An Overview on Atopic Dermatitis, Oxidative Stress, and Psychological Stress: Possible Role of Nutraceuticals as an Additional Therapeutic Strategy.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a considerable impact on patients' quality of life. Its etiology is multifactorial and, among the predisposing factors, a role is played by oxidative stress. Pollution, recurrent infections, and psychological stress contribute to oxidative stress, amplifying the production of proinflammatory cytokines and worsening barrier damage. There are various oxidative stress mechanisms involved in the pathogenesis of AD. Moreover, AD often appears to be associated with psychological disorders such as alexithymia, depression, and anxiety due to severe itching and related insomnia, as well as social distress and isolation. The increasing incidence of AD requires the evaluation of additional therapeutic approaches in order to reduce the psychological burden of this condition. Our review aims to evaluate the role of some nutraceuticals in AD treatment and its related psychological comorbidities. The combination of some natural compounds (flavonoids, alkaloids, terpenes, isothiocyanates) with traditional AD treatments might be useful in improving the effectiveness of therapy, by reducing chronic inflammation and preventing flare-ups, and in promoting corticosteroid sparing. In addition, some of these nutraceuticals also appear to have a role in the treatment of psychological disorders, although the underlying oxidative stress mechanisms are different from those already known for AD.

Association between urticaria and nematode infections.

BACKGROUND: The association between parasites and urticaria was first suggested in the last century. A wide range, 0-75.4%, of the prevalence of parasitic infection has been reported with chronic urticaria (CU). Moreover, urticaria may be detected in patients with parasitosis. Nematodes are a type of helminth that infect hundreds of millions of people throughout the world. OBJECTIVE: The aim of this work was to collect and review the published studies and cases of urticaria associated with nematode infections. METHODS: A search of scientific literature data bases from January 1960 until May 2017 was carried out. RESULTS: Numerous nematode infections have been associated with urticaria and/or angioedema: Anisakis simplex, Ascaris species (spp.), Dirofilaria spp., Enterobius vermicularis, Gnathostoma spp., Loa loa, Mansonella streptocerca; Necator americanus, Onchocerca volvulus, Strongyloides stercoralis, Toxocara spp., Trichinella spp., and Wuchereria bancrofti. The pathogenesis of urticaria in these infections generally remains unexplained. In some cases, skin manifestations were caused by the presence of the worm in the skin (Filaria, Gnathostoma); in other cases, such as A. simplex and S. stercoralis infections, there was a clear immunoglobulin E-mediated mechanism that led to allergic reactions, and infection and allergy coexisted; for other nematodes, the association was anecdotal and only a few cases were reported. CONCLUSION: It is difficult to detect a certain causal effect, except when urticaria improves or disappears after infection treatment. Cases of isolated urticaria not associated with other symptoms rarely may be caused by helminths. In the current guideline for urticaria, parasitosis is considered to be a rare possible cause of CU in developed industrial countries, Therefore, although a routine screening of parasitic infection in CU is not recommended, in our opinion, testing a patient with urticaria for parasites is a physician's choice based on the characteristics of the patient, such as associated symptoms, dietary habit, provenance country and previous travel.

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 4: Solidago virgaurea-Vitis vinifera.

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph - now (since 2014) called a 'European Union herbal monograph' - has been produced. The present part 4 addresses species from Solidago virgaurea L. to Vitis vinifera L.

Involvement of microRNAs in skin disorders: A literature review.

BACKGROUND: miRNAs are a class of noncoding RNA molecules that modulate gene expression after transcription. It is known that miRNAs are involved in various cellular processes of both normal and diseased skin. Recently, differential expressions of miRNAs have been reported and associated with several immunologic and inflammatory disorders, which indicate a common role in fundamental biologic processes. OBJECTIVE: To collect and review data from the literature on involvement of miRNA in inflammatory skin disorders. METHODS: A bibliographic search of scientific literature was carried out independently by two researchers in scientific data bases and search engines. The MeSH terms used were the following: "microRNAs" combined with "skin," "dermatitis," "urticaria," "eczema," "hypersensitivity." All research articles from inception until April 2016 were considered. RESULTS: A total of 11 research articles on the study of miRNAs in inflammatory skin disorders (atopic dermatitis, delayed-type hypersensitivity, eczema, toxic epidermal necrolysis) were identified. All the studies confirmed the main role of endogenous noncoding RNAs in diseases such as atopic dermatitis, allergic contact dermatitis, eczema, and toxic epidermal necrolysis. CONCLUSION: The miRNAs seem to influence regulatory mechanisms of inflammation in both inducing and contrasting acute and chronic skin inflammation. They also seem to be useful instruments in identifying and staging diseases such as dermatitis and other inflammatory skin diseases. Also, the potential application of miRNAs in genetic therapies demonstrated its efficacy on animal models.

Involvement of new oxidative stress markers in chronic spontaneous urticaria.

INTRODUCTION: Oxidative stress is a result of an imbalance between endogenous production of free reactive oxygen species and reduced effectiveness of antioxidant defence mechanisms. Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) are compounds formed by transformation of macromolecules, including proteins which can serve as markers of oxidative stress and inflammation in several diseases. AIM: To investigate the role of AGEs and AOPPs as new markers of oxidative stress and inflammation in patients with chronic spontaneous urticaria (CSU). MATERIAL AND METHODS: Advanced glycation end products and AOPP levels were determined in the sera of 85 patients with CSU and 64 healthy controls, using spectrofluorimetry and spectrophotometry, respectively. RESULTS: Advanced oxidation protein products levels in patients were statistically higher than those in controls. These levels were not affected by the presence of positive autologous serum test results or autologous plasma test results. No statistically significant differences were found between AGE levels in patients and controls. CONCLUSIONS: Formation of AGEs and AOPPs may be accelerated in immunological and allergic disorders. Depending on the sites evaluated, the presence or absence of oxidative stress in chronic urticaria is controversial. To our knowledge, this is the first study showing the possible involvement of AOPPs in CSU. The different behaviour observed for these two biomarkers is very likely due to the activation of specific related biochemical pathways associated with the condition under study.

Association between urticaria and virus infections: A systematic review.

BACKGROUND: The association between urticaria and virus infections has rarely been reported in the literature. The lack of reported cases is probably due to the difficulty in establishing a cause-and-effect relationship. It is not possible to challenge the patient with an etiologic agent. OBJECTIVE: The purpose of this work was to perform a systematic review on the association between urticaria and virus infections. METHODS: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles from January 1, 2008, through May 2015, by using two key terms related to urticaria and virus diseases, "urticaria" and one key term related to virus infections, "virus disease," then "urticaria" and the name of each virus family, and of the most representative virus serotypes. RESULTS: We reported cases of patients affected either by acute or chronic urticaria with a concurrent virus infection. Previous other causes of urticaria had to be excluded. Herpesviridae infections and urticaria were the most frequently reported associations in children. However, hepatitis virus infections would appear to be the most-frequent cause of urticaria in adults. CONCLUSIONS: Data obtained indicated viral infection as a potential trigger and sometimes as the main etiologic agent in causing acute or chronic urticaria. In every case, urticarial manifestation cleared up after either healing or controlling of the viral infection. However, prospective studies and well-structured research is needed to better clarify the role of viruses in the pathogenesis of urticaria and their relative prevalence.

Lethal Anaphylactic Reaction to Intravenous Gelatin in the Course of Surgery.

Plasma volume expanders (PVEs) are widely used to increase circulating blood volume. Gelatins used as PVEs are heterogeneous mixtures of polypeptides, usually prepared by hydrolysis of bovine collagen containing large amounts of proline and hydroxyproline residues. It has been shown that gelatins can cause anaphylactic reactions. We describe the case of a 73-year-old man who during surgery for intestinal obstruction presented a lethal anaphylactic reaction after the administration of a PVE containing gelatin lysate. The reaction occurred 10 minutes after the start of plasma expander infusion. Then, patient became comatose, and he died without awakening after 76 days. Necroptic aspects and histologic evaluation suggested the occurrence of anaphylactic reaction. According to pharmacovigilance algorithm, the causality relationship between PVE administration and adverse reaction has been considered as probable. We described a new lethal adverse reaction caused by PVEs containing gelatin. It is currently considered a very rare event, but we believe that it represents an important signal suggesting for a critical surveillance comprising a complete evaluation of individual's allergic susceptibility.

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - Part 3: Mentha × piperita - Solanum dulcamara.

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph - now (since 2015)(†) called a European Union herbal monograph - has been produced. Part 3: Mentha × piperita L.-Solanum dulcamara L.

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 2: Echinacea purpurea-Lavandula angustifolia.

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench-Lavandula angustifolia Mill.

Flare up reaction during provocation test to glatiramer acetate in a patient with allergy to interferon beta1a.

Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-ß1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test.

Urticaria and bacterial infections.

The association between urticaria and infectious diseases has been discussed for >100 years. However, a causal relationship with underlying or precipitating infection is difficult to establish. The purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. We give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. We did a Medline search, for English language articles published until January 2014, using the key words "urticaria" and "bacteria/bacterial disease"; a second analysis was performed in groups of bacteria and using each germ name as a key word. Many bacterial infections have been associated with urticaria manifestation, such as Helicobacter pylori, Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella, Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica. In some cases the skin manifestations, described as urticaria, could be caused by the presence of the microorganism in the skin, or for the action of their toxins, or to the complement activation mediated by circulating immune complexes. Although only a weak association with urticaria of unclear pathogenesis exists, clinicians should consider these bacterial agents in the workup of the patients with urticaria. The eradication of the infection could, in fact, lead to the resolution of urticaria. Prospective studies and well-structured research are obviously needed to better clarify the real role of bacteria in the pathogenesis of urticaria and their relative prevalence.

Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 1: Achillea millefolium-Curcuma longa.

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 1: Achillea millefolium L.-Curcuma longa L.

Urticaria and thyroid autoimmunity.

BACKGROUND: Chronic urticaria is a common clinical condition whose etiology, in about 75% of cases, is unknown and is therefore called chronic idiopathic urticaria (CIU). A link between CIU and autoimmune thyroid diseases was proposed several decades ago. Here we review this topic. SUMMARY: Several studies have been performed to determine if and to what degree there is an association between CIU and autoimmune thyroid diseases, particularly autoimmune thyroiditis. Many of these studies were not well controlled, however. Approximately one-fourth of CIU patients have serological evidence of thyroid autoimmunity, suggesting that these two disorders are associated. The mechanisms for the apparent association between CIU and serological evidence of thyroid autoimmunity are not clear. There are no data regarding the correlations between CIU and histological features of autoimmune thyroiditis or hypothyroidism. Despite this, there are anecdotal reports regarding L-thyroxine administration in patients with CIU. CONCLUSIONS: Screening for thyroid autoimmunity is probably useful in patients with CIU. More solid evidence, based on still lacking well-conducted controlled studies, is desirable to determine if there is a therapeutic role for L-thyroxine treatment in ameliorating the skin manifestations of urticaria.

Hypersensitivity to tranexamic acid: a wide spectrum of adverse reactions.

CASES DESCRIPTION: This is a retrospective study, based on analysis of data from patients with previous adverse drug reactions admitted to the Allergy and Clinical Immunology Division of both the University of Messina and the University of Bari in the last 4 years. We observed five patients: four of them (two males and two females) with a well documented history of tranexamic acid hypersensitivity reactions and one female who showed a positive response to an intradermal challenge test with tranexamic acid. CONCLUSIONS: Although the risk of immunogenic and severe allergic reactions to tranexamic acid is significantly lower than those associated with administration of other drugs, our experience points out that adverse reactions to tranexamic acid can occur. This drug may be responsible for a wide and various spectrum of hypersensitivity reactions characterized by different pathogenetic mechanisms (immunologic and non-immunologic). Etamsylate was a well tolerated alternative drug to tranexamic acid in all examined patients.

Fatal anaphylactic shock due to a dental impression material.

Materials used for dental impressions are usually safe. This study describes a case of fatal anaphylaxis that appeared immediately after the oral mucosa came into contact with an alginate paste used for dental impressions. The cadaveric examination and the postmortem toxicology report confirmed that the cause of death was anaphylactic shock. The patient was affected by both cardiovascular and lung diseases that worsened the condition and forbade the use of epinephrine. To the authors' knowledge, dental impression materials, and alginate in particular, have not been reported previously as being a cause of anaphylaxis.

Eosinophilic fasciitis associated with autoimmune phenomena after bone marrow transplantation: report of two cases.

Between January 1992 and May 2004, 189 patients underwent allogeneic bone marrow transplantation (BMT) for haematological malignancies from HLA-identical sibling donors in our transplantation unit. Of the 189 patients, 2 developed eosinophilic fasciitis (EF). The first patient developed Hashimoto's thyroiditis and EF 11 and 21 months after BMT, respectively. In the second patient EF occurred 9 months after BMT, accompanied by antinuclear antibodies, antiextractable nuclear antigens and antigliadin antibodies. Both patients were treated with extracorporeal photochemotherapy (ECP), resulting in improvement of fasciitis in both and normalization of antithyroid antibodies in the first patient. Our data confirm the rarity of fasciitis after BMT and the efficacy of ECP, recently applied experimentally in one patient for the treatment of fasciitis after BMT. Moreover, we report for the first time the association of fasciitis with autoimmune phenomena after BMT. The correlation between the two entities is supported by remission of Hashimoto's thyroiditis after ECP treatment for fasciitis.

Montelukast-induced generalized urticaria.

OBJECTIVE: To report a case of generalized urticaria induced by montelukast treatment. CASE SUMMARY: A 28-year-old man with allergic rhinitis and moderate persistent asthma developed generalized urticaria 5 days after the initiation of montelukast and inhaled fluticasone. Symptoms disappeared within one day after suspension of both drugs. Two months later, after the resumption of montelukast and fluticasone, the patient developed generalized urticaria and eyelid angioedema, which were successfully treated with intravenous betamethasone, achieving complete remission within hours. After 2 days, the patient resumed inhaled fluticasone only and continued this therapy for several months without any adverse reaction. DISCUSSION: We attributed the adverse reaction to montelukast because of the temporal relationship between use of montelukast and urticaria, the absence of other identified causative factors and other explanations for allergic reactions, and the positive dechallenge and rechallenge. The Naranjo probability scale showed a probable relationship between skin manifestations and montelukast treatment. CONCLUSIONS: The use of antileukotrienes is increasing in asthma therapy. In cases of generalized urticaria in asthmatic patients undergoing montelukast therapy, physicians should be aware of a potential adverse reaction to this drug.

Cadmium concentration in maternal and cord blood and infant birth weight: a study on healthy non-smoking women.

The aim of our study was to measure, at delivery, maternal and cord blood cadmium levels (by means of atomic absorption spectrometry) in 45 healthy non-smoking pregnant women exposed to a low cadmium challenge, and to evaluate the relationship between these cadmium levels and the birth weight of the infants. Our results showed fairly low cadmium levels in maternal blood, in accordance with the fact that all women enrolled in this study lived in areas with low toxic metal contamination and that they did not smoke during their pregnancy. Furthermore, a highly significant direct correlation was found between maternal and cord blood cadmium concentrations. Since cadmium concentration appeared of the same order of magnitudine both in cord and maternal serum, one could speculate that cadmium is transferred easily from the mother to the fetus through the placenta. Finally, we found that birth weight is inversely correlated with maternal and cord blood cadmium concentrations; thus birth weight might be negatively influenced by cadmium levels as a result of the toxic effects of the metal on the placenta. Although preliminary, our data show that (also not-predictable) prenatal exposure to even low cadmium levels might be a risk factor for developmental impairment in infants.