ALL Metrics
-
Views
-
Downloads
Get PDF
Get XML
Cite
Export
Track
Case Report

Case Report: Paradoxical acrodermatitis of Hallopeau-like eruption following anti-IL-17 therapy

[version 1; peer review: 2 approved]
PUBLISHED 26 Mar 2019
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

Abstract

Psoriasis is a chronic immune-mediated inflammatory disease. Up to 40% of patients with psoriasis may develop psoriatic arthritis.  Currently, interleukin (IL)-17/IL-23 pathways are identified as key factors in the immunopathogenesis of both conditions. Here we describe the case of a patient who developed psoriasiform skin lesions 10 months after the initiation of anti-IL17 therapy for psoriatic arthritis. The underlying disease had responded well to the therapy, but the patient developed a striking pustular eruption at the fingers with nail involvement, onycholysis, yellow discoloration, and subungual keratosis. Clinical and histological findings were consistent with an acrodermatitis continua of Hallopeau-like eruption. Skin lesions subsided after discontinuation of the responsible anti-IL17 agent. The interpretation of this paradoxical side effect of biological therapies remains unclear but may relate to an unbalanced inflammatory cytokine response induced by the inhibition of TNF activity. It is likely that patients, who are genetically prone, may respond exaggeratedly to a cytokine imbalance. The identification of this kind of patient, in the future, could be useful in order to choose the correct therapy.

Keywords

IL-17, psoriasis, Acrodermatitis continua of Hallopeau, paradoxical reaction

Introduction

Psoriasis is an immune-mediated inflammatory disease characterized by a chronic course and a systemic involvement. Numerous cytokines are involved in the pathogenesis of psoriasis, but the interleukin (IL)-23/17 axis has been identified as one of the key pathways1. Up to 40% of patients with psoriasis may develop psoriatic arthritis (PsA). Both conditions share common pathogenic mechanisms2. Among the therapies that can be used for both skin and joint manifestations, anti-TNF agents and new biologics targeting IL-17 have shown impressive efficacy3. We report the case of a patient who presented with an acrodermatitis continua of Hallopeau (ACH)-like paradoxical reaction to anti-IL17 therapy for PsA.

Case report

A 52-year-old-woman affected by PsA presented to our Dermatology Unit complaining of a painful eruption of pustules with scaling and tender swelling on the fingers of both hands (Figure 1), which had begun one month before. Her medical history revealed concurrent PsA in complete remission after 10 months of the, the anti-IL-17 drug, secukinumab, at the dosage of 150mg every 4 weeks. The patient did not suffer from any other relevant disease and there was no family history of psoriasis.

42ebc6c8-b540-48a4-b1b7-8ff124a8af83_figure1.gif

Figure 1. Eruption of pustules with scaling, tender swelling over fingers of both hands in a patient with psoriatic arthritis.

A skin biopsy was taken, and the subsequent histopathological examination showed a stratified squamous epithelium with parakeratosis, hyperkeratosis and irregular elongation of the rete ridges of the epidermis with some lymphocytes and subcorneal collections of neutrophils forming spongiform pustules of Kogoj. This result, together with clinical features and negative results of multiple cultures confirmed our suspect of an ACH-like eruption4.

It was then decided to stop anti-IL-17 therapy. A subsequent treatment plan comprised topical clobetasol propionate, once daily, and acitretin 10mg daily.

At the follow-up visit 2 months later, the lesions had visibly regressed and the patient referred a 70% reduction in symptoms measured with Dermatology Life Quality Index questionnaire. The interruption of secukinumab notwithstanding, PsA showed no recrudescence.

Discussion

The natural history of psoriasis has been modified in the last years by new biologic agents that have allowed specific targeting of key cytokines such as TNF alpha, IL-12, IL-23 and IL-17.

TNF alpha inhibitors are the oldest, and therefore most studied, biologic drugs that have been introduced in the therapy of psoriasis. By inhibiting the whole pathway, TNF alpha blockers determine a stronger alteration of cytokine network5. This has been associated not only with impressive efficacy, but also remarkable side effects, such as infections, autoimmune diseases, lymphomas and cutaneous adverse events, mainly represented by paradoxical psoriasis6.

In the last years, new biologic therapies targeting cytokines situated downstream to TNF alpha, such as ustekinumab, secukinumab and, more recently, ixekizumab have shown even higher efficacy due to their selectivity in blocking cytokines specific to the pathogenic pathways. Also for this drug, although uncommon, important adverse reactions such as opportunistic infections, can be observed7.

In the literature, one case of paradoxical psoriasic reaction has recently been described in association to secukinumab8. In our case report we have observed an unexpected case of paradoxical ACH-like eruption, which to the best of our knowledge, has not been described in literature as an adverse event of secukinumab.

It is possible that secukinumab, by blocking IL-17, has induced a rearrangement of the cytokine pattern in this patient, determining a paradoxical increase of other pathogenic molecules, such as TNF alpha. This hypothesis has already been suggested for paradoxical reactions to ustekinumab, which exerts a blockade of IL12 and IL239. On the other hand, is also possible that the inhibition of IL17 induced a negative feedback in the IL23-IL17 axis, thus determining an increase of IL23 which, in turn, stimulated Th17 cells to produce other cytokines, such as IL-22, which also exerts proliferation and activation of keratinocytes. Activated keratinocytes could induce the chemotaxis of neutrophils (IL-8 etc), causing the clinical presentation that we have observed in our patient10. This is the first case report describing ACH-like lesions induced by secukinumab; therefore few studies are available in the literature elucidating the pathogenesis of this paradoxical reaction. Hence, our experience needs to be reinforced by further investigations.

It is likely that our patient was genetically prone to respond exaggeratedly to a cytokine imbalance. The distinction of such patients could be useful in the future, in order to predict this type of adverse reaction and, therefore, suggesting them an alternative to biologic therapies.

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 26 Mar 2019
Comment
Author details Author details
Competing interests
Grant information
Copyright
Download
 
Export To
metrics
Views Downloads
F1000Research - -
PubMed Central
Data from PMC are received and updated monthly.
- -
Citations
CITE
how to cite this article
Tadiotto Cicogna G, Messina F, Nalotto L et al. Case Report: Paradoxical acrodermatitis of Hallopeau-like eruption following anti-IL-17 therapy [version 1; peer review: 2 approved]. F1000Research 2019, 8:336 (https://doi.org/10.12688/f1000research.18493.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
track
receive updates on this article
Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 26 Mar 2019
Views
4
Cite
Reviewer Report 05 Aug 2019
Melinda J. Gooderham, SKiN Centre for Dermatology, Peterborough, ON, Canada 
Approved
VIEWS 4
An interesting case of a 'paradoxical' reaction to a biologic agent, secukinumab, which is used to treat psoriatic disease. In this case, acrodermatitis of Hallopeau developed in this patient being treated successfully with secukinumab for psoriatic arthritis. It is important to report ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Gooderham MJ. Reviewer Report For: Case Report: Paradoxical acrodermatitis of Hallopeau-like eruption following anti-IL-17 therapy [version 1; peer review: 2 approved]. F1000Research 2019, 8:336 (https://doi.org/10.5256/f1000research.20235.r51595)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 09 Mar 2020
    Mauro Alaibac, Unit of Dermatology, Department of Medicine, University of Padua, Padova, 35121, Italy
    09 Mar 2020
    Author Response
    Dear Reviewer,

    Thank for your thoughtful and constructive comments. We do agree with you that similarly to TNF-alpha, IL-17 may show unexpected "paradoxical" eruptions and further experimental and clinical observations are ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 09 Mar 2020
    Mauro Alaibac, Unit of Dermatology, Department of Medicine, University of Padua, Padova, 35121, Italy
    09 Mar 2020
    Author Response
    Dear Reviewer,

    Thank for your thoughtful and constructive comments. We do agree with you that similarly to TNF-alpha, IL-17 may show unexpected "paradoxical" eruptions and further experimental and clinical observations are ... Continue reading
Views
15
Cite
Reviewer Report 15 May 2019
Archana Gopalakrishnan, University of Maryland, Baltimore, Baltimore, MD, USA;  Rutgers University - The State University of New Jersey, New Brunswick, NJ, USA 
Approved
VIEWS 15
Paradoxical effects of anti-cytokine therapy is a very important area that the authors have highlighted in this case study. As has been well documented, the use of therapies, such as anti-TNF, although groundbreaking does raise a multitude of issues - ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Gopalakrishnan A. Reviewer Report For: Case Report: Paradoxical acrodermatitis of Hallopeau-like eruption following anti-IL-17 therapy [version 1; peer review: 2 approved]. F1000Research 2019, 8:336 (https://doi.org/10.5256/f1000research.20235.r48170)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 09 Mar 2020
    Mauro Alaibac, Unit of Dermatology, Department of Medicine, University of Padua, Padova, 35121, Italy
    09 Mar 2020
    Author Response
    Dear Reviewer,

    Thank you  for the very careful review of our paper. 

    Please find below a point by point response to your constructive comments 
    1. Would decreasing the dosage of the
    ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 09 Mar 2020
    Mauro Alaibac, Unit of Dermatology, Department of Medicine, University of Padua, Padova, 35121, Italy
    09 Mar 2020
    Author Response
    Dear Reviewer,

    Thank you  for the very careful review of our paper. 

    Please find below a point by point response to your constructive comments 
    1. Would decreasing the dosage of the
    ... Continue reading

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 26 Mar 2019
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
Sign In
If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.

The email address should be the one you originally registered with F1000.

Email address not valid, please try again

You registered with F1000 via Google, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Google account password, please click here.

You registered with F1000 via Facebook, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Facebook account password, please click here.

Code not correct, please try again
Email us for further assistance.
Server error, please try again.