Diagnostic approach in allergic and irritant contact dermatitis

Contact dermatitis is a highly frequent disease with a significant impact on the quality of life of the affected patients and a relevant socioeconomic impact. According to the pathophysiological mechanisms involved, two major types of contact dermatitis may be recognized: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). The two types may, and often do, coexist. Differentiating between ICD and ACD is often difficult in the clinical setting. The basis for a diagnosis of either ICD or ACD is mainly established by a comprehensive clinical history and physical examination, as well as by performing appropriate diagnostic patch testing. The only useful and reliable method for the diagnosis of ACD remains the patch test. Positive patch test results, the current and/or past relevance of which has to be assessed, are confirmative of contact sensitization. Additional tests, such as the repeated open application test or the provocative use test, are sometimes necessary to confirm a causal relationship. This algorithmic diagnostic approach will allow the adoption of rational measures of allergen or irritant avoidance and the implementation of realistic patient information and education.     

Atopic dermatitis and allergic reactions to individual fragrance chemicals

Background:  Allergic contact dermatitis prevalence is reported as equal in atopic and nonatopic dermatitis. Atopic dermatitis is under‐represented in those with allergic contact dermatitis to agents having cutaneous and dietary exposure. We compared rates of atopic dermatitis between patients with allergic contact dermatitis arising out of individual fragrance chemicals with known oral/cutaneous exposure against exclusively cutaneous exposure. Methods:  Between 1982 and 2007, 37 065 dermatitis patients were tested with Fragrance mix I. Those who were positive were tested for individual fragrance allergy. Chemicals were categorized according to whether their exposure pattern was solely cutaneous, oral or mixed. Current and past atopic dermatitis rates were compared between the whole population and groups allergic to individual fragrances. Age and gender were controlled. Results:  Cinnamic alcohol and cinnamal allergy groups had reduced rates of both ‘current’ [24/266 (9.0%) P = 0.0008, 38/364 (10.4%) P = 0.0005] and ‘past’ atopic dermatitis [44/266 (16.5%) P = 0.009, 70/346 (19.2%) P = 0.037]. Atopic dermatitis rates in groups allergic to Evernia prunastri and hydroxycitronellal (cutaneous exposure only) were not reduced [120/597 (20.1%) and 41/153 (26.8%)]. Groups allergic to cinnamic alcohol (P < 0.0001, P < 0.0001) and cinnamal (P < 0.0001, P < 0.004) had reductions in ‘current’ and ‘past’ atopic dermatitis, compared with Evernia prunastri. Conclusions:  Patients allergic to individual fragrances with dietary exposure have reduced rates of atopic dermatitis. This suggests that patients with atopic dermatitis have heightened oral tolerance to dietary haptens, in contrast to the known close association of atopic dermatitis with food‐protein allergy. Haptens may interfere with food protein tolerance by binding to soluble protein to alter its configuration and immunogenic profile.     

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children

Background:  There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment.
Objectives:  To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization.
Methods:  Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization.
Results:  Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5–7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2–6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1–5.9).
Conclusions:  Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.     

Absence of specific IgE antibodies in allergic contact sensitivity to formaldehyde

Immunologic reactions are customarily divided into two broad categories, cell-mediated and antibody-mediated. An interplay between these two pathogenetic principles is indicated by reactions such as cutaneous basophil hypersensitivity, late-phase reaction, and cutaneous lesions indistinguishable from regular allergic contact dermatitis lesions after sensitization with IgE antibodies against certain haptens. In the present study, 23 patients with a history of a positive epicutaneous test to formaldehyde participated. On retest, 15 showed a positive reaction. Eight patients were Phadiatop® positive, indicating an atopic diathesis, and eight had a history of or ongoing atopic dermatitis. On RAST test®, only two, nonatopic patients had specific IgE antibodies to formaldehyde. In the cellular infiltrates of biopsies from epicutaneous test sites, cells reactive with monoclonal antibodies against IgE were found in positive and negative formalin tests, both in atopies and nonatopics, as well as in control biopsies from nonlesional skin. Double immunofluorescence staining experiments showed that IgE occurred on Langerhans' cells. The proportion of IgE-positive cells correlated to the level of serum IgE, but not to atopy. These cells were also found both in the epidermis and in the dermis in nonatopic patients. ICAM-1 occurred on keratinocytes in all patient groups. This study does not support the hypothesis that specific IgE antibodies are active in the pathogenesis of contact sensitivity to formaldehyde either in atopic or in nonatopic patients.     

Natural killer T cells expressing IFN-γ and IL-4 in lesional skin of atopic eczema

Background:  The inflammation of atopic eczema (AE) is orchestrated not only by T cells predominantly but also B cells, eosinophils and dendritic cells. Recently, a role of invariant natural killer T (NKT) cells has been reported in bronchial asthma and allergy. Natural killer T cells express a restricted repertoire of T-cell receptor α/β and produce interferon (IFN)-γ and/or interleukin (IL)-4 upon activation.
Aim of the study:  To determine the presence of NKT cells in lesional AE skin in comparison with other eczematous disorders and to analyse their cytokine expression.
Methods:  Immunofluorescence stainings were carried out using antibodies recognizing NKT cells, CD3+ and CD4+ cells, IFN-γ and IL-4.
Results:  Natural killer T cells have been detected in small numbers in the majority of AE specimens as well as in atopy patch test (APT) reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). In AE, the proportion of NKT cells among CD3+ cells was approximately 5%. NKT cells expressed both IFN-γ and IL-4 in AE, APT and ACD but predominantly IFN-γ in ICD.
Conclusion:  Natural killer T cells are part of the inflammatory infiltrate of AE as well as APT, ACD and ICD, suggesting a pathogenic role of NKT cells in eczematous skin disorders. The pattern of IFN-γ and IL-4 cytokine expression by NKT cells varied depending on the type of eczematous disease.     

T-cell subpopulations in the development of atopic and contact allergy

Remarkable progress has been made in our understanding of the pathogenesis of skin diseases mediated by T cells. T-cell subsets responsible for the expression and regulation of allergic contact dermatitis to small chemicals or 'haptens' have been defined further, and the dynamics of T cells involved in the pathogenesis of atopic dermatitis have been clarified. In addition, studies are beginning to reveal the important contribution of skin resident cells to atopic dermatitis and the underlying molecular mechanisms.     

Mast cells and basophils in cutaneous immune responses

Mast cells and basophils share some functions in common and are generally associated with T helper 2 (Th2) immune responses, but taking basophils as surrogate cells for mast cell research or vice versa for several decades is problematic. Thus far, their in vitro functions have been well studied, but their in vivo functions remained poorly understood. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for mast cells and basophils in several skin disorders. Newly developed mast cell‐deficient mice provided evidence that mast cells initiate contact hypersensitivity via activating dendritic cells. In addition, studies using basophil‐deficient mice have revealed that basophils were responsible for cutaneous Th2 skewing to haptens and peptide antigens but not to protein antigens. Moreover, human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of skin diseases ranging from atopic dermatitis to autoimmune diseases. In this review, we will discuss the recent advances related to mast cells and basophils in human and murine cutaneous immune responses.