Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children

Background:  There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment.
Objectives:  To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization.
Methods:  Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization.
Results:  Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5–7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2–6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1–5.9).
Conclusions:  Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.     

Increase of CC chemokine receptor 4-positive cells in the peripheral CD4+ cells in dogs with atopic dermatitis or experimentally sensitized to Japanese cedar pollen

BACKGROUND: Since dogs frequently develop allergic diseases, similar to those in humans, dogs represent a possible animal model for allergy in humans. In human atopic dermatitis (AD), CC chemokine receptor 4 (CCR4) has been shown to play an important role in the development of allergic inflammation of AD; however, the association between allergic reaction and CCR4 is not well understood in dogs. OBJECTIVE: To examine CCR4 expression in peripheral blood CD4+ cells in dogs that had AD and were experimentally sensitized with Japanese cedar pollen. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 17 dogs with AD. The proportion of CCR4+ cells in peripheral blood CD4+ cells (CCR4/CD4) was evaluated by flow cytometry and compared with that in 10 healthy dogs. Similarly, in dogs that were experimentally sensitized to Japanese cedar pollen antigen, the proportion of CCR4/CD4 was examined pre- and post-sensitization. RESULTS: The proportion of CCR4/CD4 in dogs with AD was 40.3+/-3.3%, which was significantly higher than that in normal dogs (23.6+/-4.3%) (P<0.01). In the experimentally sensitized dogs, the proportion of CCR4/CD4 was 25.4+/-2.6% at pre-sensitization and it was significantly increased (29.8+/-2.9%) at post-sensitization (P<0.01). CONCLUSION: The proportion of CCR4+ cells in peripheral blood CD4+ cells was measured in dogs with allergic conditions. The present findings indicate that CCR4+ cells may be involved in the pathogenesis of allergy in dogs as in humans.     

Association of allergic contact dermatitis with a promoter polymorphism in the IL16 gene

BACKGROUND: There is evidence that IL-16, a cytokine that induces chemotactic responses in CD4(+) T cells, eosinophils, and dendritic cells, plays an important role during different types of cutaneous inflammatory responses, including allergic contact dermatitis (ACD) and atopic dermatitis (AD). OBJECTIVES: We sought to test for association between a promoter polymorphism in the IL16 gene (T to C transition at position -295) and ACD and AD, respectively. METHODS: IL16 -295 genotypes were determined in samples from 2 separate case-control studies with white individuals. The first study included healthy individuals (n = 310) and patients with ACD (n = 86). These patients were polysensitized as defined by a contact sensitization to para-substituted aryl compounds and at least one other structurally unrelated allergen. The second study comprised healthy subjects (n = 214) and patients with AD (n = 94). RESULTS: IL16 -295 genotypes were differently distributed among polysensitized and healthy control subjects (P =.0021). In particular, the IL16 -295*C/C genotype was overrepresented among polysensitized individuals (7.0% vs 1.0% in the control group; odds ratio, 7.68; 95% CI, 1.59-48.12). In contrast, there was no evidence for an association between the IL16 -295 polymorphism and AD. CONCLUSION: The IL16 -295 promoter polymorphism might influence susceptibility to contact allergy.     

Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration in the skin. In order to assess the roles of inflammatory cells in this disease, we analysed the activation status and surface markers of various leucocytes in the IL-4 transgenic mouse model of atopic dermatitis, by flow cytometry, immuofluorescence microscopy, and T cell proliferation assays. The studies were performed with a nontransgenic mouse control and transgenic mice at three disease stages: before disease onset, early skin disease, and late skin disease, so that we can delineate the immunological sequence of events. As the skin disease evolves, the skin draining lymph node cells from IL-4-Tg mice show a spontaneous proliferation and a progressively enhanced proliferative response to stimulants including anti-CD3, Con A, PHA, and Staphylococcus enterotoxins A and B. As the disease evolves, the percent of lymphoid organ T cells expressing activation molecules (CD44 and CD69) and costimulatory molecules (ICOS and PD-1) are progressively increased; the percent and total number of T cells are reduced in an incremental manner in the secondary lymphoid organs while the number of T cells infiltrating the skin increases in an incremental fashion; the total number of dendritic antigen presenting cells, macrophages, and NK cells gradually increases in the lymphoid organs. Collectively, our results suggest that there is a continued and progressive migration of activated inflammatory cells from the secondary lymphoid organs into the skin where they participate in immune responses resulting in the pathology associated with inflammation.     

Efficacy of mizolastine, a new antihistamine, compared with placebo in the treatment of chronic idiopathic urticaria

A two-centre, double-blind, randomized, placebo (P)-controlled, parallel-group study was conducted in the UK to examine the efficacy and safety of mizolastine (M), a new H₁-receptor antagonist, as a once-daily 10-mg dose in chronic idiopathic urticaria. Fifty-six outpatients (M: n = 28; P: n = 28) with a mean age of 38 ± 15 years, a duration of disease of more than 3 years, and symptoms of urticaria at least twice a week in the absence of treatment were recruited. After a single-blind placebo run-in period, patients were allocated to one of two treatment groups and were evaluated after 7 and 28 days. The main characteristics (age, duration of disease, number of urticarial episodes, and total score) of the two groups were comparable at inclusion. Mizolastine was shown to improve the urticaria symptoms: at the end of the study, mizolastine produced a significantly greater decrease in the global symptom score comprising itch, wheals, and erythema (M: 2.1 ± 2.1 vs P: 0.4 ± 2.0; P = 0.002). The patient-rated global discomfort from symptoms measured by visual analog scale was significantly improved with mizolastine (M: 31.4 ± 36.7) compared to placebo (P: 5.4 ± 27.6; P = 0.003), with respectively more M responders (74.1%) than P responders (28.6%, P = 0.001), a responder being a patient with a ≥50% decrease in VAS. Premature dropouts due to lack of efficacy and loss to follow-up mainly occurred at the first evaluation (day 7) and were more often observed in patients in the placebo group ( n = 17) than in the mizolastine group ( n = 8) ( P = 0.031). No serious adverse events were recorded. Somnolence was reported in two mizolastine patients, one of whom discontinued the study. Thus, mizolastine may be considered a new treatment option for the symptoms of chronic urticaria.     

Development of a new orthotopic animal model of metastatic liver cancer in the rabbit VX2 model: effect on metastases after partial hepatectomy,intra-arterial treatment with 3-bromopyruvate and chemoembolization

Aim The aim of our study was to compare the influence of partial hepatectomy, intra-arterial treatment with 3-BrPA and TACE on regional and distant metastases. In order to achieve our objective, we tested the feasibility of both resection, intra-arterial therapy with 3-BrPA and TACE of VX2 liver cancer in New Zealand White rabbits. Methods VX2 tumors were implanted in the left lateral lobe of the liver of 20 rabbits. Tumors were allowed to grow for 14 days. Rabbits were divided in four groups. Group 1 (n = 2) was sacrificed 14 days post implantation. Group 2, 3 and 4 (n = 6) underwent left lateral hepatectomy, a 1 h intra-arterial infusion with 3-BrPA and TACE respectively. Animals in each group were further subdivided into three groups of two animals each corresponding to the time-point of sacrifice after the procedure (7, 14 and 21 days respectively). After sacrifice, organs were harvested, fixed and analyzed. Results Pathologic examination showed lung metastases in all 20 rabbits. Abdominal cavity dissemination was seen in five rabbits in Group 2, two rabbits in Group 3 and all rabbits in Group 4. Kidney metastases were seen in two rabbits treated with TACE. Conclusion The VX2 rabbit model of liver cancer is a suitable model to compare the influence of partial hepatectomy, intra-arterial treatment with 3-BrPA and TACE on tumor recurrence in the form of regional and distant metastases. Our results indicate that intra-arterial delivery of 3-BrPA may result in a favorable metastatic profile when compared to both liver resection and TACE. Josephina A. Vossen and Manon Buijs have contributed equally to this work.