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EADV 2020 | Psoriasis: Classical vs Paradoxical

Biologics, Quality of life, Topical therapies 2020

Presented by Curdin Conrad, MD

 A report from the 29th Congress of the European Academy of Dermatology and Venereology

Since their approval, TNF-α blockers have remained a vital treatment for many inflammatory conditions. However, some patients develop a characteristic psoriasiform rash on therapy, deemed ‘paradoxical psoriasis’.

Dr. Conrad studied this TNF-inhibitior (TNFi) induced paradoxical psoriasis in patients, and found that paradoxical psoriasis: is a class effect of all TNFi, is selective for TNFi, is a side effect of TNFi (it is not de novo psoriasis), and resolves when switching to alternate class. Comparing several psoriasis cytokines, his team found a massive accumulation of plasmacytoid dendritic cells (pDCs) with ensuing Type-1 interferon (IFN-α) overexpression in paradoxical psoriasis compared to classical psoriasis.

In vitro models demonstrated that TNF-blockade on activated pDCs induces IFN-α production, whereas adding back TNF-α significantly decreased production. Similarly, in vivo tape-stripping mouse models revealed transient pDC influx and IFN-α production, and subsequent TNF-blockade prolonged this response. After 7 days TNF-blockade mice had a psoriasiform phenotype, but when IFN-α was also blocked this phenotype resolved.

These data suggest that TNF- α controls the expression of IFN from pDCs via a negative feedback loop, and that paradoxical psoriasis has complete dependence on IFN-α. Additionally, T-cells were not required to induce this psoriasiform rash in mice; CD8+ intraepidermal T-cells are were almost non-existent, in stark comparison to classical psoriasis.23

In summary, paradoxical and classical psoriasis are quite different despite clinical similarity. Importantly, paradoxical psoriasis completely resolves when switching from TNF-blockade to another class, and there is potential for future anti-IFN therapeutics.

Section Pearls:

  • Psoriasis is a systemic inflammatory state. Early intervention with biologics may prevent or diminish the development of metabolic, cardiovascular, and arthritis comorbidities.

  • Psoriasis patients are at increased risk for depression, anxiety, and suicidality regardless of disease extent. Young and severely affected patients are at higher risk. Early recognition and psoriasis treatment may prevent depressive symptoms.

  • Despite clinical similarity to classical psoriasis, TNF-blockade induced “paradoxical psoriasis” is a distinct entity. Paradoxical psoriasis is a class effect of all TNF-inhibitors, and drug cessation or switching to another medication class resolves the rash.
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