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ORIGINAL ARTICLE
Year : 2017  |  Volume : 18  |  Issue : 1  |  Page : 31-35

The study of clinical outcome of systemic methotrexate uses in moderate to severe childhood psoriasis


1 Department of Dermatology, Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Uttar Pradesh, India
2 Department of DVL, Muzaffarnagar Medical College, Muzaffarnagar, Uttar Pradesh, India
3 Department of Pathology, Muzaffarnagar Medical College, Muzaffarnagar, Uttar Pradesh, India

Date of Web Publication12-Dec-2016

Correspondence Address:
Tarang Goyal
Department of Dermatology, Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2319-7250.195570

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  Abstract 


Background: Currently, very few studies exist regarding the use of systemic methotrexate (MTX) in childhood psoriasis.
Aim: The aim is to study the effect of systemic MTX with respect to overall efficacy and safety in varied spectrum of severe childhood psoriasis patients and to assess the degree of improvement objectively by measuring psoriasis area severity index (PASI) at each visit.
Materials and Methods: All patients <18 years of age having PASI >10, not responding to topical therapy and without having any contraindication to systemic MTX use were included in the study done during a period of two years. MTX was prescribed orally at a dose of 0.2–0.4 mg/kg/week and folic acid on daily basis except on the day of MTX to all the patients. Both clinical and laboratory follow-ups were done weekly for the first 2 weeks and then at 15 days interval for 1 month and monthly after that for measuring PASI and to rule out any side effects of MTX. After 75% improvement in PASI score the dose was decreased at rate of 2.5 mg/week and stopped after complete resolution of the lesions.
Results: Out of nine cases (M/F - 6/3), quickest response to MTX was seen in pustular psoriasis (4.5 weeks) and one case of plaque psoriasis (5 weeks) and slowest response was seen in rupoid variant (13 weeks). Mean duration to achieve 50% and 75% improvement in PASI overall were 4.6 ± 2.46 weeks and 7.6 ± 3.36 weeks, respectively. The mean cumulative dose of MTX in all cases was 231.1 ± 176.1 mg without any major side effects.
Conclusion: MTX is a safe therapeutic option in severe refractory cases of childhood psoriasis if used with proper monitoring and follow-up.

Keywords: Childhood psoriasis, methotrexate, pustular psoriasis, rupoid psoriasis


How to cite this article:
Goyal T, Pradhan S, Varshney A. The study of clinical outcome of systemic methotrexate uses in moderate to severe childhood psoriasis. Indian J Paediatr Dermatol 2017;18:31-5

How to cite this URL:
Goyal T, Pradhan S, Varshney A. The study of clinical outcome of systemic methotrexate uses in moderate to severe childhood psoriasis. Indian J Paediatr Dermatol [serial online] 2017 [cited 2019 Aug 22];18:31-5. Available from: http://www.ijpd.in/text.asp?2017/18/1/31/195570




  Introduction Top


Psoriasis is a chronic, inflammatory condition of the skin having prevalence rates between 1% and 3% in the general population.[1],[2] Every year approximately 20,000 children younger than 10 years of age are diagnosed with psoriasis, with an overall prevalence of pediatric psoriasis estimated at 1–2%.[3] It significantly affects the quality of life of children and adds great psychological distress.[4],[5]

There is varied spectrum of childhood psoriasis-like guttate, plaque, intertriginous variants to severe forms such as pustular and erythrodermic psoriasis described in the literature. Various management options such as topical treatments, photo (chemo) therapy, conventional systemic treatments, and biologics are available for treatment of psoriasis. Although most of the childhood psoriasis patients can be managed with topical therapy alone those presenting with severe disease and not responding to topical need systemic treatment. Among systemic treatment modalities methotrexate (MTX) is regarded as the therapy of choice and has been used in the treatment of childhood psoriasis by various workers.[6],[7],[8]


  Materials and Methods Top


All the patients <18 years of age with severe psoriasis not responding to topical therapy, with psoriasis area severity index (PASI) >10 and having no contraindication to systemic MTX use were included in the study done during a period of two years. Those children with active infection and having any other contraindication to MTX were excluded from the study. Diagnosis of various patterns of psoriasis was made clinically and was confirmed by histopathology. Detail demographic characteristics, duration of disease, body surface area involved, and morphological type of psoriasis were recorded [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Those patients fulfilling the inclusion criteria were prescribed systemic MTX. MTX was administered orally at a dose of 0.2–0.4 mg/kg/week and folic acid was prescribed on a daily basis except on the day of MTX intake to ameliorate side effects and toxicity of MTX. The response to MTX was measured objectively by recording the value of PASI in each visit. The treatment was continued till 75% improvement in PASI and after that dose was decreased at a rate of 2.5 mg/week and stopped after complete cure of disease. Those patients who showed an increase in PASI by 50% of the last dose of MTX after complete stoppage of therapy were considered to have relapse and were restarted with MTX. Response to therapy was graded as good (50–75% decrease in PASI) and excellent (>75% decrease). The patients were followed up weekly for the first 2 weeks and then at 15 days interval for 1 month and monthly after that for measuring improvement in PASI and to rule out any side effects of MTX clinically and by laboratory monitoring. Baseline laboratory investigations such as complete blood count, liver function tests, renal function tests, chest X-ray, serological tests for hepatitis B and HIV was carried out in all cases before the commencement of systemic MTX therapy as well as in follow-up visits. An appropriate Institutional Review Board had approved the project before starting the study and informed consent was appropriately obtained from parents of the patients before enrolling them for the study.
Figure 1: The thick crusted scales of rupoid psoriasis in a young boy

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Figure 2: Erythrodermic psoriasis variant in a young boy

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Figure 3: Plaque psoriasis not responding to topical treatment in a young boy

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Figure 4: A very severe case of pustular psoriasis in a young boy

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  Results Top


Totally 9 patients were included in the study within 2 years of the study of which 6 were male and 3 were female [Table 1]. Mean age was 12.78 ± 1.9 years. The mean duration of onset disease was 7.2 ± 3.7 months. Of 9, 4 had chronic plaque psoriasis, 1 had erythrodermic psoriasis, whereas rupoid and pustular psoriasis constituted two patients each. Mean BSA involvement and mean baseline PASI were 64.0 ± 1.71% and 29.7 ± 9.5, respectively. All patients responded dramatically to oral MTX except the patients of rupoid psoriasis who took longer time to achieve 75% improvement in PASI. The mean duration required to achieve 50% and 75% improvement in PASI overall were 4.6 ± 2.46 weeks and 7.6 ± 3.36 weeks, respectively. The total duration of treatment to achieve complete clearance of disease was 8.8 ± 3.83 months. Out of nine patients, six patients are continuing 2.5 mg of MTX per week now and rest three cases of pustular, erythrodermic and chronic plaque psoriasis are off from the drug since 3, 5, and 6 months, respectively and are being followed up. The total cumulative dose of MTX in all cases to till present is 231.1 ± 176.1 mg [Table 2] and [Table 3]. No major side effects and derangement in laboratory parameters were noted in any patients except nausea and vomiting in two cases. Scalp involvement was found in cases of rupoid and chronic plaque psoriasis. Nail examination revealed nail plate thinning and few pits in two cases.
Table 1: Demographic details of the patients

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Table 2: The details of patients with respect to disease type, severity, and methotrexate use

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Table 3: The psoriasis area severity index scoring and methotrexate response

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  Discussion Top


Psoriasis in children in generally managed with topical treatments, but systemic treatment is required in these patients with severe plaque psoriasis and life-threatening variants such as pustular, rupoid, and erythrodermic psoriasis. Childhood psoriasis adds significant psychosocial morbidity. There are many reports of childhood psoriasis being managed with drugs such as ciclosporin, retinoids, MTX, and biologicals. Recently, in a few studies by Collin et al.,[7] Kaur et al.,[8] systemic MTX has been proved to be an effective agent in managing childhood psoriasis.

MTX inhibits the enzymes dihydrofolate reductase and thymidylate synthase, as well as other enzymes involved in de novo purine synthesis. In this way, they deplete the intracellular reserve of fully reduced folates, and thus affect transmethylation reactions inhibition of thymidylate synthesis is the most important effect exerted by MTX, which results in DNA synthesis, thus inhibiting replication and function of T and B lymphocytes also interferes with epidermal cell kinetics.[9] In addition, MTX decreases DNA synthesis and induces apoptosis in keratinocytes.[10],[11] MTX acts by various mechanisms in psoriasis mostly target the immune system, i.e. aberrant T-cell response.[12] It impairs complement C5a-induced skin response and leukotriene B4-induced intraepidermal penetration of granulocytes.[13] Recently, it has been found that MTX significantly reduces serum levels of interleukin-22, a cytokine that promotes keratinocyte proliferation and dermal inflammation in psoriasis.[14] MTX also acts through a reduction in the mRNA levels of peroxisome proliferator-activated receptor b/δ, a member of the nuclear hormone receptor superfamily that contributes to psoriasis pathogenesis.[15] Also by inhibiting 5-aminoimidazole-4 carboxamide ribonucleoside transformylase, MTX induces the release of adenosine, which inhibits generation of oxygen free radicals by polymorphonuclear cells (PMNs), adhesion of PMNs, macrophage-induced modulation of tumor necrosis factor-α, and proliferation of lymphocytes, thereby playing a role of anti-inflammatory and immune modulatory agent in psoriasis.[16]

Currently, there are no guidelines for use of MTX in childhood psoriasis although it has been extensively studied in the case of adults. Knowing all the adverse effects, it should be always used as a reserve drug in psoriasis not responding to topical treatments and severe form of psoriasis such as pustular, erythrodermic variants as well as recalcitrant chronic plaque psoriasis. In a few studies conducted on efficacy and safety of systemic MTX in childhood psoriasis, no side effects were observed, and it was proved to be a safer drug if monitored properly. However, the side effects such as bone marrow suppression, liver fibrosis could not be underestimated in case of long-term use of MTX and it should be always used to control the disease rather than a cure option and should be stopped after achieving 75% improvement in PASI and to be restarted in case of flare up of disease as psoriasis itself decreases in severity in summer and flares up in winter.

Although there are other drugs such as retinoids, cyclosporine, hydroxyurea, biologicals, and PUVA therapy available safety profile, long-term use and cost are constraints to use them in childhood psoriasis.[17] Retinoids have an effect on bone growth, cyclosporine being a reno-toxic drug could not be used for long-term.[18],[19] The experience of hydroxyurea and biological is limited.[20],[21] Hence, larger number of studies are required to weigh the risk-benefit ratio of use of such drugs in case of children having psoriasis.

In our study also the response to systemic MTX was dramatic, and safety profile was good without any major side effects. Most of the patients achieved clearance in 8.8 months, and the mean duration required to achieve 50% and 75% improvement in PASI overall were 4.6 ± 2.46 weeks and7.6 ± 3.36 months respectively with very few gastrointestinal (GI) side effects.

Except in the case of rupoid psoriasis, improvement was quick in all cases. In two cases MTX has been stopped, and they are now in follow-up and in rest 5 cases are in 2.5 mg/week of MTX along with folic acid 5 mg. Hence, we conclude that systemic MTX can be considered as a safer treatment option in severe refractory cases of childhood psoriasis if proper monitoring and follow-up is done.

Limitation

However, limitations of our study were small sample size, absence of investigations to rule out liver toxicities III procollagen amino-terminal propeptide level and liver biopsy


  Conclusion Top


MTX is a safe therapeutic option in severe refractory cases of childhood psoriasis and can be used as a safe option with mean duration required to achieve 50% and 75% improvement in PASI overall were 4.6 ± 2.46 weeks and 7.6 ± 3.36 months with very few GI side effects.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Prevalence and treatment of psoriasis in the United Kingdom: A population-based study. Arch Dermatol 2005;141:1537-41.  Back to cited text no. 1
    
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Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc 2004;9:136-9.  Back to cited text no. 2
    
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Augustin M, Glaeske G, Radtke MA, Christophers E, Reich K, Schäfer I. Epidemiology and comorbidity of psoriasis in children. Br J Dermatol 2010;162:633-6.  Back to cited text no. 3
    
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Rasmussen JE. Psoriasis in children. Dermatol Clin 1986;4:99-106.  Back to cited text no. 4
    
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de Jager ME, de Jong EM, van de Kerkhof PC, Seyger MM. Efficacy and safety of treatments for childhood psoriasis: A systematic literature review. J Am Acad Dermatol 2010;62:1013-30.  Back to cited text no. 6
    
7.
Collin B, Vani A, Ogboli M, Moss C. Methotrexate treatment in 13 children with severe plaque psoriasis. Clin Exp Dermatol 2009;34:295-8.  Back to cited text no. 7
    
8.
Kaur I, Dogra S, De D, Kanwar AJ. Systemic methotrexate treatment in childhood psoriasis: Further experience in 24 children from India. Pediatr Dermatol 2008;25:184-8.  Back to cited text no. 8
    
9.
Heenen M, Laporte M, Noel JC, de Graef C. Methotrexate induces apoptotic cell death in human keratinocytes. Arch Dermatol Res 1998;290:240-5.  Back to cited text no. 9
    
10.
Ranganathan P, McLeod HL. Methotrexate pharmacogenetics: The first step toward individualized therapy in rheumatoid arthritis. Arthritis Rheum 2006;54:1366-77.  Back to cited text no. 10
    
11.
Saporito FC, Menter MA. Methotrexate and psoriasis in the era of new biologic agents. J Am Acad Dermatol 2004;50:301-9.  Back to cited text no. 11
    
12.
Jeffes EW 3rd, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: Differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate. J Invest Dermatol 1995;104:183-8.  Back to cited text no. 12
    
13.
Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993;92:2675-82.  Back to cited text no. 13
    
14.
Meephansan J, Ruchusatsawat K, Sindhupak W, Thorner PS, Wongpiyabovorn J. Effect of methotrexate on serum levels of IL-22 in patients with psoriasis. Eur J Dermatol 2011;21:501-4.  Back to cited text no. 14
    
15.
El Eishi N, Hegazy R, Abou Zeid O, Shaker O. Peroxisome proliferator receptor (PPAR) β/δ in psoriatic patients before and after two conventional therapeutic modalities: Methotrexate and PUVA. Eur J Dermatol 2011;21:691-5.  Back to cited text no. 15
    
16.
Cronstein B. How does methotrexate suppress inflammation? Clin Exp Rheumatol 2010;28 5 Suppl 61:S21-3.  Back to cited text no. 16
    
17.
Mahé E, Bodemer C, Pruszkowski A, Teillac-Hamel D, de Prost Y. Cyclosporine in childhood psoriasis. Arch Dermatol 2001;137:1532-3.  Back to cited text no. 17
    
18.
Burden AD. Management of psoriasis in childhood. Clin Exp Dermatol 1999;24:341-5.  Back to cited text no. 18
    
19.
Cooney GF, Habucky K, Hoppu K. Cyclosporin pharmacokinetics in paediatric transplant recipients. Clin Pharmacokinet 1997;32:481-95.  Back to cited text no. 19
    
20.
Juanqin G, Zhiqiang C, Zijia H. Evaluation of the effectiveness of childhood generalized pustular psoriasis treatment in 30 cases. Pediatr Dermatol 1998;15:144-6.  Back to cited text no. 20
    
21.
Hawrot AC, Metry DW, Theos AJ, Levy ML. Etanercept for psoriasis in the pediatric population: Experience in nine patients. Pediatr Dermatol 2006;23:67-71.  Back to cited text no. 21
    


    Figures

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

  [Table 1], [Table 2], [Table 3]



 

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