Patient Experiences on the Diagnosis,Management,and Burden of Generalized Pustular Psoriasis: An International Web Survey and Qualitative Interview Study

Abstract

Background

Generalized pustular psoriasis (GPP) is a rare, serious, chronic, neutrophilic skin disease, distinct from plaque psoriasis, characterized by recurrent flares of cutaneous erythema and widespread sterile pustules. Patient-centric data on the quality of life (QoL) impacts of GPP remain limited.

Objective

To evaluate the physical and emotional QoL impacts of GPP.

Methods

We used a web-based survey and 90-minute telephone interviews with open-ended questions to evaluate the experiences of adults with GPP across China, Japan, the UK, and the USA. Quantitative measures included the Dermatology Life Quality Index (DLQI), Psoriasis Symptom Scale (PSS), and Worst GPP Pain Numeric Rating Scale (NRS).

Results

21 participants completed the survey; 9 completed telephone interviews. The journey to diagnosis was complicated, with 48% of participants seeing ≥4 physicians before the diagnosis. Impacts of GPP on participants physical and mental QoL were substantial, such as the anxiety of not being able to plan life and work with confidence, both in general and during flares. The mean DLQI was 10.2, and the PSS and Worst GPP Pain NRS were highest in participants experiencing recent flares. Participants’ biggest worries included risk of flares, distress from symptoms, inadequate treatment, and passing on the disease to their children. Limitations included a small sample size and short recall timeframe.

Conclusion

Participants reported multiple impacts of GPP on their daily lives even in the absence of acute flares, highlighting the need for greater disease awareness and understanding among healthcare professionals.

Plain Language Summary

Why was the study done?

Generalized pustular psoriasis (GPP) is a life-long condition that causes skin redness and inflammation, sterile blisters (referred to as pustules), as well as fever, tiredness, and pain. It is known that GPP symptoms have a negative effect on people’s quality of life. However, the lived experience of people with GPP has not been investigated in depth. Our study aimed to better understand how people feel about their diagnosis and GPP’s impact on their lives.

What did the researchers do?

A total of 21 people with GPP completed an internet-based survey. They provided direct feedback about their symptoms and quality of life using different scales. Nine people were also interviewed by telephone.

What did the researchers find?

Participants generally reported difficulties in receiving a diagnosis of GPP; almost half of them had seen at least 4 different doctors before a GPP diagnosis (mean time to diagnosis was 2.4 years). Using a standard scale called the Dermatology Life Quality Index, the average score (10.2) showed a moderate impact of GPP on their lives. Other scales and patient interviews revealed that GPP had a substantial negative impact on people’s quality of life (all participants reported emotional and physical function impacts, and 75% reported depression). It affected the physical and mental health aspects of their lives, not only when they were having a flare but also in general. Symptoms and pain associated with GPP were worst in those who recently had a GPP flare. Participants most often reported that their biggest concerns were the risk of having another GPP flare, the GPP symptoms, receiving inadequate treatment, and the risk of passing on the disease to their children.

What do the findings mean?

There is a high unmet need to better understand people’s lived experience of GPP, which is not always clearly demonstrated by the standard measurement scales. Our study allowed participants to directly report the effects of GPP on their lives. These results will help to increase the awareness and understanding of GPP among clinicians and other healthcare professionals.

Graphical Abstract

Introduction

Generalized pustular psoriasis (GPP) is a rare, serious, chronic, neutrophilic, and systemic inflammatory disease, distinct from plaque psoriasis, characterized by macroscopically visible sterile pustules on an erythematous base that are not restricted to the acral region or within psoriatic plaques. ¹ In addition to causing these widespread sterile, neutrophilic pustules, GPP can cause extracutaneous symptoms, including fever, chills and malaise, arthritis and arthralgia, and asthenia and fatigue. ² Periods of GPP flaring can vary in frequency and severity,^3,4 with the most severe flares potentially causing life-threatening complications, such as sepsis/septic shock and cardiovascular complications, if left untreated.^2,5,6 The journey to GPP diagnosis can be convoluted, with multiple differential diagnoses and frequent comorbidities to navigate, and involvement of multiple specialists.^3,6-9

Due to its chronic and unpredictable nature, GPP requires continuous systemic treatments to control symptoms and reduce the risk of flares.^2,10,11 In a recent US survey, only about one-third of patients with GPP felt their condition was well controlled. ³ Moreover, claims data in Japan indicate that many patients need changes to treatment with relative frequency, with each treatment lasting a median of ∼3 months and a maximum of ∼50 months. ¹² A systematic analysis of small studies using the Dermatology Life Quality Index (DLQI) indicated a moderate-to-very-large effect on health-related quality of life (QoL), ¹³ with GPP commonly affecting daily activities, even in periods between flares. ³

Despite insights from previous studies using patient-reported outcomes (PROs), the lived experiences of patients with GPP have not been explored in depth nor are they well documented in the literature. Through a quantitative survey and qualitative interviews, we aimed to understand the real-world impact of GPP on patients’ physical and emotional well-being, including their paths to diagnosis and treatment, particularly in relation to flares.

Methods

Design Overview

This was a cross-sectional, non-interventional, international study using a web-based survey and qualitative telephone interviews to gather the experiences of adults (aged ≥18 years) with GPP and palmoplantar pustulosis (PPP) across Canada, China, Japan, Spain, the UK, and the USA. This analysis focuses on GPP. Inclusion criteria for participants with GPP included a diagnosis of GPP ≥12 months before screening, ≥1 flare in the past 12 months, and a diagnosis of GPP per the European Rare and Severe Psoriasis Expert Network criteria. ¹⁴ Main exclusion criteria included conditions with overlapping symptoms, enrollment in a clinical trial for GPP or PPP, or any impairment that would interfere with participation. The study was performed in compliance with the protocol, the principles outlined in the Declaration of Helsinki, and Guidelines for Good Pharmacoepidemiology Practice.

Recruitment and Screening

Given the rarity of GPP, participants were recruited through patient advocacy groups (PAGs), recruitment vendors, and clinical sites. All recruitment procedures complied with country-specific regulations and were approved by an institutional review board/ethics committee. In the UK, clinical site staff prescreened participants seen routinely in clinics. Informed consent was obtained from all eligible, potential participants for participation in the web-based survey and optional telephone interviews.

Web-Based Survey

The web-based survey was developed through a literature review, study reports, advisory board transcripts, and PAG feedback; data collection was conducted between October 17, 2021, and June 30, 2023. PRO measures included the Psoriasis Symptom Scale (PSS; 4 items, recall period past 24 hours), DLQI (10 items, past week), Worst GPP Pain Numeric Rating Scale (NRS; single-item; past 24 hours), Patient Global Impression of Severity (PGI-S; single-item, 5-point, at this time), and 12-Item Short-Form Survey (SF-12^®; 12 items, same day/past week). According to country-specific regulations, only participants in China were remunerated for their time.

Qualitative Interviews

Trained interviewers used a semi-structured qualitative interview guide to pose open-ended questions. Interviews lasted ∼90 minutes and were audio recorded with interviewees’ permission. Non-English interviews were conducted by fluent bilingual interviewers, and transcripts were translated into English.

Data Analysis and Handling of Missing Data

All quantitative analysis was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA), with unanswered questions coded as missing unless prespecified by PRO instrument developers. Qualitative analysis of transcripts was performed using ATLAS.ti version 22 (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany).

Results

Study Participation and Sociodemographic Data

Of the 21 participants who completed the web survey, 9 also completed telephone interviews. The mean age (±standard deviation [SD]) was 40.7 (12.0) years; the mean time since diagnosis was 16.1 (15.0) years (Table 1). Supplemental Figures S1A and C, S2, and S3A, D, and F show results by country.

Table 1.

Sociodemographic Characteristics of Survey Participants

Characteristic
Age, years (mean [SD])	40.7 [12.0]
Time since diagnosis, years (mean [SD])	16.1 [15.0]
Time of first symptoms, years (mean [SD])	27.6 [16.7]
Time of diagnosis, years (mean [SD])	29.3 [17.1]
Female (n (%))	12 (57.1%)
Married (n (%))	11 (52.4%)
Living with partner, spouse, family, friend (n (%))	14 (66.7%)
Completed
High school education (n (%))	21 (100%)
Higher education (n (%))	9 (42.9%)
Worked
Full-time (n (%))	12 (57.1%)
Part-time (n (%))	3 (14.3%)

Abbreviations: SD, standard deviation.

Journey to Diagnosis

The mean (±SD) time to diagnosis was 2.4 (5.5) years, with the majority (61.9%) of participants receiving ≥1 misdiagnosis, most commonly eczema (n = 3/13, 23.1%) and plaque psoriasis/psoriasis vulgaris or impetigo (n = 2/13, 15.4%; for each). Delays to diagnosis were concerning and frustrating to participants, with one stating that “…they still don’t know what it is, why are they still not able to make a diagnosis, and I was worrying how long this would go on.” Overall, 10 participants (47.6%) saw ≥4 physicians before receiving a diagnosis and 45.0% did not receive educational materials after their GPP diagnosis.

In total, 62.5% (n = 5/8) of interviewees expressed concerns or fears about their diagnosis (Figure 1A). One participant described their long-term fears as “…my skin’s condition was quite bad so I was quite terrified when I thought that this disease, as the doctor had said, would never go away, and that I would have to spend the rest of my life like this.”

Figure 1.

Quantitative and qualitative data on the impact of GPP.

Symptoms

In the survey, 9 participants (42.9%) indicated they experienced GPP symptoms every day, with >50% experiencing pustules, itching, not feeling well/discomfort, inflammation, fatigue, mental discomfort/irritability, redness, dryness/dry skin, peeling skin, or fever/shivering in the previous 12 months. Participants most commonly listed pustules, itching, and not feeling well/discomfort as their top 3 most bothersome symptoms in the past 12 months (Supplemental Figure S4).

In the 24 hours before the survey, the mean PSS total score (SD) was 5.2 (4.7; range: 0 [no symptoms] to 16 [very severe symptoms]), indicating moderate symptoms; the mean Worst GPP Pain NRS was 3.4 (3.8; range: 0 [no pain] to 10 [worst possible pain]), indicating mild pain intensity (Supplemental Figure S1A and C). However, 11 participants (57.2%) had moderate or higher overall severity on the PGI-S (Supplemental Figure S2).

Flares

All participants experienced ≥1 flare within the past 12 months, with a mean (±SD) of 2.1 (1.8) flares. Four participants were experiencing a flare at the time of the survey, with 4 participants experiencing a flare 1-3 months ago and 10 participants >3 months ago (Supplemental Figure S1B). Participants often stated their flares varied in their duration: “It could be anywhere from four to 6 weeks to months.” Across participants who provided details, flares could range from 4-7 days to >6 months. Commonly reported triggers for flares included stress (n = 15, 71.4%), sudden withdrawal of medications (n = 8, 38.1%), and sunlight/ultraviolet light or an infection (n = 5, 23.8%; for each).

Of surveyed participants, 56.3% reported that their most recent flare had a moderate impact on their daily activities, with 31.3% reporting a severe impact. Pustules were the most commonly reported as one of the most bothersome symptoms during their most recent flare (47.6%).

Participants who reported the highest mean (±SD) PSS score were currently experiencing a flare (n = 4, PSS 6.0 [3.6]) or had experienced one in the past 1-3 months (n = 4, PSS 6.5 [6.5]), with lower values for participants who had experienced a flare >3 months ago (n = 10, PSS 4.9 [4.8]; Supplemental Figure S1B). Similarly, the mean Worst GPP Pain NRS (moderate score: 4-6; mild: 1-3) was also highest in those currently experiencing a flare (n = 15, mean 5.0 [3.6] or those who had a flare in the past 1-3 months (n = 6, 5.7 [4.5]), with lower scores in those with less recent flares (n = 17, 2.7 [3.4]; Supplemental Figure S1D).

Qualitative Data on QoL

All 9 interviewees stated that GPP impacted their emotional and physical function, either generally or due to flares (Figure 1B). Greatest impacts were noted on sleep (88.9%), dressing/clothes choices, finances, social life, and work (77.8%; for each) (Figure 2).

Figure 2.

Interviewee-cited concepts regarding the impact of GPP on daily activities. Abbreviation: GPP, Generalized Pustular Psoriasis

Function Impacts

All interviewees reported emotional impacts of GPP generally or due to flares, with 8 (88.9%) reporting emotional impacts outside of flares — most commonly depression (75.0%) and stress (37.5%) (Figure 1C). For example, a participant reported “I could feel… extreme depression” and that “my appearance was very stressful for me.” Other participants reported anxiety “When the fever occurred, I know I was about to have an occurrence, I would be very anxious.”

Similarly, all interviewees reported physical impacts of GPP generally or due to flares, with 7 (77.8%) experiencing at least 1 impact outside of flares. The most frequently reported physical impacts were difficulty/inability to walk (85.7%), followed by a difficulty/inability to use their hands (42.9%; Figure 1D), such as “opening a soda can or twisting a bottle. I have very bad difficulty with it.”

Treatment Impacts

All interviewees were receiving treatment for GPP. In total, 77.8% reported side effects of their current treatment, 55.6% expressed worries over lack of efficacy or treatment consequences, and 33.3% expressed worries regarding the risk of potential treatment consequences or side effects (Figure 3A).

Figure 3.

Participant-reported worries over GPP during telephone interviews. (A) Reported concerns over treatments. (B) Quotes indicating the biggest worries for participants with GPP. Abbreviation: GPP, Generalized Pustular Psoriasis

Over half of participants surveyed had previously used or were currently using topical corticosteroids (76.2%), biologics (61.9%), and methotrexate or emollients (52.4%; for each). All participants were at least somewhat satisfied with biologics, whereas satisfaction for topical corticosteroids, emollients, and oral or injectable corticosteroids was predominately negative for symptom control and mixed for symptom prevention. The length of time that participants had been on their current and previous treatments varied greatly, ranging from <1 month to >5 years.

Frequency of visits to healthcare providers varied from monthly through to > every 6 months, with 3 participants having no routine follow-up. Overall, most participants (83%) reported spending 30 minutes to 2 hours traveling to their appointments and 57% reported spending up to 60 minutes a day on applying medications.

Participants’ Biggest Worries Regarding GPP

Five interviewees described their biggest worries regarding GPP: risk of a future flare and organ failure, distress from skin symptoms, pain associated with skin symptoms, fear of passing GPP to their children, and feeling that there is no ideal treatment for them (Figure 3B). These feelings were often combined with potential social impacts (eg, embarrassment or stigma; Figure 3B, quote 2) and conflicting emotions (eg, Figure 3B, quote 5).

Quantitative Findings on QoL Impact

DLQI

The mean DLQI total score (±SD) was 10.2 (10.4; range: 0-30), indicating a moderate effect of GPP on participants’ QoL (Figure 4A). Based on total score categories, the scale of impact varied between participants, with the highest impacts in those experiencing flares in the last 3 months (Supplemental Figure S3B). The mean scores (±SD) for the subdomains’ symptoms and feelings, daily activities, and leisure were >1 point higher for participants with a current flare vs those with a flare >3 months ago (Figure 4A; Supplemental Figure S3C).

Figure 4.

PRO scores for the 7 days prior to the survey.

Many participants reported being embarrassed or self-conscious because of the condition of their skin “very much” or “a lot of the time” in the week before the survey, as well as interfering with daily activities such as shopping and working/studying (Figure 4B).

SF-12

The mean (±SD) SF-12 physical and mental component scores were 41.1 (11.5) and 41.2 (15.8), respectively (Figure 4C). Participant responses varied, with a notable proportion indicating poor health, physical limitations, or emotional impacts of their skin condition (Figure 4D).

Discussion

This study results reveal that patients’ experiences on GPP varied, reflecting the condition’s heterogeneous clinical course. Most participants had a moderate severity of disease, with chronic symptoms and a moderate-to-severe impact on their QoL and daily activities. Even mild symptoms (eg, pain) had substantial impacts on QoL, with many interviewees reporting symptoms that fluctuate between mild and severe. The biggest worries participants had about GPP included the risk of a future flare and organ failure, distress from skin symptoms, pain, feeling that the treatment does not meet their needs, and passing the disease to their children.

For many participants, the journey to diagnosis was long, involving misdiagnoses and visits to multiple physicians. Only half of the participants received educational materials after their diagnosis, highlighting an unmet need to ensure that participants are informed and provided with the necessary support and care networks to manage their condition.

Overall, the impacts of GPP on participants’ physical and mental QoL were substantial, both during and outside of flares, with symptoms having significant impacts on their daily life. Avoidance was common, with 1 participant stating “I generally try not to go to places where there are many people and where my skin needs to be exposed, such as swimming pools,” while another stated “I probably avoid social situations…I get more embarrassed by it.” In line with this, both depression and stress were common among participants, potentially creating a vicious cycle because stress was also identified as one of the leading triggers of flares. Nearly all participants reported that flares had a moderate-to-severe impact on their daily activities. As most participants experienced flares for 1-3 months, with a mean of 2 flares per year, many participants therefore experienced flares for at least half the year — a significant disease burden. The unpredictability of flares has been noted to be one of the major factors contributing to the mental health burden of patients with GPP^15,16; therefore, any treatment that can reduce the risk of flares can potentially improve patients’ emotional and mental QoL. A recent global consensus study concluded that long-term GPP treatment goals should include prevention of flares ¹⁷ ; participants’ concerns over chronic symptoms, flares, and existing treatments in our study highlight the need for effective, continuous treatment strategies that provide sustained symptom relief and improve their QoL.

While few studies have qualitatively evaluated patients who experienced GPP, some have previously quantitatively evaluated the impacts on QoL. In a survey of 83 patients in Japan, patients with GPP had lower SF-36 scores for physical functioning, physical roles, body pain, general health, and emotional roles than the Japanese national standard values. ¹⁸ While we used a more concise SF-12 PRO, these findings align with our results, where many patients with GPP report limitations to both physical and emotional function. Similarly, the DLQI total and component scores found in our study correspond to those found in other studies, indicating that our study population was reasonably representative of patients with GPP.^13,19

Moreover, a survey of 66 patients with GPP living in the USA found themes broadly similar to those of the current study with regard to flare triggers, delays in diagnosis, emotional impacts, and treatment effectiveness. The study concluded that GPP impacted patient lives even in the absence of flares and that many of the patients felt that their physician was unaware of emotional, psychological, and physical impacts of the disease. ³

Many physicians are unaware of the true burden of diseases such as GPP to patients. While PROs allow us to quantify patient experiences, they do not truly capture the whole patient experience. Qualitative research, such as that conducted in this study, can add a more nuanced element to aid dermatologists in a more comprehensive understanding of the patient experience, particularly their specific concerns and worries. For example, we found that even mild GPP symptoms can have a substantial impact on patients’ QoL, symptoms that may be overlooked with quantitative PRO measures. One of the main strengths of this study was the ability to combine both quantitative and qualitative evidence to give an overall picture of the impacts of GPP from a patient perspective. Despite this, there remain a few limitations in our study, including the small sample size, which precluded statistical analysis. As GPP is a rare disease, recruitment was unfortunately challenging, with sample sizes for the survey and interviews of 60% and 64% of planned numbers, respectively. Additionally, for some participants, there was a time lag of 1-4 months between the survey and interview, which may have resulted in some discrepancies in responses. Further limitations included this being a cross-sectional web survey performed at a single point in time; therefore, not all participants had symptoms or flares at the time the survey was conducted, and completion was biased towards people who were comfortable using an online platform. As the PROs used in the survey have a short recall timeframe of a day to a week, responses may have been dependent on symptoms at the time of the survey and may underestimate the impact of GPP during flare periods. Finally, discussion on personal, mental, and physical health, as well as the shame associated with the disease, potentially reduced the number of patients willing to participate in surveys, particularly from certain cultures, and/or limited the number of questions they felt comfortable responding to.

Given the concerns shared by the participants of this study, there is a need to identify and develop educational materials for patients. Despite available therapies for GPP, patients remain concerned about potential side effects and/or lack of efficacy. Future GPP clinical trials should routinely include PROs to assess whether treatments can improve QoL and reduce the burden of this chronic, systemic disease on the lives of patients. Additionally, further research on specific impacts of flares on patient experiences is warranted, as there are currently little available data focusing specifically on this aspect of the disease.

Conclusion

In this cross-sectional, international, non-interventional study, participants reported feelings of fear and related negative emotions throughout the disease course of GPP, with nearly all participants reporting multiple impacts on their daily lives. Although larger effects were seen in participants who had flares more recently, many participants reported chronic symptoms and QoL-related burden in the past year. Participants’ concerns over chronic symptoms, flares, and existing treatments highlight the need for effective, continuous treatment strategies that provide sustained symptom relief and improve their QoL. Overall, this study provides a better understanding of the symptom burden and emotional impact of GPP, especially important due to the ongoing need for greater disease awareness and understanding among healthcare professionals.

Supplemental Material

Supplemental Material - Patient Experiences on the Diagnosis, Management, and Burden of Generalized Pustular Psoriasis: An International Web Survey and Qualitative Interview Study

Supplemental Material for Patient Experiences on the Diagnosis, Management, and Burden of Generalized Pustular Psoriasis: An International Web Survey and Qualitative Interview Study by Mark Lebwohl, Hideki Fujita, Kilian Eyerich, Andrew E. Pink, Min Zheng, Iris Chen-Yin Lai, David Trigos, Anne M. Skalicky, Julia R. Correll, Ana C. Hernandez Daly, and Tadashi Terui in Journal of Psoriasis and Psoriatic Arthritis®