Azathioprine pulse therapy in the treatment of psoriasis nail: A case series

Case Report

Azathioprine pulse therapy in the treatment ofpsoriasis nail: A case series

Ramji Gupta *

Consultant Dermatologist, Department of Dermatology, Indraprastha Apollo Hospital, Sarita Vihar,New Delhi, 110076, India

1. Introduction

Psoriasis, an autoimmune disorder due to activated T lympho-cyte cells, secretes cytokines. Cytokines are responsible for

manifestation of psoriasis and nail changes. Psoriasis presentscommonly as well-defined erythematous scaly plaques on theskin which becomes silvery on scratching.

Involvement of nails is common in psoriasis which includepitting, onycholysis, dystrophy, subungual hyperkeratosis,

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a r t i c l e i n f o

Article history:

Received 27 February 2015

Accepted 6 May 2015

Available online 6 June 2015

Keywords:

Azathioprine pulse therapy

Dystrophy nail

Nail psoriasis

Pitting nail

White nail

a b s t r a c t

Background: Various treatmentsavailable for treatingnail changes inpsoriasisareable toclear

the lesions but relapse is common.While treatingpsoriasiswith azathioprine pulse therapy, it

was observed that the lesion of nails including pitting, dystrophy, etc. was also cleared.

Aim: To check whether intermitted high dose (IHD) with continuous low dose azathioprine

given to clear psoriasis could also clear the nail changes and produce prolonged remission.

Methods: 7 out of 60 psoriasis patients treated with azathioprine pulse therapy (APT) had

psoriatic lesion on nails also. All the 60 patients received azathioprine pulse therapy for

treating psoriasis, which contain azathioprine 500 mg given on 3 consecutive days and was

repeated every month on the same date along with azathioprine100 mg orally in between

the IHD. The entire treatment schedule was divided into four phases. Phase I continued till

complete clearance of all lesions on the skin. In Phase II, 9 more APTs are given. In Phase III,

only azathioprine 100 mg is continued for 9 months. In Phase IV, 100 mg was also stopped

and patients were followed up without any treatment.

Results: Out of 7 patients, 5 had pitting of nails which cleared in 2–13 months. All the nails

having pitting are in remission from 14 to 106months. One patient had dystrophy of all nails

of 2-yr duration, which cleared in 3 months. However, he developed relapse along with

relapse of psoriasis after 26 months in remission, which subsequently cleared in 10 months

on continuing APT and he is in remission since 62months.White nails in 1 patient cleared in

17 months, and she/he is in remission since 17 months.

Conclusion: Azathioprine pulse therapy regimen is able to put psoriatic nail changes into

prolonged remission.

# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights

reserved.

* Correspondence to: 47-C Pocket-B, Sidhartha Extension, New Delhi 110014, India. Tel.: +91 11 26347405.E-mail address: drramjigupta@yahoo.co.in

Available online at www.sciencedirect.com

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journal homepage: www.elsevier.com/locate/apme

http://dx.doi.org/10.1016/j.apme.2015.05.0120976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.

discoloration of nail plate, white nail, uneven nail surface, andoccasionally acute and chronic paronychia.

Variety of treatments have been used for nail psoriasis1,2

but with limited success. None have produced a completeremission. Biologics have significantly reduced the morbidityof severe nail psoriasis.

It was previously shown that azathioprine pulse therapy(APT), where azathioprine 500 mg orally is given on 3consecutive days and repeated every month on the samedate in combination with azathioprine 100 mg given daily inbetween, put the psoriasis into remission up to 65–93months.3–6

While treating psoriasis with APT, it was observed thatpatients having lesion on their nails such as pitting, dystrophy,and white discolorations also cleared along with psoriasis.Here, we report all those patients.

2. Materials and methods

Nine patients having nail psoriasis out of 60 psoriasis patientstreated with APT were included in the study. The diagnosiswas made mainly on clinical grounds. In patients having naildystrophy and white nail, KOH examination was done to ruleout dermatophyte. Laboratory evaluation included hemoglo-bin, total and differential leukocyte counts, platelet counts,erythrocyte sedimentation rate, blood urea, creatinine, SGOT,SGPT, alkaline phosphatase, and TPMT enzyme test. Theseinvestigations were undertaken before starting of the treat-ment and were done regularly before giving IHD azathioprineduring follow-up. Psoriasis Area Severity Index (PASI) wascharted in each patient on a special pro forma before startingthe treatment.

Informed written consent was taken from each patient.Ethical approval was obtained from the institution EthicsCommittee of Prayatna before starting of the treatment.

The treatment regimen consisted of intermittent high dose(IHD) azathioprine (500 mg orally on 3 consecutive days. Thiswas repeated on amonthly basis on the same date.) alongwithcontinuous low dose (CLD) azathioprine (100 mg orally givendaily between IHD). The entire treatmentwas divided into fourphases. During Phase I, treatment with IHD and CLD

azathioprine was continued till psoriatic lesions on skincleared. Once the skin lesions cleared completely after variedcourses of IHD, patients would proceed to Phase II whilecontinuing treatment with IHD and CLD azathioprine, whichwas given for a period of 9 months. In Phase III, IHD wasstopped but CLDwas continued. Subsequently, after 9 monthsof Phase III treatment, CLD azathioprine was also withdrawnandpatientswere followedup for any relapse till the end of thestudy (Phase IV). Nothing extra was given for nail disorders. Inaddition to azathioprine, most patients also received topicalcoal tar 6% ointment during Phase I to assist in symptomcontrol of psoriasis from skin.

3. Results

Two patients were lost to follow-up. All the remaining 7patients had plaque type of psoriasis along with nail lesionsand were 23–49 yrs of age. Pitting of nail was seen in 5patients with 6 months–16 yrs of duration. Pitting in all nailscleared in 2–13 months. All are in remission since 14–106months and without any treatments since 8.5–84.5 months(Table 1). One patient had dystrophy of all nails of 2-yrduration, which cleared in 3 months. However, he developedrelapse along with relapse of psoriasis after 26 months inremission. The nail lesion subsequently cleared withcontinuation of APT in 10 months and is in remission since62 months and without any treatment since 50.5 months.One patient had white nails, which cleared in 17 months andis in remission since 17 months and without any treatmentsince 11 months.

3.1. Side effects

Common side effects seen out of 7 patients were nausea andvomiting in 2 patients, which were controlled with ranitidine,weakness and fatigue in 1 patient, and giddiness in 2 patients.Liver function tests were elevated in 1 patient in Phase I and 1patient in Phase II. Leucopenia was seen in 1 patient in Phase I,which returned to normal in 3 weeks after stopping azathio-prine. Similar transient side effects in long-term use ofazathioprine were seen in other study also.

Table 1 – APT in nail psoriasis.

S.no.

Age/sex

Type ofpsoriasis

Type of nailinvolvement

No. ofnail

involved

Duration ofinvolvement

Treatmentduration(months)

Relapse afterremission(months)

Duration toclear relapse(months)

Completeremissionperiod

(months)

Remissionperiod afterAPT wasstopped(months)

1 25 F Plaque Pitting All 13 yrs 12 – – 8.03.07 (94) 6.12.07 (84.5)2 48 M Plaque Dystrophy All 2 yrs 3 26 10 15.11.09 (62) 1.11.10 (50.5)3 49 M Plaque Pitting All 4 yrs 4 – – 19.11.07 (34)

Exp 9.8.1031.01.09 (18)Exp 9.08.10

4 48 M Plaque Pitting 4 6 months 2 – – 25.03.06 (106) 20.03.08 (82)5 28 M Plaque Pitting All 5 yrs 4 – – 30.03.07 (94) 20.11.10 (50)6 34 M Plaque Pitting All 16 yrs 13 – – 14.11.13 (14) 29.04.14 (8.5)7 23 F Plaque White nail All 4 yrs 17 – – 1.09.13 (17) 8.02.14 (11)

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4. Discussion

Association of nail changes has been frequently observed indifferent types of psoriasis. Out of 7 patients of psoriasis,which had nail involvement and was treated with APT, 5 hadpitting of nails, 1 dystrophy, and another white nail. All thelesions in nail cleared during treatment of psoriasis with APTand remained free of lesions till the end of the study.Remission period varied from 14 to 106 months (Table 1)and without treatment from 8.5 to 84.5 months.

Various topical therapies used in nail psoriasis includecorticosteroids like clobetasol propionate 0.05% cream, dithra-nol 0.4–2% ointment, fluorouracil 1% vitamin D analogs likecalcipotriol, calcitriol and tacalcitol, tacrolimus 0.1–0.03%ointment, cyclosporine, and tazarotene 0.1% with limitedefficacy.1,2

Intralesional therapy includes triamcinolone acetonide andmethotrexate7 with less pronounced response. Both causepain during injection. Photo-therapy with narrow band UVBand PUVA had a limited effect.8 Similarly, superficial radio-therapy, electron beam, and Grenz rays were found to havetemporary effects. Photodynamic therapy and pulsed dyelaser9 have shown significant improvement in a few patients.

Systemic therapy includes retinoid-like etretinate 0.2–0.3 mg/kg/day and acitretin 0.5 mg/kg/day,10 and oral cyclo-sporine 3.5–4.5 mg/kg/day11 with or without methotrexate.Methotrexate is more effective on nail matrix lesion, whilecyclosporine does so on nail bed involvement.12

Biologic agents, adalimumab,13 etanercept,14 and alefa-cept15 have been also found to be useful in nail psoriasis whenused for the treatment of psoriasis.

Most of the above drugs improve and evenmake the lesionsto disappear but long-term follow-up is lacking in themajorityof the studies.

In our series of 7 cases (5 pitting, 1 dystrophy, and 1 whitenail plates), lesions of all nails cleared and all nails remain freefrom the psoriasis till the end of the study. Thosewho relapsed(1 patient) went into remission on continuing the APT forpsoriasis.

Nail changes in psoriasis are supposed to be due toactivated T lymphocyte cells, which secrete cytokines whichis supposed to be responsible for nail changes. Azathioprine isimmunosuppressive which acts on activated lymphocytes,which reduce or stop cytokines secretion leading to correctionof nail changes.

The effect of methotrexate on nails is short lived as also onpsoriasis lasting up to 94 days or so only and relapses arefrequent with or without relapse of psoriasis, where the effectof APT is prolonged and long lasting even up to 79–93 months.With methotrexate, the response is less pronounced ascompared to APT.

The number of cases having nail changes is very less, whichis a limitation to this study.

5. Conclusions

Azathioprinepulse therapy regimen is able to put psoriatic nailchanges into prolonged remission.

Conflicts of interest

The author has none to declare.

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