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Diagnosis

Generalized pustular psoriasis (GPP) is a rare, severe form of psoriasis characterized by recurrent episodes of eruptions of pus-filled lesions. GPP can potentially become life-threatening due to complications, such as acute renal failure, sepsis, acute respiratory distress syndrome, or congestive heart failure.¹

Accurate and rapid diagnosis of GPP can prevent such complications; however, diagnosis can prove challenging due to the rarity of the condition, inconsistencies in definitions, and the variety of diagnostic criteria that have been proposed.¹

Clinical Assessments for GPP Diagnosis

Patients with GPP present with an acute onset of widespread, sterile, pustular lesions, measuring 2 to 3 millimeters on top of inflamed, erythematous skin. These pustular lesions may expand and combine to form larger pus-filled “lakes.” Cutaneous symptoms may consist of pruritus, burning, and pain.¹

In addition to this hallmark feature of GPP, patients often present with constitutional symptoms indicating systemic inflammation, including^1,2:

High-grade fever
Chills
Dehydration
Malaise/fatigue
Loss of appetite
Nausea
Diarrhea
Arthralgias
Tachycardia
Seizures

Other characteristic features associated with GPP include a geographic or fissured tongue, a documented medical history of psoriasis vulgaris, cheilitis, ocular inflammation (iritis, uveitis, conjunctivitis), and pregnancy.^1,2 Other clinical findings may include lower extremity edema, jaundice, and nail abnormalities.¹

Read more about GPP clinical features

Laboratory Testing for GPP Diagnosis

Laboratory testing is strongly recommended, as it can help determine the severity of the patient’s current status and identify potential complications related to GPP.¹

Laboratory testing should include¹:

Complete blood count (CBC) with differential
Comprehensive metabolic panel
Cultures and Gram staining of blood and pus samples

Characteristic CBC abnormalities found in patients with GPP include¹:

Leukocytosis with neutrophilia
Elevated erythrocyte sedimentation rate (ESR)
Lymphopenia

Characteristic metabolic panel findings in patients with GPP may reveal¹:

Hypocalcemia
Hypoalbuminemia
Elevated liver enzymes
Elevated bilirubin levels
Electrolyte abnormalities

Cultures are performed to rule out infections and other potential causes of pustulosis.¹

Read more about GPP testing

Skin Biopsy for GPP Diagnosis

Biopsy of affected skin is essential for confirming a GPP diagnosis and excluding other conditions with similar histologic presentations, such as psoriasis vulgaris and acute generalized exanthematous pustulosis (AGEP).¹

Read more about GPP differential diagnosis

Histopathological findings may include¹:

Kogoj’s spongiform pustules consisting of neutrophils that collect under the stratum corneum
Hyperkeratosis/parakeratosis
Acanthosis
Munro’s microabscesses
Dilation of capillaries in the papillary dermis
Rete ridge elongation
Superficial perivascular mononuclear cell infiltrations

The histological finding of Kogoj’s spongiform pustules is included in currently proposed GPP diagnostic criteria. The other potential dermal abnormalities listed above are seen in classic cases of psoriasis.¹

Read more about GPP histology

Genetic Testing for GPP Diagnosis

Although not routinely recommended, genetic testing may reveal mutations in 3 genes that have been associated with the development of GPP: IL36RN, AP1S3, and CARD14.¹ IL36RN mutations occur more commonly in patients with a younger onset of GPP. Genetic testing for this specific mutation is recommended in patients who develop GPP before the age of 30 years.¹

Read more about GPP genetics

Diagnostic Guidelines for GPP

In 2003, Umezawa and colleagues published guidelines to aid in the diagnosis of GPP. Their diagnostic criteria suggested that patients with GPP demonstrated³:

Systemic symptoms, including fever and fatigue
Multiple, isolated, septic pustules on erythematous skin
Kogoj’s spongiform pustules on histopathological examination
Laboratory abnormalities, such as left shift leukocytosis, elevated C-reactive protein (CRP), elevated ESR, elevated antistreptolysin O antibodies, elevated immunoglobulin G (IgG) or A (IgA), hypocalcemia, and hypoproteinemia
Recurrent episodes of the histological and clinical findings listed above

In 2017, the European Rare and Severe Psoriasis Expert Network (ERASPEN) proposed further diagnostic criteria for GPP in a consensus statement.^1,4 ERASPEN’s diagnostic criteria for GPP required the presence of “primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is restricted to psoriatic plaques).”⁴Subclassifiers for GPP included⁴:

With or without systemic inflammation
With or without psoriasis vulgaris
Either relapsing episodes (>1 episode) or persistent (>3 months)

In 2018, the Japanese Dermatological Association collaborated with the Study Group for Rare Intractable Skin Diseases to update Umezawa’s 2003 diagnostic guidelines for GPP.^1,3,5The 2018 Japanese criteria required primary parameters for the diagnosis of GPP, including⁵:

Constitutional systemic symptoms, such as fatigue and fever
Systemic or extensive flush along with multiple sterile pustules that may coalesce to form lakes of pus
Neutrophilic subcorneal pustules characterized by Kogoj’s spongiform pustules upon histopathological examination
Recurrent episodes of the histological and clinical findings listed above

Using the 2018 guidelines, clinicians can definitively diagnose GPP in individuals with all 4 features and strongly suspect GPP if individuals exhibit the second and third features. One noticeable difference between Umezawa’s criteria and the 2018 Japanese criteria is the removal of laboratory abnormalities from the diagnostic criteria due to a lack of sensitivity and specificity. However, laboratory testing is still required to assess for severity and potential complications of GPP.¹

Read more about GPP guidelines

References

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
Benjegerdes KE, Hyde K, Kivelevitch D, Mansouri B. Pustular psoriasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:131-144. doi:10.2147/PTT.S98954
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
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
Fujita H, Terui T, Hayama K, et al; Japanese Dermatological Association Guidelines Development Committee for the Guidelines for the Management and Treatment of Generalized Pustular Psoriasis. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the new pathogenesis and treatment of GPP. J Dermatol. 2018;45(11):1235-1270. doi:10.1111/1346-8138.14523

Reviewed by Hasan Avcu, MD, on 5/18/2023.

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.

Generalized Pustular Psoriasis (GPP)