Vitamin D supplementation in patients with atopic dermatitis, chronic urticaria and contact irritant and allergic dermatitis - possible improvement without risk.

Abstract.

The Influence of Psychological Stress on HPV Infection Manifestations and Carcinogenesis.

Psychological stress is an important factor involved in disease manifestations of human papillomavirus (HPV) infection, and it can participate in HPV-associated carcinogenesis. The impact or effect which stress can have (exert) depends on a person's genetic pool, experiences and behaviors. Due to inconsistencies in some study results, this issue remains a subject of research. Concerning the course of HPV manifestations, it has been observed that a higher number of life stressors in at least the previous 6 months, the absence of social support and the types of personal coping mechanisms employed, all influence HPV progression. In women with cervical dysplasia, a connection between greater stress experiences and dysregulation of specific immune responses has been observed. Once HPV enters a cell via the α6 integrin there are three possible sequences: latent infection, subclinical infection, and clinically manifest disease. HPV proliferation in differentiated epithelial cells induces morphologically cytopathic changes (koilocytosis, epidermal thickening, hyperplasia, hyperkeratosis). Oncogenic transformation requires the integration of the virus genome into the host genome. In doing so, DNA in the E1 region of E2 breaks down, leading to transcription disorders of E6 and E7. For the formation of irreversible malignancy, the following sequence is necessary: initial expression of E6 and E7 genes followed by suppression of apoptosis and the stabile expression of E6 and E7 proteins that protect transformed cells from apoptosis. A successful immune response is characterized by a strong, local cell-mediated immune response. Several factors are important for the regression of HPV manifestation/infection, among which is psychological stress which can prolong the duration and severity of HPV disease. Stress hormones may reactivate latent tumor viruses, stimulate viral oncogene expression, and inhibit antiviral host responses. In the regression of HPV infection, increased activity of Th1 cells was observed. However, during psychosocial stress, a decrease in the Th1 type of immune response is seen, and there is a shift towards a Th2 response. Understanding perceived stress and biological changes in stress, as well as the evaluation of immune parameters, gives researchers a better picture of how stress influences HPV infections and how to improve disease management and outcomes.

Chronic inducible urticaria: classification and prominent features of physical and non-physical types.

Chronic inducible urticaria (CIndU) is a common inflammatory skin condition characterized by the recurrence of itchy wheals and/or angioedema that lasts more than 6 weeks and is induced by specific physical or environmental stimuli (cold, heat, exercise, pressure, sunlight, vibration, water, etc.). According to the current international classification, it includes physical urticarias (dermographism, delayed-pressure urticaria, exercise-induced urticaria, cold urticaria, heat urticaria, solar urticaria, and vibratory urticaria) and non-physical urticarias caused by exposure to specific stimuli (cholinergic urticaria, contact urticaria, and aquagenic urticaria). In terms of frequency, more common types of CIndU are dermographism, cholinergic urticaria, and delayed-pressure urticaria. In clinical practice, it is often difficult to define the exact type of CIndU; management thus begins with accurate identification of a possible trigger and its avoidance. The definite diagnosis for CIndU requires obtaining a detailed medical history of a patient with comprehensive information about predisposing factors, physical examination, and provocation testing (challenge tests). It is always necessary to recognize the prophylactic options for all the types and to have access to different therapies (primarily second-generation H1 antihistamines, but also H2 antihistamines, hydroxyzine, doxepin, oral glucocorticoids, omalizumab/anti-IgE therapy, phototherapy, physical desensitization, immunomodulatory agents, etc.) individualized for each patient.

Determination of Psychological Stress, Serum Immune Parameters, and Cortisol Levels in Patients With Human Papilloma Virus.

PURPOSE: Because the results of studies investigating the relation between human papilloma virus (HPV) infection and the effects of psychological stress are inconsistent, this study was conducted to expand on previous research by analyzing patient stress levels, serum immune parameters, and cortisol levels in patients with clinical HPV manifestations. It also looked for differences in clinical manifestations of HPV depending on patient level of experienced stress. METHODS: This cross-sectional study included 213 subjects (94 women and 119 men aged ≥18 years; average age, 41 years) with clinical manifestations of HPV infection (165 subjects with extragenital manifestations and 48 with genital manifestations) who were treated at the Department of Dermatovenerology, Karlovac General Hospital, from January 1, 2012, to December 31, 2015. Psychological, neurohormonal and immune parameters (serum values of leukocytes, alpha2-globulins, beta-globulins, albumins, and proteins), and serum cortisol levels were analyzed. Questionnaires were used to determine patients' perception of stress: the Recent Life Changes Questionnaire, the Perceived Stress Scale, and the Brief Cope Test. One group of subjects had confirmed stressful experiences, defined by the Recent Life Changes Questionnaire as a period of 1 year with at least 500 life change units; the control group included patients with no significant stressful experiences. FINDINGS: Patients with confirmed significant stress experience had a statistically significant higher degree of perception of stress. There were no statistically significant differences in terms of the impact of stress on clinical HPV manifestations (genital and extragenital), sex, lesional duration, or recurrence. In patients with significant stress experience, significantly higher values of leukocytes (6.68 × 109/L), alpha2-globulins (6.85 g/L), and beta-globulins (7.33 g/L) were observed. Adaptive coping and a lower perception of stress significantly reduced the chances of having extragenital manifestations by 2.63 times. A higher perception of stress significantly increased the likelihood of genital manifestations. IMPLICATIONS: Although this study found that stress increased the values of leukocytes, alpha2-globulins, and beta-globulins, no evidence was found that it affected clinical manifestations of HPV infection. The redundancy of the immune system could account for this finding. This study is among the first to investigate the correlation between psychological, neurohormonal, and immune indicators of stress.

Stress-induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters.

PURPOSE: Although scientific articles mention the impact of psychological stress on skin diseases, few review the latest research on factors involved in this correlation. The skin actively responds to psychological stress, with involvement of skin immune cells, hormones, neurotransmitters. Skin immune cells actively regulate tissue inflammation with their proinflammatory and anti-inflammatory effects. Stress-induced skin reactions primarily include cytokine secretion (e.g. interleukin-6, interleukin-1, interferon-γ) and activation of skins peripheral corticotropin-releasing hormone (CRH)-proopiomelanocortin (POMC)-adrenocorticotropic hormone (ACTH)-corticosteroids axis, which leads to acute/chronic secretion of corticosteroids in the skin. METHODS: This narrative review presents the current knowledge and latest findings regarding the impact of psychological stress on skin diseases, including information concerning psychoneuroimmune factors in stress-induced skin responses. Recent articles published in English available through the PubMed database and other prominent literature are discussed. FINDINGS: Stress mediators, including cortisol, ACTH, and CRH from hypothalamus-pituitary-adrenal axis activation, induce various skin immune responses. Skin cells themselves can secrete these hormones and participate in skin inflammation. Thus, the local skin CRH-POMC-ACTH-corticosteroids axis plays a prominent role in stress-induced responses. Also, keratinocytes and fibroblasts produce hypothalamic and pituitary signal peptides and express receptors for them (CRH with receptors and POMC degradation peptides with melanocortin receptors), which allows them to respond to CRH by activating the POMC gene, which is then followed by ACTH and subsequently corticosteroids excretion. In addition, keratinocytes can express receptors for neurotransmitters (e.g. adrenaline, noradrenaline, dopamine, histamine, acetylcholine), neurotrophins, and neuropeptides (e.g. substance P, nerve growth factor), which are important in linking psychoneuroimmunologic mechanisms. IMPLICATIONS: Psychoneuroimmunology provides an understanding that the skin is target and source of stress mediators. This locally expressed complex stress-induced network has been confirmed as active in many skin diseases (e.g. vulgar psoriasis, atopic dermatitis, chronic urticaria, human papillomavirus infections/warts, hair loss, acne). Skin reactions to stress and its influence on skin diseases may have implications for disease severity and exacerbation frequency, given the effect of locally secreted corticosteroids and other mediators that affect skin integrity, inflammation, and healing potential. Studies have also shown that introducing psychiatric treatment (drugs or psychotherapeutic methods) can have positive effects on dermatologic diseases influenced by psychological stress exposure. We hope this review provides clinicians and scientists with more complete background for further research in this field of skin psychoneuroimmunology.

Oral allergy syndrome--the need of a multidisciplinary approach.

Oral allergy syndrome (OAS) is one of the most common types of food allergy. The syndrome includes itching and swelling of the lips, palate and tongue, usually after consuming fresh fruits and vegetables. The underlying pathogenic mechanism is cross-reactivity between IgE antibodies specific to pollen, and antigens in food, such as fresh fruits, vegetables and nuts that are structurally similar to pollen. Both pollen and food antigens can bind to IgE and trigger type I immune reaction. Diagnosis is primarily based on the patient's history, and confirmed by skin tests, in vitro tests, and oral provocation tests. Differential diagnoses include many diseases (such as burning mouth syndrome, angioedema, hay fever, various other oral diseases, etc.), and for this reason a multidisciplinary approach is necessary, as different specialists need to be involved in the diagnostic procedure. Therapy includes avoiding, or thermal processing of, fruit and vegetables known to trigger a reaction, and antihistamine medications. If a more severe anaphylactic reaction develops, more aggressive therapy is required. The goal of this article is to present OAS, its etiopathogenesis, clinical picture, and symptoms, diagnostic approach and therapy for OAS.

Psychoneuroimmunologic aspects of skin diseases.

As mental and psychological issues are important in the development of many dermatologic diseases, these factors are of special interest in research. Psychoneuroimmunology is the study of interaction between psychological processes and the nervous and immune systems of the human body, and it was comprehensively described for the first time about 30 years ago. Communication between the mind and the skin involves the psycho-immuno-endocrine-cutaneous system, encompassing the activities of the brain, the immune system and the skin, with participation of different neuropeptides, interleukins, and immune system messengers. Many common dermatologic diseases have some form of psychomediated pathogenesis that partially accounts for the development of skin lesions. There is a link between emotional stressors (acute or chronic), psychiatric diseases, and dermatoses (e.g., psoriasis, atopic dermatitis, urticaria, viral warts, herpes simplex, vitiligo, acnes, alopecia, prurigo, etc.) and different cytokines and mediators produced in the skin and involved in their pathogenesis. A prominent role is played by those agents that belong to the hypothalamic-pituitary-adrenal axis.

DRESS syndrome with mild manifestations as a diagnostic and therapeutic problem: case report.

The group of severe cutaneous drug reactions with systemic symptoms includes several syndromes: toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions occur several days to six weeks after introducing the incriminating drug. The skin and internal organs (liver, kidneys, lungs, etc.) are usually involved. A great possibility of lethal outcome is a critical characteristic of these syndromes. A patient with pyelonephritis diagnosed during emergency room workup is described. Ciprofloxacin was prescribed and the patient was discharged. After ten days, the patient came back with worsening condition, general inflammatory response, skin changes, liver and kidney damage, and eosinophilia. DRESS syndrome was diagnosed based on clinical and other findings. The diagnosis and treatment of severe drug reactions with cutaneous and systemic symptoms pose a medical challenge.