International consensus statement on generalised pustular psoriasis aims to standardise diagnosis on a global scale.
The International Psoriasis Council has released new guidelines for generalised pustular psoriasis in a bid to achieve more timely and accurate diagnosis and better access to treatment.
IPC board member and co-author of the statement, Associate Professor Siew Eng Choon described it as “a landmark development in dermatology, promising to standardise the approach to diagnosing and treating this challenging condition worldwide”.
“As these criteria are adopted and implemented, we anticipate significant improvements in patient care and outcomes, particularly for those in underrepresented populations or with severe disease manifestations,” she said.
“This initiative enhances our understanding of GPP and exemplifies the power of global collaboration in health care.”
GPP is a rare and potentially life-threatening form of psoriasis that can present at any age, although the median age of onset is around 50 years. The disease is characterised by widespread areas of inflamed skin with pustules, and its severity can fluctuate, with periods of flare-ups followed by remission.
Flares may be triggered by multiple factors, such as rapid withdrawal of systemic corticosteroids, infections, pregnancy, and even stress. GPP flares can be life-threatening if untreated, owing to potential serious complications such as sepsis and cardiovascular failure.
The cause of GPP is not fully understood, but emerging evidence implicates a multifactorial interplay of genetic, environmental, and immune dysregulation factors. Mutations in genes such as IL36RN, highlights the crucial role of the IL-36 pathway in the pathogenesis of GPP.
Currently, GPP is treated with non-biologics and biologics approved for treating psoriasis. The only approved treatment option specifically for GPP is spesolimab, an interleukin-36 receptor antibody.
The TGA approved spesolimab for the treatment of flares in adult patients with GPP in November last year. The drug has been included in the Black Triangle Scheme for five years.
The IPC’s consensus statement was published in JAMA Dermatology this month. The researchers acknowledged the difficulties with diagnosing GPP.
“GPP is a heterogeneous disease with a wide range of clinical presentations, making accurate diagnosis and differentiation from other pustular dermatoses challenging,” they wrote.
“The severity and impact of GPP on patients’ physical and mental health, as well as their overall quality of life, underscore the urgent need for prompt diagnosis and effective treatment to alleviate patients’ suffering and mitigate potential life-threatening complications such as sepsis or kidney, liver, respiratory, and cardiovascular failure.
“Reported mortality rates ranging from 4% to 24% emphasise the gravity of the condition. A unified and precise set of diagnostic criteria is paramount to facilitate timely and accurate identification of GPP cases, enabling appropriate treatment and thereby reducing the risk of complications and improving patient outcomes.
“This becomes particularly pertinent with the recent approval of a highly efficacious targeted treatment for GPP.”
The IPC established a Pustular Psoriasis Working Group of international experts and used a modified Delphi approach to develop the statement. Eight working group members were joined by a panel of 33 GPP experts who contributed actively to the consensus study.
They reviewed 69 challenging cases, which the authors said highlighted the “remarkable diversity” in the clinical presentations of GPP and the inherent challenges in distinguishing it from common mimics, such as AGEP, SPD, and pustular forms of pemphigus.
“The submitted cases provided invaluable insights and made a compelling argument for the pivotal role of histopathology, complemented by direct immunofluorescence, in the accurate diagnosis of GPP,” they wrote.
“Although GPP may start with discrete pustules, these often evolve over time to form lakes of pus. The presence of numerous persistent discrete pustules without coalescence and hypopyon pustules should prompt dermatologists to consider performing a skin biopsy to confirm GPP and rule out potential mimicking conditions.”
The authors noted that erythema, particularly in patients with darker skin, was a challenge.
“While it initially did not achieve consensus due to the difficulty in appreciating erythema in individuals with darker skin tones, the panel eventually agreed that erythema, although potentially challenging to discern in individuals with darker skin, is an essential feature of GPP, reflecting the inflammatory nature of GPP, and should be included in the condition’s definition aside from pustules that reflect the neutrophilic nature of the GPP,” they wrote.
“Moreover, it was established that features such as desquamation, scaling, and crusting, which represent the evolution of pustules, are not mandatory for diagnosing GPP. The extent of body surface area (BSA) affected and the duration of pustulation were also deemed nonessential for diagnosis because GPP is a life-threatening disease.
“Therefore, diagnosis should not be delayed by any predefined duration of pustulation or BSA.”
Other key points from the diagnostic criteria include:
- Acral Distinction: Unlike other consensuses, the IPC recognises that pustular lesions on the palms and soles can occur during GPP flares but should not rule out a GPP diagnosis alone. This acknowledgment is crucial as it addresses the coexistence of GPP with other localised forms of pustular psoriasis, ensuring appropriate and urgent treatment.
- Incorporation of Erythema: The new criteria identify erythema as an essential feature of GPP. This addition is vital as erythema indicates the inflammatory nature of the disease. Nearly 80% of the reviewed GPP cases involved individuals with darker skin tones, where erythema might be less discernible yet still significant.
- Implementation of Criteria: For dermatologists suspecting GPP, thorough patient history and physical examination, guided by the new criteria, is paramount. The criteria also recommend specific steps like a biopsy to confirm the diagnosis, particularly when distinguishing GPP from other dermatoses like AGEP and SPD.
- Role of Biopsy and Direct Immunofluorescence (DIF): While biopsy/histopathology remains highly recommended for confirming GPP, the role of DIF in diagnosis appears limited, with only a minor consensus supporting its utility in ruling out other skin conditions.
- Utility Across Medical Disciplines: These criteria are designed to be used by dermatologists and general practitioners. This broader applicability ensures timely referrals and appropriate care, potentially improving patient outcomes.
“We look forward to seeing the positive changes this new consensus will bring to the lives of patients with generalized pustular psoriasis worldwide,” said Professor Choon, an Associate Professor at the Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Malaysia.
