Patch Testing With Nickel, Cobalt, and Chromium in Patients With Suspected Allergic Contact Dermatitis.

Background: Allergic contact dermatitis is frequently caused by metals, including multiple metals simultaneously. Objectives: To assess characteristics and associations of positive and clinically relevant patch test (PT) reactions with solitary and concurrent metal sensitization. Methods: A retrospective analysis of PT results for nickel, cobalt, and/or chromium from the North American Contact Dermatitis Group between 2001 and 2018 (n = 43,522). Results: 18.0% had a positive/allergic reaction to nickel sulfate hexahydrate, 7.3% to cobalt chloride hexahydrate, and 3.0% to potassium dichromate. 87.9% patients had a currently relevant reaction to 0, 9.4% to 1, and 2.7% to multiple metals tested. Patients with 1 versus no currently relevant reactions to metal were more likely to have a primary dermatitis site of trunk, feet, and ears; patients with currently relevant reactions to multiple metals had more dermatitis affecting the trunk and ears. Metal sources varied by co-reacting metal, especially for patients with cobalt and chromium allergy. Jewelry was the most commonly identified source of nickel and cobalt for both solitary and concurrent metal allergy. Conclusions: Sensitization to multiple metals occurred in 6% of patients. Allergen sources varied between patients with sensitivity to 1 metal versus those who had concurrent sensitivity to cobalt and/or chromium.

Contact Allergens in Prescription Topical Ophthalmic Medications.

BACKGROUND/OBJECTIVE: Both active and inactive ingredients in topical ophthalmic agents may cause allergic contact dermatitis. Here, we examined ingredients in prescription topical ophthalmic medications available in the United States. METHODS: A comprehensive list of topical ophthalmic medications was generated using AccessPharmacy. Categories included antiglaucoma, antibiotic, antibiotic/corticosteroid, corticosteroid, antiviral, antifungal, mydriatic, and miotic agents. For each formulation, ingredients were investigated using the National Institutes of Health US National Library of Medicine database and/or manufacturer websites. Counts and proportions were calculated for inactive ingredients, including those in the American Contact Dermatitis Society (ACDS) Core 90 Allergen Series. RESULTS: Two hundred sixty-four unique prescription ophthalmic medications met the inclusion criteria. The most common ACDS Core 90 allergen/cross-reactor inactive ingredient was benzalkonium chloride (68.1%, 180/264), followed by sorbates (11.7%, 31/264), parabens (6.8%, 18/264), sodium metabisulfite (3.8%, 10/264), propylene glycol (3.0%, 8/264), and lanolin (3.0%, 8/264). Approximately 21% (20.8%, 55/264) of products had no ACDS Core 90 allergens/cross-reactor inactive ingredients. The most common ACDS Core 90 allergen/cross-reactor active ingredients were aminoglycoside antibiotics, bacitracin/polymyxin B, and corticosteroids. Important non-ACDS Core 90 allergens included inactive ingredients, such as EDTA 28.0% and thimerosal 2.7%, as well as active ingredients, especially ß-blockers. CONCLUSIONS: Benzalkonium chloride, sodium metabisulfite, propylene glycol, and lanolin were common inactive ingredient allergens. Most ophthalmic categories had low allergen formulations available for patients with contact allergy.

Formaldehyde Release From Predispersed Tattoo Inks: Analysis Using the Chromotropic Acid Method.

BACKGROUND: Allergic contact dermatitis to tattoo ink may last from weeks to years. Formaldehyde is a strong sensitizer that may be present in predispersed tattoo inks. OBJECTIVES: The aim of this study was to evaluate the presence of formaldehyde in predispersed tattoo inks using the chromotropic acid method. METHODS: Tattoo inks from 39 companies were evaluated. Inclusion criteria included availability to purchase inks online through US tattoo product wholesalers or individual Web sites. Brands were grouped based on prevalence of use: common, uncommon, or rare. For common brands, 8 colors (primary colors, secondary colors, black, and white) were purchased. For uncommon and rare brands, 5 colors (primary colors, black, and white) were purchased. Each ink was tested with standard chromotropic acid method procedures; concentration of formaldehyde released was quantified using spectrophotometry. RESULTS: In total, 127 tattoo inks were purchased and tested. Ninety-three (73%) tested positive for formaldehyde release; 34 (27%) tested negative. Formaldehyde release did not correlate with color or brand. At least 1 ink from all brands (except 1) was positive for formaldehyde release. CONCLUSION: Approximately three-quarters of selected US tattoo inks tested positive for formaldehyde release. Clinicians should be aware of tattoo ink as a potential source of formaldehyde.

Cutaneous Reactions to Aluminum.

: Cutaneous exposure to aluminum may occur via contact with metal items, medications, and personal care products. Despite the widespread use of aluminum, allergic contact dermatitis is relatively rare. Sensitization is often incidentally identified during patch testing with aluminum-based chambers. This article presents several cases along with a literature review summarizing prevalence and clinical manifestations of cutaneous reactions to aluminum, recommendations for patch testing, sources of aluminum, and reproducibility of aluminum allergy over time.

Occupationally Related Nickel Reactions: A Retrospective Analysis of the North American Contact Dermatitis Group Data 1998-2016.

BACKGROUND: The epidemiology of nickel allergy in occupational settings is not well understood. OBJECTIVE: The aim of the study was to characterize occupationally related nickel allergy (ORNA). METHODS: This is a retrospective cross-sectional analysis of 44,378 patients patch tested by the North American Contact Dermatitis Group from 1998 to 2016. Characteristics of individuals with ORNA were compared with those with non-ORNA (NORNA). RESULTS: A total of 7928 (18.2%) individuals were positive to nickel sulfate 2.5%. Two hundred sixty-eight (3.4%) had ORNA. As compared with NORNA, ORNA was statistically associated with the male sex (41.0% vs 12.9%, P < 0.001), a diagnosis of irritant contact dermatitis (22.4% vs 12.0%, P < 0.001), and no history of eczema (81.7% vs 75.7%, P = 0.0217). The most common sites of ORNA dermatitis were hand (39.9%) and arm (18.1%), which were significantly more common than in NORNA (P < 0.0001). Sixteen industry categories and 22 occupation categories were identified for ORNA; the most common industries were durable goods manufacturing (24.6%) and personal services (15.7%), and the most frequent occupations were hairdressers/cosmetologists/barbers (14.3%), machine operators (9.3%), and health care workers (7.1%). Overall 30% of ORNA occupations were in metalworking. Of 215 ORNA sources identified, instruments/phones/other equipment (16.3%), vehicles/machinery (15.8%), and tools (15.3%) were the most common. CONCLUSIONS: Occupational nickel allergy is distinct from nonoccupational nickel allergy.

Formaldehyde Release From Baby Wipes: Analysis Using the Chromotropic Acid Method.

BACKGROUND: Formaldehyde is a common preservative and strong sensitizer. OBJECTIVE: The aim of the study was to evaluate the release of formaldehyde from baby/toddler wet wipes using the chromotropic acid method (CAM). METHODS: An online search of best-selling baby wipes was conducted. None declared formaldehyde or formaldehyde-releasing preservatives. Standard CAM procedures were used: a 1 × 1-in square of fresh wipe was placed in a bottle with an open vial of 4 mg/1 mL of chromotropic acid and sulfuric acid solution, sealed, and stored for 48 hours. Formalin and water served as controls. A blinded investigator graded color change (negative, indeterminate, mild, moderate, or strong). For quality control, 20% of all samples as well as all positives were retested. RESULTS: Fifty-one popular and highly reviewed baby and toddler wet wipe products were tested using CAM. Twelve wipes (24%) released formaldehyde (8 mild, 4 moderate/strong). Chromotropic acid method testing of 9 wipes (18%) was indeterminate and 30 (59%) were negative. CONCLUSIONS: Almost one quarter of baby/toddler wet wipes released formaldehyde when evaluated with CAM. Patients and clinicians should be aware of this potentially undeclared source of this common allergen.

Formaldehyde Release From Clothing and Upholstery Fabrics Using the Chromotropic Acid Method.

BACKGROUND: Formaldehyde resins may be used in textiles. OBJECTIVE: The aim of the study was to investigate the presence of formaldehyde in textiles using the chromotropic acid method. METHOD: Clothing scraps (from local department store tailors, n = 77) and upholstery fabric cuttings (from a furniture reupholstery store, n = 22) were collected. Each fabric was cut into a 1-cm square and tested using the chromotropic acid method. Samples were retested in a systematic fashion (every 10th sample) to assess reproducibility. RESULTS: All 99 clothing and upholstery fabrics tested negative for formaldehyde release. CONCLUSIONS: Our study suggests that textile manufactures may be using nonformaldehyde resins for durable press finishing in clothing likely to be tailored as well as fabrics used for furniture reupholstery. Additional studies involving other metropolitan areas and a variety of fabrics are needed to confirm these findings.

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.

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.

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

Allergic Contact Dermatitis From Methylisothiazolinone in Residential Wall Paint.

A 33-year-old woman presented to our clinic for suspected photoallergic contact dermatitis with a recent episode of severe, vesicular dermatitis involving exposed skin and correlating with relocation to a new home. Biopsy results showed spongiotic and lichenoid dermatitis with eosinophils. Patch test results showed a very strong (+++) reaction to methylisothiazolinone (MI), mild (+) reaction to MI/methylchloroisothiazolinone, and no reaction to benzisothiazolinone. These allergens were found in several personal products. However, the patient was suspicious of 4 wall paints recently used in her home. Semiopen patch tests to 3 Behr interior paints showed positive results. Nine controls showed negative results. High-performance liquid chromatography demonstrated MI and benzisothiazolinone in all 4 paints at concentrations ranging from 50 to 100 ppm and 290 to 340 ppm, respectively. Although MI has been reported to cause occupational airborne contact dermatitis in European household painters, to our knowledge, this is the first documented case of paint-related MI allergy in the United States.

Allergic Contact Dermatitis to Ophthalmic Medications: Relevant Allergens and Alternative Testing Methods.

Allergic contact dermatitis is an important cause of periorbital dermatitis. Topical ophthalmic agents are relevant sensitizers. Contact dermatitis to ophthalmic medications can be challenging to diagnose and manage given the numerous possible offending agents, including both active and inactive ingredients. Furthermore, a substantial body of literature reports false-negative patch test results to ophthalmic agents. Subsequently, numerous alternative testing methods have been described. This review outlines the periorbital manifestations, causative agents, and alternative testing methods of allergic contact dermatitis to ophthalmic medications.

Incidental melanomas detected in veterans referred to dermatology.

BACKGROUND: Early detection of melanoma is integral to preventing morbidity and mortality. OBJECTIVE: We sought to characterize and compare incidental versus consult melanomas detected in veterans referred to the Minneapolis, MN, Department of Veterans Affairs Medical Center dermatology clinic. METHODS: We retrospectively reviewed charts of all dermatology consults between January 2004 and March 2012. RESULTS: Of the 28,405 consults sent during the study period, 17,174 met inclusion criteria. There were 231 melanomas identified in 221 patients. In all, 144 melanomas were identified on the consult and 87 melanomas were discovered incidentally. The incidental melanoma detection rate was 0.5% (84/17,174). Consult melanomas were more likely to be invasive than incidental melanomas (relative risk 1.51, 95% confidence interval 1.23-1.86, P < .0001) and less likely to have a Breslow depth of less than 1.00 mm (relative risk 0.73, 95% confidence interval 0.61-0.88, P = .0036). Incidental melanomas were smaller than consult melanomas (mean diameter 0.98 vs 1.3 cm, respectively) and thinner (mean Breslow depth 0.64 vs 1.74 mm). Consult melanomas were more likely to be detected on the head/neck (relative risk 1.25, 95% confidence interval 1.03-1.52, P = .0295). LIMITATIONS: Nondiverse patient population is a limitation. CONCLUSION: Melanomas detected during an in-person skin examination by a dermatologist were more likely to be detected at an earlier stage of disease.

Cutaneous Delayed-Type Hypersensitivity to Surfactants.

BACKGROUND: Repeated and prolonged use of surfactants can cause irritant as well as allergic contact dermatitis. OBJECTIVE: This study reports the frequency of positive patch test results to surfactants tested on the North American Contact Dermatitis Group screening series including cocamidopropyl betaine (CAPB), amidoamine (AA), dimethylaminopropylamine (DMAPA), oleamidopropyl dimethylamine (OPD), and cocamide diethanolamide (CDEA), and correlations of positive reactions between CAPB and the other surfactants. METHODS: This was a retrospective analysis of 10 877 patients patch tested between 2009 and 2014 to the surfactants CAPB, AA, DMAPA, OPD, and CDEA. Frequencies of positive reactions to these surfactants were calculated, and trends of reactivity between the surfactants analyzed. CONCLUSIONS: The OPD had the highest rate of positive patch reactions (2.3%) followed by DMAPA (1.7%), and CAPB (1.4%). The AA and CDEA had the lowest rate of positive reactions (0.8%). There was a high degree of overlap in positive patch tests between the surfactants. The CDEA was the least likely to coreact with another surfactant.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial.

IMPORTANCE: Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE: To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS: Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES: This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS: The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE: Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00847912.

Incidental lesions found in veterans referred to dermatology: the value of a dermatologic examination.

BACKGROUND: Few studies have evaluated the detection of incidental skin cancers. OBJECTIVE: We sought to evaluate the rate of incidental cutaneous malignancies in routine dermatology consults. METHODS: This was a retrospective chart review of all dermatology consults at the Minneapolis Department of Veterans Affairs Medical Center over 8.25 years. Inclusion criteria included an in-person clinic visit within 18 months of the initial consult date. Patients with an in-person skin examination by a dermatologist in the 18 months before consult date were excluded. RESULTS: Of 28,405 consults sent during the study period, 17,174 met inclusion criteria. In all, 2257 (13.1%) patients had 1 or more biopsied incidental lesions. Half (50.3%; n = 1674) of the 3328 biopsied incidental lesions were malignant, which included 1187 patients. The per-person detection rate for an incidental malignant lesion was 6.9% (1187/17,174). There were 87 incidental melanomas identified in 84 patients. The per-person detection rate for an incidental melanoma was 0.5% (84/17,174). The most frequent anatomical location for biopsied incidental malignancies was the head and neck (53.9%). Incidental melanomas were most frequently located on the back (33.3%). LIMITATIONS: Nondiverse patient population and conservative detection rate estimates are limitations. CONCLUSION: An in-person skin examination by a trained dermatologist is important for detection of skin malignancies. This may have implications for teledermatology.