Generalized pustular psoriasis induced by systemic steroid dose reduction.

Generalized pustular psoriasis, or psoriasis of von Zumbusch, is an acute and severe clinical form of psoriasis, which usually occurs in patients with psoriasis undergoing aggravating factors. In this work, we report the case of a female patient, 70 years old, who developed generalized pustular psoriasis symptoms while reducing the dose of oral corticosteroids, improperly introduced for the treatment of alleged acute generalized exanthematous pustulosis. The differential diagnosis of generalized pustular psoriasis should be made with other pustular dermatoses, such as subcorneal pustulosis, IgA pemphigus and especially with acute generalized exanthematous pustulosis. Personal history of psoriasis and histopathological findings with psoriasiform changes and subcorneal pustule favored the diagnosis. She was treated with acitretin 30 mg / day, progressing to complete regression of the lesions.

INTRODUCTION

Pustular psoriasis is an infrequent clinical variant of psoriasis, characterized by the presence of sterile pustules, non-follicular, that arise in an erythematous area. It may be classified as generalized, annular, exanthematous and localized. These clinical forms are differentiated by their extension, topography, configurations of lesions and by their response to the treatment.[1] Generalized pustular psoriasis (GPP), or psoriasis of von Zumbusch, is an acute and potentially grave clinical form, which occurs usually in patients with psoriasis who undergo aggravating factors, but which may arise in patients without previous history of psoriasis.[2] Among the aggravating factors the infections, sunburns, use of certain medications (lithium, salicylates, tar, chloroquine and beta-blockers) and, especially, the use and later interruption in the use of systemic corticosteroids stand out.[3] In this work, the case of a patient who developed grave symptoms of GPP while reducing the dose of prednisone is reported.

CASE REPORT

Female patient, 70 years old, was diagnosed with palmoplantar psoriasis in 2003. She was treated with topical medications and oral methotrexate, with regression of lesions. In 2012, she developed cutaneous symptoms with erythema and generalized pustules, accompanied by systemic symptoms. She searched another dermatology service, where she was diagnosed with acute generalized exanthematous pustulosis (AGEP). She underwent corticotherapy by injection, in the pulse therapy scheme, and then oral prednisone. There was improvement of clinical conditions, but, when she was in the process of reducing the dose of prednisone, symptoms worsened. At that moment, the dose of prednisone was increased to 80 mg/day, orally. However, during the reduction of prednisone dosage, there was worsening of clinical manifestations, then she decided to abandon treatment and search for another medical service. In July of 2013, she was attended to in our premises presenting generalized erythema and edema, followed by pustular lesions with some crusted areas (Figure 1). Additionally, there was confluence of pustular lesions, forming lakes of pus, mainly in the lower limbs (Figure 2). There was also general involvement with anorexia, nausea, malaise, shivering and burning sensation at the site of lesions. Due to the seriousness of symptoms, hospitalization was indicated, with intensive care. As for the laboratory tests, hemogram showed leukocytosis and elevated erythrocyte sedimentation rate. Histopathological examination revealed subcorneal spongiform pustule, acanthosis and exocytosis in neutrophils. In the dermis, there was a mononuclear cell infiltrate and neutrophils (Figure 3). The patient was treated with acitretin orally at 30 mg / day and saw significant improvement of lesions, being discharged 21 days after hospitalization. She is still under care, using acitretin, with total regression of lesions and with no relapses to this day – 16 months after introduction of the oral retinoid (Figure 4).

Figure 1

Generalized erythema and edema, accompanied by pustular lesions with some crusted areas

Figure 2

Confluence of pustular lesions in the lower limbs, forming lakes of pus

Figure 3

Subcorneal spongiform pustule, acanthosis and exocytosis of neutrophils. In the dermis, mononuclear cells and neutrophils infiltrate (HE, 100x and 400x)

Figure 4

Total regression of lesions, without relapses, 16 months after the introduction of oral retinoid

DISCUSSION

GPP is a severe form of psoriasis, which physiopathogeny is not completely clarified. Some authors propose that GPP without previous history of psoriasis has a different etiopathogenic mechanism than the GPP that arises in patients with previous diagnosis of the disease.[4] Despite the fact that the disease is considered polygenic, more recent studies demonstrate that mutations in genes CARD14 and IL36RN may be associated to familial cases of GPP. GPP triggered by mutations in gene IL36RN, which codifies the interleukin 36 (IL-36) receptor antagonist, has also been named as IL-36 receptor antagonist (Ditra) and defined by some authors as a new hereditary inflammatory disease.[5] Other studies also point out that certain cytokines may be related to the severity of the disease. Elevated serum levels of IL-4, IL-8, CXCL-1 e CCL-3 were positively correlated with severity scores, while levels of IL-10 and IL-22 usually are diminished after start of treatment.[6] Differential diagnosis of GPP must be done especially with subcorneal pustulosis, IgA pemphigus and AGEP. Previous history of psoriasis and histopathological findings with psoriasiform alterations helps the diagnosis of GPP, and these factors were present in this case. The diagnostic difficulty between GPP and AGEP may be the cause of many cases of pustular psoriasis being treated with systemic corticotherapy, causing worsening of cutaneous symptoms and severe systemic involvement. It is important to emphasize that histological examination of AGEP usually reveals a predominantly eosinophilic infiltrate, with exocytosis of eosinophils, and, in some cases, necrosis of keratinocytes.[7] The histopathology of the present case showed a neutrophilic infiltrate with exocytosis of neutrophils, in addition to subcorneal pustule, which corroborated the diagnosis of GPP. The drug of choice for the treatment of GPP is acitretin, although good results have already been obtained with methotrexate, cyclosporine and immunobiologicals. Most recent studies report that GPP cases associated to mutations of gene IL36RN have presented good response to the use of anakinra, an IL-1 receptor antagonist.[8,10]