Pustular psoriasis is a rare, immune-mediated systemic skin disorder characterized by yellowish pustules on an erythematous base with a variety of clinical presentations and distribution patterns. Pustular psoriasis is considered a variant of psoriasis vulgaris. The pustules can be widespread or localized and are characterized by a sterile, predominantly neutrophilic infiltrate. Unlike chronic plaque psoriasis (the most common variant of psoriasis vulgaris), lesions of pustular psoriasis are often tender to palpation. Pustular psoriasis can be further subdivided based on the clinical presentation and the location of pustules.
Subtypes of pustular psoriasis include:
Pustular psoriasis occurs in genetically susceptible individuals and can be triggered by certain risk factors leading to neutrophil chemotaxis and accumulation in the epidermis. Patients with pustular psoriasis have an increased frequency of the HLA-B27 allele compared to the general population. Most cases of pustular psoriasis are idiopathic, however, risk factors that may have a role in the etiology of pustular psoriasis include :
Pustular psoriasis is a rare disease. It usually affects both genders equally and has no sexual predilection. It has a bimodal presentation; affecting adults and children. In the adult age group, the disorder appears between ages 40 to 50, whereas in the pediatric age group, it tends to present in infancy. Asians tend to be more affected than Caucasians. The pustular variants of psoriasis represent approximately 1% of all clinical cases of psoriasis vulgaris.
The exact pathogenesis of pustular psoriasis has not been fully elucidated. However, based on the expression of certain cytokines and responses to specific medications, several mechanisms have been proposed. A combination of genetic susceptibility and exposure to certain inciting factors (e.g., withdrawal of systemic corticosteroids) lead to an upregulation of specific cytokines and accumulation of neutrophils in the epidermis. Additionally, dermal dendritic cells release elastase, which may play a role in the formation of pustules. Both pustular psoriasis and chronic plaque psoriasis exhibit overexpression of IL-1, IL-17, IL-23, IL-36, TNF-alpha, and IFN-gamma. However, the expression of IL-1 and IL-36 are more prominent in pustular psoriasis. Studies have also identified an IL-36 receptor antagonist deficiency in patients with pustular psoriasis and patients with pustular psoriasis have also been successfully treated with a novel monoclonal antibody against the IL-36 receptor. Therefore, IL-36 likely plays a critical role in the pathogenesis of pustular psoriasis.
The histopathological features of pustular psoriasis mimic that for classical psoriasis vulgaris in having retention of the nuclei in the stratum corneum (parakeratosis), a thick stratum spinosum (hyperkeratosis), elongation of rete ridges, reduced stratum granulosum, and thinning of the suprapapillary epidermis. In addition to the classic histologic features of psoriasis vulgaris, there is also a prominent neutrophilic infiltrate in the papillary dermis and epidermis, causing basal keratinocytes to herniate into the papillary dermis disrupting desmosomal junctions of keratinocytes (spongiosis), and leading to the development of superficial micro-abscesses. Neutrophilic infiltration of the epidermis is more prominent in pustular psoriasis than other variants of psoriasis vulgaris.
Pustular psoriasis appears as numerous discrete and confluent superficial, yellowish pustules on a background of erythema. Pustular psoriasis can be diffuse or localized. A full body skin examination should be performed, including careful evaluation of the mucous membranes and the nails for signs of psoriasis and to exclude other causes of pustulosis.
Pustular psoriasis starts as red papules or plaques that quickly evolves into yellowish, superficial pustules on a background of erythema. The generalized von Zumbusch subtype usually presents with systemic symptoms like fever, joint pain, headaches, and leukocytosis. In contrast, the exanthematic subtype presents as an acute pustular eruption without systemic symptoms. The annular subtype is seen more frequently in children as annular lesions with pustules along the advancing edge. Acrodermatitis continua of Hallopeau affects the finger, toes, and nailbeds. Palmoplantar psoriasis, which can be seen as part of SAPHO syndrome, affects the palms and soles.
The clinician should inquire about the trigger factors in patients who present with pustular psoriasis, especially the use of medications like corticosteroids. Family history is important to ascertain since there is a genetic element responsible for the disease.
Patients with suspected pustular psoriasis require careful evaluation, as the von Zumbusch subtype can be life-threatening. Laboratory investigations should include a complete blood count (CBC) to evaluate for leukocytosis, an electrolyte panel to assess for hypocalcemia, and a liver panel to assess for aspartate transaminase, alanine transaminase, and levels of albumin. A pregnancy test should be ordered in women of childbearing age. A punch biopsy can be performed in all equivocal cases.
The first step in managing cases of pustular psoriasis is the identification of the triggering factors. Generalized pustular psoriasis (e.g., von Zumbusch subtype), require admission to the hospital. Systemic symptoms including fever and joint pain will require treatment with antipyretics and anti-inflammatory medications. Disease-specific medications include systemic retinoids (acitretin, isotretinoin), methotrexate, cyclosporine, and infliximab. In the pediatric age group, acitretin, cyclosporine, methotrexate, and etanercept are considered the first line options.
Second line options include systemic treatments like etanercept and adalimumab or topical treatments like corticosteroids, calcipotriene, and tacrolimus. All of these options can be monotherapy choices or in combination with the first line options. Phototherapy is another treatment option. Early delivery is recommended in pregnant patients with impetigo herpetiformis.
Recent reports indicate the successful use of L-1 receptor antagonists (e.g., anakinra) and IL-36 receptor antagonists in treating pustular psoriasis. Tocilizumab, a monoclonal antibody against the IL-6 receptor, has also shown efficacy in some recalcitrant cases of pustular psoriasis.
Pustular psoriasis is a chronic disease marked by recurrent episodes or flares. Treatment is aimed to shorten the duration of relapse, prevent complications, and extend disease-free periods. Compared to other subtypes, the von Zumbusch subtype of pustular psoriasis has a higher risk of mortality because of systemic involvement, especially with underlying comorbidities, such as cancer, renal failure, or liver failure. The localized subtypes of pustular psoriasis have a much lower risk of mortality.
Patients with psoriasis should be educated to avoid abrupt steroid withdrawal, which can trigger episodes of pustular psoriasis. Flaccid lesions should be treated with proper wound care to avoid complications and secondary infections.
Management of pustular psoriasis requires an interprofessional team approach, including providers from primary care, dermatology, and infectious disease. A detailed history and complete physical examination are critical in diagnosing cases of pustular psoriasis. A dermatologist can help in the initial diagnostic workup and to assess for complications. Depending on the surface area involved, admission to the hospital may be required (e.g., von Zumbusch subtype). In equivocal cases, a biopsy can be performed, as the differential diagnosis for pustulosis is rather vast. Treatment is targeted to prevent relapses and shorten the duration of flares.
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