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Original Article

Azathioprine Pulse Therapy in the treatment ofpsoriatic arthritis: A case series

Ramji Gupta*,1

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 30 July 2014

Accepted 29 October 2014

Available online xxx

Keywords:

Azathioprine pulse therapy

Continuous low dose azathioprine

Intermittent high dose azathioprine

Psoriatic arthritis

* 47-C Pocket e B Siddhartha Extension, NE-mail address: drramjigupta@yahoo.co.i

1 Institution where work was done, Praya

Please cite this article in press as: GuptaApollo Medicine (2014), http://dx.doi.org/

http://dx.doi.org/10.1016/j.apme.2014.10.0020976-0016/Copyright © 2014, Indraprastha M

a b s t r a c t

Background/objective: Treatment available for treating psoriasis of joint are able to clear the

lesions but relapse is common. While treating psoriasis with Azathioprine Pulse Therapy, it

was observed that the involvement of joints (arthritis of small and big joints) also cleared. To

seewhether intermittenthighdose (IHD)andcontinuous lowdose (CLD)azathioprinegiven to

clear psoriasis also clear the joint involvements and produce prolong/permanent remission.

Methods: Six out of 60 psoriasis patients treated with azathioprine pulse therapy (APT) had

joints involvement. All received azathioprine pulse therapy for treating psoriasis which

contain azathioprine 500 mg given on three consecutive days and was repeated every

month on the same date along with azathioprine100 mg orally in between the IHD. The

entire treatment was divided into four phases. Phase I, continued till clearance of all le-

sions of psoriasis. In phase II nine more APT is given. In phase III only azathioprine100 mg

was continued for 9 months. In phase IV azathioprine100 mg was also stop and patients

were followed up without any treatment for any recurrence till the end of the study.

Result: Six patients with joint pain and arthritis cleared in 1e12 months and are in

remission since 35e95 months.

Conclusions: Thus azathioprine pulse therapy regimen is able to put psoriatic arthritis into

prolong/permanent remission.

Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

Psoriasis, an auto-immune disorder due to activated

T-lymphocyte cells which secrete cytokines responsible for

manifestation of psoriasis and joint changes.1 Psoriasis pre-

sent commonly as well defined erythematous scaly plaques

ew Delhi 110014, India. Tn.tna, M�54 Lajpat Nagar II

R, Azathioprine Pulse T10.1016/j.apme.2014.10.

edical Corporation Ltd. A

on the skin which become silvery on scratching. Sometime

psoriasis may be associated with arthritis. Polyarthritis is the

most common pattern of arthritis.2

Drugs found useful in treating psoriatic arthritis include

methotrexate, etretinate, infliximabs, adalimumab, eta-

nercept, alefacept, cyclosporine, acetretin and azathioprine.

el.: þ91 11 26347405.

, New Delhi 110024, India.

herapy in the treatment of psoriatic arthritis: A case series,002

ll rights reserved.

eriod

after

pped

Rem

issionperiod

ofpso

riasisafter

APTwasstopped

.09(20)

9.4.08R25.12.09(20)

1.9.11(31)

14.3.09(63)

9.10.09(57)

3.3.08(76)

16.4.13(15)

9.11.132(8)

a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1e32

None has produced complete and prolonged remission. Re-

lapses are common.

It was previously shown that Azathioprine Pulse Therapy

(APT) where azathioprine 500 mg orally is given on three

consecutive days which was repeated monthly along with

azathioprine 100 mg given daily in between IHD put the pso-

riasis into prolonged remission up to 65e93 months.3e5

While treating psoriasis with APT it was observed that

patients having arthritis also cleared along with psoriasis.

Here we report all those patients in details.

arthritis.

Typeofjoints

involve

Durationof

involvement

Treatm

ent

durationin

month

s

Relapse

after

inm

onth

sDurationto

clearrelapse

Com

plete

rem

ission

byin

month

s

Rem

issionp

ofpso

riasis

APTwassto

Right2nd

interp

halyngial

joint

10Y

26M

3rd

and4th

interp

halyngial

joints

15Month

7/6/08(73)

9.4.08R25.12

1.9.11(34)

Both

knees

2Y

1e

e4/8/06(95)

14.3.09(63)

Both

knees

andelbow

6M

12

ee

6/11/08(68)

9.10.09(57)

Interp

halyngial

jointof(L)ring

finger

4M

5e

e5/06/06(97)

3.3.08(76)

Arthritistoe,

ankle,kneefinger,

wrist,sh

oulder

3Y

3.5

ee

30.07.11(35)

16.4.13(15)

Both

knee

3years

5month

se

e15/5/11(33)

15.5.11(33)

2. Material and methods

Six patients having arthritis of different joints out of 60

patients of psoriasis treated with APT were included in the

study. The diagnosis was made initially on clinical ground.

X-ray was done in all the patients to confirm the diagnosis.

Laboratory evaluation included hemoglobin, total and dif-

ferential leukocyte counts, platelet counts, erythrocyte

sedimentation rate, blood urea, creatinine, SGOT, SGPT,

TPMT enzyme and alkaline phosphatase. These in-

vestigations were undertaken before starting treatment and

were done regularly before giving IHD azathioprine during

follow-up. Psoriasis Area Sensitive Index (PASI) was recor-

ded on a special proforma before starting the treatment and

was charted regularly during follow-up along with evalua-

tion of arthritis.

Active systemic diseases like hepatitis, malignancies,

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 before starting

treatment.

The treatment consisted of two components. Intermittent

High Dose (IHD) azathioprine (500 mg orally given on three

consecutive days which was repeated on every month on the

same date). Continuous Low Dose (CLD) azathioprine (100 mg

orally daily between the courses of IHD). The entire treatment

was divided into four phases. During phase I, treatment with

IHD and CLD azathioprine was continued till psoriatic lesions

cleared. Once the skin lesions cleared completely after varied

courses of IHD, patients would proceed to phase II while

continuing treatment with IHD and CLD azathioprine which

war given for another 9 months. In Phase III IHD was stopped

but CLD was continued. Subsequently, after 9 months of

phase III treatment, CLD azathioprine was also withdrawn

and patients were followed-up for any relapse till the end of

the study (phase IV). Nothing extra was given for joint

disorders.

Table

1e

APTin

Pso

riatic

S.No

Age/

sex

Typeof

pso

riasis

151M

Eryth

ro

derm

ic

259F

Plaque

338F

Plaque

428M

Plaque

531M

Plaque

634F

Plaque

3. Results

Out of six patients, five had plaque type and one had eryth-

rodermic psoriasis and were 28e59 years of age. X-ray of all

joints revealed sclerosis in articular and subarticular portion

consistent with psoriatic arthritis. Pain of joints clear in 1e12

months with clearance of X-ray findings. They are in remis-

sion since 35e95 months without pain and joint changes. One

Please cite this article in press as: Gupta R, Azathioprine Pulse Therapy in the treatment of psoriatic arthritis: A case series,Apollo Medicine (2014), http://dx.doi.org/10.1016/j.apme.2014.10.002

a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1e3 3

patients having arthritis of 3rd and 4th interphalyngial joint

developed relapse 6months after being in remission. The pain

cleared with continuation of APT in 15 months and continued

to be in remission since73 months.

4. Discussion

Association of joint pain and changes has been often seen in

different types of psoriasis.2 Six patients of psoriasis who had

pain in different joints and was treated with APT for psoriasis,

the pain and X ray changes of joints also cleared during

treatment of psoriasis with APT and remained free of pain and

joint lesions till the end of study. Remission period varied

from 35months to 95 months (Table 1) and 8e76 months after

APT was stopped.

Treatment used for psoriatic arthritis include nonsteroidal

anti-inflammatory drugs initially, DMARDs like metho-

trexate,6 sulfasalazine, leflunomide7 and oral cyclosporine8

and retinoid like etretinate and acitretin.

Biologic agents like infliximab 0.5 mg/kg IV for 4e6 injec-

tion repeated every 8 weeks, adalimumab 40 mg every other

week, etanercept 50 mg twice weekly for 3 months,9 alefacept

7.5e15 mg IMI for 12 week has been found useful in psoriatic

arthritis when given for treatment of psoriasis.

Most of the above drugs improve and evenmake the lesion

to disappear but long term follow-up is needed to assess the

effect.

Azathioprine has been usedwidely for prolonged period for

treating psoriatic arthritis with good result even up

to100e200 mg daily,10,11 but most of the patients developed

relapse after variable period after drug was stopped.

In our series of six cases of arthritis with psoriasis, le-

sions of all the patients cleared and all remained free from

arthritis till the end of the study. Those who relapsed (one

patient) went into remission on continuing the APT for

psoriasis.

Please cite this article in press as: Gupta R, Azathioprine Pulse TApollo Medicine (2014), http://dx.doi.org/10.1016/j.apme.2014.10.

Disclosure

Conflict of interest

No conflict of interest.

r e f e r e n c e s

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3. Gupta Ramji. Azathioprine pulse therapy in the treatment ofpsoriais. J Pak Assoc Dermatol. 2013;23:120e125.

4. Gupta Ramji. Can psoriasis be cured. Delhi Med Asso News Bull.May 10, 2013;12:22.

5. Gupta Ramji. Intermittent high dose and continous low doseazathioprine in psoriaisis. Indian J Dermatol. 2014 [in press].

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10. Feldges DH, Barnes CG. Treatment of psoriatic arthropathywith either azathioprine or methotrexate. Rheumat Rehab.1974;13:120e124.

11. Lee JCT, Gladman DD, Schentag CT, Cook RJ. The long-termuse of azathioprine in patients with psoriatic arthritis. J ClinRheumat. 2001;7:160e165.

herapy in the treatment of psoriatic arthritis: A case series,002