Successfully reported this slideshow.

Prolong remission of psoriasis with azathioprine pulse therapy

238 views

Published on

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.

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

Prolong remission of psoriasis with azathioprine pulse therapy

  1. 1.                                                                                                                                             Prolong remission of psoriasis with azathioprine pulse therapy 
  2. 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 After 9 months of phase III treatment, CLD was also withdrawn, and patients were followed-up without any treatment (Phase IV).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. 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. 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 1. Das RP, Jain AK, Ramesh V. Current concepts in the pathogenesis of psoriasis. Indian J Dermatol. 2009;54:7e12. 2. Gupta R. Azathioprine pulse therapy in the treatment of psoriasis. J Pak Assoc Dermatol. 2013;23:120e125. 3. Gupta R. Can psoriasis be cured. Delhi Med Assoc News Bull. May 10, 2013;10:22. 4. Gupta R. Prolong remission of psoriasis with azathioprine pulse therapy. Indian J Dermatol. 2014 [in press]. 5. Roenigk Jr HH, Auerbach R, Maibach HI, Weinstein GD. Methotrexate in psoriasis: revised guidelines. J Am Acad Dermatol. 1988;19:145e156. 6. Lebwohl M, Abel E, Zanolli M, Koo J, Drake L. Topical therapy for psoriasis. Int J Dermatol. 1995;34:673e684. 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. 5. 7. Lee JCT, Gladman DD, Schentag CT, Cook RJ. The long-term use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol. 2001;7:160e165. 8. Kravetz RE, Balsam T. Treatment of psoriasis with mercaptopurine. Arch Dermatol. 1961;84:597e600. 9. Greaves MW, Dawber R. Azathioprine in psoriasis. Br Med J. 1970;2:237e238. 10. Feldges DH, Barnes CG. Treatment of psoriatic arthropathy with either azathioprine or methotrexate. Rheumatol Rehabil. 1974;13:120e124. 11. Du Vivier A, Munro DD, Verbov J. Treatment of psoriasis with azathioprine. Br Med J. 1974;1:49e51. 12. Benenson E, Fries JWU, Heilig B, Pollok M. High-dose azathioprine pulse therapy as a new treatment option in patients with active Wegener's granulomatosis and lupus nephritis refractory or intolerant to cyclophosphamide. Clin Rheumatol. 2005;24:251e257. 13. Aries PM, Hellmich B, Reinhold-Keller E, Gross WL. High-dose intravenous azathioprine pulse treatment in refractory Wegener's granulomatosis. Rheumatology. 2004;43:1307e1308. a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e44 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
  6. 6. Apollohospitals:http://www.apollohospitals.com/ Twitter:https://twitter.com/HospitalsApollo Youtube:http://www.youtube.com/apollohospitalsindia Facebook:http://www.facebook.com/TheApolloHospitals Slideshare:http://www.slideshare.net/Apollo_Hospitals Linkedin:http://www.linkedin.com/company/apollo-hospitals Blog:Blog:http://www.letstalkhealth.in/

×