Topical Conversations

In this episode of Topical Conversations, Brad Glick, DO, and Erin Boh, MD, explore the evolving treatment landscape for generalized pustular psoriasis (GPP), with a focus on disease categorization, diagnostic challenges, and the role of spesolimab in managing both acute flares and chronic symptoms. Defining the spectrum of GPP Dr Boh categorizes GPP into 2 distinct clinical phenotypes: acute GPP, which often presents as a dermatologic emergency requiring immediate intervention, and chronic GPP, where patients exhibit persistent, low-grade symptoms punctuated by periodic flares. She emphasizes that understanding this distinction is critical for guiding treatment decisions. Compared to traditional plaque psoriasis, patients with chronic GPP often experience more prolonged flares and persistent systemic symptoms, necessitating tailored therapeutic strategies. Spesolimab: The only FDA-approved therapy for GPP Dr Glick outlines spesolimab’s approval as the first and only FDA-indicated treatment specifically for GPP. The intravenous (IV) formulation is approved for managing acute flares, and more recently, a subcutaneous (SC) formulation has been approved for use in patients between flares to address smoldering, chronic symptoms. Dr Boh explains her evolving approach to managing patients with chronic symptoms. Initially, she investigates potential flare triggers such as systemic steroids, infections, smoking, or other medications, and comorbidities like diabetes or cardiovascular disease for which patients may be receiving treatments from other providers. Historically, she used IV spesolimab for acute flares followed by maintenance with conventional biologics. However, with the SC formulation now available, she considers spesolimab monotherapy as a new maintenance option. Importantly, she stresses the need to distinguish between chronic plaque psoriasis with pustular features and true GPP, as the latter is more likely to benefit from spesolimab-based therapy. Pathophysiologic considerations and precision treatment Dr Boh discusses the evolving understanding of GPP's immunopathology. While IL-36 dysregulation is central, she notes overexpression of other cytokines such as IL-17 and IL-23 as well. This complexity raises questions about how patients may respond to IL-36 blockade alone versus requiring combination or sequential biologic therapy. Looking ahead, she sees potential for more personalized treatment approaches based on cytokine profiling. Chronic symptom burden and the role of maintenance therapy Dr Glick points out that, historically, no agent was specifically indicated for month-to-month stabilization in GPP. He highlights the unpredictable and often burdensome nature of flares compared to plaque psoriasis, making the new SC formulation of spesolimab a valuable addition for long-term control. Dr Boh adds that patients with GPP frequently report ongoing fatigue, pain, and emotional distress even after skin symptoms improve. She incorporates holistic strategies such as nutrition counseling, mindfulness, and therapy referrals into her care plans. She references findings from the Effisayil-2 trial, where continuous spesolimab treatment led to reductions in fatigue, pain, anxiety, and flare frequency, supporting a proactive treatment model over episodic flare-based management. Diagnostic challenges in GPP When patients present outside of a flare, diagnosing GPP can be difficult. Dr Glick asks how clinicians can differentiate GPP from other pustular presentations. Dr Boh explains that in acute settings, clinicians must rule out conditions like AGEP, drug reactions, steroid withdrawal, or infections. For more chronic or mixed presentations, such as plaque psoriasis with intermittent pustules, differentials include secondary infection, candida, vasculitis, or drug-induced eruptions. She distinguishes palmoplantar pustulosis as a separate entity within the pustular psoriasis spectrum. Ultimately, recognizing the degree and pattern of pustulation help guide diagnosis and treatment selection. An evolving practice model Dr Glick concludes by reiterating the clinical value of having both IV and SC formulations of spesolimab. The IV option offers rapid control during acute flares, while the SC formulation supports long-term maintenance. He highlights that in Effisayil-2, nearly half of the patients achieved complete skin clearance. With these new tools, dermatologists can now adopt a more structured and sustained approach to treating GPP, not only improving skin outcomes, but also enhancing overall quality of life for patients navigating this complex disease. Key takeaways Two distinct GPP phenotypes: Acute GPP requires immediate intervention, while chronic GPP involves ongoing low-grade symptoms and periodic flares, each requiring different therapeutic approaches Spesolimab for both acute and chronic GPP: IV spesolimab is approved for acute flares, and the SC formulation offers an option for maintenance therapy between flares Differentiating GPP from plaque psoriasis: Accurate diagnosis is essential, especially when pustular features overlap with other conditions. Misclassification may delay appropriate treatment. Precision medicine potential: While IL-36 plays a central role, other cytokines like IL-17 and IL-23 may also contribute to disease expression, raising the possibility of tailored biologic regimens Evolving treatment strategies: The availability of SC spesolimab has shifted management from flare-based intervention to continuous control, with some patients now managed with spesolimab monotherapy Quality-of-life impact: Chronic GPP symptoms extend beyond the skin. Fatigue, pain, and psychological distress persist even after flares resolve, supporting a holistic, proactive care model

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.

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

GPP Diagnosis and Treatment: What Every Dermatologist Should KnowIn this episode of Topical Conversations, Dr Aaron Farberg and Dr Neal Bhatia explore the challenges and advancements in diagnosing and treating generalized pustular psoriasis (GPP). emphasizing the need to shift the paradigm in managing GPP from viewing it as an acute, episodic condition to recognizing it as a chronic disease that requires sustained treatment and management. The diagnostic challenge Dr Bhatia identified diagnosis as the foremost challenge in GPP management, noting that many patients present to primary care physicians, urgent care centers, or emergency departments where their condition is misdiagnosed as folliculitis, acute generalized exanthematous pustulosis, or drug eruptions. He explains that misdiagnoses when it comes to GPP are often the result of an awareness gap, as many health care providers are simply not trained to recognize it. Without a timely and accurate diagnosis, patients are frequently prescribed unnecessary antibiotics or steroids in the absence of dermatologic input. Dr Farberg highlighted the importance of collaboration between dermatologists and community physicians, urging primary care providers to involve dermatologists immediately when encountering pustules and rashes. He emphasized the need for dermatologists to make themselves accessible for same-day or next-day appointments to ensure patients receive the appropriate care without delays. Educating dermatologists on rare diseases Both stressed the importance of education on rare dermatologic conditions like GPP. Dr Bhatia noted that medical dermatology topics often receive insufficient attention at conferences due to their perceived rarity. However, he cautioned that dermatologists will likely encounter these conditions during their careers and must be prepared. He encouraged dermatologists not only to remain vigilant for GPP but also to educate their colleagues to bridge the existing knowledge gap. Advancements in GPP treatment Historically, GPP has been difficult to treat, but the FDA-approved therapy spesolimab has transformed the treatment landscape. Drs. Farberg and Bhatia discussed the availability of spesolimab in both intravenous (IV) and subcutaneous formulations, each serving a distinct role in managing the disease. The IV formulation is designed to treat acute flares, providing rapid control of the disease, while the subcutaneous version is intended for long-term maintenance, aiming to prevent flares altogether. Dr Bhatia noted that clinical trials for the subcutaneous formulation enrolled patients in remission to test its ability to maintain disease quiescence. He also highlighted the trial’s rescue component, where patients experiencing flares received IV spesolimab, often achieving prompt symptom relief. Dr Farberg underscored the importance of distinguishing between the 2 formulations, advising against substituting multiple subcutaneous injections for an IV dose during acute flares, as the absorption profiles differ. He reassured dermatologists that the IV option, included in the clinical study design, provides an effective fallback for flare management. Shifting the paradigm Both Drs Farberg and Bhatia emphasized the need to redefine how dermatologists approach GPP, noting that it’s not only an acute condition but a chronic disease that causes a significant quality of life decline for patients. He advocated for transitioning patients on other biologics to spesolimab, which directly targets the IL-36 pathway specific to GPP. Dr Bhatia highlighted the significant improvement in quality of life that spesolimab offers, allowing patients to move from crisis management to a state of controlled disease. Addressing access and coverage Access to spesolimab has been streamlined, with both Dr Farberg and Dr Bhatia commending the support systems in place to facilitate rapid availability of the drug. Dr Farberg noted that he has encountered no significant barriers to obtaining it for his patients, a promising step toward closing both the educational and access gaps in GPP care. A comprehensive approach With spesolimab, dermatologists now have a powerful tool to manage this complex and rare condition effectively. By combining timely diagnosis, interdisciplinary collaboration, education, and advanced therapies, dermatologists can redefine the standard of care for GPP, ensuring patients receive comprehensive treatment.

In this episode of Topical Conversations, Brad P. Glick, DO, MPH, and Aaron Farberg, MD, explore the advancements in treating generalized pustular psoriasis (GPP) with the introduction of subcutaneous spesolimab. They discuss the chronic nature of GPP, the trial data that led to the drug’s approval, and its significant impact on the treatment landscape and patient experience. A targeted agent for a challenging condition The conversation begins with an overview of spesolimab IV, highlighting its significance as the first FDA-approved systemic therapeutic agent for acute GPP flares. They discuss the challenges in managing this chronic, heterogeneous condition, which previously lacked specific therapeutic options, noting that spesolimab now provides a targeted treatment for the quiescent yet active phases of the disease. Addressing the educational gap and increased GPP awarenessDr Farberg notes that he anticipates an increase in GPP diagnosis and treatment as awareness and education improve. He stresses the importance of having an effective, approved medication for GPP, noting the substantial impact compared to older, less targeted treatments. He also discusses the recent approval of subcutaneous spesolimab, which offers a new dosing option for sustained disease management between flares. Clinical insights on GPP management Dr Glick shares his clinical experiences managing GPP, particularly in acute settings such as hospitals and emergency rooms. He underscores the IL-36 pathway’s pivotal role in GPP pathogenesis and how spesolimab effectively targets this pathway. He highlights the transition from IV dosing in acute flares to subcutaneous dosing for ongoing disease control, enhancing long-term patient outcomes. Effisayil-2 data: chronic GPP treatment insights The conversation then addresses the Effisayil-2 trial data, a randomised, placebo-controlled, dose-finding phase 2b trial that assessed the efficacy and safety of spesolimab for GPP flare prevention. The study identified a higher dose every 4 weeks as most effective in preventing flares and maintaining disease control. This dosing regimen, which kept about 90% of subjects clear at 48 weeks, offers a promising long-term management strategy for this often unpredictable disease. Comparing IV and subcutaneous dosing Addressing a common clinical question, Drs Glick and Farberg discuss the differing roles of IV and subcutaneous spesolimab and whether subcutaneous dosing can be used in place of intravenous. The subcutaneous dose is 150 mg, while the IV dose is 900 mg; achieving the same bioavailability with subcutaneous dosing would require a high number of injections, highlighting the distinct roles of each. Dr Farberg recommends the IV version for acute flares due to its higher dosage and rapid effect. Dr Glick concurs, noting that patients with acute GPP require aggressive treatment, whereas subcutaneous dosing is ideal for maintaining stability between flares. The necessity of ongoing GPP management and flare prevention Dr Farberg emphasizes the importance of treating the chronic aspects of GPP to prevent flares, which significantly impact patients’ quality of life. The Effisayil-2 trial supports proactive management to mitigate these severe episodes and improve long-term outcomes. Safety and efficacy of subcutaneous spesolimab The doctors review safety and efficacy data from the Effisayil-1 and Effisayil-2 trials. While some patients experienced fatigue, infections, flu-like symptoms, and injection site reactions with the IV drug, the subcutaneous dosing showed fewer side effects, with some urinary tract infections being the most notable. Quality of life improvements The stable dosing regimen of subcutaneous spesolimab greatly enhances the quality of life for patients, their families, and caregivers. It simplifies the treatment process, making disease management more feasible and maintaining almost clear or clear conditions. This underscores the importance of having both IV and subcutaneous options, providing flexibility and comprehensive care for patients with GPP. Drs Glick and Farberg conclude that the availability of both IV and subcutaneous spesolimab marks a significant advancement in GPP management. These therapies not only improve patient outcomes but also enhance the overall treatment experience, offering improved quality of life for those affected by this challenging condition.

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.

In this installment of Topical Conversations, Mark Lebwohl, MD, and Boni Elewski, MD, discuss spesolimab, the first FDA-approved treatment for generalized pustular psoriasis (GPP). Dr Elewski recounts the case of a patient who experienced a severe GPP flare after receiving systemic steroids and experienced rapid improvement after a single intravenous infusion of spesolimab 900 mg along with triamcinolone 0.1% ointment and hydrocortisone 1% cream. Spesolimab, an IL-36 receptor antagonist, initially approved for the treatment of GPP flares, has now also received an expanded subcutaneous indication for maintenance therapy, recognizing that the chronic nature of GPP requires continuous management beyond just reactive treatment for flares. This expansion was majorly based on results from the Effisayil 2 clinical trial, a 48-week clinical trial that showed that spesolimab significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab subcutaneous treatment in the high-dose group (n=30).

In this episode of Topical Conversations, Raj Chovatiya, MD, PhD, and Laura Ferris, MD, PhD, explore the complexities of generalized pustular psoriasis (GPP), highlighting its chronic nature and the challenges it poses for both patients and providers. They stress the importance of recognizing and treating GPP not just during acute flares but throughout its chronic course. Longitudinal disease activity and the patient-provider disconnect Dr Chovatiya emphasizes that while some patients with GPP may present for the first time in the hospital with severe flares requiring intensive care, many others experience longitudinal activity with symptoms that persist over time. These patients may have less severe manifestations, such as scaly or pustular lesions covering only a small percentage of their body surface area. There exists a disconnect between patients and HCPs, with patients often downplaying their chronic symptoms and HCPs underestimating the severity of the disease unless it presents in its most extreme form. Continuous management and between-flare challenges Dr Ferris echoes the sentiment that GPP is a chronic condition that requires continuous management. She emphasizes 2 key aspects of care: preventing flares and addressing the symptoms that persist between flares. Despite not reaching the severity seen during hospitalization, patients still endure discomfort and impairment in their day-to-day lives. However, historically there has been a lack of effective treatment options for managing these in-between symptoms. A comprehensive approach to GPP management Dr Chovatiya advocates for a comprehensive approach to managing GPP, consisting of 3 steps: treating acute flares, preventing future flares, and providing ongoing control to minimize disease activity over time. By adopting this strategy, the goal is to achieve long-term disease remission or low disease activity. He also suggests that GPP may be more prevalent than commonly thought, emphasizing the need for improved diagnostic accuracy and targeted therapies. Future directions Both physicians acknowledge the current limitations in accurately diagnosing and effectively treating GPP, particularly during periods of low disease activity. They advocate for the development of more targeted therapies that address the underlying mechanisms of the disease to better manage patients' symptoms and improve their quality of life. Ultimately, their discussion underscores the importance of recognizing GPP as a chronic condition that requires continuous monitoring and intervention to minimize its impact on patients.