Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p-phenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.

Skin barrier damage after exposure to paraphenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). Both private and occupational exposure to PPD is frequent, but the effect of PPD exposure in nonallergic occupationally exposed subjects is unknown. OBJECTIVE: We sought to investigate the effects of PPD exposure on the skin of occupationally exposed subjects with and without clinical symptoms. METHODS: Skin biopsy specimens were collected from 4 patients with mild and 5 patients with severe PPD-related ACD and 7 hairdressers without contact dermatitis on day 4 after patch testing with 1% PPD in petrolatum. RNA sequencing and transcriptomics analyses were performed and confirmed by using quantitative RT-PCR. Protein expression was analyzed in skin from 4 hairdressers and 1 patient with ACD by using immunofluorescence staining. Reconstructed human epidermis was used to test the effects of PPD in vitro. RESULTS: RNA sequencing demonstrated downregulation of tight junction and stratum corneum proteins in the skin of patients with severe ACD after PPD exposure. Claudin-1 (CLDN-1), CLDN8, CLDN11, CXADR-like membrane protein (CLMP), occludin (OCLN), membrane-associated guanylate kinase inverted 1 (MAGI1), and MAGI2 mRNA expression was downregulated in patients with severe ACD. CLDN1 and CLMP expression were downregulated in nonresponding hairdressers and patients with mild ACD. Filaggrin 1 (FLG1), FLG2, and loricrin (LOR) expression were downregulated in patients with ACD. Confocal microscopic images showed downregulation of CLDN-1, FLG-1, and FLG-2 expression. In contrast, 3-dimensional skin cultures showed upregulation of FLG-1 in response to PPD but downregulation of FLG-2. CONCLUSION: PPD-exposed skin is associated with extensive transcriptomic changes, including downregulation of tight junction and stratum corneum proteins, even in the absence of clinical symptoms.

Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Intranasal corticosteroids (INS) (corticosteroid nasal sprays) and oral antihistamines (OA) are two of the most common treatments for patients with allergic rhinitis (AR). To our knowledge, there are no systematic reviews on this topic including trials published after 2007. OBJECTIVE: To compare INS with nonsedating OAs as treatments for AR. METHODS: The systematic review and meta-analysis were based on the Grades of Recommendation, Assessment, Development, and Evaluation principles and the Patient, Intervention, Comparison, and Outcome approach. Primary literature was searched up to January 22, 2015. Criteria for eligibility were randomized controlled trials that compared the efficacy and/or adverse effects of INS and OA in patients with AR. Continuous outcome data were analyzed by using standardized mean differences (SMD) for multiple outcome measures, and mean differences in the case of a single study or outcome. Pooled estimates of effects, 95% confidence interval (CI), were calculated by using random-effects models. RESULTS: The meta-analysis included five randomized controlled trials with a total of 990 patients. INS were superior to OAs in improving total nasal symptoms score (SMD -0.70 [95% CI, -0.93 to -0.47]) and in relieving the following: nasal obstruction (SMD -0.56 [95% CI, -0.82 to -0.29]), rhinorrhea (SMD -0.47 [95% CI, -1.00 to 0.05]), nasal itching (SMD -0.42 [95% CI, -0.65 to -0.18]), sneezing (SMD -0.52 [95% CI, -0.73 to -0.32]), and quality of life mean difference -0.90 [95% CI, -1.18 to -0.62]). There was no difference in relief of ocular symptoms (SMD -0.08 [95% CI, -0.23 to 0.08]). In addition, four randomized controlled trials were included in a narrative analysis. The results in the narrative analysis were comparable with those found in the meta-analysis. CONCLUSION: INS were superior to OAs in improving nasal symptoms and quality of life in patients with AR.

Contact allergy to chlorhexidine in a tertiary dermatology clinic in Denmark.

BACKGROUND: Chlorhexidine is a widely used disinfectant in the healthcare setting and in cosmetic products. A high prevalence of chlorhexidine contact allergy was reported in Denmark in the 1980s (2.0-5.4% of patients patch tested). It is unknown whether the prevalence is still high, which products cause the contact allergy, and whether accidental re-exposure occurs in some patients. OBJECTIVES: To estimate the prevalence of chlorhexidine contact allergy in a tertiary dermatology clinic in Denmark; to investigate whether patch testing with both chlorhexidine diacetate and chlorhexidine digluconate is necessary; to investigate how many patients have combined immediate-type allergy and contact allergy; and to identify which products cause chlorhexidine contact allergy, and whether patients are accidentally re-exposed. METHODS: This was a retrospective study including all patients patch tested with chlorhexidine during 2003-2013 at the Department of Dermato-Allergology at Copenhagen University Hospital Gentofte (n = 8497). All patients with a positive patch test reaction to chlorhexidine were sent a questionnaire comprising questions about the cause of the allergy and re-exposure. RESULTS: Overall, 1.0% (n = 82) of all patients patch tested with chlorhexidine were positive. A decrease in the prevalence was observed over time, most likely because of lowering of the test concentration from 1.0 to 0.5% in 2008. Of the 82 patients, 28 (0.3%) had positive test reactions to both chlorhexidine salts, 43 (0.5%) had a positive test reaction only to chlorhexidine diacetate, and 11 (0.1%) had a positive test reaction to chlorhexidine digluconate. Three patients were both patch test-positive and prick test-positive. A known cause of the allergy was reported by 19 patients (40%) in the questionnaire: the products used in the healthcare setting were mainly reported, but some reported cosmetic products. Accidental re-exposure was reported by 15 patients (32%), of whom 13 reported symptoms. CONCLUSIONS: The prevalence of chlorhexidine contact allergy does not seem to be higher in Denmark than in other European countries. Patch testing with both chlorhexidine diacetate and chlorhexidine digluconate may be beneficial. Testing for immediate-type allergy in patients with a positive patch test reaction to chlorhexidine is recommended. Chlorhexidine-containing products used in the healthcare setting and in cosmetics are potential causes of sensitization and allergy. Re-exposure is common, highlighting the fact that patients and healthcare personnel need to be well informed about possible sources of exposure.

Chlorhexidine in cosmetic products - a market survey.

BACKGROUND: Chlorhexidine may cause type I and type IV allergy. Some chlorhexidine-allergic individuals have been exposed in the healthcare setting as patients or healthcare workers, but for others the source of sensitization is unknown. Chlorhexidine may be used as a preservative or an antimicrobial agent in cosmetic products at a concentration up to 0.3%, as set by the European Cosmetics Directive (now Regulations). OBJECTIVES: To identify cosmetic product types containing chlorhexidine, and to measure the concentration of chlorhexidine in selected products. METHODS: Between February 2013 and April 2013, we checked for chlorhexidine in cosmetic products in 14 supermarkets, one hairdressing salon and one beauty and retail store in Copenhagen, Denmark by reading the ingredient labels. The chlorhexidine concentration was measured in 10 selected products by high-performance liquid chromatography (HPLC) with an ultraviolet (UV) detector. RESULTS: Chlorhexidine was found in 80 of 2251 checked products (3.6%) in the following categories: hair products (57/760), creams (9/324), face washes (4/24), wet wipes (4/63), skin tonics (3/22), make-up removers (2/25), and mouth washes (1/17). Chlorhexidine concentrations were 0.01-0.15%. CONCLUSIONS: We found chlorhexidine in various cosmetic product types, predominantly aimed at females, and in hair products. The measured chlorhexidine concentrations were all within the permitted limit. The relevance for allergic sensitization should be further explored.

Methylisothiazolinone contact allergy--growing epidemic.

BACKGROUND: The prevalence of contact allergy to the isothiazolinone preservative methylchloroisothiazolinone (MCI) in combination with methylisothiazolinone (MI) and MI alone has increased in the last couple of years. OBJECTIVES: To investigate the prevalence of contact allergy to MI, MCI/MI and benzisothiazolinone (BIT) among patch tested patients at Gentofte Hospital, as well as the use of MI in cosmetic products. METHODS: Patients patch tested with either MI, MCI/MI or BIT from 2010 to 2012 were included in the study. The MOAHLFA index was registered in all patch tested patients, and relevant exposures were determined in patients with an isothiazolinone allergy. In a market survey, the ingredient labels of cosmetic products were investigated for MI content. RESULTS: The prevalence of MI and MCI/MI contact allergy increased significantly from 2010 to 2012: from 2.0% to 3.7% for MI (n = 2766), and from 1.0% to 2.4% for MCI/MI (n = 2802). MI-allergic patients had occupational, hand and face dermatitis significantly more often, and were aged > 40 years. Cosmetics were the most common substances causing relevant exposure found in both MCI/MI-allergic and MI-allergic patients. MI was found in 3.3% of cosmetics on the Danish retail market. CONCLUSIONS: The increase in MI contact allergy is alarming, and urgent action is needed.