Exacerbation Of Atopic Dermatitis Research Articles

Efficacy of Crisis Intervention Treatment with Topical Corticosteroid Prednicarbat with and without Partial Wet-Wrap Dressing in Atopic Dermatitis

Background: The wet-wrap treatment has been reported to be beneficial in acute episodes of atopic dermatitis (AD) skin lesions. Objective: The efficacy of topical corticosteroid prednicarbat with and without additional wet-wrap dressing was investigated in a prospective, randomized and controlled study. Methods: In the left-right comparison study, 24 adults and children with an acute episode of AD were included. One arm or leg was randomly treated with the topical corticosteroid prednicarbat plus wet-wrap dressing; only prednicarbat was applied on the leg or arm of the other side. Results: After 48–72 h of treatment, in both groups an improvement of the local SCORAD was observed. In comparison to the side of the body treated with corticosteroid alone, the decrease of the local SCORAD in the corticosteroid plus wet-wrap dressing group was significantly better. The severity of AD improved in the wet-wrap group at an average of 4.4 points, in the corticosteroid group 3.0 (p < 0.011). Conclusions: Wet-wrap therapy with a topical corticosteroid is an effective treatment option in patients with exacerbated AD. The treatment is helpful in improving skin conditions, shortening the time of corticosteroid application.

Exacerbation of atopic dermatitis in the emergency department

A 38-year-old man was admitted to the Emergency Department suffering from an exacerbation of atopic dermatitis, fever and a burning sensation in the eyes. He was first treated with systemic corticosteroids. A subsequent dermatological and ophthalmological examination established the diagnosis of Kaposi-Juliusberg disease or eczema herpeticum with bilateral herpetic keratitis. Eczema herpeticum is an uncommon herpes simplex virus infection that occurs in patients with atopic dermatitis. Because it is a possible life-threatening condition, this disease must be recognized by all emergency physicians. The association with herpetic keratitis is not frequent but is a major ophthalmological problem. Treatment consists of the administration of high-dose intravenous acyclovir and acyclovir ophthalmic ointment.

Aktuelles zur Nahrungsmittelallergie bei atopischer Dermatitis

Food allergy is a common problem in patients with atopic dermatitis, particularly in children. Cow's milk, hen's egg, soy and wheat have been identified as frequent food allergens in this age group. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. We have investigated the importance of food for the induction of late eczematous reactions in children with atopic dermatitis aged 1 - 10 years. This article shows the results of our study and discusses the previous literature. 46% of our challenges were related to a clinical reaction. 43% of these reactions were associated with an isolated immediate reaction. An exacerbation of atopic dermatitis (late eczematous reaction) commonly occured 24 hours after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. 45% of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. We correlated the clinical outcome to the results of specific IgE determinations and atopy patch tests, which resulted in poor predictive values for both in-vitro and skin tests particularly for the late eczematous reactions. Therefore, food challenges have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with atopic dermatitis.

Presence of staphylococcal exfoliative toxin A in sera of patients with atopic dermatitis.

It has been reported that the toxins that Staphylococcus aureus produces are associated with the exacerbation of atopic dermatitis (AD). It has been shown in many studies that staphylococcal enterotoxin (SE) A and SEB contribute to AD by humoral immunity through IgE production as a superantigen. On the other hand, little attention has been paid to the relationship between AD and exfoliative toxin x (ETx). We investigated the toxins that are frequently detected from the skin of patients and how these toxins affect AD. S. aureus, isolated from the skin of 100 patients with mild to severe AD, were examined for the producibility of toxins by polymerase chain reaction. Serum samples were obtained from 21 patients with mild and moderate AD. The levels of SEB, ETA, total IgE, specific IgE, and specific IgG in sera were measured by ELISA. SEB was most frequently detected from S. aureus on the skin of these patients as previously reported. And ETx, to which little attention has been paid so far, was frequently detected next to SEB. Furthermore, ETA was detected from the sera of almost all the AD patients. SEB was not detected at all. Although the level of ETA in the AD group was significantly higher than that of controls, ETA-specific IgE was not detected from their sera. High levels of ETA tended to be detected from infantile patients. Although there were no significant differences in the levels of ETA-IgG between AD and the controls, its prevalence was more than twice as high as the controls in AD. These results suggest that many AD patients were exposed to ETx. We conclude that ETx may contribute to exacerbation of AD, particularly in infants, by a mechanism that is not through specific IgE production, unlike SEB.

Effects of Neuropeptides In The Development Of The Atopic Dermatitis Of Mouse Models

Neuropeptides are considered to be factors that trigger, exacerbate or modulate allergic diseases and inflammatory skin reactions. In addition, it has been indicated that allergic diseases are highly correlated with stress. 2,4,6-Trinitrochlorbenzene (TNCB) and crowding stress were applied to mouse atopic dermatitis (AD) models for the purpose of provoking chronic dermatitis. In addition, TNCB-sensitized mice were given olopatadine hydrochloride (10 or 3 mg/kg), an anti-allergic agent, orally. The neuropeptide content in the skin tissues and serum IgE levels were measured in these mice. Repeated local application of TNCB solution induced itching skin lesions, together with an increase in levels of substance P, a decrease in calcitonin generelated peptide levels and early augmentation of IgE production. Treatment with crowding stress brought about a transient increase in substance P. Furthermore, we observed significant decreases in substance P and serum IgE levels when the administration of olopatadine hydrochloride was started before the elicitation of chronic dermatitis caused by repeated application of TNCB solution. These changes were more definite in the group administered a higher dose of the drug (10 mg/kg). It is suggested that repeated contact allergic dermatitis or mental stress may promote the development and exacerbation of AD and that substance P has a role in this response. In addition, it seems that an anti-allergic drug, such as olopatadine hydrochloride, possibly downregulates substance P, thereby suppressing the development of AD. In the future, the development and clinical application of a drug that strongly influences the release of neuropeptides, such as substance P, and the expression of neuropeptide receptors would be expected for the treatment of AD.

Characterization of recombinant cat albumin.

Indoor allergens derived from animals and mites often contribute to exacerbation of skin manifestations in atopic dermatitis (AD) patients. To produce and characterize recombinant cat albumin, a cross-reactive animal allergen. A complete cDNA coding for cat albumin was obtained by RT-PCR amplification from cat liver RNA. Recombinant cat albumin was expressed in Escherichia coli as hexahistidine-tagged protein, purified by nickel affinity chromatography and studied for IgE reactivity with sera from cat-allergic patients by ELISA and immunoblotting. Furthermore, CD203c expression of basophils from cat-allergic patients upon exposure to recombinant cat albumin was analysed. Recombinant cat albumin, a cross-reactive animal allergen sharing most IgE epitopes with its natural counterpart, was produced in E. coli. It was recognized preferentially by IgE from AD patients and elicited IgE-dependent basophil activation in sensitized patients. Recombinant cat albumin may be used as a paradigmatic tool to analyse mechanisms of allergen-triggered exacerbation of AD, for diagnostic and, perhaps for therapeutic purposes.

High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress

Pentosidine is an advanced glycation end product formed by sequential glycation and oxidation. The formation of pentosidine is increased in diseases associated with oxidative stress, such as inflammatory conditions. The aim of the present study was to determine the urinary concentration of pentosidine in atopic dermatitis (AD) and its relationship to the inflammatory status of AD. Urine samples of 32 children with AD and 30 age-matched healthy control subjects were assayed for pentosidine, pyrraline (another advanced glycation end product formed by nonoxidative glycation), and 8-hydroxy-2’-deoxyguanosine (8-OHdG) (an established marker of oxidative stress). Of these 3 markers, urinary concentrations of pentosidine were significantly higher in patients with acute exacerbation of AD than in healthy controls and patients with stable AD. Urinary concentrations of 8-OHdG were significantly higher in AD patients with and without acute exacerbation than in healthy controls. Urinary pentosidine levels correlated significantly with those of 8-OHdG when all data of healthy controls and AD patients were plotted. In patients with acute exacerbation of AD, both urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of treatment. Our findings in patients with acute exacerbation of AD suggest that pentosidine levels are partly determined by the prevailing oxidative stress in these patients.

Blunted cortisol responses to psychosocial stress in asthmatic children: a general feature of atopic disease?

Atopy is defined by the individual predisposition to develop a group of inflammatory disorders in response to certain food or environmental substances that are otherwise innocuous for the host. In previous studies we could demonstrate a reduced responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to psychosocial stress in young and adult patients with atopic dermatitis (AD), a chronic atopic skin disorder. With respect to the important immunoregulatory role of the HPA axis, especially under stress, this observation could be of clinical relevance and may at least partly explain stress-induced exacerbation of AD. The present study was designed to investigate whether attenuated responsiveness of the HPA axis to stress represents a characteristic feature of AD or whether it can also be found in other chronic manifestations of atopy. Children (aged 7-12) with allergic asthma (AA; N = 17) and age- and sex-matched healthy controls (N = 18) were exposed to the "Trier Social Stress Test for Children"(TSST-C), which mainly consists of a free speech and mental arithmetic tasks in front of an audience. Salivary cortisol was measured in ten-minute intervals before and after the TSST-C, while heart rate was monitored continuously. In addition, early morning cortisol levels (after awakening, +10, +20, +30 minutes) were assessed on three consecutive days. Data analysis yielded a significant increase of cortisol concentrations (F (9297)= 16.79; p <.001) and heart rates (F(32,992)= 9.16; p <.001) after the stressor with no between-group difference in heart rate responses. However, AA children showed a significantly blunted cortisol response to the TSST-C when compared with the control group (F(9297)= 2.95; p <.01). Awakening in the morning was accompanied by a significant rise of cortisol levels on all three experimental days in AA and control subjects (all p <.001) that was not different between the two groups. These findings suggest that a blunted adrenocortical response to stress may represent a common feature of chronic allergic inflammatory processes that may be relevant in different forms of chronic manifestation of atopy.

Protein oxidative damage in the stratum corneum: Evidence for a link between environmental oxidants and the changing prevalence and nature of atopic dermatitis in Japan.

The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation. To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls. Carbonyl moieties in skin biopsies from 75 patients with AD were assessed using both spectrophotometric and immunohistochemical detection of the formation of dinitrophenylhydrazone (DNP) from dinitrophenylhydrazine (DNPH). These were compared with diseased and normal controls. Lipid peroxidation was also assessed by staining with antibody to 4-hydroxy-2-nonenal (4-HNE), an aldehyde product of oxidized omega-6-fatty acids. In addition, the activity of superoxide dismutase (SOD), an effective scavenger of ROS, was assessed and compared with controls. The level of protein carbonyl moieties in patients' skin was elevated and correlated directly with the severity of the disease. In contrast, DNP formation was not significantly increased in diseased controls, when compared with healthy volunteers, and no statistical significance was found between the two control groups. SOD activity was increased except for those with extra-severe disease. Positive staining with anti-DNP antibody and anti-4-HNE antibody were found in the most superficial layers of the stratum corneum. This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD.

Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis

The underlying mechanisms of skin inflammation in atopic dermatitis (AD) are not completely understood. The purpose of the present study was to examine the involvement of oxidative stress and antioxidant defenses in children with acute exacerbation of AD. We studied 13 children who were hospitalized for acute exacerbation of AD with purulent skin infection by Staphylococcal aureus (age, 1.5 to 10.0 years), and 28 age-matched healthy subjects (controls). Urine samples obtained from the patients on admission, on 2nd and 7th–9th hospital days, as well as from the controls were analyzed for 8-hydroxy-2′-deoxyguanosine (8-OHdG) (a marker of oxidative DNA damage), acrolein-lysine adducts (a marker of lipid peroxidation), bilirubin oxidative metabolites (BOM) (a marker of antioxidant activity of bilirubin under oxidative stress) and nitrite/nitrate (NOx−) (a marker of endogenous nitric oxide production). Of these, urinary concentrations of 8-OHdG, acrolein-lysine adducts and BOM, but not NOx−, were significantly higher in AD children on admission than those in control subjects. Response to treatment was associated with significant falls in the concentrations of 8-OHdG and acrolein-lysine adducts. Urinary concentrations of acrolein-lysine adducts, but not 8-OHdG, were still significantly higher in AD patients on the 7th–9th hospital day relative to the control. Urinary BOM remained almost constant and significantly high in AD children during hospitalization. Our findings indicate that oxidative stress and altered antioxidant defenses are involved in the pathophysiology of acute exacerbation of AD, and that suppression of oxidative stress might be a potentially useful strategy for the treatment of AD.

The relationship between atopic dermatitis and contact dermatitis

Atopic dermatitis (AD) and contact dermatitis are common eczematous disorders mediated through inflammatory mechanisms. As with other eczematous disorders, they are both characterized by a serous accumulation in the epidermis and a dermal inflammatory infiltrate, expressed clinically as erythema, with or without concomitant edema and/or blistering. AD is a recurrent, hereditary eczematous condition that typically begins in childhood, affecting patients with a personal or family history of hayfever, asthma, and/or chronic dermatitis. Multiple genetic abnormalities render atopics susceptible to flares of disease activity in the presence of environmental triggers including various allergens, as well as climate and temperature change. Exacerbation of AD can, however, occur in the absence of a known environmental stimulus. Contact dermatitis is an inflammatory condition caused by direct skin exposure to an offending chemical with or without a requirement for ultraviolet light. There are two distinct types of contact dermatitis: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is an inflammatory reaction caused by a chemical insult that results in direct cellular injury upon skin contact. The majority of cases of ICD are associated with soaps, detergents, solvents, acids, and alkali. There are two categories of ICD: acute reactions that develop minutes to hours after exposure to a very strong irritant chemical, and cumulative insult reactions, which follow repeated contact with milder irritants. Since ICD is essentially an injury, all individuals will develop an eruption when certain parameters of chemical concentration and frequency of exposure are exceeded. ACD, like AD, is an eczematous disease mediated through immune mechanisms. ACD is an acquired skin disorder that occurs at sites of contact with small chemical haptens in only those individuals who have been previously exposed to, and immunologically sensitized to, a particular chemical. In contrast to ICD, only a small percentage of the population develops an eruption when exposed to chemicals causing ACD. The most common chemical allergens causing the condition in North America include nickel sulfate, found in everything from keys to buttons on clothing, as well as the pentadecylcatechols, the active moiety in plants of the Rhus family, which include poison ivy, poison oak, and poison sumac. Active skin disease, such as ICD or AD, which disturb the integrity of the body’s epidermal barrier, can be predisposing factors for ACD, allowing easier access of potential chemical allergens to the immune system. Despite differing etiologies, AD and contact dermatitis have been the focus of many studies examining the potential association of the two conditions. In the past, it was believed that patients suffering from AD were less likely to suffer from ACD. However, more recent studies indicate that ACD is equally prevalent among atopics and nonatopics. Current research also indicates that AD patients may be more prone to suffer from ICD. Understanding the potential links between AD and contact dermatitis, and the parallel aspects of their pathogenesis, diagnosis, and treatment, can be helpful to clinicians caring for patients suffering from the disorders.

アトピー性皮膚炎患者におけるＭａｌａｓｓｅｚｉａの菌相とその遺伝子多型の解析

To elucidate the role of Malassezia species in atopic dermatitis (AD) requires investigation of the Malassezia microflora on the skin of AD patients. Previously, M. furfur was considered the dominant species in the microflora, however, this microorganism has been reclassified into five species and reanalysis of the microflora based on the current Malassezia taxonomy is therefore needed. Malassezia is more difficult to isolate and culture than other pathogenic yeasts such as Candida and Cryptococcus, making it difficult to elucidate the microflora of AD patients accurately. We developed a PCR-based non-culture method that does not require the use of isolation or culture techniques. Of the members of the genus Malassezia, M. globosa colonized the skin of both AD patients and healthy subjects more frequently than other Malassezia species. In addition, we found polymorphisms in the intergenic spacer 1 region of the M. globosar RNA gene. The genotypes of the microorganisms obtained from AD patients were significantly different from those obtained from healthy subjects. We believe that a specific genotype of M. globosa is responsible for exacerbation of AD.

A patient with hyper-IgE syndrome: A multisystem disorder

A patient with hyper-IgE syndrome came to our attention with an exacerbation of atopic dermatitis. The medical evaluation showed typical features of hyper-IgE syndrome and a low number of cytotoxic T cells in the peripheral blood. This case serves as a reminder that hyper-IgE syndrome is a multisystem disorder. (J Am Acad Dermatol 2002;47:S268-9.)

Reactivity of anti-Blomia tropicalis IgG and IgE in patients with atopic dermatitis.

Patients with atopic dermatitis (AD) commonly develop antibodies of subclasses IgG and IgE to house dust mites, such as Dermatophagoides pteronyssinus and D. farinae. The domestic mite Blomia tropicalis is prevalent in Brazil and can cause the exacerbation of AD. The objectives of this study were to assess skin reactivity to B. tropicalis extracts of AD patients and a control group of nonallergic subjects, and to determine the in vitro reactivity of anti-B. tropicalis IgG and IgE in the serum of AD patients and a control group of nonallergic individuals. Subjects were 36 patients with confirmed AD and the controls were 25 nonallergic individuals. Skin sensitivity to B. tropicalis extracts was tested by the prick-test, and anti-B. tropicalis IgG reactivity in the serum was detected by the Western blot. Anti-B. tropicalis IgE reactivity in the serum was measured by RAST. Patients with AD reacted 7.12 times more often to extracts from B. tropicalis than the control group. A positive association was observed between the presence of anti-B. tropicalis IgG and IgE and AD. AD patients showed a high degree of sensitization to B. tropicalis; it can thus be considered a risk factor for the development of AD exacerbations in patients exposed to this mite species.

Treatment of Refractory Atopic Dermatitis Using ‘Wet-Wrap’ Dressings and Diluted Corticosteroids: Results of Standardized Treatment in both Children and Adults

Background: ‘Wet-wrap’ dressings with diluted corticosteroids form an alternative treatment in patients with refractory atopic dermatitis (AD). Objective: To evaluate a standardized treatment, using wet-wrap dressings with diluted corticosteroids, in patients with refractory AD. Methods: Results of treatment, complications and possible side effects were retrospectively evaluated in 14 children and 12 adults. Results: Skin lesions improved dramatically during 1 week of inpatient treatment. A significant decrease in early-morning serum cortisol levels was measured. Levels below the normal range were only observed after 1 week in 2 adults and on day 4 in 3 children. Suppression of the hypothalamus-pituitary-adrenal-cortex axis in 1 adult and a new exacerbation of AD in 2 children and 3 adults complicated long-term treatment at home. Additional complications included folliculitis, a Pseudomonas aeruginosa infection, a secondary bacterial infection and refractory skin lesions between bandages. Conclusion: Wet-wrap dressings and diluted corticosteroids form an effective treatment in patients with refractory AD.

Topical Steroids under Wet-Wrap Dressings in Atopic Dermatitis – A Vehicle-Controlled Trial

Background: The wet-wrap dressing technique has proved to be beneficial in cases of exacerbated atopic dermatitis (AD) skin lesions. Objective: The effect of wet-wrap dressings was investigated in a controlled trial comparing a steroid (mometasone furoate 0.1%)-containing and a steroid-free (vehicle) preparation in an in-patient comparison study. Methods: 20 children aged 2–17 years with exacerbated AD were treated twice daily with wet-wrap dressings over a 5-day period. Results: AD in treated areas significantly improved in both study arms; however, the effect was significantly better in the mometasone-treated group (p < 0.01). Transepidermal water loss improved in both arms without any significant differences. Staphylococcus aureus colonization decreased during the first 3 days of active treatment independently of the therapeutic modalities chosen. At day 5, colony counts further dropped on the steroid-treated lesions. Conclusion: Application of the wet-wrap dressing technique for exacerbated AD lesions is effective, combination with a topical steroid being superior to a steroid-free application without bearing the risk of a bacterial superinfection.

Epidemiology, clinical features, and immunology of the "intrinsic" (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis).

Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

Different expression of cytokine and membrane molecules by circulating lymphocytes on acute mental stress in patients with atopic dermatitis in comparison with healthy controls

Background: Mental stress is believed to induce an exacerbation of atopic dermatitis (AD). Until now, however, only few psychoneuroendocrinologic mechanisms underlying the link between psychological stress and exacerbation or maintenance of AD have been described. Objective: Our purpose was to conduct an investigation of immunologic parameters in the form of membrane molecules and cytokines with potential relevance for the cutaneous inflammation in an established psychological laboratory stress model. Methods: Patients with AD (n = 15) and healthy controls (n = 15) were exposed to mental stress, as described in a previous report. In vitro analyses were completed 1 hour before, immediately after, and 1 hour after mental stress exposure. Lymphocyte subpopulations, the cutaneous lymphocyte-associated antigen (CLA), the membrane molecule CD69+ (early activation antigen), and intracellular IL-4, IL-5, and IFN-γ in blood-derived lymphocytes were analyzed by flow cytometry. IL-4 in the supernatant of concanavalin-A–stimulated PBMCs was determined by ELISA. Results: An increase in heart rate and blood pressure was demonstrated during psychological stress in patients with AD and healthy volunteers. We found significantly higher stress-induced increase of CLA+ lymphocytes, T helper cells expressing IL-5, and both CD4+ and CD8+ lymphocytes expressing IFN-γ on mitogenic stimulation in patients with AD in comparison with healthy controls. In addition, we observed an earlier increase in the secretion of IL-4 in the supernatant of mitogen-stimulated lymphocytes during psychological stress in patients with AD in comparison with healthy volunteers. Conclusion: A higher stress-induced increase of CLA+ cells in the circulation in patients with AD compared to healthy controls might indicate an increased ability of T lymphocytes in AD to migrate to the skin during this psychological condition. In addition, the data of this study suggest a different stress-induced cytokine profile in circulating lymphocytes in patients with AD compared to healthy controls. (J Allergy Clin Immunol 2001;108:455-62.)

Neuropeptides in atopic dermatitis

The nervous system, the immune system, and the cutaneous system are not independent systems, but are closely associated and use the same language of cytokines and neurotransmitters. Atopic dermatitis (AD) is exacerbated by several factors, such as emotional stress, scratching and sweating. This review presents the role of neuropeptides (NP) in AD. In AD, abnormalities occur in distribution of some types of neural filaments and in the associated active NP. Nerve fibre increases. Nerve fibres for substance-P (SP) and calcitonin gene-related peptide (CGRP) are positive, The cutaneous concentration of SP decreases while vasoactive-intestinal polypeptide (VIP) increases. Immunohistochemical examination has revealed neuropeptide-Y (NPY)-positive dendritic epidermal cells in AD lesions but no somatostatin (SOM) fibres. Neuromediators modulate functions of all cutaneous cellular types, which are all part of the neuroimmunocutaneous system (NCIS): endothelial cells, glandular cells, fibroblasts, epidermal cells and immune cells. Conclusion: during the course of AD, the NICS is destabilized. Evidence show that NP can also be responsible for the induction and maintenance of the cutaneous inflammation process and confirm an involvement in the pathogenesis of AD. Release of the NP by cutaneous nerve potentially explains the role of emotional stress, scratching and sweating in exacerbation of AD. (Med J Indones 2001; 10: 197-200)

Perforin hyperreleasability and depletion in cytotoxic T cells from patients with exacerbated atopic dermatitis and asymptomatic rhinoconjunctivitis allergica

Background: As a plasma membrane pore-forming protein, perforin is essential for T-cell cytotoxicity mediated by lytic granules. Recent studies on the immune system of perforin knockout mice demonstrated striking similarities to the immunopathology of atopic diseases. Objective: We sought to investigate the perforin system of atopic patients. Methods: Monoclonal antibodies were used to characterize perforin-positive PBMCs of patients with exacerbated atopic dermatitis (AD) and asymptomatic rhinoconjunctivitis allergica (RCA) by means of immunoflow cytometry. In addition, a perforin release assay was developed to quantify the velocity of ionomycin and phorbol 12-myristate 13-acetate–induced secretion of lytic granules. Results: In atopic patients significantly fewer lymphocytes contained perforin-positive lytic granules compared with those of healthy control subjects (patients with AD: 14% ± 5%, n = 13, P < .0001; patients with RCA: 24% ± 5%, n = 9, P < .01; healthy control subjects: 33% ± 11%, n = 13). Of all CD8hi+ cytotoxic T lymphocytes (CTLs), only 18% ± 9% and 17% ± 12% were perforin-positive in patients with AD and RCA, respectively, compared with 44% ± 13% in control subjects (P < .0001). In addition, perforin-positive CD8hi+ CTLs of atopic patients released their perforin twice as fast and more completely than control CTLs. This means that 50% of initially perforin-positive CD8hi+ CTLs from patients with AD and RCA released their perforin completely within 32 ± 16 and 36 ± 19 minutes, respectively, and an over 85% release was reached within 113 ± 41 and 118 ± 60 minutes, respectively. In CTLs of healthy control subjects, however, it took 64 ± 40 minutes to achieve a 50% release of lytic granules, and an 85% depletion was not reached in 60% of healthy control subjects, even after 180 minutes. Conclusion: The perforin hyperreleasability explains, at least in part, the decreased percentage of perforin-positive CD8hi+ CTLs in atopic patients. These distortions in the system of lytic granules of atopic patients may contribute to the functional defects observed in T-cell cytotoxicity in vivo and in vitro in patients with AD and RCA. (J Allergy Clin Immunol 2001;107:878-86.)