Pustular Psoriasis

Updated: Oct 03, 2019
  • Author: Clay J Cockerell, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Pustular psoriasis is an uncommon form of psoriasis consisting of widespread pustules on an erythematous background, as shown in the image below.

Note the clearly defined, raised bumps on the skin Note the clearly defined, raised bumps on the skin that are filled with pus (pustules). The skin under and around these bumps is reddish. Courtesy of Hon Pak, MD.

See Psoriasis: Manifestations, Management Options, and Mimics, a Critical Images slideshow, to help recognize the major psoriasis subtypes and distinguish them from other skin lesions.

Pustular psoriasis may result in erythroderma. Cutaneous lesions characteristic of psoriasis vulgaris can be present before, during, or after an acute pustular episode, but are not required for diagnosis of pustular psoriasis.

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Types of Pustular Psoriasis

Generalized pustular psoriasis is a chronic and relapsing condition that presents with a sudden onset of rash and pustules located on nonacral skin. Generalized pustular psoriasis also commonly presents with systemic symptoms, including fever, pain, and malaise, the severity of which vary case-by-case, as well as psoriasis vulgaris. [1] However, the presence of systemic inflammation and psoriasis vulgaris are not necessary for diagnosis. [1, 2]

The annular (or circinate) type is also known as subacute generalized pustular psoriasis. It tends to run a subacute or chronic course with fewer systemic manifestations. A disproportionately high number of cases are found in the pediatric population. [3]

Palmoplantar pustulosis is a localized form of pustular psoriasis and presents with chronic pustular eruptions of the palms and soles. [4] Palmoplantar pustulosis is not typically associated with the life-threatening complications seen in generalized pustular psoriasis; however, possible complications include skeletal and joint disease. [1]

Acrodermatitis continua of Hallopeau is a chronic form of pustular psoriasis characterized by pustular eruptions of the tips of the fingers and toes, which spare the underlying joints and bone. [1] Cases are generally refractory to treatment. Subsets of these cases are considered variants of pustular psoriasis, particularly since they are indistinguishable histologically and in early clinical presentation. [2, 5]

Mixed forms of pustular psoriasis are commonly seen in patients with pustule types and locations specific to several of the above-described forms of pustular psoriasis. [2]

A juvenile or infantile type of pustular psoriasis has been described, but it is the least common form.

Additionally, several disease entities are considered, by some, to be variants of pustular psoriasis. These include the following:

  • Pregnancy-associated impetigo herpetiformis: Occurring predominately in the third trimester, this is a variant of acute pustular psoriasis that carries an increased risk of subsequent stillbirth or fetal abnormalities. [6]
  • Sneddon-Wilkinson syndrome or subcorneal pustular dermatosis (SCPD): The disease follows a relapsing and remitting course that may develop into generalized pustular psoriasis. Occurring predominately in patients middle-aged or older, SCPD is associated with underlying malignancies (most commonly multiple myeloma and IgA monoclonal gammopathy) and pyoderma gangrenosum. [7]
  • Acute generalized exanthematous pustulosis (AGEP): Characterized by a widespread rash evolving into pustules, AGEP is associated with a prescribed drug in over 90% of cases. Typical drugs include pristinamycin and amoxicillin, as well as other antibiotics. [1] A minority of patients develop systemic involvement, most commonly of the hepatic, renal, and pulmonary systems. AGEP is associated with IL36RN mutations similar to those found in pustular psoriasis, palmoplantar pustulosis, and acrodermatitis continua of Hallopeau, which is not surprising given the similarities in clinical and immunologic features of these diseases. Taken together, some consider AGEP a drug-induced form of pustular psoriasis. [8]
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Etiology

Enhanced polymorphonuclear leukocyte (PMNL) chemotaxis is much more pronounced in pustular psoriasis than in psoriasis vulgaris. [9] This observation has been attributed to either an intrinsic PMNL defect or to the presence of chemoattractants in the psoriatic epidermis. Although the principal stimulus that triggers the phenomenon of massive PMNL migration from the vasculature to the epidermis is unknown, several new pathways involved directly and indirectly with neutrophil chemotaxis have been the topic of recent investigations.

The interleukin (IL)‒36 receptors are expressed constitutively on dermal dendrocytes, CD4+ T cells, and macrophages and, when activated, promote maturation of monocyte-derived dermal dendrocytes and inductions of cytokines, including IL-1, IL-6, IL-23, tumor necrosis factor-alpha (TNF-a) , and interferon-gamma (INF-g), which promote neutrophil migration. [10]

A subset of IL-23‒responsive CD4+ T-cells, identified as Th17 cells, induce IL-17 and IL-22, which, in turn, induce production of IL-6, IL-8, and CXCL5, which promote differentiation, activation, and migration of neutrophils and provide a positive feedback loop for Th17 cell differentiation. Significantly increased levels of IL-17 have been identified in lesional skin of pustular psoriasis versus nonlesional skin of the same patients. [10]

IL-6 signaling has gained recent attention for its role in the pathogenicity of pustular psoriasis. The IL-6-receptor subunit functions as both a membrane-bound receptor and a soluble receptor. This dual functionality separates it from all other known cytokine receptors that function only as membrane-bound forms. The IL-6/IL-6R complex, together with the ubiquitously expressed gp130, activate the JAK/STAT kinase and the RAS/MEK/ERK/MAPK kinase pathways, which ultimately augment nuclear gene expression. The downstream effects of IL-6 include synthesis of acute phase reactants, B-cell maturation, T-cell differentiation, positive influence on Th17 cell development, maturation neutrophils from myeloid progenitors, increased expression of ICAM-1 and other endothelial adhesion molecules that enhance neutrophil migration, and release of proinflammatory cytokines, such as IL-23 and IL-17, to further promote the Th17 positive feedback loop. [10]

Electron microscopic studies have shown the presence of basal keratinocyte herniations in lesions of pustular psoriasis. These are cytoplasmic processes from basal keratinocytes that protrude into the dermis through gaps in the basal lamina. These herniations are mostly clustered over collections of neutrophils in the dermis. This finding suggests an increased production of neutrophilic proteolytic enzymes in the dermis of pustular psoriasis patients.

Immunohistochemical methods have determined the involvement of some of these proteases and their inhibitors in the development of pustules.

Elastase is a proteolytic enzyme released by PMNLs during the process of extravasation and migration through the dermoepidermal junction. One study found an epidermal elastase inhibitor (skin-derived antileukoproteinase) expressed in psoriatic skin prior to the influx of PMNLs, which disappeared when the composition of the infiltrate changed. This finding was not confirmed by other studies.

Additional studies investigating other potential mechanisms have shown decreased natural killer cell activity in generalized pustular psoriasis. An increased incidence of HLA-B27 also has been found among patients with pustular psoriasis. This haplotype is seen in psoriasis patients with peripheral arthritis, as well as in patients with ankylosing spondylitis and reactive arthritis.

Homozygous, compound heterozygous, and single heterozygous missense mutations in a gene (IL36RN) that encodes a soluble anti-inflammatory cytokine, an IL-36‒receptor antagonist, have been associated with an increased incidence of pustular psoriasis, as well as an earlier age of onset. [1] Disease severity varies between these genotypes, with individuals completely lacking the protein having the worst prognosis. [1] These mutations predispose individuals to autosomal recessive inherited and sporadic generalized pustular psoriasis, AGEP, acrodermatitis continua of Hallopeau, and, to a lesser extent, palmoplantar pustulosis. [4, 8, 11, 12] Mutations affecting the IL36RN gene lead to unopposed release of inflammatory cytokines, including IL-6, IL-8, IL-1a, IL-1b, IL-23, TNF-a, and INF-g, which promote neutrophil activation and migration as well as dysregulated activation of dendritic cells and T cells. [1, 10] Individuals with these mutations have a lower rate of concurrent plaque psoriasis compared with patients with pustular psoriasis without the mutation. [1]

Studies have also identified two other gene mutations seen in individuals with pustular psoriasis. One of these, CARD14 (caspase-activating recruitment domain, member 14), has been shown to be up-regulated in individuals with generalized pustular psoriasis and palmoplantar pustulosis. This up-regulation leads to increased amounts of NF-kB, IL-8, and IL-36G. [1] The other gene, AP1S3, leads to increased amounts of IL-36A, and also causes disturbances in the innate immune response through disruption of Toll-like receptor-3. [1] It is most commonly seen in individuals with generalized pustular psoriasis and acrodermatitis continua of Hallopeau.

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Risk Factors for Pustular Psoriasis

The following factors can reportedly trigger an eruption of pustular psoriasis:

  • Withdrawal of systemic steroids, [13] potent topical steroids, [14] or cyclosporine [15]
  • Drugs, including salicylates, iodine, lithium, phenylbutazone, oxyphenbutazone, trazodone, penicillin, hydroxychloroquine, calcipotriol, interferon-alpha, recombinant interferon-beta injection, [16]  terbinafine, [17] and bCG vaccination [18]
  • Strong, irritating topical medications, including tar, anthralin, steroids under occlusion, and zinc pyrithione in shampoo
  • Cutaneous infections (eg, Staphylococcus aureus, Streptococcus epidermidis) [19]
  • Sunlight or phototherapy
  • Cholestatic jaundice
  • Hypocalcemia
  • Smoking, especially for palmoplantar pustulosis and in individuals with concurrent psoriasis [4]
  • Pregnancy [1]
  • Idiopathic in many patients
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Epidemiology

Pustular psoriasis is uncommon in the United States. The prevalence of pustular psoriasis in Japan is 7.46 cases per 1 million people.

Race predilection

Pustular psoriasis affects all races.

Sex predilection

The male-to-female ratio for pustular psoriasis is 1:1 in the United States. Globally, a female predominance has been reported, with a female-to-male ratio of 1.5, 1.7, and 3.5, respectively, for individuals with acrodermatitis of Hallopeau, generalized pustular psoriasis, and palmoplantar pustulosis. [4, 20, 21] The female-to-male ratio is 3:2 in children.

Age predilection

The average age among adult patients with pustular psoriasis is reported between 48 and 50 years, [20] while the average age of onset of acute generalized pustular psoriasis is 31 years. [4] Palmoplantar pustulosis and acrodermatitis continua of Hallopeau have mean ages of onset of 43.7 and 51.8 years, respectively. [4]

Children aged 6 weeks to 10 years can be affected, although rarely. One case described generalized pustular psoriasis in a 6-week-old infant. [22] The mean age of onset for annular pustular psoriasis in pediatric populations is 6 years. [3]

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Prognosis

Older patients with generalized pustular psoriasis have a poor prognosis. Death can result from sepsis or renal, hepatic, or cardiorespiratory failure during the acute erythrodermic stage.

Patients with a history of chronic psoriasis vulgaris prior to generalized pustular eruption tend to have a better prognosis than patients with more atypical forms of psoriasis.

In children, as long as serious secondary infections are avoided, episodes of pustular psoriasis have a good prognosis.

There is no cure for pustular psoriasis. Recurrent flares are common, even years after diagnosis. Patients often require continued therapy and avoidance of precipitating factors. [20]

Death in pustular psoriasis may occur secondary to cardiorespiratory failure. This usually occurs in untreated patients.

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Patient Education

For patient education information, see the Skin Conditions & Beauty Center, as well as the patient education articles Psoriasis, Plaque Psoriasis, and Types of Psoriasis.

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