Use of 308 nm excimer laser for the treatment of chronic hand and foot eczema.

BACKGROUND: Chronic hand and foot eczema (CHFE), a prevalent debilitating disorder affecting approximately 15% of the population, presents a socioeconomic and psychosocial burden for patients and often follows a chronic course, refractory to conventional therapies. Thus, a large need exists for more effective therapeutics; the excimer laser (308 nm) is effective for some inflammatory skin diseases, but its efficacy has not been evaluated for CHFE. METHODS: The study is a retrospective chart review conducted on 30 patients with recalcitrant CHFE (19 with hand involvement, four with foot involvement, and seven with both) treated twice weekly with excimer laser (308 nm) single wavelength ultraviolet (UV)B radiation between January 2013 and December 2014. RESULTS: Improvements in clinical scores included a 69% reduction in average physician's global assessment (PGA) scores (from 2.77 at baseline to 0.87 after treatment, P < 0.0001) with a parallel reduction in average modified total lesion/symptom scores of 70% (from 10.2 to 3.1, P < 0.0001). Only mild sunburn-like reactions were observed. CONCLUSION: This report evaluates excimer laser for patients with refractory CHFE and shows excellent and sustained efficacy for this treatment. Compared to other UV therapies, excimer laser offers lower cumulative doses of UV radiation by targeting specific areas. This effective treatment should be considered alone or in combination with other established or newer therapies.

Diverse activation and differentiation of multiple B-cell subsets in patients with atopic dermatitis but not in patients with psoriasis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis pathogeneses involve skin barrier impairment and immune dysregulation; however, the contribution of B-cell imbalances to these diseases has not yet been determined. OBJECTIVE: We sought to quantify B-cell populations and antibody-secreting cells in the blood of patients with AD, patients with psoriasis, and control subjects. METHODS: We studied 34 adults with moderate-to-severe AD (mean SCORAD score, 65), 24 patients with psoriasis (mean Psoriasis Area and Severity Index score, 16), and 27 healthy subjects using an 11-color flow cytometric antibody panel. IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies of plasmablasts and naive, memory, transitional, and activated B cells. RESULTS: We measured increased CD19(+)CD20(+) B-cell counts in the skin and blood of patients with AD (P < .01). Significantly higher frequencies of chronically activated CD27(+) memory and nonswitched memory B cells were observed in patients with AD (P < .05), with lower values of double-negative populations (4% for patients with AD vs. 7% for patients with psoriasis [P = .001] and 6% for control subjects [P = .02]). CD23 expression was highest in patients with AD and correlated with IgE levels (P < .01) and disease severity (r = 0.6, P = .0002). Plasmablast frequencies and IgE expression were highest in all memory subsets of patients with AD (P < .01). Finally, CD19(+)CD24(++)CD38(++) transitional and CD19(+)CD24(-)CD38(-) new memory B-cell counts were higher in patients with AD versus those in patients with psoriasis (2.8% vs. 1.4% [P = .001] and 9.2% vs. 5.7% [P = .02], respectively). CONCLUSIONS: AD is accompanied by systemic expansion of transitional and chronically activated CD27(+) memory, plasmablast, and IgE-expressing memory subsets. These data create a critical basis for the future understanding of this debilitating skin disease.

Petrolatum: Barrier repair and antimicrobial responses underlying this "inert" moisturizer.

BACKGROUND: Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed. OBJECTIVE: We sought to define the cutaneous molecular and structural effects induced by petrolatum. METHODS: Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only. RESULTS: Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human ß-defensin 2 [DEFB4A]/FCH, 4.96; P < .001 for all) and innate immune genes (IL6, IL8, and IL1B; P < .01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects. CONCLUSIONS: Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease with limited treatment options. Several microarray experiments have been conducted on lesional/LS and non-lesional/NL AD skin to develop a genomic disease phenotype. Although these experiments have shed light on disease pathology, inter-study comparisons reveal large differences in resulting sets of differentially expressed genes (DEGs), limiting the utility of direct comparisons across studies. METHODS: We carried out a meta-analysis combining 4 published AD datasets to define a robust disease profile, termed meta-analysis derived AD (MADAD) transcriptome. RESULTS: This transcriptome enriches key AD pathways more than the individual studies, and associates AD with novel pathways, such as atherosclerosis signaling (IL-37, selectin E/SELE). We identified wide lipid abnormalities and, for the first time in vivo, correlated Th2 immune activation with downregulation of key epidermal lipids (FA2H, FAR2, ELOVL3), emphasizing the role of cytokines on the barrier disruption in AD. Key AD "classifier genes" discriminate lesional from nonlesional skin, and may evaluate therapeutic responses. CONCLUSIONS: Our meta-analysis provides novel and powerful insights into AD disease pathology, and reinforces the concept of AD as a systemic disease.

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.

BACKGROUND: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. OBJECTIVE: We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. METHODS: Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). RESULTS: Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01). CONCLUSIONS: These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.

Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population.

BACKGROUND: Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. OBJECTIVE: We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8(+) T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA(-) T-cell subsets in patients with AD and control subjects. METHODS: We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations. RESULTS: We measured increased TH2/TC2/IL-13(+) and TH22/TC22/IL-22(+) populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA(+) T-cell numbers (P < .01). A significantly lower frequency of CLA(+) IFN-γ-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4(+) and CD8(+) T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA(+) cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4(+) IL-22(+) and IL-17(+) cell frequencies, which were highly significant among CLA(-) cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA(+) T cells (IL-22: 11 vs 7.5, P = .04). CONCLUSIONS: Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.

Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. OBJECTIVE: We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. METHODS: Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). RESULTS: Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. CONCLUSIONS: Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and negative regulator levels compared with those seen in non-AD skin.

New pathogenic and therapeutic paradigms in atopic dermatitis.

Atopic Dermatitis (AD) is a common inflammatory skin disease with increasing prevalence in industrialized countries. Up to one-third of adults with AD have moderate-to-severe disease, leading to a large, unmet need for effective treatments. While current therapeutics focus mainly on symptom control, major advances have been made in translational research, with the goal of developing drugs to eradicate disease. A translational revolution is now occurring in AD, similar to the one that has occurred in psoriasis over the past decade. Research has focused on elucidating immune pathways responsible for AD, including Th2, Th22, and Th17 pathways, with testing of immune antagonists specific to these axes. An IL-4R antagonist, dupilumab, is the first drug that shows great promise in phase II trials. By studying clinical and molecular responses following treatment with specific immune antagonists, our understanding of and ability to treat AD will expand.

Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to surfactants.

BACKGROUND: Patients with atopic dermatitis (AD) have abnormalities in skin barrier function, and are predisposed to developing cutaneous delayed-type hypersensitivity. Soap and detergents are known to exacerbate the breakdown of the skin barrier. OBJECTIVE: We sought to assess whether atopic patients in our database were more likely than nonatopic patients to patch test positive to the surfactants cocamidopropyl betaine (CAPB) and cocamide diethanolamide (DEA), or to the surfactant precursor amidoamine. METHODS: Between January 1, 2001, and the present, a total of 1674 patients underwent patch testing to the North American Contact Dermatitis Group standard screening series. The incidence of positive patch test results to CAPB, cocamide DEA, and amidoamine among patients with AD (n = 242) and without AD (n = 1422) was assessed. Statistical analysis was done using a χ(2) test. RESULTS: AD was associated with contact hypersensitivity to CAPB, but not to cocamide DEA or amidoamine. LIMITATIONS: This was a retrospective study of patients evaluated for suspected allergic contact dermatitis and, therefore, matching for gender, age, or other parameters was not possible. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. CONCLUSIONS: Patients with AD should avoid the use of skincare products containing the surfactant CAPB.

Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to topical preservatives.

BACKGROUND: Patients with atopic dermatitis (AD) have chronic dry skin to which they frequently apply skin care products containing preservatives, and they are predisposed to developing cutaneous delayed-type hypersensitivity. OBJECTIVE: We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD and to assess whether atopic patients in our database were more likely to patch test positive to preservatives. METHODS: A total of 2453 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reaction among patients with AD (n = 342) and without AD (n = 2111) was assessed. Statistical analysis was done using a χ(2) test. RESULTS: Compared with nonatopic patients, patients with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to quaternium-15, imidazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane-1,3-diol but not to parabens, formaldehyde, or diazolidinyl urea. LIMITATIONS: Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. CONCLUSIONS: Patients with AD should avoid the use of skin care products preserved with formaldehyde releasers.

Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis.

BACKGROUND: Literature on the relationship between atopic dermatitis (AD) and cutaneous delayed-type hypersensitivity is inconclusive. OBJECTIVE: We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD, and, to assess whether atopic patients in our database were more likely to patch test positive to certain classes of allergens. METHODS: A total of 2305 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reactions among patients with AD (n = 297) and without AD (n = 2008) was assessed. Statistical analysis was done using a χ(2) test with Yates continuity correction. RESULTS: Compared with nonatopic patients, those with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to nickel, cobalt, and chromium, but was not associated with contact sensitization to fragrances. LIMITATIONS: Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City (including Kansas City, MO, Kansas City, KS, and the adjoining suburbs). CONCLUSION: Compared with nonatopics, patients with AD are significantly more likely to have at least 1 positive patch test reaction and to develop contact hypersensitivity to metal allergens.