Diagnosing TNF-Induced Psoriasis: What Providers Need to Know

TNF-inhibitor therapies are commonly used among patients with psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). However, they are associated with psoriatic eruptions or worsening of preexisting psoriatic skin disease.

In a recent review, Sara Jiayang Li, BS, Lourdes M. Perez-Chada, MD, MMSc, and Joseph F. Merola, MD, MMSc, at the Brigham and Women’s Hospital, Harvard Medical School in Boston, MA conducted a literature review to determine a novel treatment algorithm for managing patients treated with anti-TNF inhibitors who develop or experience this adverse event.¹

They discussed their algorithm (Table) and what providers should consider when treating TNF-induced psoriasis in an interview with The Dermatologist.

The Dermatologist: Could you briefly explain the features of TNF-inhibitor induced psoriasis to providers?

Authors: Some distinctive features of anti-TNF induced psoriasis include:

1. The temporal relationship between the onset of the anti-TNF therapy and the appearance of cutaneous lesions. The average latency between treatment initiation and onset of anti-TNF psoriasis is 10.5 months; however, this may span from a few days to several years.^2-4 
2. The overlapping morphologies including plaque-type, pustular psoriasis (generalized/pustular), guttate, inverse, nail and/or scalp psoriasis. The most common presentations include pustular palmoplantar psoriasis, plaque psoriasis, and an overlapping morphology of eczematous-psoriasiform dermatitis.^5,6
3. The histopathological spectrum including 3 distinct patterns which may appear simultaneously: 1) classic psoriatic pattern; 2) eczematous pattern with spongiosis; 3) lichenoid pattern with interface dermatitis.⁷ However, the diagnosis is generally clinical, with few cases requiring histological evaluation of the lesions.
4. The clinical improvement observed after discontinuation of therapy and subsequent recurrence of psoriatic lesions after switching to another anti-TNF agent or restarting the same agent.
5. The absence of a personal or family history of psoriasis reported in the majority of the cases.

The Dermatologist: When determining which treatment option to follow, what are the key or most important aspects?

Authors: The patient and the physician should carefully discuss whether it is prudent to withdraw the anti-TNF agent. Ultimately, the decision should be based on three key elements: 1) the severity of TNF-induced psoriasis; 2) the severity of the underlying disease process; 3) the availability of other treatment options for the underlying disease.⁸ In general, a “treat through” approach with typical psoriasis therapies could be considered in mild-to-moderate cases.

The Dermatologist: If a patient has mild psoriasis eruption but reports poor health-related quality of life, will this determine a more or less aggressive treatment option for the psoriasis? What are the challenges of treating anti TNF-induced psoriasis?

Authors: In our algorithm, we defined “mild psoriatic eruption” as those cases in which both the extension of the disease and the impact on quality of life are considered tolerable by the patient. So, if a patient has poor health-related quality of life, the skin eruption severity should be considered, at least, moderate.

In moderate and severe cases of TNF-inhibitor induced psoriasis, the treatment will depend on the state of the underlying disease. If the underlying disease is well controlled, switching to a different anti-TNF agent can be considered, though most cases will not respond to this approach. Now, if the underlying disease is not well controlled or if the patients did not respond to a different anti-TNF agent, we propose switching to a different class of treatments. The choice of the new class of agents will depend on the treatment armamentarium available for the underlying disease.

The Dermatologist: What should providers know or ask patients prior to selecting a TNF inhibitor to attempt to prevent or reduce the risk of TNF-induced psoriasis? How should they discuss this risk with patients?

Authors: Predictors of anti-TNF induced psoriasis remain unclear, although there are a higher number of cases reported in patients treated with infliximab (Remicade).⁹  Most studies report that women and men are equally affected by TNF-induced psoriasis^2,10,11 and previous family or personal history of psoriasis was not identified as a predisposing factor.^4,11 However, among patients with inflammatory bowel disease, being female and having a history of smoking were identified as risk factors for anti-TNF induced psoriasis.^9,11 Because only few of the patients treated with anti-TNF develop this condition, it is likely that this phenomenon is related to genetic predisposition.^4,12

To best counsel patients about the risk of experiencing anti-TNF induced psoriasis, providers should be aware that this phenomenon occurs in about 5% of the cases² and be familiar with the several treatment strategies available for patients.

The Dermatologist: What and how should providers discuss expectations for resolution of psoriasis eruptions in these patients, especially those who are switching to a new TNF inhibitor?

Authors: Counseling on realistic expectations on the outcome is highly important. Patients should be aware about the possibility of not achieving complete resolution of symptoms after intervention. Furthermore, response to treatment depends on the severity and clinical subtype of psoriasis. In most mild cases, a “treat through” strategy with targeted therapies for psoriasis is effective. Switching to a different anti-TNF is usually less effective.^2,4,9 In severe or refractory cases, switching to a different class has shown promising results.^9,12

The Dermatologist: What areas still require further research to predict, prevent, and manage TNF-induced psoriasis?

Authors: Dysregulation of IFN-alpha and the IL23/Th17 axis may contribute to the pathogenesis of anti-TNF induced psoriasis. However, the precise mechanism remains unclear. Genetic evaluation of patients with anti-TNF induced psoriasis may provide valuable information to understand the pathogenesis of this condition. In addition, genetic studies may help identify genetically susceptible patients for risk stratification.

The Dermatologist: What key takeaways would you like our audience to leave with?

Authors:

• Anti-TNF induced psoriasis occurs independently of the type of anti-TNF agent used (although infliximab may be associated with a higher risk) and tends to resolve after discontinuation of the agent. Data seems to suggest a TNF class effect rather than a drug-specific effect.
• While most cases occur during the first year of treatment, this phenomenon can occur at any time during the treatment course.
• The patient and the physician should carefully discuss whether it is prudent to withdraw the anti-TNF agent considering the severity of TNF-induced psoriasis, the severity of the underlying disease process, and the availability of other treatment options for the underlying disease.
• In general, a “treat through” approach with typical psoriasis therapies could be considered in most mild-to-moderate cases.

References

1. Li SJ, Perez-Chada LM, Merola JF. TNF inhibitor-induced psoriasis: Proposed algorithm for treatment and management. J Psoriasis Psoriatic Arthritis. 2019;4(2):70-80. doi:10.1177/2475530318810851

2. Ko JM, Gottlieb AB, Kerbleski JF. Induction and exacerbation of psoriasis with TNF-blockade therapy: A review and analysis of 127 cases. J Dermatol Treat. 2009;20(2):100-108. doi:10.1080/09546630802441234

3. Bruzzese V, De Francesco V, Hassan C, et al. New onset or worsening of psoriasis following biologic therapy: A case series. Int J Immunopathol Pharmacol. 2017;30(1):70-72. doi:10.1177/0394632016688221

4. Brown G, Wang E, Leon A, et al. Tumor necrosis factor-alpha inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience. J Am Acad Dermatol. 2017;76(2):334-341. doi:10.1016/j.jaad.2016.08.012

5. Lee HH, Song IH, Friedrich M, et al. Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol. 2007;156(3):486-491. doi:10.1111/j.1365-2133.2007.07682.x

6. Flendrie M, Vissers WH, Creemers MC, de Jong EM, van de Kerkhof PC, van Riel PL. Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: A prospective study. Arthritis Res Ther. 2005;7(3):R666-676. doi:10.1186/ar1724

7. Mylonas A, Conrad C. Psoriasis: Classical vs. paradoxical. The yin-yang of TNF and type I interferon. Front Immunol. 2018;9:2746. doi:10.3389/fimmu.2018.02746

8. Li SJ, Perez-Chada LM, Merola JF. TNF inhibitor-induced psoriasis: Proposed algorithm for treatment and management. J Psoriasis and Psoriatic Arthritis. 2019;4(2):70-80. doi:10.1177/2475530318810851

9. Guerra I, Perez-Jeldres T, Iborra M, et al. Incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in patients with inflammatory bowel disease: A nationwide cohort study. Inflamm Bowel Dis. 2016;22(4):894-901. doi:10.1097/MIB.0000000000000757.

10. Collamer AN, Guerrero KT, Henning JS, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: A literature review and potential mechanisms of action. Arthritis Rheum. 2008;59(7):996-1001. doi:10.1002/art.23835

11. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: Clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40(3):233-240. doi:10.1016/j.semarthrit.2010.04.003

12. Tillack C, Ehmann LM, Friedrich M, et al. Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-gamma-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014;63(4):567-577. doi:10.1136/gutjnl-2012-302853