Various therapies used for the treatment of psoriasis though are able to produce remission but relapses remain the common problem. Treatment with Azathioprine Pulse Therapy (intermittent high dose (IHD) and continuous low dose (CLD) azathioprine) can produce prolonged and durable remission in psoriasis was observed.

1.
Prolong remission of psoriasis with azathioprine
pulse therapy

2. Original Article
Prolong remission of psoriasis with azathioprine
pulse therapy
Ramji Gupta*
Consultant Dermatologist, Department of Dermatology, Indraprastha Apollo Hospital, Sarita Vihar,
New Delhi 110076, India
a r t i c l e i n f o
Article history:
Received 21 May 2014
Accepted 19 July 2014
Available online xxx
Keywords:
Azathioprine pulse therapy
APT
Psoriasis
Prolong remission
a b s t r a c t
Background: Various therapies used for the treatment of psoriasis though are able to pro-
duce remission but relapses remain the common problem. Treatment with Azathioprine
Pulse Therapy (intermittent high dose (IHD) and continuous low dose (CLD) azathioprine)
can produce prolonged and durable remission in psoriasis was observed.
Methods: Sixty patients with psoriasis were treated with monthly IHD azathioprine (500 mg
on 3 consecutive days), CLD azathioprine (100 mg orally) was given daily in between IHD.
The entire treatment schedule was divided into four phases. During phase I, treatment
with IHD and CLD azathioprine was continued till complete clearance of lesions, when
patients proceeded to phase II while continuing treatment with IHD and CLD. After
continued remission for a period of 9 months, treatment with IHD was stopped, but CLD
was continued (Phase III). After 9 months of phase III treatment, CLD was also withdrawn,
and patients were followed-up without any treatment (Phase IV).
Results: Forty five patients completed treatment and are in remission without any
treatment.
Conclusions: Out of 45 patients in phase IV, 25 patients are in continuous remission for more
than 3 years (maximum 93 months), 9 are in remission for 1e3 years, while 11 are less than
1 year in continuous remission after all treatment was stopped. Thus azathioprine pulse
therapy regimen produced prolonged remission in psoriasis.
Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Various therapies used to treat psoriasis, clear the lesions but
are unable to prevent relapse. Psoriasis is known to be caused
by activated T lymphocyte cells which produce cytokines.
Cytokines lead to the proliferation of keratinocytes
responsible for development of psoriasis lesions.1
Azathio-
prine is known to suppress activated T lymphocyte cells
which in turn stop production of cytokines which ultimately
stop the proliferation of keratinocytes responsible for devel-
opment of psoriasis. To achieve clearance of the lesions as
well as prolong period of remission an arbitrarily designed
regimen of azathioprine was studied2
in the management of
* 47-C Pocket B Siddhartha Extension, New Delhi 110014, India. Tel.: þ91 11 26347405.
E-mail address: drramjigupta@yahoo.co.in.
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e4
Please cite this article in press as: Gupta R, Prolong remission of psoriasis with azathioprine pulse therapy, Apollo Medicine
(2014), http://dx.doi.org/10.1016/j.apme.2014.07.005
http://dx.doi.org/10.1016/j.apme.2014.07.005
0976-0016/Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

3. psoriasis. Azathioprine was used as intermittent high dose
(IHD) azathioprine (500 mg on 3 consecutive days, repeated
every month on the same date) with continuous low dose
(CLD) azathioprine (100 mg orally) given daily in between IHD.
The entire treatment was divided into four phases.3,4
During phase I, treatment with IHD and CLD azathioprine
was continued till clearance of lesions. Once the lesions
cleared completely patient would proceed to phase II, while
continuing IHD and CLD azathioprine. After the patient had
remained lesions free for a period of 9 months, treatment with
IHD azathioprine was stopped, but CLD azathioprine
continued (Phase III). Subsequently, after 9 months of phase III
treatment with no recurrence, CLD azathioprine was also
withdrawn and patients were followed-up without any
treatment (Phase IV). This entire treatment is known as
Azathioprine Pulse Therapy (APT) regimen. Initially to clear
the lesion fast and in patients of pustular psoriasis, eryth-
rodermic psoriasis and extensive plaque psoriasis, metho-
trexate 15 mg per week5
and topical coal tar 6% with salicylic
acid 3%6
was also used in phase I as azathioprine takes few
weeks to start action.
2. Materials and method
Diagnosis of psoriasis was made clinically (Fig. 1); histopathol-
ogy was done in some patients only (Fig. 3). Laboratory evalu-
ation included hemoglobin, total and differential leukocyte
counts, platelet counts, erythrocyte sedimentation rate, blood
urea, creatinine, SGOT, SGPT and alkaline phosphatase. These
investigations were undertaken before starting treatment and
regularly before giving IHD. Psoriasis Area Severity Index (PASI)
was charted in each patient. TPMT enzyme screening was not
done initially due to its unavailability but later on done in every
patient when it became available. Patient having PASI more
than 8 was included while patient with active systemic disease
like hepatitis, cirrhosis of liver; acute and chronic nephritis,
malignancy, pregnant women, lactating mother and children
were excluded from the study. Informed written consent was
taken from each patient. Ethical approval was obtained from
the Institution Ethics Committee of Prayatna.
In addition to azathioprine, most patients also received
topical coal tar 6% with salicylic acid 3% ointment and
methotrexate 15 mg weekly during phase I to assist in fast
symptom control.
3. Statistical analysis
On the basis of available data, an analysis was done in the
study period. Mean duration of remission is 40.14 ± 22.56
(17.58e62.70) months.
4. Results
Sixty patients (54 psoriasis vulgaris, 4 pustular and 2 eryth-
rodermic) between 25 and 72 years of age with 2e50 years
disease duration were included in the study. The average PASI
score was 19.60 ± 7.64. Before coming to us most of the pa-
tients had taken methotrexate, coal tar and PUVA with re-
lapses at variable interval. All previous treatments were
stopped for four weeks before commencing azathioprine
pulse therapy. In addition to APT, 28 patients also received
topical coal tar 6% ointment and oral methotrexate 15 mg per
Fig. 1 e Psoriasis axilla before treatment.
Fig. 2 e Histopathology of psoriasis plaque e (H & E £10).
Fig. 3 e Psoriasis axilla after treatment.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e42
Please cite this article in press as: Gupta R, Prolong remission of psoriasis with azathioprine pulse therapy, Apollo Medicine
(2014), http://dx.doi.org/10.1016/j.apme.2014.07.005

4. week during phase I which varies from 2 to 9 weeks. 45 pa-
tients completed the therapy and are in phase IV (Fig. 2).
The duration of continuous remission in 25 patients is
more than 3 years (maximum 93 months), in 9 patients 1e3
years and in 11 patients less than 1 year. Mean duration of
remission is 40.14 ± 22.56 months (Table 1).
4.1. Relapse
Seven patients relapsed after being in phase IV for 7e23
months. 3 patients were restarted on APT and are in phase IV
from 10 to 42 months. Remaining 4 patients were lost to
follow-up.
4.2. Side effects
Common side effects seen were nausea and vomiting in 18
patients, which was controlled with ranitidine, weakness and
fatigue in 4 patients, giddiness in 2 patients, loss of appetite,
sleeplessness and generalized malaise in 1 patient each. Liver
function tests were elevated in 8 patients in phase I and 5
patients in phase II. Leucopenia was seen in 3 patients in
phase I, which returned to normal in 3 weeks after stopping
azathioprine. Lee et al7
have also reported similar transient
side effects in long term use of azathioprine (Table 2).
5. Discussion
It is usually believed that complete and durable remission of
psoriasis is extremely difficult to obtain. Our present findings
and earlier published report3,4
suggest that it may be possible
to induce long term remission by azathioprine pulse therapy
regimen.
Systemic azathioprine has been extensively investigated for
the treatment of psoriasis. In 1961 Kravetz and Balsam8
first
time used azathioprine in psoriasis; they used 2 mg/kg daily in
12 patients, 1e4 courses with improvement. Majority of them
developed relapse within 1.5e6 months after the last dose. In
1970 Greaves and Dawber9
used 2.5 mg/kg/day for 6 weeks in 10
patients with 25% clearance of the lesions in 5 patients in 2e6
weeks. Relapse was seen 1 month after stoppage of azathio-
prine. Fledges and Barnes10
in 1974 used 2.5 mg/kg/day in 10
patients for 4½ months to 5½ years with almost complete
clearance of skin lesions in 6 patients. Azathioprine was dis-
continued after remission lasting for 1 year. However all
developedrelapseafterstoppage oftreatment.In 1974DuVivier
et al11
used 100e300 mg azathioprine daily for 2e24 weeks with
75e100% clearance of psoriasis lesions with maintenance dose
of 75e200 mg daily in 13 out of 29 patients. One patient who was
free of the lesions developed relapse 6 months after complete
stoppage of azathioprine. Lee et al7
used 200e300 mg azathio-
prine daily for 12e24 months in psoriatic arthritis with
improvement with few transient side effects.
Azathioprine in high dose in pulse form (800 mg daily on 3
consecutive days repeated every month and 200 mg daily in be-
tween for 12e24 months) has recently been evaluated in limited
patients with Wegner's granulomatosis and lupus nephritis12,13
with very few side effects. The present study lies in using
azathioprine pulse therapy in this particular dosage schedule.
In summary, treatment with azathioprine pulse therapy
regimen can induce durable clinical remission in patients
with psoriasis with an acceptable safety profile. More studies
using this regimen by other investigators will further confirm
our findings.
Conflicts of interest
The author has none to declare.
Acknowledgment
Author thanks Mr. Anil Gupta, Center for Social Medicine and
Community Health, Jawaharlal Nehru University, New Delhi,
India for statistical assistance.
r e f e r e n c e s
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Table 1 e Details of patient in remission.
Time No of patients
3 yrs and above (up to 93 months) 25
1e3 years 9
Less than 1 yr 11
Total 45
Table 2 e Side effects of APT.
Phase I Phase II Phase III Phase IV
Liver function tests
(SGOT, SGPT,
alkaline phosphatase)
8 5
Leucopenia 3
Nausea and vomiting 5 2
Nausea 1
Weakness 4
Giddiness 2
Restlessness 2
Uneasiness 1
Loss of appetite 1
Hair loss 1
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e4 3
Please cite this article in press as: Gupta R, Prolong remission of psoriasis with azathioprine pulse therapy, Apollo Medicine
(2014), http://dx.doi.org/10.1016/j.apme.2014.07.005

5. 7. Lee JCT, Gladman DD, Schentag CT, Cook RJ. The long-term
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azathioprine pulse therapy as a new treatment option in
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a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e44
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(2014), http://dx.doi.org/10.1016/j.apme.2014.07.005

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