The performance of a component-based allergen-microarray in clinical practice.

BACKGROUND: Currently, the diagnosis of IgE-mediated allergy is based on allergen-specific history and diagnostic procedures using natural allergen extracts for in vivo and in vitro tests. OBJECTIVE: The aim of the study was to comparatively analyse a new component-based allergen-microarray and the 'quasi-standard' ImmunoCAP for their clinical relevance in patients with allergic rhinoconjunctivitis to five aeroallergens [house dust mite (HDM), cat dander, birch, grass and mugwort pollen] in a prospective, double-centre study. METHODS: We enrolled 120 subjects at the two study centres. Allergic patients were defined as having an allergen-specific history plus a concomitant positive skin-prick test (SPT) to natural allergen extracts and specific serum IgE was measured by both methods. Each allergen was analysed separately. RESULTS: The microarray performed equally well in receiver-operating characteristic curve (ROC) analyses when compared with the CAP in cat (23 allergic vs 97 non-allergic, ROC area under the curve microarray 0.950 vs CAP 0.894, P = 0.211), birch (31/89, 0.908 vs 0.878, P = 0.483) and grass pollen (47/73, 0.923 vs 0.915, P = 0.770). It was slightly less sensitive in HDM-allergic subjects (26 allergic vs 94 non-allergic, ROC area microarray 0.808 vs CAP 0.911, P = 0.053) and displayed a reduced sensitivity in the mugwort pollen-allergic patients (17/103, 0.723 vs 0.879, P = 0.032). CONCLUSIONS: Component-based testing and the whole-allergen CAP are equally relevant in the diagnosis of grass-, birch- and cat-allergic patients. Although slightly less sensitive, the microarray is sufficient for the diagnosis of HDM-allergic patients, but needs alternative and/or additional components for detecting mugwort allergy.

Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type.

Severe pustular psoriasis von Zumbusch type is a therapeutic challenge not only in adults, but even more in children. We report a 3(1/2)-year-old boy who developed a generalized flare of diffusely scattered pustules on erythematous skin which rapidly progressed to large exuding areas. The clinical presentation and investigations including histopathological examination of a biopsy and negative bacterial cultures were consistent with the diagnosis of pustular psoriasis von Zumbusch type. Upon initial treatment with methylprednisolone, acitretin and antibiotics the extent of the disease declined. However, several attempts to reduce the dose of the oral corticosteroid were followed by immediate severe flares. Additional treatment with narrowband ultraviolet B (NB-UVB, 311-313 nm UVB) resulted in a rapid arrest of disease activity and allowed the corticosteroid to be tapered off. After 10 irradiations the patient was both off steroid and disease free. NB-UVB therapy was subsequently reduced to twice-weekly exposures and acitretin gradually diminished to a maintenance dose of 0.3 mg kg(-1) daily. We conclude that NB-UVB in conjunction with acitretin is a potent therapeutic regimen for the treatment of severe pustular psoriasis von Zumbusch type in childhood.

Management of urticaria: a consensus report.

This consensus report is the result of a panel discussion during the International Clinically Oriented ESDR Symposium Urticaria 2000. Urticaria has a profound impact on the quality of life and effective treatment is required. The most important are nonsedating H1 antihistamines. They have been proven to be effective in double-blind controlled studies, but concentrations higher than those recommended may be necessary. Due to different urticaria subtypes and the individual variation in the course of the disease and response to treatment, however, alternative therapies may be required. Immunosuppressive drugs like cyclosporine A and corticosteroids should not be used long term due to undesirable side-effects.

Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema.

Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment.

Cyclosporin A suppresses ICAM-1 expression by papillary endothelium in healing psoriatic plaques.

To analyze the mode of action of Cyclosporin A (CsA) in psoriasis, we examined the phenotypic profile of resident and passenger skin cells in seven psoriatic patients before and after 2 weeks of CsA treatment using a large panel of monoclonal antibodies in a three-step immunoperoxidase technique. For comparison, skin biopsies from psoriatic patients receiving psoralen + UVA (PUVA) therapy were examined. Although both treatment protocols were equally effective in inducing resolution of psoriatic lesions, the phenotypic changes induced by CsA differed greatly from those seen after PUVA. In CsA-treated patients there was a dramatic reduction in the ICAM-1 expression by papillary endothelial cells, but density, pattern, and phenotype of infiltrating inflammatory cells remained essentially unchanged. In contrast, PUVA therapy had no visible effect on ICAM-1 expression by papillary endothelial cells, but resulted in a significant reduction of the hemopoietic resident and infiltrating mononuclear cells within the epidermis. These results favor, but do not prove, the assumption that the CsA regimen chosen in this study exerts its anti-psoriatic effect primarily at the level of the keratinocyte, i.e., by inhibiting events leading to keratinocyte proliferation as well as by interfering with the secretion of mediators responsible for ICAM-1 expression by papillary endothelial cells.

Anti-retroviral therapy in HIV-1-infected persons: concepts and strategies.

HIV has several characteristics that make it difficult to combat; namely its ability to integrate into the host genome, its tendency to mutate, and its ability to infect at least one organ (the brain) with limited regenerative potential. Although these features of HIV make it quite unlikely that a curative therapy for HIV-induced diseases will be found in the near future, it is very encouraging that, in the brief period since HIV was identified as the etiological agent of AIDS, a variety of drugs have been shown to possess anti-retroviral activity. At least one of them (AZT) has already been proven to decrease morbidity and to prolong survival in ARC/AIDS patients. While several single agents with anti-HIV activity in vitro are now being tested for a beneficial clinical effect in HIV-infected patients, it is likely that combination drug therapy will ultimately be more effective in these patients than one drug alone. Such a combination therapy may allow interference with two or even more stages of the HIV life cycle, may lessen the chance of mutation-induced resistance, and may permit additive antiviral activity without additive toxicity of the drugs.

Effects of physicochemical agents on murine epidermal Langerhans cells and Thy-1-positive dendritic epidermal cells.

The possibility that Thy-1-positive dendritic epidermal cells (Thy-1+DEC) may contribute to the immunologic functions of murine epidermal cells (EC) prompted us to simultaneously assess the effects of certain immunomodulating physicochemical agents on both Thy-1+DEC and Ia-bearing Langerhans cells (LC). C3H/He mice received one of the following treatment modalities: UV-B irradiation (four consecutive days); psoralen plus UV-A (PUVA; three times a week for three consecutive weeks); topically and systemically applied glucocorticosteroids (GCS). Beginning 2 days after the last treatment, animals were sacrificed and the structure and surface marker expression of Ia+EC and Thy-1+DEC were assessed by immunohistologic means on epidermal sheet preparations from ear skin by using appropriate monoclonal antibodies. Whereas low-dose UV-B irradiation (4 X 100 or 200 J/m2) had little, if any, effect on either Ia+EC or Thy-1+DEC, high-dose UV-B (4 X 700 or 1000 J/m2) or PUVA treatment led to an almost complete disappearance of both surface characteristics. Immunoelectron microscopic studies revealed that in the case of LC, high-dose UV-B or PUVA treatment results in the disappearance of their anti-Ia reactivity but leaves their ultrastructural morphology intact. In sharp contrast, Thy-1+DEC escape ultrastructural detection after PUVA treatment and are greatly reduced in number after high-dose UV-B. Ia+EC continuously reappeared with both treatment modalities over a course of 4 to 6 wk, whereas even after 14 to 22 wk Thy-1+DEC were present only in negligible numbers. Similar to high-dose UV-B or PUVA therapy, administration of GCS resulted in the disappearance of both anti-Thy-1- and anti-Ia-reactive cells. Ultrastructural studies disclosed, however, that these steroid-induced alterations in the surface characteristics were accompanied by a dramatic reduction of the LC population but were not paralleled by morphologic changes of Thy-1+DEC. In the course of 7 wk after cessation of steroid treatment, the number of both Ia+EC and Thy-1+DEC had returned to normal values. The selective removal of either of these two dendritic epidermal cell populations by physicochemical agents may provide an excellent strategy to further clarify the functional properties of both LC and Thy-1+DEC.

[The Netherton syndrome: clinical characteristics, differential diagnosis and new ways of therapy]. / Das Netherton-Syndrom: Klinische Charakteristik, differential-diagnostische Abgrenzung und neue Wege der Therapie.

The Netherton-syndrome is a rare disease which is probably inherited through an autosomal recessive trait. It is defined by a triad of symptoms: congenital ichthyosiform erythrodermia , trichorrhexis invaginata et nodosa ("bamboo hair") and atopy. Additional disorders affect the immune system, the metabolism of amino acids and the physical development. On the basis of a new case, the cellular immune defect and the genetic background of the disease are more clearly defined. A new form of treatment--a combination of photochemotherapy (PUVA) and systematic application of aromatic retinoid--has so far proved to be successful. In order to establish an accurate diagnosis--a prerequisite for this promising therapeutic approach--diseases with similar symptoms are discussed for comparison.

Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients.

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.