Clinical Severity Of Atopic Dermatitis Research Articles

Plasma endothelin-1 levels during exacerbation of atopic dermatitis.

Endothelin (ET) -1 was found to participate in the pathogenesis of bronchial asthma. At present, there is no information regarding the role of ET-1 in the pathophysiology of atopic dermatitis (AD). We assessed blood ET-1 levels during the exacerbation of AD and during the 4 months postexacerbation period, to assess the relationships between blood ET-1 levels and clinical severity of AD and pruritus. Patients with AD and during exacerbation were recruited from the dermatology department at the Chita Medical Academy (Chita, Russia). Objective Severity Scoring of Atopic Dermatitis index, itch intensity, plasma concentrations of ET-1, and serum total immunoglobulin E levels were measured at study entry and after 4 months. Eighty-two patients with AD, 35 women (45.1%) and 47 men (54.9%), mean (SD) age of 42.2 ± 11.5 years were included. Thirty healthy volunteers served as controls. The mean (SD) objective Severity Scoring of Atopic Dermatitis index score during AD exacerbation was 48.8 ± 19.4 and at the 4 months postexacerbation period was 16.1 ± 8.3 (p < 0.01). Mean (SD) itch score during AD exacerbation was 6.9 ± 1.9 and, at 4 months postexacerbation was 2.6 ± 0.7 (p < 0.01). Mean (SD) plasma levels of ET-1 in patients with AD (0.74 ± 0.45 fmol/mL) were significantly higher than in healthy subjects (0.43 ± 0.24 fmol/mL) (p < 0.001). Significant correlations were found between plasma ET-1 levels with the objective Severity Scoring of Atopic Dermatitis index (r = 0.51; p < 0.001), Itch severity (r = 0.62; p < 0.001), and with serum immunoglobulin E levels (r = 0.63; p < 0.001) at the exacerbation time point in patients with AD. During AD exacerbation, plasma ET-1 levels were elevated and were positively correlated with AD clinical severity, itch intensity, and serum IgE levels.

Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children

Atopic dermatitis, 25-hydroxyvitamin D, SCORAD index Purpose: Vitamin D deficiency has been suggested to play a role in the pathogenesis of atopic dermatitis. In addition, inverse correlationship between serum 25-hydroxyvitamin D concentration and severity of atopic dermatitis has been suggested. Methods: Clinical and laboratory parameters including serum 25-hydroxyvitamin D level and serum total IgE of 251 patients with atopic dermatitis who were 13 months to 18 years were measured. Severity of atopic dermatitis was assessed with SCORing Atopic Dermatitis (SCORAD) index. Statistical analysis was performed using Pearson correlation coefficient, one-way analysis of variance test and chi-square test. Results: Among 251 patients, vitamin D deficiency (25-hydroxyvitamin D<20 ng/mL, group 1) was present in 76 subjects (30.3%), vitamin D insufficiency (25-hydroxyvitamin D 20-29 ng/mL, group 2) was present in 101 (40.2%), and vitamin D sufficiency (25-hydroxyvitamin D≥30 ng/mL, group 3) was present in 74 (29.5%). There was a statistically significant inverse correlation between serum concentration of 25-hydroxyvitamin D and values of SCORAD index (R=-0.24, P<0.000). Serum concentration of 25 hydroxyvitamin D were inversely correlated with total IgE (R=-0.29, P<0.000), and age (R=-0.49, P<0.000). Conclusion: The results from this study indicate that serum concentration of 25-hydroxyvitamin D is inversely correlated with clinical severity of atopic dermatitis in children. (Allergy Asthma Respir Dis 2014;2:114-121)

Double‐Filtration Plasmapheresis for the Treatment of Patients With Recalcitrant Atopic Dermatitis

The management of recalcitrant atopic dermatitis (AD) is a challenging issue for both clinicians and patients. In this study, we evaluate the clinical efficacy and safety of double-filtration plasmapheresis (DFPP) in patients with recalcitrant AD. Eighteen patients with recalcitrant AD whose clinical condition had not been effectively controlled by current standard medical therapies were treated by either a single course of DFPP (N = 9) or with standard medical therapies only (N = 9). Clinical severity of AD was measured at baseline and at 1 and 4 weeks after treatment in patients in the DFPP group and at the corresponding time points in the control group using the standardized clinical severity scoring system for atopic dermatitis (SCORAD). In the nine patients who underwent DFPP, SCORAD values significantly decreased from 80.6 ± 16.7 (mean ± SD) at baseline to 65.9 ± 20.1 at 1 week and 69.8 ± 20.4 at 4 weeks after DFPP treatment (Wilcoxon signed-rank test, P < 0.05). No significant side-effects were observed during DFPP treatment. In the nine patients with recalcitrant AD who were treated with standard medical therapies, there were no significant differences between the SCORAD values at baseline (70.6 ± 13.9), 1 week (68.0 ± 14.4), and 4 weeks (69.8 ± 17.7) (P > 0.05). DFPP resulted in significant clinical improvements in patients with recalcitrant AD. Further studies are needed to evaluate the long-term clinical usefulness of DFPP in the treatment of patients with recalcitrant AD.

OX40 ligand and OX40 are increased in atopic dermatitis lesions but do not correlate with clinical severity

The interaction between the OX40 ligand (OX40L) and OX40 has been suggested to have pathogenetic significance in atopic dermatitis (AD). The purpose of this study was to investigate the expression and relevance of OX40L and OX40 in AD skin. OX40L and OX40 were stained immunohistochemically on the cryosections of the lesional and non-lesional skin of 17 subjects with moderate-to-severe AD and of 10 patients with psoriasis vulgaris. Phorbol myristate acetate (PMA) stimulated keratinocytes and cell membrane preparations from PMA-stimulated keratinocytes or LAD-2 mast cells were incubated with peripheral blood mononuclear cells (PBMC) in the presence or absence of blocking monoclonal antibodies to OX40L, CD30L or ICAM-1. We show for the first time that the staining intensity of OX40L and the number of OX40(+) cells are significantly greater in the lesional dermis than in the healthy-looking dermis in AD (P < 0.001 in both comparisons) and also in psoriasis (P = 0.01 and P < 0.001 respectively), but neither molecule correlate significantly with the clinical severity of AD. Living keratinocytes and cell membranes from LAD-2 mast cells and keratinocytes increased the PBMC proliferation response. Anti-OX40L antibody inhibited, in a similar fashion as anti-ICAM-1 and anti-CD30L, PBMC proliferation induced by LAD-2 membranes, but stimulated that induced by keratinocytes. Our findings provide evidence for the involvement of OX40 and OX40L in the pathogenesis of AD though they are not specific to AD and in vitro results suggest complex interaction.

Atopic dermatitis: correlation between non‐damaged skin barrier function and disease activity

Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langeland's criteria. Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.

The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis

The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD). We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer. Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86-0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1. Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.

Analysis of Colonization and Genotyping of the Exotoxins ofStaphylococcus aureusin Patients with Atopic Dermatitis

BackgroundThe skin of atopic dermatitis (AD) patients has a high susceptibility to Staphylococcus aureus colonization, and the toxins produced by S. aureus may aggravate AD by acting as superantigens.ObjectiveThe purpose of this study was to evaluate the relationship of the skin barrier function, colonization of S. aureus, and the clinical severity of AD. We also examined the predominant toxin genes produced in Korean AD patients.MethodsThirty-nine patients with AD were evaluated for clinical severity and skin barrier function by using Severity Scoring of Atopic Dermatitis (SCORAD) index and transepidermal water loss (TEWL). S. aureus was isolated from the forearm, popliteal fossa, and anterior nares of AD patients (n=39) and age-matched controls (n=40); the toxin genes were analyzed by performing multiplex polymerase chain reaction.ResultsTEWL showed a statistically significant correlation with clinical severity in patients with AD (p<0.05). TEWL was correlated with the number of S. aureus colonization sites and the presence of nasal colonization, but these results were not statistically significant. S. aureus strains were isolated in 64.1% of the 39 AD patients. The SCORAD index and AD severity were strongly correlated with the number of colonization sites. The predominant toxin gene found in AD patients was staphylococcal enterotoxin a (sea) only, which was produced in 52.6% of patients. The toxin genes sea and toxic shock syndrome toxin-1 (tsst-1) were found together in 42.1%, while tsst-1 only was found in 5.3% of the patients.ConclusionS. aureus strains were isolated in 64.1% of the 39 AD patients. Skin barrier function, as measured by TEWL, revealed a statistically significant correlation with clinical severity in AD patients. The SCORAD index and severity of AD was strongly correlated with the number of colonization. The most common toxin gene was sea in the Korean AD patients and this gene might have an important role in the pathogenesis of AD.

High levels of LIGHT and low levels of soluble herpesvirus entry mediator in sera of patients with atopic dermatitis

Conflict of interest: none declared. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by infiltration of activated T cells.1 Serum chemokine (C‐C motif) ligand (CCL)17 levels are associated with activity of AD.2 LIGHT (lymphotoxin‐like inducible protein that competes with glycoprotein D for herpesvirus entry mediator on T lymphocytes), also known as herpesvirus entry mediator (HVEM) ligand, is a tumour necrosis factor (TNF) superfamily member known for its role in T‐cell development.3 HVEM is a member of the TNF receptor superfamily involved in T‐cell activation. Ligation of HVEM on immune cells (including T cells) by LIGHT leads to activation of their effector functions.4 We evaluated serum levels of LIGHT and soluble (s)HVEM in patients with AD. The medical ethics committee of the University of Tokyo approved the study, and it was conducted according to the principles of the Declaration of Helsinki. The study enrolled 39 patients with AD (27 men, 12 women; mean ± SD age 34.5 ± 10.9 years, range 10–53). Clinical severity of AD was evaluated according to the criteria of Ranikin and Langeland5 as mild (n = 13), moderate (n = 13) or severe (n = 13). Informed consent was obtained from patients and healthy controls. Immunoreactive LIGHT and sHVEM in sera were quantified by ELISA (Human LIGHT/TNFSF14 ELISA Kit and HVEM/TNFRSF14 Duo Set; both R & D Systems, Minneapolis, MN, USA). The control group consisted of 17 healthy volunteers (eight men, nine women; mean ± SD age 36.5 ± 15.4 years, range 12–59).

Beneficial effect of a diet containing heat-killed Lactobacillus paracasei K71 on adult type atopic dermatitis

The purpose of this study was to investigate the clinical effect of a supplementary diet containing heat-killed lactic acid bacterium Lactobacillus paracasei K71 (LAB diet) on adult patients with atopic dermatitis (AD). A randomized, double-blind, placebo-controlled study was conducted in 34 adult type AD subjects who were treated with conventional topical corticosteroid and tacrolimus. LAB diet or placebo was added over 12 weeks. The primary end-point was the clinical severity of AD which was evaluated by a severity scoring system proposed by the guideline of the Japanese Dermatological Association. The effect was also secondarily evaluated by itch scores of visual analog scales (VAS), quality-of-life (QOL) impairment scores of Skindex 16 and consumption amounts of topical therapeutics. Data on these four assessment variables were collected at baseline and at week 4, 8 and 12. Within the study population, the skin severity scores were significantly decreased from baseline at week 8 (P<0.05) and at week 12 (P<0.01) in the LAB diet group but not in the placebo group. Influence of LAB diet on itch scores or QOL impairment scores was not evident. The consumption of topical therapeutics in the placebo group was 1.9-times greater in total amount compared with the corresponding value in the LAB diet group during the intervention period, although there was no significant difference. No LAB diet- or placebo-related adverse events were observed. We concluded that the LAB diet may have some benefits as a complementary therapy for adult AD patients who are managed with the conventional treatment.

Human Papillomavirus DNA in Plasma of Patients with HPV16 DNA-positive Uterine Cervical Cancer

The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment.

Efficacy of a 5-HT1a receptor agonist in atopic dermatitis

Atopic dermatitis (AD) can be aggravated by mental stress. We recently showed that pretreatment with tandospirone citrate (TC), a serotonin (5-HT) agonist for the 5-HT(1A) receptor subtype, significantly inhibits stress-induced degranulation of mouse dermal mast cells. To evaluate the efficacy of TC in treatment of AD. Changes in anxiety levels, depression symptoms and the clinical severity of AD after administration of TC were examined. Data were collected for 20 patients with AD who received TC 30 mg/day for 4 weeks and 17 patients with AD who did not receive the drug. Profile of Mood States (POMS) scores were used to measure several types of mental stress. Severity of AD was evaluated using the SCORAD Index, and the patients' level of stress and sleeping status were evaluated using visual analogue scales. Before TC administration, all scores were markedly different in the 37 patients compared with 37 normal healthy controls matched for age and gender. POMS scores for tension-anxiety (T-A) and the SCORAD Index decreased significantly in patients who received TC, but did not change significantly in the untreated patients. The two groups had significantly different treatment responses based on changes in T-A scores. There was a significant correlation between changes in the T-A score and SCORAD Index. These data suggest that anxiolytic drugs such as 5-HT(1A) agonists are useful in the clinical management of stress-associated aggravation of AD. Inhibition of stress-induced mast cell degranulation may be one of the mechanisms underlying the clinical efficacy.

Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity

The goals were to determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus colonization in patients with atopic dermatitis and to determine whether suppression of S aureus growth with sodium hypochlorite (bleach) baths and intranasal mupirocin treatment improves eczema severity. A randomized, investigator-blinded, placebo-controlled study was conducted with 31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections. All patients received orally administered cephalexin for 14 days and were assigned randomly to receive intranasal mupirocin ointment treatment and sodium hypochlorite (bleach) baths (treatment arm) or intranasal petrolatum ointment treatment and plain water baths (placebo arm) for 3 months. The primary outcome measure was the Eczema Area and Severity Index score. The prevalence of community-acquired methicillin-resistant S aureus in our study (7.4% of our S aureus-positive skin cultures and 4% of our S aureus-positive nasal cultures) was much lower than that in the general population with cultures at Children's Memorial Hospital (75%-85%). Patients in the group that received both the dilute bleach baths and intranasal mupirocin treatment showed significantly greater mean reductions from baseline in Eczema Area and Severity Index scores, compared with the placebo group, at the 1-month and 3-month visits. The mean Eczema Area and Severity Index scores for the head and neck did not decrease for patients in the treatment group, whereas scores for other body sites (submerged in the dilute bleach baths) decreased at 1 and 3 months, in comparison with placebo-treated patients. Chronic use of dilute bleach baths with intermittent intranasal application of mupirocin ointment decreased the clinical severity of atopic dermatitis in patients with clinical signs of secondary bacterial infections. Patients with atopic dermatitis do not seem to have increased susceptibility to infection or colonization with resistant strains of S aureus.

Are there predominant strains and toxins of Staphylococcus aureus in atopic dermatitis patients? Genotypic characterization and toxin determination of S. aureus isolated in adolescent and adult patients with atopic dermatitis

The colonization of Staphylococcus aureus is one of the most important aggravating factors of atopic dermatitis (AD). Until now, the importance of S. aureus in AD and a positive correlation between colonization with S. aureus and clinical severity/skin barrier function has been demonstrated. The aim of this study was to determine whether there are certain clones of S. aureus which colonize the skin of AD patients. For this purpose, the genotype of S. aureus isolated from AD patients was examined by newly-developed typing methods. With 36 strains of S. aureus isolated from 35 patients with AD, spa typing, multi-locus sequence typing (MLST), and staphylococcal toxin gene assay by multiplex polymerase chain reaction, were performed. Clinical severity and skin barrier function were evaluated with eczema area and severity index (EASI) and with transepidermal water loss (TEWL). Among 36 strains of S. aureus, 14 sequence types (ST) and 20 spa types were identified, suggesting a very heterogeneous genetic composition of S. aureus and the absence of a prevailing genotype in S. aureus colonized with AD patients. Furthermore, there was no specific genotype of S. aureus which was associated with the clinical severity of AD or skin barrier dysfunction. A toxin gene assay, however, showed the predominance of S. aureus strains carrying sea and/or tsst-1. To the best of our knowledge, this is the first report to show the genetic composition of S. aureus strains isolated from AD patients determined by sequence-based typing methods.

Serum concentrations of CCR4 ligands in relation to clinical severity of atopic dermatitis in Egyptian children

T helper 2 (Th2) lymphocytes, the key effector cells in pathogenesis of atopic dermatitis (AD), express CCR4 receptors. CCR4 ligands (macrophage-derived chemokine 'MDC' and thymus and activation-regulated chemokine 'TARC') direct trafficking and recruitment of Th2 cells into lesional skin in AD. These chemokines appear to be useful inflammatory markers for assessing severity of AD in adults. However, the same results have not been replicated in children. Therefore, we were stimulated to elucidate the expression of CCR4 ligands in children with AD and their relation to clinical disease severity. To investigate this, serum concentrations of CCR4 ligands were determined in 60 children, of whom 30 had AD and 30 were healthy matched subjects. Patients were classified into mild (n = 8), moderate (n = 12) and severe (n = 10) according to the objective scoring AD (obj-SCORAD) index. Serum concentrations of MDC and TARC were significantly increased in children with AD (2697 +/- 982.6 pg/ml and 945.5 +/- 494.7 pg/ml, respectively) compared with controls (357.2 +/- 233.2 pg/ml and 214.2 +/- 116.6 pg/ml, respectively, p < 0.0001). Serum levels of both chemokines went hand in hand with disease severity as they were significantly higher in severe than moderate and in moderate than mild AD. In addition, they correlated positively with obj-SCORAD (r = 0.99 for both, p < 0.0001). Furthermore, both chemokines had significant positive correlations to blood eosinophil counts and serum immunoglobulin E. In conclusion, serum CCR4 ligands may be useful inflammatory markers for assessing AD severity in children. Further studies may pave way for CCR4 ligands antagonism among the adjuvant therapeutic strategies of AD.

Assessing itch in children with atopic dermatitis treated with tacrolimus: Objective versus subjective assessment

This study was undertaken to evaluate the clinical efficacy of tacrolimus for itch reduction in children with atopic dermatitis (AD). Seven children (3 boys and 4 girls) with AD were treated with topical tacrolimus for a consecutive 2-wk period after a 1-wk run-in. The clinical severity of AD was assessed with the SCORing Atopic Dermatitis (SCORAD) scale. Sleep disturbance, as reported by patients, and nocturnal scratching documented by a wrist movement monitor (DigiTrac), were evaluated at baseline and throughout treatment. The median (interquartile range) objective SCORAD scores before and after treatment were 27.2 (24.8-36.7) and 23.9 (22.6-36.5), respectively (P=.248). Overall SCORAD scores before and after treatment were 36.1 (32.8-45.7) and 29.4 (24.8-45.4), respectively (P=.05). Scores on the itch and sleep disturbance components of the SCORAD were reduced from 5.0 (5.0-6.5) and 4.0 (3.5-5.0) to 4.0 (2.0-5.0) and 3.0 (0.5-4.5), respectively. Total SCORAD was reduced in 6 patients (range, 8%-36% reduction) and remained similar in 1 patient. No significant change in the area or intensity component of the SCORAD was detected 14 d after treatment began (P=.48 and P=.115, respectively). Scratching activity, as documented by the DigiTrac movement recorder, was reduced from 115.0 g/min (64.8-215.5) to 71.5 g/min (51.0-118.0) (P=.028) after 2 wk of treatment. Daily symptom scores (n=6 pairs) for sleep disturbance reported separately each day by patients and parents correlated strongly with each other (intraclass coefficient, 0.60-0.98). The findings of this study show that tacrolimus is effective in relieving itch in children with AD. Investigators suggest that scratching movements, objectively measured with the use of DigiTrac, provide a reliable indicator of AD severity in children.

No effects of probiotics on atopic dermatitis in infancy: a randomized placebo‐controlled trial

Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD). The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy. We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation. No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA. We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.

The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis.

Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD) are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN-γ and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN-γ were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls (P < .001). There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 (P = .227). A statistically significant relationship between SCORAD values and serum levels of total IgE (P < .001), IL-18 (P < .001), and IL-12/p40 (P < .001) was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.

Increase in macrophage migration inhibitory factor levels in lacrimal fluid of patients with severe atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disorder that often involves some ophthalmic features. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is associated with the generation of cell-mediated immune responses. Although serum MIF levels may be elevated in severe atopic dermatitis, the quantity of MIF in regional ocular fluid remains unknown. We measured MIF levels in tears (lacrimal fluid) of patients with atopic dermatitis. Tear samples were collected from 16 patients with atopic dermatitis, 10 patients with allergic conjunctivitis, and 15 healthy control subjects. The clinical severity of atopic dermatitis was evaluated according to the Scoring Atopic Dermatitis (SCORAD) index. The index was calculated by summing the following scores: extent criteria, intensity criteria, and subjective symptoms. Macrophage migration inhibitory factor levels were determined by a human MIF enzyme-linked immunosorbent assay. All comparisons were two-tailed, and P values <0.01 were considered as statistically significant. The mean MIF concentration in lacrimal fluid collected from healthy control subjects was 0.69+/-0.2 ng/ml. The mean tear MIF levels were 17.87+/-6.3 ng/ml in moderate-to-severe atopic dermatitis (SCORAD> or =15, P=0.002), 0.93+/-0.08 ng/ml in mild atopic dermatitis (SCORAD<15), and 2.76+/-0.86 ng/ml in allergic conjunctivitis (P=0.008). A proinflammatory cytokine MIF level was elevated in tears as well as serum in cases of severe atopic dermatitis. These results suggest that MIF may play an important role in the induction or enhancement of ophthalmic features related to severe atopic dermatitis.

Brief case series: Montelukast, at doses recommended for asthma treatment, reduces disease severity and increases soluble CD14 in children with atopic dermatitis

Background: The choice of oral therapeutic agents for the treatment of atopic dermatitis (AD) in children is limited. Montelukast, a specific cysteinyl leukotriene (LT) receptor antagonist, may be useful in alleviating AD symptoms. Objective: To evaluate the clinical and immunological effects of montelukast in children with AD. Methods: After a 2‐week run‐in, children with AD were started on oral montelukast 5 mg once‐daily for children <12 years of age and 10 mg for older children. The clinical severity of AD as indicated by the SCORing Atopic Dermatitis (SCORAD) score, and serum soluble CD14 and urinary leukotriene E4 (LTE4) concentrations were evaluated at baseline and the end of a 3‐month treatment period. Results: Four boys and three girls, with a median (range) age of 12 (3–16) years, participated in the study. The total SCORAD was reduced in five patients (by 30–84%) and remained similar in two patients. Their median (range) SCORAD scores before and after treatment were 34.7 (16.5–54.8) and 17.0 (6.9–36.9) (p = 0.046). The intensity component of SCORAD also decreased from 5 (2–10) to 3 (1–7) (p = 0.042). Serum sCD14 levels increased significantly from 5533 (4575–6452) ng/ml to 6259 (5617–8988) ng/ml (p = 0.028), whereas urinary LTE4 levels remained the same (p = 0.735). Conclusions: Montelukast, at doses recommended for asthma treatment, resulted in over 30% reduction in the total SCORAD in some children. Treatment with montelukast may also be associated with deviation of the immune system towards the Th1‐specific pathway.

Expansion of activated eosinophils in infants with severe atopic dermatitis

There is increasing concern in Japan over infants with atopic dermatitis (AD) who present with severe systemic complications, such as hypoproteinemia, electrolyte disturbances, and delayed growth and development. They are often associated with extremely increased numbers of circulating eosinophils. However, the clinical significance of eosinophil expansion has not been thoroughly investigated. This study attempted to determine the significance of eosinophilia and eosinophil activation in infant cases of AD by comparing multiple clinical parameters, indexes of eosinophil activation, and levels of serum cytokines. CD69 expression was determined by flow cytometry. The clinical severity of AD was graded by the severity SCORing of atopic dermatitis (SCORAD) method. Patients were classified into two groups, with and without CD69 on eosinophils. Nuclear lobes were evaluated under a microscopy. Serum levels of eosinophil-derived neurotoxin (EDN), interleukin (IL)-12, IL-18, IL-4, IL-5 and interferon (IFN)-gamma were determined by enzyme-linked immunosorbent assay. Patients with CD69-positive eosinophils had significantly higher numbers of eosinophils and platelets, total IgE, and eosinophil nuclear lobes. They also showed growth failure, developmental delay, low serum albumin, and electrolyte disturbances. EDN and IL-18 levels were significantly increased in this group, but the levels of IL-4, IL-5 and IL-12 were not significantly different between the two groups. IFN-gamma was not detectable in all patients with AD. Surface expression of CD69 indicates intense systemic allergic inflammation induced in severe cases of AD. Evaluation of eosinophil activation and early therapeutic intervention is mandatory for the treatment of severe AD during infancy.