Generic selectors
Exact matches only
Search in title
Search in content
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 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 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 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
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Studies
Study Letter
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
Tables
Technology
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF
Letter to the Editor - Observation Letter
2016:82:6;727-729
doi: 10.4103/0378-6323.186477
PMID: 27716725

Imatinib mesylate-induced pseudoporphyria in a patient with chronic myeloid leukemia

Meenakshi Batrani1 , Manish Salhotra2 , Asha Kubba1 , Manjul Agrawal3
1 Delhi Dermpath Laboratory, Delhi Dermatology Group, New Delhi, India
2 Department of Pathology, Rao Tula Ram Hospital, New Delhi, India
3 Department of Dermatology, Fortis Hospital, New Delhi, India

Correspondence Address:
Meenakshi Batrani
10, Aradhana Enclave, RK Puram, Sector 13, New Delhi - 110 066
India
How to cite this article:
Batrani M, Salhotra M, Kubba A, Agrawal M. Imatinib mesylate-induced pseudoporphyria in a patient with chronic myeloid leukemia. Indian J Dermatol Venereol Leprol 2016;82:727-729
Copyright: (C)2016 Indian Journal of Dermatology, Venereology, and Leprology

Sir,

Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL, c-kit and platelet-derived growth factor receptors. It is the first-line agent in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia and c-kit-positive gastrointestinal stromal tumors.[1]

Cutaneous reactions are one of the most common adverse effects of imatinib. The incidence of cutaneous reactions may vary from 7–88.9%, with maculopapular rash and superficial edema being the most frequent.[1] Rarely, porphyria cutanea tarda and pseudoporphyria have also been reported.[1]

A 75-year-old woman with chronic myeloid leukemia, on treatment for 11 months with imatinib 400 mg twice daily, presented with a 1 month history of blisters on the hands and feet. There was no history of photosensitivity. On examination, intact tense hemorrhagic bullae and erosions with scarring and milia formation were present on the dorsum of the hands and toes [Figure - 1]. A diagnosis of bullous pemphigoid was clinically suspected. A punch biopsy from the right little finger revealed a pauci-cellular subepidermal blister with festooning of dermal papillae into the blister cavity [Figure - 2]a. Periodic acid–Schiff staining revealed thickening of the small vessel walls in the papillary dermis [Figure - 2]b. Direct immunofluorescence demonstrated homogenous deposits of IgG, IgM and C3 in the vessel walls and a weak band at the dermoepidermal junction with IgG and C3 [Figure - 3]. The total urinary porphyrin level was within normal limits. Thus, with the clinical and laboratory findings, a diagnosis of imatinib-induced pseudoporphyria was made.

Figure 1: Hemorrhagic tense bullae on the (a) hands and (b) feet with erosions and scarring
Figure 2: (a) Pauci-cellular subepidermal blister with festooning of dermal papillae into the cavity (H and E, ×100). (b) Homogenous thickening of wall of small vessels in papillary dermis (Periodic acid–Schiff, ×200)
Figure 3: Direct immunofluorescence demonstrating homogeneous deposit of IgG in walls of small blood vessels and a weak linear band along the dermo-epidermal junction (×400)

The differential diagnoses of pauci-cellular subepidermal blisters include bullous pemphigoid, epidermolysis bullosa acquisita, porphyria cutanea tarda and pseudoporphyria. Bullous pemphigoid clinically presents with pruritus and blisters on an erythematous base with a predilection for flexural regions. Scarring and milia formation are not generally seen and there is no mechanical fragility or photodistribution of lesions. Epidermolysis bullosa acquisita exhibits clinical features overlapping with pseudoporphyria. Direct immunofluorescence findings are useful in distinguishing bullous pemphigoid and epidermolysis bullosa acquisita from porphyria cutanea tarda/pseudoporphyria. In bullous pemphigoid and epidermolysis bullosa acquisita, direct immunofluorescence studies show a sharp linear band at the dermoepidermal junction while the vessel wall immune deposits characteristic of porphyria cutanea tarda/pseudoporphyria are absent. The distinction between porphyria cutanea tarda and pseudoporphyria is based on porphyrin levels which are raised in the former.

In our patient, skin lesions resolved within 3 weeks of drug withdrawal. Imatinib had to be reintroduced after 2 months due to worsening of the underlying hematological disorder. Her cutaneous symptoms recurred, but were milder because of photoprotection.

Pseudoporphyria is a disorder with clinical, histopathological and immunofluorescence features that are similar to porphyria cutanea tarda but without the biochemical porphyrin abnormalities. It presents as blistering and skin fragility on sun-exposed sites. Unlike porphyria cutanea tarda, hypertrichosis, hyperpigmentation, dystrophic calcification and sclerodermoid changes are seldom associated with pseudoporphyria.[2] The various causes of pseudoporphyria include ultraviolet A exposure, chronic renal failure/dialysis and a wide range of drugs, particularly nonsteroidal anti-inflammatory drugs, diuretics, antibiotics and retinoids.[2]

Imatinib has been implicated occasionally in causing both pseudoporphyria and porphyria cutanea tarda. We were able to find seven previously reported cases of imatinib-induced pseudoporphyria and three cases of imatinib precipitated/reactivated porphyria cutanea tarda in the English literature.[2],[3],[4] Two cases which were originally reported as skin fragility and blistering due to imatinib were subsequently categorized as pseudoporphyria in a review by Mahon et al.[3],[5],[6]

The pathogenesis of pseudoporphyria may differ depending on the causative factor; however, ultraviolet A exposure seems to be a common prerequisite. Various patho-mechanisms have been hypothesized in the causation of imatinib-induced pseudoporphyria. It has been suggested that imatinib, by inhibiting c-kit signaling in skin, might disrupt normal melanocyte biology leading to decreased photoprotection.[2],[3] A recent experimental study has proposed that direct photosensitization by imatinib or its metabolites is unlikely and that photosensitive disorders might be due to impaired melanogenesis or accumulation of endogenous porphyrins.[7]

Treatment of pseudoporphyria often includes discontinuation or reducing the dose of the offending drug or switching to a non-implicated drug and/or photoprotection. However, clinicians and patients have to reach a decision together, after weighing the adverse effects and therapeutic benefits of the implicated drug.

Considering the widespread use of imatinib in hematological malignancies and various other indications, clinicians must be aware that pseudoporphyria and porphyria cutanea tarda are possible adverse effects of the drug.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References
1.
Pretel-Irazabal M, Tuneu-Valls A, Ormaechea-Pérez N. Adverse skin effects of imatinib, a tyrosine kinase inhibitor. Actas Dermosifiliogr 2014;105:655-62.
[Google Scholar]
2.
Timmer-de Mik L, Kardaun SH, Kramer MH, Hayes DP, Bousema MT. Imatinib-induced pseudoporphyria. Clin Exp Dermatol 2009;34:705-7.
[Google Scholar]
3.
Mahon C, Purvis D, Laughton S, Bradbeer P, Teague L. Imatinib mesylate-induced pseudoporphyria in two children. Pediatr Dermatol 2014;31:603-7.
[Google Scholar]
4.
Au WY, Lee J. Imatinib mesylate (STI-571) and porphyria cutanea tarda in a Chinese patient. Haematologica 2005;90:ECR18.
[Google Scholar]
5.
Verma SM, Murphy G. Skin fragility and blistering with imatinib mesylate. J Eur Acad Dermatol Venereol 2010;24:496-8.
[Google Scholar]
6.
Reddy H, Horne HL, Maung Z. Skin fragility and blistering secondary to imatinib. Clin Exp Dermatol 2012;37:572-3.
[Google Scholar]
7.
Nardi G, Lhiaubet-Vallet V, Miranda MA. Photosensitization by imatinib. A photochemical and photobiological study of the drug and its substructures. Chem Res Toxicol 2014;27:1990-5.
[Google Scholar]

Fulltext Views
139

PDF downloads
61
Show Sections