|Year : 2016 | Volume
| Issue : 3 | Page : 173-178
Combination treatment of extensive and recalcitrant alopecia areata with oral and topical steroids with topical minoxidil: An open-label study of efficacy and safety in pediatric patients
Vivek Kumar Dey
Department of Dermatology, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India
|Date of Web Publication||5-Jul-2016|
Vivek Kumar Dey
LG-112, Minal Shopping Mall, J. K. Road, Bhopal- 462 037, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Background: Alopecia areata (AA) is an autoimmune disorder characterized by nonscarring alopecia affecting scalp and body hair. Treatment of AA in pediatric age group is challenging because of unpredictable course, uncertain natural history, potential side effects of medicines, and psychological morbidity. Moreover, no clear guidelines for treatment of pediatric AA are available.
Objective: The objective of this study is to assess efficacy and safety of a combination treatment of extensive and recalcitrant AA with oral and topical steroids with topical minoxidil.
Materials and Methods: Sixteen children (nine girls and seven boys) aged 6–15 years with severe and recalcitrant AA were included in this study. All were prescribed the regimen of combination of oral and topical steroid with topical minoxidil 2% solution. Oral steroid was tapered over 12 weeks, and topical steroid was withdrawn at the end of 24 weeks. Patients were maintained on topical minoxidil for next 9–12 months and closely followed up.
Results: The average age of participants was 10.81 years, and the duration of disease was ranged from 3 months to 30 months. Response to our regimen was good in cases of extensive AA and ophiasis, compared to alopecia totalis. The participant having alopecia universalis did not respond at all to the regimen. Participants tolerated the regimen well with mild and easy to manage side effects and only few relapses.
Conclusion: Finding an effective and safe treatment regimen for AA, especially in children is difficult. Our regimen allows for more rapid lowering of oral doses with maintaining the cosmetic response and minimizing the side effects. Therefore, a trial course of this regiment would seem to be a reasonable approach for nearly hopeless but highly motivated pediatric patients of extensive and recalcitrant AA.
Keywords: Alopecia areata, alopecia totalis, alopecia universalis, hair loss, hair treatment, minoxidil, nonscarring alopecia, ophiasis
|How to cite this article:|
Dey VK. Combination treatment of extensive and recalcitrant alopecia areata with oral and topical steroids with topical minoxidil: An open-label study of efficacy and safety in pediatric patients. Indian J Paediatr Dermatol 2016;17:173-8
|How to cite this URL:|
Dey VK. Combination treatment of extensive and recalcitrant alopecia areata with oral and topical steroids with topical minoxidil: An open-label study of efficacy and safety in pediatric patients. Indian J Paediatr Dermatol [serial online] 2016 [cited 2022 May 26];17:173-8. Available from: https://www.ijpd.in/text.asp?2016/17/3/173/179484
| Introduction|| |
Alopecia areata (AA) is an idiopathic nonscarring disorder with multifactorial autoimmune pathogenesis affecting hair resulting in patches of noncicatricial baldness on scalp, face, and other hair-bearing skin of the body., This lymphocyte mediated inflammatory process not only targets hair follicles, but also affects the quality of life greatly. The disease can present with one or more well-circumscribed focal bald patch enlarging centrifugally. Alopecia totalis (AT) and alopecia universalis (AU) are other extensive but less common form which affect entire scalp hair and all body hair, respectively., Sometimes AA may present in a unique pattern of hair loss localized to the sides and lower back of the scalp known as ophiasis (OP).
Pediatric AA is frequently encountered in our daily practice. Up to one-third of newly diagnosed cases are aged 20 years or less., AA may be associated with other autoimmune diseases, such as thyroid disease, celiac disease, vitiligo, irritable bowel syndrome, SLE, rheumatoid arthritis, diabetes mellitus, and atopy., Nail changes, including twenty nail dystrophy syndrome and a positive family history, have also been associated with pediatric AA.
Factors such as unpredictable course, uncertain natural history, frequent relapses, risk of progression to AT or AU, significant psychosocial morbidity in children, and possible adverse effects of medicines make the management of pediatric AA more challenging., Recalcitrant and extensive AA requires even more comprehensive approach.
In this study, we used a combination of daily oral prednisolone in tapering dose, topical mometasone furoate, and topical minoxidil 2% lotion in extensive and recalcitrant AA. This combination was chosen because systemic prednisolone checks the progression of disease activity, while topical minoxidil and mometasone furoate supplement systemic steroids initially and facilitate early withdrawal of systemic steroids by maintaining hair growth and reducing relapse.
The objective of this study is to assess efficacy and safety of a combination treatment of extensive and recalcitrant AA with oral and topical steroid along with topical minoxidil.
| Materials and Methods|| |
Sixteen children, nine females, and seven males, aged 6–15 years with extensive and recalcitrant AA attending the hair clinic from January 2009 to December 2011 were recruited for this study. We labeled AA as extensive if patient had more than 50% scalp involvement or there is a presence of OP, AT, or AU at presentation  and recalcitrant if patient had received various modalities of treatment in the form of oral steroid, pulse therapy, levamisole, tacrolimus, minoxidil, intralesional corticosteroid therapy, or herbal products with poor/partial response or relapse on discontinuing therapy. A wash-out period of 3 months was allowed before starting these patients on the new study regime. Any patient with a history of uncontrolled bacterial, viral, fungal, mycobacterial, or opportunistic infection (e.g., systemic fungal infections or parasites) was excluded from the study. Patients with significant pulmonary or cardiovascular disease, liver disease, or abnormal hepatic function were also not permitted to enter the study.
The nature of the study and possible adverse effects of the therapy was explained and written consent including the consent of medical photography was taken from parents of all patients. All patients were then treated with the study regimen of combination therapy.
All patients were started with once daily oral prednisolone (1 mg/kg) along with topical mometasone and 2% topical minoxidil solution. Oral prednisolone was reduced to 30% of the initial dose at completion of 2 weeks, then tapered down slowly to stop completely in 12 weeks. One milliliter of topical minoxidil was applied to the affected scalp 12 hourly. Topical mometasone solution was applied twice daily 2 h after the last application of minoxidil. The dose of topical mometasone solution was reduced according to the response of the patient and completely withdrawn at the end of 24 weeks. Topical minoxidil was continued for further 12 months as maintenance therapy which included tapering the number of applications of topical minoxidil from twice daily to once a day then alternate days. First 12 weeks were considered as phase I when all the three drugs were continued. phase II was the next 12 weeks when patients were on topicals only without oral steroid and last 12 months of maintenance with topical minoxidil was labeled as Phase III.
All patients underwent a comprehensive workup at baseline, 1st month and at the end of the 3rd month which included weight and growth assessment, complete physical examination, and investigations such as complete hemogram, blood sugar levels, liver and renal function tests, chest X-ray, and ophthalmological examination. The extent of AA was noted. After completion of the 3rd month, only hair growth was assessed at monthly interval. The response was classified as cosmetically acceptable, partial response, and no response. “Cosmetically acceptable” has been defined as amount of terminal hair growth sufficient to cover the scalp and conceal the areas of residual loss or patient no longer needing a wig or cap to conceal hair loss, but when the amount of dense patches of terminal hair are not sufficient to conceal the area of residual loss or does not obviate the need of a wig or cap, is taken as partial response. Nonresponder or failure is defined as no growth or vellus hair only, even after 24 weeks of therapy.
| Results|| |
Total 16 patients from age 6 to 15 years were recruited in the study, including nine girls and seven boys (M:F ratio was 1:1.28) average age was 10.81 years (standard deviation = 2.73). The average duration of disease at the time of presentation was 12 months for boys and 9.66 months for girls, ranged from 3 months to 30 months. Among all recruited patients, 1 had AU, 3 had AT, 1 had OP, and 11 had extensive AA (more than 50% scalp involvement). Details of all patients are given in [Table 1]. Out of 11 patients with extensive AA, 3 attained good cosmetic response at 12–14 weeks only [Figure 1]. Cosmetically acceptable response was attained in 56% of the patients [Figure 2] and [Figure 3], whereas 31% patients showed a partial response. Poor or no response was seen in the patient with AU and in one of the three patients of AT. All responders were maintained on minoxidil solution 2% and followed up for next 12 months. No responder developed relapse during treatment with oral steroids (Phase I). Relapse was seen in one patient with AT and three patients of extensive AA in Phase II. All were mild to moderate and treated with addition of topical steroids. Topical steroids were withdrawn gradually without any further relapse. Same three responders with severe AA relapsed in Phase III also. Topical minoxidil solution 2% was also withdrawn gradually over the 12 month follow-up period without any new relapse except those three patients. Details of response and relapse are shown in [Table 2].
|Figure 1: A 9-year-old girl with extensive alopecia areata attained cosmetic response at 12 weeks only|
Click here to view
|Figure 2: A 13-year-old girl with 5 months history of more than 50% involvement of alopecia areata. Cosmetic response was attained over 24 weeks of treatment|
Click here to view
|Figure 3: Good cosmetic response in extensive alopecia areata at week 24|
Click here to view
Most commonly seen side effects were weight gain and acneiform eruptions in 50% of the patients and folliculitis on the scalp in 25%. Side effects were mild which required no changes in the doses and were controlled with topical therapy and planned tapering of the doses of oral steroids. Two patients complained of scalp pruritus in first 2 weeks of therapy, probably caused by minoxidil solution but subsided spontaneously.
Two of the sixteen patients had an abnormal level of thyroid stimulating hormone and one of them also had elevated levels of thyroid autoantibodies. Personal history suggestive of atopy was found in one patient. The family history of AA was found in three patients.
| Discussion|| |
AA is a common human disease with a lifetime risk of 1.7% in general population  and the lifetime incidence of approximately 2% worldwide. It may be observed at any age and has no clear sex predominance. A study done in North India showed a preponderance in men (M:F = 2:1) but in another clinical study of childhood AA done in Chandigarh, India, the F:M ratio was found to be 1.4:1. The same finding was seen in a studies done in Kuwait and Singapore, where girls outnumbered boys by a 2.5:1 and 1.3:1 ratio, respectively., We also found a slight female preponderance in extensive and recalcitrant AA (F:M = 1.28:1).
There are several topical and systemic modalities for treatment of AA described in literature but there is a paucity of well-designed randomized trials for treatment guideline, especially for childhood AA. Many different regimens of systemic corticosteroids, including single-dose, short-term with high dose, alternate day dosing, or tapering dosing by oral or intravenous (IV) route have been tried with different success rates, but long-term safety data are not well-established.,,,,, The only placebo-controlled randomized study on oral prednisolone was done by Kar et al. where pulse therapy of 200 mg oral prednisolone over 3 months showed regrowth in 60% of the patients compared with no regrowth in the placebo arm. But relapse was seen in 25% of the responders. In two other studies, 300 mg oral prednisolone once a month showed cosmetically acceptable response in 82% patients over 3–6 months, and in 58% of patients with extensive AA and AT/AU in 4 months period.
Regimen using alternate day prednisolone was not found to be substantially effective and beneficial in the natural course of AA in long-term. Moreover, this regimen reported the occurrence of side effects such as striae, acne, obesity, mild hypertension lenticular opacities, and impaired adrenocorticotropic hormone reserve.
Large single-dose of prednisolone was also tried and found to be unsatisfactory in a study done by Burton and Shuster where they used prednisolone as a single 2 g dose IV or 500 mg orally for 5 days in patients with AT.
Pulse IV methylprednisolone has been found to be beneficial in several studies. Friedli et al. showed 50–100% regrowth in 60% patients of multifocal, patchy AA, but this regimen was found ineffective in patients with AT, AU, or OP., In children with extensive patchy AA or AT/AU, high dose pulse methylprednisolone was shown to have a poor long-term outcome in one study whereas few other studies found pulsed oral corticosteroids effective.,, In a comparative study between dexamethasone 0.5 mg/day for 6 months, intramuscular triamcinolone acetonide 40 mg once a month for 6 months followed by 40 mg once every 1.5 months for 1 year and pulse therapy with oral prednisolone at 80 mg for three consecutive days once every 3 months, best response was found with intramuscular triamcinolone acetonide in patients with multifocal AA and relapse rates were found to be the lowest in the patient who received pulse therapy with oral prednisolone.
In few other studies, treatment with oral prednisolone in tapering dose was combined with or followed by topical minoxidil daily. The tapering dose of prednisolone offered potential for regrowth with predictable and transient side effects and topical minoxidil helped to limit poststeroid hair loss., The mechanism by which topical minoxidil stimulates hair regrowth is unknown, but a direct follicular effect is thought to be present. When used as monotherapy, topical minoxidil is not very effective for those with 100% scalp hair loss, but it is an effective, easy, and safe treatment for those with AA affecting 25–99% of the scalp. Therefore, it was hypothesized that combining minoxidil with oral steroid has synergistic action and is more effective than monotherapy of either.
In 1978, Unger and Schemmer suggested low-dose oral prednisone combined with intralesional and topical corticosteroids in patients with AT and AU and found virtually all scalp hair regrowth in about 46% patients and all patients were able to discontinue oral corticosteroids without recurrence of AT or AU. In view of above studies, we proposed a combined therapy consisting of oral and topical steroids and topical minoxidil, with gradual tapering down of oral steroid first followed by topical steroid and lastly minoxidil solution as it is the least harmful drug.
In our study, the cosmetic response was seen in 56% and partial response in 31% of the total patients. All patients with extensive AA (excluding AT and AU) responded to our regimen, 66.6% showed cosmetic response whereas only partial response was achieved in 33.3% of them. About 25% responders relapsed in Phase I and II and could not show satisfactory response after stopping the oral medication. Patient with OP showed good response without any relapse. Among the patients with AT, 66% patients responded with the regimen but 33% relapsed in Phase II. Relapse was managed effectively without any further relapse in the maintenance phase. Patient with AU failed to respond our regimen. In general, success rates are found to be much better in multifocal extensive AA with systemic corticosteroids compared with AT and AU.,, We also found the same in our study. The drawbacks of systemic corticosteroids are their side effect profile and the fact that they do not alter the long-term prognosis. Side effects of long-term systemic steroids include growth retardation, hyperglycemia, osteoporosis, cataracts, immunosuppression, obesity, dysmenorrhea, acne, weight gain, mood changes/emotional lability, and Cushing's syndrome,,, but tapering course of short-term systemic corticosteroid does not produce any major adverse effects even in children. In our study, side effects were predictable, mild and reversible, in the form of local scalp irritation, weight gain, acneiform eruptions, and folliculitis.
A small number of patients was the major limitation in our study, as the results of this study may not represent the actual effect of our regimen in all pediatric patients of AA in general population. Inability to perform long-term follow-up was another major limitation as long-term prognosis could not be assessed. Because of the high rate of spontaneous hair regrowth, which is almost 50% with limited disease, studies with a large number of patients are required either after exclusion of spontaneous remission by treating each patient on one-half of the scalp only or by conducting double-blind, placebo-controlled studies.
| Conclusion|| |
AA can persist for many years or even for life. Therefore, therapeutic approaches showing severe side effects are inappropriate for treatment in the long run. The actual challenge is to choose a treatment modality suitable for long-term treatment with least side effects. Although there are no well-designed large trials examining the effects of daily systemic corticosteroids in childhood AA, it has been shown to be able to induce regrowth in adult AA. But serious adverse effects of long-term corticosteroid therapy limit its use in children. Hence, it should be reserved for patients with rapid onset or rapidly progressive, extensive and active AA, and oral prednisolone should be slowly tapered over 2 months, not exceeding 3 months. Still the maintenance of hair growth is difficult and unpredictable. On the other hand, alternate day steroids or pulsed dosing may be inadequate. However, using topical corticosteroids and minoxidil along with oral prednisolone allows for more rapid lowering of oral doses with maintaining the cosmetic response and minimizing the side effects. Therefore, a trial course of oral and topical corticosteroid treatment with topical minoxidil would seem to be a reasonable approach for extensive, treatment-resistant, and nearly hopeless but highly motivated pediatric patients of AA.
Declaration of Patient Consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gordon KA, Tosti A. Alopecia: Evaluation and treatment. Clin Cosmet Investig Dermatol 2011;4:101-6.
Wang E, Lee JS, Tang M. Current treatment strategies in pediatric alopecia areata. Indian J Dermatol 2012;57:459-65.
MacDonald Hull SP, Wood ML, Hutchinson PE, Sladden M, Messenger AG; British Association of Dermatologists. Guidelines for the management of alopecia areata. Br J Dermatol 2003;149:692-9.
Tan E, Tay YK, Giam YC. A clinical study of childhood alopecia areata in Singapore. Pediatr Dermatol 2002;19:298-301.
Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India. Int J Dermatol 1996;35:22-7.
Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: A systematic review. Clin Cosmet Investig Dermatol 2015;8:397-403.
Tosti A, Bellavista S, Iorizzo M. Alopecia areata: A long term follow-up study of 191 patients. J Am Acad Dermatol 2006;55:438-41.
Deshpande D, Dhurat R, Saraogi P, Mishra S, Nayak C. Extensive alopecia areata: Not necessarily recalcitrant to therapy! Int J Trichology 2011;3:80-3.
Olsen EA. Investigative guidelines for alopecia areata. Dermatol Ther 2011;24:311-9.
Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ 3rd
. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc 1995;70:628-33.
Sharma VK, Kumar B, Dawn G. A clinical study of childhood alopecia areata in Chandigarh, India. Pediatr Dermatol 1996;13:372-7.
Nanda A, Al-Fouzan AS, Al-Hasawi F. Alopecia areata in children: A clinical profile. Pediatr Dermatol 2002;19:482-5.
Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore – A study of 219 Asians. Int J Dermatol 2002;41:748-53.
Kar BR, Handa S, Dogra S, Kumar B. Placebo-controlled oral pulse prednisolone therapy in alopecia areata. J Am Acad Dermatol 2005;52:287-90.
Ait Ourhroui M, Hassam B, Khoudri I. Treatment of alopecia areata with prednisone in a once-monthly oral pulse. Ann Dermatol Venereol 2010;137:514-8.
Sharma VK. Pulsed administration of corticosteroids in the treatment of alopecia areata. Int J Dermatol 1996;35:133-6.
Winter RJ, Kern F, Blizzard RM. Prednisone therapy for alopecia areata. A follow-up report. Arch Dermatol 1976;112:1549-52.
Burton JL, Shuster S. Large doses of glucocorticoid in the treatment of alopecia areata. Acta Derm Venereol 1975;55:493-6.
Friedli A, Labarthe MP, Engelhardt E, Feldmann R, Salomon D, Saurat JH. Pulse methylprednisolone therapy for severe alopecia areata: An open prospective study of 45 patients. J Am Acad Dermatol 1998;39 (4 Pt 1):597-602.
Im M, Lee SS, Lee Y, Kim CD, Seo YJ, Lee JH, et al.
Prognostic factors in methylprednisolone pulse therapy for alopecia areata. J Dermatol 2011;38:767-72.
Hubiche T, Léauté-Labrèze C, Taïeb A, Boralevi F. Poor long term outcome of severe alopecia areata in children treated with high dose pulse corticosteroid therapy. Br J Dermatol 2008;158:1136-7.
Sharma VK, Muralidhar S. Treatment of widespread alopecia areata in young patients with monthly oral corticosteroid pulse. Pediatr Dermatol 1998;15:313-7.
Sharma VK, Gupta S. Twice weekly 5 mg dexamethasone oral pulse in the treatment of extensive alopecia areata. J Dermatol 1999;26:562-5.
Kurosawa M, Nakagawa S, Mizuashi M, Sasaki Y, Kawamura M, Saito M, et al.
A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata. Dermatology 2006;212:361-5.
Price VH. Treatment of hair loss. N Engl J Med 1999;341:964-73.
Olsen EA, Carson SC, Turney EA. Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata. Arch Dermatol 1992;128:1467-73.
Price VH. Topical minoxidil in extensive alopecia areata, including 3-year follow-up. Dermatologica 1987;175 Suppl 2:36-41.
Unger WP, Schemmer RJ. Corticosteroids in the treatment of alopecia totalis. Systemic effects. Arch Dermatol 1978;114:1486-90.
Lester RS, Knowles SR, Shear NH. The risks of systemic corticosteroid use. Dermatol Clin 1998;16:277-88.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]