Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience

doi:10.1016/j.jaad.2016.08.012

Journal of the American Academy of Dermatology

Volume 76, Issue 2, February 2017, Pages 334-341

https://doi.org/10.1016/j.jaad.2016.08.012 Get rights and content

Background

Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis.

Objective

To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis.

Methods

Systematic review of published cases of TNF-α inhibitor-induced psoriasis.

Results

We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%).

Limitations

Retrospective review that relies on case reports and series.

Conclusion

While TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.

Section snippets

Methods

We conducted an electronic literature search to identify studies, case reports, and case series that documented new-onset psoriasiform lesions in patients being treated with a TNF-α inhibitor (Fig 1).

Clinical and histopathologic characteristics

Of the 190 full-text articles assessed for eligibility, 88 articles met inclusion criteria for the final analysis. We extracted a total of 216 cases of new-onset TNF-α inhibitor-induced psoriasis from these publications. Demographic features of patients with TNF-α inhibitor-induced psoriasis are summarized in Table I.

Women comprised 72.2% of the cases, with a female predominance in RA and CD (89.9% and 63.2%, respectively). Ages of psoriasis onset ranged from 7 years to 83 years; the mean age

Discussion

Psoriasiform lesions are a well-documented complication of TNF-α inhibitor therapy that can occur at any time during the treatment course.² However, in our analysis, we found the majority (69.9%) occur within the first year of treatment. Furthermore, our review of published photographs suggests that many patients had generalized involvement with more than one morphological type. The typical presentations include plaque or palmoplantar pustular psoriasis, though various clinical morphologies

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La aparición de una reacción paradójica no siempre obliga al cambio de tratamiento biológico, puesto que se ha observado la resolución de las lesiones cutáneas con un tratamiento tópico y/o sistémico adicional en más de la mitad de los pacientes, sin necesidad de suspender el anti-TNF. Si la afectación es grave, se debe plantear el cambio de tratamiento biológico, siendo más eficaz iniciar un fármaco dirigido a una diana terapéutica distinta al anti-TNF.
Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions.
Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain.
We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution.
Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.
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In recent years, identifying the pathophysiologic mechanisms underlying autoimmune arthritides and systematic diseases has led to the use of biological drugs. The primary targets of those biological therapies are cytokines, B cells, and co-stimulation molecules. So far, these targeted therapies have shown good clinical improvement and an acceptable toxicity profile. However, by blocking components of an intact immune system, autoimmune phenomena and paradoxical inflammation have emerged, and among them many cutaneous immune-related adverse events (irAEs).
In this article, we review the current state of knowledge on the clinical features and mechanisms of specific cutaneous irAEs observed during treatment with biological therapies. Among those, psoriatic skin lesions are the most commonly observed. Herein, we also report new cases of cutaneous irAEs recently seen in our clinic to help physicians treating inflammatory arthritides recognize cutaneous irAEs early and better manage patients receiving biologic therapies.
Paradoxical psoriasis: The flip side of idiopathic psoriasis or an autocephalous reversible drug reaction?
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Biotechnological monoclonal antibodies and receptor antagonists capable of targeting specific inflammatory actors, such as cytokines, cytokines receptors, co-stimulatory molecules or leukocyte populations, have emerged as an alternative to conventional therapies for treating systemic inflammatory diseases with immune pathogenesis. However, there is no doubt that, with a frequency that is not exceptionally high but also not negligible, immunotherapies can favour the development of systemic and organ-specific immune-mediated disorders. It has become increasingly evident that interference with a specific immune pathway may favour the activation of opposing compensatory signalling, which may exacerbate underlying subclinical disorders or cause immune-mediated diseases completely different from the underlying disease. The ‘compensatory immunological switch’ has emerged primarily in patients treated with tumor necrosis factor (TNF) -α inhibitors, the first biological drugs approved for treating systemic inflammatory diseases with immune pathogenesis. In this Review, we describe the clinical features and predisposing factors of the main TNF-α inhibitor-related autoimmune disorders, organising them into subclinical serological autoimmunity, autoimmune disorders other than those for which TNF-α inhibitors are indicated, and paradoxical reactions. We also discuss the underlying pathogenetic mechanisms and precautions for use in the therapeutic management of these patients. Better understanding of the complex phenomenon of the ‘compensatory immunological switch’, which TNF-α inhibitors and other biological drugs might trigger, can help not only appropriately managing immune-mediated disorders, but also better interpreting the heterogeneity of the pathogenetic mechanisms underlying certain chronic inflammatory conditions that, although different from each other, are arbitrarily placed in the context of overly generic nosological entities.
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View all citing articles on Scopus

: Drs Brown and Wang are co-first authors.

: Supported in part by grants from the National Institutes of Health (R01AR065174 and K08AR057763) to WL. National Clinical and Translational Science Institute (8KL2TR000143) to EL, and Dermatology Foundation Career Development Awards to EL and AH.

: Conflicts of interest: None declared.

View full text

ReviewTumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience

Background

Objective

Methods

Results

Limitations

Conclusion

Section snippets

Methods

Clinical and histopathologic characteristics

Discussion

J Am Acad Dermatol

Mayo Clin Proc

J Invest Dermatol

Gastroenterology

Semin Arthritis Rheum

Tumor necrosis factor alpha antagonist-associated psoriasis in inflammatory diseases: an analysis of the FDA adverse event reporting system

Inflamm Bowel Dis

Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action

Arthritis Rheum

Histopathologic spectrum of psoriasiform skin reactions associated with tumor necrosis factor-alpha inhibitor therapy. A study of 16 biopsies

Am J Dermatopathol

Connections between psoriasis and Crohn's disease

J Am Acad Dermatol

Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis

Arch Dermatol

Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?

Ann Rheum Dis

Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study

Arthritis Res Ther

Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction

Arthritis Rheum

The yin and yang of TNF-(alpha) inhibition

Arch Dermatol

Review
Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience