about 19% patients of alopecia areata will progress to extensive alopecia ( alopecia universalis , alopecia totalis , ophiasis and patients having more than 50% scalp involvement ) . systemic corticosteroids in daily therapy , mini - pulse therapy , and pulse therapy were used in the past with varied success from 36 to 75% in various studies.[24 ] winter et al . , reported the occurrence of side effects such as striae , acne , obesity , hypertension while using alternate day prednisolone . the author concluded that alternate day therapy does not appreciably alter the course of aa . however sharma et al . , have used oral mini - pulse dexamethasone twice weekly in extensive alopecia and found this treatment to be safe and effective for cosmetically acceptable regrowth in 63% cases . with this existing understanding of alopecia areata , we embarked on a study using a combination of oral bethametasone mini - pulse , topical minoxidil and short contact anthralin in treatment - resistant , extensive alopecia areata . the rationale behind choosing this regime was to use oral bethametasone pulse to halt the progression of disease activity , at the same time topical minoxidil and anthralin were added with the intention of initially supplementing the effect of oral steroids and later minimizing relapses on discontinuation of oral steroids . fifteen patients , 10 females and 5 males , aged 7 years to 45 years with extensive alopecia attending the hair clinic in our hospital from 2008 to 2010 were recruited for this study . history of diabetes mellitus , peptic ulcer , psychosis , severe hypertension , cardiac failure , acute and chronic infection , nephropathy , or endocrine disorder was ruled out in our patients . the duration of disease at the time of presentation ranged from 3 to 10 years . all patients had received various modalities of treatment in the past in the form of steroid pulse therapy , dinitrochlorobenzene , tacrolimus or herbal products with poor / partial response or relapse after discontinuing therapy . a wash out period of six months was allowed before starting these patients on the new study regime . of the total 15 patients , 7 patients were receiving some alternate form of therapy at our center itself for a year with poor / partial response or relapse on tapering therapy or developed significant side effects of therapy necessitating withdrawal of therapy . all of these 7 patients were then treated with the study regimen of combination therapy . of these 7 patients , note worthy was a nine - year - old girl with alopecia universalis who was treated with topical dinitrochlorobenzene . however , she had complications of the treatment in the form of repeated scalp abscesses , erratic response in the form of either profound dermatitis post application or no reaction at all . another 27-year - old man was treated with 100 mg once a month dexamethasone intravenous pulse therapy for a year with good response but complete relapse on discontinuation of treatment . two of the fifteen patients had elevated levels of thyroid auto - antibodies with a normal level of t 3 , t 4 and thyroid stimulating hormone . the baseline investigations like complete hemogram , blood sugars , liver and renal function tests , chest x - ray and ophthalmological examination were performed . all patients were started on oral betamethasone mini - pulse ( 0.1 mg / kg / body weight on two consecutive days per week ) along with 2 - 5% topical minoxidil and 1.15% anthralin cream . oral minipulse was continued till the patient achieved a cosmetic response and then it was maintained for 6 to 9 months depending on the response attained . the oral minipulse was gradually tapered by 20% every three weekly after cosmetic response and then stopped . one milliliter of topical minoxidil was applied to the affected scalp and then was reapplied 12 h later . anthralin cream was applied daily in the night 2 h after the last application of minoxidil for 10 min ( contact time ) initially , and thereafter the contact time was escalated every three weekly till mild erythema was seen . maximum contact time achieved was 1 h. the patients were instructed to clean the treatment area with mineral oil and water after the specified contact time . maintenance therapy included tapering the number of applications of topical minoxidil to once a day , as well as anthralin to once or twice weekly . response was assessed at monthly intervals using a severity of alopecia tool ( salt ) score . response was classified as cosmetically acceptable where regrowth of hair obviates the need of a wig / cap , partial response where dense patches of terminal hair are seen and does not obviate the need of a wig / cap , non - responders or failure defined as no growth or vellus hair even after six months of therapy . fifteen patients , 10 females and 5 males , aged 7 years to 45 years with extensive alopecia attending the hair clinic in our hospital from 2008 to 2010 were recruited for this study . history of diabetes mellitus , peptic ulcer , psychosis , severe hypertension , cardiac failure , acute and chronic infection , nephropathy , or endocrine disorder was ruled out in our patients . the duration of disease at the time of presentation ranged from 3 to 10 years . all patients had received various modalities of treatment in the past in the form of steroid pulse therapy , dinitrochlorobenzene , tacrolimus or herbal products with poor / partial response or relapse after discontinuing therapy . a wash out period of six months was allowed before starting these patients on the new study regime . of the total 15 patients , 7 patients were receiving some alternate form of therapy at our center itself for a year with poor / partial response or relapse on tapering therapy or developed significant side effects of therapy necessitating withdrawal of therapy . all of these 7 patients were then treated with the study regimen of combination therapy . of these 7 patients , note worthy was a nine - year - old girl with alopecia universalis who was treated with topical dinitrochlorobenzene . however , she had complications of the treatment in the form of repeated scalp abscesses , erratic response in the form of either profound dermatitis post application or no reaction at all . another 27-year - old man was treated with 100 mg once a month dexamethasone intravenous pulse therapy for a year with good response but complete relapse on discontinuation of treatment . two of the fifteen patients had elevated levels of thyroid auto - antibodies with a normal level of t 3 , t 4 and thyroid stimulating hormone . the baseline investigations like complete hemogram , blood sugars , liver and renal function tests , chest x - ray and ophthalmological examination were performed . all patients were started on oral betamethasone mini - pulse ( 0.1 mg / kg / body weight on two consecutive days per week ) along with 2 - 5% topical minoxidil and 1.15% anthralin cream . oral minipulse was continued till the patient achieved a cosmetic response and then it was maintained for 6 to 9 months depending on the response attained . the oral minipulse was gradually tapered by 20% every three weekly after cosmetic response and then stopped . one milliliter of topical minoxidil was applied to the affected scalp and then was reapplied 12 h later . anthralin cream was applied daily in the night 2 h after the last application of minoxidil for 10 min ( contact time ) initially , and thereafter the contact time was escalated every three weekly till mild erythema was seen . maximum contact time achieved was 1 h. the patients were instructed to clean the treatment area with mineral oil and water after the specified contact time . maintenance therapy included tapering the number of applications of topical minoxidil to once a day , as well as anthralin to once or twice weekly . response was assessed at monthly intervals using a severity of alopecia tool ( salt ) score . response was classified as cosmetically acceptable where regrowth of hair obviates the need of a wig / cap , partial response where dense patches of terminal hair are seen and does not obviate the need of a wig / cap , non - responders or failure defined as no growth or vellus hair even after six months of therapy . of the 15 patients ( age range 7 - 45 years ) recruited in the study , 10 patients were in adolescence age group . of these 15 patients , 7 had alopecia universalis ( au ) , one alopecia totalis ( at ) , 4 ophiasis , and 3 had more than 50% scalp involvement [ table 1 ] . pattern of alopecia in cases out of eight patients with au / at , two attained cosmetic response as early as three months , two at six months and one had partial response . cosmetic response was attained in all four patients with ophiasis and all three patients with more than 50% scalp involvement at six months [ tables 2 and 3 ] [ figures 1a  b and 2a  b ] . the total duration of oral minipulse administered to all responders was 9 - 12 months only . among a total of twelve responders ( 80% ) , two with all the three patients who did not respond had au and disease duration of 8 to 10 years . type of alopecia and response type of alopecia and maintenance ( a ) a seven - year - old girl with six - year history of aa ( b ) cosmetic response seen after six months of treatment ( a ) a 15-year - old girl with two - year history of more than 50% involvement of aa ( b ) cosmetic response seen after six months of treatment systemic agents used are corticosteroids , azathioprine , sulfasalazine , cyclosporine , methotrexate and biologicals [ table 4 ] . systemic corticosteroids have been used in majority of the reported studies with a varying success of 30 to 80% . however , the relapse rates and side effects were 30 - 40% with steroid monotherapy.[15 ] combination treatment for extensive alopecia areata fiedler et al . , used topical minoxidil and anthralin in 51 patients having extensive treatment - resistant alopecia and cosmetic response was seen in 11% with maintenance in 80% . it was hypothesized in this study that combination of topical anthralin and minoxidil was synergistic and more effective than monotherapy alone . the mechanism by which it stimulates hair regrowth is unknown , although emerging evidence suggests that direct follicular effects are likely to be present . the nature of its irritant mechanism is unknown and is obscured further as other irritants like croton oil do not elicit hair regrowth . sharma et al . , administered oral prednisolone as pulses in doses of 300 mg at 4-week intervals , for a minimum of 4 doses or until cosmetically acceptable hair growth in 24 patients and eight patients separately received 1000 mg prednisolone pulses . out of 32 patients evaluated , only one patient out of 5 patients of au / at attained a cosmetic response with oral pulse at six months and 2 patients ( au and at each ) with 1000 mg pulse at nine months . in another study , sharma et al . , reported a cosmetic response in 16 ( 63.3% ) out of 30 ( 25 extensive alopecia areata , 5 alopecia areata ) patients at five months treated with dexamethasone oral minipulse . khaitan et al . , illustrated a cosmetic response in 7 ( 43.7% ) out of 10 patients with au / at at the end of six months of treatment with betamethasone oral minipulse . cosmetic response was seen in 2 of 8 au / at as early as three months and another two patients at six months . all 12 responders have maintained a response at the end of one year after stoppage of oral steroids . side effects were seen in only two patients and were mild and reversible , in the form of local scalp irritation . conventionally a combination of anthralin and steroid is not recommended based on the logic that steroids would decrease the irritation potential of anthralin , and thereby its efficacy . however , in our study , all the patients in spite of being on oral steroid had developed local erythema and scalp irritation on anthralin application . steroids have been useful in the treatment of alopecia areata . however , daily doses of steroids have significant treatment - related side effects . on the other hand , alternate day steroids or therefore , the combination of topical minoxidil with anthralin along with oral mini - pulses of systemic steroid used in our study yields effective response , while being safe at the same time . maintenance of cosmetic response can easily be achieved with only topical minoxidil and anthralin while gradually tapering and finally discontinuing oral steroids . we propose that this combination therapy would provide a new approach in treatment - resistant , extensive , long - standing alopecia areata .
background : extensive alopecia areata includes alopecia universalis , alopecia totalis , ophiasis and patients having more than 50% scalp involvement . 
 alopecia universalis ( au ) and totalis ( at ) are considered to be resistant to single modalities of treatment . 
 our study highlights the efficacy and safety of combination therapy in extensive alopecia areata.aim:to evaluate the efficacy and safety of a combination treatment with oral bethametasone mini - pulse , topical minoxidil and short contact anthralin in long - standing , treatment - resistant , extensive alopecia areata.materials and methods : fifteen patients aged 7 to 45 years with extensive , treatment - resistant alopecia areata ( au : 7 ; at : 1 ; ophiasis : 4 ; patients with more than 50% scalp involvement : 3 ) were treated with betamethasone oral mini - pulse ( 0.1 mg per kg body weight per dose on two consecutive days per week ) along with short contact anthralin ( 1.15% ) and 2 - 5% minoxidil lotion daily , till response . 
 the response was assessed by the severity of alopecia tool ( salt ) score . 
 cosmetic response was defined as regrowth obviating the need of a wig . 
 failure of treatment was defined as no growth or vellus hair on the scalp.results:out of eight patients with au / at , two attained cosmetic response as early as three months , two at six months and one had partial response . 
 cosmetic response was attained in all four patients with ophiasis and all three patients with more than 50% scalp involvement at six months . 
 all responders maintained their response without systemic steroids beyond 12 months . among a total of twelve responders ( 80% ) , two with 
 au showed a mild relapse and were effectively treated with intralesional steroids . 
 side effects to therapy were mild and reversible.conclusion:a combination therapy of oral steroid minipulse with topical anthralin and minoxidil acts synergistically , being effective as well as safe in treatment - resistant , extensive , long - standing alopecia areata .