Generalized Pustular Psoriasis (GPP)

Generalized pustular psoriasis (GPP) is a rare, chronic, immune-mediated condition affecting the skin.¹ It is a severe form of psoriasis characterized by widespread skin inflammation, redness, and pus-filled blisters (pustules). Other symptoms may include fever, fatigue, weakness, systemic inflammation, and increased white blood cell count.²

Inflammatory GPP symptoms subside and recur during flares. Triggers, such as infection, pregnancy, menstruation, certain medication exposures or withdrawals, and/or stress, may contribute to these inflammatory flares.²

Acute Generalized Pustular Psoriasis

Acute GPP, also known as the von Zumbusch subtype, is characterized by widespread inflammation and pustular eruption. It is often accompanied by systemic constitutional symptoms, such as fever, arthralgia, chills, nausea, decreased appetite, and fatigue/malaise.^1,3 As the pustules erupt and expand, they may join together to form larger lesions.¹ 

Clinical Features of Acute GPP

Individuals with acute GPP may exhibit additional clinical features, including the development of pustules underneath the nails (subungual) and geographic tongue, identified by a loss of papillae and smooth, red patches with raised borders on the tongue.^1,4 Laboratory abnormalities in people with acute GPP may include hypocalcemia and hypoalbuminemia.¹ 

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Epidemiology of Acute GPP

Around 65% of people with acute GPP report a medical history of psoriasis vulgaris.¹ The average age at onset of acute GPP is estimated at 40.9 years, regardless of psoriasis vulgaris history.^1,5

Although some studies report conflicting evidence, most research suggests that women develop acute GPP more frequently than men.¹ Women tend to exhibit an earlier onset of the condition at around age 39.4 years vs 44.3 years in men.^1,5 

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Triggers of Acute GPP

Systemic corticosteroid use and withdrawal, pregnancy, infections, stress, and the use of medications such as methotrexate, nonsteroidal anti-inflammatory drugs (NSAIDS), Stelara^® (ustekinumab), and tumor necrosis factor (TNF)-α inhibitors may trigger acute GPP flares. In particular, systemic corticosteroid use and withdrawal is one of the main causes of acute GPP episodes.¹

Acute GPP Treatment

Paradoxically, some of the potential medication triggers for acute GPP are also used as treatments for the condition. Recommended first-line therapies for acute GPP include Soriatane^® (acitretin), cyclosporine (sold as Gengraf^®, Neoral^®, and Sandimmune^®), and methotrexate. In addition to cyclosporine, Remicade^® (infliximab), a TNF-α inhibitor, is often used to treat severe cases of acute GPP.¹

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Exanthematic Pustular Psoriasis

Cases of acute pustular eruption without accompanying systemic symptoms that resolve over a period of days are classified as exanthematic subtypes of GPP.³

Pustular Psoriasis of Pregnancy

Pustular psoriasis occurring during pregnancy is also known as impetigo herpetiformis.^1.3 It most commonly occurs during the second half to third trimester of pregnancy, but some reports suggest that it may appear as soon as the first month of pregnancy.¹

Clinical Features of Pustular Psoriasis of Pregnancy

Individuals with pustular psoriasis of pregnancy often demonstrate widespread pustule eruption over annular or polycyclic erythematous patches. Lesions usually appear within skin folds and advance outward from these points. The face, palms, and soles of the feet typically remain unaffected by this condition.¹ 

In addition to skin lesions, constitutional symptoms of pustular psoriasis during pregnancy may include fever, chills, fatigue/malaise, nausea, diarrhea, arthralgias, dehydration, and sometimes seizures and tachycardia.¹

Read more about GPP signs and symptoms

Laboratory abnormalities of this subtype may consist of anemia, hypoalbuminemia, hypophosphatemia, hypocalcemia, vitamin D deficiency, leukocytosis (especially with neutrophils), and increased erythrocyte sedimentation rate (ESR).¹

Prognosis of Pustular Psoriasis of Pregnancy

Pustular psoriasis of pregnancy increases the risk of poor neonatal outcomes such as placental insufficiency, stillbirth, early neonatal death, and fetal abnormalities. Poor neonatal outcomes are often associated with disease severity and duration.¹ 

Disease-related maternal mortality may also occur. For women who develop this condition, recurrence is common in subsequent pregnancies.¹

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Triggers of Pustular Psoriasis of Pregnancy

Pregnancy-related triggers include rising progesterone levels during the third trimester and previous use of hormonal contraception. Pregnancy may also trigger acute GPP episodes. Other possible triggers may include hypothyroidism, hypocalcemia, decreased elafin levels, increased stress levels, bacterial infections, the use of certain medications, and seasonal changes.¹ 

Treatment of Pustular Psoriasis of Pregnancy

The best option to treat pustular psoriasis of pregnancy is early induction of labor. If this is not a viable option, first-line medications to treat the condition may include systemic or topical corticosteroids such as prednisone along with cyclosporine and Remicade. Stelara may be required to treat severe, intractable cases despite increased fetal risk. Following delivery, psoralen plus ultraviolet-A (PUVA) and ultraviolet-B (UVB) phototherapies may be beneficial second-line treatments.¹

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Infantile/Juvenile Pustular Psoriasis

Pustular psoriasis occurring in people under 18 years of age is very rare, but possible. Infantile/juvenile pustular psoriasis occurs twice as often in boys, with an average age of onset between 6.6 and 7.6 years.^1,6,7

Clinical Features of Infantile/Juvenile Pustular Psoriasis

One study reported that the most common form of juvenile pustular psoriasis is annular pustular psoriasis.⁷ Annular pustular psoriasis presents as ring-shaped lesions with pustules along the advancing edge or border.^1,3,8 This same study indicated that children often demonstrated more promising prognoses than adults.⁷

In addition to skin lesions, children affected by pustular psoriasis demonstrate systemic clinical features, such as fever.^1,6 Juvenile pustular psoriasis recurs often, sometimes with an annual recurrence pattern.^1,6,7

Laboratory abnormalities may include leukocytosis and elevated ESR.^1,6

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Triggers of Infantile/Juvenile Pustular Psoriasis 

Infantile/juvenile pustular psoriasis has been found to occur in families, suggesting a possible genetic etiology of the condition. Other triggers for juvenile pustular psoriasis may include infection, vaccination, and withdrawal from corticosteroid use.¹

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Treatment of Infantile/Juvenile Pustular Psoriasis

First-line therapies for infantile/juvenile pustular psoriasis are similar to the adult treatments, including Soriatane, cyclosporine, methotrexate, and Enbrel^® (etanercept). Second-line therapies may include adalimumab, Remicade, and UVB phototherapy.¹

Annular Pustular Psoriasis

Annual pustular psoriasis, also known as the Milian-Katchoura type, is also a rare subtype of GPP. Annual pustular psoriasis (APP) exhibits a subacute, limited, recurrent clinical course. Lesions rapidly develop into ring-like erythema; however, the pustules last less than a day and are often unseen. Usually, the patient does not report a family history of the condition.⁹ 

Typical treatments for APP include topical corticosteroids, methotrexate, cyclosporine, dapsone, Tegison^®(etretinate), and Remicade.⁹

References

1. 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
2. Generalized pustular psoriasis. MedlinePlus. Updated May 1, 2017. Accessed May 18, 2023.
3. 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 18, 2023.
4. Geographic tongue. Mayo Clinic. March 6, 2018. Accessed May 18, 2023.
5. 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
6. Xiao T, Li B, He CD, Chen HD. Juvenile generalized pustular psoriasis. J Dermatol. 2007;34(8):573-576. doi:10.1111/j.1346-8138.2007.00334.x
7. Zaraa I, Fazaa B, Zeglaoui F, et al. [Pustular psoriasis in childhood in 15 cases]. Tunis Med. 2004;82(7):679-683. French.
8. Unwala R. Approach to the patient with annular skin lesions. UpToDate. Updated February 8, 2023. Accessed May 18, 2023.
9. Chennamsetty K, Kolalapudi S, Chennamsetty T. Annular pustular psoriasis responding to itraconazole masquerading dermatophytosis both clinically and therapeutically. J Am Acad Dermatol. 2017;76(6):AB45. doi:10.1016/j.jaad.2017.04.194

Reviewed by Kyle Habet, MD, on 5/25/2023.

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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.