Liborija Lugović-Mihić

Acrylates and methacrylates are common sources of skin and mucosal changes. Adverse, occupation-related reactions, such as allergies to acrylic resin monomers, have historically predominantly affected dental personnel. Nowadays, acrylic compounds are widely used in commercial products, the cosmetics industry, medical equipment, engineering and graphics; therefore, allergic reactions are common, especially in strongly sensitized patients. Generally, the most critical allergens among (meth)acyrlates are hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), ethylene glycol dimethacrylate (EGDMA), methyl methacrylate (MMA), ethylene methyl acrylate (EMA), etc. Cross-reactivity between different acrylate and methacrylate compounds can also occur. Given the increasing number of occupational allergic reactions due to skin and mucosal contact with products containing (meth)acrylates, this review aims to present the latest data on reactions to these compounds across different professions. Greater awareness of (meth)acrylate allergies as a result of occupational exposure may improve patient safety and prevent chronic occupational skin and mucosal diseases.

Background and Objectives: To examine the potential association between acrylate exposure, skin condition, and allergic and non-allergic (irritant/toxic) skin and mucosal reactions among dental professionals and students. Materials and Methods: A total of 136 dental personnel (dental technicians, dentists, dental assistants/nurses, and students) completed a questionnaire on dentistry-related unwanted reactions to acrylates, and 53 additionally agreed to a dermatologic examination, including assessment of hand skin condition using the Osnabrück Hand Eczema Severity Index (OHSI) and allergy testing. Patch testing for acrylates and common dentistry-related substances, as well as prick testing for inhalant allergens, was performed. Results: In the total sample, 88/136 participants (64.7%) reported work- or study-related skin changes, with the highest prevalence among dental technicians and dental assistants/nurses (78.3% and 76.9%, respectively). Among dermatologically examined participants, dental technicians had the highest OHSI scores, indicating the most severe hand skin changes. The most commonly reported manifestations in the total sample were hand eczema and fingertip skin fissuring (29.4%), followed by facial eczema (14.7%), periungual dermatitis (11.8%), nail dystrophy (7.4%), generalized dermatitis (6.6%), mucosal symptoms (6.6%), and other reactions. Among dermatologically examined participants, those reporting reactions to acrylates had higher OHSI scores than those without such reactions (median 2 vs. 1; p = 0.005; r = 0.384). OHSI scores differed significantly across categories of work-related skin changes (p = 0.048; ε = 0.117). In total, 6/53 (11.3%) positive allergic reactions to acrylates were found, which were present in 4/53 (7.5%) of tested participants. Positive reactions to methyl methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA) were observed in 2/53 (3.8%) participants each. Conclusions: The low prevalence of confirmed acrylate allergy in patch testing compared with the high frequency of reported work-related skin and mucosal changes suggests that allergies to acrylates are uncommon and that other factors may cause or contribute to these lesions. Preventive measures are particularly important for dental technicians, who show the greatest severity of hand skin changes.

Background and Objectives: Although the diagnosis of chronic spontaneous urticaria (CSU) is primarily clinical, detailed history taking and selected laboratory findings are important for patient evaluation and management. Materials and Methods: This explorative prospective study included 41 CSU patients who were followed for 3 months during antihistamine treatment. Saliva and blood samples were collected, and disease-related questionnaires were completed at baseline (T1) and at follow-up (T2). Salivary IL-6 and amylase, serum IL-6, and standard laboratory parameters, including differential blood count, erythrocyte sedimentation rate and/or C-reactive protein (CRP), total IgE, TSH, T4, and anti-TPO antibodies, were measured and compared with disease activity (UAS7), disease control (UCT), and quality of life (DLQI and CU-Q2oL). Results: Salivary IL-6 showed a weak correlation with serum CRP. Neither salivary nor serum IL-6 showed a consistent association with CSU severity, disease control, or quality-of-life scores. Serum IL-6 showed significant correlations with selected inflammatory and thyroid-related parameters. Salivary IL-6 values at baseline (T1) were more frequently increased in patients experiencing a major disease impact on quality of life (CU-Q2oL-measured) than in those with a moderate impact on CU-specific quality of life. Also, higher salivary IL-6 values were expressed in patients with uncontrolled CSU than in well-controlled CSU, as measured by the UCT questionnaire, although without significant difference between these parameters. Conclusions: Salivary IL-6 showed a weak correlation with CRP, but no consistent association with CSU clinical features. Salivary IL-6 is of exploratory interest, but larger controlled studies are needed before any clinical utility can be inferred.

Background: Atopic dermatitis (AD) is a common inflammatory dermatosis often accompanied by itching and sleep disturbances. Various treatment options exist, including antihistamines (AHs), even though current clinical recommendations do not mention them. Methods: This prospective exploratory study measured and recorded salivary melatonin at two timepoints (T1 and T2) in three groups of participants: those not treated with AHs, those who discontinued H1-AHs, and those for whom H1-AHs were introduced. Also assessed were disease severity (Scoring Atopic Dermatitis/SCORAD and Eczema Area and Severity Index/EASI), pruritus severity (Peak Pruritus Numeric Rating Scale/NRS), and sleep quality (Pittsburgh Sleep Quality Index/PSQI). Results: The EASI scores were significantly inversely correlated with salivary melatonin levels (p = 0.009) at the first timepoint (T1), but not at the second timepoint (T2). At T2, SCORAD correlated with EASI, NRS, and PSQI (ρ = 0.304–0.842; p ≤ 0.022). EASI correlated with NRS and PSQI (ρ = 0.281–0.453; p ≤ 0.035). Those who discontinued AHs showed increased AD severity indicators (SCORAD, EASI, NRS), whereas participants for whom AHs were introduced showed decreases in the same scores. After adjusting for baseline values, a significant main effect was detected for the treatment group for T2 SCORAD scores (p < 0.001, η² = 0.493). Pairwise comparisons confirmed significant differences among all treatment arms/measures (all p values ≤ 0.023). Changes in melatonin levels between the three groups were not significant when baseline SCORAD values were controlled for. Conclusions: Our exploratory study observed an inverse association between melatonin levels and AD severity at T1, but this was not replicated at T2. This association should be interpreted with caution due to study limitations. Changes in AD severity and pruritus scores following AH initiation or discontinuation were observed, but the study’s non-randomized design and baseline differences between groups preclude a definitive causal inference, and further research on this topic is needed.

Both poliosis (circumscribed depigmentation of the hair in any area of the body) and halo nevi (a melanocytic nevus which acquires a surrounding depigmented rim) are characterized by depigmentation driven by a T-cell-mediated loss of functional melanocytes within the epidermis and hair bulbs. Halo nevi and poliosis are a relatively frequent phenomenon occurring in 1% of the children and adolescents with an average age of onset of 15 years and has no gender predisposition. Both can be associated with vitiligo and are occasionally seen together as the same cytotoxic immune response (specifically CD8+ T cells) that destroys nevus melanocytes which can attack the same melanocyte-specific targets surrounding epidermal and follicular melanocytes. While poliosis is frequently seen on the scalp, halo nevi on the scalp have been scarcely reported in the literature. The timing of occurrence of the destruction of both epidermal and follicular melanocytes may be supported by a case of a 13-year-old Caucasian male with three halo nevi on the trunk which preceded the development of four scalp patches of poliosis. This may indicate that the halo nevi on the trunk induced a temporary systemic autoimmune reaction during the halo phenomenon, collaterally destroying melanocytes at distance on the scalp causing poliosis.

Formaldehyde is a well-known, ubiquitous chemical agent and a widely used skin sensitizer. There are reports of cases of systemic and localized allergic reactions attributed to formaldehyde (or formaldehyde-containing resins), which can occur during occupational exposure or daily life activities. It is included in many materials, such as cosmetic and household products, dental care products, topical medications, building materials, furniture and paints. In dentistry, patients may be exposed to formaldehyde and paraformaldehyde released from endodontic materials. Several side effects have been noted and published in the literature; however, up-to-date data are lacking. Our case report emphasizes the possibility that formaldehyde can cause an immediate hypersensitivity reaction and contact dermatitis. Therefore, the application should be reconsidered in dental treatment, especially if previously documented allergies are known.

Atopic dermatitis (AD) is a common inflammatory dermatosis often accompanied by itching and sleep disturbances. Various treatment options exist, including antihistamines (AHs) even though current clinical recommendations do not mention them. This prospective study measured and recorded salivary melatonin at two timepoints in three groups of participants: those not treated with AHs, those who discontinued H1-AHs, and those for whom H1-AHs were introduced. Also assessed were disease severity (Scoring Atopic Dermatitis/SCORAD and Eczema Area and Severity Index/EASI), pruritus severity (Peak Pruritus Numeric Rating Scale/NRS), and sleep quality (Pittsburgh Sleep Quality Index/PSQI). Initially, EASI scores significantly negatively, linearly correlated with salivary melatonin levels (p = 0.009). At the second measurement, SCORAD correlated with EASI, NRS, and PSQI (p < 0.001; p = 0.022, and p < 0.001; respectively). EASI correlated with NRS and PSQI (p = 0.003; p < 0.001). In those who discontinued AHs, AD severity indicators significantly increased (SCORAD, EASI, NRS) (p = 0.012; p = 0.012; p = 0.010), while in those for whom AHs were introduced, a significant decrease was observed in SCORAD, EASI, NSR (p = 0.012; p = 0.012; p = 0.010). Those who discontinued AHs showed increased AD severity indicators (SCORAD, EASI, NRS), whereas participants for whom AHs were introduced showed decreases in the same scores. The results support an association between melatonin levels and AD severity, as well as AHs' significant treatment efficacy in AD.

The spectrum of syndromes associated with chronic urticaria (CU) is broad, ranging from monogenic autoinflammatory diseases (a single gene defect drives disease through dysregulated innate immunity) to multifactorial and acquired conditions (urticaria arises as part of a broader, polygenic or immune-mediated systemic process). Monogenic autoinflammatory conditions presenting with urticaria include cryopyrin-associated periodic syndromes (CAPS)—encompassing familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID/CINCA) and the broader group of familial cold urticarias. Monogenic conditions with well-characterized gain-of-function NLR family pyrin domain containing 3 (NLRP3) variants present with recurrent hives, a cardinal feature associated with recurrent fevers. Multifactorial and acquired autoinflammatory or immune-mediated conditions include Schnitzler syndrome, adult-onset Still’s disease, hypereosinophilic syndrome, Gleich syndrome, Wells syndrome, and Sjögren syndrome. Multifactorial conditions, including Schnitzler syndrome and Still’s disease, manifest similarly, with CU as an initial sign and a shared pathogenic mechanism of innate immune dysregulation, with interleukin-1β playing a central, pro-inflammatory role as a major pyrogen. Here, we also present a female patient with clinically established Andersen–Tawil syndrome (ATS) who developed recurrent hives on her extremities within minutes after vigorous exercise. To our knowledge, this is the first report of a co-occurrence of CU and ATS. The hives were successfully attenuated by oral intake of effervescent potassium chloride during physical activity. This observation raises the possibility that chronic inducible urticaria may represent a previously unrecognized cutaneous ATS manifestation and suggests a potential pathophysiological link between potassium-channel dysfunction and mast cell activation. Distinguishing whether hives are an isolated symptom or part of a broader syndrome is critically important, as it might be crucial for the patient outcome.

Both poliosis (circumscribed depigmentation of the hair in any area of the body) and halo nevi (a melanocytic nevus which acquires a surrounding depigmented rim) are characteri-zed by depigmentation driven by a T-cell-mediated loss of functional melanocytes within the epidermis and hair bulbs. Halo nevi and poliosis are a relatively frequent phenomenon occurring in 1% of the children and adolescents with an average age of onset of 15 years and has no gender predisposition. Both can be associated with vitiligo and are occasio-nally seen together as the same cytotoxic immune response (specifically CD8+ T cells) that destroys nevus melanocytes can attack the same melanocyte-specific targets surrounding epidermal and follicular melanocytes. While poliosis is frequently seen on the scalp, halo nevi on the scalp have been scarcely reported in the literature. The timing of occurrence of the destruction of both epidermal and follicular melanocytes may be supported by a case of a 13-year-old Caucasian male with three halo nevi on the trunk which preceded the deve-lopment of four scalp patches of poliosis. This may indicate that the halo nevi on the trunk induced a temporary systemic autoimmune reaction during the halo phenomenon, collate-rally destroying melanocytes at distance on the scalp causing poliosis.

Background: The interaction between coagulation pathways, inflammatory markers, and hematological parameters has not been sufficiently clarified in patients with chronic angioedema (AE) and urticaria. This study aimed to validate previously observed associations and to further explore their relationship with clinical disease control. Methods: In this cross-sectional validation study, 102 participants were enrolled and stratified into three groups: isolated AE (n = 33), AE associated with urticaria (AE/Urt; n = 34), and healthy controls (n = 35). Serum levels of coagulation factors (D-dimer, fibrinogen, factor VII), inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and complete blood count parameters were analyzed. Disease control was assessed using the Angioedema Control Test (AECT). Appropriate non-parametric statistical tests were applied. Results: Only D-dimer values differed significantly between groups and were higher in patients with AE/Urt than in controls. At the same time, D-dimers were significantly more often elevated in both AE groups than in healthy individuals. Additionally, CRP values in both AE groups were significantly more often elevated than in controls, with significantly higher values in both AE groups (in both groups 85%) than in controls (57%). Coagulation markers and CRP demonstrated a positive correlation with age (r = 0.268–0.392; p ≤ 0.007), with fibrinogen of all coagulation markers showing the strongest age dependency (r = 0.334; p = 0.001). Gender-related differences in coagulation parameters were not statistically significant, although elevated fibrinogen levels were more common in male participants (p = 0.030). Disease control did not correlate linearly with any inflammatory markers, coagulation factor, age or gender. Conclusions: The findings support a contributory role of coagulation pathway activation and systemic inflammation in the pathophysiology of chronic angioedema and urticaria. These mechanisms may influence clinical disease expression and could represent potential targets for improved diagnostic stratification and therapeutic approaches. However, the interpretation of the present results should be approached with caution in light of several important study limitations, including demographic heterogeneity between the study groups and the relatively limited sample size.