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ORIGINAL ARTICLE
Year : 2020  |  Volume : 21  |  Issue : 2  |  Page : 98-104

Cyclosporine a in recalcitrant pediatric dermatoses – A retrospective analysis of thirty children


1 Department of Skin and VD, Hi-Tech Medical College and Hospital, Utkal University, Bhubaneswar, Odisha, India
2 Department of Skin and VD, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
3 Department of Paediatrics, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India

Date of Submission30-Sep-2019
Date of Decision23-Oct-2019
Date of Acceptance10-Feb-2020
Date of Web Publication01-Apr-2020

Correspondence Address:
Maitreyee Panda
Department of Skin and VD, IMS and SUM Hospital, SOA University, Bhubaneswar - 751 003, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_97_19

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  Abstract 


Background: The therapeutic use of cyclosporine is gradually extending to various dermatoses including both in adults and children. There are meager studies from India supporting its safe use in pediatric dermatoses. Aims and Objectives: The aim is to study the safety and efficacy profile of children treated with cyclosporine for recalcitrant dermatoses. Materials and Methods: A retrospective analysis of the case files of children below 18 years of age where cyclosporine A (CsA) was used within the past 5 years was done. Results: A total of thirty cases were studied. The CsA dose used in our patients ranged from 3 to 4 mg/kg/day for a time period varying from 4 to 24 weeks. A good to excellent response was seen in 23 (76.66%) cases. Few children developed side effects mostly reversible with dose modification. Conclusion: Cyclosporine within the therapeutic range can be used safely in recalcitrant pediatric dermatoses.

Keywords: Alopecia areata, atopic dermatitis, cyclosporine A, pediatric dermatosis, psoriasis


How to cite this article:
Patro N, Panda M, Dash M. Cyclosporine a in recalcitrant pediatric dermatoses – A retrospective analysis of thirty children. Indian J Paediatr Dermatol 2020;21:98-104

How to cite this URL:
Patro N, Panda M, Dash M. Cyclosporine a in recalcitrant pediatric dermatoses – A retrospective analysis of thirty children. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Nov 24];21:98-104. Available from: https://www.ijpd.in/text.asp?2020/21/2/98/281738




  Introduction Top


Cyclosporine A (CsA), an immunosuppressive agent, has been widely accepted for the treatment of various dermatological conditions in adults, notably being in psoriasis, atopic dermatitis, graft versus host disease, chronic idiopathic urticaria, etc. Its efficacy and safety profile in children is also being studied over the years in cases of recalcitrant atopic dermatitis, psoriasis, alopecia areata, and chronic idiopathic urticaria. The most common side effects encountered with CsA use are nephrotoxicity and hypertension. The risk of these side effects (though they are dose dependent) and toxicities associated with CsA therapy still continues to hinder its wide consideration in pediatric dermatoses.

The aim of this study was to summarize our experience with CsA use in recalcitrant pediatric dermatoses patients retrospectively on grounds of efficacy and safety profile.


  Materials and Methods Top


Medical records of patients attending the dermatology outpatient department between January 2014 and December 2018 who were under 18 years of age and treated with oral CsA were retrospectively analyzed.

Patient's demographic data such as age, gender, family history, associated comorbidities, and other relevant data including treatment history, dose and duration of CsA therapy, response to treatment, side effects, and follow-up of up to 12 months post-CsA therapy were retrieved from the medical records. Along with general physical examination, routine baseline investigations included complete blood counts, blood pressure (BP) measurement, serum urea, creatinine, electrolytes, magnesium, lipid profile, and urinalysis as per the department protocol for CsA therapy initiation. Serum creatinine levels, full blood counts, and BP were assessed at each follow-up visit on monthly interval till continuation of CsA.

The assessment of treatment response was evaluated retrospectively from the patient's medical records according to the Psoriasis Area and Severity Index (PASI) scores in psoriasis patients, Three-Item Severity (TIS) score[1] in atopic dermatitis patients, and Physician Global Assessment scores in alopecia areata patients. The TIS score is a simplified modification of severity scoring of atopic dermatitis in atopic dermatitis and is the sum of the three clinical findings, i.e., erythema, edema, and excoriation, scored on a scale from 0 to 3, on the most representative lesion for each. The severity of atopic dermatitis in TIS scoring has been graded as mild (0–2), moderate (3–5), and severe (6–9). Institutional ethics committee approval was obtained prior to initiation of the study IMS/IEC/237-EC number.


  Results Top


A total of 30 case files with the diagnosis of atopic dermatitis (14 patients), psoriasis (11 patients), and alopecia areata (5 patients) were included in our study with the age ranging from 1 month to 14 years.

[Table 1],[Table 2],[Table 3] summarize the demographic characteristics, CsA dose and duration, course of the disease, and side effect profile for our study patients. The CsA dose ranged from 3 to 4 mg/kg/day and was continued for a time period varying from 4 to 24 weeks. In most of the patients, tapering was initiated at 4–8 weeks of therapy, and in one patient with generalized pustular psoriasis, the dose was decreased to twice weekly pulse dosing due to elevated creatinine levels.
Table 1: Overview of clinical, therapeutic, and outcome parameters of children with atopic dermatitis treated with cyclosporine A

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Table 2: Overview of clinical, therapeutic and outcome parameters of children with psoriasis treated with cyclosporine A

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Table 3: Overview of clinical, therapeutic, and outcome parameters of children with alopecia areata treated with cyclosporine A

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CsA therapy in atopic dermatitis showed complete remission in 9 (64.29%) patients and partial response [Figure 1] in 5 (35.71%). Complete remission in patients was described as TIS score decreasing to 0 within the therapeutic period. The response to CsA in psoriasis patients was recorded as PASI75 achieved in 7 cases at 8 weeks and in one case at 12 weeks. Total clearance of lesions was achieved in 2 cases at 8 weeks and 6 cases at 12 weeks of CsA therapy. One infant with plaque psoriasis [Figure 2]a and [Figure 2]b did not achieve PASI75 even at 12 weeks, and one patient with erythrodermic psoriasis [Figure 2]c and [Figure 2]d was lost to follow-up after 8 weeks while not yet achieved PASI75. Patients with alopecia areata [Figure 3] showed a 70%–90% improvement in hair regrowth at 12–16 weeks of therapy. One patient with erythrodermic psoriasis and one with alopecia areata were lost to follow-up after 8 and 12 weeks of CsA therapy, respectively.
Figure 1: (a) Atopic dermatitis presenting as dry scaly patches and facial erythema, (b) partial clearance post 4 weeks of cyclosporine A therapy

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Figure 2: (a) Extensive plaque psoriasis in an infant, (b) post 12 weeks of cyclosporine A therapy, (c) psoriatic erythroderma in a neonate, (d) post 8 weeks of cyclosporine A therapy

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Figure 3: (a) Extensive alopecia areata in a teenager, (b) post 8 weeks of cyclosporine A in combination therapy

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The most common side effects observed in our study were hypertrichosis (three cases), weight gain (two cases), nausea and pain abdomen (three cases), and elevated creatinine (one case).


  Discussion Top


Cyclosporine is an immunosuppressant which acts by inhibiting T-cell function and interleukin-2. There are no specific guidelines or consensus yet on CsA use in pediatric dermatosis, and all the data available are experience-based retrospective analysis, mostly in cases of atopic dermatitis and psoriasis. The broad and long-lasting experience in the safety and efficacy profile of CsA in adult dermatoses has led to its increasing use in children nowadays.

The dosage for CsA in children has been extrapolated from studies in adults. The dose used in our patients varied between 3 and 4 mg/kg/day for 4–24-week duration. Higher dosage as compared to adults is recommended in view of different pharmacokinetics of CsA in children (including intestinal absorption, distribution, metabolism, and up to four times increased clearance rates). However, doses higher than 5 mg/kg/day have not been warranted as it may be associated with increased toxicity.[2] Two different dosing regimens are being used in atopic dermatitis: low-dose (2–3 mg/kg/day) continuous therapy and high-dose (5–6 mg/kg/day) short-course therapy. Studies[3] supporting low-dose continuous therapy suggest that it helps decrease the risk of relapse in atopic dermatitis, whereas high-dose short-course therapy helps in achieving faster responses.[4],[5] Similarly, in childhood psoriasis, several small case series [2,6-14] have found effective results with equivalent doses as recommended in adults, except by Mahé et al.[15] where higher doses of 10 mg/kg/day were needed. Gradual tapering, lowest possible maintenance dose, shortest treatment period along with switch in therapy to alternate drugs are recommended while using CsA in childhood psoriasis.[2],[6],[13],[16]

The average time taken for maximum clinical response in our patients with chronic dermatoses such as atopic dermatitis, psoriasis, and alopecia areata was around 8–12 weeks which suggests a faster induction of clearance. Relapse of the disease was encountered in 17 patients [Table 4] in the 12 months posttherapy follow-up period, and it was well managed with either intermittent short courses of CsA and/or addition of other appropriate drugs. Our patients experienced an average of 6 months of disease-free period following CsA therapy, and those with relapses presented with lower disease severity. The faster onset of disease clearance and long remission period achieved with CsA therapy enables the child to resume normal academic and physical activities and helps improve the quality of life of both child and the parents.
Table 4: 1-year follow-up data of patients presenting with relapse

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The children presenting with extensive alopecia areata recalcitrant to systemic corticosteroid therapy showed 70%–90% hair regrowth within 12–16 weeks of CsA addition. As already been published,[17] the children presented with relapse on discontinuation, but could be managed with re-addition of low-dose/pulse-dose CsA.

It has been proposed that children can tolerate CsA better than adults as they have a higher CsA clearance rate and reduced absorption rate.[18] The common adverse effects of CsA such as hypertension and decreased renal function are dose related and can be reduced by avoiding doses more than 5 mg/kg/day and elevations in serum creatinine more than 30% of the baseline. No serious adverse effects were encountered in our patients apart from hypertrichosis, weight gain, and elevated creatinine, all of which were reversible on dose reduction or stoppage of the drug. Hence, in chronic dermatoses needing prolonged therapy such as atopic dermatitis, psoriasis, and alopecia areata, the side effect profile of CsA can be prevented or reversed by tapering or discontinuation of the drug after induction of disease clearance.

A PubMed search [Table 5] for literature regarding cyclosporine use in pediatric dermatoses showed only one study[2] from India. Various studies[2],[3],[4],[5],[16],[18],[19],[20],[21],[22],[23],[24] and case reports[7],[8],[9],[10],[11],[12],[13],[14] have described the use of CsA in atopic dermatitis and psoriasis affecting children. The dose of CsA varied mostly from 1 mg/kg to 5 mg/kg, and the duration of therapy ranged from 3 weeks to 3 years. Almost all of the studies documented results as a complete, good, and excellent response. Apart from few documenting renal dysfunction in the form of elevated creatinine levels, no major adverse effects were noted.
Table 5: Review of articles in PubMed for cyclosporine A therapy in pediatric dermatoses

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  Conclusion Top


Cyclosporine is emerging as a wonderful drug in many dermatological conditions in both adults and children. However, the associated side effects and risk factors (which are mostly theoretical) along with the cost factor limit its wide use. Accordingly, we suggest a tailored treatment approach taking into consideration of patient's age, severity of disease, and impact on quality of life. CsA should be considered if not otherwise contraindicated in severe recalcitrant disease for at least 8–12 weeks (if no side effects observed) before tapering or stopping for maximum results.

Limitation

Considering the retrospective nature of our study, limited follow-up period and restricted data available for analysis were some of the shortcomings.

Acknowledgment

We would like to acknowledge the assistance of Mr. Somadatta Das, Data Entry Operator, Central Research Laboratory, IMS and SUM Hospital, S “O” A University, Bhubaneswar, Odisha, for his contributions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Willemsen MG, van Valburg RW, Dirven-Meijer PC, Oranje AP, van der Wouden JC, Moed H. Determining the severity of atopic dermatitis in children presenting in general practice: An easy and fast method. Dermatol Res Pract 2009;2009:357046.  Back to cited text no. 1
    
2.
Dogra S, Mahajan R, Narang T, Handa S. Systemic cyclosporine treatment in severe childhood psoriasis: A retrospective chart review. J Dermatolog Treat 2017;28:18-20.  Back to cited text no. 2
    
3.
Sibbald C, Pope E, Ho N, Weinstein M. Retrospective review of relapse after systemic cyclosporine in children with atopic dermatitis. Pediatr Dermatol 2015;32:36-40.  Back to cited text no. 3
    
4.
Harper JI, Ahmed I, Barclay G, Lacour M, Hoeger P, Cork MJ, et al. Cyclosporin for severe childhood atopic dermatitis: Short course versus continuous therapy. Br J Dermatol 2000;142:52-8.  Back to cited text no. 4
    
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Kiliç SS, Hacimustafaoǧlu M, Celebi S, Karadeniz A, Ildirim I. Low dose cyclosporin A treatment in generalized pustular psoriasis. Pediatr Dermatol 2001;18:246-8.  Back to cited text no. 7
    
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Alli N, Güngör E, Karakayali G, Lenk N, Artüz F. The use of cyclosporin in a child with generalized pustular psoriasis. Br J Dermatol 1998;139:754-5.  Back to cited text no. 8
    
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Torchia D, Terranova M, Fabbri P. Photosensitive psoriasis in a vitiligo patient. J Dermatol 2006;33:880-3.  Back to cited text no. 9
    
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Xiao T, Li B, He CD, Chen HD. Juvenile generalized pustular psoriasis. J Dermatol 2007;34:573-6.  Back to cited text no. 10
    
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Kim HS, Kim GM, Kim SY. Two-stage therapy for childhood generalized pustular psoriasis: Low-dose cyclosporin for induction and maintenance with acitretin/narrowband ultraviolet B phototherapy. Pediatr Dermatol 2006;23:306-8.  Back to cited text no. 12
    
13.
Pereira TM, Vieira AP, Fernandes JC, Sousa-Basto A. Cyclosporin A treatment in severe childhood psoriasis. J Eur Acad Dermatol Venereol 2006;20:651-6.  Back to cited text no. 13
    
14.
Perrett CM, Ilchyshyn A, Berth-Jones J. Cyclosporin in childhood psoriasis. J Dermatolog Treat 2003;14:113-8.  Back to cited text no. 14
    
15.
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. 15
    
16.
Di Lernia V, Stingeni L, Boccaletti V, Calzavara Pinton PG, Guarneri C, Belloni Fortina A, et al. Effectiveness and safety of cyclosporine in pediatric plaque psoriasis: A multicentric retrospective analysis. J Dermatolog Treat 2016;27:395-8.  Back to cited text no. 16
    
17.
Patro N, Panda M, Patro S, Mohapatra M. Extensive childhood alopeacia areata responding to combination of oral cyclosporine and corticosteroid therapy – Clinical experience in four patients. Indian J Paediatr Dermatol 2018;19:269-71.  Back to cited text no. 17
  [Full text]  
18.
Yee GC, Lennon TP, Gmur DJ, Kennedy MS, Deeg HJ. Age-dependent cyclosporine: Pharmacokinetics in marrow transplant recipients. Clin Pharmacol Ther 1986;40:438-43.  Back to cited text no. 18
    
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Berth-Jones J, Finlay AY, Zaki I, Tan B, Goodyear H, Lewis-Jones S, et al. Cyclosporine in severe childhood atopic dermatitis: A multicenter study. J Am Acad Dermatol 1996;34:1016-21.  Back to cited text no. 19
    
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Zaki I, Emerson R, Allen BR. Treatment of severe atopic dermatitis in childhood with cyclosporin. Br J Dermatol 1996;135 Suppl 48:21-4.  Back to cited text no. 20
    
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Bunikowski R, Staab D, Kussebi F, Bräutigam M, Weidinger G, Renz H, et al. Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: Clinical and immunological effects. Pediatr Allergy Immunol 2001;12:216-23.  Back to cited text no. 21
    
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Haw S, Shin MK, Haw CR. The efficacy and safety of long-term oral cyclosporine treatment for patients with atopic dermatitis. Ann Dermatol 2010;22:9-15.  Back to cited text no. 22
    
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Beaumont DR, Arkwright PD. Factors determining the effectiveness of oral ciclosporin in the treatment of severe childhood atopic dermatitis. J Dermatolog Treat 2012;23:318-22.  Back to cited text no. 23
    
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Hernández-Martín A, Noguera-Morel L, Bernardino-Cuesta B, Torrelo A, Pérez-Martin MA, Aparicio-López C, et al. Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients. J Eur Acad Dermatol Venereol 2017;31:837-42.  Back to cited text no. 24
    


    Figures

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

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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