Assessment of 11 β-Hydroxysteroid Dehydrogenase Type I Activity in Patients with Psoriasis Vulgaris

Abstract Psoriasis is a chronic relapsing dermatological disease that affects around 1–3% of the world’s population and the prevalence has been increasing globally over the past years. A complex multifactorial etiology is suggested to be the underlying mechanism, involving both genetic and environmental factors that can initiate psoriatic inflammation, including mild trauma, sunburn, or chemical irritants. The interaction between these factors can disrupt the epidermal homeostasis, which triggers a viscous inflammatory circle that leads to epidermal hyperplasia and psoriasis. This inflammatory cascade is the outcome of interaction between epidermal DCs, T lymphocytes and keratinocytes. However, the initial stimulus for DCs stimulation and T cells differentiation is still unclear. In psoriasis, there is a hormonal disturbance in the form of defective GC secretion associated with HPA axis dysfunction. Recently, accumulating evidence established the presence of cutaneous steroidogenesis. The most important of this pathway is the final step controlled by 11βHSD. This enzyme by its 2 types can control local levels of activated GCs in the skin. The balance between 11βHSD1 and 11βHSD2 enzymes, which convert active cortisol/inactive cortisone, is the key to maintain skin barrier function, hence a healthy skin. This case-control study was conducted at Ain Shams University hospitals. The study was conducted on thirty-one patients with dermatologist-confirmed diagnosis of chronic plaque psoriasis and thirty age matched healthy controls. Punch biopsies were taken from lesional and non lesional sites in patients and from controls for assessment of the enzyme by ELISA, besides histopathological and immunohistochemical assessment. Our study showed that 11βHSD1 activity was significantly decreased in psoriasis patients in comparison to healthy volunteers. Besides, 11βHSD1 enzyme level was found to be decreased in lesional than non lesional skin in psoriasis patients. Further histopathological assessment revealed that the lower enzyme levels are associated with greater epidermal acanthosis and higher degree of immunostaining by anti-FGF-2, which indicates the major role of 11βHSD1 in controlling psoriatic inflammation. This was supported by the positive correlation between the non lesional enzyme level and the longest period of remission that we detected in our patients. Surprisingly, there was no significant correlation between the lesional or non lesional enzyme levels in patients with PASI score. Yet, the calculation of PASI score depends on several external factors that should be considered. Interestingly, PSS was not correlated with 11βHSD1 level in psoriasis patients but was negatively correlated with the enzyme level only in healthy controls. This supports the role of stress in modifying enzyme activity, however, in psoriasis epidermal proliferation and the presence of inflammatory infiltrate definitely affects the enzyme level. Better understanding of the complex symphony between all the players of psoriasis pathogenesis will reveal the role of 11βHSD1 and factors affecting its level in psoriasis vulgaris.