Feeding of a fat-enriched diet causes the loss of resistance to contact hypersensitivity.

BACKGROUND: Low-molecular weight chemicals or metal ions can cause allergic contact dermatitis, an inflammatory skin disease. Mice lacking Toll-like receptors 2 and 4 (TLR2/4 mice) are resistant to contact hypersensitivity (CHS). In the Western population obesity is increasing, which is known to have a proinflammatory impact. OBJECTIVES: The aim of this study was to investigate the impact of a high-fat diet (HFD) on the sensitization and elicitation of CHS. We hypothesized that a proinflammatory micromilieu can be caused by an increase in adipose tissue, which might be sufficient to break the resistance of TLR2/4 mice. METHODS: Four weeks prior to sensitization, wild-type (wt) or TLR2/4 mice were fed normal chow (NC), control diet (CD), or HFD. The effects on CHS and inflammation were analysed by measuring the ear swelling response, using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The reaction of wt mice to 2,4,6-trinitro-1-chlorobenzene (TNCB) was increased by HFD. While NC-fed TLR2/4 mice were still resistant to CHS, HFD and, unexpectedly, CD feeding broke the resistance of TLR2/4 mice to TNCB. CONCLUSIONS: These experiments suggest that the increased fat content or the different fatty acid composition of the diets increases inflammation and, therefore, the likelihood of developing CHS.

Mutations in 3ß-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3ß-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3ß-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

Effectiveness of Support Groups for Patients With Contact Dermatitis: A Pilot Study.

BACKGROUND: Contact dermatitis can be difficult to manage and overwhelming for patients, often requiring significant lifestyle changes. OBJECTIVE: The aim of the study was to investigate whether a contact dermatitis support group could help patients find community and learn from others who share similar experiences. METHODS: Hour-long, monthly support group meetings facilitated by a social worker, research fellows, and a faculty dermatologist were held for approximately 1.5 years. A 32-question, cross-sectional survey was administered to assess perception of contact dermatitis and overall usefulness of the group. RESULTS: Between 2 and 5 patients attended each group session; 9 participants completed the survey. Most were female (77.8%) and white (77.8%), with an average age of 68.8 years. Eight participants (88.9%) reported that it was important or somewhat important to socialize with others affected by contact dermatitis. Three group members (33.3%) had met with attendees outside of the monthly sessions. The majority (77.8%) reported that the support group had a positive effect on their understanding of contact dermatitis and would recommend the group to others (88.9%). CONCLUSIONS: Support groups may be helpful for patients learning to cope with the challenges associated with contact dermatitis. Although preliminary feedback is promising, further investigation is warranted to determine whether these groups are effective on a larger scale.

Allergic contact dermatitis: From pathophysiology to development of new preventive strategies.

As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a significant public health burden. Among skin disorders, allergic contact dermatitis (ACD) is the most prevalent occupational disease and the most common form of immunotoxicity in humans. ACD is a T-cell-mediated skin inflammation resulting from the priming and expansion of allergen-specific CD4+ and CD8+ T cells. The clinical condition is characterized by local skin rash, itchiness, redness, swelling, and lesions, being mainly diagnosed by the patch test. Upon ACD diagnosis, avoiding the exposure to the triggering allergen is the mainstay of treatment to prevent future flares. In cases where avoidance is not possible, the use of a standard of care interim treatments such as steroid creams or ointments, barrier creams, and moisturizers are strongly recommended to alleviate symptoms. In this review, we sought to provide the reader with an overview of the pathophysiology of ACD as well as the currently available pharmacological treatment options. Furthermore, a comprehensive outline of several preventive strategies is also provided.

A Case Report on Stomatitis Venenata Due to the Use of Lip Balm.

INTRODUCTION: Allergic reactions can manifest in various forms ranging from mild, almost unnoticeable reactions to life threatening anaphylaxis. Stomatitis venenata or contact stomatitis is described as a contact allergy of the oral mucosa which can occur due to repeated contact with the causative agent. Dental and cosmetic products, dental materials and dental therapeutic agents are the common allergens of the oral cavity. These allergies show varied clinical presentations, from swelling, pain, burning sensations to vesiculation, ulcerations, crusting and sloughing. Contact stomatitis due to cosmetic products have been on a rise recently due to the ease of availability and increase in their usage among individuals. AIM: The aim of this article is to present a case reports on an allergic reaction in a 17-year-old female triggered by the use of cosmetics. CASE REPORT: In the present article, we report a case of stomatitis venenata due to lip balm in a 17-year-old female for its rarity. CONCLUSION: Stomatitis venenata is a rare allergic condition that causes significant morbidity in an affected individual. Prompt recognition and elimination of the causative allergen followed by an appropriate therapy would help in complete resolution of this condition.

Alcohol-Related Dermatitis: A Review.

: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Oral provocation of patients allergic to sesquiterpene lactones with German chamomile tea to demonstrate possible systemic allergic dermatitis.

BACKGROUND: Most patients with contact allergy to Asteraceae plants are patch test positive to sesquiterpene lactone mix (SLM). There are several reports among these patients of a flare-up of hand eczema after ingestion of food and beverages originating from Asteraceae plants. AIM: To investigate whether German chamomile tea can elicit systemic allergic dermatitis. PATIENTS AND METHODS: Individuals with or without contact allergy to SLM were patch tested with an extract of German chamomile tea. Six weeks later, they were provoked with capsules containing either freeze-dried German chamomile tea or placebo capsules containing lactose, in a double-blind, randomized study. A numerical rating scale (NRS) was used to ascertain the volunteers' opinion of their hand eczema status. The study individuals were examined to detect a possible flare-up of healed patch test reactions to chamomile. RESULTS: None of the subjects had a flare-up of healed patch test reactions. According to the NRS, SLM-positive individuals experienced a significant worsening of hand eczema, independently of whether they received chamomile or lactose capsules. CONCLUSION: No evidence suggestive of systemic allergic dermatitis was found.

Proinflammatory and regulatory mechanisms in allergic contact dermatitis caused by methylchloroisothiazolinone and methylisothiazolinone.

BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the cause of an increasing number of contact allergies. Understanding the mechanisms by which MCI/MI induces proinflammatory and regulatory factors production is necessary to understand the outcome of allergic contact dermatitis (ACD). OBJECTIVES: To evaluate the dysfunction of proinflammatory cytokines and regulatory factors in the positive MCI/MI patch test at the transcriptional and protein expression levels. Moreover, to analyse the cytokines production induced by MI in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: The selected patients had positive MCI/MI patch test results. The expression of proinflammatory factors was evaluated by q-PCR and immunochemistry at 48 hours of positive MCI/MI patch test. The MCI/MI- or MI- induced secretion of IL-1ß, TNF and IL-6 by PBMC was analysed by flow cytometry. RESULTS: The results showed a decreased TLR4 expression with upregulated IL6, FOXP3, IL10 and TGFß mRNA expression as assessed by q-PCR at the site of the MCI/MI skin reaction. We detected increased protein levels of TLR4, FOXP3 and IL-10 in the dermis layer in the ACD reaction by immunocitochemistry. Moreover, MCI/MI induced proinflammatory cytokine production by PBMC through the NF-κB signalling pathway. CONCLUSION: Considering the altered innate immune response triggered by MCI/MI sensitization, these findings indicate that the regulatory process at the induction phase of ACD is a crucial mechanism. Given the increase in occupational and domestic exposure to MCI/MI, the underlying immunological mechanisms should be understood.

Validating Responsiveness of a Quality-of-Life Instrument for Allergic Contact Dermatitis.

BACKGROUND: Although many generic dermatological quality-of-life (QoL) instruments exist, none have been specifically designed for patients with allergic contact dermatitis (ACD). In the preceding publication-Validating a Quality-of-Life Instrument for Allergic Contact Dermatitis-we developed and validated a QoL instrument specific to the ACD population. OBJECTIVE: The aim of this study was to assess whether this ACD-specific QoL instrument appropriately captures change in QoL after patch testing in ACD patients. METHODS: One hundred individuals completed the previously validated 17-item QoL survey plus 2 global questions and the Skindex-29 before patch testing. Two months after patch testing and allergen avoidance, the participants repeated the same questionnaires. We used statistical methods to evaluate the capacity of the ACD questionnaire to measure change in QoL in comparison with the Skindex-29. CONCLUSIONS: The novel ACD-specific questionnaire was more sensitive to change in QoL than the generic Skindex-29. Eleven of the original 17 items were found to capture change in QoL, and of the 3 domains (emotions, symptoms, functioning), the emotional aspect of the disease was most burdensome and responsive to change 2 months after patch testing. Providers can reliably use this index to assess changes in QoL over time.

Foot allergic contact dermatitis to mixed dialkyl thioureas.

A 12-year-old boy presented with severe, bilateral foot dermatitis. Extended patch testing was performed, revealing a significant positive reaction to mixed dialkyl thioureas. A thorough review of his history revealed that he was likely being exposed through his neoprene taekwondo shoes. After implementation of allergen avoidance measures, his dermatitis resolved. This case emphasizes awareness of potential allergen exposures and offers helpful avoidance strategies.

Alternative skin sensitization prediction and risk assessment using proinflammatory biomarkers, interleukin-1 beta (IL-1ß) and inducible nitric oxide synthase (iNOS).

As an alternative to animal tests for skin sensitization potency and risk assessment, cell viability and biomarkers related to skin sensitization were analyzed in THP-1 human monocytic leukemia cells. Cell viabilities of 90% (CV90) and 75% (CV75) were determined for 24 selected test chemicals. Further biomarkers related to skin sensitization were also determined under equivalent comparative conditions. In cell viability analyses, potent skin sensitizers exhibited high cytotoxicity, but non-sensitizers did not display this tendency. In biomarker analyses, interleukin-I beta (IL-1ß), inducible nitric oxide synthase (iNOS), IL-1ß+iNOS, and THP-1 IL-1ß+Raw 264.7 IL-1ß were found to be suitable for prediction of skin sensitization potency following classification as either skin sensitizers or non-sensitizers (accuracies of 91.7%, 87.5%, 83.3%, and 82.6%, respectively). A significant positive correlation was found between biomarkers and skin sensitization potency, with a correlation coefficient (R) of 0.7 or more (correlation coefficients of 0.77, 0.72, 0.7, and 0.84, respectively). Finally, the skin sensitization potency effective threefold concentration (EC) 3% was predicted using a biomarker equation, with resulting prediction rates (match rate with actual data) of 58.3%, 54.2%, 62.5%, and 60.9%, respectively. The prediction accuracy for the EC3 value obtained from animal data was calculated as 83.3%, 79.2%, 79.2%, and 73.9%, respectively. Thus, these biomarkers, IL-1ß and iNOS, may be alternatively used to predict skin sensitization potency and risk assessment.

CCL2/CCR2 signaling elicits itch- and pain-like behavior in a murine model of allergic contact dermatitis.

Spontaneous itch and pain are the most common symptoms in various skin diseases, including allergic contact dermatitis (ACD). The chemokine (C-C motif) ligand 2 (CCL2, also referred to as monocyte chemoattractant protein 1 (MCP-1)) and its receptor CCR2 are involved in the pathophysiology of ACD, but little is known of the role of CCL2/CCR2 for the itch- and pain-behaviors accompanying the murine model of this disorder, termed contact hypersensitivity (CHS). C57BL/6 mice previously sensitized to the hapten, squaric acid dibutyl ester, applied to the abdomen were subsequently challenged twice with the hapten delivered to either the cheek or to the hairy skin of the hind paw resulting in CHS at that site. By 24 h after the 2nd challenge to the hind paw CCL2 and CCR2 mRNA, protein, and signaling activity were upregulated in the dorsal root ganglion (DRG). Calcium imaging and whole-cell current-clamp recordings revealed that CCL2 directly acted on its neuronal receptor, CCR2 to activate a subset of small-diameter, nociceptive-like DRG neurons retrogradely labeled from the CHS site. Intradermal injection of CCL2 into the site of CHS on the cheek evoked site-directed itch- and pain-like behaviors which could be attenuated by prior delivery of an antagonist of CCR2. In contrast, CCL2 failed to elicit either type of behavior in control mice. Results are consistent with the hypothesis that CHS upregulates CCL2/CCR2 signaling in a subpopulation of cutaneous small diameter DRG neurons and that CCL2 can activate these neurons through neuronal CCR2 to elicit itch- and pain-behavior. Targeting the CCL2/CCR2 signaling might be beneficial for the treatment of the itch and pain sensations accompanying ACD in humans.

Allergic contact dermatitis to chlorhexidine in pediatric patients.

Chlorhexidine is one of the most widely used antiseptics in our environment. Allergic contact dermatitis to chlorhexidine is common in adults, but is quite rare in the pediatric population. Its diagnosis is important because it can mimic other dermatoses common during childhood, and it can also lead to acute immediate hypersensitivity reactions following successive exposures.

Evaluation of positive patch test reactions using optical coherence tomography: A pilot study.

INTRODUCTION: Patch testing is the gold standard for evaluating allergic contact dermatitis (ACD), yet current interpretation methods are limited by their subjectivity and possible variability between observers. Optical coherence tomography (OCT) imaging enables noninvasive in vivo skin visualization and holds promise as an objective method of patch test interpretation. OBJECTIVE: To evaluate the micromorphological changes of patch test reactions and identify objective, quantitative OCT markers that correlate with clinically graded patch test reactions. RESULTS: A total of 25 patch test reactions (7 grade-0, 4 grade-1+, 14 grade-2+) from 7 patients underwent OCT evaluation. Increased epidermal thickness and density was qualitatively observed in grade 1+ and grade 2+ allergic reactions while well-demarcated, signal-free cavities were observed in all grade 2+ reactions. Attenuation coefficients significantly increased across the three reaction grades (2.58 ± 0.092, 2.96 ± 0.121, 3.05 ± 0.065; P < 0.01). Cutaneous blood flow at 0.35 mm monotonically increased with reaction grade severity and blood measurements significantly differed across the three reaction grades (0.053 ± 0.011 mm/s, 0.078 ± 0.015 mm/s, and 0.121 ± 0.008 mm/s; P < 0.01). CONCLUSIONS AND RELEVANCE: Attenuation coefficient and cutaneous blood flow at 0.35 mm correlate with clinically graded patch test reactions and hold promise as objective, quantitative markers. OCT may help dermatologists differentiate clinical scoring of allergic reactions in patch test and thereby improve their diagnostic accuracy and interpretation of patch test reactions.

Experience in patch testing: A 6-year retrospective review from a single academic allergy practice.

BACKGROUND: Patch testing is the "gold standard" to identify culprit allergen(s) causing allergic contact dermatitis (ACD), but there are limited studies of patch testing from allergy practice settings. OBJECTIVE: We sought to explore patch test findings in a large academic allergy practice, including patch testing results, history of atopy, location of dermatitis, and referral source. We also wanted to determine whether patch testing using an extended panel, such as the North American screening series, compared with a limited series, such as the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) Test, increased the sensitivity. METHODS: A retrospective chart review was conducted of patients referred for patch testing over a 6-year period. RESULTS: A total of 585 patients (mean age 48.7 years, 71.6 % female) underwent patch testing over the 6-year period, of which 369 (63%) had a positive test. Of those who tested positive, 202 (55%) reported a history of atopy. The extremities were the most commonly involved site, followed by the head/neck and trunk. The 5 most common positive allergens were nickel sulfate, gold sodium thiosulfate, methylchloroisothiazolinone, thimerosal, and bacitracin. Three hundred fourteen (53.6%) patients were positive to at least 1 allergen on TRUE testing. Extended screening series identified an additional 10.8% of patients with positive tests who were negative to T.R.U.E. test allergens. CONCLUSION: Patch testing is a valuable diagnostic tool for the practicing allergist and provides early identification of culprit allergens in ACD. Performing an extended screening series such as the North American Contact Dermatitis Group (NACDG) or supplemental panel of allergens increased sensitivity when compared with a limited series.

Retrospective review of insurance coverage for patch testing.

BACKGROUND: There is a paucity of data on the burden of insurance limitations for patients undergoing patch testing. OBJECTIVE: To characterize the burden of insurance limitations and its impact on differences in management and execution of patch testing. METHODS: A retrospective chart review was performed on patients with a diagnosis of contact dermatitis (International Classification of Disease [ICD], Ninth Edition, code ICD 692) who received patch testing (Current Procedural Terminology code 95044) at the George Washington Medical Faculty Associates Dermatology Clinic between January 1, 2015 and June 30, 2017. Variables including allergen limitations were compared between government-sponsored insurance and private insurance providers (eg, Insurers A, B, C, and D). RESULTS: A total of 371 records were identified. Government-sponsored insurance patients encountered allergen limitations more frequently than private insurance patients (86.8% vs 14.2%, P < .0001). Insurer C and D patients were least likely to encounter allergen limitations (1.2% vs 0%, P < .0001) and were tested to the most allergens (mean = 146 vs 152, P < .0001). Insurer A patients had the least allergens tested among those privately insured. CONCLUSION: Considering modification of insurance policies to allow patch testing with a larger number of allergens without restrictions is needed, with the goal of improving quality of life of these patients while saving costs from chronic use of topical corticosteroids.