Masami Uehara

Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis

The density and fine structure of the peripheral nerve system in various skin lesions of 64 patients with atopic dermatitis (AD) was quantitatively analyzed by immunohistochemical staining with antibodies directed against protein gene product (PGP) and substance P (SP). The density of PGP-positive peripheral nerves was 2.5 × 103μm2/Δs (Δs = 0.24 mm2 selected area) in early acute lesions, 3.8 × 103μm2/Δs in subacute lesions, 4.9 × 103μm2/Δs in lichenified lesions and 7.1 × 103μm2/Δs in prurigo lesions of AD. The density of nerve fibers in subacute, lichenified and prurigo lesions was significantly higher than in uninvolved skin of AD patients (2.0 × 103μm2/Δs). Electron microscopically, bulging of axons with many mitochondria and a loss of their surrounding sheath of Schwann cells suggests that the free nerve endings in skin lesions of AD are in an active state of excitation. Many pinocytotic vesicles in the periphery of basal keratinocytes facing nerve endings which contained many neurovesicles suggests reciprocal effects between keratinocytes and nerve endings. The number of SP-positive nerve fibers in AD lesions was far less than one-tenth of the number of PGP-positive nerve fibers.

Blood eosinophilia in atopic dermatitis

Blood eosinophil levels were examined in 200 (100 mild and 100 severe) patients with atopic dermatitis. Eosinophil levels roughly correlated with disease severity. However, the pattern of eosinophilia was not homogeneous. Very high eosinophilia counts were common in severe cases of atopic dermatitis who had a personal or family history of respiratory atopy, while normal or moderately elevated eosinophil values were obtained in severe cases of‘pure’ atopic dermatitis who had neither personal nor family history of respiratory atopy. It is suggested that disease severity and personal or family history of respiratory atopy are important factors in determining high blood eosinophil levels in atopic dermatitis.

Essential Contribution of Germline-Encoded Lysine Residues in Jγ1.2 Segment to the Recognition of Nonpeptide Antigens by Human γδ T Cells

Human γδ T cells display unique repertoires of Ag specificities largely imposed by selective usages of distinct Vγ and Vδ genes. Among them, Vγ2/Vδ2+ T cells predominate in the circulation of healthy adults and respond to various microbial small molecular mass nonpeptide Ags. The present results indicate that the primary Vγ2/Vδ2+ T cells stimulated with the distinct groups of nonpeptide Ags, including monoethyl pyrophosphate, isobutyl amine, and aminobisphosphonate, invariably exhibit Jγ1.2 in the Vγ2+ TCR-γ chains. Gene transfer studies revealed that most of the randomly cloned Vγ2/Jγ1.2+ TCR-γ genes bearing diverse Vγ/Jγ junctional sequences could confer the responsiveness to all these nonpeptide Ags, while none of the Vγ2/Jγ1.1+ or Vγ2/Jγ1.3+ TCR-γ genes could do so. Furthermore, mutation of the lysine residues encoded by the Jγ1.2 gene, which are unique in human Jγ1.2 and absent in other human or mouse Jγ segments, completely abrogated the responsiveness to all the nonpeptide Ags without affecting the response to anti-CD3 mAb. These results strongly suggested that the positively charged lysine residues in the TCR-γ chain CDR3 region encoded by the germline Jγ1.2 gene play a key role in the recognition of diverse small molecular mass nonpeptide Ags.

Skin barrier function in patients with completely healed atopic dermatitis

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.

Upregulating promoter polymorphisms of RANTES relate to atopic dermatitis

It has been reported that a functional polymorphism in the promoter of the RANTES gene (−403G/A) is associated with atopic dermatitis in a German population. Although there are several reports on the association of RANTES promoter polymorphisms (−403G/A and −28C/G) with asthma, the association of these polymorphisms with atopic dermatitis has not yet been confirmed in other populations. We therefore aimed to test whether the RANTES promoter polymorphisms relate to atopic dermatitis in a well‐defined Japanese population. We conducted an association study of upregulating promoter polymorphisms of RANTES (−403G/A and −28C/G) in 389 patients with atopic dermatitis and 177 healthy control subjects. There was a significant association between the upregulating variant of RANTES −28G and atopic dermatitis, while −403A variant showed a significant association with atopic dermatitis with high IgE productivity. These results support a role for RANTES promoter polymorphisms in susceptibility to atopic dermatitis.

Atopic Cataracts in a Japanese Population

Atopic cataract was observed in 19 (12.4%) of 153 Japanese adolescent and young adult patients with atopic dermatitis. Of the 19 patients, 4 had gross cataract which produced impairment of vision, and

Heterogeneity of interleukin 5 genetic background in atopic dermatitis patients: significant difference between those with blood eosinophilia and normal eosinophil levels

BACKGROUND Blood eosinophil levels in patients with atopic dermatitis vary widely during exacerbation of the disease. We considered that in addition to environmental factors, the genetic background involved with elevating blood eosinophil levels might be heterogeneous among atopic dermatitis patients. OBJECTIVE We attempted to determine whether a polymorphism of the interleukin (IL)5 gene plays a role in atopic dermatitis, particularly in those patients with blood eosinophilia. Due to the close relation of blood eosinophilia to high IgE productivity, we also assessed these polymorphisms in patients with high IgE concentrations. METHODS We determined the genotype of the IL5 polymorphism -703C/T in 451 atopic dermatitis patients and 116 normal subjects. The patients were classified into three groups by blood eosinophil levels; less than 7%, from 7 to 15%, and more than 15%, as well as by serum IgE concentrations; less than 500 IU/ml, from 500 to 2000 IU/ml, and more than 2000 IU/ml. RESULTS IL5 -703C/T was not significantly associated with either total atopic dermatitis patients or individual patients who had both blood eosinophilia and high IgE productivity. However, the distribution of the IL5 -703C/T genotype was significantly different between patients with either blood eosinophilia or high IgE productivity and those without either condition (P=0.0476, P=0.0088, respectively). CONCLUSION These results suggest that the IL5 gene may play a role in blood eosinophilia associated with atopic dermatitis. We also considered that the IL5 -703C/T gene polymorphism does not have a direct relationship to disease specificity.

Genetic homogeneity of Trichophyton mentagrophytes var. interdigitale isolated from geographically distant regions.

To evaluate the genetic homogeneity of Trichophyton mentagrophytes var. interdigitale, restriction enzyme analysis of mitochondrial(mt) DNA was performed on 29 isolates of T. mentagrophytes var. interdigitale isolated from Belgian or Indian patients with dermatophytosis. The restriction enzyme profiles of these mtDNAs were compared with those of the teleomorphic members composing the T. mentagrophytes complex. Using the restriction enzymes MspI, HaeIII, HindIII and BglII the restriction profiles of all the examined clinical isolates showed the same profiles as those of Arthroderma vanbreuseghemii. T. mentagrophytes var. interdigitale isolates found in Japan have been shown to have the same profiles as those of A. vanbreuseghemii. Therefore, T. mentagrophytes var. interdigitale is considered to be a highly homogeneous taxon phylogenetically related to A. vanbreuseghemii.

Use of soap in the management of atopic dermatitis

One hundred and thirty patients with atopic dermatitis, who had used no soap for at least a month, were allowed to use common toilet soaps when having a shower to keep the skin clean. Immediately after bathing, the skin lesions and areas of dry skin were treated with topical medications.

Role of Foods in Irregular Aggravation of Atopic Dermatitis

Although it is well known that patients with atopic dermatitis often show unpredictable, irregular aggravation of skin lesions, there are no previously published studies examining trigger factors for such unpredictable aggravation. We investigated whether foods play a role in the unpredictable, irregular worsening of atopic dermatitis. The patient group included 195 Japanese adult patients with atopic dermatitis who showed unpredictable, irregular aggravation of skin lesions. They were hospitalized and openly challenged with suspected foods. Photographs of representative skin lesion sites were taken at baseline and before and after the challenge. Challenge‐positive foods were determined by evaluating the comparable before‐after challenge photographs. One to three (average: 1.7) challenge‐positive foods were confirmed in 86 (44%) of the 195 patient examined. Predominant offending foods were chocolate, cheese, coffee, yogurt and some Japanese foods such as glutinous rice cake, soy sauce and fermented soybeans. Specific IgE values to the offending foods were mostly negative. Patients were asked to exclude challenge‐positive foods from their diets. They were then discharged and followed up for 3 months at our outpatient clinic. Exclusion of the offending foods for 3 months brought about a progressive improvement of the disease. These results suggest that foods play an important role in unpredictable, irregular aggravation of skin lesions in patients with atopic dermatitis.