Two Psoriasis Variants, Two Very Different Diseases 

In this episode of Topical Conversations, Jason Hawkes, MD, and Tina Bhutani, MD, discuss how generalized pustular psoriasis (GPP) differs from plaque psoriasis in presentation, immunopathogenesis, and treatment. With the emergence of targeted therapies, distinguishing between these conditions is more important than ever for effective management. 

Clinical Presentation: Sudden Flares vs Chronic Plaques 

Plaque psoriasis typically follows a chronic course, with well-demarcated plaques on the scalp, elbows, and knees. GPP, by contrast, is marked by abrupt flares of monomorphic pustules on an erythematous base. These flares may be episodic, severe, and unpredictable—sometimes occurring years apart—and are often mistaken for plaque flares or infections. Dr Bhutani emphasizes the importance of recognizing GPP early, particularly when it coexists with background plaque psoriasis. 

Immunology and Genetics: IL-23 vs IL-36 

Dr Hawkes highlights the distinct immune pathways driving each disease. Plaque psoriasis is driven largely by IL-23 and IL-17 signaling, with T cells playing a central role. GPP, however, is primarily mediated by innate immune mechanisms, including overproduction of IL-36 by keratinocytes. In some patients, mutations in the IL-36 receptor antagonist (IL36RN) gene further amplify this response. These differences in immunology and genetics reinforce the need for tailored therapeutic strategies. 

Diagnosis and Initial Management 

Prompt recognition and stabilization are key when managing GPP. Dr Bhutani advises ruling out infection and allergic reactions but stresses that treatment should not be delayed for biopsy results. Dr Hawkes adds that clinical history and physical findings—particularly the presence of sterile pustules and systemic symptoms—can strongly support a diagnosis of GPP. Laboratory tests may assist with assessing organ function or ruling out sepsis, but immediate therapy is often warranted. 

Targeted Therapy and Clinical Impact 

In the past, GPP was treated with systemic immunosuppressants like cyclosporine or methotrexate, which carried significant risks. Today, therapies targeting IL-36 offer faster and safer relief. Dr Bhutani underscores the dramatic improvement in outcomes for patients receiving these treatments, noting that they not only control flares but also reduce long-term disease burden and improve quality of life. 

Improving Quality of Life Through Timely Care 

GPP’s unpredictability can severely impact patients’ physical, emotional, and social well-being. Both physicians agree that faster diagnosis, patient education, and early use of targeted treatments are essential. For many patients, these interventions can prevent hospitalization and even save lives. 

Key Takeaways 

• GPP and plaque psoriasis are distinct conditions with different presentations, immune drivers, and treatment needs.
• GPP is characterized by episodic, severe pustular flares and systemic symptoms, with a risk of organ failure and mortality.
• IL-36 plays a central role in GPP pathogenesis, and targeted therapies now offer rapid, effective control.
• Diagnosis should not be delayed for biopsy results; early recognition and stabilization are critical.
• Treating GPP promptly and appropriately improves both outcomes and patient quality of life.