Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Therapy Letter
90 (
2
); 238-240
doi:
10.25259/IJDVL_362_2023
pmid:
38031706

Treatment of recalcitrant paediatric prurigo nodularis with tofacitinib, an exquisite example of bench-to-bedside translation of JAK-STAT expression

Department of Dermatology, ABVIMS & Dr. Manohar Lohia Hospital, Baba Kharak Singh Rd, Gurudwara Bangla Sahib, Connaught Place, Delhi, New Delhi, India
Department of Dermatology, Venkateshwara Institute of Medical Science, Jyotiba Phule Nagar, Gajraula, Uttar Pradesh, Gajraula, India.

Corresponding author: Dr. Kabir Sardana, Department of Dermatology, ABVIMS & Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Rd, Gurudwara Bangla Sahib, Connaught Place, Delhi, New Delhi, India. kabirijdvl@gmail.com

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Sardana K, Mathachan SR, Agrawal D. Treatment of recalcitrant paediatric prurigo nodularis with tofacitinib, an exquisite example of bench-to-bedside translation of JAK-STAT expression. Indian J Dermatol Venereol Leprol. 2024;90:238–40. doi: 10.25259/IJDVL_362_2023.

Dear Editor,

Prurigo nodularis is characterised by hyperkeratotic, eroded papulonodular lesions, distributed symmetrically on the extensors and trunk, often triggered by intense pruritus lasting more than 6 weeks, often restricted to middle-aged and older persons (5th decade), and rarely in children. Most therapies have high failure rates evident by the varied agents administered, including pregabalin, gabapentin, cyclosporine, methotrexate and thalidomide.1 Given the diverse array of mechanism involved in the pathogenesis of paediatric prurigo nodularis, a combination of agents is needed for effective treatment. Although tofacitinib, a non-selective Janus kinase (JAK) inhibitor, has been utilised in adult prurigo nodularis cases, there is currently limited translational data available regarding its use, specifically in relation to JAK-STAT expression in paediatric prurigo nodularis.2

A 13-year-old non-atopic boy, presented to the dermatology outpatient department of ABVIMS and Dr. Ram Manohar Lohia Hospital, New Delhi, with generalised excoriated papulonodular lesions on both upper and lower limbs (extensors more than flexors) and trunk for four years [Figure 1]. Skin biopsy revealed compact orthokeratosis with focal parakeratosis, a prominent granular layer, and irregular acanthosis. The papillary dermis showed moderate lymphoplasmacytic infiltration and vertically oriented collagen bundles [Figure 2]. The baseline pruritus grading system score (PGSS) was 16 out of 19. Treatment history included the unsuccessful use of methotrexate, thalidomide, topical steroids, and antihistamines. A detailed investigative panel to rule out any secondary cause of prurigo nodularis [complete blood count, fasting sugar levels, liver and kidney function tests, thyroid function tests, viral markers (HIV-ELISA, hepatitis B and C serology)] was normal. Based on our previous study on STAT expression with a heightened expression of T-helper (Th2) cytokines and the published data on the use of tofacitinib in adult prurigo nodularis, we offered the parents tofacitinib.2 Baseline investigations, including a complete hemogram, liver and kidney function tests, Mantoux test, IGRA (Interferon-Gamma Release Assay), chest X-ray, fasting lipid profile, and viral markers, were done prior to the initiation of tofacitinib, which was started in a dose of 5 mg twice daily along with topical steroid and salicylic acid combination (clobetasol propionate 0.05% and salicylic acid 3%), emollients and antihistamines. There was a dramatic improvement in pruritus within one week after starting the therapy, and continued therapy led to the complete resolution of lesions in 3 months, after which the dose was reduced to 5 mg once daily and stopped after a month, with no adverse sequelae [Figure 3]. The patient achieved a PGSS score of 2 and is in remission for three months since the discontinuation of the medication.

Multiple papulonodular lesions distributed on the trunk (baseline PGSS score-16, severe)
Figure 1:
Multiple papulonodular lesions distributed on the trunk (baseline PGSS score-16, severe)
Epidermis shows compact orthokeratosis with focal parakeratosis, prominent granular layer and irregular acanthosis. The papillary dermis shows moderate lymphoplasmacytic infiltrate and vertically oriented collagen bundles (H&E, 100x)
Figure 2:
Epidermis shows compact orthokeratosis with focal parakeratosis, prominent granular layer and irregular acanthosis. The papillary dermis shows moderate lymphoplasmacytic infiltrate and vertically oriented collagen bundles (H&E, 100x)
Improvement in the lesions after 3 months of treatment with tofacitinib (post-treatment PGSS -2, mild)
Figure 3:
Improvement in the lesions after 3 months of treatment with tofacitinib (post-treatment PGSS -2, mild)

The literature on prurigo nodularis in children is currently limited. However, in a study by Huang et al. in 2021, the estimated prevalence of paediatric prurigo nodularis was 21.6 cases per 100,000 individuals.3 The morphology of prurigo nodularis in children is characterised by hyperkeratotic, pruritic dome-shaped nodules, papules or plaques with hyperpigmented margins, similar to the presentation observed in adults. However, prurigo nodularis is more commonly associated with atopic dermatitis in children than in adults.3

The pathophysiology of prurigo nodularis is characterised by crosstalk between inflammatory cells, proinflammatory cytokines, neuropeptides and hyperplasia of cutaneous neurons, resulting in a vicious itch-scratch cycle.4 There is an increased expression of interleukin (IL) 4, IL 13, IL 31, IL22 and IL 17 in prurigo nodularis, which mediate their action via the JAK-STAT pathway. IL‐4α establishes a JAK1‐dependent, chronic itch cycle by stimulating sensory neurons. The predominant Th2 cytokines, IL-31 and IL-4, remain the major mediators that bridge the gap between immune cells, the nervous system, and the skin, and a systemic and cutaneous Th2 immune polarisation is characteristic of prurigo nodularis2,4 [Figure 4]. Our previous study highlighted the increased expression of STAT 3 and 6 in lesional skin biopsies of prurigo nodularis, which implied a role for Th2, Th17 and Th 22 cells in the pathogenesis of prurigo nodularis.2 Logically, a drug class that can inhibit multiple cytokines is needed, and thus instead of biologics like dupilumab and nemolizumab, which target IL4R α and IL31RA respectively, a JAK inhibitor drug would be ideal. Tofacitinib, a JAK 1, 3 inhibitor, would inhibit Th2 and Th17 expression and specifically inhibit the signalling of IL4 (JAK1, JAK3, STAT6) and IL31 (JAK1, STAT3, STAT5), making it a justifiable and cost-effective treatment option in prurigo nodularis1,2,5,6 [Figure 4]. We recommend a tapering approach for tofacitinib treatment once the clinical response has been achieved. Gradually reducing the dosage allows a smooth transition to other topical agents and antihistamines. In cases where relapse occurs upon discontinuation, a low dose of tofacitinib and other topical treatments can be continued. This combined approach, along with regular lab monitoring, can effectively manage symptoms and prevent relapse in these individuals. However, more data needs to be generated in the paediatric age group and the existent treatment options for prurigo nodularis are detailed in Table 1.1

The predominant mediators of prurigo nodularis are IL 4, 13, 31, which mediate their action via the T helper 2 cells, and the signal pathway is JAK1, 3 and STAT 1,3,5,6 which indicates a Th2 response. Published data have implicated STAT 6, and thus a JAKi drug that inhibits the signal pathway of Th2 cells would effectively abrogate the effect of the cytokines, tofacitinib is an ideal prototype JAKi for this action.
Figure 4:
The predominant mediators of prurigo nodularis are IL 4, 13, 31, which mediate their action via the T helper 2 cells, and the signal pathway is JAK1, 3 and STAT 1,3,5,6 which indicates a Th2 response. Published data have implicated STAT 6, and thus a JAKi drug that inhibits the signal pathway of Th2 cells would effectively abrogate the effect of the cytokines, tofacitinib is an ideal prototype JAKi for this action.
Table 1: Stepwise approach for the management of prurigo nodularis
Treatment Neural targets Immunological targets
1st Line

Topical capsaicin

Topical ketamine/lidocaine

Topical/intralesional corticosteroids

Topical calcineurin inhibitors

Topical calcipotriol

2nd Line

NK1receptor antagonist

High dose gabapentinoids

Antidepressants(SNRI, SSRI, TCA)

Cyclosporine

Methotrexate

NBUVB/PUVA

3rd Line Thalidomide

IL31 inhibitors

Azathioprine

Dupilumab

4th line Cannabinoids

JAK inhibitors

Mycophenolate mofetil

SNRI: Serotonin and norepinephrine reuptake inhibitors, SSRI: Selective serotonin reuptake inhibitors, TCA: Tricyclic antidepressants, NBUVB: Narrowband ultraviolet-B, PUVA: psoralen plus ultraviolet-A radiation, IL: Interleukin, JAK: Janus kinase

Our case translates the tissue-based JAK-STAT expression in prurigo nodularis which is the signal pathway for cytokines and tofacitinib with its action on the implicated cytokines and the itch pathway would be a effective drug in recalcitrant cases of prurigo.1,5,6

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. , , , , , . A prospective study examining the effect of selected topical and systemic drugs on pruritus grading system score and STAT 6 expression in patients of prurigo nodularis. Indian J Dermatol. 2021;66:638-44.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  2. , , , , , . A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications. J Cosmet Dermatol. 2022;21:4009-15.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , , et al. Real-world disease burden and comorbidities of pediatric prurigo nodularis. J Am Acad Dermatol. 2022;86:655-57.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , , et al. Pathophysiology, diagnosis, and pharmacological treatment of prurigo nodularis. Expert Rev Clin Pharmacol. 2021;14:67-77.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , . Successful treatment of recalcitrant nodular prurigo with tofacitinib. Clin Exp Dermatol. 2020;45:918-20.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , , , et al. Successful treatment of prurigo nodularis with tofacitinib: The experience from a single center. Int J Dermatol. 2023;62:e293-e295.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
3,080

PDF downloads
1,159
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections