A Comprehensive Review of Neutrophilic Diseases

Abstract

Neutrophilic dermatoses are a group of conditions characterized by the accumulation of neutrophils in the skin and clinically presenting with polymorphic cutaneous lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers. In these disorders, the possible involvement of almost any organ system has lead to coin the term 'neutrophilic diseases'. Neutrophilic diseases have close clinicopathological similarities with the autoinflammatory diseases, which present with recurrent episodes of inflammation in the affected organs in the absence of infection, allergy and frank autoimmunity. Neutrophilic diseases may be subdivided into three main groups: (1) deep or hypodermal forms whose paradigm is pyoderma gangrenosum, (2) plaque-type or dermal forms whose prototype is Sweet's syndrome and (3) superficial or epidermal forms among which amicrobial pustulosis of the folds may be considered the model. A forth subset of epidermal/dermal/hypodermal forms has been recently added to the classification of neutrophilic diseases due to the emerging role of the syndromic pyoderma gangrenosum variants, whose pathogenesis has shown a relevant autoinflammatory component. An increasing body of evidence supports the role of pro-inflammatory cytokines like interleukin (IL)-1-beta, IL-17 and tumour necrosis factor (TNF)-alpha in the pathophysiology of neutrophilic diseases similarly to classic monogenic autoinflammatory diseases, suggesting common physiopathological mechanisms. Moreover, mutations of several genes involved in autoinflammatory diseases are likely to play a role in the pathogenesis of neutrophilic diseases, giving rise to regarding them as a spectrum of polygenic autoinflammatory conditions. In this review, we focus on clinical aspects, histopathological features and pathophysiological mechanisms of the paradigmatic forms of neutrophilic diseases, including pyoderma gangrenosum, Sweet's syndrome, amicrobial pustulosis of the folds and the main syndromic presentations of pyoderma gangrenosum. A simple approach for diagnosis and management of these disorders has also been provided.

Keywords: Amicrobial pustulosis of the folds; Autoinflammation; Neutrophilic diseases; Pyoderma gangrenosum; Sweet’s syndrome.