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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 643-649

Intralesional methotrexate vs intralesional 5-fluorouracil in the treatment of localized plaque psoriasis: a comparative clinical and dermoscopic study


Department of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

Date of Submission25-Sep-2019
Date of Decision25-Sep-2019
Date of Acceptance14-Nov-2019
Date of Web Publication10-Feb-2020

Correspondence Address:
MBBCh Hagar O.I Attia
Department of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, 11517 Al-Abbaseya, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_76_19

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  Abstract 


Background Multiple treatment options are introduced in the treatment of localized plaque psoriasis. However, long-term remission and total clearance can only be achieved in few patients.
Aim The aim was to compare the efficacy and safety of intralesional methotrexate (MTX) and 5-fluorouracil (5-FU) in the treatment of localized plaque psoriasis both clinically and dermoscopically.
Patients and methods Twenty patients with localized plaque psoriasis were enrolled in this study. Each patient was treated by split-body therapy where one psoriatic plaque was treated with intralesional MTX (25 mg/ml) and another plaque with intralesional 5-FU (50 mg/ml). A total of four injections were given at weekly intervals. The target lesions were clinically and dermoscopically evaluated at baseline, 1 week, 1 month, and 2 months after treatment.
Results At the end of the study, the response rate was 85% on the MTX side and 95% on the 5-FU side. There was no significant difference between both sides regarding clinical response or side effects. Overall, there was a significant correlation between clinical response and the percentage of dermoscopic red dots. The recurrence rate was 15% on both sides. Notably, all recurring lesions on both sides were characterized by lack of clinicodermoscopic correlation.
Conclusion Intralesional MTX and 5-FU are found to be an effective therapeutic modality in the treatment of localized plaque psoriasis with no significant side effects. Dermoscopy might be a useful tool for evaluating the response of psoriatic lesions to treatment and for early detection of recurrence of psoriasis.

Keywords: 5-fluorouracil, intralesional, localized, methotrexate, plaque psoriasis


How to cite this article:
Attia HO, Kawy FA, Hafiz HS. Intralesional methotrexate vs intralesional 5-fluorouracil in the treatment of localized plaque psoriasis: a comparative clinical and dermoscopic study. Sci J Al-Azhar Med Fac Girls 2019;3:643-9

How to cite this URL:
Attia HO, Kawy FA, Hafiz HS. Intralesional methotrexate vs intralesional 5-fluorouracil in the treatment of localized plaque psoriasis: a comparative clinical and dermoscopic study. Sci J Al-Azhar Med Fac Girls [serial online] 2019 [cited 2020 Feb 29];3:643-9. Available from: http://www.sjamf.eg.net/text.asp?2019/3/3/643/278042




  Introduction Top


Psoriasis is a common chronic inflammatory immune-mediated disease [1] with different clinical types, the most common of which is chronic plaque psoriasis [2]. Dermoscopy of plaque psoriasis typically shows a characteristic pattern consisting of diffuse white scales and symmetrically and regularly distributed dotted vessels on a light or dull red background [3].

Topical therapy is the first line of treatment of localized plaque psoriasis, but poor adherence of patients with psoriasis to topical treatment was reported [4] as topical treatment may be greasy and time-consuming [5]. Intralesional injection may be used to treat localized lesions of psoriasis as it provides a higher concentration of the drug at the site of injection, while avoiding the known adverse effects of systemic therapies. Also, it overcomes the problem of poor drug penetration encountered with topical treatment [6].

Methotrexate (MTX) and 5-fluorouracil (5-FU) are antimetabolites which act through the inhibition of dihydrofolate reductase and thymidylate synthase enzymes, respectively, block DNA synthesis, and therefore decrease epidermal proliferation. So, MTX and 5-FU can be used for the treatment of many dermatological disorders characterized by a high mitotic rate such as psoriasis [7],[8]. The aim of this study was to compare the efficacy and safety of intralesional MTX and 5-FU in the treatment of localized plaque psoriasis both clinically and dermoscopically.


  Patients and methods Top


This prospective, randomized, split-body comparative study included 20 adult patients with localized plaque psoriasis (body surface area ≤10%) and it was approved by the Research Ethics Committee of the Faculty of Medicine for Girls, Al-Azhar University. Pregnant and lactating women, immunocompromised patients, and patients with chronic hepatic, renal, pulmonary, or hematological disorders were excluded from the study. Patients with a history of hypersensitivity to MTX or 5-FU and patients who received any systemic anti-psoriatic medications within 8 weeks before the study were also excluded. Informed written consent was obtained from all patients before participation in this study. A detailed history and general examination was conducted in each case. Complete blood count and liver function tests were done for each patient at baseline and at 2 months after treatment.

Taking aseptic precautions, one psoriatic plaque was treated with intralesional MTX (25 mg/ml) at a dosage of 0.1 ml/cm2 and another plaque on the other side was treated with intralesional 5-FU (50 mg/ml) at a dosage of 0.1 ml/cm2. Patients have taken their sessions weekly for 4 weeks. They were followed up at 1 week, 1 month, and 2 months after treatment. Clinical and dermoscopic images were captured from the target lesions at baseline, 1 week, 1 month, and 2 months after treatment. Clinical assessment was done using the total sign score (TSS), also known as psoriasis severity index, which is the summation of erythema, induration, and scale points and ranges between 0 and 12, where each point was given a grade (0 none, 1 mild, 2 moderate, 3 severe, and 4 very severe) [5],[9]. The response to treatment was graded as shown in [Table 1].
Table 1 Grades of improvement evaluated by total sign score psoriasis severity index score [9]

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Dermoscopic images were evaluated by two blinded dermatologists for the percentage of dermoscopic red dots and presence or absence of white scales. Patients were also evaluated for side effects including pain, erosions, necrosis, and hyperpigmentation.

Recurrence area was evaluated at 2 months after treatment in relation to the baseline lesion using a 10-point scale: grade 0 (no recurrence), grade 1 (1–10%), grade 2 (11–20%), grade 3 (21–30%), grade 4 (31–40%), grade 5 (41–50%), grade 6 (51–60%), grade 7 (61–70%), grade 8 (71–80%), and grade 9 (81–100%) [5]. Patient’s satisfaction was measured 2 months after the last treatment.

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 23; IBM Corp., Armonk, New York, USA).The quantitative data were presented as mean, SD, and ranges when parametric and median with interquartile range when nonparametric. Also, qualitative variables were presented as number and percentages.

Comparison between groups regarding qualitative data was done by using the χ2-test when the expected count in any cell is found to be less than 5. Comparison between two independent groups with quantitative data and parametric distribution was done using independent t-test while with nonparametric data were done using the Mann–Whitney test. The comparison between two related groups with quantitative data and nonparametric data were done by using the Wilcoxon signed rank test. Comparison between more than two related groups with quantitative data and parametric distribution was done using repeated measures analysis of variance while with nonparametric data were done by using the Friedman test. Comparison between more than two independent groups with quantitative data and nonparametric data was done using the Kruskal–Wallis test.

Spearman correlation coefficients were used to assess the correlation between two quantitative parameters in the same group. P values less than 0.05 were considered statistically significant. P values less than 0.01 were considered statistically highly significant.


  Results Top


This study included 20 patients with localized plaque psoriasis. There was a statistically highly significant reduction in TSS on MTX and 5-FU sides at 1 week, 1 month, and 2 months after treatment (P=0.000), with statistically insignificant difference between both sides ([Figure 1]).
Figure 1 Total sign score on methotrexate and 5-fluorouracil sides.

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At the end of the study, the response rate was 85% on the MTX side, while it was 95% on the 5-FU side. The grade of improvement evaluated by TSS on both sides is shown in [Table 2]. There was no statistically significant difference between both sides regarding the grade of improvement. There was no statistically significant correlation between the grade of improvement on both sides and clinicodermographic data of all patients (age, sex, duration of psoriasis, family history of psoriasis, pruritis, and smoking).
Table 2 Grade of improvement on methotrexate and 5-fluorouracil sides

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No systemic adverse events were observed in all patients on MTX and 5-FU sides. Only local side effects such as pain, hyperpigmentation, erosions, and crustations were observed on both sides with no statistically significant difference between them except for erosions and crustations which were more on the 5-FU side (P=0.022), while necrosis occurred only in three (15%) patients on the 5-FU side. Three (15%) patients experienced recurrence of psoriasis on the MTX side; all of them were of grade 9. Also, three (15%) patients experienced recurrence of psoriasis on the 5-FU side; among those three patients, one patient was of grade 5, one patient was of grade 8, and one patient was of grade 9. There was no statistically significant difference between both sides regarding recurrence or the grade of recurrence. There was statistically significant difference between MTX and 5-FU sides regarding patient satisfaction, where patient satisfaction was higher on the MTX side (P=0.046).

[Figure 2] shows statistically highly significant reduction in the percentage of dermoscopic red dots on MTX and 5-FU sides at 1 week, 1 month, and 2 months after treatment (P=0.000), with statistically insignificant difference between both sides.
Figure 2 Percentage of dermoscopic red dots on methotrexate and 5-fluorouracil sides.

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[Table 3] shows statistically highly significant positive clinicodermoscopic correlation on the MTX side at 1 month and 2 months after treatment (r=+0.758 and +0.916, respectively, P=0.000). [Table 4] shows statistically highly significant positive clinicodermoscopic correlation on the 5-FU side at 2 months after treatment (r=+0.824, P=0.000).
Table 3 Correlation between total sign score and percentage of dermoscopic red dots on the methotrexate side

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Table 4 Correlation between total sign score and percentage of dermoscopic red dots on the 5-fluorouracil side

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[Figure 3] and [Figure 4] show statistically highly significant reduction in the percentage of dermoscopic red dots at 1 week, 1 month, and 2 months after treatment in cases where there was no recurrence on MTX and 5-FU sides, respectively (P<0.001), while in cases of recurrence on both sides, there was no statistically significant reduction in the percentage of dermoscopic red dots at 1 week, 1 month, and 2 months after treatment. [Figure 5] and [Figure 6] show examples of response to treatment on MTX and 5-FU sides
Figure 3 Change in the percentage of dermoscopic red dots in cases with and without recurrence on the methotrexate side.

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Figure 4 Change in the percentage of dermoscopic red dots in cases with and without recurrence on the 5-fluorouracil side.

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Figure 5 Clearance of the psoriatic plaque over the right elbow after intralesional methotrexate. (a) Clinical photograph before treatment (total sign score=8); (b) clinical photograph 2 months after treatment showing a significant decrease in total sign score which became 0; (c) dermoscopic photograph before treatment (the percentage of red dots=100%); (d) dermoscopic photograph 2 months after treatment showing significant decrease in the percentage of red dots which became 0% with disappearance of white scales.

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Figure 6 Clearance of the psoriatic plaque over the right elbow after intralesional 5-fluorouracil. (a) Clinical photograph before treatment (total sign score =7); (b) clinical photograph 2 months after treatment showing significant decrease in total sign score which became 0; (c) dermoscopic photograph before treatment (the percentage of red dots=100%); (d) dermoscopic photograph 2 months after treatment showing significant decrease in the percentage of red dots which became 0% with disappearance of white scales.

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  Discussion Top


Psoriasis is a chronic, autoimmune, inflammatory papulosquamous disorder, the treatment of which remains challenging [2]. MTX acts through competitive inhibition of the enzyme dihydrofolate reductase leading to the inhibition of DNA and RNA synthesis. It is considered a potential treatment option for rapidly growing cells and has an anti-inflammatory effect through the inhibition of the polyamine pathway in autoimmune diseases such as psoriasis [10]. 5-FU is an antimetabolite that inhibits thymidylate synthase enzyme leading to inhibition of DNA synthesis as well as RNA processing and therefore decreases epidermal proliferation as in the case of psoriasis [9]. The advantage of intralesional MTX and 5-FU is that it allows higher drug concentration in the lesion for longer duration in comparison to topical treatment, while avoiding the systemic adverse effects of these toxic drugs [9],[11].

At the end of the study, the response rate was 85% on the MTX side; three (15%) patients showed clearance, nine (45%) patients showed excellent improvement, five (25%) patients showed moderate improvement, and three (15%) patients did not respond to treatment. The results in our study were better than the results of the study of Chakravdhanula et al. [11] where the monotherapy group which received intralesional MTX showed only improvement in the range of 35–40% relative to baseline PASI. Our results are comparable to the results of the combinational treatment group (which received intralesional MTX and platelet-rich plasma) in their study, where all patients achieved PASI 50, 62.5% achieved PASI 75, and 2.5% achieved PASI 90 although we injected only intralesional MTX in our study.

The response rate was 95% on the 5-FU side; four (20%) patients showed clearance, five (25%) patients showed excellent improvement, nine (45%) patients showed moderate improvement, one (5%) patient showed mild improvement, and one (5%) patient did not respond to treatment. Our findings agree with the study of Mahajan and Singla [9] and Pearlman et al. [12] where the response rate was 87.5 and 82%, respectively. Similar results were observed in the study of Taheri et al. [13] which reported 70–90% improvement in 61% patients and greater than 90% improvement in 33.3% patients and the study of Lowe et al. [14] where 60% of the plaques had definite improvement.

In our study, there were only local side effects on both sides such as pain, hyperpigmentation, erosions, and crustations. Our results are similar to previous studies related to intralesional MTX and 5-FU in which no systemic adverse events were observed [9],[11],[12],[13],[14]. On the 5-FU side, necrosis occurred only in three (15%) patients and healed gradually during the follow-up period. Most of the patients remained in remission or improved further during the follow-up period. Only three patients experienced recurrence on both sides.

The clinicodermoscopic correlation in our study was significant during the follow-up period. Our findings suggest that dermoscopy might enable an early detection of recurrence of psoriasis, since all recurring lesions in our study were characterized by lack of clinicodermoscopic correlation. Specifically, although clinically there was a decrease in TSS on both sides, the percentage of dermoscopic red dots remained constant on the MTX side at 1 week, 1 month, and 2 months after treatment, while on the 5-FU side, the percentage of dermoscopic red dots remained constant at 1 week after treatment and was slightly reduced at 1 month and 2 months after treatment (the reduction in the percentage of dermoscopic red dots on the 5-FU side at 1 month and 2 months after treatment was out of proportion to the reduction in TSS).


  Conclusion Top


This study demonstrated that intralesional MTX and 5-FU are found to be a promising treatment for localized plaque psoriasis with no significant difference between them and no significant side effects. Also, dermoscopy can be a useful tool for evaluating the response of psoriatic patients to treatment and for early detection of recurrence of psoriasis.

Recommendations

Further studies with increasing number of sessions and combination with other lines of treatment of localized plaque psoriasis such as topical corticosteroid are recommended to give more satisfactory results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kim WB, Jerome D, Yeung J. Diagnosis and management of psoriasis. Can Fam Physician 2017; 63:278–285.  Back to cited text no. 2
    
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Lallas A, Kyrgidis A, Tzellos TG, Apalla Z, Karakyriou E, Karatolias A et al. Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol 2012; 166:1198–1205.  Back to cited text no. 3
    
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Kamel AM, Abdelghani R. Carboxytherapy for treatment of localized chronic plaque psoriasis: clinical and histopathologic evaluation. J Cosmet Dermatol 2018; 17:527–532.  Back to cited text no. 5
    
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Wang TS, Tsai TF. Intralesional therapy for psoriasis. J Dermatolog Treat 2013; 24:340–347.  Back to cited text no. 6
    
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Ceilley RI. Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders. J Dermatolog Treat 2012; 23:83–89.  Back to cited text no. 8
    
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Mahajan BB, Singla M. Evaluation of intralesional 5% 5-fluorouracil in resistant localized plaque psoriasis. Indian Dermatol Online J 2014; 5:287–290.  Back to cited text no. 9
    
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Vena GA, Cassano N, Iannone F. Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis. Ther Clin Risk Manag 2018; 14:105–116.  Back to cited text no. 10
    
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Chakravdhanula U, Anbarasu K, Verma VK, Beevi SS. Clinical efficacy of platelet rich plasma in combination with methotrexate in chronic plaque psoriatic patients. Dermatol Ther 2016; 29:446–450.  Back to cited text no. 11
    
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Pearlman DL, Youngberg B, Engelhard C. Weekly psoriasis therapy using intralesional fluorouracil. J Am Acad Dermatol 1987; 17:78–82.  Back to cited text no. 12
    
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Taheri S, Asilian A, Faghihi G. Efficacy of 5-fluorouracil plus epinephrine, pulsed dye laser and betamethasone on the improvement of psoriatic plaques (a comparative study). Iran J Dermatol 2009; 12:36–41.  Back to cited text no. 13
    
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Lowe NJ, Nychay S, Orenberg EK, Korey A. Intradermal fluorouracil and epinephrine injectable gel for treatment of psoriatic plaques. Arch Dermatol 1995; 131:1340–1341.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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