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
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
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
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
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
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
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:

Case Letter
ARTICLE IN PRESS
doi:
10.25259/IJDVL_56_2024

Flagellate-like presentation of Stevens-Johnson syndrome: Toxic epidermal necrolysis after gefitinib therapy

Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Corresponding author: Dr. Rahul Mahajan, Department of Dermatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. drrahulpgi@yahoo.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: Patra KSL, Baskaran N, Chatterjee D, Mahajan R. Flagellate-like presentation of Steven Johnson syndrome-Toxic epidermal necrolysis after gefitinib therapy. Indian J Dermatol Venereol Leprol. doi: 10.25259/IJDVL_56_2024

Dear Editor,

Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, plays a pivotal role in targeted therapy for non-small cell lung cancer (NSCLC). Targeted therapies have been implicated in severe cutaneous adverse reactions (SCARs) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). While other EGFR inhibitors such as afatinib have been associated with SJS-TEN, reports of SJS as a result of gefitinib use are comparatively infrequent and uncommon.1 This case report provides an insight into a patient who developed SJS after gefitinib therapy which had clinical manifestations similar to flagellate dermatitis.

A 64-year-old woman with stage IIIA NSCLC was initiated on oral gefitinib at a standard dose of 250 mg/day as EGFR activating exon 19 mutation was detected in the tumour. Ten days after initiating the gefitinib regimen, she presented with a pruritic erythematous macules spanning her trunk and limbs. Remarkably, the macular eruption assumed a linear and whip-like pattern akin to a flagellate dermatitis over the trunk [Figures 1 and 2]. The evolution was rapid, progressing to blistering, epidermal detachment and oral and genital mucosal involvement and mild conjunctival erythema. The total body surface area involved was 14–15%. Other drugs which the patient was taking were non-steroidal anti-inflammatory drugs and proton pump inhibitors. However, temporal correlation was established only for gefitinib. The patient’s clinical status deteriorated swiftly, necessitating intensive care unit admission with a diagnosis of gefitinib-induced SJS. Histopathological examination of skin from two sites (flagellate dermatitis–like morphology [trunk area] and from the typical SJS-like skin lesions [buttock area]) showed epidermal necrosis with basal cell vacuolisation and numerous apoptotic keratinocytes, thereby corroborating with the clinical presentation [Figure 3]. Serology for recent mycoplasma pneumoniae or herpes simplex virus was non-reactive. Therapeutic interventions encompassed immediate cessation of gefitinib, tapering course of cyclosporine at 5 mg/kg/day for 14 days, meticulous wound care and vigilant fluid management. Over the ensuing weeks, the cutaneous lesions exhibited gradual resolution with post-inflammatory hyperpigmentation as the residual sequelae and the mucosal involvement ameliorated.

Flagellate rash wherein linear lesions are erythematous and raised, following a serpentine pattern with some areas exhibiting mild scaling.
Figure 1:
Flagellate rash wherein linear lesions are erythematous and raised, following a serpentine pattern with some areas exhibiting mild scaling.
Close-up images show well-defined epidermal erosion with minimal inflammation over the buttock area.
Figure 2:
Close-up images show well-defined epidermal erosion with minimal inflammation over the buttock area.
Histopathological examination shows epidermal necrosis with basal cell vacuolisation and numerous apoptotic keratinocytes with epidermal separation (Haematoxylin and Eosin, 100x).
Figure 3:
Histopathological examination shows epidermal necrosis with basal cell vacuolisation and numerous apoptotic keratinocytes with epidermal separation (Haematoxylin and Eosin, 100x).

SJS is a rare and severe mucocutaneous disorder, often triggered by medications, characterised by epidermal detachment and systemic involvement. In the context of targeted therapies, the emergence of SJS remains a complex and infrequent phenomenon. Our case sheds light on the convergence of gefitinib, an EGFR tyrosine kinase inhibitor used in NSCLC with the distinctive clinical presentation of SJS resembling flagellate dermatitis. Flagellate dermatitis, recognised by its linear, erythematous streaks reminiscent of whipping marks, has been predominantly linked to bleomycin and docetaxel.2 This patient presented with linear streaks which rapidly evolved into blisters, erosions and mucosal involvement – hallmarks of SJS. The flagellate dermatitis–like presentation of SJS can be attributed to the amount of intense pruritus associated with gefitinib therapy.3 EGF fosters keratinocyte proliferation by augmenting Ki67 and filaggrin expression via the mitogen-activated protein kinase kinase.4 In addition, EGFR governs the terminal differentiation of keratinocytes through the phospholipase C-γ1-protein kinase C pathway, upholding continuous epidermal barrier renewal.5 Disruption of the epidermal barriers, both physical and immune, due to EGFR inhibitors, like gefitinib, contributes to skin-related complications such as dryness and rashes. Claudins, vital for tight junction assembly, significantly contribute to maintaining the skin barrier’s integrity. Gefitinib potentially impairs the skin barrier by modulating claudin-1, claudin-4 and claudin-2 expressions in keratinocytes, thereby leading to skin toxicity.6

Other differential diagnosis which can be considered in such a setting of gefitinib therapy is necrolytic migratory erythema (NME). It presents as erythematous scaly plaques which blister centrally forming ulceration and crusting. As the central portion of the ulcer heals, the erythema may expand outward with new vesicles developing over the advancing edges. It mostly involves the intertriginous area such as inguinal creases and popliteal fossa with rare mucosal involvement. The histopathological hallmark of NME is the necrosis of the upper spinous layer of epidermis rather than basal cell vacuolisation.7 Both the clinical and histopathological criteria were absent in our case. Therefore, the possibility of necrolytic migratory erythema was ruled out.

In summary, the convergence of gefitinib-induced SJS with clinical features resembling flagellate dermatitis serves as a compelling reminder of the complexities within the realm of cutaneous adverse events. This case not only broadens our understanding of the potential manifestations of SJS but also underscores the need for heightened vigilance and interdisciplinary collaboration in managing adverse reactions associated with targeted therapies.

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.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

References

  1. , , , . Toxic epidermal necrosis associated with afatinib: A case report and literature review. Front Oncol. 2023;12:1010052.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  2. , , . Flagellate dermatoses. Indian J Dermatology, Venereol Leprol. 2014;80:149.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , , et al. Aprepitant for gefitinib-induced refractory pruritus in chinese malignancy population. Ann Transl Med. 2019;7:54.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  4. , , , , , , et al. EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins. Int J Mol Med. 2019;43:1522-30.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. rhEGF Treatment improves EGFR inhibitor-induced skin barrier and immune defects. Cancers (Basel). 2020;12:3120.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  6. , , , , . ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways. Sci Rep. 2016;6:39780.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  7. , , , , , , et al. Putting the pieces together: necrolytic migratory erythema and the glucagonoma syndrome. J Gen Intern Med. 2013;28:1525-9.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]

Fulltext Views
721

PDF downloads
1,607
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections