Generalized Pustular Psoriasis (GPP)

Generalized pustular psoriasis (GPP) is a rare, severe, immune-mediated disorder in which widespread pustules form on the skin. The condition is often accompanied by constitutional symptoms, such as fever, chills, fatigue, and decreased appetite. Complications such as infection and organ failure can become life-threatening.¹ 

Optimal treatment of GPP requires prompt differential diagnosis from other pustular skin disorders characterized by similar clinical features and symptoms, such as acute generalized exanthematous pustulosis (AGEP), subcorneal pustular dermatosis (SPD), annular pustular psoriasis (APP), localized forms of pustular psoriasis, impetigo herpetiformis, pemphigus foliaceus, and IgA pemphigus.^1-3

Acute Generalized Exanthematous Pustulosis

AGEP is the most important entity in the differential diagnosis of GPP.⁴ This is a rare, severe, adverse cutaneous reaction, mainly to medications, typically certain antibiotics and calcium channel blockers.⁵ 

AGEP shares several features with GPP: multiple sterile pustules disseminated on an erythematous base, fever, and neutrophilia.^3,4 In AGEP, the pustules vary in size and may extend through several layers of the epidermis. Mucosal involvement is reported in up to 25% of patients.²

The pustules in AGEP are less prominent than those in GPP,² and the onset of disease is more abrupt, usually occurring within 48 hours. In addition, the duration is short, and AGEP typically resolves after 2 weeks. It does not recur, and patients do not have a personal or family history of psoriasis vulgaris.^3-5 Histopathological examination of a skin biopsy specimen can be useful in the diagnosis of AGEP.⁵

Some cases of AGEP have been shown to be associated with mutations of the IL36RN gene, which encodes the interleukin 36 receptor antagonist.⁶

Read more about GPP testing

Subcorneal Pustular Dermatosis

SPD, or Sneddon-Wilkinson disease, is a rare, relapsing neutrophilic dermatosis in which sterile pustules form in the most superficial layers of the skin.^2,6 This disorder typically affects middle-aged or older women.² 

The pustules, which are mostly flaccid and several millimeters in diameter, form on a normal or mildly erythematous base. They are usually distributed in an annular or serpiginous pattern and localized on flexural surfaces or intertriginous skin.⁶ Rarely, the face, palms, and soles are affected.²

In contrast to GPP, SPD is a chronic benign condition and not associated with systemic symptoms.⁶

Read more about GPP clinical features

Annular Pustular Psoriasis

APP is a chronic relapsing disease characterized by erythematous lesions that are usually polycyclic, small sterile pustules around the circumference of the lesions, and fine peeling. The abdomen, trunk, and proximal extremities may be affected.²

In contrast to the lesions in GPP, those in APP are not confluent. Patients may experience fever, malaise, and arthralgia, but their clinical condition is more favorable than that of individuals with GPP.²

Localized Forms of Pustular Psoriasis

The differential diagnosis for localized subtypes of pustular psoriasis includes palmoplantar pustular psoriasis (PPP), acrodermatitis continua of Hallopeau (ACH), dyshidrotic eczema, and nail infection (in ACH).⁵ PPP is a recurrent, chronic inflammatory skin disorder. Patients present with erythema, scales, and pustules on the palms and soles. In advanced stages of the disease, pustules form on an erythematous squamous base.²

ACH affects the fingers and toes, including the nails. Like GPP, this localized chronic disorder may be triggered by trauma to the distal portions of the fingers or by infection.²

In dyshidrotic eczema, clusters of vesicles that are clear blisters form on the palms and soles. Patients experience intense pruritus.⁵

Nail infection (and nail infection in ACH) can be ruled out by examination of the pustular matter. Gram stain can be used to evaluate for bacterial infection, potassium hydroxide testing for fungal infection, and polymerase chain reaction for herpetic whitlow.⁵

Read more about GPP diagnosis

Impetigo Herpetiformis

Impetigo herpetiformis is a well-defined form of dermatosis of pregnancy that may develop during the third trimester and in subsequent pregnancies. Pustules form on erythematous patches in areas such as the axillae and skin folds of the breasts. Symptoms include fatigue, fever, diarrhea, and delirium.²

In severe cases, the rash can progress to erythroderma and lead to sepsis.²

Read more about GPP complications

Pemphigus Foliaceus and IgA Pemphigus

Pemphigus foliaceus is a benign disease characterized by the formation of superficial blisters, typically on the trunk. The course is chronic, and mucosal involvement is limited or absent. The blisters may cause erosions, and the lesions can persist for years on the trunk, face, and scalp.⁷

One of several types of pemphigus is IgA pemphigus, in which tissue-bound as well as circulating IgA autoantibodies target the desmosomal proteins of the epidermis.⁸

References

1. Shah M, Al Aboud DM, Crane JS, Kumar S. Pustular psoriasis. StatPearls [Internet]. Updated August 8, 2022. Accessed May 9, 2023.
2. 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
3. Ly K, Beck KM, Smith MP, Thibodeaux Q, Bhutani T. Diagnosis and screening of patients with generalized pustular psoriasis. Psoriasis (Auckl). 2019;9:37-42. doi:10.2147/PTT.S181808
4. Reich K, Augustin M, Gerdes S, et al. Generalized pustular psoriasis: overview of the status quo and results of a panel discussion. J Dtsch Dermatol Ges. 2022;20(6):753-771. doi:10.1111/ddg.14764
5. Crowley JJ, Pariser DM, Yamauchi PS. A brief guide to pustular psoriasis for primary care providers. Postgrad Med. 2021;133(3):330-344. doi:10.1080/00325481.2020.1831315
6. Rivera-Díaz R, Daudén E, Carrascosa JM, Cueva P, Puig L. Generalized pustular psoriasis: a review on clinical characteristics, diagnosis, and treatment. Dermatol Ther (Heidelb). 2023r;13(3):673-688. doi:10.1007/s13555-022-00881-0
7. Schwartz RA. Pemphigus foliaceus. Medscape. Updated April 24, 2023. Accessed May 9, 2023
8. Plaza J. IgA Pemphigus. Medscape. Updated June 18, 2021. Accessed May 9, 2023.

Reviewed by Harshi Dhingra, MD, on 5/24/2023.

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Diana Diez Gaspar, PharmD, PhD

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.