Age-related differences in patch testing results among children: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

BACKGROUND: An updated understanding of allergic contact dermatitis is needed, particularly in children. OBJECTIVES: To compare positive and clinically relevant reactions in children versus adults referred for patch testing. METHODS: Retrospective analysis of 1871 children and 41,699 adults from the North American Contact Dermatitis Group (NACDG) from 2001-2018. RESULTS: Both final diagnosis of allergic contact dermatitis (55.2% versus 57.3%; chi square, P = .0716) and prevalence of ≥ 1 currently relevant reaction to a NACDG screening allergen (49.2% vs 52.2%; P = .1178) were similar between children and adults. Currently in children, the most common relevant allergens were nickel sulfate (17.3%), hydroperoxides of linalool (7.8%), methylisothiazolinone (7.7%), cobalt chloride (7.0%), and fragrance mix I (4.9%). Approximately a fifth of children had a positive reaction to a non-NACDG allergen. CONCLUSION: Over half of children referred for patch testing were diagnosed with allergic contact dermatitis. The most common relevant allergens in children were nickel sulfate, cobalt chloride, and hydroperoxides of linalool. Twenty percent of children had at least 1 positive reaction to allergens/substances not on the NACDG screening series, underscoring the need for comprehensive testing.

Hand dermatitis in adults referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2000 to 2016.

BACKGROUND: Hand eczema (HE) is a heterogeneous and burdensome disorder. OBJECTIVE: To characterize the clinical characteristics, etiologies and allergen relevance in adults with HE referred for patch testing. METHODS: Retrospective analysis (2000-2016) of North American Contact Dermatitis Group data (n = 37,113). RESULTS: Overall, 10,034 patients had HE, with differences of overlap between allergic contact, irritant contact, and atopic dermatitis. Allergic contact HE fluctuated, whereas atopic HE steadily increased, and irritant HE decreased over time. HE was associated with higher proportions of positive patch tests (67.5% vs 63.8%; χ2, P < .0001). The five most common clinically relevant allergens were methylisothiazolinone, nickel, formaldehyde, quaternium-15, and fragrance mix I. HE was associated with significantly higher odds of positive patch test reactions and clinical relevance in 13 and 16 of the 25 most common allergens, respectively, including preservatives, metals, topical medications, and rubber accelerators. LIMITATIONS: No data on HE phenotype. CONCLUSION: HE in adults was associated with higher proportions of positive patch tests, with a heterogeneous profile of allergens. Patch testing remains an important tool in the evaluation of patients with HE.

Eyelid dermatitis in patients referred for patch testing: Retrospective analysis of North American Contact Dermatitis Group data, 1994-2016.

BACKGROUND: Eyelid dermatitis is a common dermatologic complaint. OBJECTIVE: To characterize patients with eyelid dermatitis. METHODS: Retrospective analysis (1994-2016) of North American Contact Dermatitis Group data. RESULTS: Of 50,795 patients, 2332 (4.6%) had eyelid dermatitis only, whereas 1623 (3.2%) also had dermatitis of the eyelids and head or neck. Compared with patients without eyelid involvement (n = 26,130), groups with eyelid dermatitis only and dermatitis of the eyelid and head or neck were significantly more likely to be female, white, and older than 40 years, and to have a history of hay fever, atopic dermatitis, or both (P < .01). Final primary diagnoses included allergic contact dermatitis (eyelid dermatitis only: 43.4%; dermatitis of the eyelid and head or neck: 53.5%), irritant contact dermatitis (eyelid dermatitis only: 17.0%; dermatitis of the eyelid and head or neck: 9.8%), and atopic dermatitis (eyelid dermatitis only: 13.1%; dermatitis of the eyelid and head or neck: 13.8%). Top 5 currently relevant allergens included nickel sulfate (eyelid dermatitis only: 18.6%; dermatitis of the eyelid and head or neck: 22.5%), fragrance mix I (eyelid dermatitis only: 16.5%; dermatitis of the eyelid and head or neck: 18.3%), methylisothiazolinone (eyelid dermatitis only: 16.5%; dermatitis of the eyelid and head or neck: 17.7%), gold sodium thiosulfate (eyelid dermatitis only: 14.7%; dermatitis of the eyelid and head or neck: 11.4%), and balsam of Peru (eyelid dermatitis only: 11.9%; dermatitis of the eyelid and head or neck: 12.6%). Both eyelid-involvement groups were significantly more likely to react to gold sodium thiosulfate, carmine, shellac, dimethylaminopropylamine, oleamidopropyl dimethylamine, and thimerosal (P < .05) compared with the no eyelid involvement group. LIMITATIONS: Lack of specific distribution patterns of eyelid dermatitis and no long-term follow-up data. CONCLUSION: Patch testing remains a critical tool in evaluating patients with eyelid dermatitis.

Contact dermatitis associated with preservatives: Retrospective analysis of North American Contact Dermatitis Group data, 1994 through 2016.

BACKGROUND: Preservatives are often necessary components of commercial products. Large-scale North American studies on preservative allergy are limited. OBJECTIVE: To evaluate demographics, positive patch test reactions (PPTRs), clinical relevance, and trends for preservatives tested by the North American Contact Dermatitis Group. METHODS: We conducted a retrospective cross-sectional analysis of North American Contact Dermatitis Group patch testing results of preservatives from 1994 through 2016. RESULTS: A total of 50,799 patients were tested; 11,338 (22.3%) had a PPTR to at least 1 preservative. The most frequent reactions were to methylisothiazolinone 0.2% aqueous (aq) (12.2%), formaldehyde 2% aq (7.8%), formaldehyde 1% aq (7.8%), quaternium-15 2% petrolatum (pet) (7.7%), and methyldibromo glutaronitrile/phenoxyethanol 2% pet (5.1%). Paraben mix 12% pet (1%), iodopropynyl butylcarbamate 0.1% pet (0.4%), benzyl alcohol 1% pet (0.3%), and phenoxyethanol 1% pet (0.2%) had the lowest PPTRs. Linear regression analysis of preservatives tested showed that only methylchloroisothiazolinone/methylisothiazolinone 0.01% aq (parameter estimate, 0.42; 95% CI, 0.17-0.66; P < .005) had a significant increase in PPTRs over time. LIMITATIONS: Collected variables are dependent on clinical judgment. Results may be prone to referral selection bias. CONCLUSIONS: This large North American study provides insight on preservative PPTRs and trends from 1994 through 2016.

Prevalence and trend of allergen sensitization in patients with nummular (discoid) eczema referred for patch testing: North American Contact Dermatitis Group data, 2001-2016.

BACKGROUND: Few studies have examined the relationship between nummular (discoid) eczema (NE) and allergic contact dermatitis (ACD). OBJECTIVE: To examine trends, associations, and clinical relevance of ACD in patients with NE who were referred for patch testing. METHODS: Retrospective analysis of 38 723 patients from the North American Contact Dermatitis Group. RESULTS: Overall, 748 patients (1.9%) were diagnosed with NE; 23.9% had a concomitant diagnosis of ACD. The prevalence of NE fluctuated over time between 2001 and 2016, with no overall change in prevalence in diagnosed NE. In multivariable logistic regression models, NE increased steadily with age and was associated with male sex and Asian and other race/ethnicity, and inversely associated with a history of atopic dermatitis (AD) and hay fever. Patients with NE had lower proportions of one or more positive allergic reactions and lower odds of a positive reaction in multiple individual allergens. The most commonly relevant allergens in patients with NE were formaldehyde 2.0% aq., methylisothiazolinone, quaternium 15, fragrance mix I, and propylene glycol. CONCLUSION: NE is a heterogeneous disorder with distinct subsets of lesional distributions and a profile of relevant allergens, especially formaldehyde and formaldehyde releasers. Nearly one in four patients with NE had ACD, supporting the role of patch testing in patients with NE.

Prevalence and trend of allergen sensitization in patients referred for patch testing with a final diagnosis of psoriasis: North American Contact Dermatitis Group data, 2001-2016.

BACKGROUND: Little is known about the relationship between psoriasis and allergic contact dermatitis (ACD). OBJECTIVE: To examine the associations with ACD, related clinical characteristics, and common positive and clinically relevant allergens of patients with a final diagnosis of psoriasis who were referred for patch testing. METHODS: Retrospective analysis of 38 723 patients from the North American Contact Dermatitis Group. RESULTS: Patients with a final diagnosis of psoriasis had lower proportions of ACD than those without psoriasis (32.7% vs 57.8%). In multivariable logistic regression models, psoriasis was inversely associated with female sex, Black or Asian race, and history of atopic dermatitis and hay fever. Patients with a final diagnosis of psoriasis were less likely to have one or more positive allergic patch-test reactions or to have a current clinically relevant patch-test reaction to the majority of the most commonly positive and/or relevant allergens. The most clinically relevant allergens included nickel sulfate, methylisothiazolinone, and fragrance mix I. CONCLUSION: Approximately one-third of patients who were referred for patch testing with a final diagnosis of psoriasis were also diagnosed with ACD. In select patients with suspected psoriasis who also have a clinical presentation suggestive of ACD, patch testing may be helpful.

Epidemiology of nickel sensitivity: Retrospective cross-sectional analysis of North American Contact Dermatitis Group data 1994-2014.

BACKGROUND: Nickel is a common allergen. OBJECTIVE: To examine the epidemiology of nickel sensitivity in North America. METHODS: Retrospective, cross-sectional analysis of 44,097 patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. Nickel sensitivity was defined as a positive patch test for nickel. We evaluated the frequency of nickel sensitivity and patient demographics. For each positive reaction to nickel, we tabulated clinical relevance, occupational relatedness, and exposure sources. RESULTS: The average frequency of nickel sensitivity was 17.5% (1994-2014). Nickel sensitivity significantly increased over time (from 14.3% in 1994-1996 to 20.1% in 2013-2014 [P < .0001]). Nickel-sensitive patients were significantly more likely to be female, young, nonwhite, and atopic (have eczema and asthma) and/or have dermatitis affecting the face, scalp, ears, neck, arm, or trunk (P values ≤ .0474). Overall, 55.5% of reactions were currently clinically relevant; this percentage significantly increased over time (from 44.1% in 1994-1996 to 51.6% in 2013-2014 [P < .0001]). The rate of occupational relatedness was 3.7% overall, with a significant decrease over time (from 7.9% in 1994-1996 to 1.9% in 2013-2014 [P < .0001]). Jewelry was the most common source of nickel contact. LIMITATIONS: Tertiary referral population. CONCLUSIONS: Nickel allergy is of substantial public health importance in North America. The frequency of nickel sensitivity in patients referred for patch testing has significantly increased over a 20-year period.

Patients with negative patch tests: Retrospective analysis of North American Contact Dermatitis Group (NACDG) data 2001-2016.

BACKGROUND: Little is known regarding the characteristics of patients with negative patch test (NPT) results. OBJECTIVE: To characterize patients with NPT results. METHODS: Retrospective cross-sectional analysis of 34,822 patch tested patients. NPT results were defined as negative or irritant final interpretations of all North American Contact Dermatitis Group screening allergens and no relevant allergens on supplemental series. RESULTS: Almost one-third of patients (n = 10,888 [31.3%]) had NPT results. Patients with NPT results were significantly more likely to be male (P < .0001), be age 40 years or younger (P = .0054), be nonwhite (P = .0005), and have dermatitis primarily having a scattered generalized distribution (P = .0007) or primarily located on the lips (P = .0214) or eyelids (P = .0364). However, the absolute differences in age, race, and site were small and may not be clinically meaningful. Patients with NPT results were significantly less likely to have occupationally related skin disease (P < .0001). Overall, 8.3% of patients with NPT results had occupationally related skin disease, with precision production worker/machine operator (28.5%), health care worker (17.0%), and mechanic/repairer (7.5%) being the most commonly related occupations. In all, 22.9% of patients with NPT results had relevant irritants and 41.6% of irritants were occupationally related; cosmetics/health care products and soaps were common sources for both occupationally related and non-occupationally related irritants. LIMITATIONS: Retrospective cross-sectional study of tertiary referral population. CONCLUSIONS: Patients with NPT results have distinct characteristics.

Epidemiology of pediatric nickel sensitivity: Retrospective review of North American Contact Dermatitis Group (NACDG) data 1994-2014.

BACKGROUND: Nickel is a common allergen responsible for allergic contact dermatitis. OBJECTIVE: To characterize nickel sensitivity in children and compare pediatric cohorts (≤5, 6-12, and 13-18 years). METHODS: Retrospective, cross-sectional analysis of 1894 pediatric patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. We evaluated demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources. RESULTS: The frequency of nickel sensitivity was 23.7%. Children with nickel sensitivity were significantly less likely to be male (P < .0001; relative risk, 0.63; 95% confidence interval, 0.52-0.75) or have a history of allergic rhinitis (P = .0017; relative risk, 0.74; 95% confidence interval, 0.61-0.90) compared with those who were not nickel sensitive. In the nickel-sensitive cohort, the relative proportion of boys declined with age (44.8% for age ≤5, 36.6% for age 6-12, and 22.6% for age 13-18 years). The most common body site distribution for all age groups sensitive to nickel was scattered/generalized, indicating widespread dermatitis. Jewelry was the most common source associated with nickel sensitivity (36.4%). LIMITATIONS: As a cross-sectional study, no long-term follow-up was available. CONCLUSIONS: Nickel sensitivity in children was common; the frequency was significantly higher in girls than in boys. Overall, sensitivity decreased with age. The most common source of nickel was jewelry.

Chlorine Dioxide Complex Cleanser: A New Agent With Rapid Efficacy for Keratosis Pilaris.

Chlorine dioxide complex™ is a new molecule to dermatology that is a unique, non-toxic, broad spectrum anti-microbial and keratolytic compound. Chlorine dioxide has been used as an antiseptic in industrial settings for decades, primarily in water treatment facilities for municipal water supplies and food preparation. The compound has exceptional antiseptic properties with no known potential for development of resistance. It is a true keratolytic and anti-inflammatory, but is non-toxic to human tissue due to its unique mechanism of action. Chlorine dioxide's use in consumer products was previously limited because it is inherently an unstable molecule that had to be used quickly after it was produced. However, the recent development of a complexed form of chlorine dioxide that retains its antimicrobial and keratolytic activity has allowed the development of products (AsepticMD, Aseptic Plus, Nashville, TN) that take advantage of the properties of this unique molecule. Here we report a case series demonstrating its efficacy as a cleanser in keratosis pilaris. J Drugs Dermatol. 2018;17(5):554-556.

Anti-Pruritic Efficacy of Itch Relief Lotion and Cream in Patients With Atopic History: Comparison With Hydrocortisone Cream.

Objective: To evaluate the speed of onset and duration of relief of two ceramide-containing formulations with 1% pramoxine hydroxide (CeraVe® Itch Relief Lotion and Cream,Valeant Pharmaceuticals North America LLC, Irvine, CA) in patients with atopic history, including those with active flare and the comparative efficacy of CeraVe Itch Relief Cream to hydrocortisone 1% cream and night-time itch relief with continued use. METHODS: Two double-blind, split-body, randomized studies in 66 male and female subjects, ages 11+ years, with history of atopic dermatitis (AD). Itch severity was assessed on a 10-point scale (where 0=none and 7-9=severe). Study one: single applications of ceramide-containing lotion or cream incorporating 1% pramoxine hydrochloride applied to opposite sides of the body. Study two (part 1): single application of ceramide-containing cream or hydrocortisone 1% cream. Study two (part 2): ceramide-containing pramoxine cream applied up to 4 times in a 24-hour period, over the course of 6 days. Itch relief assessed at baseline, 2, and 5 minutes, 1 (2 in study two), 4, and 8 hours post-application. Efficacy and aesthetic attributes were assessed at the same timepoints. Clinical evaluation of performance and mildness of the ceramide-containing 1% pramoxine hydrochloride cream at day 6 (study two, part 2). RESULTS: Study one: Relief of itching was rapid and long-lasting with significant reductions in severity after 2 minutes, and continued improvement over the 8 hour test period (P less than .001 versus baseline at all timepoints). Mean itch severity scores reduced progressively from 6 (moderate) at baseline to 1-2 (mild) after 8 hours, with all patients experiencing relief from itching. Rapid and long-lasting relief to dry, itchy, irritated skin was confirmed through patient self-assessment. Both lotion and cream formulations were non-greasy, absorbed quickly and easily, and were non-irritating. Study two: Ceramide-containing cream incorporating 1% pramoxine hydrochloride provided comparable improvement in itch relief (24.6% reduction in mean itch severity 2 minutes post-application, and 58.0% reduction 8 hours post-application) compared to hydrocortisone cream 1% (18.5% reduction and 59.7% reduction, respectively). Daily use of the ceramide-containing 1% pramoxine cream over 6-days provided all-night relief (87.5% agreement), and perception of skin looking and feeling healthier with each use (71.9% and 81.3% agreement, respectively). LIMITATIONS: Results of study one and subsequent comparative study with hydrocortisone 1% cream are based on a single application. There were no placebo controls. CONCLUSIONS: Ceramide-containing lotion or cream containing 1% pramoxine provides both rapid and long-lasting relief of itching following a single application in atopic patients with or without active flare. Both formulations were well tolerated with aesthetic appeal. Comparable itch relief to hydrocortisone 1% cream was seen with the ceramide-containing cream over an 8-hour period following a single application. Further ceramide-containing 1% pramoxine hydrochloride cream was well tolerated with continued use over 6 days, delivering comfort and all-night relief for patients with atopic history suffering from reoccurrant itching.

J Drugs Dermatol. 2017;16(3):243-247.

A Novel Multifactorial Approach to Developing Mild Laundry Detergents and Assessing Their Relative Mildness

INTRODUCTION: Dermatologists are becoming more aware of the irritant and allergic potential of laundry detergents that incorporate harsh surfactants and potentially sensitizing ingredients. It is difficult however for the physician to distinguish one laundry detergent from another because the only distinguishing feature advertised tends to be the lack of dyes and fragrances. DESIGN: A new objective method was developed for measuring the harshness of laundry detergents using a three-pronged laboratory testing approach consisting of zein, corneosurfametry, and cytokine testing. Combing these methods, a Detergent Mildness Index was created which conveniently provides a single value by which products can be compared. RESULTS: A new mild laundry detergent was formulated with ingredients carefully selected by dermatologists who are experts in con-tact dermatitis. The irritancy potential of the formula was measured using the Detergent mildness index score. Compared to 11 other commercial laundry detergents marketed for sensitive skin, the new formula is measurably the mildest formula. DISCUSSION: The Detergent Mildness Index provides dermatologists with an objective method to compare commercial laundry deter-gents. Currently the only method available is patch testing, this new test is able to more finely differentiate between products and thus enables more informed recommendations on laundry detergent choices for their patients with sensitive skin.

Potential role of reduced environmental UV exposure as a driver of the current epidemic of atopic dermatitis.

The basis for the sudden and dramatic increase in atopic dermatitis (AD) and related atopic diseases in the second half of the 20th century is unclear. The hygiene hypothesis proposes that the transition from rural to urban living leads to reduced childhood exposure to pathogenic microorganisms. Hence instead of having the normal TH1 bias and immune tolerance because of repeated exposure to pathogens, urban dwellers have TH2 cell immune activity and atopic disease in a more sterile environment. Various other environmental exposures have been implicated in the explosion of AD (and atopic disorders in general), including breast-feeding, tobacco smoking, alcohol consumption, and exposure to domesticated furry pets. Notably, the key role of a compromised barrier of neonatal skin as a predisposing factor in the development of childhood AD has recently been demonstrated. In this article we review the salubrious effects of suberythemogenic doses of UVB irradiation for the skin barrier. We then discuss how the lack of sufficient UVB exposure could have contributed to the rapid increase in the incidence of AD in developed countries. This hypothesis offers a separate but not competing partial explanation, which should be viewed as not discounting the role of the etiopathogenic factors that also could influence the prevalence of atopic disorders.

Onychomycosis: epidemiology, diagnosis, and treatment in a changing landscape.

Onychomycosis is an often overlooked and/or undertreated disease. This may be in part due to an under appreciation among both physicians and patients of its impact on quality of life and the potential for significant complications, from tinea corporis and cruris, to bacterial superinfection. Some health care providers are unaware of the effective low-risk treatments currently available. Changing demographic characteristics such as the relative aging of the population; the increasing prevalence of diabetes and peripheral vascular disease, and widespread iatrogenic immunosuppression; and changes in lifestyle practices such as earlier and greater participation in sports, are likely to lead to an increased prevalence of onychomycosis in both adults and children. Two topical onychomycosis treatments, efinaconazole 10% solution, and tavaborole 5% solution were recently approved by the FDA. This article reviews the state of knowledge and describes, briefly, these new treatment options.

Systemic contact dermatitis to foods: nickel, BOP, and more.

Systemic contact dermatitis (SCD), a cutaneous reaction that is a direct manifestation of systemic exposure to a known allergen in a sensitized individual, has been increasingly recognized as a cause of persistent cutaneous contact dermatitis that is refractory to conventional therapies. While SCD in response to drugs has been described well in the literature, SCD to allergens in common foodstuffs is a less well-articulated phenomenon. Several foods that are universally consumed throughout the world contain potent allergens including nickel, balsam of Peru, trace metals, urushiol, and sesquiterpene lactones as well as a host of others that may cause a distinctive clinical picture. In this review article, the authors review the typical presentation and prevalence of SCD to foods, pathophysiology, the most common offensive ingestible food allergens, several appropriate diets, and effectiveness of dietary avoidance for situations in which SCD is suspected.

A retrospective descriptive study of oral azole antifungal agents in patients with patch test-negative head and neck predominant atopic dermatitis.

BACKGROUND: Head and neck dermatitis is a subtype of atopic dermatitis driven by Malassezia yeast. OBJECTIVE: We sought to evaluate the response of these patients to systemic azole antifungals. METHODS: We queried the electronic medical records from our institution for patients that were referred for allergy patch testing, were ultimately given the diagnosis of head and neck dermatitis, and were treated with oral azole antifungals over a 2-year period. RESULTS: Twenty-four patients met inclusion criteria and were analyzed. Most patients noted their characteristic flare beginning during their teenage, young adult, or adult years. All were noted to have some involvement of the head and neck, and 17 responded to treatment. The mean time taking an azole antifungal medication was 8 months, with a mean overall follow-up of 10 months. LIMITATIONS: This was a retrospective descriptive study, from a single institution, of a limited number of patients, and did not use a validated scoring system. CONCLUSION: Itraconazole and other azole antifungals were an effective treatment for more than two-thirds of adult patients with head and neck predominant atopic dermatitis.