The COVID-19 Pandemic and Recent Earthquake in Zagreb Together Significantly Increased the Disease Severity of Patients with Atopic Dermatitis.

BACKGROUND/OBJECTIVE: Stress may affect patients with atopic dermatitis (AD). The aim of this study was to examine the impact of the COVID-19 pandemic and the earthquake in Zagreb, Croatia (March 2020), on AD patients and their disease severity, symptoms/itch, and perceived stress. METHODS: Our observational cross-sectional study included three groups of AD patients diagnosed by a physician: group 1 (n = 50), who experienced both the pandemic (quarantine) and the earthquake; group 2 (n = 50), who experienced only the pandemic; and group 3 (n = 50), the comparison group, who experienced neither disaster (patients examined 2018-2019). Groups 1 and 2 were examined May-June 2020, immediately after the national lockdown/quarantine. Disease severity (SCORAD), data from the Perceived Stress Scale (PSS), and information on patients' confirmed allergies were recorded for all groups, while groups 1 and 2 additionally completed a questionnaire concerning their disease, hand hygiene, and experience during the pandemic and/or earthquake. RESULTS: The patients exposed to both disasters reported more pronounced AD worsening (p < 0.001; r = 0.388) and more frequent itching (p < 0.001; r = 0.350) than those exposed to the pandemic only. Notably, we found certain differences by gender: during the pandemic, women significantly more frequently washed their hands (81% of women washed "very frequently," while 52% of men washed "quite often") and had significantly higher PSS levels than men (p < 0.05). Concerning allergies, present or absent, during the pandemic, there was no significant difference in SCORAD between groups 1 and 2, neither when analyzed separately for indoor nor for outdoor allergens. The most commonly reported psychological disturbances during the pandemic were concern (46%), anger (18%), anxiety (16%), depression (9%), and increased alcohol, cigarette, and opioid agent use (6%). CONCLUSION: The COVID-19 pandemic together with the earthquake significantly increased disease severity and influenced AD worsening, itching, and psychological disturbances. This indicates that stressful events meaningfully affect the course of AD.

Main Clinical Features of Patients with Irritant and Allergic Contact Dermatitis on the Hands in Correlation with Skin CD44 Expression: A Prospective Study.

Contact dermatitis (CD), including its irritant (ICD) and allergic (ACD) types, is a complex, often chronic and therapy-resistant disease that significantly affects patient quality of life and healthcare systems. Objective of this study was to examine the main clinical features of patients with ICD and ACD on the hands through follow-up in correlation with baseline skin CD44 expression. Our prospective study involved 100 patients with hand CD (50 with ACD; 50 with ICD) who initially underwent biopsies of skin lesions with pathohistology, patch tests to contact allergens, and immunohistochemistry for lesional CD44 expression. The patients were subsequently followed-up on for a year, after which they filled out a questionnaire designed by the authors examining disease severity and disturbances/issues. Patients with ACD had significantly higher disease severity than those with ICD (P<0.001), with more frequent systemic corticosteroid treatments (P=0.026) and greater areas of affected skin (P=0.006), exposure to allergens (P<0.001), and impairment of everyday activities (P=0.001). No correlation between ICD/ACD clinical features and initial lesional CD44 expression was observed. Due to the commonly severe course of CD, especially ACD, more research and prevention are needed, including the analysis of the role of CD44 in connection with other cell markers.

CAN SKIN BE A MARKER FOR INTERNAL MALIGNANCY? EVIDENCE FROM CLINICAL CASES.

Although there are many single case reports on paraneoplastic dermatoses in the literature, there are very rare articles containing multiple cases. A retrospective study was performed to examine paraneoplastic dermatoses and accompanying malignancies based on skin manifestations and appropriate diagnostic evaluations. We recorded outcomes, current conditions, and surgical/oncologic treatments. Analysis revealed paraneoplastic dermatoses in 17 patients with various skin lesions, i.e. eczematous dermatitis, vasculitis, subacute cutaneous lupus erythematosus, pruritus, chronic urticaria/angioedema, alopecia areata, flushing, bullous pemphigoid, dermatomyositis, and localized scleroderma (morphea). They were associated with different solid and hematologic malignancies (3 gastric, 2 prostate, 2 bladder, 2 thyroid, and 2 lymphoma), along with 1 case each of the following: lung, hepatocellular, esophageal, endometrial, kidney, and multiple myeloma. The majority of skin lesions gradually regressed after malignancy treatment. To our knowledge, our three cases of paraneoplastic eczematous dermatitis are the first to be associated with gastric, prostate and endometrial cancer. Additionally, we report a case of a patient with alopecia areata of the beard associated with thyroid cancer. Early malignancy detection based on skin markers makes early introduction of surgical/oncologic therapy possible and usually leads to skin lesion regression while reducing revolving door visits to specialists and the (financial) burden on the healthcare system.

CD44 expression in human skin: High expression in irritant and allergic contact dermatitis and moderate expression in psoriasis lesions in comparison with healthy controls.

BACKGROUND: Previous research using animal models demonstrated that CD44 expression may contribute to directing inflammatory cells into skin lesions during inflammation development in allergic contact dermatitis (ACD). OBJECTIVES: To examine CD44 expression in patients with ACD and irritant contact dermatitis (ICD), and to compare it to patients with psoriatic lesions and healthy controls' (HCs) skin. METHODS: This study included 200 patients comprising four groups of 50 each: ACD, ICD, psoriasis vulgaris, and HCs. CD44 expression was determined by immunohistochemical analysis using an optical microscope, and the results were visualized semiquantitatively by determining the percentage of immunoreactive cells in the epidermis, dermis, and on lymphocytes. RESULTS: The highest CD44 expression was found in ICD, followed by ACD, psoriasis vulgaris, and lastly, the HCs (P < .001). Epidermal CD44 expression was significantly higher in contact dermatoses (especially in ICD) compared with psoriasis and healthy skin (P < .001). Similarly, CD44 expression in the dermis and on lymphocytes was strongest in ICD, although less pronounced than in the epidermis. CONCLUSIONS: Because significantly elevated CD44 expression in ICD might be related to its function in maintaining and preserving the skin barrier in affected patients, further research on disease pathogenesis and new treatment options is needed.

Melanoma Development: Current Knowledge on Melanoma Pathogenesis.

The pathogenic features of melanomas include growth and amplification of atypical melanocytes associated with several features (self-sufficiency of growth factors, insensitivity to growth inhibitors, evasion of cellular apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion, and metastasis). These melanoma pathogenic events can be triggered by activating oncogenes or inactivating tumor-suppressor genes by means of molecular mechanisms such as dotted mutations, deletions, and translocations or epigenetic mechanisms such as microRNA expression and promoter methylation. In melanomas, an analysis of the gene aberrations in the genome has led to the discovery of the complex interaction of signaling pathways. Progression of melanomas also involves genetic instability and selective growth of cells with favorable mutations. Additional factors include genetic predisposition, mutagenesis, and suppressed host immune response. Some of the most important signaling pathways involved in the pathogenesis of melanoma are the MAPK, PI3K/PTEN/AKT, and MITF signaling pathways. Obtaining insight into the biology of melanocytes and pathogenesis of melanomas is important for the development of a targeted therapy (such as vemurafenib, dabrafenib, trametinib) as well as the immunotherapy (e.g. pembrolizumab, nivolumab, ipilimumab), which has enabled a substantial breakthrough in the treatment of patients with melanoma.

Cutaneous Pseudolymphoma: A Case Report.

Pseudolymphoma is a benign, reversible, inflammatory, reactive, and polyclonal lymphocyte proliferation, which regresses spontaneously or heals after elimination of the causal factor. A female patient, aged 33, presented with a painful, erythematosus, radiant tumor formation on the skin in the temporal region. The patient had enlarged lymph nodes on the right side of the neck before the appearance of that tumor formation. The dermatoscopic finding was nonspecific. After the tumor biopsy was performed, the diagnosis of reactive lymphatic proliferation - pseudolymphoma or cutaneous lymphoma of B-cell immunophenotype - was established histologically. After we completely excised the skin change, the immunohistochemical finding indicated fluoride skin lymphocyte hyperplasia of B- and T-lymphocytes. The results of other findings were normal (serologic test for Borrelia burgdoferi, ultrasound of the cervical and supraclavicular lymph nodes, as well as ultrasound of the abdomen and axillary and inguinal regions). However, the etiology of the disease remains unknown. This case report confirms that the correlation between clinical presentation, dermatoscopic examination, histologic and immunohistochemical analysis, and the therapy response is crucial for diagnosis of pseudolymphoma and patient outcome.

Analysis of Dental Professionals' and Dental Students' Care for their Skin.

OBJECTIVES: To determine prevalence of undesirable, work-related skin lesions and their localizations in dental professionals and students, and to collect data about diagnostic procedures they undergo and skin care they take when these lesions occur. SUBJECTS AND METHODS: Our research included 444 respondents (dentists, dental assistants, dental technicians, dental students) who filled out a questionnaire. They were asked to specify if they had observed any lesions on their skin and where; if they had undergone any treatments and in what way; if they had undergone any allergy tests; and if they had taken any protective measures. RESULTS: Of all the respondents that took part in the survey, 249 (56.1%) reported undesirable skin reactions commonly on their hands and fingers (96%). Before our survey, only 15% of them had seen a dermatologist, while 33% had undergone allergy tests (without a dermatologists' clinical examination). Also, 45% of them sometimes used soaps for sensitive skin and the majority (61%) of them used protective hand creams 1-2 times per day. CONCLUSION: Although a large number of dental professionals and students have noticed work-related skin lesions, only some of them sought dermatologists' professional help and most of them did not take care of their skin adequately when those lesions occurred. According to the results of this study, it is necessary to take additional preventive measures to increase dental professionals' and students' awareness of occupational dermatoses and adequate skin care.

Psychological Stress in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a frequent dermatosis with a growing incidence and multifactorial and complex pathogenic mechanisms that are still being investigated. Although the connection between AD and psychological stress has been known for a long time, there is a lack of reliable and objective indicators for the characterization of this association. Psychological stress triggers complex immune pathways. Therefore, acute stress quickly triggers a high release of cortisol and adrenalin or noradrenalin which then stimulates the immune system, primarily T-helper type 1 (Th1 cells) to produce pro-inflammatory cytokines, resulting in a cellular immune response and inflammation. On the other hand, chronic stress increases basal cortisol levels and decreases the capacity to mount an acute stress response, with the immune system shifting from a cellular response (which is active in acute stress) to a humoral response. Furthermore, skin keratinocytes contain receptors for neurotransmitters and hormones (muscarinic, adrenergic, glucocorticosteroid, androgenic, estrogenic), thus actively participating in psychoneuroimmunological pathways. The measurement of plasmatic cortisol has been used routinely, but in recent years, particularly in research, preference has been given to measurement of salivary cortisol. Reliable psychological tests are an important additional parameter for assessment of a patient's psychological state. We hope that future studies will supplement our current knowledge on the influence of psychological stress in AD.

IRRITANT AND ALLERGIC CONTACT DERMATITIS - SKIN LESION CHARACTERISTICS.

- Contact skin lesions may be the consequences of contact with various irritants or allergens, or due to other factors (e.g., UV radiation, microbials), intrinsic factors (e.g., in autoimmune responses), or even their combination. There are many substances related to irritant contact dermatitis (CD), causing irritant or toxic effects, e.g., chemical and physical agents, plants, phototoxic agents, airborne irritants, etc. Impaired barrier function (e.g., aberrancies in epidermal pH buffering capabilities) also participates by promoting bacterial biofilms and creating an environment favoring sensitization. Development of allergic CD skin lesions includes complex immune pathways and inflammatory mediators, influenced by both genetic (predominantly filaggrin mutations) and environmental triggers. In the pathogenesis of allergic CD, antimicrobial peptides play a prominent role; they are produced by various skin cells (e.g., keratinocytes, sebocytes) and move to inflamed lesions during an inflammation process. Also, in allergic CD skin lesions, the skin shows different types of immune responses to individual allergens, although clinical manifestations do not depend on the causative allergen type, e.g., nickel stimulates immune activation primarily of the Th1/Th17 and Th22 components. Also important are alarmins, proteases, immunoproteomes, lipids, natural moisturizing factors, tight junctions, smoking, etc. We expect that future perspectives may reveal new pathogenetic factors and scientific data important for the workup and treatment of patients with CD.

OCCUPATIONAL CONTACT DERMATITIS AMONGST DENTISTS AND DENTAL TECHNICIANS.

Since the working medical personnel including dentists and dental technicians mainly use their hands, it is understandable that the most common occupational disease amongst medical personnel is contact dermatitis (CD) (80%-90% of cases). Development of occupational CD is caused by contact of the skin with various substances in occupational environment. Occupational etiologic factors for dental personnel are foremost reactions to gloves containing latex, followed by various dental materials (e.g., metals, acrylates), detergents, lubricants, solvents, chemicals, etc. Since occupational CD is relatively common in dental personnel, its timely recognition, treatment and taking preventive measures is needed. Achieving skin protection at exposed workplaces is of special importance, as well as implementing necessary measures consequently and sufficiently, which is sometimes difficult to achieve. Various studies have shown the benefit of applying preventive measures, such as numerous protocols for reducing and managing latex sensitivity and other forms of CD in dentistry. Active involvement of physicians within the health care system, primarily dermatologists, occupational medicine specialists and general medicine doctors is needed for establishing an accurate medical diagnosis and confirmation of occupational skin disease.