Generalized Pustular Psoriasis (GPP)


Generalized pustular psoriasis (GPP), a rare, immune-mediated form of psoriasis with severe systemic manifestations, is characterized by relapsing/recurrent or persistent widespread eruptions of sterile, pus-filled blisters on inflamed, erythematous skin.1,2 Without treatment, GPP may become life-threatening if complications affect the circulatory system, kidneys, heart, or lungs.3

GPP is a rare form of psoriasis. Previous studies estimated that GPP accounts for approximately 1% of all cases of psoriasis; however, these estimates were based on unclear, inconsistent definitions of GPP, so they may be inaccurate.2 An awareness of the clinical features of GPP may assist the clinician in differentiating GPP from other psoriatic conditions; however, skin biopsy and laboratory studies must be conducted to confirm the presence of Kogoj spongiform pustules, leukocytosis, and neutrophilia, as these features are required for an official diagnosis of GPP.4  

Constitutional Symptoms

Although not all patients with GPP have constitutional symptoms related to systemic inflammation,4-6 in most cases, the abrupt onset of systemic symptoms is followed by dermatological manifestations. Systemic symptoms may include5-7:

  • High fever;
  • Chills;
  • General malaise/fatigue;
  • Nausea;
  • Diarrhea;
  • Loss of appetite;
  • Arthralgia;
  • Headache; and
  • Edema.

Read more about GPP signs and symptoms

Dermatological Features

The hallmark clinical feature of GPP is relapsing/recurrent or persistent inflammatory flares, characterized by the rapid development of widespread eruptions of superficial, painful, severely pruritic, sterile pus-filled blisters measuring between 2 and 3 millimeters in diameter.2,7 The blisters may spread and merge to form “lakes of pus.”3 The pustules may develop on normal-appearing skin or on fiery, erythematous patches of skin (plaque psoriasis) over large regions of the body.8 

A 2013 single-center study in Malaysia analyzed the clinical features of 102 patients with GPP, 95 of whom were diagnosed with the acute-onset subtype. Within this group of 95, the study reported that flares affecting more than 30% of the body surface area could be classified as severe or significant. The patients in whom more than 30% of the body surface area was affected more frequently had symptoms of systemic inflammation, such as pain (96.8%), fever (95.8%), and leukocytosis (69.5%).3,9

Read more about GPP clinical trials

Episodes may recur several times a year, with long periods of dormancy between flares.2 Usually, the pustules resolve within several days to weeks, but the erythema persists, along with extensive desquamation in sheets, hair loss (telogen effluvium) after 2 to 3 months, and sometimes erosions that mimic severe skin burns or toxic epidermal necrolysis.7,8 

Like severe burns, GPP with severe skin manifestations can interfere with normal skin function, including regulating body temperature, preventing hypothermia, maintaining hydration, and protecting the body from infection as the first line of defense. Conservative treatments are often required, such as encouraging fluid and protein intake, treating infections with antibiotics, monitoring fluids, and preventing hypothermia.10

Circinate or annular pustular psoriasis is the predominant form of GPP that begins in childhood. This type of GPP is generally characterized by milder symptoms, fewer systemic symptoms, and a subacute disease course. Pustules and scaling often occur along the edges of circular lesions, which appear mainly on the torso and spread peripherally. The lesions heal from the center outward over hours to days.7

Read more about GPP types

Mucosal Features

Clinical features associated with mucosal involvement in GPP include3-5:

  • Geographic tongue;
  • Fissured tongue;
  • Cheilitis;
  • Genital lesions; and 
  • Ocular involvement (conjunctivitis, uveitis, iritis).

Clinical Features of GPP With Extracutaneous Organ Involvement 

Extracutaneous findings may include3,10,11:

  • Nail abnormalities;
  • Arthralgia;
  • Cholestasis;
  • Jaundice; 
  • Lower-extremity edema; and 
  • Acute respiratory distress (rarely).

Nail tissue may be affected if pustules form beneath the nails (subungual pustules or abscesses), as commonly occurs in individuals with the acute-onset subtype of GPP.12

Read more about GPP complications

Triggers of Flares

A comprehensive history may reveal triggers of acute GPP flares in predisposed individuals, including5,10:

  • Bacterial or viral infection, especially upper respiratory tract infection;
  • Pregnancy (usually in the third trimester);
  • Medications, especially corticosteroids, but also potentially Lamisil® (terbinafine), propranolol (sold as Inderal®, InnoPran®, and Hemangeol®), Wellbutrin® (bupropion), lithium, salicylates, potassium iodide, coal tar, and dithranol/anthralin;
  • Menstruation; 
  • Hypocalcemia; and
  • Psychological stress.

Many individuals with GPP have a medical history of psoriasis vulgaris; however, GPP and psoriasis vulgaris (plaque psoriasis) are 2 distinct clinical entities.2 

Read more about GPP diagnosis

References

  1. Generalized pustular psoriasis. MedlinePlus. Accessed May 19, 2023.
  2. 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
  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. 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
  5. Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(1):21-29. doi:10.1007/s40257-021-00654-z
  6. Hoegler KM, John AM, Handler MZ, Schwartz RA. Generalized pustular psoriasis: a review and update on treatment. J Eur Acad Dermatol Venereol. 2018;32(10):1645-1651. doi:10.1111/jdv.14949
  7. Cockerell CJ. Pustular psoriasis clinical presentation: history. Medscape. Updated October 8, 2021. Accessed May 19, 2023.
  8. Boehner A, Navarini AA, Eyerich K. Generalized pustular psoriasis – a model disease for specific targeted immunotherapy, systematic review. Exp Dermatol. 2018;27(10):1067-1077. doi:10.1111/exd.13699
  9. 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
  10. Mirza HA, Badri T, Kwan E. Generalized pustular psoriasis. StatPearls [Internet]. Updated September 12, 2022. Accessed May 19, 2023. 
  11. Viguier M, Allez M, Zagdanski AM, et al. High frequency of cholestasis in generalized pustular psoriasis: evidence for neutrophilic involvement of the biliary tract. Hepatology. 2004;40(2):452-458. doi:10.1002/hep.20305
  12. Haneke E. Nail psoriasis: clinical features, pathogenesis, differential diagnoses, and management Psoriasis (Auckl). 2017;7:51-63. doi:10.2147/PTT.S126281

Reviewed by Harshi Dhingra, MD, on 5/30/2023.

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