Generalized pustular psoriasis (GPP) is a rare and severe variant of psoriasis characterized by widespread sterile pustules and systemic inflammation. This article reports the case of a 74-year-old white man with a history of psoriatic arthritis and congestive heart failure who presented with two separate episodes of GPP. Both of these episodes were associated with hypocalcemia and required inpatient hospitalization.
Introduction
GPP is a rare inflammatory skin disorder characterized by episodic eruptions of sterile pustules on erythematous skin, often accompanied by fever, leukocytosis, and systemic symptoms. Unlike plaque psoriasis, GPP may occur independently of prior psoriasis diagnosis and poses a high morbidity risk, especially in older adults or those with comorbid conditions.¹ Hypocalcemia is often known to trigger GPP. Hypoalbuminemia is a common lab abnormality associated with GPP.² Recent advances, such as the IL-36 receptor antagonist spesolimab, have improved acute management; however, therapeutic access and compliance remain challenges.3
Case Presentation
A 74-year-old male with known psoriatic arthritis, chronic systolic heart failure, hypothyroidism, and history of deep vein thrombosis presented to a local hospital in September 2024 with an acute eruption of pustules. He described a crawling sensation over his skin, followed by the sudden appearance of pustules from his feet to his neck. Within 48 hours, he developed fever and chills, prompting emergency department evaluation.
Dermatology was consulted, and a diagnosis of GPP was made clinically. The patient was admitted to inpatient care for systemic management, where he received intravenous spesolimab and was initiated on cyclosporin. His pustular eruption and systemic symptoms improved over the course of his hospital stay.
Figure 1. Diffuse pustular eruption involving the upper trunk, chest, and arms, characteristic of acute generalized pustular psoriasis.
Figure 2. Closer view of various sized pustules on the upper arm and chest.
In January 2025, the patient discontinued both spesolimab and cyclosporine due to financial constraints. He also started taking a variety of supplements to improve his health. In March 2025, he started a one-month course of oral prednisone from his rheumatologist.
In April 2025, he presented to the dermatology clinic with diffuse pustules covering more than 50% of his total body surface area as well as impressive pedal edema and shortness of breath. He reported severe pain rated 11/10 and associated constitutional symptoms of fatigue, chills, and malaise Laboratory evaluation revealed a calcium of 8.5 (8.6-10.3 mg/dL). We were concerned that he was experiencing a relapse of his GPP and worsening heart function.
Figure 3. Diffuse involvement of the anterior chest and abdomen with pustule studded erythematous papules and plaques.
Figure 4. Pustules scattered over the knees and thighs, several demonstrating erythematous halos.
Figure 5. Generalized pustules on the abdomen and arms, with notable erythema.
Figure 6.Numerous pustules with early crusting on the legs.
Figure 7. Localized flare with deep red pustules and scattered erosions on the lateral flexed knee.
We referred him to our tertiary medical center for cardiac evaluation. While in the hospital, he was started on cyclosporin. We have been attempting to get the patient back on spesolimab and are currently working with the manufacturer to do that.
Discussion
This case highlights key considerations in managing GPP. With a distinct clinicopathologic entity, GPP is often triggered by medication withdrawal, infections, or hypocalcemia.4 This patient had rapid resolution of GPP and associated comorbidities when treated with spesolimab in the hospital. His relapse was most likely multifactorial–he has a history of GPP, he was no longer taking spesolimab or cyclosporine, he was tapering a 1-month course of oral prednisone, he was taking numerous supplements, and he was slightly hypocalcemic. His second flare was complicated by worsening cardiac function and he was treated with hospitalization and cyclosporine, resulting in slower resolution of symptoms.
Spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, was approved for GPP flares following a pivotal trial showing rapid pustule clearance.3 Our patient responded well initially but was unable to maintain therapy due to cost, a limitation noted in real-world applications.5
Additionally, this case reinforces the importance of calcium homeostasis in pustular flares, as hypocalcemia has been linked to flare induction in GPP.6
Conclusion
GPP is rare, but it is a potentially life-threatening condition that requires prompt and sustained therapy. Discontinuation of biologic or immunosuppressive agents can lead to rapid disease recurrence. Extensive skin disease may precipitate other systemic diseases, including exacerbation of heart failure, electrolyte abnormalities, and hypoalbuminemia. Clinicians should emphasize treatment adherence, address access barriers, and discuss disease course. Dermatologic providers should be aware of GPP triggers and associations.
Informed consent was obtained from the patient for publication of this case report and the use of clinical images.
1. Navarini AA, Burden AD, Capon F, et al. European consensus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792–1799.
2. Wang R, Cruz-Inigo AE, Kerdel FA. Pustular psoriasis: from pathophysiology to treatment. Biomedicines. 2021;9(12):1746.
3. Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431–2440.
4. Choon SE, Lebwohl M, Marrakchi S, et al. Clinical practice guidelines for the management of generalized pustular psoriasis. Int J Dermatol. 2014;53(6):689–700.
5. Viguier M, Alexandre M, Daoud W, et al. Real-world efficacy and access limitations of spesolimab in GPP management. Dermatol Ther. 2023;36(1):e15847.
6. Akilov OE, Mumcuoglu KY. Demodex mites and skin disease: relevance in immunocompromised patients. Dermatol Clin. 2020;38(1):73–81.
7. Fujioka Y, Fujioka A, Morimoto Y, et al. Hypocalcemia-induced flare in generalized pustular psoriasis. Case Rep Dermatol. 2020;12(2):261–265.
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