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Generalized Pustular Psoriasis: Provider and Payer Considerations for Care
Generalized pustular psoriasis (GPP) is a rare and severe form of psoriasis that can be life threatening if not properly treated.1 The clinical burden of GPP is significant because of the condition’s severity and the need for aggressive treatment, which can also result in a considerable economic burden.2,3 By targeting the IL-36 pathway, which is involved in the onset of GPP, researchers are developing new medications that can reduce the severity of GPP symptoms and prevent relapse.4 In a recent Peer Exchange, experts who specialize in treating patients with GPP were joined by professionals from the insurance industry to provide an overview of GPP and how the disease presents and manifests, discuss current standards of care for management, explore patient perspectives, and review the evolving treatment landscape. The session was moderated by Ryan Haumschild, PharmD, MS, MBA, director of pharmacy services at Emory Healthcare and Winship Cancer Institute in Atlanta, Georgia.
Characteristics and Epidemiology
GPP is a rare, severe, and potentially life-threatening autoinflammatory skin disease characterized by the sudden onset of widespread, painful, sterile pustules on the skin that can compromise skin functions such as temperature regulation and protection against infection. Patients with GPP may also develop systemic manifestations of inflammation.1,5,6 GPP may be relapsing with recurrent flares or persistent with intermittent flares.5 GPP flares are associated with significant morbidity and mortality and may involve fever, sepsis, acute respiratory distress syndrome (ARDS), renal failure, and congestive heart failure. Hospitalization is often required, and patients may need intensive care.5,6 The quality of life of patients with GPP is significantly reduced.7,8 In addition, patients frequently experience comorbidities and high medication use.8,9
GPP can be triggered by the initiation and withdrawal of various medications, in particular the withdrawal of corticosteroids, and by infections, stress, and other conditions.1,5,6,10 Patients with a history of psoriasis have an increased risk of developing GPP, but it may also occur de novo. Impetigo herpetiformis, a form of GPP that may occur during pregnancy, is associated with high rates of maternal and fetal morbidity.1,5
There is a large degree of variability in the prevalence of GPP, with estimates ranging from 1.76 cases per 1 million individuals in France to 88 to 124 per 1 million in the Republic of Korea. However, these differences should be interpreted with caution because different methodologies, populations, and definitions of GPP were used across these studies. It is likely that this variation results from these methodological differences and the challenges associated with studying a relatively unknown disease, as well as the distribution of genetic variants and cofactors in separate populations.11 Reported mortality rates range between 2% and 16% and vary depending on the medication used to treat the flare.6 Although infants and children may develop GPP, it typically develops in adulthood and is more common in women than in men.12
GPP, Pustular Psoriasis, and Psoriasis Vulgaris
Pustular psoriasis (PP) refers to a clinically heterogeneous group of diseases characterized by neutrophil-containing pustules on an erythematous background.13-15 PP is classified into 3 types: acrodermatitis continua of Hallopeau, palmoplantar pustulosis, and GPP.10,15 As described for GPP, PP generally follows a relapsing and remitting course requiring long-term disease management.14
Psoriasis vulgaris (PV, also called plaque psoriasis) and GPP were historically thought to be related conditions, with GPP being a subtype or variant of PV. However, there is increasing evidence that GPP and PV are distinct diseases, even though some patients with GPP may have a history of PV.13 PV is a relatively common chronic disease and the most common of the conditions that fall under the psoriasis umbrella, accounting for approximately 90% of cases.13 PV and GPP can be distinguished based on differences in dermatologic features, histology, clinical features, comorbidities, underlying genetics, gene expression, and immunology.13
Whereas PV is characterized by localized discrete plaques with excess scale resulting from abnormal differentiation of keratinocytes, in GPP there is a widespread eruption of neutrophilic, noninfectious pustules.13 Another key difference is the notable acute presentation of GPP, frequently requiring hospitalization, compared with the chronic nature of PV, typically managed in an outpatient setting.13 Furthermore, the genetic and molecular differences between the 2 conditions support the idea that they are separate entities. Many cases of GPP are familial, following a seemingly monogenic Mendelian model, whereas PV follows a complex polygenic model. The key genetic driver in PV is HLA*C0602, which is not associated with GPP. On the other hand, GPP is frequently associated with mutations in IL36RN, which are not seen in PV.13 It is important to recognize GPP as a distinct disease because this will allow for a more targeted approach to understanding its causes and treating it effectively. Indeed, many therapies that are effective for PV may not work for GPP, so it is important to develop therapies specifically for GPP.13
Diagnosis
Diagnosis of GPP is based on several criteria, including the presence of sterile pustules, systemic signs of inflammation, laboratory tests, histopathologic confirmation of spongiform pustules of Kogoj, possible medical and family history, and recurrence of symptoms.16 When evaluating a patient who may have GPP, it is important to consider and rule out other cutaneous pustular diagnoses, such as acute generalized exanthematous pustulosis (AGEP). AGEP is differentiated from GPP by the presence of eosinophils and necrotic keratinocytes on histopathologic examination and is commonly associated with the recent initiation of certain medications, including penicillins, macrolides, and quinolones. In contrast, GPP can be related to the withdrawal of corticosteroids or the initiation of certain biologic medications, including anti–tumor necrosis factor (TNF) agents, and may occur in patients with or without a history of psoriasis. AGEP typically has a more abrupt onset and resolution compared with GPP, with pustules clearing within a few days to weeks after the triggering factor is removed.1
Stakeholder Insights
Mark G. Lebwohl, MD, dean for clinical therapeutics and professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, and Aaron Farberg, MD, dermatologist and Mohs surgeon at Derm Texas in Dallas, both emphasized that GPP is often a dermatologic emergency. Patients with GPP are often sick, in significant pain, and in danger, so it is important to treat them as soon as possible. GPP has an enormous impact on quality of life. Lebwohl described how devastating the disease can be. Patients are covered in pus, are febrile and tachycardic, have swollen legs, cannot walk, and are shivering because their temperature is falling. “They cannot go to work. They cannot do anything,” he said. Even for patients with the more chronic type of GPP, with low-grade presence of pus on limited areas of the body, the disease is very uncomfortable and negatively affects quality of life.
Maria Lopes, MD, MS, former chief medical officer at MagellanRx, said that, from a payer’s perspective, it is important to quantify the resource use—meaning the total costs associated with a condition, including avoidable costs in terms of emergency department (ED) visits, hospitalizations, and intensive care unit (ICU) stays—as well as organ damage. Although quality of life is part of the story and of paramount importance for patients, it is viewed as secondary from the perspective of payers.
Patients may experience a variety of symptoms and complications. These may include fever or hypothermia caused by the skin’s impaired ability to regulate body temperature, as well as an increased risk of staphylococcal sepsis and other infections. Patients may also develop anemia, elevated white blood cell count, low albumin levels, hypocalcemia, electrolyte imbalances, and shock. They may experience high-output cardiac failure, swelling in the legs, and multiple organ failure and may be at risk of death in severe cases. Many patients need intensive care. Lebwohl referred to results from a hospital network in France, where 25% of patients admitted for GPP needed to spend time in the ICU and the death rate was 2% to 3%. These results demonstrate the need for new treatments for patients with GPP.
Wihdrawal of systemic steroids is a common trigger for the development of GPP. This often occurs when patients are treated with systemic steroids for other indications and then experience a breakout of GPP when the steroid dose is reduced. Other medications can also trigger GPP; Lebwohl highlighted antimalarial medications.
GPP’s rareness and severity make educating patients, providers, and payers important so that they can recognize and manage the symptoms and administer appropriate care. Although it is a dermatologic disease, family practice physicians and emergency medicine practitioners also must be able to quickly identify GPP so that they can refer the patient to a dermatologist as quickly as possible, Farberg said.
Lopes also emphasized the need for education, including for payers that usually associate psoriasis with a very different patient subtype; it is important that they understand why this disease is life threatening. Payers also need to know that the cost of the disease may be high, especially if the patient is admitted to the hospital and requires intensive care. Patients also might need specialists and various laboratory evaluations because the diagnosis is not always easy. The hope with new treatments is to prevent visits to the ED and hospital admissions by treating patients at infusion centers or in another appropriate setting. Lebwohl agreed that it is important that payers understand GPP: “You can’t wait for a prior authorization to go through when you have a patient dying.” Since the approval of spesolimab-sbzo (Spevigo), there have been situations in which patients needed immediate treatment because of the severity of their conditions. This has required hospitals to produce solutions for quickly approving the administration of the drug, and the panelists agreed that payers must continue to work on solving this dilemma.
From a payer perspective, preventing patients from going to the hospital or the ED is a successful outcome, Lopes said. However, even if a patient does need to go to the ED or to be admitted briefly, the cost of care will be lower than if they are in the hospital for an extended period and require intensive care. The ideal situation would be for patients to recognize symptoms of GPP and know the nearest medical facility that carries the drug and can administer it without prior authorization. It is possible to develop these systems if payers and providers work together. Haumschild said that, from the payer lens, there is a need to look at the total cost of care value proposition outside of just the acquisition of the drug, including reduced hospitalization time.
Diagnosing GPP should not be difficult, according to Lebwohl. GPP is characterized by generalized pustules and systemic symptoms. The most common condition with similar symptoms is AGEP, which is a drug reaction that is not as severe as GPP and is easy to distinguish based on clinical presentation. Chronic, recurrent, low-grade GPP can be mistaken for subcorneal pustular dermatosis, but because these conditions are less severe, there is not the same urgency in getting the correct diagnosis.
Treatment
Spesolimab is the only approved treatment for GPP; off-label treatment options for patients with GPP can include retinoids, cyclosporine, and methotrexate.1,4 Although systemic therapies usually are needed to fully control symptoms, adjunctive topical interventions (eg, bland emollients, corticosteroids, calcineurin inhibitors, vitamin D derivatives) may be used to soothe skin symptoms.1
Effective management of GPP requires providing adequate supportive care and addressing any temperature, fluid, or electrolyte imbalances that may arise. To reduce the risk of fatal complications, including systemic infection and sepsis, it is important to identify and manage any secondary infections that may be present. In addition, precautions must be taken to prevent serious end organ damage, including liver, kidney, and respiratory dysfunction.1 The main immediate treatment goal for patients with GPP is resolution of the flare: to improve skin symptoms (rapid control of pustules and prevention of new eruptions; control of itch, redness, and edema; and control of pain), reduce systemic manifestations (fever control), and prevent complications (cardiac, ARDS, comorbid cholangitis, renal failure). Long-term goals focus on prevention of new flares or worsening of persistent lesions, as well as the management of comorbidities to improve quality of life of the patient.4
Until September 1, 2022, when spesolimab was approved by the FDA, there were no GPP-specific treatments approved in the United States or Europe.4,17 In addition to this new treatment, researchers are investigating the potential benefits of combining different medications in the management of GPP. This approach, known as combination therapy, may be more effective in controlling symptoms and preventing relapse.1
Nonbiologic Systemic Therapies
These include the most-used drugs: methotrexate, cyclosporine, and retinoids. Methotrexate is used for autoinflammatory and autoimmune conditions, including GPP, although its mechanism of action in treating GPP is not well defined. The efficacy of methotrexate in the prevention of GPP flares has not been demonstrated in clinical trials; however, there is limited evidence of efficacy from case studies. On the other hand, methotrexate is associated with liver and gastrointestinal toxicity and increased risk of infection.1,4 Cyclosporine, an immunosuppressive agent, is a calcineurin inhibitor also commonly used to treat patients with GPP, despite limited evidence of efficacy. Adverse events associated with cyclosporine include hypertension, nephrotoxicity, and increased risk of infection.1,4 Finally, retinoids are the third group of commonly used drugs for treating GPP. There is also limited, although more promising, evidence for the use of these nonimmunosuppressive drugs in GPP. However, retinoids are teratogenic and are associated with liver, mucocutaneous, and skeletal toxicities, as well as hyperlipidemia.1,4 Other nonbiologic agents sometimes used to manage GPP include mycophenolate mofetil, hydroxyurea, apremilast, and colchicine.4
Nonbiologic Topical Therapies
Although topical therapies are not recommended for GPP flares, they are sometimes used as maintenance therapy following a flare or as adjuvant therapy to manage symptoms. For example, calcipotriene and tacrolimus can be combined with systemic therapies to treat severe disease or used as monotherapy for localized lesions. Other alternative treatment modalities include the use of wet body wraps with triamcinolone, photochemotherapy with psoralen plus UV lights, and granulocyte/monocyte adsorption apheresis.4
Biologic Systemic Therapies
Open-label, phase 3 studies of the IL-17A/IL-17R monoclonal antibodies brodalumab (NCT01782937), secukinumab (NCT01952015), and ixekizumab (NCT01624233) showed their effectiveness in the long-term (52 weeks) management of GPP. In all studies, most patients achieved clinical remission or improved clinical status by week 12 and almost all by week 52.1,4 Similarly, 80% of patients treated subcutaneously with guselkumab, a monoclonal IL-23 inhibitor, in an open-label, phase 3 study (NCT02343744) achieved treatment success by week 52.4 Additionally, ustekinumab, an IL-23 and IL-12 inhibitor, showed effectiveness in a case series of patients with treatment-refractory GPP.1,4 Finally, recent case reports of IL-1 inhibitors, including gevokizumab, anakinra, and canakinumab, have shown promising results. However, more studies are needed to confirm the efficacy of these agents.1,4
IL-36 Inhibitors
The IL-36 pathway is involved in the development of GPP; therefore, targeting this pathway may help reduce symptoms and improve outcomes for patients. Loss-of-function mutations in the IL-36 receptor antagonist gene (IL36RN) have been reported in approximately 21% to 37% of GPP cases overall and in up to 82% of GPP cases without PV.1,13 Mutations in IL-36–associated genes (CARD14, AP1S3, SERPINA3, and MPO) also have been described in patients with GPP.13
Spesolimab, a selective IL-36 receptor blocker, is the only FDA-approved treatment for patients with GPP.17 Approval was based on results from the placebo-controlled, 2:1 randomized, phase 2 Effisayil 1 trial (NCT03782792).17 The trial enrolled adult patients with a history of GPP who were experiencing a flare of moderate to severe intensity. Patients received a single intravenous dose of 900 mg of spesolimab or placebo on day 1, followed by a single open-label dose of 900 mg of spesolimab on day 8 for all patients (including those in the placebo group) who had persistent symptoms.18 At the end of week 1, 54% of patients in the spesolimab group had no visible pustules compared with 6% in the placebo group. A further 43% of patients in the spesolimab group had clear or almost clear skin compared with 11% with placebo.18 Adverse events were reported in 82% of patients who received at least 1 dose of spesolimab, with 12% having a serious adverse event, by week 12. Infections had occurred in 47% of patients at week 12.18 Other IL-36 inhibitors under development include imsidolimab and A-552.4
Stakeholder Insights
Spesolimab, an IL-36 blocker, is the first and only medication approved to treat patients with GPP. Off-label medications previously used to treat GPP include oral retinoids such as acitretin, methotrexate, and cyclosporine, which is an immunosuppressant drug. Biologics, such as TNF inhibitors and IL-17 and IL-23 blockers, are also commonly used to treat GPP. Farberg explained that the variety of treatment options available reflects the lack of a therapy widely recognized as superior until the recent approval of spesolimab. “If there was one that worked so much better, then that would be the one that we would all use,” which is currently spesolimab, he said.
The availability of medications and insurance coverage can affect treatment options in real time, Farberg said. It is important for health care professionals to consider the severity of the patient’s condition and choose the most appropriate treatment option. In severe cases, spesolimab or IL-17 or IL-23 blockers may be used. For milder or chronic cases, topical treatments or oral retinoids may be more appropriate. It may also be necessary to combine medications to effectively manage the patient’s symptoms. It is important to regularly assess patient needs and adjust treatment regimens as necessary.
Topical treatments, such as whirlpool baths and topical steroids, are primarily used for symptom relief, Lebwohl explained. The most-used topical treatment is triamcinolone acetonide because it comes in large tubs and patients often need to use it on large skin surfaces. Lebwohl advised using medications that are not easily absorbed or using fluticasone, which is a small molecule that is broken down, to avoid the risk of Cushing syndrome.
Taking patients out of the danger zone as quickly as possible is the most important indication of successful treatment in GPP, Lebwohl said, followed by restoring skin and normal life. The best score to assess how a patient is doing is the pustulation score.
In terms of safety, Lebwohl strongly advised against using systemic steroids. The primary concern with methotrexate is effects on the liver and bone marrow; with cyclosporine, it is effects on the kidneys. Long-term use of cyclosporine is also associated with lymphomas and skin cancer. On the other hand, biologics are fairly benign, Lebwohl said, with the main worry being the increased risk of infections. In particular, the TNF blocker infliximab should not be used in patients with sepsis. IL-17 and IL-23 blockers have a lower risk of infection and when given by themselves should be safe. The concern comes when combining biologics, which might increase risk of sepsis. Retinoids do not affect the immune system and are safe to combine with any biologics.
Clinical and Economic Burden of GPP
GPP can have a significant impact on quality of life and overall health. The severity of the condition and need for aggressive treatment result in a significant clinical burden for patients and health care systems.2,7,19 In addition to often requiring hospitalization, including in ICUs, patients with GPP may also require long-term treatment with medications to control symptoms and prevent relapse. This also results in a significant economic burden for patients and health care systems.2,3 A recent analysis from Sweden found that patients with GPP had significantly higher numbers of inpatient stays and physician visits and increased use of psoriasis-related drugs compared with both the general population and patients with PV.3 This resulted in mean annual direct costs per patient that were more than 3 times higher compared with the general population and nearly double compared with patients with PV.3 Drug treatment represented 70% of the cost attributable to GPP, of which a large fraction was represented by biologics.3
Emerging Therapies and Unmet Needs
Farberg discussed the impact of GPP relapses on patients, who often worry about potential recurrence. Dermatologists want to prevent these relapses whenever possible. However, flares can sometimes last weeks or months, which can be difficult for patients and doctors. The key to preventing these flares is getting patients on the right treatments, but this is not always easy. Personalized medicine, using biomarkers to identify the right drug for each patient, is the goal. The use of drugs such as spesolimab, which targets the IL-36 pathway, can be helpful in treating these patients. However, many questions remain about how best to use this medication to prevent flares.
Investigators have identified IL-36 as a key target in the treatment of GPP. Spesolimab has been shown to be highly effective in managing GPP and should be adopted as the standard of care, Lebwohl said. In clinical trials, spesolimab was able to produce a significant improvement in patients within a week, with many patients seeing a complete resolution of their pustular psoriasis in this period. Other treatments may take weeks or months to produce a similar effect. Spesolimab is given intravenously, but the hope is to have subcutaneous or even oral formulations soon. There is another IL-36 antibody in development, imsidolimab, and Lebwohl expects that the future of GPP therapies will be in biologics because of how targeted they are. Small molecules such as methotrexate and cyclosporin have adverse effects that affect other organs, whereas the antibodies are safer and more effective. The main adverse effect to keep an eye on with antibodies is infection, which can be hard to quantify as GPP also makes patients more vulnerable to infections.
“I think the biggest unmet need is simply awareness, both from the public and from the clinicians. Now that we have treatments available for this disease, if we can identify it early and correctly at the earliest moment possible, we know we can have a significant impact on these patients,” Farberg said. Because GPP can be severe, it is possible that in moments of panic and urgency, practitioners may not always follow protocol and may delay calling a dermatologist because they are worried about other organ involvement. It is important to bring all specialists as quickly as possible to the bedside so that the diagnosis can be made. Although not all clinicians will be able to recognize GPP, it is an easy diagnosis to make for dermatologists, so they should be involved as soon as possible.
The second unmet need identified by Farberg is the lack of medications. The recent approval of spesolimab has had a significant impact for patients. “Now we’re still trying to gain the clinical experience to really fine-tune and understand the best way to utilize this medication for our…patients [with GPP],” Farberg said. From the payer’s perspective, the approval of spesolimab increased the need for accurate diagnosis of GPP. It is important that patients are not misdiagnosed with this rare condition, Lopes said, especially considering the approval of a new treatment.
When thinking about adding spesolimab to formularies and deciding on prior authorization protocols, payers must be educated on the severity of GPP, the treatment options and clinical guidelines, and the effectiveness of spesolimab at reducing hospitalization length, as well as how it is administered. The argument for hospitals to carry spesolimab, in addition to its being a lifesaving medication, is that it can decrease their costs by shortening hospitalization for patients, Lopes said.
In the outpatient setting, once the requirements for prior authorization have been met, there are opportunities to reduce costs with the setting where the infusion will be administered. Infusions administered outside of hospitals, be it in infusion centers, doctors’ offices, or at home, are less expensive. The other consideration for payers is the frequency of administration, Lopes said. There is an important need to educate payers about the acute flares that can occur with GPP. This means patients will need to know where they can go when they have a flare, and the facility will need to have the medication on-site or rapid access to it. This also has implications in terms of the shelf life of the drug, especially given that GPP is a rare disease. Therefore, depending on where a patient lives, it might not be possible to make outpatient care cost-effective for payers, Haumschild said.
References
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2. Kharawala S, Golembesky AK, Bohn RL, Esser D. The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review. Expert Rev Clin Immunol. 2020;16(3):239-252. doi:10.1080/1744666X.2019.1708193
3. Löfvendahl S, Norlin JM, Schmitt-Egenolf M. Economic burden of generalized pustular psoriasis in Sweden: a population-based register study. Psoriasis (Auckl). 2022;12:89-98. doi:10.2147/PTT.S359011
4. Krueger J, Puig L, Thaçi D. Treatment options and goals for patients with generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(suppl 1):51-64. doi:10.1007/s40257-021-00658-9
5. Bachelez H. Pustular psoriasis: the dawn of a new era. Acta Derm Venereol. 2020;100(3):adv00034. doi:10.2340/00015555-3388
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7. Sampogna F, Tabolli S, Söderfeldt B, Axtelius B, Aparo U, Abeni D; IDI Multipurpose Psoriasis Research on Vital Experiences (IMPROVE) Investigators. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol. 2006;154(5):844-849. doi:10.1111/j.1365-2133.2005.07071.x
8. Reisner DV, Johnsson FD, Kotowsky N, Brunette S, Valdecantos W, Eyerich K. Impact of generalized pustular psoriasis from the perspective of people living with the condition: results of an online survey. Am J Clin Dermatol. 2022;23(suppl 1):65-71. doi:10.1007/s40257-021-00663-y
9. Hanna ML, Singer D, Bender SD, Valdecantos WC, Wu JJ. Characteristics of hospitalizations and emergency department visits due to generalized pustular psoriasis in the United States. Curr Med Res Opin. 2021;37(10):1697-1703. doi:10.1080/03007995.2021.1951192
10. Navarini AA, Burden AD, Capon F, et al; ERASPEN Network. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792-1799. doi:10.1111/jdv.14386
11. Zheng M, Jullien D, Eyerich K. The prevalence and disease characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(suppl 1):5-12. doi:10.1007/s40257-021-00664-x
12. Morita A, Kotowsky N, Gao R, Shimizu R, Okubo Y. Patient characteristics and burden of disease in Japanese patients with generalized pustular psoriasis: results from the Medical Data Vision claims database. J Dermatol. 2021;48(10):1463-1473. doi:10.1111/1346-8138.16022
13. Bachelez H, Barker J, Burden AD, Navarini AA, Krueger JG. Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion. Expert Rev Clin Immunol. 2022;18(10):1033-1047. doi:10.1080/1744666X.2022.2116003
14. Menter A, Van Voorhees AS, Hsu S. Pustular psoriasis: a narrative review of recent developments in pathophysiology and therapeutic options. Dermatol Ther (Heidelb). 2021;11(6):1917-1929. doi:10.1007/s13555-021-00612-x
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16. Umezawa Y, Ozawa A, Kawasima T, et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res. 2003;295(suppl 1):S43-S54. doi:10.1007/s00403-002-0371-6
17. FDA approves the first treatment option for generalized pustular psoriasis flares in adults. News release. Boehringer Ingelheim. September 1, 2022. Accessed December 19, 2022. https://www.boehringer-ingelheim.us/press-release/fda-approves-first-treatment-option-generalized-pustular-psoriasis-flares-adults
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19. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2014;53(6):676-684. doi:10.1111/ijd.12070
