Various drugs used to treat pemphigus can cause remission, but none can provide permanent remission as relapses are common. With the introduction of DCP in pemphigus in 1984, patients started being in prolonged/permanent remission. This study was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in combination.

1. Efficacy and safety of dexamethasone cyclophosphamide
pulse therapy in the treatment of pemphigus – An open
randomized controlled study

2. Original Article
Efficacy and safety of dexamethasone
cyclophosphamide pulse therapy in the treatment
of pemphigus – An open randomized controlled
study
Ramji Gupta a,
*, Sachi Gupta a
, Anil Gupta b
a
Consultant Dermatologist, Department of Dermatology Indraprastha Apollo Hospital, Sarita Vihar, New Delhi
110076, India
b
Jawaharlal Nehru University, New Delhi 110036, India
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x
a r t i c l e i n f o
Article history:
Received 10 August 2015
Accepted 10 September 2015
Available online xxx
Keywords:
Dexamethasone cyclophosphamide
pulse therapy
DCP
Corticosteroids
Cyclophosphamide
Pemphigus
a b s t r a c t
Background: Various drugs used to treat pemphigus can cause remission, but none can
provide permanent remission as relapses are common. With the introduction of DCP in
pemphigus in 1984, patients started being in prolonged/permanent remission. This study
was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in
combination.
Methods: Patients were allocated into two treatment groups. Group A received treatment
with DCP pulse regimen while group B was treated with oral corticosteroids and cyclophos-
phamide lasting for 4 years.
Results: 18 out of 20 patients in DCP group entered into remission, 1–29 months after
complete stoppage of treatment. The two patients relapsed, one in phase III and another
in phase IV of DCP. Both were reverted back to phase I and again treated with IV phase
regimen of DCP. All the 20 patients in oral corticosteroids and cyclophosphamide group
developed repeated relapses (4–6 times) during the study period.
Conclusion: This study shows that DCP therapy can put pemphigus into prolonged/perma-
nent remission as compared to corticosteroid-cyclophosphamide group where relapses are
frequent. Lately, some dermatologists have questioned the efficacy of DCP in treating
pemphigus. However, this could be due to usage of wrong combination of drugs or short
study duration.
# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights
reserved.
* Corresponding author at: 47-C Pocket B, Siddhartha Extension, New Delhi 110014, India. Tel.: +91 11 26347405.
E-mail address: drramjigupta@yahoo.co.in (R. Gupta).
APME-320; No. of Pages 5
Please cite this article in press as: Gupta R, et al. Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the treatment
of pemphigus – An open randomized controlled study, Apollo Med. (2015), http://dx.doi.org/10.1016/j.apme.2015.09.001
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
http://dx.doi.org/10.1016/j.apme.2015.09.001
0976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.

3. 1. Introduction
Introduction of corticosteroids, in early 1950s, for the
treatment of pemphigus, led to a decline in mortality rate
with better prognosis.1
However, due to its severity and
potentially life threatening nature, placebo-controlled studies
for steroid use in pemphigus, were rendered unethical. Hence,
evidence to prove its efficacy is lacking.2
However, corticosteroids have been the drug of choice for
treating pemphigus. Subsequently, different doses and routes
have been compared for better treatment out come.3
Also drugs
namely cyclophosphamide,4
azathioprine, cyclosporine,5
plasma exchange, IVIG, and biologics including etanercept,
infliximab,6
rituximab etc. have been added to the treatment
armamentarium, alone or in combination with corticosteroids.1
All these modalities can control pemphigus and even cause
remission to varying degrees, but none are able to provide a
permanent remission and relapses are common.
Since the introduction of dexamethasone cyclophospha-
mide pulse therapy (DCP) in 1984,7
by Pasricha and Ramji
Gupta for the treatment of pemphigus, it has become the
preferred modality for the treatment of pemphigus.8–12
Subsequently, DCP has also been used for other diseases such
as, systemic sclerosis,13
systemic lupus erythematous,14
lichen amyloidosus15
and even rheumatoid arthritis.16
The
DCP regimen has been proved to be effective in putting
pemphigus in remission for more than 5–10 years after
complete stoppage of the treatment.9–12
This regimen is quite popular in India, due to its efficacy in
curing pemphigus permanently. However, evidence is lacking
as placebo-controlled studies are unethical and randomized
trial or randomized controlled trial have not been done. Hence,
recently some dermatologists have questioned the efficacy of
DCP in pemphigus.17–20
Thus this study, an open randomized
controlled study of DCP compared with oral corticosteroids
and cyclophosphamide.
2. Materials and methods
Forty patients with pemphigus (vulgaris – 37, foliaceus – 3)
were included in this open randomized study. Diagnosis of
pemphigus was made on the basis of clinical presentation,
histopathological finding, and direct and indirect immuno-
fluoresence test for IgG and desmoglein. Informed consent was
taken from all the patients. Ethical clearance was taken from
institute review committee of Prayatna. Most of the patients
were treated in the outpatient department (OPD) barring those
having severe and widespread lesions that required admis-
sion. Before starting the treatment, investigations were done
in all patients which included blood pressure, hemoglobin,
total and differential leukocyte counts, platelets counts, urine
examination including presence of red blood cells, blood sugar
levels, serum electrolytes, SGOT (serum glutamic oxaloacetic
transaminase), SGPT (serum glutamic pyruvic transaminase),
serum alkaline phosphatase, ECG (Electro Cardio Gram),
Skiagram of the chest, stool examination for occult blood,
ophthalmic examination especially for cataract and weight
charting. Pus was sent for culture and sensitivity test if
patient's lesions were infected. These investigations were
repeated after the last dose of first DCP pulse and subsequently
after 2–3 months in DCP group and every month in corticoste-
roids group.
Patients were allocated into two treatment groups each
comprising of 20 patients. All odd number patients, who came
to the outpatient department were put on DCP therapy (group
A), while all the even number patients were given oral
corticosteroids and cyclophosphamide (group B). Those
patients who had not completed their family, in both groups,
were given azathioprine in place of cyclophosphamide.
DCP therapy consists of transfusing 100 mg dexametha-
sone dissolved in 500 ml of 5% dextrose over 1.5–2 h, repeated
on three consecutive days. On day 2, the patient is also given
cyclophosphamide 500 mg through the same drip. This is
repeated every 28 days. In between pulses, the patient receives
50 mg cyclophosphamide orally daily. This is called DCP pulse
therapy and is divided into four phases. In Phase I, where
duration is variable, the patient may continue to have
recurrence of clinical lesions between pulses, which however
subside with subsequent DCPs. In Phase II, after the patient
achieves complete clinical remission, he is given 9 more DCPs
at an interval of 4 weeks. In phase III, if patient is still in clinical
remission, DCPs are stopped and patient takes only cyclo-
phosphamide 50 mg orally daily for the next 9 months. If the
patient still continues to be in remission, cyclophosphamide is
also withdrawn, and patient is followed up for any relapse
without any treatment for as many years as possible. This is
called Phase IV. All patients in group B were given predniso-
lone 40–120 mg/day, depending on the severity of lesions,
along with cyclophosphamide 50 mg/day. With the clearance
of lesions, prednisolone was tapered slowly to 10–15 mg/day,
while cyclophosphamide or azathioprine was continued. At
the end of study period, all patients of group B were transferred
to DCP therapy.
2.1. Statistical analysis
In the present study author has attempted to compare two
different treatment regimens namely dexamethasone cyclo-
phosphamide pulse (DCP) therapy and corticosteroids with
cyclophosphamide. These two regimes were considered for
the treatment of pemphigus in a group of 20 patients each
during 2009–2013.
On the basis of the analysis about both the treatment
regimens applied on a group of patients of pemphigus, we
found that use of DCP has resulted in early remission (with in
3–4 days). The side effects commonly found in patients using
corticosteroids namely weight gain, electrolyte imbalance,
diabetes mellitus, hypertension, acne etc. were rarely reported
in a group of patients using DCP regimen. Our primary data
give ample evidence to recognize superiority of DCP in the
treatment of pemphigus in a similar setup.
3. Results
All the patients (P. vulgaris – 18, P. foliaceus – 2) in DCP group
required additional oral betamethasone 1–4 mg daily in phase
I along with DCP to cut short the duration of phase I. Three
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x2
APME-320; No. of Pages 5
Please cite this article in press as: Gupta R, et al. Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the treatment
of pemphigus – An open randomized controlled study, Apollo Med. (2015), http://dx.doi.org/10.1016/j.apme.2015.09.001

4. patients also needed additional dexamethasone pulse which
consists of transfusing 100 mg dexamethasone dissolved in
500 ml of 5% dextrose over 1.5–2 h, repeated on two consecu-
tive days, at least 15 days after DCP, in phase I. This helped in
healing the lesions quickly and tapering the oral betametha-
sone faster. One patient developed relapse of mucosal lesions
during the seventh month of phase III while another patient
developed relapse while in 6th month in phase IV. They were
reverted back to phase I and treated accordingly with IV phase
regimen. All patients have been in continuous clinical
remission for the last 12 to 40 months and without any
treatment (phase IV) for the last 1 to 29 months (Table 1).
Indirect immune-florescence test was positive in 18 patients
(1:10 to 1:100) before starting treatment. Direct immune-
florescence test was positive on skin of 10 patients. 10 patients
on whom IIF and DIF were repeated after phase III showed
decrease or negative result.
Group B comprised of 20 pemphigus (P. vulgaris – 19, P.
foliaceus – 1) patients. 17 patients showed positive IIF (1:20–1:80)
and desmoglein (+ to +++) in their blood and positive DIF in 16
skin biopsies. Lesions in all the patients were controlled with
prednisolone 40–120 mg/day in 1–6 months, following which
prednisolone was tapered slowly to 10–15 mg/day in 4–5
weeks. The maintenance dose was 5–20 mg/day (Table 2) in all
the patients till the next relapse which usually occurred in 1–9
months.
Along with prednisolone, cyclophosphamide 50 mg or
azathioprine 50 mg daily was given to all the patients. 3
patients with mucosal lesions took a longer time to clear. One
patient showed negative IgG, while another showed increased
desmoglein at the end of the study. All other patients showed
decrease in their titer of IgG and desmoglein. Most of the
patients developed 4–6 relapse (Table 3) during the study
period with maintenance dose of 5–20 mg prednisolone/day.
3.1.1. Side effects
In DCP group two patients noticed hiccups with few DCPs that
were controlled in 2–3 days with prochlorperazine hydrochlo-
ride 5 mg thrice daily. One patient developed psychosis that
was treated with imipramine hydrochloride 5 mg thrice daily.
Invariably, all patients needed systemic antibiotics in phase I
to control the secondary bacterial infections of the skin. Those
having oral ulcers (16 patients) needed oral fluconazole
therapy till the clearance of oral candidiasis. However, no
one required any oral antibiotic or antifungal medicine in
phase II and III. Six patients who already had moon faces and
obesity due to daily corticosteroids before coming to us, lost
their excess weight and reverted back to their normal
appearance as treatment with DCP progressed. Generalized
weakness and lethargy were reported by five patients
following DCP, which was treated with 0.5 mg dexamethasone
orally daily for 3–4 days. Metallic taste was noticed by three
patients, which continued for 4–5 days after DCP. One patient
Table 2 – Maximum daily dose of prednisolone given
during remission in corticosteroids + cyclophosphamide
group.
Dose (mg/day) Number of patients
5–10 11
11–15 5
16–20 4
Total 20
Table 3 – Number of relapses during study in corticos-
teroids + cyclophosphamide group.
No of relapses No of patients
4 2
5 3
6 15
Total 20
Table 1 – Duration of remission in DCP group.
Duration in months No of patients
0–3 3
4–6 3
7–12 4
13–24 5
<25 5
Total 20
Table 4 – Side effects in DCP and corticosteroids + cyclophosphamide group.
Side Effect DCP Corticosteroids + cyclophosphamide
Weight gain 4# 8
Electrolyte imbalance 6
Diabetes mellitus 2# 4
Hypertension 3# 3
Acne 2
Moon faces and obesity 6# 8
Hiccups 2 10
Psychosis 1
Bacterial infection In 16 patients in phase I only In 16 patients with every relapse
Candidal infection In 16 patients with oral lesions only in phase I In 16 patients with majority of relapses
Generalized weakness 5
Lethargy 5
Metallic test 3
Reactivation of tuberculosis 1
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x 3
APME-320; No. of Pages 5
Please cite this article in press as: Gupta R, et al. Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the treatment
of pemphigus – An open randomized controlled study, Apollo Med. (2015), http://dx.doi.org/10.1016/j.apme.2015.09.001

5. developed reactivation of tuberculosis which was treated with
anti-tuberculosis drugs along with DCP.
In corticosteroids group, 10 patients developed hiccups for
which prochlorperazine hydrochloride 5 mg 2–3 time daily was
given off and on throughout the study period. Invariably all
patients needed systemic antibiotics to control the secondary
bacterial infections of the skin. Those with oral candidiasis (16
patients) anti-candidal treatment was also given till the
clearance, eight patients developed moon faces and obesity,
four patients developed diabetes mellitus which was con-
trolled with antidiabetic medicine, three patients developed
hypertension and two developed acne (Table 4).
4. Discussion
The chief advantage of DCP is induction of quick remission with
all the skin lesions improving within three to four days. Other
advantages include no side-effects commonly seen with daily
doses of corticosteroids including weight gain, electrolyte
imbalance, diabetes mellitus, hypertension, acne, etc. The main
problem with DCP is increased susceptibility to infections,
bacterialaswellascandidalinphaseIofthetreatmentwhenthe
skin and mucosa are eroded. However, both are controlled by
giving suitable antibiotics and/or anticandida drugs. Another
problem requiring attention is reactivation of tuberculosis,9
which can be treated by appropriate anti-tubercular treatment
while DCP is continued. Duration of post treatment disease-free
period has been an average of 12–40 months (Table 1). Relapse
occurred in two patients, in one patient, 6 months after
completion of DCP and other patient developed mucosal lesion
in phase III. Both the patients were reverted back to phase I and
treated completely with 4-phase DCP regimen.
A relapse after receiving complete and regular treatment or
during treatment does not mean that DCP therapy has failed
completely. A second course of DCP regimen in such cases
usually achieves the desired results.
Total time taken to clear the lesion is less in DCP than with
oral corticosteroids and cyclophosphamide. The duration of
clearance is one time in majority of DCP patients as compared
to corticosteroids and cyclophosphamide group where recur-
rence is the rule (Table 3).
The remission period produced by DCP is usually prolonged
(1 to 29 months) after stopping all treatment as compared
to multiple remissions and relapses in corticosteroids group
(0.5–6 month) during the study period.
Side effects with DCP are much less as compared to
corticosteroid group (Table 4).
Rose et al.18
used a different regimen of DCP than what is
used now a day's.8,9
DCP pulse they used is same but they did
not use 4-phase regimen. In phase I, DCP is usually repeated at
interval of 4 weeks. Cyclophosphamide 50 mg orally is given
in between. If patient has widespread lesions, DP is also given
after 2 weeks of DCP for 2 days. DCP and cyclophosphamide
were continued in phase I, till all the lesions cleared, and
patients entered into phase II, where they were given
treatment for another 9 months, instead of 6 months as Rose
et al. had used. This may be the reason, why they got different
results. In phase III, if patient is still in clinical remission, DCPs
are stopped and patient takes only cyclophosphamide 50 mg
orally daily for the next nine months. If the patient still
continues to be in remission, cyclophosphamide is also
withdrawn and patient is followed up for any relapse without
any treatment for as many years as possible. Similarly Mentink
et al.19
used the same treatment but withdrew the treatment
very fast as Rose et al.,18
did and got the same resultas Rose et al.
Most drugs used in pemphigus are able to clear the lesions
and produce remissions (lasting few months to one year
followed by relapses). However, DCP produces prolonged
remission in majority of cases as shown in this study.
Infection is more in DCP patients in phase I but quickly
controlled with systemic antibiotics, whereas recurrent infec-
tion with every relapse needs more antibiotics and antic-
andidal drug in corticosteroid's group.
About the toxicity of prolonged cyclophosphamide it is
already suggested to use azathioprine in patients who have
not completed their family to avoid gonado-toxicity of
cyclophosphamide. Systemic antibiotic should be used only
whenever needed.20
Jonkman21
has given high dose of prednisolone, i.e. 80 mg/
day along with 2–3 mg azathioprine daily to both groups,
which itself is able to control the disease in majority of
patients. In addition to this, giving placebo or DCP to either
group will produce more or less the same result in both the
groups. In this study and the other study which has produced
prolonged remission6,8–12
if all the patients were followed for
15–20 years after DCP withdrawal, most of the patients would
be in remission.
We have not used dexamethasone all through the study
except in phase I. Statistical difference will be found, if patients
are followed up for a prolonged period i.e. at least 4–5 years or
more in a disease like pemphigus.
Conflicts of interest
The authors have none to declare.
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of pemphigus – An open randomized controlled study, Apollo Med. (2015), http://dx.doi.org/10.1016/j.apme.2015.09.001

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APME-320; No. of Pages 5
Please cite this article in press as: Gupta R, et al. Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the treatment
of pemphigus – An open randomized controlled study, Apollo Med. (2015), http://dx.doi.org/10.1016/j.apme.2015.09.001