Risk Factors for Psoriasis Flares: A Narrative Review

Figures & data

Table 1 Classic Risk Factors for Psoriasis Development

Classic Risk Factors	Definition		Mechanism of Action
Mechanical stress	Various types of trauma to sites not involved in psoriatic lesions can cause them to appear. This phenomenon is called reactive isomorphism or Koebner’s phenomenon		Increased production of cathelicidin LL-37, an antimicrobial peptide that increases in response to damage and forms complexes with genetic material from the damaged cells themselves, which in turn stimulate plasmacytoid dendritic cells to secrete type 1 interferons (IFN)
Infection and dysbiosis	S. Pyogenes, S. Aureus, Candida spp, Malassezia spp, EBV, VZV, CMV, HIV.		Hyperactivation of the immune system
Environment and pollution	C6H6, CO, PM10, PM2.5, cadmium		Oxidative stress with formation of ROS which damage cellular structures and hyperactivate the immune system
Lifestyle	Smoking, alcohol, obesity		Increase in inflammatory cytokines and innate immunity
Common drugs	Lithium, beta-blockers, synthetic antimalarial drugs, antibiotics (especially tetracyclines), ACE inhibitors, and interferons	Drug-induced decrease of intracellular cAMP levels, resulting in increased cell proliferation and lack of differentiation
Psychological stress	State of worry or mental tension caused by a difficult situation	Disturbance of the hypothalamic-pituitary-adrenal axis with reduced cortisol response to stress that has been observed in patients with psoriasis, with generally lower cortisol levels compared to higher levels of adrenaline and adrenocorticotropic hormone
Hormonal and metabolic alterations	Reduction in blood levels of estrogen and progesterone, increase in FFAs	Increase in inflammatory cytokines and innate immunity

Table 2 Emerging Risk Factors for Psoriasis Development

Emerging Risk Factors	Definition	Mechanism of Action
Biological drugs: Paradoxical Psoriasis	Paradoxical psoriasis is a drug side effect that results in the development of psoriasis during biological therapy for different diseases	The selective inhibition of specific cytokines may inadvertently disrupt the immune balance, leading to the onset or worsening of psoriasis.
Immunotherapy for oncologic disease	Anti CTLA4 (Ipilimumab) Anti PD-1 (Nivolumab, Pembrolizumab, Cemiplimab) Anti PD-L1 (Atezolizumab, Durvalumab, Avelumab) Sorafenib, Imatinib	Overactivation of Th1, Th17, and Th22 lymphocytes secondary to inactivation of the PD1 pathway (ICIs) Alteration of the balance between the regulatory and the effector function normally carried out by T cells (Sorafenib, Imatinib)
Covid-19	SARS-CoV-2 infection	Binding of SARS-CoV-2 to ACE2 receptors present in cutaneous blood vessels, epithelial cells of eccrine glands and the basal layer of hair follicles
Vaccines	Influenza vaccine, Pneumococcal vaccine, Td vaccine, yellow fever vaccine, COVID-19 vaccine	Induction of immune response leading to an inflammatory state and activation of the immune system

Data Sharing Statement

Data are reported in the current study.