Generalized pustular psoriasis: A global Delphi consensus on clinical course, diagnosis, treatment goals and disease management

Abstract

Background Generalized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP. Objectives Conduct a Delphi panel study to identify current evidence and gain advanced insights into GPP. Methods A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%. Results Twenty‐one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the ‘clinical course and flare definition’, ‘diagnosis’, ‘treatment goals’ and ‘holistic management of GPP’ domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long‐term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed. Conclusions Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice.

Health‐related quality of life in patients with generalized pustular psoriasis: A systematic literature review

“…People with GPP experience recurrent flares of widespread erythema and extensive, macroscopically visible aseptic pustules causing pain, itching and burning 1 . Systemic symptoms of fever, malaise and fatigue typically also occur, and laboratory tests may show raised C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR), indicating high levels of systemic inflammation 1 . The flares can last for weeks, during which time the pustules can merge to form a ‘lake of pus’ 1 …”

“…Systemic symptoms of fever, malaise and fatigue typically also occur, and laboratory tests may show raised C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR), indicating high levels of systemic inflammation 1 . The flares can last for weeks, during which time the pustules can merge to form a ‘lake of pus’ 1 …”

“…Finally, it is essential to determine the best methods to measure HRQoL accurately and reliably in this F I G U R E 1 GPP: a severe autoinflammatory disease with a high clinical burden that impacts HRQoL measures and other PROMs. Adapted from Puig 2023, 1 Prinz 2023, 3 Bachelez 2022, 17 Crowley 2021, 10 Hanna 2021, 11 Lebwohl 2022, 20 Morita 2021. 12 COPD, chronic obstructive pulmonary disease; GPP, generalized pustular psoriasis; HRQoL, health-related quality of life; plaque PsO, plaque psoriasis; PROM, patient-reported outcome measure.…”

“…1,4 Flares can occur de novo or be caused by different triggers including withdrawal of systemic steroids, infections, stress and pregnancy. 1,4,6,7 If left untreated, serious complications can arise such as infection and sepsis, resulting in hospitalisation and even death, most commonly due to septic shock or cardiac or renal failure. 3,8 Common comorbidities associated with GPP include arthralgia, arthritis, psoriatic arthritis, metabolic and cardiovascular conditions such as obesity, diabetes, hyperlipidaemia, hypertension and cardiovascular disease, as well as hepatic and renal abnormalities (Figure 1).…”

“…1 The clinical course of GPP is highly variable: patients may experience multiple flares per year or only a flare every few years, 1,4,5 and each flare can differ in severity of cutaneous and extracutaneous symptoms. 1,4 Flares can occur de novo or be caused by different triggers including withdrawal of systemic steroids, infections, stress and pregnancy. 1,4,6,7 If left untreated, serious complications can arise such as infection and sepsis, resulting in hospitalisation and even death, most commonly due to septic shock or cardiac or renal failure.…”