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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Our patient was a 46-year-old man who had been diagnosed with plaque psoriasis 27 years earlier and reported no previous axial or peripheral joint signs&#46; Over the preceding years he had responded poorly to narrowband ultraviolet-B phototherapy&#44; methotrexate&#44; cyclosporine&#44; etanercept&#44; adalimumab&#44; ustekinumab&#44; and infliximab&#46; At the time of the consultation he had numerous generalized plaques &#40;psoriasis area and severity index &#91;PASI&#93;&#44; 10&#41;&#46; Treatment was started with subcutaneous ixekizumab at the usual dose&#46; After the first dose of 160&#160;mg&#44; the patient reported generalized migratory arthralgias that intensified and became disabling after the second dose of 80&#160;mg&#44; prompting an emergency visit to the rheumatology service&#46; Physical examination revealed pain and marked limitation of cervical spinal cord mobility with no involvement of the lumbar or sacroiliac spinal cord &#40;normal response in the Schober test and negative response to sacroiliac manipulation&#41;&#44; pain and limited mobility of the scapular and pelvic girdles&#44; pain and mild swelling of the carpal joints&#44; and pain without swelling in the ankles&#44; knees&#44; and the small joints of the fingers&#46; The painful joint count &#40;PJC28&#41; was 10 &#40;carpal joints&#44; knees&#44; shoulders&#44; and second and third bilateral metacarpophalangeal joints&#41;&#44; and the swollen joint count &#40;SJC28&#41; was 2 &#40;carpal joints&#41;&#46; Based on these findings&#44; the patient was diagnosed with paradoxical arthritis&#46; With the patient&#39;s consent ixekizumab treatment was discontinued&#44; and he was treated with a tapering dose of oral prednisone &#40;20&#160;mg&#47;d&#41; for 10 days&#44; resulting in almost complete resolution of the joint problems&#46; Upon reaching the end of the corticosteroid regimen&#44; the patient was treated with secukinumab at the usual dose &#40;300&#160;mg&#41;&#46; After 10 months of coordinated monitoring by the dermatology and rheumatology services&#44; the patient&#39;s psoriasis had markedly improved &#40;PASI&#44; 1&#41;&#44; with no adverse effects or joint symptoms&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Ixekizumab is a humanized IgG4 monoclonal antibody that acts to neutralize IL-17A&#44; and in clinical trials has shown high efficacy in patients with plaque psoriasis<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> and psoriatic arthritis&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> with an acceptable safety profile<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> and no adverse effects on joints&#46; In the present case&#44; the coincidence of ixekizumab injections and the sudden onset of joint symptoms in a patient with no history of arthritis&#44; together with the progressive disappearance of these symptoms after ixekizumab discontinuation&#44; suggest a causal relationship between ixekizumab and this adverse effect&#46; The literature describes several cases of so-called paradoxical psoriatic arthritis coinciding with the use of biological treatments for plaque psoriasis&#44; including efalizumab&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> etanercept&#44; adalimumab&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> infliximab&#44; and ustekinumab&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> but none involving IL-17 inhibitors&#46; The appearance of paradoxical psoriatic arthritis in this case underscores the pathogenic complexity of this disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In conclusion&#44; despite the absence from the literature of any reports of adverse joint effects caused by ixekizumab&#44; we describe a case of paradoxical arthritis that was associated with ixekizumab treatment&#44; discontinuation of which was ultimately required&#46; Long-term follow-up studies will be necessary to determine the frequency and causality of this adverse effect&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Vol. 110. Núm. 3.
Páginas 255-256 (abril 2019)
Vol. 110. Núm. 3.
Páginas 255-256 (abril 2019)
Case and Research Letters
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Paradoxical Arthritis Due to Ixekizumab in a Patient With Plaque Psoriasis
Artritis paradójica por ixekizumab en un paciente con psoriasis en placas
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D. Vidala,
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david.vidal@sanitatintegral.org

Corresponding author.
, S. Rosb, D. Reinac
a Servicio de Dermatología, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, España
b Servicio de Reumatología, Hospital de Viladecans, Viladecans, Barcelona, España
c Servicio de Reumatología, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, España
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To the Editor:

Our patient was a 46-year-old man who had been diagnosed with plaque psoriasis 27 years earlier and reported no previous axial or peripheral joint signs. Over the preceding years he had responded poorly to narrowband ultraviolet-B phototherapy, methotrexate, cyclosporine, etanercept, adalimumab, ustekinumab, and infliximab. At the time of the consultation he had numerous generalized plaques (psoriasis area and severity index [PASI], 10). Treatment was started with subcutaneous ixekizumab at the usual dose. After the first dose of 160 mg, the patient reported generalized migratory arthralgias that intensified and became disabling after the second dose of 80 mg, prompting an emergency visit to the rheumatology service. Physical examination revealed pain and marked limitation of cervical spinal cord mobility with no involvement of the lumbar or sacroiliac spinal cord (normal response in the Schober test and negative response to sacroiliac manipulation), pain and limited mobility of the scapular and pelvic girdles, pain and mild swelling of the carpal joints, and pain without swelling in the ankles, knees, and the small joints of the fingers. The painful joint count (PJC28) was 10 (carpal joints, knees, shoulders, and second and third bilateral metacarpophalangeal joints), and the swollen joint count (SJC28) was 2 (carpal joints). Based on these findings, the patient was diagnosed with paradoxical arthritis. With the patient's consent ixekizumab treatment was discontinued, and he was treated with a tapering dose of oral prednisone (20 mg/d) for 10 days, resulting in almost complete resolution of the joint problems. Upon reaching the end of the corticosteroid regimen, the patient was treated with secukinumab at the usual dose (300 mg). After 10 months of coordinated monitoring by the dermatology and rheumatology services, the patient's psoriasis had markedly improved (PASI, 1), with no adverse effects or joint symptoms.

Ixekizumab is a humanized IgG4 monoclonal antibody that acts to neutralize IL-17A, and in clinical trials has shown high efficacy in patients with plaque psoriasis1 and psoriatic arthritis,2 with an acceptable safety profile3 and no adverse effects on joints. In the present case, the coincidence of ixekizumab injections and the sudden onset of joint symptoms in a patient with no history of arthritis, together with the progressive disappearance of these symptoms after ixekizumab discontinuation, suggest a causal relationship between ixekizumab and this adverse effect. The literature describes several cases of so-called paradoxical psoriatic arthritis coinciding with the use of biological treatments for plaque psoriasis, including efalizumab,4 etanercept, adalimumab,5 infliximab, and ustekinumab,6 but none involving IL-17 inhibitors. The appearance of paradoxical psoriatic arthritis in this case underscores the pathogenic complexity of this disease.

In conclusion, despite the absence from the literature of any reports of adverse joint effects caused by ixekizumab, we describe a case of paradoxical arthritis that was associated with ixekizumab treatment, discontinuation of which was ultimately required. Long-term follow-up studies will be necessary to determine the frequency and causality of this adverse effect.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References
[1]
A. Azevedo, T. Torres.
Clinical Efficacy and Safety of Ixekizumab for Treatment of Psoriasis.
Actas Dermosifiliogr, 108 (2017), pp. 305-314
[2]
P. Nash, B. Kirkham, M. Okada, P. Rahman, B. Combe, G.R. Burmester, et al.
Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: Results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial.
Lancet, 389 (2017), pp. 2317-2327
[3]
B. Strober, C. Leonardi, K.A. Papp, U. Mrowietz, M. Ohtsuki, R. Bissonnette, et al.
Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data.
J Am Acad Dermatol, 76 (2017), pp. 432-440
[4]
M. Colina, G. Cianco, M. Khodeir, S. Sferra, P. Scanavacca, M. Corazza, et al.
De novo onset of arthritis in patients previously treated with efalizumab: An observational case series.
Clin Exp Rheumatol, 29 (2011), pp. 141
[5]
M. Napolitano, N. Balato, F. Caso, L. Costa, M. Megna, T. Cirillo, et al.
Paradoxical onset of psoriatic arthritis during treatment with biologic agents for plaque psoriasis: A combined dermatology and rheumatology clinical study.
Clin Exp Rheumatol, 35 (2017), pp. 137-140
[6]
A. Asahina, Y. Umezawa, M. Momose, H. Honda, K. Yanaba, H. Nakagawa.
New onset or transition of disease state of psoriatic arthritis during treatment with ustekinumab: A single-center retrospective study.
J Dermatol, 44 (2017), pp. 1380-1384

Please cite this article as: Vidal D, Ros S, Reina D. Artritis paradójica por ixekizumab en un paciente con psoriasis en placas. Actas Dermosifiliogr. 2019;110:255–256.

Copyright © 2018. Elsevier España, S.L.U. and AEDV
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