In this episode of Topical Conversations, Ron Vender, MD, and Raj Chovatiya, MD, discuss the varied presentations of generalized pustular psoriasis (GPP) and the importance of early diagnosis and targeted treatment. They explore how GPP appears across different skin tones and levels of disease involvement and share insights for improving patient outcomes. 

Understanding GPP: beyond plaque psoriasis 

They begin by explaining that GPP is a distinct clinical entity from plaque psoriasis, presenting with widespread pustules, redness, and scaling rather than thick plaques and induration. While it can occur in patients with a history of psoriasis, it is not merely an extension of plaque disease. Dr. Chovatiya highlights that GPP is often misperceived as an extreme, acute condition, when many patients experience chronic, smoldering symptoms that may be misdiagnosed in nondermatology settings. 

Recognizing GPP across skin types 

GPP’s redness and pustules can look different across various skin tones. In lighter skin, erythema often appears bright red, while in darker skin, it may be more purple or brown, and pustules may look duskier rather than yellow-white. According to Drs Chovatiya and Vender, diagnosing GPP requires a careful clinical exam, a detailed patient history, and sometimes biopsy or bacterial swabs to rule out infection, though Dr Vender cautions not to wait for biopsy results to begin treatment. 

The importance of rapid diagnosis and treatment 

Drs Vender and Chovatiya emphasize that GPP is a potentially life-threatening condition with risks of sepsis, infection, and organ failure. Delaying treatment can have severe consequences, making early recognition and intervention critical. 

Spesolimab: a targeted approach to GPP 

Spesolimab, an IL-36 receptor antagonist, is the first treatment designed specifically for GPP. It is available in 2 formulations: 

• Intravenous (IV) infusion for acute flares to quickly control pustulation 
• Subcutaneous injection for long-term maintenance to help prevent flares 

Because GPP’s pathophysiology is IL-36 driven, spesolimab is not particularly effective for plaque psoriasis, reinforcing the need for accurate diagnosis and appropriate treatment selection. Dr. Vender emphasizes that educating patients about this targeted therapy can improve adherence and outcomes. 

By recognizing GPP’s diverse clinical presentations, diagnosing it early, and initiating appropriate treatment, dermatologists can significantly improve patient care and reduce disease burden. 

Key takeaways 

• GPP is distinct from plaque psoriasis and requires a different diagnostic and treatment approach 
• Smoldering GPP cases may be overlooked; taking a thorough patient history is critical 
• GPP presents differently across skin tones—erythema may appear red, purple, or brown 
• Early diagnosis and treatment are essential due to the risk of sepsis and organ failure 
• Spesolimab is the first targeted therapy for GPP, available as an IV forumulation for acute flares and a subcutaneous formulation for maintenance