Haptenos,proteínas y dermatitis atópica

Atopic dermatitis is a chronic inflammatory disease that is multifactorial in nature. Allergic contact dermatitis and protein contact dermatitis are allergic conditions that may occur in the context of atopic dermatitis and be the cause of exacerbations. Although the prevalence of allergic contact dermatitis is similar in atopic patients and the general population, these 2 conditions are frequently associated because atopic inflammation disrupts the skin barrier. Skin tests are therefore recommended in atopic individuals. Dupilumab could be useful for treating allergic contact dermatitis if it is mediated by type 2 helper T cells but could exacerbate inflammation if mediated by T_H1 cells: further study is needed before conclusions can be drawn. Although the mechanism by which exposure to environmental proteins exacerbates atopic dermatitis remains under discussion, such exacerbations are routinely seen in clinical practice. Prick testing is recommended in symptomatic atopic dermatitis. When prick-test findings are positive, patients should be advised to avoid the culprit substances.     

Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis

Abstract  The CD30 molecule has been proposed as a marker for a subset of CD4⁺CD45RO⁺ (memory) T cells with potent B cell helper activity producing IL-5 and IFN-γ and as a specific marker for Th2 cells. Recently, an association has been demonstrated between elevated serum levels of soluble CD30, which is shed by CD30⁺ cells in vitro and in vivo, and atopic dermatitis but not respiratory atopic disorders or allergic contact dermatitis. We studied the expression of CD30 in the inflammatory infiltrate of atopic dermatitis compared with that of allergic contact dermatitis, with special regard to skin disease activity (acute vs subacute/ chronic). Biopsies were obtained from 16 patients suffering from atopic dermatitis (acute n = 6, subacute/ chronic n = 10), from 7 patients with acute allergic contact dermatitis and from 5 positive patch-test reactions. Paraffin-embedded as well as snap-frozen material was stained with anti-CD30 and anti-CD45RO mAbs according to standard procedures. Double-staining procedures for CD30CD3, CD30CD4, CD30CD45RO and CD30CD68 were also performed. Abundant CD45RO⁺ cells were detected both in atopic dermatitis and in allergic contact dermatitis lesions. We found scattered CD30⁺ cells in only one of six formalin-fixed paraffin-embedded acute atopic dermatitis biopsies, but in all of the respective snap-frozen specimens, possibly because CD30 expression on atopic dermatitis infiltrating cells is weak and sensitive to formalin fixation and paraffin embedding. CD30CD3 and CD30CD4 double staining identified CD30⁺ cells to be helper T lymphocytes. No significant CD30 expression (either in paraffin-embedded or in frozen material) could be found in subacute/chronic atopic dermatitis lesions or in any of the specimens of allergic contact dermatitis. The results suggest a specific regulatory function of CD30⁺ T cells in acute atopic dermatitis. With respect to the view that CD30 is a marker for Th2 cells, our observations confirm previous findings that Th2 cells predominate in the infiltrate particularly of acute atopic dermatitis. CD30 expression in acute atopic dermatitis but not in acute allergic contact dermatitis might be helpful in the histological differentiation of these disorders and in the further characterization of atopy patch testing. Received: 1 April 1998 / Received after revision: 28 May 1998 / Accepted: 3 July 1998     

Sensitizing agents found in children and adolescents with recalcitrant atopic dermatitis: a cross-sectional study with a pediatric battery

BackgroundAtopic dermatitis is the most common inflammatory skin disease in childhood and has an important impact on quality of life, especially severe cases or those that are recalcitrant to treatments. Sensitization to allergens with the potential for allergic contact dermatitis is a factor associated with cases of recalcitrant atopic dermatitis. Understanding the relationship between atopic dermatitis, allergens, and allergic contact dermatitis is essential. In Brazil, there are no studies on sensitization to allergens found in patch tests with pediatric batteries in patients with atopic dermatitis.ObjectivesTo verify the main sensitizing agents, the prevalence of allergic contact dermatitis and the epidemiological and clinical profile of children and adolescents with atopic dermatitis.MethodsCross-sectional, prospective study in patients between 4 and 18 years of age, with recalcitrant atopic dermatitis, treated at the Sanitary Dermatology Outpatient Clinic (RS). All patients underwent patch tests with a battery of pediatric allergens.ResultsThe prevalence of sensitization and allergic contact dermatitis in the evaluated patients was 37.07% (20/54) and 27.7% (15/54), respectively. The most frequent allergens were: nickel sulfate (16.7%), disperse blue (5.6%), and fragrance mix I (5.6%). Nickel was associated with the female sex (p = 0.019).Study limitationsSample size and selection, absence of a control group.ConclusionsA proportion of patients with recalcitrant atopic dermatitis may be sensitized to different allergens and may even have developed allergic contact dermatitis. Recognizing this context is important in the prevention strategy and management of the disease.     

A comparison of expression of surface-bound immunoglobulin E on antigen-presenting cells in cutaneous tissue between patients with allergic, irritant and atopic dermatitis

The expression of surface-bound immunoglobulin E by dendritic cells within cutaneous tissue has been compared in atopic and contact dermatitis. 45 patients were recruited into 4 groups using clinical criteria and patch testing to a standard series of allergens: atopic (12 cases), allergic contact dermatitis (14 cases), irritant contact dermatitis (10 cases) and the control group (9 cases); using clinical criteria and patch testing to a standard series of allergens. Skin biopsies from each patient were analysed by the indirect immunofluorescence technique. This differentiated 3 patterns of cutaneous IgE distribution: (i) no detectable cutaneous IgE; (ii) detection of IgE solely within the dermis; (iii) detection of IgE within both epidermis and dermis. Detection of IgE within the epidermis was always associated with the presence of IgE within the dermis. In each case, IgE was surface-bound by dendritic cells. Immunoglobulin E was detected within both epidermis and dermis in skin biopsies from 8 (66.7%) atopic patients and 2 (20%) patients with irritant contact dermatitis. No other cases demonstrated IgE deposition within both the epidermis and dermis. Atopic patients were significantly more likely to have detectable IgE deposition, within both epidermis and dermis, than patients with contact dermatitis (allergic and irritant groups combined, p = 0.0011) or controls (p = 0.0049). This finding suggests that the demonstration of IgE within both epidermis and dermis supports a diagnosis of atopic dermatitis. It would therefore be of value in differentiating between atopic and contact dermatitis, where clinical diagnosis is in doubt.     

Occupational dermatitis in bakers: a clue for atopic contact dermatitis

6 patients are described who developed contact dermatitis after cereal contact on atopic skin for periods of 2 to 20 years. 2 patients were wheat flour patch-test-positive. They had punch biopsies taken for standard histological and immunohistochemical investigation by labeling with monoclonal antibodies, anti-DR and anti-IgE. Sections showed features of contact dermatitis. There were many dendritic cells located perivascularly in the papilla and in the epidermidis, intensely positive for monoclonal anti-IgE antibody. In control atopic subjects, there were a few perivascular IgE positive cells, probably mastocytes. This study shows that there may be a relationship between some allergens and atopic eczema in patients exposed to them in the course of their work. In some cases, there was a true allergic contact dermatitis, seen through the clinical and histological characteristics, and the results of immunohistochemical study.     

Periorbital dermatitis: Causes,differential diagnoses and therapy

Periorbital dermatitis is common and frequently difficult to treat. Patients with periorbital dermatitis often suffer severely because their disease is in such a visible location. Because of the variety of clinical appearance, the differential diagnostic considerations are often difficult. We examined the causes of periorbital dermatitis and compared the data of 88 patients from the Department of Dermatology, University Hospital Erlangen to those of the German IVDK (Information Network of the Departments of Dermatology). Between 1999 and 2004, predominant causes of periorbital dermatitis were allergic contact dermatitis (Erlangen 44 %, IVDK 32 %), atopic eczema (Erlangen 25 %, IVDK 14 %), airborne contact dermatitis (Erlangen 10 %, IVDK 2 %) and irritant contact dermatitis (Erlangen 9 %, IVDK 8 %). Less frequent causes for secondary eczematous periocular skin lesions were periorbital rosacea, allergic conjunctivitis or psoriasis vulgaris. Female gender, atopic skin diathesis and age of 40 years and older were identified as risk factors for periocular dermatitis. Common elicitors of periorbital allergic contact dermatitis were leave‐on cosmetic products (face cream, eye shadow) and eye drops with the usual allergens being fragrances, preservatives and drugs. Exact identification of relevant contact allergens and allergen elimination are essential for successful treatment. Calcineurin inhibitors are the first‐line therapy for facial atopic eczema. They may be also effective in periocular eczematous lesions of other origins although they are not approved for such use.     

Nickel dermatitis in infants

8 cases of allergic contact dermatitis to nickel in infants are reported. All showed a papular dermatitis matching the sites of contact. Patch testing was performed on 3 patients, 2 were tested to nickel sulfate in pet. at concentrations of 1.0%, 1.5%, 2.0%. 1 was tested to 2.5% alone. All developed ++ reactions at each concentration tested. We observed a strong association of nickel dermatitis with atopy; 7 of 8 patients had a family history of atopy and 5 of 8 had features of coexistent atopic dermatitis. The relationship between atopy and allergic contact dermatitis is briefly reviewed. Nickel dermatitis may aggravate atopic dermatitis; avoidance of metal contact is crucial in the management of these patients.     

Leukotrienes orchestrating allergic skin inflammation

Leukotrienes constitute a group of lipid mediators, which may be subdivided into two groups, with leukotriene B₄ on the one hand and cysteinyl leukotrienes on the other. Although leukotrienes are abundantly expressed in skin affected by diverse chronic inflammatory diseases, including atopic dermatitis, psoriasis, pemphigus vulgaris and bullous pemphigoid, their pathological roles in these diseases have remained elusive. Recent data now reveal that both leukotriene B₄ and cysteinyl leukotrienes are indispensable in the pathogenesis of atopic dermatitis, with leukotriene B₄ initiating the recruitment of inflammatory cells, particularly neutrophils and T_H2 cells into the skin, and cysteinyl leukotrienes later inducing characteristic structural alterations of chronically affected skin, specifically skin fibrosis and keratinocyte proliferation. Thus, these results reveal a sequential cooperation of LTB₄ and cysteinyl leukotrienes to initiate and perpetuate allergic skin inflammation. These new insights highlight leukotrienes as promising therapeutic targets in allergic skin inflammation and should encourage more research into the role of leukotrienes in other inflammatory skin diseases.     

Impaired monocyte-mediated cytotoxicity in atopic dermatitis

Summary Twenty-three adult patients with atopic dermatitis of different severity and extent all without present cutaneous infection were investigated for antibody-dependent cytotoxicity mediated by purified monocytes. Compared to a healthy control group the monocyte cytotoxicity was significantly decreased for patients with more widespread dermatitis. Eight patients with acute contact dermatitis and 13 patients with extrinsic asthma or allergic rhinitis showed normal cytotoxicity. Decreased monocyte cytotoxicity in atopic dermatitis was not related to the serum IgE level. In vitro cultivation of defective monocytes from atopics did not increase cytotoxicity, nor did normal monocytes preincubated with patient serum show abnormal function. In atopic dermatitis the total number of Fc receptor bearing monocytes was normal. However, the affinity of this receptor was lower than in normals.Serial studies are needed to establish whether reduced monocyte function is a basic pathophysiologic defect in atopic dermatitis.     

Inhibition of the IL-2-inducible tyrosine kinase (Itk) activity: a new concept for the therapy of inflammatory skin diseases

T-cell-mediated processes play an essential role in the pathogenesis of several inflammatory skin diseases such as atopic dermatitis, allergic contact dermatitis and psoriasis. The aim of this study was to investigate the role of the IL-2-inducible tyrosine kinase (Itk), an enzyme acting downstream of the T-cell receptor (TCR), in T-cell-dependent skin inflammation using three approaches. Itk knockout mice display significantly reduced inflammatory symptoms in mouse models of acute and subacute contact hypersensitivity (CHS) reactions. Systemic administration of a novel small molecule Itk inhibitor, Compound 44, created by chemical optimization of an initial high-throughput screening hit, inhibited Itk's activity with an IC50 in the nanomolar range. Compound 44 substantially reduced proinflammatory immune responses in vitro and in vivo after systemic administration in two acute CHS models. In addition, our data reveal that human Itk, comparable to its murine homologue, is expressed mainly in T cells and is increased in lesional skin from patients with atopic dermatitis and allergic contact dermatitis. Finally, silencing of Itk by RNA interference in primary human T cells efficiently blocks TCR-induced lymphokine secretion. In conclusion, Itk represents an interesting new target for the therapy of T-cell-mediated inflammatory skin diseases.     

Elevated serum levels of soluble CD30 are associated with atopic dermatitis, but not with respiratory atopic disorders and allergic contact dermatitis

Type 2 helper T-cell immune responses can be demonstrated in the human atopic disorders atopic dermatitis and allergic asthma/rhinoconjunctivitis. The CD30 (Ki-1) antigen, originally described on Hodgkin and Reed-Sternberg cells, has recently been proposed as a marker of T cells with potent B-cell helper activity producing IL-5 and γ-IFN, as well as on CD4+ and CD8+ T cells with a Th2 cytokine profile. As a soluble form of CD30 (sCD30) is released by CD30+ cells in vivo , we studied its clinical significance in atopic disorders compared with allergic contact dermatitis and healthy controls. Elevated sCD30 levels were associated with atopic dermatitis ( P  < 0.0001), but not with respiratory atopic disorders or allergic contact dermatitis. sCD30 levels in patients with atopic dermatitis were independent of serum IgE. The particular occurrence of serum sCD30 in patients with atopic dermatitis indicates a special regulatory function of CD30+ cells in this disease.     

Sites of dermatitis in a patch test population: hand dermatitis is associated with polysensitization

Background  Sites of dermatitis in larger series of contact allergic patients are rarely reported. Increased risk of polysensitization has been linked only to stasis dermatitis and leg ulcers. However, a large proportion of polysensitized individuals may have dermatitis in other skin areas.
Objectives  To examine the site of dermatitis at time of first appearance in contact allergic individuals with special focus on the distribution of dermatitis in polysensitized individuals and to examine if widespread dermatitis is more frequent in polysensitized than in single/double-sensitized patients.
Methods  A matched case–control study was carried out including 394 polysensitized and 726 single/double-sensitized patients who responded to a postal questionnaire. All subjects were recruited from a hospital patch test population.
Results  The hands were the most frequent and the anogenital region was the least frequent skin area affected with dermatitis. Dermatitis on the hands/wrists [odds ratio (OR) 1·58], in the armpits (OR 1·56) and on the back (OR 1·91) was positively associated with polysensitization. The hands were the only skin area with dermatitis which maintained the association to polysensitization in two subpopulations consisting of, respectively, individuals with and without atopic eczema. Dermatitis on the scalp was negatively associated with polysensitization (OR 0·66) primarily for individuals without atopic eczema. The dermatitis did not seem to be more widespread in polysensitized compared with single/double-sensitized patients.
Conclusions  Special awareness in patients with hand dermatitis seems justified either to prevent development of multiple contact allergies or to document polysensitization as an aetiological factor.     

Scratching behavior in spontaneous- or allergic contact-induced dermatitis in NC/Nga mice

NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.     

Patch testing in Israeli children with suspected allergic contact dermatitis: A retrospective study and literature review

Background/objectives

Childhood allergic contact dermatitis is recognized as a significant clinical problem. The objective was to evaluate the rate of positive patch tests in Israeli children with clinically suspected allergic contact dermatitis, identify possible sex and age differences, compare results with those in Israeli adults, and review pediatric studies in the literature.

Methods

The study sample included 343 children and adolescents (197 female, 146 male; 1‐18 years of age, mean age 11.8 years) with clinically suspected allergic contact dermatitis who underwent patch testing with a standard pediatric series of 23 allergens at a tertiary medical center from 1999 to 2012. Data on clinical characteristics and test results were collected retrospectively from the medical files.

Results

Ninety‐eight subjects (28.6%) (75 girls [38.1%], 23 boys [15.8%]) had at least one positive reaction. The most frequent reactions were to nickel sulfate, followed by potassium dichromate and cobalt chloride. Nickel sulfate sensitivity was more common in girls, especially those younger than 3 years and older than 12 years. The prevalence of contact sensitization was similar in subjects with and without atopic dermatitis (50% and 51%, respectively).

Conclusion

Nickel is the most common allergen in Israeli children, especially girls. Patch testing should be performed in children with clinically suspected allergic contact dermatitis regardless of atopic background.     

Autoimmunity in atopic dermatitis: Biomarker or simply epiphenomenon?

The idea that a mechanism of autoimmunity could play a role in the pathogenesis of atopic dermatitis gained support from the observation that patients with atopic dermatitis display IgE reactivity to a variety of human protein antigens, several of which have been characterized at molecular level. A broad spectrum of at least 140 IgE‐binding self‐antigens associated with atopic dermatitis has been demonstrated; they might promote, perpetuate, or both, skin inflammation by binding IgE antibodies or activating specific T cells. Even if the presence of autoreactivity seems to be associated with the severity of the disease and may be used as a parameter reflecting chronic tissue damage, at the state of art the role of autoimmunity in atopic dermatitis is far from clear. Data from the literature show that the use of autoantibodies as biomarkers of atopic dermatitis are still limited by the evidence that the epiphenomenon of autoreactivity is detectable only in a percentage of patients and that the involved self‐allergens often are not the same; further longitudinal case‐control studies are needed to investigate and to clarify the pathogenethic role of autoimmunity in the course of atopic dermatitis.     

Contact sensitivity in patients with recalcitrant atopic dermatitis

Patients with atopic dermatitis are usually responsive to conventional treatment such as topical steroids; however, they are sometimes refractory to the treatment. The influence of contact sensitivities on the course of patients with recalcitrant atopic dermatitis is not known. The aim of this study was to investigate whether contact sensitivities affect the course of patients with recalcitrant atopic dermatitis. We evaluated 45 patients with atopic dermatitis who had failed conventional therapy. Patch testing was performed with the Japanese standard series, metal series and/or suspected items. A total of 15 patients had a positive patch test reaction to at least one allergen. The most common allergens were nickel, topical drugs and rubber accelerators. Avoidance of products or food containing allergic substances greatly or partially improved skin symptoms in nine patients. These results suggest that contact allergens and metals may be critical factors causing eczematous lesions in patients with recalcitrant atopic dermatitis.     

Increased “in vivo” lymphocyte blastogenesis in the peripheral blood of patients with atopic dermatitis and allergic contact dermatitis

Summary The spontaneous ³H-thymidine (³HT) labelling of some lymphocyte subpopulations has been studied in the peripheral blood of five patients with atopic dermatitis and five with widespread allergic contact dermatitis and compared with that in 10 healthy subjects. One hour after addition of ³HT to heparinized blood, lymphocytes were separated and processed with two different rosetting techniques (E-rosette test and Active-E-rosette test). The cell suspensions were cytocentrifuged and autoradiography undertaken.An increased number of ³HT labelled lymphocytes was observed in the peripheral blood of patients with dermatitis as compared to controls. These labelled lymphocytes were E-rosette-forming cells (T cells) and E-non-rosetteforming cells (non-rosette-forming T cells and non-T cells). The ratio between the labelling index (LI) of E-rosette- to the LI of non-E-rosette-forming cells was in favour of T cells in allergic contact dermatitis (ratio=3.09) whereas in atopic dermatitis (ratio=0.93) the DNA synthesis was relatively greater in the non-rosette-forming cells.It is suggested that this increased LI of peripheral blood lymphocytes could be related to the increased dermal mononuclear cell ³HT-labelling that has been reported previously in these inflammatory skin diseases.D. Van Neste is recipient of a grant from INSERM, Paris and Administration des relations culturelles internationales (ARCI), Bruxelles     

TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines

BACKGROUND: Skin-infiltrating T cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES (regulation on activation, normal T cell expressed and secreted; CCL5), TARC (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell attracting chemokine; CCL27). OBJECTIVES: To investigate which T-cell-attracting chemokines are involved in allergic contact dermatitis in mice. METHODS: Allergic contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid diflorasone diacetate were studied in mouse ears. RESULTS: RANTES and TARC were elevated in both models of allergic contact dermatitis 24 h after challenge, whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by diflorasone diacetate in the DNCB model but was highly induced in the TDI model; in contrast, TARC was not influenced by cilomilast. CONCLUSIONS: TARC and RANTES, but not CTACK, are involved in these two models of allergic contact dermatitis.     

Periorbital dermatitis--a recalcitrant disease: causes and differential diagnoses

Background Periorbital dermatitis is common and frequently recalcitrant to treatment. Due to the exposed and visible location, patients often suffer severely from periorbital dermatitis. Objectives To determine the frequency and causes of periorbital dermatitis including contact sensitizers. Methods We investigated two cohorts of patients (Erlangen and IVDK without Erlangen) between 1999 and 2004. Results The differences between the two cohorts with periorbital dermatitis [Department of Dermatology at University Hospital Erlangen (n = 88) and the German Information Network of Departments of Dermatology (IVDK) collective (n = 2035)] were determined by the MOAHLFA (male, occupational dermatosis, atopic eczema, hand dermatitis, leg dermatitis, facial dermatitis, age ≥ 40 years) index. Statistically significant factors for periocular eczema are female sex, atopic skin diathesis and age ≥ 40 years. In both cohorts allergic contact dermatitis was the main cause of periorbital eczema (Erlangen 44·3%, IVDK 31·6%), followed by periorbital atopic dermatitis (Erlangen 25%, IVDK 14·1%), airborne dermatitis (Erlangen 10·2%, IVDK 1·9%), irritant contact dermatitis (Erlangen 9·1%, IVDK 7·6%), periorbital rosacea (Erlangen 4·5%, IVDK 2·2%), allergic conjunctivitis (Erlangen 2·3%, IVDK included in ‘others’) and psoriasis (Erlangen 2·3%, IVDK included in ‘others’). The most relevant allergens/allergen sources inducing periorbital eczema were consumers’ products (facial cream, eye shadow and ophthalmic therapeutics) (31%), fragrance mix (19%), balsam of Peru (10%), thiomersal (10%) and neomycin sulphate (8%); 12·5% of patients with allergic periocular dermatitis could be exclusively elucidated by testing patients’ own products. Conclusions Our data demonstrate the multiplicity of causes for periorbital eczematous disease manifestation, which requires patch testing of standard trays as well as consumers’ products to elucidate the relevant contact sensitization.