Definitions and Diagnostic Criteria of Generalized Pustular Psoriasis Require Continuity, Accuracy, Researchers Report

Researchers recently published a review article in the Journal of the European Academy of Dermatology and Venereology aiming to provide accuracy and continuity related to diagnostic criteria and definitions of generalized pustular psoriasis (GPP).¹

At present, they noted that there is a lack of consensus and alignment, which ultimately hinders the course of appropriate, timely treatment. Due to its complexity and variability, diagnosing GPP poses a challenge for clinicians.²

Image Credit: © DermNet

Findings

Accurate diagnosis of GPP relies on adhering to internationally accepted classification criteria. At present, 3 key organizations—the European Rare and Severe Psoriasis Network (ERASPEN),³ the Japanese Dermatological Association (JDA),⁴ and the International Psoriasis Council (IPC)⁵—have outlined specific criteria to aid clinicians in diagnosing GPP.

Existing Criteria

The ERASPEN notes that primary lesions, systemic involvement, association with plaque psoriasis, and clinical course considerations are crucial. Their criteria attests that GPP is marked by primary, sterile pustules visible on non-acral skin. Diagnosis can be further refined based on the presence or absence of systemic inflammation, with presence or absence of plaque psoriasis being another classification factor. GPP may also be categorized as relapsing or persistent in nature.³

The JDA's criteria considers systemic symptoms, pustular eruptions, histopathological findings, and recurrent features, noting that patients often exhibit systemic symptoms such as fever and fatigue. GPP is characterized by systemic or extensive flushing accompanied by multiple sterile pustules, with histopathology revealing characteristic neutrophilic subcorneal pustules. A suspicion of GPP can be based on the presence of pustules and systemic symptoms alone.⁴

The IPC's criteria considers primary lesions, systemic symptoms, association with other psoriasis types, and clinical variability, identifying macroscopically visible sterile pustules on an erythematous base that are not confined to acral regions or within psoriatic plaques. Pustular eruption may occur with or without systemic symptoms, and the presence or absence of other forms of psoriasis can influence classification. GPP may also present acutely with widespread pustular eruptions or as a subacute form with an annular phenotype.⁵

Diagnostic and Clinical Evaluation Tools

Accurate diagnosis of GPP involves a comprehensive approach, considering both clinical presentation and laboratory findings related to liver, biliary tract, and kidney function.

At present, assessment tools for research and clinical trials include the Generalized Pustular Psoriasis Area and Severity Index and the Generalized Pustular Psoriasis Physician Global Assessment. Researchers noted, however, that the application of these measurement tools may be less useful or applicable in real-world clinical settings.⁶

Distinguishing GPP from Plaque Psoriasis and Other Conditions

GPP and plaque psoriasis share overlapping inflammatory pathways, yet they are distinct conditions. Both involve activation of inflammatory cytokines, but GPP is particularly associated with IL-36, while plaque psoriasis is more closely linked to TNF-α, IL-17, and IL-23.⁶

Several conditions can mimic GPP, complicating diagnosis, including acute generalized exanthematous pustulosis or autoinflammatory conditions like DIRA, PAPA syndrome, SAPHO syndrome, and Netherton syndrome. Cutaneous infections such as impetigo, folliculitis, and candidiasis should be considered.

Conclusions

Authors of the review noted that raising awareness about GPP among health care providers, especially those in emergency, internal medicine, family practice, and pediatrics, is vital for early diagnosis and effective management.

"More than 100 years since it was first reported, an understanding of GPP is finally coming into focus: IL-36 is the primary mediator," according to study authors Prajapati et al. "A clear definition of GPP and alignment on diagnostic criteria are crucial to providing appropriate and timely treatment."

Study authors noted that moving forward, awareness efforts and clinical documentations of disease course in patients are crucial to better understanding and improving care and treatment options.

References

1. Prajapati VH, Lynde CW, Gooderham MJ, et al. Considerations for defining and diagnosing generalized pustular psoriasis. J Eur Acad Dermatol Venereol. September 6, 2024. https://doi.org/10.1111/jdv.20310
2. Rivera-Díaz R, Daudén E, Carrascosa JM, Cueva P, Puig L. Generalized pustular psoriasis: A review on clinical characteristics, diagnosis, and treatment. Dermatol Ther (Heidelb). 2023;13(3):673-688. doi:10.1007/s13555-022-00881-0
3. Navarini AA, Burden AD, Capon F, Mrowietz U, Puig L, Köks S, et al. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017; 31: 1792–1799.
4. Fujita H, Terui T, Hayama K, Akiyama M, Ikeda S, Mabuchi T, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the new pathogenesis and treatment of GPP. J Dermatol. 2018; 45: 1235–1270.
5. Choon SE, van de Kerkhof P, Gudjonsson JE, de la Cruz C, Barker J, Morita A, et al. International consensus definition and diagnostic criteria for generalized pustular psoriasis from the International Psoriasis Council. JAMA Dermatol. 2024; 160: 758–768. https://doi.org/10.1001/jamadermatol.2024.0915
6. Fujita H, Gooderham M, Romiti R. Diagnosis of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(Suppl 1):31-38. doi:10.1007/s40257-021-00652-1