Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine in p-phenylenediamine highly allergic volunteers using allergy alert test: the Italian experience.

Summary: Background. Allergic contact dermatitis after exposure to p-phenylenediamine (PPD)-containing hair dye products is a common and important clinical problem. Because there is a high rate of cross-elicitation of allergic contact dermatitis to other important hair dye products (such as p-toluene diamine [PTD] and other aminophenol hair dyes) in PPD allergic patients, safer alternative dyes with excellent hair coloring options are needed. We studied 2-methoxy methyl-PPD (Me-PPD), a chemical derivative of PPD for tolerance versus cross-elicitation in a cohort of eight PPD-allergic volunteers. Objective. To study tolerance to Me-PPD in a PPD highly allergic Italian cohort. Methods. Eight volunteers with a history of contact dermatitis to hair dyes or other PPD-containing chemicals and positive patch tests to 1% PPD in petrolatum, were recruited to study their immediate and delayed skin reactivity to PPD, vehicle control and 2-methoxy-methyl-PPD (Me-PPD), using the allergy alert test (simulating hair dyeing conditions) on volar forearm skin. This is a short-contact open patch test. Results. All eight volunteers reacted to PPD allergy alert test (100%); none reacted to vehicle (0%), and seven of eight reacted to Me-PPD allergy alert test (88%). However, in those seven volunteers who exhibited cross-elicitation to Me-PPD, their aggregate skin test reactivity to Me-PPD was significantly less than that of PPD (figure 3, p minore 0.0062, highly significant, paired two-tailed, students t test). Conclusions. Me-PPD may offer a safer alternative for PPD-allergic patients with an absent or reduced elicitation response in the allergy alert test simulating hair dye use conditions. Even patients with strong patch test reactions, with appropriate selection by allergy alert test and counselling, may be able to tolerate hair dyeing with Me-PPD containing products.

S100A8/A9 promotes parenchymal damage and renal fibrosis in obstructive nephropathy.

Despite advances in our understanding of the mechanisms underlying the progression of chronic kidney disease and the development of fibrosis, only limited efficacious therapies exist. The calcium binding protein S100A8/A9 is a damage-associated molecular pattern which can activate Toll-like receptor (TLR)-4 or receptor for advanced glycation end-products (RAGE). Activation of these receptors is involved in the progression of renal fibrosis; however, the role of S100A8/A9 herein remains unknown. Therefore, we analysed S100A8/A9 expression in patients and mice with obstructive nephropathy and subjected wild-type and S100A9 knock-out mice lacking the heterodimer S100A8/A9 to unilateral ureteral obstruction (UUO). We found profound S100A8/A9 expression in granulocytes that infiltrated human and murine kidney, together with enhanced renal expression over time, following UUO. S100A9 KO mice were protected from UUO-induced renal fibrosis, independently of leucocyte infiltration and inflammation. Loss of S100A8/A9 protected tubular epithelial cells from UUO-induced apoptosis and critical epithelial-mesenchymal transition steps. In-vitro studies revealed S100A8/A9 as a novel mediator of epithelial cell injury through loss of cell polarity, cell cycle arrest and subsequent cell death. In conclusion, we demonstrate that S100A8/A9 mediates renal damage and fibrosis, presumably through loss of tubular epithelial cell contacts and irreversible damage. Suppression of S100A8/A9 could be a therapeutic strategy to halt renal fibrosis in patients with chronic kidney disease.

Plasticity of immune system vs. memory therapy IST.

BACKGROUND: Pharmacotherapy and immunotherapy are the main treatments for allergic diseases to inhalants. OBJECTIVE: This study investigates whether to repeat short cycles of immunotherapy after 3 or 5 years the from interruption of the first therapeutic cycle, lasting 3-4 years, to maintain immune memory in individuals subjected to IST. METHODS AND RESULTS: We have compared two groups, one of 452 patients who, after the first treatment for 3-4 years of IST, performed a cycle of four months after three and 10 years from the suspension, and a second group of 126 individuals who have performed only the IST treatment for 3-4 years. The best results were obtained in the first group. CONCLUSIONS: These results are due to the immune system's plasticity, a very important concept in clinical practice.

Successful of subcutaneous and oral hyposensitizing therapy in 30 patients.

SUMMARY: Background. Pharmacotherapy and immunotherapy are the main treatment modalities for respiratory allergy. The aim of this paper has been to evaluate the efficacy and tolerability of subcutaneous and sublingual immunotherapy in association in allergic patients, and to demonstrate that the patients who have performed a second oral vaccination cycle after 4-5 years from the first subcutaneous treatment, derive benefits that may last for years. This is due to immune system's plasticity. Methods. The study was conducted in 30 allergic patients which had previously executed a full cycle of classical subcutaneous immunotherapy, with a partial remission of symptoms. After 4-5 years, they were subjected to sublingual immunotherapy for the same allergen, improving the results obtained. Results. All the patients reported a decrease or absence of clinical symptoms, a reduction in the use of anti-allergic drugs, and lower values of PRIST and RAST after the treatment. Conclusions. The results of this clinical study confirm the improvement of results when subcutaneous and sublingual immunotherapy are associated.

Chemical research on red pigments after adverse reactions to tattoo.

Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

Trends of thyroid function and autoimmunity to 5 years after the introduction of mandatory iodization in Italy.

Background. Mandatory iodine fortification of salt was introduced in Italy in 2005. The purpose of our study is to estimate the trend of thyroid diseases in Italy before and after mandatory iodization in Italy. Methods. 7976 patients (6802 females; 1174 males) were examined between 2003 and 2010. We divided the patients into categories according to their clinical diagnosis. Later, we evaluated for each patient if there was the positivity for antibodies anti TPO. Finally, we collected data about TSH values of all patients who did not use therapy for thyroid disease at the time of the examination. To evaluate the differences percentages for categorical variables, χ2-Pearson test was used; to evaluate the percentage differences of TSH values we used the Kruskal-Wallis test. Values were considered statistically significant at p < 0.05. Results. We considered diagnosis of "toxic adenoma / goiter", diagnosis of "Graves' disease" and diagnosis of "hyperthyroidism / thyrotoxicosis" before and after the introduction of mandatory iodization in Italy, to demonstrate the possible presence of iodine-induced hyperthyroidism. Diagnosis of toxic adenoma / goiter before 2005 were 3.7%, while after 2005 they were reduced to 3.1%. Diagnosis of Graves' disease before 2005 were 2.4%, and they remained unchanged after 2005. Finally, diagnosis of hyperthyroidism / thyrotoxicosis decreased from 2.5% to 2.1%. Comparing these results, there were no significant differences (P = 0.261) between the percentages of diagnosis of hyperthyroidism before and after the introduction of mandatory iodization. We considered diagnosis of Hashimoto's thyroiditis before and after 2005 to demonstrate a link between the administration of iodine and thyroid autoimmunity. Prevalence of Hashimoto's thyroiditis between 2003 and 2005 was 37%; prevalence between 2006 and 2010 dropped to 34.7%. This small difference has a borderline statistical significance (P = 0.049). Stratifying TSH values from year to year, we found a small increase in TSH value, which, in any case, remains in the normal range. TSH values passed from 1.37 in 2003, to 1.61 in 2010. Although this increase is modest, it is statistically significant (P values < 0.001). Conclusion. In this study there isn't a connection between iodine fortification and iodine-induced hyperthyroidism, and between iodine fortification and Hashimoto's thyroiditis. This small increase of TSH values can not find a clear explanation yet. We considered several mechanisms to explain this phenomenon: alterations of Na/I symporter reduce intracellular levels of iodine, and cause a state of hypothyroidism; excessive levels of iodine can increase apoptosis of thyrocytes, as it is demonstrated by several studies; interference from external agents (endocrine disruptors).

Heavy metal and tattoo: an allergy and legislative problem.

We presented an interesting clinical case of a 23 years old man presented with a 2-week history of pruritus, erythema and papules on legs, arms and trunk. These lesions developed 2 months after tattooing. It showed positive patch test reaction to Copper and Disperse Blu.

A case of hypersensitivity to progesterone presenting as an eczematous eruption.

Hypersensitivity to progesterone is a rare condition, and it represents a hypersensitivity reaction to endogenous progesterone. Here we report a case of a woman who presented to our attention for evaluation of a rash for a few years on her posterior elbows, forearms, and right lateral lower extremity. We report this case because it describes a rare clinical entity, with an atypical clinical presentation pemphigoid-like, that is rarely described in literature.

Ultrastructural age-related changes in the sensory corpuscles of the human genital skin.

In human genital skin the majority of superficial sensory corpuscles is represented by glomerular corpuscles. These corpuscles show an own morphology. Our aim is to compare the ultra-structure of superficial sensory corpuscles in the penis skin of younger and older subjects. In this report the ultra-structure of the sensitive corpuscle in the penis skin of the younger and older subjects was compared, showing that the genital skin of the older humans contains more simple complexes than the younger ones. Our findings support the view that the age-related changes that can be observed in human glomerular genital corpuscles are consistent with an increase of the simple complexes and a strong decrease of the poly-lamellar one in the older people. These findings demonstrate that human genital corpuscles underwent age-related changes. Moreover our morphological findings can be correlated in relation to the clinical evolution of the sensitivity in the genital skin.

T-cell subpopulations express a different pattern of dopaminergic markers in intra- and extra-thymic compartments.

An involvement of dopamine in regulation of the immune function has been assessed and dopaminergic system has been found widely represented in thymus. Nevertheless detail on the characterization of dopaminergic system in assisting thymocytes development and lymphocytes mature physiology are still lacking. The present study was designed to characterize dopamine plasma membrane transporter (DAT), vesicular dopamine transporters (VMAT)-1 and -2, and dopamine D1-like and D2-like receptors in rat thymocytes, splenocytes and peripheral blood mononuclear cells. Western blot and RT-PCR analyses, performed on these cells, showed an expression of dopamine transporters and receptors during thymocyte development (when of CD4 and CD8 markers are differently expressed). Furthermore FACS analysis, indicates that DAT and dopamine D1-like receptors are expressed at high levels in thymocytes, splenocytes, and peripheral lymphocytes. The percentage of CD4+ CD8+ (double-positive) thymocytes expressing dopaminergic markers was significantly higher compared to the percentage of double-negative ones. The percentage of CD8+ single positive cells expressing dopaminergic markers was significantly higher than that of CD4+ cells. The results suggest that the dopaminergic system plays a role in the thymus microenvironment during T-cell development. The more pronounced expression of dopaminergic markers in CD8+ subsets suggests that dopamine plays a role in development of cytotoxic T-cells. Our findings indicate dopaminergic system to have a role during the maturation and selection of lymphocytes, and support its involvement in the active phases of immune response.

CD63 cell expression detected by flow-cytometric determination of basophil activation in allergic patients.

Flow cytometry analysis of in vitro activated basophils (BATs) based on the detection of CD63 up-regulation on basophil membrane provides the physician and the clinical laboratory with a novel diagnostic approach, proposed as a promising alternative method for in vitro diagnosis of IgE and non-mediated reactions. We performed an optimized flow cytometric procedure to assess CD63 expression on activated basophils on twenty allergic patients, and compared the results with specific IgE determination (RAST) and skin testing (Prick test).

Psoriasiform dermatitis in a non-psoriatic patient treated with adalimumab.

Anti-TNF drugs may be associated with various adverse reactions including cutaneous ones. We describe the case of a 45-year-old woman affected by undifferentiated spondyloarthritis who presented a localized psoriasiformis dermatitis during treatment with adalimumab, without any medical history of psoriasis.

A case of periocular contact dermatitis caused by cypress allergy.

Airborne contact dermatitis is a dermatological disease manifesting predominantly on the face, neck and arms, which is caused by volatile substances which settle on exposed skin. Although the diagnosis is not difficult, the finding of causative allergens and the exclusion of differential diagnoses are still lacking by the treating dermatologists.

Chronic idiophatic urticaria and Helicobacter pylori: a specific pattern of gastritis and urticaria remission after Helicobacter pylori eradication.

Chronic urticaria (CU) is defined as the occurrence of spontaneous wheals for a duration of more than 6 weeks and is the most frequent skin disease, with prevalence ranging between 15 and 25%, and is a seriously disabling condition, with social isolation and mood changes causing a significant degree of dysfunction and quality of life impairment to many patients. The main clinical features of CU are the repeated occurrence of transient eruptions of pruritic wheals or patchy erythema on the skin that last less than 24 hours and disappear without sequelae. CU is often defined as chronic idiopathic urticaria (CIU) because the causes of CU remain unknown in the great majority (70-95%) of patients. Drugs, food, viruses, alimentary conservative substances or inhalant substances often seem to be involved in determining CIU skin flare. Despite a general agreement that bacteria infections and parasitic infestations can be involved in the pathogenesis of CIU, proven evidence of these relationships is lacking. The aim of the present study is to evaluate the prevalence of Helicobacter pylori (Hp) infection, and the extension and severity of gastritis in a group of CIU patients compared to controls and to evaluate the effectiveness of eradication of Hp on the CIU symptomatology, and the role of Hp infection in pathogenesis of CIU.

Effects of oral hyposensitization therapy with nickel on haemoglobin and haematocrit values in sensitized patients.

Nickel deficiency leads to reduced iron content in organs and to reduced hemoglobin levels and haematocrit counts. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel on a group of 20 patients affected by systemic allergy to this sensitizer element and with a chronic relapsing low hemoglobin level and haematocrit count. We obtained interesting results on maintaining these values in treated patients.