Pustular psoriasis is an uncommon form of psoriasis consisting of widespread pustules on an erythematous background, as shown in the image below.
View Image | 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 .... |
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.
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:
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.
The following factors can reportedly trigger an eruption of pustular psoriasis:
Pustular psoriasis is uncommon in the United States. The prevalence of pustular psoriasis in Japan is 7.46 cases per 1 million people.
Pustular psoriasis affects all races.
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.
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]
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.
For patient education information, see the Skin Conditions & Beauty Center, as well as the patient education articles Psoriasis, Plaque Psoriasis, and Types of Psoriasis.
In generalized pustular psoriasis, the skin initially becomes fiery red and tender. Constitutional signs and symptoms include headache, fever, chills, arthralgia, malaise, anorexia, and nausea. Within hours, clusters of nonfollicular, superficial, 2- to 3-mm pustules may appear in a diffuse pattern.
Flexural and anogenital areas are most commonly involved in pustular psoriasis. Less often, facial lesions occur. Pustules can appear on the tongue and develop subungually, resulting in dysphagia and nail shedding, respectively.[23] Pustules coalesce within 1 day to form lakes of pus that dry and desquamate in sheets, leaving behind a smooth, erythematous surface on which new crops of pustules may recur.
Episodes of pustulation occur for days to weeks, causing the patient severe discomfort and exhaustion. A telogen effluvium type of hair loss may develop in 2-3 months.
Upon remission of pustules, most systemic symptoms disappear. However, patients can experience an erythrodermic state or residual lesions of psoriasis vulgaris. Patients with a history of psoriasis may show a predilection for particular pustular psoriasis subtypes, particularly generalized pustular psoriasis and acrodermatitis of Hallopeau[4] ; however, a preceding history of psoriasis is not a requirement.[14]
Circinate or annular-type pustular psoriasis predominates in childhood and runs a more subacute course with less severe manifestations. Often, recurrent episodes of annular or circinate erythematous plaques are seen, with pustules and scaling along the periphery.[3] These lesions appear primarily on the trunk and undergo peripheral expansion with central healing over hours to days. Other systemic signs and symptoms are either mild or absent.
The juvenile/infantile type of pustular psoriasis typically has a benign course. Systemic involvement is not common, and spontaneous remissions frequently occur.
Patients appear distressed, often tachypneic, tachycardic, and febrile. The oropharyngeal mucosa may be hyperemic, and a geographic tongue or fissured tongue may be appreciated. Skin findings include a generalized or patchy erythema studded with interfollicular pustules that may have an annular or generalized/nonspecific configuration.
Lesions appear on the trunk, extremities, and, rarely, on the face. Flexural and anogenital accentuation may be present. Pustulation may also involve the nail beds, resulting in onychodystrophy, onycholysis, and defluvium unguium.
Peripheral scaling may be observed, especially in areas that have undergone pustulation. The rest of the physical examination depends on systemic complications.
Occasionally, acute respiratory distress syndrome may complicate generalized pustular psoriasis.
Other possible complications in pustular psoriasis include the following:
Findings include the following:
The overall architecture of the epidermis is similar to patients with psoriasis vulgaris, exhibiting parakeratosis, elongation of rete ridges, and thinning of the suprapapillary epidermis. The superficial dermis shows a mononuclear infiltrate and numerous neutrophils migrating from papillary capillaries to the epidermis. Neutrophils in the epidermis can aggregate between keratinocytes, where there is also spongiosis, forming pustules known as spongiform pustules of Kogoj, a characteristic histologic feature.[25]
There is no criterion standard therapy for pustular psoriasis. Disease severity and extent of skin involvement help guide treatment.
Current recommendations include initiation of systemic medications together with the proper supportive measures. Oral retinoids (acitretin, isotretinoin), methotrexate, cyclosporine, and infliximab are considered first-line therapies by the National Psoriasis Foundation Medical Board.[26] Hydroxyurea and 6-thioguanine have also been used with success.[27, 28]
In children, acitretin, cyclosporine, methotrexate, and etanercept are options for first-line therapy; however, no randomized controlled trials exist to confirm efficacy.[26]
Second-line therapies include biologic agents (etanercept, adalimumab, ustekinumab, secukinumab) or topical treatments (corticosteroids, calcipotriene, tacrolimus) for more localized disease on the palms and soles.[26] An example of the palmoplantar condition is seen in the image below.[29] Guidelines regarding these second-line therapies are needed, as anecdotal reports describe paradoxical induction of pustular psoriasis with some biologics.[30, 31]
Combination therapy with use of a first- and second-line agent can also be considered.[26]
View Image | Palmoplantar pustular psoriasis, a type of pustular psoriasis that appears on the palms of the hands or the soles of the feet. Courtesy of Hon Pak, MD.... |
The study of IL35RN gene mutations in the pathogenesis of generalized pustular psoriasis has led to new advances in treatment. Case reports have documented success with IL-1 receptor antagonists (eg, anakinra), and clinical trials are currently underway.[32, 33]
Case reports describe the efficacy of the drug tocilizumab in the treatment of biologic-induced plantar pustular psoriasis.[34] Tocilizumab is a monoclonal antibody that blocks IL-6 activity at both soluble and membrane-bound complexes, thus inhibiting IL-6‒dependant STAT1/STAT3 activation. However, reports describe rheumatoid arthritis patients treated with tocilizumab who develop paradoxical biologic-induced psoriasiform dermatitis.[35] Tofacitinib, a Janus kinase inhibitor, has also been tested as a potential therapy for psoriasis, but efficacy in pustular psoriasis is still undetermined.[36]
Several case reports discuss treatment of pustular psoriasis in pregnancy. Cyclosporine has been used with success in such cases, as well as infliximab (5 mg/kg).[37] The woman on infliximab delivered a healthy female baby via cesarean delivery. The neonate breastfed for 1 month and developed normally. No detectable adverse effects were noted, despite potential exposure to infliximab throughout gestation and breastfeeding.[38]
Also see Guidelines.
Patients usually have too much systemic toxicity and erythema during a flare to tolerate oral psoralen plus ultraviolet-A (PUVA). Treatment also requires frequent clinic visits (up to 4 d/wk), which is logistically difficult.
However, several studies have reported that PUVA is safe and effective in controlling flares of pustular psoriasis. Typically, PUVA is started once the patient has been stabilized on acitretin. PUVA has also successfully been used in combination with oral cyclosporine.[26]
While little is written regarding the use of phototherapy for pustular psoriasis,[39] narrow-band UV-B may be a reasonable choice since it has achieved therapeutic effects similar to those of PUVA in other forms of psoriasis.
Acitretin is administered first at 0.2-0.5 mg/kg for 7 days, and then PUVA is added 3 times per week. As lesions resolve, acitretin can be withdrawn, and maintenance phototherapy with PUVA or narrowband UV-B can be continued as needed.
Patients with generalized pustular psoriasis eruptions may require hospitalization to ensure adequate hydration, bed rest, and avoidance of excessive heat loss. Supportive therapy with bland topical compresses and saline or oatmeal baths helps sooth and debride affected areas.
Request consultations with medical subspecialists according to the degree of systemic involvement.
Guidelines on the management and treatment of psoriasis with phototherapy were released in September 2019 by the American Academy of Dermatology and the National Psoriasis Foundation.[40]
Phototherapy using narrowband ultraviolet B (NB-UVB) is recommended as monotherapy for adults with plaque psoriasis.
For adults with generalized plaque psoriasis, the recommended NB-UVB phototherapy starting dose should be based on the minimal erythema dose or it should be determined based on a fixed-dose or skin-phototype protocol.
For adults with generalized plaque psoriasis, a treatment phase of thrice-weekly dosing of NB-UVB phototherapy is recommended.
For adults with psoriasis, treatment with short-term psoralen plus ultraviolet A (PUVA) monotherapy is more effective than NB-UVB.
Owing to its increased safety, higher convenience, and lower cost, NB-UVB is preferred over PUVA monotherapy for psoriasis in adults, even though it is less effective.
In adults with generalized plaque psoriasis, NB-UVB is recommended over broadband ultraviolet B (BB-UVB) monotherapy.
Treatment with NB-UVB monotherapy is recommended for guttate psoriasis patients, regardless of their age.
For appropriate patients with generalized plaque psoriasis, home-based NB-UVB phototherapy is recommended as an alternative to in-office NB-UVB phototherapy.
Treatment with NB-UVB phototherapy is recommended for pregnant patients who have guttate psoriasis or generalized plaque psoriasis.
As a measure to possibly improve efficacy, NB-UVB phototherapy can be safely augmented with concomitant topical therapy using retinoids, vitamin D analogues, and corticosteroids.
Oral retinoids can be combined with NB-UVB phototherapy in appropriate patients with generalized plaque psoriasis if they have not responded adequately to monotherapy.
Owing to an increased risk of developing skin cancer, long-term combination therapy with NB-UVB and cyclosporine is not recommended for adults with generalized plaque psoriasis.
Apremilast combined with NB-UVB phototherapy can be considered for adult patients with generalized plaque psoriasis if they have not responded adequately to monotherapy.
To reduce the risk of genital skin cancer, all patients receiving NB-UVB phototherapy should be provided genital shielding.
To reduce the risk of ocular toxicity, all patients receiving NB-UVB phototherapy should be provided eye protection with goggles.
Owing to the risk of photocarcinogenesis, use caution when administering NB-UVB phototherapy to patients with a history of melanoma or multiple nonmelanoma skin cancers, arsenic intake, or prior exposure to ionizing radiation.
Folate supplementation is recommended for females of childbearing age who are receiving NB-UVB phototherapy.
To maintain the clinical response from NB-UVB phototherapy, maintenance therapy can be considered.
In adults with generalized plaque psoriasis, BB-UVB phototherapy is recommended as monotherapy if NB-UVB is not available.
In adults with generalized plaque psoriasis, BB-UVB monotherapy is considered less efficacious than NB-UVB or oral PUVA monotherapy.
Monotherapy with BB-UVB may be considered for adults with guttate psoriasis.
To reduce the risk of genital skin cancer, all patients being offered BB-UVB phototherapy should be provided with genital shielding.
To reduce the risk of ocular toxicity, all patients receiving BB-UVB phototherapy should be provided eye protection with goggles.
Owing to the risk of photocarcinogenesis, use caution when administering BB-UVB phototherapy to patients with a history of melanoma or multiple nonmelanoma skin cancers, arsenic intake, or prior exposure to ionizing radiation.
Combination therapy with acitretin and BB-UVB can be considered in adults with generalized plaque psoriasis.
The recommended targeted UVB phototherapy for adults with localized plaque psoriasis (< 10% body surface area), for individual plaque psoriasis lesions, or for patients with more extensive disease includes excimer 308-nm laser, excimer 308-nm light, and targeted NB-UVB 311- to 313-nm light.
For maximal efficacy, the recommended treatment frequency for targeted UVB phototherapy in adults with localized plaque psoriasis is 2-3 times per week, rather than once every 1-2 weeks.
In adults with localized plaque psoriasis, the initial dose of targeted UVB phototherapy is based on the minimal erythema dose or by a fixed-dose or skin-phototype protocol.
For treating localized plaque psoriasis in adults, the most effective targeted UVB phototherapy is excimer 308-nm laser, followed by excimer 308-nm light, followed by localized NB-UVB 311- to 312-nm light.
For adults with plaque psoriasis (including palmoplantar psoriasis), a recommended targeted UVB phototherapy includes excimer 308-nm laser and excimer 308-nm light.
Treatment of plaque psoriasis in adults with excimer 308-nm laser may be combined with topical steroid therapy.
A recommended targeted UVB phototherapy treatment for adults with scalp psoriasis is excimer 308-nm laser.
In the treatment of localized plaque psoriasis in adults, particularly those with palmoplantar psoriasis or palmoplantar pustular psoriasis, topical phototherapy with PUVA is deemed superior to NB-UVB 311- to 313-nm light.
A recommended treatment for psoriasis in adults is oral PUVA.
A recommended treatment for moderate-to-severe psoriasis in adults is bath PUVA.
Photodynamic therapy with either aminolevulinic acid or methyl aminolevulinate is not recommended for adults with localized psoriasis, including the palmoplantar variety or nail psoriasis.
Evidence is insufficient to recommend grenz ray therapy (long-wavelength ionizing radiation) for the treatment of psoriasis.
Sufficient evidence exists to recommend climatotherapy (temporary or permanent relocation geographically) for the treatment of psoriasis.
Evidence is insufficient to recommend the use of visible light (blue or red) as a more effective treatment for psoriasis, except in nail psoriasis.
Sufficient evidence exists to recommend Goeckerman therapy (coal tar in combination with UVB phototherapy) for the treatment of psoriasis.
Pulsed-dye laser can be considered for nail psoriasis.