Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the Phase 3 randomized, controlled trial (THRIVE-AA1).

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

BACKGROUND: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. OBJECTIVES: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. METHODS: In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. RESULTS: Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. CONCLUSIONS: The results support the further development of roflumilast foam for treating scalp and body psoriasis.

Unexpected Clinical Lessons Learned From IL-4 and IL-13 Blockade.

In 2017, dupilumab became the first FDA approved systemic therapy for atopic dermatitis. Since its approval, extensive clinical experience and continued research have revealed a number of unexpected effects that are highly clinically relevant. We will review these clinical effects and the supporting evidence.J Drugs Dermatol. 2023;22(10):1007-1008 doi:10.36849/JDD.7249.

The Safety and Efficacy of Roflumilast Cream 0.15% and 0.05% in Patients With Atopic Dermatitis: Randomized, Double-Blind, Phase 2 Proof of Concept Study.

BACKGROUND: Patients with atopic dermatitis (AD) need safe and effective topical treatments. OBJECTIVE: To assess safety and efficacy of roflumilast cream in patients with mild to moderate AD. METHODS: In this phase 2, proof of concept trial, patients (N=136) aged ≥12 years with AD were randomized to once-daily roflumilast cream 0.15%, roflumilast cream 0.05%, or vehicle cream for 4 weeks. Absolute change from baseline in Eczema Area and Severity Index (EASI) score at week 4 (primary endpoint), percentage change and responder rates, Validated Investigator Global Assessment-AD (vIGA-AD), and safety were assessed. RESULTS: At week 4, mean absolute changes in EASI were −6.4 (P=0.097 vs vehicle), −6.0 (P=0.356), and −4.8 with roflumilast 0.15%, roflumilast 0.05%, and vehicle, respectively. Significant improvements were observed for percentage change from baseline in EASI, patients reaching 75% improvement in EASI, and patients achieving vIGA-AD score of “clear” or “almost clear.” Treatment-related adverse events (AEs) occurred in 2 (2.2%) patients receiving roflumilast (mild rash and moderate application site pain). Only 1 (1.1%) patient receiving roflumilast discontinued study/drug due to an AE. LIMITATIONS: Small number of patients. CONCLUSIONS: Results support additional larger clinical trials of roflumilast cream to assess its potential as a once-daily, nonsteroidal topical AD treatment. CLINICALTRIALS: gov identifier NCT03916081 J Drugs Dermatol. 2023;22(2):139-147. doi:10.36849/JDD.7295.

Unmet needs for patients with seborrheic dermatitis.

Seborrheic dermatitis (SD) is a common skin disease with signs and symptoms that may vary by skin color, associated medical conditions, environmental factors, and vehicle preference. Diagnosis of SD is based on presence of flaky, "greasy" patches, and/or thin plaques accompanied by erythema of the scalp, face, ears, chest, and groin and is associated with pruritus in many patients. The presentation may vary in different skin types and hyper- or hypopigmentation may occur, with or without erythema and minimal or no scaling. While the pathogenesis is not certain, 3 key factors generally agreed upon include lipid secretion by sebaceous glands, Malassezia spp. colonization, and some form of immunologic dysregulation that predisposes the patient to SD. Treatment involves reducing proliferation of, and inflammatory response to, Malassezia spp. Topical therapies, including antifungal agents and low potency corticosteroids, are the mainstay of treatment but may be limited by efficacy and side effects. Few novel treatments for SD are currently being studied; however, clinical trials assessing the use of topical phosphodiesterase-4 inhibitors have been completed. Improving outcomes in SD requires recognizing patient-specific manifestations/locations of the disease, including increased awareness of how it affects people of all skin types.

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.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5).

BACKGROUND: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults. OBJECTIVE: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy. METHODS: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement. RESULTS: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P < .001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P < .001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies. LIMITATIONS: Short-term clinical trial results may not be generalizable to real-world settings. CONCLUSION: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks.

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.