Adverse Effects of Parenteral Dbxamethasone in the Treatment of Pemphigus Vulgaris

Background: Pemphigus vulgaris is associated with high morbidity as well as significant mortality rate. Today the risk of death in pemphigus from the side effect of oral prednisolone is greater than risk of death from the disease itself. Objective: To observe the adverse effects of parenteral dexamethasone compared with oral prednisolone in the teatunent of pemphigus vulgaris. Methods: An interventional study was carried out in the departrrent of Derrnatology and Venereology, Bangabandu Sheilh Mujib Medical University, Dhaka, Bangladesh. Total number of patients was thirty and among them fifteen patients were treated with parenteral dexamethasone (Group-A) and other fifteen were treated with oral prednisolone (Group-B). Results: The study showed statistically significant differences of skin lesion as well as mucosal lesion of pemphigus after 6 weeks of therapy between of two groups (P<0.05). The most common adverse effects were increased body weight(A0%), increased appetite(40Yo), and puffr face(4}%) in dexamethasone group. In prednisolone group, these side effects were 60%o of the subjects. Other side effects in dexamethasone group were hyperglycemia (33.33%), hypertension (26.66%), and sleep disturbance (13.33%). In prednisolone group, other side effects were hyperglycemia(33.33%), hypertension(40%), gastritis (33.33%), nausea, vomiting (13.33%) in each, reactivation of tuberculosis , herpes zoster infection, sleep disturbance, and mood change were 6.66Yo in each group. Conclusion: In the light of the findings of the study, we conclude that each of the treafinent of dexamethasone group and prednisolone group is individually effective and safe in the treatment of pemphigus wlgaris but adverse effects are less in parenteral dexamethasone group than oral prednisolone group. So parenteral dexamethasone can be used as an alternative drug in the heatrnent of pemphigus vulgaris.


Introduction:
Pemphigus vulgaris (PV) is the most cofirmon variant and it constitutes 80% of patients with pemphigus.tAbout 0.8% of all dermatologic patients suffer from pemphigus.2The prevalence of pemphigus vulgaris is about equal in men and women.The mean age of onset is fourth to sixth decades.'There is strong genetic background to pemphi- gus vulgaris and there is also HLA association in pemphi- gus vulgaris.2 In about 5A-70% of the cases the disease begins with oral lesion, which may precede the cutaneous lesions by several months.Cutaneous lesions canbe local- ized or generalized and usually present primarily as flaccid Address of correspondence: Dr. Mohammad Jamal Uddin, Assistant Professor, Department of Dermatology and Venereology, BSMMU, Dhaka, Bangladesh.IBSMMU J 2013; 6 (I): 3B-43J vesicles or bullae varying in size from less than 1 cm to several cm.The scalp, sternum, genitalia, axillae and groin are frequent sites of involvement.The blisters rupture easily and produce painful raw denuded areas.aThe Nikolsky's sign is the absence of cohesion in the epidermis, so the upper layers of the epidermis may easily",be removed by a twisting pressure with the fingertip, leaving a moist surface.The bulla spreading phenom- ena can be tested by pressure on an tntact bulla, gently forcing the fluid to wander under the skirl away from site.
'Pemphigus vulgaris is associated with high morbidity as well as significant mortality rate, before the advent of systemic corticosteroid therapy Ln 1950s.The mortality rate was reported varies from 70% to 100% before systemic corticosteroid use.The use of corticosteroid dramatically reduced the death rute to a mean of 3To6.sThecourse of pemphigus vulgaris is almost chronic.
Dexamethasone is a long acting, synthetic steroid and prednisolone is an intermediate acting synthetic corticosteroid.'Todaythe risk of death in pemphigus from the side effect of oral prednisolone is greater than risk of death from the disease itself.Death from sepsis and other complications of ther apy (Diabetes, hypertension, electrolyte imbalance) occurs in 5% to 10% of treated cases.Untreated disease is usually fatal.In India mortality of pemphigus vulgaris is >90% it untreated.The prognosis has dramatically improved with the use of systemic corticosteroids and various immunosuppressive agents.6 However, efficacy and safety of prednisolone is estab- lished therapy to achieve a good control of PV but associ- ated with several distressing side-effects.Several studies also carried out previously to determine the efficacy of ,dexamethasone and there is no doubt about the effectiveness.So, an endeavor had been made here to find out the adverse effects of dexamethasone, there by we use dexamethasone to control the pemphigus vulgaris in stead of prednisolone. Vlethods: An interventional study was carried out in the department of Dermatology and Venereology, Bangabandu Sheikh Mujib Medical University, Dhaka.The period of study was from January 2004 to June 2005.Total number of patient was thirty and among them, 15 patients were treated with injection dexamethasone(Group-A) and other 15 were treated with oral prednisolone(Group-B).Random sampling done and data were collected in pre-designed questionnaie.A detailed history was taken from the patient.In case of female, special attention was given regarding menstrual history and use of contraceptives.
Clinical assessment was done at baseline, after every one week upto 6 weeks.Clinical assessment tools include number of skin lesion of pemphigus, number of mucous membrane lesion of pemphigus, positive Nikolsky's sign, presence of bulla spreading phenomen a andother physical examination.Laboratory assessment was done at baseline and two weeks after therapy and at the end of six weeks.
Monitoring of adverse effect was done after 2 weeks, at the end of 4 weeks and after 8 weeks by query of symptoms of different systeffi, physical examination and laboratory test.
Information obtained from history physical examination and laboratory investigation (Routine blood examination-Total count, Differential count, Hb% and ESR, urine routine examination, blood sugar, blood urea, serum creatinine, liver function test, ECG, skin biopsy for histopathalogy & direct immunofluorescence test) were recorded in patient data sheet.
Thirfy patients were included in this study using random number table.15 patients were treated with injection Dexamethasone(Group-A) and 15 patients with oral prednisolone(Group-B).First on admission we gave 5mg injection Dexamethasone 8 hourly intravenously.This dose was continued until cessation appearance of new bulla.Then the dose was reduced 5mg l2hourly.After gradual, improvement of patient's condition the dose was reduced to 5mg intravenously daily.After 6 weeks we assessed the patient's outcome.The initial dose of prednisolone was (equivalent to 15mg dexamethasone) 100 mg daily in divided doses.It was continued until cessation of new bulla appeared.After that improvement, steroid doses were rapidly reduced by 2}mglweek upto dose 60 mg/week, then l0mgiweek upto dose 40 mg/week, then 5 mg/week upto 20 mglweek, then reduc- tion of 2.5 mg/week and then gradually dose were tapered during the follow-up period.After six weeks, we assess the patient's condition.
A11 statistical analysis was done by SPSS 12 software package as mean * Standard deviation (SD).95% confi- dence limit was taken as level of significance.Compari- son between two groups were done by unpaired 't' test and some qualitative data by 'Chi-square  weeks between two groups (P<0.05).In table Ill,"statistiof the subjects.Other side effects in dexamethasone cally significant differences of bulla spread phenomena of group were hyperglycemia (33.33%), hypertension pemphigus were observed after 6 weeks between two (26.66%), and sleep disturbance (13.33%).In predniso- groups (P<0.05) but regarding Nikolski's sign, no statisti-lone group other side effects were .cally sigrrificant differences were observed between two hyperglycernia(33.33%),hypertension(40%), Gastritis groups.Table IV showed that the most common adverse (33.33%), nausea, vomiting (13.33%), reactivation of effects were increased body weight(40%), increased tuberculosis , herpes zoster infection, sleep disturbance, appefie(40%), and puf$r face(4O%) in Dexamethasone and mood change were 6.660/o.group.In prednisolone group these side effects were 60Yo found both parenteral dexamethasone and oral predniso- lone significant in early management of pemphigus vulgaris.This result were consistent with the findings of other study.It appeared that parenteral dexamethasone and oral prednisolone had similar efficacy in the early management of pemphigus vulgaris.
The most common adverse effect from parenteral therapy were weight gain (40%), increase appetite (40%) and puffy face (40%).Other side effects were hyperglycemia (33.33o ), hypertension (26.66%), sleep disturbance (13,33% The age of the patients enrolled in the study group ranged from 20-69 years with mean age in dexamethasone group was 41.60*T3.27years and prednisolone group was 46.67*10.34years.In study by GG Toth, the average age was 47 .7 years.' Statistically significant improvement was observed in dexamethasone group in aLI clinical param- dyspepsia, headache, hrccups, hypertenslon, U r I (episodic), nail discoloration, amenorrhea and hair fall.
This was comparable to the side-effects noted in other studies, which included flushing (53.4%), hiccups (1-6. 1o ), dysgeusea (13%), cushingoid features (4%), diffuse hair loss (29%), weight gain (ll%), candidial (8-100% in one study) and pyogenic infection (3-100% in one study), generalized weakness (2.7%), atthralgia (33.3%), hyperglycemia (none in one study to I8o ), amenorrhea (2.7%), hypertension (none in one study to 3-1 1 oh), bradycardia(5 8%) and steroid psychosis.In the B group, the major adverse events were nausea and vomitirg, which were controlled with antiemetics, genetahzed weakness, secondary amenorrhea, diffuse hair fall and anemia.There were many side-effects attributable to concomitant daily prednisolone administration in this group, including reduced visual acuity due to posterior subcap sular catar act, hyperglycemia, weight gain, dyspnea due to weight gain, moon facies, hypertension and leuco- cytosis (100%).No patient experienced hematuria (due to concomitant MESNA administration in all cases) or leuco- penia.In other studies, patients on CP developed nausea and vomiting(44.4-100%),leucopenia (22.2%) and microscopic hematuria (0-11.53%),which cleared with the coadministration of MESNA, amenorrhea (11.5-25oh), weight gain (38.5%) and cataract (7.7%) (due to the coadministration of daily prednisolone).On comparing the two groups, in Group A, dysgeusea, hiccups, palpitation, nail discoloration, bone pain and UTI were more common while in Group B, nausea, flushing, menstrual irregulan$, secondary amenorrhea, dyspnea due to weight gain, moon facies and steroid withdrawal symptoms were more common.Steroid-associated side-effects were more in Group B, chiefly due to daily prednisolone. 6 study by Toth, they found diabetes is common side effect.They also found minor side effect like temporary facial flushing, sleep disturbance and mood change.T In prednisolone group coflrmon side effects were increased body weight (60%), increased appetite (60%), and pufry 42 nerpes zoster lnlecuon, reacllvallon oI tuDeroulosls, aru mood change (6.66%).One study reports that they found gastritis, hyperglycemia, hypertension, increased body weight, mood change and altered calcium/phosphate metabolism in prednisolone treated patient.tIt appeared that parenteral dexamethasone and oral prednisolone had similar efficacy but dexamethasone group had less adverse effocts than prednisolone group in the early management of pemphigus vulgaris.

Conclusion:
In the light of the findings of the study, we conclude that each of the treatment of dexamethasone group and prednisolone group is individually effective and safe in the treatment of pemphigus vulgaris but adverse effects are less in parenteral dexamethasone group than oral prednisolone group.So parenteral dexamethasone can be used as an alternative drug in the treatment of pemphig,rs vulgaris.A study with larger sample size with long duration follow up of all cases is recommended to prove the safety of dexamethasone in early management of pemphigus vulgaris.
test.Compari- son within group was done by paired't' test.P<0.05 was considered as a level of significance.Thirty patients of pemphigus vulgaris were enrolled in this study and of them 15 were enrolled in the injection dexamethasone group A(odd random table number) and 15 in the oral prednisolone group B. Table I showed that all demographic, clinical parameter were almost identical in two groups (P>0.05).Variable are expressed as mean*SD.Sex expressed as ratio.Nikolsky's sign and bulla spreading phenomena expressed as number of patient.TableIIshowed statistically significant differ- ences of skin lesion of pemphigus were observed after 6

Table - I
Baseline characteristics of two groups of sUdy subjects.

Table - II
Out come of number of skin lesion and mucous membrane lesion of pemphigus after 6 weelcs between two groups.
Adverse Effects of Parenteral Dexamethasone in the Treatment of Pemphieus Vulearis.

Table - III
Outcome of Nikolski's sign and Bulla spread phenomena membrane lesion of pemphigus and bulla spreading phenomena.But on Nikolsky's sign we did not found any significant difference between dexamethasone and prednisolone group after 6 weeks.This result were consistent with finding of other study.'Intheirstudy,thedose of dexamethasone was higher, 200mg daily.In study by Amrinder et al, they include cyclophosphamide with dexamethasone in the treatment of pemphigus vulgaris.8Theyfoundsignificantimprovementwith this therapy.Leela et al, used cyclophosphamide with dexamethasone in treatment of pemphigus vulgaris.They found complete remission in 82% of patient in their study.Their follow up period was one years.'Harmaneta!, in their sfudy, they used azathioprine and in some patient used methotrexate with dexamethasone.Their dexamethasone dose was also high.They found significant improvement in their study.'oIn our study we could not do follow up histopathology and immunofluronce test.But in other study they found significance reduction of antibody titer in direct and indirect immunofluronce test.11't'Statistically we eters i.e number of skin lesion of pemphigus, number of mucous

Table - IV
).A clinicaltrtal was carried out with 28 cases of PV aged 25-70 years, in department of Dermatology and Venereology, A11 India Institute of Medical Sciences, Distribution of study subjects by adverse fficts of drugs.
patients with Cyclophosphamide pulse (CP) with daily oral prednisolone.Patients in both groups experienced immediate and delayed side-effects.The main side- effects observed with group A were weight gain, hyper-