Asia-Pacific Biotech News

Unveiling the Hidden Struggle: Living with GPP

An interview with Dr Choon Siew Eng, Associate Professor, Monash University, Malaysia, to better understand generalised pustular psoriasis (GPP) and how we can build awareness.

Generalised pustular psoriasis (GPP) is a rare, lifelong, systemic skin disease that not only affects the physical health of individuals but also has a significant impact on their daily activities, social interactions, and mental well-being. Living with GPP can alter one’s social life and how they connect with their loved ones, as well as cause anxiety and depressive symptoms.

In this interview, we spoke to Dr Choon Siew Eng, Associate Professor, Monash University, Malaysia, to learn more about GPP, current and future therapy options, and how organisations can help to increase awareness of this condition.


1. Can you tell us a little more about generalised pustular psoriasis (GPP)? What causes it, how does it differ from other psoriasis, and how prevalent is this in Asia?

Generalised pustular psoriasis (GPP) is a rare and chronic systemic disease with predominant skin manifestations. It is characterised by recurrent episodes or flares of widespread painful sterile skin pustules accompanied by systemic symptoms such as fever, fatigue, and general malaise.

The exact cause of GPP is not fully understood, but disease manifestation is thought to result from a complex interplay between genetic and environmental factors, and the dysregulated overactive immune response. IL-36 is the key driver of disease pathology in GPP. The central role of IL-36 pathway in the pathogenesis of GPP is supported by the presence of IL36RN mutations in 20-80% of patients with GPP. IL36RN codes for IL-36 receptor antagonist (IL36Ra), which modulates the proinflammatory activities of IL- 36. Mutations of IL36RN leads to the synthesis of abnormal IL-36 receptor antagonist (IL36Ra), which is not able to inhibit the proinflammatory activities of IL-36 hence allowing uninhibited IL-36 signalling leading to the clinical manifestations of GPP. Triggers for GPP include infections such as upper respiratory infections, certain medications such as corticosteroids, pregnancy, and stress.

GPP differs from other forms of psoriasis in its severity and symptoms. While common plaque psoriasis typically presents with red, scaly patches of skin without systemic symptoms, GPP is characterised by the rapid appearance of painful, sterile pustules on red, inflamed skin with systemic symptoms. GPP often has recurrent acute episodes of flares followed by periods of remission, but life-threatening complications, namely sepsis and organ failure, may supervene in severe flares. The documented mortality of GPP ranged from 2%-16%.

The prevalence of GPP in Asia may vary from region to region. The reported prevalence per million population ranged from 14 in China, 20-30 in Japan, and 124 in South Korea. In Malaysia, the prevalence of GPP was estimated at 198 per million population. Its prevalence was significantly higher in women than men, and highest among Chinese, followed by Malay and Indians in our multiethnic population. The ethnic variation in the prevalence of GPP could be explained by genetic differences. IL36RN mutations were present in 27% of 40 Chinese and 17% of 75 Malay tested. But none of the 18 Indian GPP patients screened were found to have the mutation. There was only one study in which a homozygous IL36RN mutation was identified in two Pakistani siblings with GPP. Hence, IL36RN disease alleles may be rare in South Asians, explaining the lower prevalence of GPP observed in our Indian population.


2. Is GPP contagious? What are some current treatment options for individuals with GPP?

GPP is not contagious. It is an autoinflammatory disorder, which means it is caused by an abnormal immune response within the body. Unfortunately, pustules are commonly deemed a manifestation of infection. However, pustules in GPP are sterile, meaning they are not caused by an infection. You cannot “catch” GPP from someone who has it, and it is not spread through physical contact.

Treatment options for GPP depend on the severity of the condition and the individual’s overall health. Because GPP is a serious and potentially life-threatening condition, it often requires prompt medical attention and management by a healthcare professional, usually a dermatologist. Treatment goals generally include rapid resolution of the cutaneous and systemic inflammation, preventing complications, preventing further flares, and improving the overall quality of life.

Some of the treatment options for GPP include topical treatments like emollients and topical corticosteroids, which may be sufficient to resolve the skin inflammation in patients with mild GPP. For more severe cases, systemic treatments are necessary. Unfortunately, there is a lack of good-quality evidence to guide treatment choice because the rarity of GPP makes it difficult to recruit enough patients to conduct randomised controlled studies. Dermatologists use treatments approved for treating plaque psoriasis to treat GPP. These treatments include conventional systemic agents, namely acitretin and methotrexate as well as biologics like TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors.

3. Are there any new therapies that are in the pipeline?

A better understanding of the pathogenesis of GPP has paved the way for the development of therapies targeting the IL-36 pathway, which plays a crucial role in the pathogenesis of GPP. Currently, three IL36 receptor inhibitors, spesolimab, imsidolimab, and HB0034, are undergoing clinical trials as potential treatments for GPP flares. Spesolimab was already approved by the FDA for treating acute GPP flares in September 2022. The efficacy and safety of spesolimab were rigorously evaluated in Effisayil 1. Notably, Effisayil 1 is the first randomised controlled trial (RCT) designed specifically for patients with GPP, signifying a critical advancement in the research landscape for GPP. In Asia, spesolimab is also approved for treating acute GPP flares in Japan, China, and Taiwan. Imsidolimab is in advanced stages of development, with two Phase 3 clinical trials (Gemini 1 & 2 studies) underway. Developed by a Shanghai-based company, HB0034 is currently recruiting participants for its Phase 1 clinical trial. This trial is expected to conclude by the end of this year.

Further exposure and use of spesolimab are being explored in two other studies. The results of Effisayil 2, a flare prevention trial, presented at the recent 25th World Congress of Dermatology in Singapore, showed the efficacy and safety of subcutaneous spesolimab in preventing GPP trials up to 48 weeks. Effisayil On, an Open-Label Extension (OLE) study, explores the long-term effects and safety profile of spesolimab. As these therapies progress through clinical trials and gain regulatory approval, dermatologists will be able to provide highly efficacious targeted treatment for GPP flare-ups and proactively avert them in the future.


4. How can organisations help to increase awareness of this rare condition?

Raising awareness of rare conditions like GPP is essential for improving early diagnosis, treatment, and support for individuals affected by the condition. GPP not only affects the physical health of patients but also has profound implications for daily life, social interactions, and mental well-being. The journey towards an accurate diagnosis is often long and challenging, averaging about five years, leading to inadequate treatment. This prolonged period of uncertainty and suboptimal care intensifies the burden on patients, accentuating the mental toll. GPP changes how individuals engage with their social circles and loved ones, often leading to heightened feelings of anxiety and depression due to the persistent worry of future flare-ups and the reactions of others to visible symptoms. The impact on mental well-being is significant, compounded by the stigma faced by those afflicted. The physical and emotional load can be overwhelming.

Raising awareness about the complexities and far-reaching effects of GPP is paramount. This effort aims to foster a deeper understanding among various stakeholders, including the general public, patients, healthcare professionals, caregivers, and patient support networks. By increasing awareness, the intention is to bolster resources, compassion, and support for those grappling with GPP, ultimately culminating in improved diagnostic accuracy, treatment options, and overall quality of life.

Organisations can play a crucial role in raising awareness about GPP by engaging in various activities. They can create educational campaigns and materials to inform the public, healthcare professionals, and patients about the symptoms, challenges, and available treatments for GPP. Hosting workshops, seminars, and webinars with medical experts can help disseminate accurate information. Collaborating with healthcare institutions, patient advocacy groups, and online communities can create a supportive network for those affected by GPP. Additionally, using social media platforms, newsletters, and websites, organisations can share personal stories, research updates, and practical tips to increase awareness and understanding of GPP.

In a remarkable initiative, Boehringer Ingelheim joined forces with world-renowned designer Bart Hess to conceptualise and execute The Unwearable Collection™ of five designs taking inspiration from personal experiences shared by people living with GPP. Launched in 2022 and expanded in 2023, this artistic endeavour creatively captures the physical and emotional struggles experienced by GPP patients. Through this innovative project, the intention is to shine a light on the defining symptoms of GPP, reach a broader audience, and promote greater understanding through the fusion of education and art.

Additionally, Boehringer Ingelheim introduced the GPP Charter in close collaboration with patient support groups and esteemed GPP experts, which stands as a dynamic collaborative framework to empower those living with GPP and those working in the field. This Charter is a collective effort encompassing diverse perspectives to enact positive change in the status quo. Besides raising awareness, the GPP Charter also aims to improve knowledge and drive excellence in GPP care. It outlines actionable steps to elevate GPP on the agenda, highlighting the multifaceted impact of this rare disease on both physical health and emotional well-being. Remarkably, patient support groups like the International Federation of Psoriasis Network and the National Psoriasis Foundation/Psoriasis Associations across various nations, such as the US, Canada, the Philippines, and Malaysia, are now actively spearheading the implementation of the GPP Charter.

The International Psoriasis Council (IPC), a nonprofit organisation led by dermatologists committed to enhancing patient care in GPP through education, research, and advocacy, has taken substantial strides to improve knowledge and care of GPP patients. The council has organised specialised symposiums on GPP within prominent international dermatology meetings, providing a platform for in depth exploration of this rare disease. As a rare disease, GPP is often misdiagnosed and undertreated. Hence, IPC’s establishment of a pustular psoriasis working group, helmed by myself and my co-lead Prof Herve Bachelez, signifies a concerted effort to formulate a globally accepted consensus definition and diagnostic criteria for GPP, which holds promise for more accurate identification and enhanced care for individuals affected by this challenging disease.

In conclusion, organisations like Boehringer Ingelheim and IPC are making remarkable strides in enhancing awareness and care of GPP. These efforts aim to reshape perceptions, foster understanding, and drive tangible change in diagnosis, treatment, and support for individuals facing the challenges of living with GPP. [APBN]

This article was first published in the September & December 2023 print version of Asia-Pacific Biotech News.

About the Interviewee

Dr Siew Eng Choon is a senior consultant dermatologist at Hospital Sultanah Aminah, Johor Bahru, Malaysia and an Associate Professor, Clinical School Johor Bahru, Monash University, Malaysia.

She is also a board member of the International Psoriasis Council (IPC) and chairs the IPC pustular psoriasis working group, a key project team leader for COMPPASS (Core Outcome Measures for Pustular Psoriasis and Associated Systemic Symptoms), and a member of CIOMS-SCAR (Council for International Organizations of Medical Sciences- Severe Cutaneous Adverse Reaction) working group. Her research interests are mainly on potentially life-threatening skin diseases namely severe cutaneous adverse drug reactions (SCAR) and chronic inflammatory skin diseases such as psoriasis, specifically generalised pustular psoriasis, eczema and hidradenitis suppurativa.

She is currently an associate editor of Experimental Dermatology.