Current Concepts of Psoriasis Immunopathogenesis Vičić, Marijana; Kaštelan, Marija; Brajac, Ines ...
International journal of molecular sciences,
10/2021, Letnik:
22, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most ...common inflammatory skin disease, affecting an average of 2-4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.
Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral ...illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.
Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge ...about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient’s quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies ...by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden due to its major impact on patients’ social and emotional aspects of life. Given its autoimmune background, vitiligo is frequently associated with other autoimmune diseases or immune-mediated diseases. Vitiligo is a multifaceted disorder that involves both genetic predisposition and environmental triggers. In recent years, major predisposing genetic loci for the development of vitiligo have been discovered. The current findings emphasize the critical role of immune cells and their mediators in the immunopathogenesis of vitiligo. Oxidative-stress-mediated activation of innate immunity cells such as dendritic cells, natural killer, and ILC-1 cells is thought to be a key event in the early onset of vitiligo. Innate immunity cells serve as a bridge to adaptive immunity cells including T helper 1 cells, cytotoxic T cells and resident memory T cells. IFN-γ is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10. Complex interactions between immune and non-immune cells finally result in apoptosis of melanocytes. This paper summarizes current knowledge on the etiological and genetic factors that contribute to vitiligo, with a focus on immunopathogenesis and the key cellular and cytokine players in the disease’s inflammatory pathways.
The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse ...drug reactions (ADR) induced by LA in our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka, Rijeka, Croatia, for the investigation of LA hypersensitivity in the period between January 2000 and December 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition to LA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independent ADR occurring during 346 procedures. Most commonly, patients reported having only one ADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) five ADR to LA were observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independent ADR in 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate‐type reaction to bupivacaine and two patients had a delayed‐type reaction to lidocaine. Adverse reactions to LA are common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents to LA are rare.
It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study ...aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be “non‐psychosomatic”) were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.
Clinical observations suggest that the nervous system, including psychological factors, can influence the onset and course of alopecia areata (AA). The aim of this study was to determine whether ...stressful life events, stress perception, and trait‐anxiety are risk factors in the onset and course of AA. A group of 45 patients diagnosed with AA and a group of 45 healthy controls were participants in the study. The patients with AA were divided into two subgroups: patients with a first episode of AA and patients with recidivism of the disease. All participants completed questionnaires addressing sociodemographic, clinical and psychological aspects of their disorder. The frequency and types of stressful life events experienced over the previous six months were recorded. Lemyre and Tessier's Mesure de Stress Psychologique was used to measure emotional, cognitive, behavioral, and physiological aspects of distress. Anxiety was evaluated by the Spielberg's Trait Anxiety Inventory. The subgroups of AA and the control group, using the same numbers of subjects matched for age and sex, education level, marital and employment status, were statistically compared. The number of patients with four stressful life events over the previous 6 months was significantly higher in the group of AA patients with recidivism of disease compared to the control group (P=0.004). There were no differences among the other groups with respect to the frequency of life events. Examination of the relationships between the two groups regarding anxiety, as well as perceived distress, revealed that the groups differed significantly with respect to psychosocial variables studied. A significantly higher degree of trait‐anxiety and perceived distress were observed among patients in both AA subgroups (first onset and recidivism of AA) than in the healthy control group. The highest scores for anxiety and stress perception among examined groups were obtained in the group with recidivism of AA (33.42 ± 12.71 and 90.32 ± 50.74, respectively). Trait‐anxiety and stress perception constitutes risk factors that may influence the onset and exacerbation of AA. The present study does not provide evidence of a significant role of stress in the onset of AA. Life events may play an important role in triggering of some episodes.
TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory ...dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (
n
= 10) and non-lesional (
n
= 10) skin of patients with plaque psoriasis and skin of healthy volunteers (
n
= 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.
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