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Biomedical subjects

M S de Bruin-Weller

Publications and source records attributed to M S de Bruin-Weller.

14 recordsLinked to original sources
PubMed2007

Efficacy and safety of long-term treatment with cyclosporin A for atopic dermatitis.

BACKGROUND: Cyclosporin A (CsA) is being increasingly used in the treatment of severe refractory atopic dermatitis. Clinical efficacy and safety of short-term cyclosporin A treatment in atopic dermatitis patients has been proven, however, data on long-term treatment are limited. OBJECTIVE: The aim of this study was to investigate the efficacy, safety and the effect of discontinuation of cyclosporin A treatment in atopic dermatitis patients, with a particular focus on patients treated with cyclosporin A for more than 6 months. METHODS: We performed a retrospective study of clinical and adverse effects of cyclosporin A treatment in 73 atopic dermatitis patients, with an average duration of cyclosporin A treatment of 1.3 years. RESULTS: We included 73 patients (31 women and 42 men, with a mean age of 33.8 years) with severe atopic dermatitis refractory to conventional therapy that was treated with cyclosporin A. Treatment was successful in 56/73 patients. Increases in serum creatinine levels > 30% compared to baseline were reported in 7/73 patients. Arterial hypertension appeared in 11/73 patients during treatment. After discontinuation of treatment, 40/73 patients experienced a relapse and 33/73 patients experienced clinical remission for at least 3 months. No correlation between treatment duration and nephrotoxicity or hypertension was found. Strikingly, 6/73 patients experienced a rebound phenomenon. CONCLUSIONS: We conclude that CsA is an effective and safe treatment for patients with severe AD refractory to conventional treatment, provided that the recommended guidelines for its administration are strictly observed. However, in contrast to previous reports, we found that 8% (6/73) of patients experienced a rebound phenomenon after discontinuation of treatment.

Adult↗
PubMed2006

No effect of anti-interleukin-5 therapy (mepolizumab) on the atopy patch test in atopic dermatitis patients.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. METHODS: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days -2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. RESULTS: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. CONCLUSION: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils.

Adult↗
PubMed2006

Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. METHODS: Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis. RESULTS: Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc epsilon RI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. CONCLUSIONS: Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis.

Adult↗
PubMed2005

[Topical immunomodulators, such as tacrolimus and pimecrolimus, in the treatment of atopic dermatitis].

Atopic dermatitis is a chronic inflammatory skin disease with a relapsing course. Topical corticosteroids are the usual treatment of atopic dermatitis. Long-term use of topical corticosteroids may lead to local side effects, such as skin atrophy, and systemic side effects, such as induction of hypothalamus-pituitary-adrenal axis suppression. Tacrolimus and pimecrolimus are new topical immunosuppressive drugs known as topical immunomodulators (TIMs). Clinical efficacy of these drugs has been demonstrated in various long- and short-term placebo-controlled studies. The efficacy oftacrolimus is comparable to a class 2 dermatocorticosteroid and the efficacy of pimecrolimus is comparable to a class 1 dermatocorticosteroid. A major advantage of the use of TIMs is that they do not result in skin atrophy. Tacrolimus may cause local irritation, which mostly disappears after 2 weeks. Little is known about the long-term safety of TIMs. It is expected that TIMs will have an important role in the treatment of mild to moderate atopic dermatitis. Combined treatment with dermatocorticosteroids and TIMs needs further investigation. For patients with severe atopic dermatitis, the addition of TIMs to oral immunosuppressive drugs, such as cyclosporin, may allow for dose reductions of oral medication.

Administration, Topical↗
PubMed2005

Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis.

BACKGROUND: Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD. METHODS: Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of 'success' to treatment was defined as the percentage of patients with at least 'marked improvement' after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticasone propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded. RESULTS: Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05). CONCLUSION: Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.

Adult↗
PubMed2004

Atopy patch test in patients with atopic eczema/dermatitis syndrome: comparison of petrolatum and aqueous solution as a vehicle.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens. This study was designed to compare two commonly used APT methods. METHODS: In the first method, the allergen is dissolved in aqueous solution, which is applied on tape-stripped skin. In the second method, the allergen is dissolved in petrolatum and applied without tape stripping. Thirteen patients with atopic dermatitis sensitized to inhalant allergens were patch tested using both methods. Reactions were evaluated macroscopically and microscopically after 48 h. RESULTS: Nine out of 13 patients displayed a positive reaction for both methods. One patient had a positive APT for the aqueous method alone and three for the petrolatum method alone. Reactions were significantly stronger when using the petrolatum method. Histological evaluation of the nine patients positive for both methods showed no significant differences in number of eosinophils, T-cells and neutrophils. CONCLUSION: The APT using the petrolatum vehicle induces a higher number of positive reactions and is significantly stronger relative to the APT using allergen in aqueous vehicle. The cellular influx in both test methods is comparable. Both methods can be used to study the mechanisms in the induction of eczema by inhalant allergens.

Adult↗
PubMed2002

Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study.

BACKGROUND: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma. METHODS: Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period. RESULTS: There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC(20) histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group. CONCLUSION: The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance.

Adolescent↗
PubMed1999

Repeated allergen challenge as a new research model for studying allergic reactions.

Repeated allergen challenge might be a more relevant model for studying symptomatic disease, because it gives more information on the patient's handling of chronic allergen exposure. Thus, this experimental model has more resemblance to the situation of natural allergen exposure, and the allergen load can be standardized. However, the response to repeated allergen challenge in individual patients can show a large variation, that is from a strongly enhanced response to complete diminution of the response. Successful allergen immunotherapy can change the response pattern of repeated allergen challenge in the skin into down-regulation of the late reaction. Chronic or repeated allergen exposure may result in an enhanced allergen-specific allergic response, involving allergen-specific T-cell activation. Different subsets of T cells can exert either activating or suppressive effects on inflammatory cells involved in subsequent allergic reactions. CD8+ T cells might exert suppressive effects, because they seem to be associated with a subsequent down-regulation of the late skin reaction after repeated allergen challenge (Fig. 4). Further studies are needed to compare the responses to repeated allergen challenge with the response to natural seasonal allergen exposure in the same patients and to explore possible underlying mechanisms using, for example, nasal biopsies.

Allergens↗
PubMed1996

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness.

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

Adolescent↗
PubMed1996

Early and late allergic reaction in the nose assessed by whole body plethysmography.

Physiological changes during late phase nasal responses after allergen challenge are difficult to establish and different criteria are used for the definition of a positive late phase nasal reaction. The objective of this study was to assess the value of whole body plethysmography in detecting changes in nasal airway resistance after allergen challenge and to suggest criteria for the definition of early and late phase nasal reactions. Nasal challenge with allergen was performed in 15 allergic patients. Nasal resistance was followed until 10 h after allergen challenge and on a control day using whole body plethysmography. The mean percentage changes in the inspiratory nasal resistance during the early phase period (0.25-2 h) and the late phase period (4-10 h) were significantly higher on the allergen challenge day than on the control day (p=0.001 and p=0.01, respectively). The mean percentage change in the inspiratory nasal resistance during the early and late phase period on the control day plus 2 times the standard deviation served as cut-off point for a positive reaction. Using this definition, all patients had early reactions and 7 of the 15 patients (47%) also had late reactions. We conclude that whole body plethysmography is a useful, noninvasive method for the measurement of the physiological changes in the nose following allergen challenge.

Adult↗
PubMed1994

Lack of effect of cetirizine on early and late asthmatic response after allergen challenge.

BACKGROUND: Cetirizine hydrochloride has proved effective in reducing allergic symptoms and can inhibit the infiltration of eosinophils in allergic late-phase responses in the skin. Because eosinophils are likely to play an important role in allergic late-phase reactions, we studied the effect of cetirizine on early and late asthmatic reactions and on levels of eosinophil cationic protein (ECP) in the blood after allergen challenge. METHODS: The effect of 15 mg cetirizine given twice daily was studied in 16 patients allergic to house dust mites in a double-blind, placebo-controlled study. Patients were treated for 3 weeks. Before and after treatment, bronchial challenges with house-dust mites were performed. Blood ECP levels were measured 6 hours after challenge. Methacholine provocation was performed 72 hours before and 24 hours after each challenge. RESULTS: Early and late asthmatic response--measured as mean maximal fall in forced expiratory volume in 1 second (FEV1) and the provocative dose of allergen that causes a 15% fall in FEV1 (PD15 allergen)--were not significantly reduced after treatment with cetirizine, compared with placebo. There was also no significant effect on the concentration of methacholine, which causes a 20% fall in FEV1 (PC20 methacholine). The increase in the level of ECP in the blood after allergen challenge was reduced after cetirizine treatment, compared with placebo, but this difference was not statistically significant. CONCLUSION: Eighteen days of treatment with cetirizine did not significantly reduce the intensity of the early and late asthmatic responses.

Adolescent↗