Successful Use of Tofacitinib in Paediatric Prurigo Nodularis: A Report of Four Cases

Dear Editor, Prurigo nodularis (PN) is a chronic refractory, intensely pruritic disease that clinically presents as symmetrically distributed, keratinized, excoriated firm papules and nodules over extremities and sometimes all over the body. It is resistant to various therapeutic agents and significantly affects the quality of life of a child.[1] Herein, we describe the effectiveness of tofacitinib in four paediatric PN patients. The four cases of PN were diagnosed clinically and proven histopathologically (hyperkeratotic acanthotic epidermis, irregular elongated rete ridges, vertically elongated collagen fibres and perivascular neutrophils, and lymphohistiocytes). For all the patients, the following baseline investigations were performed: complete blood count, liver function test, serum urea and creatinine, fasting lipid profile, urine routine microscopy, serology for human immunodeficiency, hepatitis B and C virus, chest X-ray and Mantoux test. Oral tofacitinib was administered 5 mg twice daily (all were more than 40 kg). The demographic, clinical and treatment outcome details are summarized in Table 1. The ages of the four girls ranged from 14 to 16 years, and disease duration varied from 1 to 4 years. A history of atopy was present in three of them, and none of them had an underlying psychiatric illness or associated comorbidities. One girl had a family history of prurigo. Pruriginous papules and nodules were distributed over the bilateral upper and lower extremities, and in two cases, lesions were found on the trunk. A reduction in the size of lesions was noted within 4 to 6 weeks of initiation of tofacitinib. The numeric rating scale (NRS) itch score reduced to zero at three months in all the cases, and except for one case, the investigator global assessment (IGA) chronic prurigo (CPG) score reached zero at three months with a resolution of all the lesion leaving behind post-inflammatory hyperpigmentation [Figures 1 and 2]. The Dermatology Life Quality Index (DLQI) has significantly improved in all of them in three months. In the view of preventing relapse, tofacitinib was continued for six months, except for case four, who is in her fourth month of therapy. Repeat investigations such as CBC, serum urea and creatinine, LFT, and fasting lipid profile at the end of the first, third and sixth months (except for case 4) were normal. There were no significant side effects during tofacitinib therapy.Table 1: Clinico-demographic details and treatment outcomes of the four cases of paediatric prurigo nodularisFigure 1: (a) Multiple excoriated papules and nodules on the lower limb at baseline. (b) Complete resolution of all the lesionsFigure 2: (a) Multiple excoriated papules and nodules on the lower limb at baseline. (b) Multiple excoriated papules and nodules on the forearm at baseline. (c) Complete resolution of all the lesions on lower limbs. (d) Complete resolution of all the lesions on upper limbsThe underlying aetiology of PN remains unclear. The role of reduced intraepidermal nerve fibre density and exaggerated release of interleukin (IL) 4, 17, 22 and 31 have been linked to the pathogenesis of PN. These mediators exert their role through the JAK-STAT pathway. Recent studies have demonstrated the role of STAT 3 and 6 in the pathogenesis of PN, thus proving the role of JAK-STAT inhibitors in the management of PN.[2] Tofacitinib is a non-selective JAK inhibitor that reduces IL 4, 9, 10 and 31 levels and reduces pruritus by inhibiting the JAK-STAT pathway.[2] To date, few case reports have depicted tofacitinib’s role in PN, and the data on the pediatric population is sparse. A 65-year-old male who had an unsatisfactory response to topical steroids, phototherapy, pregabalin, thalidomide and dupilumab showed improvement in NRS and DLQI from 10, 23 to 7 and 13, respectively, following the use of tofacitinib.[3] A similar efficacy was reported from India in the case of an adult female.[4] A 13-year-old girl had a reduction in pruritus grading severity score from 15 to 2 with tofacitinib 5 mg BD, which was refractory to methotrexate and thalidomide therapy.[5] Our cases had unsatisfactory responses to prior treatments that constituted topical, intralesional, and oral steroids, cyclosporine and methotrexate. The nonresponse to allopathic drugs prompted one patient to seek Ayurveda treatment without success. Our series demonstrates the effectiveness of oral tofacitinib in reducing the itching and resolution of chronic pruriginous lesions. This significantly improved their quality of life as they could attain their school, college and social functions without any hindrance. In conclusion, we report the successful use of tofacitinib in treating four pediatric cases of PN without any adverse effects and bring new hope into PN management. 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.