Clinical and Epidemiological Characteristics of Hidradenitis Suppurativa Patients with Paradoxical Psoriasiform Reactions following Treatment with Adalimumab

Introduction: Immunomodulation using TNF-α inhibitors (anti-TNF-a), especially adalimumab, is highly effective in the treatment of hidradenitis suppurativa (HS) in cases that are poorly controlled by conventional treatments. However, paradoxical psoriasis represents a peculiar type of psoriasis that may occur de novo or as the worsening of pre-existent psoriatic lesions during treatment with adalimumab. Case Presentation: We reported 4 cases of patients suffering from HS, who developed paradoxical psoriasis after treatment with adalimumab for their HS, analyzing their clinical and epidemiological characteristics. All 4 cases were middle aged, smokers, overweight or obese. Half of the patients were males (50%). All of them were classified as Hurley stage III, with a mean duration of HS of 20 years. Two patients had a family history of psoriasis. All 4 patients had been on at least 5 months of successful treatment with adalimumab before the onset of the lesions. Conclusions: Paradoxical psoriasis emerged in 4 patients who received at least 5-month regimen of adalimumab for long-lasting HS. Although different mechanisms have been hypothesized for such events, the exact underlying pathogenetic pathway remains unclear. Consistent reporting of such rare cases, and on a larger scale, is encouraged in order to enrich the available literature. © 2022 S. Karger AG, Basel. Copyright: All rights reserved

The systemic influence of chronic smoking on skin structure and mechanical function

One of the major functions of human skin is to provide protection from the environment. Although we cannot entirely avoid, for example, sun exposure, it is likely that exposure to other environmental factors could affect cutaneous function. A number of studies have identified smoking as one such factor that leads to both facial wrinkle formation and a decline in skin function. In addition to the direct physical effects of tobacco smoke on skin, its inhalation has additional profound systemic effects for the smoker. The adverse effects on the respiratory and cardiovascular systems from smoking are well known. Central to the pathological changes associated with smoking is the elastic fibre, a key component of the extracellular matrices of lungs. In this study we examined the systemic effect of chronic smoking (>40 cigarettes/day; >5 years) on the histology of the cutaneous elastic fibre system, the nanostructure and mechanics of one of its key components, the fibrillin-rich microfibril, and the micromechanical stiffness of the dermis and epidermis. We show that photoprotected skin of chronic smokers exhibits significant remodelling of the elastic fibre network (both elastin and fibrillin-rich microfibrils) as compared to the skin of age- and sex-matched non-smokers. This remodelling is not associated with increased gelatinase activity (as identified byin situzymography). Histological remodelling is accompanied by significant ultrastructural changes to extracted fibrillin-rich microfibrils. Finally, using scanning acoustic microscopy, we demonstrated that chronic smoking significantly increases the stiffness of both the dermis and the epidermis. Taken together, these data suggest an unappreciated systemic effect of chronic inhalation of tobacco smoke on the cutaneous elastic fibre network. Such changes may in part underlie the skin wrinkling and loss of skin elasticity associated with smoking. (c) 2020 The Authors.The Journal of Pathologypublished by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Liver X receptor β: maintenance of epidermal expression in intrinsic and extrinsic skin aging

Aging in human skin is the composite of time-dependent intrinsic aging plus photoaging induced by chronic exposure to ultraviolet radiation. Nuclear hormone receptors coordinate diverse processes including metabolic homeostasis. Liver X receptor β (LXRβ) is a close human homologue of daf-12, a regulator of nematode longevity. LXRβ is positively regulated by sirtuin-1 and resveratrol, while LXRβ-null mice show transcriptional profiles similar to those seen in aged human skin. In these studies, we examined LXRβ expression in aged and photoaged human skin. Volunteers were recruited to assess intrinsic aging and photoaging. Epidermal LXRβ mRNA was examined by in situ hybridization while protein was identified by immunofluorescence. No significant changes were observed in either LXRβ mRNA or protein expression between young and aged volunteers (mRNA p = 0.90; protein p = 0.26). Similarly, LXRβ protein expression was unaltered in photoaged skin (p = 0.75). Our data therefore suggest that, while not playing a major role in skin aging, robust cutaneous expression implies a fundamental role for LXRβ in epidermal biology