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Background/Objectives : Human β-defensin 2 (HBD2) is a protein that plays an important role in activating the immune system by modulating spinal pathways and the inflammatory response. According to previous research, HBD2 was proven to be important in chronic spontaneous urticaria (CSU) (their values were significantly elevated in CSU patients, with a significant correlation between HBD2 levels and the percentage of peripheral basophils, suggesting that elevated HBD2 levels may be a potential marker of basophil and mast cell activation), which led us to additional research on the HBD2 molecule in isolated chronic angioedema. The aim of this research is to examine HBD2 values in the saliva and serum of patients with isolated angioedema, as a potential biomarker of the disease. Methods : This cross-sectional study involved a total of 102 participants, involving three groups: 33 patients with isolated chronic non-hereditary angioedema (AE) (defined as sudden onset of localized edema without chronic urticaria), 33 patients with angioedema associated with chronic urticaria (CU+AE), and 35 healthy participants (controls, CTRL). They provided a saliva sample to determine HBD2 levels using an ELISA (Enzyme-Linked Immunosorbent Assay). Subsequently, a peripheral blood sample (serum) was taken from the participants to determine HBD2 levels using the same ELISA. Results : Salivary HBD2 levels were significantly higher in those with CU+AE than in the CTRL ( p = 0.019). While salivary HBD2 values differed between those with angioedema and CTRL, the serum HBD2 values did not. Also, no correlation between the levels of HBD2 in saliva and serum was found. Conclusions : Since we found that salivary HBD2 values were significantly higher in those with CU+AE than in CTRL, this points to a possible role of the HBD2 molecule in pathogenesis of AE (namely, that it induces degranulation in mast cells and vascular permeability, and has antimicrobial properties) Therefore, more research is needed to determine how reliable salivary HBD2 measurement is, as well as its significance.

Beta defensins (β-defensins) are peptides primarily produced by epithelial cells in mammals to safeguard the skin, other organs, and mucosa from microbial colonization. These peptides are generated by epithelial cells, keratinocytes, and macrophages, mainly in response to interactions with microorganisms (bacteria, viruses, and fungi) or the influence of various pro-inflammatory cytokines. Human β-defensin (HBD) 2 plays an indirect role in allergic reactions by promoting mast cell activation and degranulation. In dermatological and allergic conditions, the role of HBD2 has been well documented. Although HBD2 is predominantly produced in keratinocytes, along with HBD3 it has also been detected in serum. Elevated serum levels of HBD2 have been observed in patients with skin diseases such as atopic dermatitis and psoriasis. In addition, HBD2 is significant in chronic spontaneous urticaria (CSU), in which urticarial skin lesions can be triggered by infections. Notably, CSU is often accompanied by angioedema, which may be related to HBD2 because patients with CSU and associated angioedema have higher serum HBD2 levels compared to those without angioedema. Current evidence suggests that HBD2 could serve as a marker of inflammation and may have potential therapeutic applications. However, due to limited data on HBD2 levels and its expression in the skin of patients with allergic skin diseases, further research is needed to elucidate the underlying causes and mechanisms of elevated HBD2 levels in these conditions.

Introduction: Recent research has shown that blood coagulation and the extrinsic coagulation cascade are involved in the pathogenesis of chronic spontaneous urticaria (CSU), but little is known about the coagulation factors in angioedema., Methods: This study included 58 participants: 29 patients with chronic angioedema (14 with isolated angioedema and 15 with angioedema with wheals) and 29 healthy controls (HCs). We compared the values of coagulation factors in patients with isolated angioedema to those with wheals. Plasma levels of D-dimer, fibrinogen, and factor VII were measured by enzyme-linked immunosorbent assay (ELISA) for all participants., Results: Significantly higher D-dimer (p = 0.016; ε² = 0.381) and fibrinogen (p = 0.044; ε² = 0.331) levels were recorded in patients with angioedema (both groups) than in the HCs, with higher levels for angioedema with wheals. Factor VII and fibrinogen levels did not differ significantly between the groups with angioedema, but coagulation factors were more often elevated in both angioedema groups than in HCs., Conclusions: One characteristic of angioedema is an elevated blood coagulation potential, which may help produce fibrin and may be important in controlling angioedema attacks.

Fluoroquinolones are a commonly prescribed class of antibiotics due to their broad spectrum of antimicrobial activity, favorable pharmacokinetic properties, ability to switch from parenteral to oral administration, and global availability. After beta-lactams, they are the second most common antibiotic class associated with drug allergies. The mechanism of fluoroquinolone-induced hypersensitivity reactions has not yet been fully understood, so the true incidence of hypersensitivity reactions remains unknown. Cross-reactivity between fluoroquinolones has been the subject of conflicting and limited clinical research. Due to their similar chemical structure, some argue for close cross-reactivity within the group. However, recent studies have produced contradictory results. We present the case of a young patient who had an anaphylactic reaction to ciprofloxacin but was tolerant to levofloxacin, as determined via a skin prick test followed by a drug provocation test. Our findings support the notion that there is little cross-reactivity between fluoroquinolones. Consequently, exposure to another fluoroquinolone in a hospital setting may be beneficial, particularly for patients who lack adequate antibiotic alternatives. However, additional research on this subject is required.

Background : Rheumatoid arthritis (RA) is a chronic systemic autoimmune and inflammatory disease. Conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), Janus kinase inhibitors, and rituximab are used to treat the disease. There are no recommendations or guidelines for the treatment of patients with both inflammatory arthritis and end-stage renal disease (ESRD), despite the safety and efficacy of the mentioned drugs. The anti-interleukin-6 receptor antibody tocilizumab (TCZ) has not been used as a long-term therapy for hemodialysis (HD) patients with RA, except in a few case reports. Case Description : We present the case of a 41-year-old patient with RA and ESRD on maintenance HD due to type 1 diabetes-related complications. Due to high RA disease activity, the patient was not a suitable candidate for a kidney transplant. Because TCZ is used to treat both RA and kidney transplant rejection, therapy with a full dose of TCZ was administered. The patient has achieved sustained clinical remission (for the past four years) with no adverse events reported. Conclusions : Herein, we present the safe and effective use of TCZ in an RA patient on HD who is also a candidate for kidney transplant. Consequently, TCZ could be the treatment of choice for RA patients with ESRD who have not achieved disease control (low activity or remission) with conventional synthetic DMARDs. Clinical studies are required to evaluate the efficacy and safety of biologic DMARDs and Janus kinase inhibitors in patients with both inflammatory arthritis and ESRD.

Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. Due predominantly to its positive influence on sleep, melatonin can be used in the treatment of sleep disturbances for those with chronic allergic diseases accompanied by intensive itching (such as atopic dermatitis and chronic spontaneous urticaria). According to the literature data, there are also many proven uses for melatonin in photoprotection and skin aging (due to melatonin's antioxidant effects and role in preventing damage due to DNA repair mechanisms), hyperpigmentary disorders (e.g., melasma) and scalp diseases (such as androgenic alopecia and telogen effluvium).

Background: The aim is to evaluate the reliability and validity of the Croatian version of the Zarit Caregiver Burden Interview (ZBI) among the population of informal caregivers of long-term mechanically ventilated patients., Subjects and Methods: After a preliminary analysis, 25 participants were selected by using strictly defined criteria and they were asked to complete the Croatian version of the ZBI. The test - retest method was used for reliability assessment while an exploratory strategy of factor analysis was used to identify real-life existent subscales., Results: After reliability and validity assessment, 3 items were removed from the original ZBI so that the Croatian version of the ZBI consists of 19 items. Internal consistency, observed through Cronbach's alpha for extracted subscales and for the whole questionnaire, were identified as high ranged from 0.875 to 0.922. Furthermore, exploratory factor analysis using Guttman-Kaiser criterion identified the 6 subscales for the ZBI., Conclusions: Due to the fact that approximately 30 % of targeted population was included in the study, the Croatian version of the ZBI can be accepted as a reliable and valid tool for measuring burden among informal caregivers of long-term mechanically ventilated patients. Family caregiver's burden level assessment can be crucial to enhance outcomes associated with future caregiving.

Background: Previous studies have reported that the allergy epidemic in developed countries has reached its plateau, while a rise is expected in developing ones. Our aim was to compare the prevalence of allergic diseases among schoolchildren from the city of Zagreb, Croatia after sixteen years., Methods: Symptoms of asthma, allergic rhinitis (AR) and atopic dermatitis (AD) and risk factors were assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. An allergic profile was determined by a skin prick test., Results: The prevalence of current, ever-in-a-lifetime and diagnosed AR of 35.7%, 42.5% and 14.9% and AD of 18.1%, 37.1% and 31.1% demonstrated a significant increase. The asthma prevalence has remained unchanged. The allergen sensitivity rate has remained similar, but pollens have become dominant. Mould and dog exposure are risks for asthma (OR 14.505, OR 2.033). Exposure to cat allergens is protective in AR (OR 0.277). Parental history of allergies is a risk factor in all conditions., Conclusion: Over sixteen years, the prevalence of AR and AD, but not of asthma, have increased. The proportion of atopy has remained high. The AR/AD symptom rise is probably a consequence of increased pollen sensitisation united with high particulate matter concentrations. The stable asthma trend could be a result of decreasing exposures to indoor allergens.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate the association of FasL gene polymorphism (rs763110) with rheumatoid arthritis occurrence, disease activity, and tumor necrosis factor-α (TNF-α) plasma concentration in Croatian patients, and to conduct an updated meta-analysis., Methods: This cross-sectional study enrolled 81 patients with rheumatoid arthritis and 94 control patients. After the assessment of the Disease Activity Score (DAS)-28, blood was taken for analysis. DNA was isolated from the whole blood to determine FasL polymorphism (rs763110) by polymerase chain reaction. Protein levels of TNF-α were determined with ELISA. After a detailed literature search, we conducted an updated meta-analysis using the Review Manager 5 software., Results: Rheumatoid arthritis patients had significantly higher TNF-α concentration in plasma (1.65 [1.2-2.42] pg/mL) than controls (0.99 [0.77-1.35] pg/mL, P<0.001). The FasL rs763110 polymorphism was not associated with rheumatoid arthritis occurrence in either codominant, dominant, recessive, overdominant, or log additive model. Furthermore, the rs763110 genotype was not associated with DAS 28 score or TNF-α concentration. After we added our results to an updated meta-analysis, the significant association previously reported for Western Eurasians was abolished., Conclusion: Our data suggest that the association between FasL rs763110 polymorphism and RA susceptibility in Western Eurasians observed in previous studies might be overestimated and should be limited to the population of Southwestern Asia until further investigations are performed.

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.

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.

During the last three decades scientists worldwide have investigated how ultraviolet radiation (UVR) influences the immune system. The vast majority of the researchers was primarily focused on the local immunomodulatory role of UVR. But today evidence is increasing in favor of plural immune activation and systemic reaction of the organism. Most of the attention is directed toward the regulatory T lymphocytes which are responsible for the local and systemic immunosuppressive response under the impact of sunlight. The role of regulatory T cells in autoimmune diseases is well studied on patients with systemic lupus erythematosus (SLE). Epidemiological research shows a proportional interdependence of latitude and prevalence of autoimmune diseases such as multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). There is evidence that UVR has direct influence on the level of antibodies against the SNF2-superfamily helicase (Mi-2), distinctive for dermatomyositis (DM). On this basis a hypothesis is established that UVR is a risk factor for DM. A Croatian epidemiologic study o f systemic sclerosis (SSc) gave results consistent with the hypothesis that there is a higher prevalence of SSc in the Mediterranean regions of Croatia. Such discoveries encouraged further studies that found that not only regulatory T cells are responsible for a systemic immunosuppressive response, but that there is a complex interactive network of immune cells and mediators such as cytokines, neuropeptides, and chromophores like urocanic acid involved. Present findings require continued research on the importance of UVR on autoimmune disease prevalence and immunopathophysiology. Finally, it is necessary to distinguish whether UVR is a protective factor for some autoimmune diseases or a risk factor for their induction.