In this episode of Topical Conversations, Jason Hawkes, MD, MS, and Saakshi Khattri, MD, discuss the complexities of generalized pustular psoriasis (GPP) and how the treatment landscape has changed with the approval of a novel targeted therapy that treats acute flares through intravenous administration and ongoing symptoms via maintenance therapy with subcutaneous injections, effectively managing the chronic manifestations of the condition. 

Clinical presentation of a challenging condition 

The conversation begins with an overview of GPP, highlighting its clinical presentation with sterile pustules on an erythematous background and its sudden onset. Historically, GPP has been rare and often difficult to diagnose, sometimes being mistaken for other conditions. Dr Khattri adds to this by discussing the inflammatory nature of GPP, its symptoms including pain, itching, and systemic involvement, and its distinction from plaque psoriasis. 

A distinct mechanism of disease 

The conversation then addresses the immunological differences between GPP and plaque psoriasis. Dr Hawkes explains that while plaque psoriasis is primarily driven by cytokines IL-23 and IL-17, GPP is driven by IL-36, leading to keratinocyte proliferation and recruitment of neutrophils. This distinction is crucial as it affects treatment approaches, with traditional psoriasis treatments often ineffective for GPP. 

Emergence of a novel therapy 

They discuss the challenges in managing GPP before the approval of the targeted therapy spesolimab, an IL-36 receptor antibody. Historically, treatment options were limited, and management relied on adapting treatments for plaque psoriasis. 

Dr Hawkes highlights the complexity of GPP management, noting the overlap with plaque psoriasis and the need for personalized care. He emphasizes the significance of having targeted treatments like spesolimab, which can effectively address the underlying immune pathways driving GPP. 

The patient experience and counseling tips 

Dr Khattri shares her experience using spesolimab in practice, sharing the case of a patient who she transitioned from intravenous spesolimab to subcutaneous injections to manage the patient’s ongoing symptoms beyond flares. 

She also shares how she manages patient expectations on the treatment and course of GPP, comparing it to hypertension in that it requires maintenance therapy to keep symptoms under control. She emphasizes that while flares are a significant aspect of the disease, they are just one part of the overall picture. 

Full-spectrum management of GPP 

Finally, they discuss practical tips for managing GPP, with Dr Khattri emphasizing the importance of recognizing it as a treatable condition now with the availability of an approved medication. She advises colleagues to consider spesolimab for both acute flares and maintenance therapy, reflecting on the positive impact of having both intravenous and subcutaneous treatment options for patients with GPP.