Is PD1 (Programmed Death-1)-induced psoriasis still considered an autoimmune condition?

PD1-Induced Psoriasis Is Considered an Autoimmune Condition

Yes, PD1-induced psoriasis is still considered an autoimmune condition, representing a specific type of immune-related adverse event (irAE) that occurs during immune checkpoint inhibitor therapy. 1

Immunological Basis of PD1-Induced Psoriasis

PD1 inhibitors work by removing the "brakes" on the immune system, which can lead to:

• Unrestrained T-cell activity creating a proinflammatory microenvironment 1
• Activation of autoreactive T cells that may target antigens present in both tumor cells and healthy tissue 1
• Elevated levels of inflammatory cytokines as a downstream effect of T-cell activation 1

These mechanisms can trigger or exacerbate autoimmune conditions, including psoriasis, which is characterized by:

• Chronic inflammatory skin disease with immune-mediated pathogenesis 2
• Involvement of activated T cells in psoriatic plaques 3
• Production of inflammatory cytokines that drive the disease process 2

Evidence from Clinical Guidelines

The NCCN Guidelines (2019) explicitly categorize psoriasis among pre-existing autoimmune disorders that may flare during immune checkpoint inhibitor therapy:

• In studies of patients with pre-existing autoimmune conditions receiving PD-1 inhibitors, 38-42% experienced autoimmune condition flares requiring immunosuppression 1
• Psoriasis is specifically listed alongside other autoimmune conditions like rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis 1
• Management approaches for psoriasis flares during immunotherapy are similar to those for other autoimmune condition flares 1

Clinical Presentation and Management

When PD1 inhibitors trigger or exacerbate psoriasis:

• Onset typically occurs within 6 weeks following the start of anti-PD-1 therapy, though it can be delayed 1
• Clinical presentations vary with focal to diffuse distributions, including flexural, inverse, and erythrodermic variants 1
• Pruritus is often severe and is the most common associated symptom 1

Management follows a stepwise approach:

1. For mild flares: Topical therapies may be sufficient (used in 53% of cases) 4
2. For moderate-severe flares: Systemic therapy may be required (needed in 21% of cases) 4
3. Only about 7% of patients require discontinuation of immunotherapy due to psoriasis flares 4

Debate in the Field

While there is some debate about whether primary psoriasis is purely autoimmune or has autoinflammatory components 5, PD1-induced psoriasis is consistently classified as an autoimmune irAE in clinical guidelines 1. The mechanism of action of PD1 inhibitors in unleashing T-cell responses supports the autoimmune nature of this adverse effect.

Prognostic Implications

Interestingly, patients who experience psoriasis flares during PD1 inhibitor therapy may have better outcomes:

• A multicenter study found significantly longer progression-free survival in patients with psoriasis flares versus those without (39 vs 8.7 months, p=0.049) 4
• This suggests that the immune activation causing the psoriasis may be linked to enhanced anti-tumor activity

Clinical Recommendation

For oncologists managing patients with pre-existing psoriasis who need PD1 inhibitor therapy:

• Pre-existing psoriasis should not prevent patients from receiving immune checkpoint inhibitors for malignancy 4
• Early dermatology consultation is recommended when psoriasis flares occur 1
• Most flares can be successfully managed with standard psoriasis treatments while continuing immunotherapy 4
• Close monitoring and interdisciplinary collaboration between oncology and dermatology are essential for optimal outcomes