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CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 5  |  Page : 597-600
Successful treatment of erythrodermic atopic dermatitis with dupilumab in a 5-year-old girl: A case report with review of literature


1 Department of Dermatology, IMS and SUM Hospital, Bhubaneswar, Odisha, India
2 Department of Paediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India
3 Department of Paediatrics, Jagannath Hospital, Bhubaneswar, Odisha, India

Date of Web Publication29-Dec-2022

Correspondence Address:
Maitreyee Panda
Department of Dermatology, IMS and SUM Hospital, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_1044_21

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How to cite this article:
Agarwal A, Dhar S, Panda M, Mishra B. Successful treatment of erythrodermic atopic dermatitis with dupilumab in a 5-year-old girl: A case report with review of literature. Indian J Dermatol 2022;67:597-600

How to cite this URL:
Agarwal A, Dhar S, Panda M, Mishra B. Successful treatment of erythrodermic atopic dermatitis with dupilumab in a 5-year-old girl: A case report with review of literature. Indian J Dermatol [serial online] 2022 [cited 2023 Feb 5];67:597-600. Available from: https://www.e-ijd.org/text.asp?2022/67/5/597/366092




Sir,

A five-year-old girl with history of atopic dermatitis (AD) since six months of age presented to the dermatology outpatient department of a tertiary care hospital in eastern India in February, 2020 with an acute exacerbation of underlying disease. She was born out of non-consanguineous marriage with no personal or family history of atopy. She also has a twin sister without any features of atopy. There was no history of allergic rhinitis or bronchial asthma. On examination, the patient was well nourished with erythema and scaling involving almost 80–90% body surface area. Features of atopy such as intractable pruritus, flexural exacerbation, along with Dennie-Morgan fold, hyperlinearity of palms and xerosis were present [Figure 1]. Oral mucosa, dentition, hair, and nail examination were normal. There were no signs of secondary infection or complications of erythroderma. The diagnosis of AD was made based on fulfilling Hannifin and Rajka criteria.
Figure 1: First presentation of the patient in March 2020 with atopic erythroderma. (a) Dennie morgan fold, (b) Hyperlinearity of palms, (c) and (d) fexural exacerbation and xerosis

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Past treatment history comprised use of oral and topical corticosteroids on and off for the past one year upon disease aggravation. There was no history of use of any homeopathic or ayurvedic medication. We initiated treatment with oral cyclosporine in the doses of 5 mg/kg/day with good initial response. The therapy was continued for 6 months with intermittent disease flare up. Due to onset of hypertrichosis and poor disease control, other treatment modalities such as methotrexate, apremilast, wet wrap therapy, and phototherapy were tried albeit with minimal response. Over the one year of treatment, she started developing signs of chronic atopic eczema such as lichenification over the ankle, knee, and cubital fossa on the background of erythroderma [Figure 2]. The quality of life based on children's dermatology quality of life index was severely impaired due to the constant itching and disturbed sleep. Given the limited options available and the desperate need to offer a treatment option, therapy with dupilumab was considered.
Figure 2: Before commencing dupilumab therapy in March 2021. (a-d) Note the features of chronic atopic eczema with lichenification over flexures in the background of erythroderma

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The parents were explained about the estimated cost of therapy, off-label use considering the age of the patient, and the potential adverse effects that could be expected. Informed consent was taken from the patient's parents. Prior to initiation of dupilumab, her baseline eczema area severity index score (EASI) and Scoring Atopic dermatitis (SCORAD) was 42.9 and 74, respectively. Taking into consideration weight of the child (35 kg), disease severity and cost of therapy, an individualized dosing of 300 mg once every three weeks was started for the patient in the month of March, 2021 along with bland moisturizers and oral levocetrizine tablet. Improvement in EASI and SCORAD was noticed after the fourth dose (week 12) onwards with remarkable improvement seen at the end of six doses in October 2021 (EASI: 11, SCORAD: 25) [Figure 3]. The erythematous lesions were the first to respond with lichenified lesions on flexures requiring longer time to resolve. During therapy, the child developed sudden onset unexplained facial redness associated with mild itching three days after the fifth dose of dupilumab. There was no history of any topical application over the area prior to eruption. The lesions resembled “Dupilumab facial redness” described in literature [Figure 4]. The lesions resolved with a course of topical mid potent corticosteroids (mometasone cream) within 5 days. No other commonly associated adverse effects were noted. After the sixth dose, frequency of dupilumab was reduced to every four weeks. The patient is currently on regular follow up with good disease control. The plan is to reduce the frequency of injection dupilumab based on disease control and add an immunosuppressive agent such as Methotrexate as maintenance therapy.{Figure 2}
Figure 3: (a-d) Remarkable response seen after six doses of Dupilumab therapy in October 2021

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Figure 4: Dupilumab facial redness

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Dupilumab is a new monoclonal antibody United States food and drug administration (US FDA) approved in the treatment of moderate to severe AD affecting children (>6 years) and adults. It is a IgG4 type of monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes.[1]

Literature on the use of dupilumab in children below six years of age is limited. Da et al.[2] have successfully and safely treated AD with dupilumab 300 mg every four weeks (for upto 12 weeks) in three children less than six years of age. Another case of an off-label successful use of dupilumab has been described in a three-year-old Caucasian girl with loading dose of 200 mg, followed by 100 mg every 2 weeks leading to a clinical resolution within 4 weeks of therapy.[3] A Phase 2 trial to evaluate effectiveness and safety after single dose of dupilumab therapy in children aged six months to six years has shown a good safety profile as well as efficacy.[4] Large scale Phase 3 trials are currently underway. Dhar et al.[5] have also demonstrated efficacy and safety of dupilumab in real-world settings in Indian AD patients (including both adolescents and adults). The existing evidence regarding dupilumab use in children has been depicted in [Table 1].
Table 1: Evidence of dupilumab use in children (≤18 years)

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Dosages for initial and subsequent dupilumab injections based on weight of the child have been determined for children above six years of age. Considering the lack of guidelines in children below six years of age, cost of therapy and weight of child being 35 kg, we decided to initiate dupilumab at 300 mg every 3 weeks. An excellent response was observed within 18 weeks of therapy.

Initially, during the first wave of covid-19 pandemic, concerns were raised regarding the safety of biologics like dupilumab given the added risk of severe infection. Subsequently, however, multiple reports have been published showing the safety and efficacy of dupilumab in AD even in patients infected with SARS-COV2 infection.[11]

Dupilumab facial erythema has been reported as a much commoner adverse effect than initially thought. It occurs around two months after starting treatment with dupilumab. In our patient, a similar eruption was noticed around the fourth month of therapy. Other adverse effects common with dupilumab therapy are Dupilumab-induced ocular surface disease (DIOSD), injection site reactions, nasopharyngitis, and rarely angioedema.[12]

The use of dupilumab offers hope in severe recalcitrant cases of AD. Our case depicts the successful off-label use of dupilumab in a 5-year-old girl with severe erythrodermic AD with a good adverse effect profile. Further results from the ongoing phase 3 trials are awaited to provide robust data to conclusively prove efficacy and safety in this age group.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Frazier W, Bhardwaj N. Atopic dermatitis: Diagnosis and treatment. Am Fam Physician 2020;101:590-8.  Back to cited text no. 1
    
2.
Da J, Ali K, Lu K, Lou H, Qiu Y, Shan J, et al. Off-label use of dupilumab for the treatment of moderate to severe atopic dermatitis in children aged below 6 years of age: a case series. Clin Exp Dermatol. 2022;47:423-5.  Back to cited text no. 2
    
3.
Dakin H, Haas C. Successful and rapid clearance of severe, treatment-resistant atopic dermatitis with dupilumab in a 3-year-old. Dermatol Ther 2020;33:e14282.  Back to cited text no. 3
    
4.
Paller AS, Siegfried EC, Simpson EL, Cork MJ, Lockshin B, Kosloski MP, et al. A phase 2, open-label study of single-dose dupilumab in children aged 6 months to<6 years with severe uncontrolled atopic dermatitis: Pharmacokinetics, safety and efficacy. J Eur Acad Dermatol Venereol 2021;35:464-75.  Back to cited text no. 4
    
5.
Dhar S, De A, Srinivas SM. Real-world effectiveness and safety of dupilumab for the treatment of moderate to severe atopic dermatitis in indian patients: A multi centric retrospective study. Indian J Dermatol 2021;66:297-301.  Back to cited text no. 5
  [Full text]  
6.
Simpson EL, Paller AS, Siegfried EC, Boguniewicz M, Sher L, Gooderham MJ, et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: A phase 3 randomized clinical trial. JAMA Dermatol 2020;156:44-56.  Back to cited text no. 6
    
7.
Cork MJ, Thaçi D, Eichenfield LF, Arkwright PD, Hultsch T, Davis JD, et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: Results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol 2020;182:85-96.  Back to cited text no. 7
    
8.
Paller AS, Siegfried EC, Thaçi D, Wollenberg A, Cork MJ, Arkwright PD, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol 2020;83:1282-93.  Back to cited text no. 8
    
9.
Deleuran M, Marcoux D, Bruin-Weller MS, Irvine AD, Baselga E, Ahn K, et al. Dupilumab provides significant clinical benefit in a phase 3 trial in adolescents with uncontrolled atopic dermatitis irrespective of prior systemic immunosuppressant use. Acta Derm Venereol 2021;101:adv00504.  Back to cited text no. 9
    
10.
Chia SY, Wee LWY, Koh MJA. Dupilumab for children and adolescents with atopic dermatitis: An Asian perspective. Dermatol Ther 2021;34:e14933.  Back to cited text no. 10
    
11.
Hansel K, Patruno C, Antonelli E, Bello GD, Napolitano M, Fabbrocini G, et al. Dupilumab in adolescents with moderate to severe atopic dermatitis: A 32-week real-world experience during the COVID-19 pandemic. Clin Exp Dermatol 2022;47:165-7.  Back to cited text no. 11
    
12.
Nahum Y, Mimouni M, Livny E, Bahar I, Hodak E, Leshem YA. Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: Clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment. Br J Ophthalmol 2020;104:776-9.  Back to cited text no. 12
    


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