Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
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Overview
Generalized pustular psoriasis (GPP) is a rare, chronic, and severe inflammatory skin disease that is characterized by the presence of widespread pustules on the skin. GPP can have a sudden onset and be associated with systemic symptoms, such as fever and malaise. This disease can be life-threatening due to the possible subsequent development of sepsis or renal, respiratory, hepatic, or cardiac failure, requiring prompt treatment.1,2
Epidemiology
The prevalence of GPP is estimated to be 1 to 7 cases per million persons. The disease can occur in both children and adults, with a female preponderance; however, the development of the disease is more common in adults, with a reported median age at diagnosis of 50 years.1 Diseases such as inflammatory polyarthritis can be associated with a GPP diagnosis. Other comorbidities include metabolic syndrome, obesity, hypertension, dyslipidemia, and diabetes.3
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Pathophysiology
Generalized pustular psoriasis is believed to be caused by a combination of genetic and environmental factors.1 Mutations in the IL36RN gene have been identified in patients with GPP, which may result in dysregulation of the immune system and development of the disease.3
Environmental triggers, such as infections, medications, withdrawal from systemic corticosteroids, pregnancy, and stress, may also play a role in the development and exacerbation of GPP.1,3
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Types
There are 4 subtypes of GPP. These are classified according to the onset of flares and the morphology of lesions1:
- Von Zumbusch: This form of GPP has a rapid onset and is a life-threatening condition.
- Annular: In this type of GPP, patients develop annular lesions with peripheral pustules within 7 days to 3 months. It is typically associated with mild symptoms.
- Chronic acral: In this type of GPP, lesions spread and form a generalized pustular flare.
- Mixed: In this form of GPP, patients present with features from more than 1 type of the disease.
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Signs and Symptoms
The hallmark feature of GPP is the development of flares with the presence of painful erythema and widespread pustules on the skin, which may coalesce. The severity of symptoms in GPP is variable from patient to patient and can also differ between flares.2
Patients can also experience extracutaneous symptoms during flares. Common symptoms of GPP include fever, malaise, fatigue, and disabling edema.2
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Diagnosis
The diagnosis of GPP is based on clinical features, including widespread pustules on the skin, fever, and systemic symptoms. A skin biopsy may be necessary to confirm the diagnosis and rule out other conditions.1
Although there are no specific laboratory tests for diagnosing GPP, several laboratory analyses can be performed, including4:
- Complete blood cell count;
- Erythrocyte sedimentation rate;
- C-reactive protein;
- Plasma globulins (immunoglobulin [Ig] G or IgA); and
- Blood chemistries.
Genetic testing may also be performed to identify mutations in the IL36RN gene, which is associated with GPP.3,4
Differential diagnosis is based on skin symptoms, potential disease triggers, medical history, histopathologic features, laboratory test results, and the clinical course of the disease.4
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Treatment
Systemic symptoms, like fever and joint pain, require treatment with antipyretics and anti-inflammatory medications. First-line therapies in adults include systemic retinoids (Soriatane® [acitretin], isotretinoin), methotrexate, cyclosporine, and infliximab. In pediatric patients, first-line therapy includes Soriatane, cyclosporine, methotrexate, and etanercept.5
Second-line therapies may be used as stand-alone treatment or in combination with first-line approaches, such as etanercept and adalimumab. They may also be used as topical treatments, such as corticosteroids, when the disease is localized.5
Studies on interleukin-36 (IL-36)-targeted therapies have shown that IL-36 pathway inhibitors, such as Spevigo® (spesolimab) and imsidolimab, may be new therapeutic approaches for GPP. Spevigo has been recently approved for the treatment of GPP flares in adults in the United States and Japan.1
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References
- Rivera-Díaz R, Daudén E, Carrascosa JM, de la Cueva P, Puig L. Generalized pustular psoriasis: a review on clinical characteristics, diagnosis, and treatment. Dermatol Ther (Heidelb). 2023;13(3):673-688. doi:10.1007/s13555-022-00881-0
- Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(Suppl 1):21-29. doi:10.1007/s40257-021-00654-z
- Mirza HA, Badri T, Kwan E. Generalized pustular psoriasis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated September 12, 2022. Accessed May 5, 2023.
- Fujita H, Gooderham M, Romiti R. Diagnosis of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(Suppl 1):31-38. doi:10.1007/s40257-021-00652-1
- Shah M, Al Aboud DM, Crane JS, Kumar S. Pustular psoriasis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated August 8. 2022. Accessed May 5, 2023.
Reviewed by Hasan Avcu, MD, on 5/18/2023.
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