or even thoughts of suicide due to vitiligo? This may sound farfetched, but multiple studies have shown a significant impact on quality of life in vitiligo sufferers.2,3 The stigma associated with vitiligo in certain cultures adds to the tremendous anxiety, stress, depression, and feelings of hopelessness many patients feel from the disfigurement associated with vitiligo. In such cases, the risk of withholding systemic corticosteroid treatment may outweigh the risk of treatment. Indeed, many of the studies of systemic steroids cited in this article were performed in India, where vitiligo is often associated with severe stigmatization, affecting the patient's ability to get married or find a job. Each patient interaction is unique and the physician must take the particular needs and desires of the individual patient into account, weighing the risks against the benefits for each decision, including the decision to use systemic corticosteroids for vitiligo. It is also critical to work with the patient to make such a decision together.

We have been using systemic corticosteroids in selected patients with actively spreading vitiligo at UT Southwestern Medical Center in Dallas for more than 1 year. The dose we have selected is dexamethasone 4 mg on 2 consecutive days per week, based on evidence from the literature and easy availability of this dose in our community pharmacies. Thus far, we have seen good results in stabilizing active disease with the use of this regimen for 4-12 months. However, our patients have also had side effects, including insomnia, weight gain, anxiety, depression, emotional lability, and menstrual irregularities, often leading to discontinuation of the drug. Discussion of the benefits and risks of treatment, as well as close follow up, is essential when considering this treatment.

 

Conclusions

There is now significant evidence to support that systemic corticosteroids help not only in arresting the progression of vitiligo, but may also help repigment affected skin. Periodic evaluation, adjustment of the dose, and monitoring of side effects are important in avoiding long-term complications. Since autoimmunity against melanocytes is the predominant hypothesis regarding the pathogenesis of non-segmental vitiligo, systemic corticosteroids should not be considered for segmental vitiligo or focal limited vitiligo, in which autoimmunity likely does not play a significant role. More studies using systemic corticosteroids for vitiligo need to be performed to better understand their efficacy and safety for this disorder.

 

References

  1. Alikhan A, Fasten LM, Daly M, et al. Vitiligo: A comprehensive overview. Part I: Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol 2011;65:473-91.
  2. Richmond JM, Frisoli ML, Harris JE. Innate immune mechanisms in vitiligo: danger from within. Curr Opin Immunol 2013;25:676-82.
  3. Bertolotti A, Boniface K, Vergier B, et al. Type I interferon signature in the initiation of the immune response in vitiligo. Pigment Cell Melanoma Res 2014;27:398-407.
  4. Rashighi M, Agarwal P, Richmond JM, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 2014;6:223ra23.
  5. Khaitan B, Kathuria S. Oral and systemic corticosteroids in management of vitiligo. In: Pigmentary disorders a comprehensive compendium. 1st ed. India: Jaypee Brothers Medical Publishers, 2014.p.205-12.
  6. Parsad D, De D. Corticosteroid minipulses. In: Vitiligo. 1st ed. New York: Springer, 2010.p.319-24.
  7. Felsten LM, Alikhan A, Petronic-Rosic V, et al. Vitiligo: A comprehensive overview. Part II: Treatment options and approach to treatment. J Am Acad Dermatol 2011;65:493-514.
  8. 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.
  9. Pasricha JS, Khaitan BK. Oral mini-pulse therapy with betamethasone in vitiligo patients having extensive or fast-spreading disease. Int J Dermatol 1993;32:753-7.
  10. Kanwar AJ, Dhar S, Dawn G. Oral minipulse therapy in vitiligo. Dermatology 1995;190:251-2.
  11. Radakovic-Fijan S, Fürnsinn-Fried AM, Hönigsmann H, et al. Oral dexamethasone pulse treatment for vitiligo. J Am Acad Dermatol 2001;44:814-7.
  12. Majid I, Masood Q, Hassan I, et al. Childhood vitiligo: response to methylprednisolone oral minipulse therapy and topical fluticasone combination. Indian J Dermatol 2009;54:124-7.
  13. Wolverton SE. Systemic corticosteroids. In: Comprehensive dermatologic drug therapy. 1st ed. Indianapolis: Elsevier, 2013.p.143-68.

 

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