Disease Activity In Atopic Dermatitis Research Articles

Surface expression of FcϵRI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis

Background: FcϵRI expressed on the surface of human epidermal Langerhans' cells facilitates uptake of IgE-associated allergens and plays a pivotal role in the pathogenesis of atopic dermatitis. Seminal results from studies investigating Langerhans' cell FcϵRI in skin biopsy sections or epidermal cell suspensions demonstrate the highest receptor expression in lesional skin of patients with active atopic dermatitis. Objective: We sought to investigate and localize FcϵRI expression on Langerhans' cells within a minimally disturbed tissue environment in clinically uninvolved skin and to compare receptor expression between healthy donors and patients with atopic dermatitis or other allergic diseases. Methods: Intact epidermal sheets from skin suction blisters, immunofluorescently stained with Langerhans' cell markers and anti-FcϵRIα (mAbs 15E5 and 22E7) or anti-IgE, were examined by means of confocal microscopy. Samples incubated with anti-FcϵRIα before or after cell fixation-permeabilization were compared to discriminate between cytoplasmic and membrane localization. Results: Cytoplasmic FcϵRI α chain was found in Langerhans' cells from all donors, irrespective of atopic status. Surface FcϵRI-bound IgE was detected in the skin of individuals with active atopic dermatitis and in the skin of those with active asthma or rhinitis. No surface FcϵRI was expressed in the skin of patients with a clinical history of atopic dermatitis, asthma, or rhinitis whose disease was in remission or in the skin of nonatopic individuals. Conclusion: In clinically uninvolved skin, Langerhans' cell-surface FcϵRI expression is not only linked to atopic dermatitis but is also generally associated with allergic disease. This supports the concept of a systemic regulatory mechanism associated with active allergic disease, which is further aggravated by local inflammation in atopic skin lesions. (J Allergy Clin Immunol 2003;112:411-9.)

Comparative Analysis of Mononuclear Cell Surface Markers in Atopic Processes‐A Preliminary Study

Atopic disorders are driven by the Th2 cell subset. We have determined the expression of costimulatory molecules and cell surface markers on peripheral CD4 + T cells and antigen presenting cells, in different atopic diseases, and we have also tried to correlate the expression of these markers with the severity of the disease. Cells from patients with atopic and contact dermatitis, mild or severe asthma, and symptomatic and non‐symptomatic atopic rhinitis were analyzed by flow cytometry. Our results showed that CD30, CD124, and CD152 expression on CD4 + T cells was significantly higher in atopic dermatitis than in contact dermatitis patients (p < 0.05). It was interesting to observe that the cell surface expression of CD80 in T and B cells from atopic dermatitis patients was not enhanced as opposed to the other atopic diseases we analyzed. Our results suggest that there are differences in the immune mechanisms involved in the different atopic diseases, and that expression of CD30 in CD4 + T cells might be a marker of disease activity in atopic dermatitis.

Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: Changes in barrier function provide a sensitive indicator of disease activity

Background: It is currently fashionable to consider atopic dermatitis (AD), like other inflammatory dermatoses, as immunologic in pathogenesis (“inside-outside” hypothesis). Accordingly, topical glucocorticoids and other immunosuppressive agents are mainstays of therapy, but the risk of toxicity from these agents is not insignificant, particularly in children. Alternatively, because stratum corneum (SC) permeability barrier function is also abnormal in AD, it has been hypothesized that the barrier abnormality could drive disease activity. Yet commonly used emollients and moisturizers do not correct the SC ceramide deficiency, the putative cause of the barrier abnormality. Objectives: We assessed the efficacy of a newly developed, ceramide-dominant, physiologic lipid-based emollient, when substituted for currently used moisturizers, in 24 children who were also receiving standard therapy for stubborn-to-recalcitrant AD. Methods: All subjects continued prior therapy (eg, topical tacrolimus or corticosteroids), only substituting the barrier repair emollient for their prior moisturizer. Follow-up evaluations, which included severity scoring of atopic dermatitis (SCORAD) values and several biophysical measures of SC function, were performed every 3 weeks for 20 to 21 weeks. Results: SCORAD values improved significantly in 22 of 24 patients by 3 weeks, with further progressive improvement in all patients between 6 and 20 or 21 weeks. Transepidermal water loss levels (TEWL), which were elevated over involved and uninvolved areas at entry, decreased in parallel with SCORAD scores and continued to decline even after SCORAD scores plateaued. Both SC integrity (cohesion) and hydration also improved slowly but significantly during therapy. Finally, the ultrastructure of the SC, treated with ceramide-dominant emollient, revealed extracellular lamellar membranes, which were largely absent in baseline SC samples. Conclusion: These studies suggest that (1) a ceramide-dominant, barrier repair emollient represents a safe, useful adjunct to the treatment of childhood AD and (2) TEWL is at least as sensitive an indicator of fluctuations in AD disease activity as are SCORAD values. These studies support the outside-inside hypothesis as a component of pathogenesis in AD and other inflammatory dermatoses that are accompanied by a barrier abnormality. (J Am Acad Dermatol 2002;47:198-208.)

Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis.

T(H)2 cells and eosinophils selectively express CC chemokine receptor 4 and CCR3, respectively, and their chemokine ligands are likely to play important roles in the pathogenesis of atopic dermatitis (AD). The purpose of this study was to demonstrate the presence of thymus and activation-regulated chemokine (TARC) in platelets and its release during clotting and to evaluate the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin in control subjects and patients with AD. We compared plasma and serum contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin with various clinicolaboratory parameters in patients with AD. Serum contents of TARC rapidly increased during clotting, whereas those of MDC and eotaxin increased only slightly. We demonstrated that platelets contained TARC, and its levels were dramatically elevated in patients with AD. Platelets also released TARC on stimulation with thrombin. We therefore evaluated circulating levels of these chemokines in control subjects and patients with AD by using plasma samples. Plasma TARC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P <.00001), serum lactate dehydrogenese levels (r = 0.696, P =.00001), eosinophil counts (r = 0.381, P =.007), and platelet counts (r = 0.562, P <.0001). Similarly, plasma MDC levels were significantly increased in patients with AD (P <.0001) and showed significant correlations with SCORAD index (r = 0.727, P <.0001), serum lactate dehydrogenese levels (r = 0.861, P <.0001), eosinophil counts (r = 0.505, P =.005), and platelet counts (r = 0.370, P =.01). On treatment, plasma TARC and MDC levels were dramatically decreased in accordance with improved SCORAD scores (P =.0012 and P =.0007, respectively). On the other hand, plasma eotaxin levels did not show any significant increase or correlation with any of the clinical parameters in patients with AD. Platelets from patients with AD contain high levels of TARC. Thus platelets might play an important role in AD pathogenesis by releasing T(H)2-attracting TARC on activation. Furthermore, circulating levels of TARC and MDC, but not those of eotaxin, correlate well with the disease activity of AD.

Increased levels of serum tissue inhibitor of metalloproteinase-1 but not metalloproteinase-3 in atopic dermatitis.

Matrix metalloproteinases and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), contribute to inflammation-induced tissue destruction and subsequent remodeling for maintenance of tissue homeostasis. Since the production of these enzymes and their inhibitors is regulated by mediators such as proinflammatory cytokines and growth factors, elevated levels of serum TIMPs and/or MMPs have been documented in patients with several inflammatory disorders. In this study, we examined the role of TIMPs and MMPs in the pathogenesis of atopic dermatitis (AD) by evaluating the serum levels of TIMP-1 and MMP-3 in 40 patients with AD and 20 control subjects by ELISA. The serum TIMP-1 levels were significantly higher in AD patients in exacerbation status than in nonatopic subjects, whereas serum MMP-3 levels were not significantly different between them. As a result, AD patients revealed significantly elevated TIMP-1/MMP-3 ratios. The levels of serum TIMP-1 were significantly reduced in AD patients following conventional treatments. Significantly higher values of peripheral eosinophil counts, serum levels of IgE and lactate dehydrogenase, eruption score, and eruption area were noted in the AD patients with elevated TIMP-1 levels when compared with those with normal values. Moreover, the points of chronic eruptions such as lichenification and prurigo were significantly higher in the patients with elevated TIMP-1 levels than those with normal TIMP-1, while those of acute lesions such as oozy/microvesicles and oedema were not different between these groups. Serum TIMP-1 level may be a useful marker to estimate the long-term disease activity of AD.

The role of CD30 in atopic disease.

The role of CD30 in atopic disease.

Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of TH2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4–positive (CCR4+) or CCR8+ cells. Objective: The purpose of this study was to investigate the participation of TARC in AD. Methods: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. Results: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in ke-ratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. Conclusion: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD. (J Allergy Clin Immunol 2001;107:535-41.)

Eosinophil hypersegmentation is a possible marker to monitor the disease activity of atopic dermatitis

In the present study, we tried to clarify whether nuclear hypersegmentation of peripheral blood eosinophils is correlated with peripheral eosinophil counts and/or the activity of atopic dermatitis (AD) in 79 patients. We also compared the grades of skin scores, peripheral eosinophil counts, the rate of hypersegmentation of eosinophils and serum eosinophil cationic protein (ECP) concentrations in eight patients before and after treatment. There was a positive correlation between the skin scores of AD and peripheral eosinophil counts (P < 0.01), between the skin scores of AD and the number of nuclear lobes of eosinophils (P < 0.01) and between eosinophil counts and the number of nuclear lobes of eosinophils when the number of nuclear lobes of eosinophils was fewer than three (P < 0.01). A positive correlation was observed between serum ECP concentrations and eosinophil counts and/or skin scores of AD (P < 0.001). A negative correlation was observed between serum ECP concentrations and the number of nuclear lobes fewer than two (P < 0.05). During therapy, peripheral eosinophil counts and the degree of hypersegmented eosinophils decreased significantly, and this was associated with recovery of skin conditions, but not with serum ECP concentrations. These results suggest that eosinophil hypersegmentation may reflect activated eosinophils and also that the observation of nuclear hypersegmentation in peripheral blood eosinophils is useful to recognize the disease activity of AD.

Urinary eosinophil protein X in children with atopic dermatitis: relation to atopy and disease activity.

Parameters of eosinophil inflammation have been suggested as markers of disease activity in atopic dermatitis (AD), but the value of urinary eosinophil protein X (U-EPX) in children with AD, as well as the influence of allergic sensitization, is not known. We measured U-EPX in 59 atopic and 29 nonatopic children with mild (n = 32), moderate (n = 34), and severe (n = 22) AD, as well as in 64 controls. U-EPX was increased in children with AD (110; 67-164 microg/mmol creatinine, median; quartiles) compared to controls (62; 41-95, P<0.001). Children with mild (97; 63-164, P < 0.01), moderate (108; 67-157, P < 0.01), and severe disease (152; 99-202, P < 0.001) had levels of U-EPX higher than controls. U-EPX was significantly higher in children with severe AD than in mild and moderate disease (P < 0.05 for both). Children with AD and a positive skin prick test (120; 81-176) had higher levels of U-EPX than children with a negative skin prick test (87; 56-155, P<0.05). U-EPX is significantly increased in children with AD and may reflect disease activity. U-EPX may also reflect differences in eosinophil activation between those sensitized and those not sensitized to common allergens.

Urinary eosinophil protein X and serum eosinophil cationic protein in infants and young children with atopic dermatitis: Correlation with disease activity

Background: Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) or eosinophil-derived neurotoxin (EDN) are released by eosinophil granulocytes in allergic diseases. Serum ECP (s-ECP) levels have been correlated with disease activity in atopic dermatitis (AD) in adults and young patients, and high urinary EPX (u-EPX) levels in asthmatic patients seem to reflect active disease. A relationship between AD severity and u-EPX concentration in young children has not been previously studied. Objective: This study was performed to evaluate whether the severity of AD in infants and young children was correlated with s-ECP and u-EPX levels. Methods: Fifty-four infants and children (mean age, 17.7 months; range, 4-48 months) with AD and without other allergic conditions were evaluated. The severity of AD was measured by using the SCORAD index. S-ECP, serum total IgE, serum-specific IgE for common allergens, and peripheral blood eosinophil counts (PBECs) were determined. In forty-two children u-EPX was also measured. Seven age-matched control patients underwent the same determinations. Results: S-ECP and u-EPX were significantly higher in children with AD than in control children (mean, 23.9 vs 3.5 μg/dL [P < .001] and 57.7 vs 6.0 μg/mmol creatinine [P < .001]). A significant correlation was found between SCORAD and s-ECP (P = .002), u-EPX (P = .01), and PBECs (P = .01) and between symptom index and uEPX (P = .0004). PBECs were strongly correlated to s-ECP and u-EPX (P < .0001). However, 5 patients with moderate and severe AD (11.9%) showed low levels of s-ECP, u-EPX, and PBECs. Conclusion: S-ECP and u-EPX were useful markers of AD activity in infants and young children. When taken together, the two determinations could give more information about the clinical course of the illness. Some patients seemed to have clinical exacerbations without an involvement of eosinophils and their products. (J Allergy Clin Immunol 2000;105:353-7.)

Atopy patch testing--a diagnostic tool?

Atopy patch testing--a diagnostic tool?

Elevated serum L-selectin levels and abnormal regulation of L-selectin expression on leukocytes in atopic dermatitis: Soluble L-selectin levels indicate disease severity

Background: L-selectin mediates leukocyte rolling on endothelium at sites of inflammation, suggesting that L-selectin may be involved in the development of cutaneous lesions of atopic dermatitis (AD). After leukocyte activation, L-selectin is rapidly shed from the cell surface. Objective: The purpose of this study was to assess leukocyte L-selectin expression and quantitate levels of serum soluble L-selectin (sL-selectin) in patients with AD. Methods: Serum sL-selectin levels in patients with AD (n = 70), contact dermatitis (n = 18), and psoriasis (n = 23), as well as normal control subjects (n = 30), were examined by using an ELISA. The L-selectin expression on leukocytes in heparinized blood samples from patients with AD (n = 18) and normal control subjects (n = 10) was also examined by flow cytometry. Results: Serum levels of sL-selectin in patients with AD were significantly higher than those found in normal control subjects. Furthermore, sL-selectin levels correlated positively with disease severity and total serum IgE levels in AD. The expression of L-selectin on B cells, monocytes, and neutrophils was significantly decreased in patients with AD compared with normal control subjects, although those on CD4 + or CD8 + T cells from patients with AD were similar to those from normal control subjects. Conclusion: Elevated sL-selectin levels and the abnormal expression of L-selectin on some leukocyte subsets in patients with AD may correlate with inflammation associated with AD. Furthermore, the level of sL-selectin may be a useful immunologic indicator for disease activity in AD. (J Allergy Clin Immunol 1999;104:163-8.)

Soluble E-selectin, other markers of inflammation and disease severity in children with atopic dermatitis.

E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are membrane-bound adhesion molecules which mediate the attachment of leucocytes to endothelial cells. These molecules are preferentially expressed on activated endothelium. The soluble forms of these molecules (sE-selectin, sP-selectin, sICAM-1 and sVCAM-1) are present in the circulation as a result of shedding. Some of the soluble adhesion molecules have been thought to reflect disease activity in atopic dermatitis (AD). To evaluate their potential to reflect disease activity in AD, we correlated their plasma concentration with clinical severity measured by objective SCORAD (SCORing Atopic Dermatitis). Furthermore, levels of total IgE, specific IgE, and eosinophil cationic protein (ECP) were determined. SCORAD and sE-selectin levels were significantly increased in children with specific IgE for both food and inhalation allergens (P < 0.05). ECP consistently showed an increase with the scores of SCORAD, but no statistical significance was reached. Disease activity was significantly correlated with the plasma levels of sE-selectin (rs = 0.6, P < 0.0005) but not with sP-selectin, sICAM-1 and sVCAM-1. This agrees with recent studies performed in adults with AD, and supports the potential of sE-selection as a parameter for monitoring disease activity in young children with AD.

Serum macrophage migration inhibitory factor (MIF) as a marker of disease activity in atopic dermatitis

Serum macrophage migration inhibitory factor (MIF) as a marker of disease activity in atopic dermatitis

Eosinophil cationic protein (ECP) level and its correlation with eosinophil number or IgE level of peripheral blood in patients with various skin diseases

Eosinophil cationic protein (ECP) is a cationic protein derived from eosinophil granulocytes, and has been studied mainly in atopic diseases and considered as a useful marker of disease activity in atopic dermatitis. We measured the serum ECP levels in patients with various skin diseases ( n = 875) and in normal healthy controls ( n = 79), and evaluated the correlation between ECP level and blood eosinophil number, or ECP and IgE levels. Serum ECP levels were significantly higher in patients with drug eruption (15.8 ± 1.7 μg/1), psoriasis (15.1 ± 6.0μg/1), acute urticaria (13.9 ± 1.4 μg/1) than in healthy controls (4.5 ± 0.3 μg/1) ( P < 0.05) and also significantly elevated in patients with elevated eosinophil numbers (15.2±1.0 μg/1) compared to those in patients with normal eosinophil numbers (8.8 ± 0.3 μg/l) ( P < 0.001). Serum ECP level and eosinophil number in peripheral blood were also correlated in patients with psoriasis ( γ = 0.82, P < 0.01), drug eruption ( γ = 0.31, P < 0.01) and acute urticaria ( γ = 0.20, P < 0.05). However, no correlation between ECP and IgE levels in all of the patients was found. Among the patients with chronic urticaria, ECP levels showed an increasing trend in patients with angioedema, cold urticaria and dermographic urticaria as compared with those in healthy controls. Our results suggest that, even though the role of ECP released from activated eosinophils is still unknown, its measurement might be of help to understand the pathogenesis of some skin disorders.

Monitoring of disease activity by measurement of inflammatory markers in atopic dermatitis in childhood.

Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and eosinophil cationic protein (ECP) were measured in 20 patients with atopic dermatitis before and after 4 days' treatment with prednisolone p.o. as well as in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P < 0.001), whereas ELAM-1 levels were not different between the groups. After 4 days of steroid treatment, clinical improvement was associated with a decrease of sIL-2R (P < 0.003), ICAM-1 (P < 0.004), and ECP serum levels (P < 0.003), but ELAM-1 levels remained unchanged. Both serum ECP and sIL-2R levels were significantly correlated with disease severity before as well as after steroid treatment. Changes of sIL-2R concentrations were strongly related to the changes of ECP levels. In addition, changes of serum sIL-2R and ECP levels in percentage were correlated with clinical improvement. These results indicate that the determination of sIL-2R and ECP serum levels may be useful in monitoring disease activity in atopic dermatitis in childhood, especially in treatment trials.

Serum level of major basic protein indicates disease activity in atopic dermatitis

AbstractWe evaluated the serum levels of major basic protein (MBP), assayed using an MBP radioimmunoassay kit. and the effect of an anti‐allergic agent, ketotifen, which has strong anti‐eosinophil activity, in 56 atopic dermatitis (AD) patients. The serum MBP level was significantly lower (660.11 ± 34.52 ng/ml, P &lt; 0.05) after administration of ketotifen (1 mg twice a day) for 8 weeks than before treatment (774.98 ± 48.64 ng/ml). These findings suggest that serum MBP levels are a useful indicator of AD activity and that anti‐allergic agents can have an effect on eosinophil involvement in AD.

Serum level of major basic protein indicates disease activity in atopic dermatitis

We evaluated the serum levels of major basic protein (MBP), assayed using an MBP radioimmunoassay kit, and the effect of an anti-allergic agent, ketotifen, which has strong anti-eosinophil activity, in 56 atopic dermatitis (AD) patients. The serum MBP level was significantly lower (660.11 ± 34.52 ng/ml, P < 0.05) after administration of ketotifen (1 mg twice a day) for 8 weeks than before treatment (774.98 ± 48.64 ng/ml). These findings suggest that serum MBP levels are a useful indicator of AD activity and that anti-allergic agents can have an effect on eosinophil involvement in AD.

Soluble E-selectin as a marker of disease activity in atopic dermatitis

Background: Augmentation in the expression of adhesion molecules on endothelial cells can regulate leukocyte migration. These molecules are also shed into the circulation. The level of soluble adhesion molecules in the serum is known to reflect the degree of systemic inflammation, and this level can therefore be used as a marker of inflammation. Objective: To elucidate whether soluble adhesion molecules can be used as the marker of disease severity in atopic dermatitis, we examined the levels of soluble E-selectin, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 and compared these levels with the patients' symptom scores and their total serum IgE levels. Methods: Fifty-three patients with atopic dermatitis were studied. Soluble adhesion molecules were measured by ELISA. Results: The level of soluble E-selectin was higher in patients with atopic dermatitis than in healthy control subjects ( p < 0.01). Moreover, soluble E-selectin is correlated with disease severity ( p < 0.01). Soluble E-selectin also reflected the changes in symptom scores. In contrast, there were no differences in soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 between the patients and control subjects. Conclusion: Soluble E-selectin is a good marker of disease severity and of its activity in atopic dermatitis. (J Allergy Clin Immunol 1997;99:410–6.)

Measurement of disease activity and outcome in atopic dermatitis

Many different systems have been proposed for the recording and measurement of disease activity in atopic dermatitis (AD). This review describes the techniques that have been used and published in recent years for clinical evaluation and for objective measurement of AD, as well as for recording its effects on quality of life. Recommendations are made concerning which methods should be used.