Nonspecific T-cell homing during inflammation in atopic dermatitis: expression of cutaneous lymphocyte-associated antigen and integrin alphaE beta7 on skin-infiltrating T cells

All human natural killer cells and some memory T cells express HLA class I receptors, so-called natural killer cell receptors (NKRs), a receptor class that in the past few years has been shown to include several members of the immunoglobulin superfamily and the C-type lectin CD94-NKG2A complex. NKR ligand mediated cross-linking leads to the recruitment and activation of a tyrosine phosphatase involved in downregulating the phosphorylation of effector molecules involved in cell triggering. Thus, NKR engagement leads to the inhibition of different NK and T cell functions.     

Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis

The majority of allergen-specific T cells derived from inhalant allergen patch test lesions in patients with atopic dermatitis were previously found to produce a restricted type-2 cytokine pattern. Recent studies, however, have revealed that in chronic eczematous skin lesions of patients with atopic dermatitis, expression of the type-1 cytokine interferon-gamma predominates. To evaluate cytokine production by allergen-specific T cells in chronic atopic dermatitis, we established house dust mite (Dermatophagoides pteronyssinus)-specific T-cell clones from the dermis of chronic skin lesions of sensitized adult patients with atopic dermatitis. Frequencies of skin-derived T cells proliferating in the presence of Dermatophagoides pteronyssinus were between one in 138 and one in 4255, indicating that only a minority of skin-infiltrating T cells are allergen specific. When these cells were analyzed for their capacity to produce interferon-gamma, the majority (71%) of these cells were found to express interferon-gamma mRNA and to secrete interferon-gamma protein, either alone or in combination with interleukin-4. Phenotypic analysis revealed that 15% of skin-infiltrating allergen-specific T cells were CD8+. No selection of Vbeta elements was detected in Dermatophagoides pteronyssinus-specific T-cell clones. These studies demonstrate that allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in lesional atopic dermatitis. The notion that the majority of allergen-specific, skin-infiltrating T cells are capable of producing interferon-gamma further supports the concept that interferon-gamma expression has major pathogenetic relevance for the chronic phase of atopic dermatitis.     

Promoting health in children with atopic dermatitis

Atopic dermatitis (AD), or eczema, can be a very challenging disease to manage. The etiology of the disease is not completely understood, and its incidence has risen in the past 10 years to more than 10% of the population. AD is characterized primarily by intense itching and the development of papules, scaly lesions, fissures, and crusting. The onset occurs primarily in childhood, and much of the disease management is conducted by the family. Patients and their families often experience multiple recurrences and exacerbations, repeated attempts at cures and treatments, lowered self-esteem of the child, impaired growth and development of the child, loss of sleep, discipline problems, and multiple clinic and emergency department visits for exacerbations. Management primarily consists of prevention (i.e., good daily skin care and management of environmental trigger factors such as infection, irritants, emotional stress, and allergens). These children and their families need education and the support of health care professionals. This article outlines specific techniques to help parents and children manage AD at home and minimize exacerbations.     

Candida albicans sensitization in patients with atopic bronchial asthma and atopic dermatitis

Candida albicans, a component of normal human microflora, can induce synthesis of specific IgE-antibodies in patients with atopic bronchial asthma and atopic dermatitis. The study included 25 patients with atopic dermatitis sensitized to C.albicans and 23 patients with atopic dermatitis non-sensitized to C.albicans. The sensitization was determined by the skin test and enzyme immunoassay. The patients had the history of atopic dermatitis exacerbation after taking food containing baking yeasts. Atopic dermatitis with sensitization to C.albicans is characterized by severe course correlating with the following indices: high total IgE (r = 0.6), level of IgE antibodies to C.albicans (r = 0.6), level of serum IgG (r = 0.46) and IgA (r = 0.33). Contrary to adults, children with sensitization to C.albicans had decreased relative number of CD4+, CD8+ and CD72+ of lymphocyte subpopulations. Thus, sensitization to C.albicans manifests in severe atopic dermatitis which in children is often associated with immune deficiency.     

New concepts in atopic dermatitis

Allergic bronchopulmonary aspergillosis (ABPA) occurs in 1-2% of patients with asthma and in 10% of patients with cystic fibrosis. We introduce the acronym "ARTEPICS" in this review article on ABPA to facilitate its diagnosis: A: Asthma; R: Roentgenographic infiltrates; T: Tests for Aspergillus fumigatus (Af) positive in the skin; E: Eosinophilia; P: Precipitating antibody to Af; I: IgE in serum elevated; C: Central bronchiectasis; and S: Serum specific IgE-Af and IgG-Af elevated (ARTEPICS).     

Impression cytology in atopic dermatitis

PURPOSE: This study aimed to describe the ocular surface disorder in patients with atopic dermatitis (AD). DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 44 patients with active AD seen at Kobe University School of Medicine, Department of Ophthalmology, during 1994 through 1996 and 22 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, tear film break-up time (BUT), Schirmer test, and conjunctival impression cytology. MAIN OUTCOME MEASURES: Patients and control subjects were compared for tear function parameters, goblet cell density, and conjunctival squamous metaplasia grade. The relation of duration and recurrences of AD to the ocular surface disorder also was looked for. RESULTS: The duration of atopic disease ranged from 18 to 32 years (mean, 22.8 years). The average for exacerbations was 4.5 times. Chronic allergic conjunctivitis with superficial punctate keratitis was the most frequent clinical presentation. The BUT and Schirmer test values were significantly lower in patients with AD compared with those of the control subjects. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which related to the number of recurrences of AD rather than the duration of disease. Facial atopy and allergic keratoconjunctivitis (AKC) related to the metaplasia of the ocular surface (P < 0.001). Patients with reduced goblet cell density also showed low BUT levels (P < 0.001). CONCLUSION: Ocular surface disorder of AD characterized by goblet cell loss and conjunctival squamous metaplasia seemed to evolve independently of the duration of disease but worsen with increased number of flare-ups. Direct epithelial damage by the allergic reaction, disorder of tear quality, and quantity may be important in the genesis of the atopic ocular surface disease.     

Elimination protocols in atopic dermatitis

Both dacryocystography and dacryoscintigraphy are well established in the evaluation of stenoses of the lacrimal drainage system. They provide limited information about the ductal anatomy itself and about periductal structures. MR imaging was evaluated for its capability to directly visualize the lacrimal drainage system in detail and simultaneously provide functional characterization of dacryostenosis. SUBJECTS AND METHODS: Twenty-seven lacrimal drainage systems of 23 patients suffering from epiphora were examined in an MR unit before and after conjunctival and intravenous application of Gd-DTPA using a surface coil. RESULTS: Dacryostenosis was found in 23 of 27 lacrimal systems. Stenoses were localized to the canalicular (n = 3), saccular (n = 8), and ductal (n = 12) level, and were classified as stenosis or occlusion. CONCLUSION: MR imaging with conjunctival contrast application allows within one examination both detailed morphological and functional assessment of the lacrimal drainage system with depiction of surrounding structures. Limitations arise mainly from demands on technical and patient-related preconditions.     

Immunopathologic disorders in atopic dermatitis

The atopic dermatitis is a multifactorial inheritable disease, in which pathogenesis in addition to environmental factors (climate, allergens, clothing) genetically determined multiplex metabolic differences (arachidonic acids, essential fatty acids) and immunologic alterations play an important role. Within immunologic findings the disturbances of balance in Th1 and Th2 subclasses, the increased degranulation activity of mast cells and the increased antigen presentation activity of Langerhans cells can be stressed. The clinical immunological alterations shown in the diseases, the increased production of IgE and so the type I. allergic reactions (urticaria, gastrointestinal manifestation of food allergy, allergic rhinitis, asthma bronchiale), the difference of cellular immunity of the skin can be explained by the above mentioned main immunological changes. In understanding of immunological origin of atopic dermatitis the IgE receptors expressed on the surface of Langerhans cells (connecting the immediate and delayed type of immune response) mean significant help.     

Efficacy trial of bioresonance in children with atopic dermatitis

The unfavorable breast contours resulting from a reductive mammaplasty or a mastopexy influenced the authors into developing a technique that provided reduction of the breast base and axillary pole, convenient medial position of the lateral pole and substantial conification of the breast tissue to help project the areolomamillary complex to the apex of that cone. From March 1987 to May 1996 two hundred and seventeen operations were performed with this technique that consists of construction of three glandular flaps and maximum preservation of the skin covering. The results obtained showed to be very satisfactory and more lasting.     

Probable decompression sickness in a trainee with atopic dermatitis

Hypobaric chamber training has a potential risk of inducing decompression sickness (DCS). A case of a patient with an atopic dermatitis who complained of paresthesia and numbness in his left arm and shoulder during the altitude exposure is presented here. His symptoms were severe enough for the attending medical officer to diagnose Type II DCS, but it turned out to be a probable case of simple skin bends requiring no treatment. The author can find no better explanation for this discrepancy than the contribution of dermatitis. The possibility of atopic dermatitis confounding the correct diagnosis of the severity of DCS is proposed.     

Abnormal vascular reactions in atopic dermatitis

Vascular reactions to mechanical stroking, topical application of nicotinic acid ester, and methacholine chloride were examined in both the normal and abnormal skin of 100 patients with atopic dermatitis and 20 patients with allergic contact dermatitis. White dermographism, nicotinic acid blanching, and delayed blanch with methacholine consistently occurred in areas of skin with eczematous change of patients with atopic dermatitis and those with allergic contact dermatitis. Normal skin of atopic patients did not show the abnormal vascular reactions. It is suggested that white dermographism, nicotinic acid blanching, and delayed blanch with methacholine seen in atopic dermatitis are secondary phenomena that give no definite information concerning the diagnosis of this disease.     

Flucloxacillin in the treatment of atopic dermatitis

Although colonization of atopic dermatitis by Staphylococcus aureus is universal and bacterial infection is common, it is not known whether antibiotic therapy is helpful in eczematous children who do not have any signs suggestive of bacterial infection. Fifty children aged 1-16 years with atopic dermatitis took part in a randomized double-blind placebo-controlled study of 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. The change in the mean of the log10 of the counts/cm2 of S. aureus after 4 weeks of treatment was significantly different for patients receiving treatment, compared with the change for those receiving the placebo (P = 0.008). However, the difference in the change at 14 days after stopping treatment was not significant (P = 0.32). Methicillin-resistant strains of S. aureus were cultured from five children during or after treatment. Flucloxacillin did not improve the symptoms or clinical appearance of atopic dermatitis and only temporarily changed skin colonization by S. aureus.     

Immunomodulation in the treatment of atopic dermatitis

In the submitted review the authors present information on possibilities of immunomodulating treatment of atopic dermatitis. Immunosuppressive treatment comprises systemic corticosteroid administration (possibly combined with cytostatic immunosuppressive preparations), cyclosporin A and phototherapy. Immunopotentiating treatment of AD makes use mainly of modulating preparations with the nature of physiological substances close to the immune system, substances obtained from natural biological sources (thymic hormones) or in recent years more frequently substances of recombinant origin (interferons, interleukins). The use of immunopotentiating drugs of chemical origin (synthetic substances) is used less frequently in AD. The use of intravenous immunoglobulin preparations for severe forms of atopic dermatitis is only just starting.     

Diagnostic tests in children with atopic dermatitis and food allergy

BACKGROUND: Skin testing is a common diagnostic procedure in food allergy. The skin prick test is the test of first choice for investigating the immediate IgE-mediated reaction. The skin application food test (SAFT) has been developed on the basis of the mechanism of the contact urticaria syndrome (CUS). METHODS: We studied the relevance of the SAFT in children younger than 4 years with atopic dermatitis and (suspected) food allergy as compared with the prick-prick test, the radioallergosorbent test (RAST), and the oral challenge. In the skin tests, we used fresh food, in the same state as it was consumed. RESULTS: There was a good agreement between the SAFT and the prick-prick test. A moderate agreement was observed between the SAFT and the serologic test (RAST). Significantly more positive results in the RAST were observed than in the SAFT. There was very good agreement between the SAFT and the oral challenge (kappa = 0.86). CONCLUSIONS: The SAFT is a reliable and child-friendly skin test for evaluating (suspected) food allergy in children younger than 4 years with atopic dermatitis. The very good correlation with the oral challenge indicates that one may probably consider the SAFT a "skin provocation" in children younger than 4 years.     

Undetectable interferon-alpha serum levels in a patient with atopic dermatitis

An In-111 WBC study showed intense periarticular uptake in both knees of a patient being investigated to exclude joint infection before total knee replacement surgery for advanced osteoarthritis. Infection was subsequently excluded. Patients with synovitis secondary to active osteoarthritis can have intense synovial uptake of labeled WBCs. This should be considered as a cause of false-positive scans in the investigation of septic arthritis with labeled WBCs.     

The role of T lymphocytes in patients with food-sensitive atopic dermatitis

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hen's egg or cow's milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hen's egg or cow's milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hen's egg were significantly higher than those of healthy children and patients sensitive to hen's egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.     

Clinical course of atopic dermatitis in Japanese patients

To determine which diagnoses in the emergency department (ED), apart from battering injuries, were more common among women who were living in physically abusive relationships than among women who were not, a study was conducted in 10 hospital-based EDs in two cities serving inner city, urban, and suburban populations. A total of 9,057 women between the ages of 19 and 65 years presenting to the EDs were eligible for the study. Medical records were reviewed, and a written questionnaire was used. The questionnaire was completed by 4,501 (73% of those asked, 59% of those eligible, and 50% of those presenting). Two hundred sixty-six (5.9%) were currently in a physically abusive relationship but not in the ED for battering injuries, and 3,969 (88.2%) were not currently in a physically abusive relationship. An additional 266 (5.9%) were positive, probable, or suggestive for battering injuries and excluded from diagnosis comparisons. Women in physically abusive relationships were more likely to be diagnosed with urinary tract infections, neck pain, vaginitis, foot wound, suicide attempt, and finger fracture. However, these represented only 19.8% of diagnoses in this group. The use of this knowledge alone to predict the presence of intimate violence in individual patients in the ED will not identify the majority of women at risk. These results suggest the use of routine inquiry for abuse in all women.