the occurrence of premature ovarian failure ( pof)/amenorrhoea / azoospermia leading to sterility with the administration of pulse cyclophosphamide dose led to the search for a safer regimen to circumvent this side effect .
one recommendation was to withhold the monthly cyclophosphamide pulse while allowing the daily oral cyclophosphamide 50 mg to be continued for the phases i , ii and iii .
alternatively dexamethasone azathioprine ( dap ) therapy consisting of conventional dexamethasone pulses in phases i , ii and daily oral azathioprine 50 mg in phases i , ii and iii was recommended for patients in the reproductive age group and those who had not completed their families as azathioprine has no effect on gonads .
some patients showed a poor response to conventional dcp and had a prolonged phase i. in these patients an alternative immunosuppressant was given .
methotrexate 7.5 mg orally weekly was given for the first three phases along with dexamethasone pulses in first two phases ( dmp ) .
however prior to 2004 dcp regimen used was the basic one in which the duration of phase ii was 6 months and that of phase iii was 12 months .
this retrospective and prospective study was carried out on native kashmiri patients of pemphigus from october 2004 to october 2010 .
the diagnosis of pemphigus was made on clinical grounds with confirmation being done by submitting the skin or mucosal biopsy for histopathology and direct immunoflourescence .
due to non availability of facilities , indirect immunoflourescence of serum for antibody levels could not be done .
the approval of the ethics committee of government medical college srinagar was sought for the study .
a complete demographic profile of the patients was taken including age , sex , occupation , marital status ( especially if family has been completed ) as also family history of pemphigus , menstrual history ( in case of females ) and any co morbid illness .
the variant of pemphigus diagnosed in each case was noted and the duration of disease prior to diagnosis was recorded .
the extent of skin involvement , presence and extent of mucosal involvement , presence of nikolsky 's sign was noted in each case .
exclusion criteria for pulse therapy were pregnancy , lactation , and age less than 18 years , uncontrolled diabetes , hypertension or any severe systemic disease where large dose steroids are contra indicated .
all patients were admitted in the inpatient wing of the department . after taking informed consent , baseline investigations were done . these included a complete haemogram , renal and liver function tests , blood sugar estimation , skiagram chest , electrocardiogram , mantoux test and serum amylase .
depending upon the individual patient situation bacterial culture sensitivity from infected cutaneous lesions was taken .
all patients were put on daily condys baths , rexidin gargles and sterile vaseline gauze dressings .
antibiotics and antifungal were given in individual cases depending upon the presence of cutaneous or mucosal infection .
then the patients were put on three regimens depending upon the situation : conventional dcp , dap for patients in the reproductive age group and dmp in those in whom phase i on dcp was more than 12 months . for this study only those patients with pemphigus who had completed phases i , ii and iii on dcp , phases i and ii on dap and all those put on dmp were included to simplify the results .
all diabetics were administered 10u of insulin in the dextrose 5% along with the pulse .
depending upon individual response adp or daily steroids were given in phase i. the monitoring included monthly hemogram , urine analysis , renal and liver function tests and six monthly skiagram chest for dcp , weekly hemogram for first two weeks for methotrexate , then monthly and monthly renal and liver function monitoring , weekly hemogram and liver function for azathioprine for first month and then monthly .
all patients were routinely administered daily calcium vitamin d supplements and weekly bisfosfonates . the number of treatment dropouts and mortality if any was noted .
after completion of phase iii , the patients were put on monthly follow - up .
of the 50 consecutive patients , the total number of patients included in the present study were 47 .
one patient with a clinical ( hypopyon sign positive ) and histopathological diagnosis of ig a pemphigus was not put on pulse therapy .
two other female patients who were married and had one offspring each were put on dp plus daily cyclophosphamide therapy in view of the very severe disease in them .
incidentally one of these developed secondary amenorrhoea which on investigation was secondary to premature ovarian failure .
there were 11 males and 36 females patients included in the present study ( m : f ratio being approximately 1:3 ) .
the age ranged from 18 to 70 years with an average age at presentation of disease being 40 years in males [ table 1 ] .
a significant number of female patients were in early twenties to late teens indicating an earlier onset in females in our cohort of patients .
the age distribution of all patients the patients in the reproductive age group and those yet to complete their families were nine females and three males .
socio economic conditions ranged from affluent in four , middleclass in 25 and poor in 18 .
the variants of pemphigus seen were vulgaris ( 41 ) , vegetans ( 4 ) , foliaceous ( 2 ) .
no case of erythematosus , drug - induced or paraneoplastic pemphigus were seen in the present study . the extent of skin involvement by blistering and denudation at the time of presentation ranged from 0% to more than 90% body surface area .
the duration from eruption till the time of seeking medical attention was ranging from three days to seven months with mucosal lesions being referred and diagnosed later than skin lesions .
cerebriform tongue ( premalathas sign ) was seen in our female patients with p vegetans .
palmoplantar and nail involvement was seen in one young female patient with a severe disease who subsequently succumbed to the disease .
one elderly male patient with prolonged phase i on dcp therapy presented with dyshidrosiform lesions of pemphigus .
one patients male aged 35 years presented with acral lesions predominantly and he showed a prolonged phase i. eight patients had a positive bacterial swab needing antibiotics and five had mucosal candidiasis ( oral in 5 , vaginal in 3 , esophageal in 2 ) needing antifungal at the time of admission .
30 patients were put on dcp , 12 on dap therapy and 5 on dmp therapy [ table 2 ] .
patients with disease presenting in or localised to oral mucosae were more likely to have a longer duration of disease prior to diagnosis due to lack of referral or misdiagnosis .
p vegetans was present in two females , p foliaceous in two males while all others had p. vulgaris and the extent of involvement varied [ tables 3 and 4 ] .
the variants of pemphigus on dcp therapy the extent of involvement in patients on dcp therapy mucosal involvement was seen in all except two with foliaceous .
the duration of phase i was as short as one month in one patient [ table 5 ] .
the duration of phase 1 on dcp on an average six months would suffice , it was as prolonged as 20 months in one patient ( a young male with p.foliaceous who was not coming at fixed 28 day periods ) but as the diseases activity remained mild therapy was continued .
one of these was not regular in taking treatment and relapsed in phase iv ( male with severe mucosal involvement ) .
daily steroid therapy was given in 10 patients for 4 - 7 months . 1 patient developed haemorrhagic cystitis while on dcp while rbcs in urine were seen in 5 patients .
both were young patients with a severe disease who had also taken daily oral steroids in their phase ii .
further treatment in these patients was challenging as disease and treatment side effects had to be weighed .
12 patients with pemphigus who had completed phase i and ii of dap therapy were considered for the present discussion . these included 3 males and 9 females .
one female had extensive orogenital lesions . 1 patient had concomitant diabetes and none had hypertension .
9 patients had 10 - 30% involvement of bsa and 3 had 30 - 70% involvement .
duration of phase i was less than 6 months in 1,6 - 12 months in 4 and greater than 12 months in 7 patients [ table 6 ] .
duration of phase i on dap five patients needed adp ( for 3 - 6 months ) and these five needed daily steroids also ( 4 - 6 months ) . in phase ii , one patient developed disease activity in the third month itself .
this patient subsequently died in spite of adp and daily steroids due to a very active disease leading to septicaemia .
the number of relapses on dap in phase iii five patients relapsed at 5 - 9 months . in phase
four patients had pemphigus vulgaris and one ( female , 45yrs old ) had pemphigus vegetans .
none of the patients in this category had diabetes while two had hypertension and were on calcium channel blockers for the same .
one patient had been on dcp since the last thirteen months while all others had been on dcp since 9 - 12 months .
adp had been administered in two patients and daily steroids were given to all five while on dcp .
all five patients had mucosal involvement but severe orogenital and conjunctival lesions were seen in one female patient only ( variant vegetans ) .
severity of disease on the basis of bsa was 10 - 30% in 1 and 30 - 70% in four .
all patients had completed their families . only one patient of these completed the first three phases of dmp therapy [ table 8 ] . of the others disease activity
was poorly controlled and hence one patient defaulted and in three others dmp was discontinued as patient response was poor .
the course of disease on dmp poor healing of lesions and an increased requirement for concomitant antibiotic and anti fungal therapy was felt in all five patients .
the criteria for confirmation of diagnosis did not include iif as facilities for same are not available .
the levels of anti desmoglein 1 antibodies by elisa and anti desmoglein 3 antibodies by elisa have been found to corelate with the severity of cutaneous and mucosal involvement respectively .
this led to a grey area as regards the definition of severity of disease at the time of diagnosis by a reproducible and non biased criteria with no possibility of inter observer error .
this criteria however remains controversial as a few other studies have shown that correlation of severity with antibody levels is not foolproof . recently
a clinical set of criteria for disease severity on the basis of mucosal involvement and body surface area denuded was suggested .
the same was however not available to us in the study . individualised treatment on the basis of severity was not given .
hence whether the disease was mild or severe same megadoses of steroids and immunosuppressants were given .
a paradoxical worsening of disease seen after first few pulses in patients with mild disease at presentation was seen and had a bearing on patient compliance .
the younger age of patients and an increased female proportion of patients were similar as in studies from iran . in view of these two factors marital status and whether family was completed assumed greater importance in our cohort of patients .
dap would be recommended as a safer regimen as cases of pof was seen even with dp plus daily cyclophosphamide regimen .
this corroborates the apprehensions raised in previous study that even daily cyclophosphamide 50 mg during three phases gives a high cumulative dose in grams which can have a disastrous effect on gonads even if monthly megadose has been withheld .
shortest duration of phase i , quickest onset of response even in more extensive disease and lowest relapse rates were seen with conventional dcp regimen .
however noteworthy side effects were seen here these included premature ovarian failure ( seen prior to 2005 when dap was not used ) , haemorrhagic cystitis and avascular necrosis head of femur .
pertinently only one case of unmasking of tuberculosis is in contrast to the increased incidence of tuberculosis seen in a parallel study on systemic sclerosis patients who were on dexamethasone pulsed therapy .
even though dexamethasone methotrexate pulse was given in poor responders it was seen that phase i was still the longest in this group .
this may be indicative of the more severe disease per se but poor healing of lesions with methotrexate may also contribute .
one way of circumventing this problem would be to give a higher dose of methotrexate in poor responders and to administer daily steroids on the basis of body weight .
hence only if situation so demanded was antibiotic ( quinolones for 7 - 10 days ) or anti candidial treatment ( fluconazole daily for 7 - 21 days ) given .
duration of phase i and relapses were seen more with azathioprine regimen as compared to dcp regimen suggesting that perhaps the present dap regimen needs modification - individualise the azathioprine dose rather than sticking to 50 mg daily in all cases .
a major grey area is the duration of phase ii and iii being fixed at 9months .
the decision should ideally include the elicitation of dry , wet or microscopic nikolskys sign , dif findings and antibody levels by iif at the end of phase i , ii and iii . limitations of the study : indirect immunoflourescence of the patients serum for anti desmoglein antibodies was not done due to non availability of facilities for same .
the major limitation of this study was that a randomised controlled trial was not done as the disease is a serious one and immediate treatment is needed .
 background : pemphigus has been treated with dexamethasone cyclophosphamide pulse ( dcp ) therapy since 1981 . 
 various modifications have been suggested in the original regimen . 
 these include dexamethasone azathioprine pulse ( dap ) and dexamethasone methotrexate pulse ( dmp ) therapies.aims:to report our experience on the noncomparative study of various pulse regimens dcp , dap and dmp therapies in patients with pemphigus.materials and methods : the patients were put on three regimens depending upon the situation - conventional dcp , dap in the reproductive age group , dmp in patients who showed prolonged phase i more than 12 months while on dcp.results:30 patients were put on dcp therapy . 
 the duration of phase i was on an average six months . 
 relapse was seen in 3 patients in phase iv . 
 12 patients on dap therapy were considered . in phase 
 iii 5 patients relapsed in phase iv four patients relapsed . 
 five patients were put on the dmp . 
 disease activity was poorly controlled and in three dmp was discontinued.conclusion:dcp remains the most effective regimen with quickest onset of remission and continuance of remission 
 . in dap therapy fixation of dose of azathioprine at 50 mgs daily may be counterproductive . 
 dmp does not fulfil the promise of a viable treatment option in recalcitrant pemphigus and this lacunae needs to be plugged . 
Introduction
Materials and Methods
Results
Discussion