Generalized pustular psoriasis (GPP) is a rare, severe, neutrophilic skin disease characterized by episodes of widespread eruption of sterile, visible pustules, which can occur with or without systemic inflammation and with or without plaque psoriasis. 1,2 GPP is associated with potentially life-threatening systemic complications including sepsis and cardiac failure, and is described by the Japan Ministry of Health as an intractable disease. [1][2][3][4] Mutations in IL36RN, CARD14, or AP1S3 have been found in patients with GPP. 5,6 Small Japanese studies have identified a number of different IL36RN mutations in patients with GPP. [7][8][9] Patients with these mutations may be at risk of earlier onset of disease and more severe disease. 10 Indeed, one small study (n = 31 patients with GPP)

Introduction Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening systemic and chronic autoinflammatory disease characterized by sterile, neutrophilic pustules. The standard of care for GPP varies by region, with limited information and experience of flares and their treatment. Our aim was to establish current unmet needs in GPP by better understanding the natural history of GPP, examining how dermatologists diagnose GPP and GPP flares, and establishing the range and adequacy of GPP treatment options currently prescribed by dermatologists. Methods Eligible dermatologists ( N = 29) completed a 28-question structured survey, covering ten themes, ranging from GPP diagnostic criteria to GPP symptoms and treatment. Results All dermatologists stated that pustules were necessary to diagnose a GPP flare. The most frequently reported triggering factors for GPP were steroid withdrawal (64%), infection (58%), and stress (50%). Most dermatologists indicated that available treatment options for GPP flares were adequate “most” (79%) or “all” (14%) of the time. Despite this reported adequacy, 38% of dermatologists reported that it was at least “somewhat common” for a flare to require hospitalization. Furthermore, 72% of dermatologists indicated that treatments were too slow to control flares, and 66% indicated that treatments did not adequately prevent new flares at least “sometimes”. Conclusion This survey suggests that there are key features of GPP flares, and could initiate discussion around forming consensus guidelines for diagnosis and management. While the results suggest that moderately effective therapies may exist, the need for GPP-specific treatments remains. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00493-0.

Little is known about the disease burden, health‐care resource utilization (HCRU), or treatment of patients with generalized pustular psoriasis (GPP) in Japan. This retrospective cohort study used data from the Japanese Medical Data Center database to compare the demographics, comorbidities, and medication use of patients with GPP and plaque psoriasis and estimate their all‐cause HCRU. The patient selection period was from January 1, 2015 to December 31, 2019, and patients must have had at least one confirmed inpatient claim or outpatient claim for GPP or plaque psoriasis. During the 12‐month follow‐up period, 110 patients with GPP and 20,254 patients with plaque psoriasis were identified. An age‐ and sex‐matched (4:1) comparator control cohort, including members of the general population without a diagnosis of psoriasis (but allowing for a diagnosis of psoriatic arthritis), GPP, or palmoplantar pustulosis, was used. The most prevalent comorbidities in patients with GPP included allergic rhinoconjunctivitis, hypertension, and peptic ulcer disease. Patients with GPP were more likely to experience more comorbidities than those with plaque psoriasis, including asthma, chronic obstructive pulmonary disease, interstitial pneumonia, hyperuricemia and gout, tonsillitis, psoriatic arthritis, other psoriasis, and osteoporosis. Patients with GPP were more likely to be treated with a combination therapy than those with plaque psoriasis (65.5% vs 21.7%, respectively) and less likely to be treated with a topical medication alone (20.9% vs 50.8%). Patients with GPP had more outpatient visits than patients in the plaque psoriasis or matched control cohorts (mean [standard deviation], 14.8 [8.3] vs 11.0 [7.6] and 7.8 [7.2], respectively). They were also more likely to require inpatient hospitalization (24.5% vs 6.4% and 5.0%, respectively). Despite study limitations, patients with GPP in Japan were found to have a higher disease burden, including presence of comorbidities and medication use, than those with plaque psoriasis.

Background: Generalized pustular psoriasis (GPP) is a rare, systemic disease characterized by persistent or recurrent flares of painful neutrophilic pustules. There is limited real-world evidence characterizing patients with GPP. Objectives: To establish the distinguishing characteristics of GPP relative to plaque psoriasis, and help inform future treatment decisions and improve patient outcomes. Methods: North American adults with GPP or plaque psoriasis (without pustules) identified from CorEvitas’ Psoriasis Registry were included in this dataset. Registry enrollment data, including patient sociodemographics, disease characteristics, medication use, and patient-reported outcome measures were compared for patients with GPP vs those with plaque psoriasis. This study was descriptive, and no hypothesis tests were performed. Results: In this sample, patients with GPP (N=60) reported greater median (interquartile range) pain (20 [3–62] vs 5 [0–35]), fatigue (44 [15–73] vs 20 [4–50]), and itch (59 [10–85] vs 22 [5–70]) than those with plaque psoriasis (N=4894). Descriptively, patients with GPP also reported more anxiety and depression (EQ-5D-3L: 38% vs 26%) and had more treatment experience (≥2 previous systemics: 15% vs 7%). Conclusions: A greater degree of symptom severity and impact on quality of life was reported by patients with GPP compared with plaque psoriasis in this sample. Importantly, patients with GPP had more treatment experience, suggesting that current treatment options do not adequately resolve the disease - highlighting the need to develop more effective GPP treatments.

Background Generalized pustular psoriasis (GPP) is a rare disease characterized by episodic worsening (flares). Knowledge of the burden of GPP and the experience of affected individuals is limited. Aims To conduct a survey of people living with GPP to understand how they experience GPP flares, which therapies they have received and are receiving, and how GPP impacts their activities of daily living. Methods The online survey consisted of 43 questions answered by individuals recruited from an opt-in market research database. The research team performed a targeted outreach to identify individuals with GPP. The survey included screening questions to determine if potential participants qualified for inclusion. Eligible individuals were US residents aged ≥ 18 years who self-reported that they had been diagnosed with GPP. Respondents provided consent to participate and received compensation (fair market value) for their time. Results Between August 4 and 14, 2020, 66 people living with GPP in the USA were surveyed. Most participants were female, aged 40-59 years, had been diagnosed ≥ 1 year previously, and had experienced ≥ 2 flares in the past year. A substantial proportion of respondents had symptoms for years, had consulted multiple healthcare professionals, and experienced misdiagnoses before receiving a diagnosis of GPP. Emotional stress was the most common cause of flares and many respondents reported a fear of flares. Respondents defined flares by the presence of itching, an increase in the size of the affected area, more crusts or pustules, and fatigue. A change in mood was the most burdensome symptom. Most respondents were receiving topical corticosteroids and only approximately one-third felt their condition was well controlled. GPP had an impact on activities of daily living even in the absence of flares and many respondents felt that their physician did not understand the level of emotional, psychological, or physical pain caused by GPP. Conclusions GPP imposes a substantial emotional burden on patients, with wide-ranging impacts on activities of daily living beyond the physical discomfort of skin lesions.