Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy

Abstract

Reflectance confocal microscopy (RCM) is an imaging tool, which visualizes the epidermal skin layers in vivo with a cellular resolution. Neutrophil accumulation is a characteristic feature in psoriasis and is thought to play a role in the pathophysiology of psoriasis. Until now, imaging of neutrophil accumulation in vivo is not performed. We evaluated the dynamics of neutrophil migration in active psoriatic lesions by non-invasive RCM imaging. Additionally, we evaluated the time phasing and duration of neutrophil trafficking. We performed RCM imaging prior to the start of topical treatment and for seven consecutive days with a 24-h time interval at the Radboud University Medical Center, Nijmegen, the Netherlands. Twelve psoriatic lesions in three patients with a severe exacerbation of psoriasis were included. The four most active lesions were selected in each patient based on the highest degree of redness, induration and expansion in the previous 2 weeks. In all lesions, a cyclic pattern of neutrophil migration was observed, consisting of squirting papillae, transepidermal migration, accumulation in the stratum spinosum, accumulation in the stratum corneum and degeneration of the abscesses. The time interval of a neutrophil-trafficking cycle was 5-7 days and showed a synchronic time phasing. This study is the first to establish the dynamics and time phasing of neutrophil migration in vivo in psoriatic lesions. Previously reported theories were confirmed by these novel in vivo data. RCM might distinguish between active or chronic psoriatic areas, which might contribute to new insights into the pathogenesis of psoriasis.

Neutrophil swarming: an essential process of the neutrophil tissue response

“…However, non‐invasive reflectance confocal microscopy (RSC) revealed the coordinated migration and accumulation patterns of neutrophils in psoriatic plaques of patients, monitored for several consecutive days . Since neutrophils accumulate in very superficial skin layers in active psoriatic lesions, it was possible to employ RSC and observe a cyclic pattern of neutrophil migration, consisting of squirting of the dermal papillae, transepidermal migration, accumulation in the stratum spinosum, accumulation in the stratum corneum (formation of microabscesses), and degeneration of the abscesses . These intravital imaging datasets for human tissues exemplify how transient swarming and aggregation dynamics of neutrophils contribute to the pathophysiology of a human skin disease.…”

A four‐phase strategy for the implementation of reflectance confocal microscopy in dermatology

“…Within the first phase, basic aspects of RCM were studied and experience was gained about the cellular psoriatic RCM features in correlation to histopathology . Thereafter, studies were performed to extend the knowledge and experience with RCM in chronic plaque psoriasis …”

“…For some years, non‐invasive RCM is available for in vivo detection of psoriatic morphological characteristics, such as parakeratosis, diminished or absent stratum granulosum (SG), (epi)dermal inflammatory cells, Munro and Kogoj microabscesses, papillomatosis and increased vascularisation. The correlation between histopathology and RCM imaging has been studied extensively in this inflammatory disease . In addition, some therapeutic follow‐up studies of psoriasis have been published …”

“…As previous studies have shown, RCM can be used in research settings for selected investigative clinical studies in psoriatic patients . In addition, it can serve as a clinical tool for dermatologists, especially in psoriasis expertise centres.…”

“…Moreover, the correct diagnosis of psoriasis is important to prevent treatment delay and for applying adequate therapeutic strategies. In future, it may provide new insights in the pathophysiology of non‐responders because non‐invasive information at cell morphological level and dynamic plaque changes can be monitored . Moreover, patient discomfort is less compared to a biopsy.…”