Oral lichenoid lesions and allergy to dental materials

BACKGROUND: Dental materials, oral hygiene products and food additives may cause contact allergic reactions in the mouth with varied clinical presentation. Oral lichenoid lesions (lichen planus-like lesions) can be induced by hypersensitivity to dental restorative metals, acrylates, flavorings and other substances. AIM: The aim of this study was to demonstrate contact allergy to dental materials in patients with oral lichenoid lesions using patch tests. PATIENTS AND METHODS: Routine patch tests with two sets of allergens - "European Standard" and "Dental Screening" (Chemotechnique Diagnostics, Sweden) supplemented with pulverized amalgam, iridium, indium, menthol, sorbic acid and platinum were done on a set of 25 patients with lichenoid lesions located on the buccal mucosa, tongue and lips. Application and interpretation of the tests were conducted according to ICDRG (International Contact Dermatitis Research Group). RESULTS: 15 (60 %) patients showed sensitization to 1 or more allergens, with a total of 31 positive reactions. The greatest frequency of positive reactions was to dental metals, with a total of 27 positive reactions. The order of tested metals according to frequency of positive reactions was mercury (6/25/24 %), amalgam (6/25/24 %), nickel (4/25/16 %), palladium (4/25/16 %), cobalt (3/25/12 %), gold (2/25/8 %), chrome (1/25/4 %), indium (1/25/4 %). The clinical relevance of the results with regard to the material's presence in the mouth was demonstrated in 11 (44 %) patients. In 9 patients, replacement of the positively tested materials led to healing or to significant regression of mucosal changes. CONCLUSIONS: The results of the patch tests showed the possible contribution of contact sensitization in the pathogenesis of lichenoid manifestations in the oral cavity. Due to the premalignant character of these lesions, replacement of positively tested materials and follow up of these patients is advised.     

Oral Mucosa Patch Test: A New Tool to Recognize and Study the Adverse Effects of Dietary Nickel Exposure

On contact with the skin, nickel may cause allergic contact dermatitis, which can be diagnosed by an epicutaneous patch test. Nickel exposure via the intestinal mucosa can induce diarrhea, abdominal pain, and swelling. The aim of the present study was to investigate the relationship between these symptoms and nickel intake by means of a novel oral mucosa patch test. Eighty-six patients with intestinal symptoms related to ingestion of nickel-containing foods were submitted to epicutaneous and oral mucosa patch tests for nickel. All patients with positive oral mucosa patch test results were subject to a low-nickel diet and monitored over time. Skin lesions were observed in 33 out of 86 (38.4%) patients evaluated by the epicutaneous patch test. Mucosal lesions were seen in 53 out of 86 (61.6%) patients given the oral mucosa patch test. After 2 months of a low-nickel diet, 52 out of 53 (98.1%) patients showed an improvement of their symptoms. There is a significant correlation between response time of the oral mucosa patch test and the latency of symptoms after ingestion of nickel-containing foods. Consequently, the oral mucosa patch test can be used to recognize and study the adverse effects of dietary nickel exposure that could be defined as allergic contact mucositis. A low-nickel diet is also shown to be an effective treatment for this condition.     

Contact allergy to special and standard allergens in patients with venous ulcers

The aim of the study was to determine the prevalence of contact sensitivity in patients with leg ulcers, and possible difference in the rate of contact hypersensitivity to standard series of allergens used in patch testing, and to particular topical agents used in local therapy of leg ulcers in special series, patients with and without atopy. The study included 60 patients, 45 female and 15 male, aged 37-85 (mean 68.37 female and 51.13 male), 30 of them with and 30 without allergic contact dermatitis (ACD) of the leg (control group). The mean duration of leg ulceration was 5.62 years. The two groups of patients underwent testing to standard series allergens and target series allergens including mupirocin, bepanthene, silver sulfadiazine, chloramphenicol + clostridiopeptidase, betamethasone dipropionate, hydrocortisone + oxytetracycline, momethasone, alginate, hydrocolloid, lanolin, pyrogallol, Vaseline, permanganate, Rivanol, povidone-iodine, gentamicin, i.e. local agents most frequently used by the patients. Contact allergic hypersensitivity to standard series allergens was demonstrated in 25 patients with a total of 49 positive reactions and a mean of 1.6 reactions per patient. Positive reactions were most commonly recorded to balsam of Peru, fragrance mix and neomycin sulfate. There were 12 positive reactions to target series allergens, mean 0.4 reactions per patient. Forty-five positive reactions, mean 0.1 reactions per patient, were recorded in the control group. Positive reactions were most commonly demonstrated to corticosteroid ointments, lanolin and bepanthene. Study results did not confirm a statistically significantly higher rate of sensitization to particular topical agents frequently used in the treatment of patients with venous ulcers. Patch testing to standard and special series allergens should be performed in case of prolonged leg ulcer epithelization.     

Allergic contact dermatitis: how to re-induce tolerance?

Allergic contact dermatitis (ACD) is a skin inflammatory disease mediated by activation of CD8+ cytotoxic T cells specific for haptens in contact with the skin. CD4+ T cells behave as both regulatory and tolerogenic cells since they down-regulate the skin inflammation in patients with ACD (regulation) and prevent the development of eczema (tolerance) in normal individuals. Thus, ACD corresponds to a breakdown of immune tolerance to haptens in contact with the skin. Several regulatory CD4+ T cell subsets (Treg), especially CD4+CD25+ natural Treg cells, are involved in immunological tolerance and regulation to haptens through the production of the immunosuppressive cytokines IL-10 and TGF-beta. Ongoing strategies to re-induce immune tolerance to haptens in patients with eczema include improvement of existing methods of tolerance induction (oral tolerance, low dose tolerance, allergen-specific immunotherapy, UV-induced tolerance) as well as development of new drugs able to activate IL-10 producing Treg cells in vivo. Ongoing and future progress in this area will open up new avenues for treatment of eczema and more generally autoimmune and allergic diseases resulting from a breakdown of tolerance to autoantigens and allergens, respectively.     

Adverse reactions to foods

Allergic reactions to foods represent a prominent, actual and increasing problem in clinical medicine. Symptoms of food allergy comprise skin reactions (urticaria, angioedema, eczema) respiratory (bronchoconstriction, rhinitis), gastrointestinal (cramping, diarrhea) and cardiovascular symptoms with the maximal manifestation of anaphylactic shock. They can be elicited by minute amounts of allergens. The diagnosis of food allergy is done by history, skin test, in vitro allergy diagnosis and — if necessary — oral provocation tests, if possible placebo-controlled. Avoidance of respective allergens for the allergic patient, however, is often complicated or impossible due to deficits in declaration regulations in many countries. Increasing numbers of cases including fatalities, due to inadvertent intake of food allergens are reported. It is therefore necessary to improve declaration laws and develop methods for allergen detection in foods. Allergens can be detected by serological methods (enzyme immunoassays, in vitro basophil histamine release or in vivo skin test procedures in sensitized individuals). The problem of diagnosis of food allergy is further complicated by cross-reactivity between allergens in foods and aeroallergens (pollen, animal epithelia, latex etc.). Elicitors of pseudo-allergic reactions with similar clinical symptomatology comprise low-molecular-mass chemicals (preservatives, colorings, flavor substances etc.). For some of them (e.g. sulfites) detection assays are available. In some patients classic allergic contact eczema can be elicited systemically after oral intake of low-molecular-mass contact allergens such as nickel sulfate or flavorings such as vanillin in foods. The role of xenobiotic components in foods (e.g. pesticides) is not known at the moment. In order to improve the situation of the food allergic patient, research programs to elucidate the pathophysiology and improve allergen detection strategies have to be implemented together with reinforced declaration regulations on a quantitative basis.     

Contact allergy and sociodemographic characteristics

The aim of the study was to determine the frequency of positive patch test reaction to different contact allergens according to patients age, sex, occupation and clinical features. Between 1999 and 2003, patch testing was performed in 3,293 patients with respective clinical diagnoses. Patch testing was done by the standard technique proposed by the International Contact Dermatitis Research Group (ICDRG). Study results showed statistically significant differences in patch test response according to sex and age for three allergens (cobalt chloride, nickel sulphate and thiomersal); according to occupation for nine allergens (cobalt chloride, nickel sulphate, balsam of Peru, fragrance mix, thiuram mix, wood tars, neomycin sulphate, thiomersal and detergents), and clinical diagnosis for two allergens (nickel sulphate, and wood tars). The most common and relevant allergens were: nickel sulphate, cobalt chloride and carba mix. They were found in all examinees regardless of age, sex, occupation and diagnoses. The increased awareness of allergens and their potential sources may help to limit the usage of these chemicals in manufacture of consumer products.     

The cellular and molecular basis for divergent allergic responses to chemicals.

Chemicals vary with respect to the nature of allergic reactions which they will elicit preferentially. A wide variety of environmental and industrial chemicals are known to cause allergic contact dermatitis (contact sensitivity). Some of these are able also to induce respiratory allergy. This article reviews the characteristics of immune responses to different classes of chemical allergens and the role which functional subpopulations of T helper (TH) cells and their soluble cytokine products play in the induction of allergic sensitization. In addition, new opportunities to identify and classify chemical allergens based upon characterization of divergent allergic responses is discussed.     

Contact allergy caused by fragrance mix and Myroxylon pereirae (balsam of Peru)--a retrospective study

Because of their widespread use, fragrances are among the most common causes of contact allergic dermatitis, second only to nickel. During a five-year period 3,065 patients with contact dermatitis were patch tested using a specific mix of fragrances. 509 (16.6%) patients were allergic to the fragrance mix, while 258 (8.4%) patients exhibited an allergic reaction to Myroxylon pereirae (balsam of Peru). Between those 509 patients, 157 were patch tested with eight individual substances contained in the fragrance mix: cinnamal, cinnamyl alcohol, eugenol, isoeugenol, geraniol, hydroxycitronellal, alpha-amyl cinnamal and Evernia prunastri (oak moss). The most frequent allergens were isoeugenol 57.9% (91/157), eugenol 55.4% (87/157), cinnamyl alcohol 34.4% (54/157) and Evernia prunastri (oak moss) 24.2% (38/157). There were 62 patients (39.5%) who exhibited an allergic reaction to both the fragrance mix and Myroxylon pereirae (balsam of Peru). The results prove the importance of avoiding allergens in daily life, especially in industrial and cosmetic products. In order to prevent ACD, better cooperation between industry and dermatologists is needed.     

Sensitivity to mugwort pollen allergens (Artemisia vulgaris)

The author has found that 42% of patients with pollinosis had positive skin reactions with mugwort (Artemisia vulgaris) pollen allergens. The majority of tested patients (139 out of 187) were also allergic to grass pollens. However, hypersensitivity to mugwort pollen allergens was isolated and did not accompany grass pollen allergy. The symptoms of pollinosis appeared in this group later than in patients sensitive to grass pollen allergens only (over 21 years of age in 71%). Bronchial asthma was diagnosed in 40% of these patients and allergic skin reactions in 25%. Sensitivity to mugwort pollen allergens was accompanied by the sensitivity to pollen allergens of Graminae family of plants in 80% of cases. The author suggests that sensitivity to mugwort pollen allergens is the second most frequent cause of the pollinosis and is diagnosed too rarely. Failures of desensitization in patients sensitive to pollen allergens of Graminae family of plants may often result from coexisting sensitivity to mugwort pollen allergens as this sensitivity produces not only season but perennial clinical symptoms in nearly 50% of patients. The author discusses also botanical relations and cross-reactions in allergy to mugwort and ragweed pollen allergens.     

The immune privilege of the oral mucosa

Despite high bacterial colonization and frequent allergen contact, acute inflammatory and allergic reactions are rarely seen in the oral mucosa. Therefore we assert that immune tolerance predominates at this site and antigen presenting cells, such as dendritic cells and different T cell subtypes, serve as key players in oral mucosal tolerance induction. In this article we describe the mechanisms that lead to tolerance induced in the oral mucosa and how they differ from tolerance induced in the lower gastrointestinal tract. Furthermore we discuss ways in which novel nonparenteral approaches for immune intervention, such as allergen-specific immunotherapy applied by way of the sublingual route, might be improved to target the tolerogenic properties of the sophisticated oral mucosal immune network.     

The Anisakis allergy debate: does an evolutionary approach help?

Allergic phenomena share common pathways with the immune response against helminth parasites. The definitions regarding allergens and their related concepts have their roots in the area of allergy research. The experience with the fish parasite Anisakis simplex-associated allergic features still nurtures an open debate on the necessity of larvae being alive to induce allergic reactions such as urticaria or anaphylaxis. Conceptual definitions of allergen, major allergen, as well as putatively crossreacting antibodies, as are used in food allergy, depend on the clinical relevance of specific IgE and deserve careful interpretation in the various forms of A. simplex-associated allergic features. Conversely, an evolutionary based interpretation of the presence of specific IgE depends on the viability of A. simplex.     

Allergy to miscellaneous household arthropods

Of the various arthropods, humans have the greatest contact with mites and cockroaches, and as a result, allergies to these two groups have been the most frequently reported. Changes in lifestyle and living environment have encouraged the growth of arthropods other than mites and cockroaches, and consequently, human exposure to antigens derived from the new arthropods has increased. Although systematic approaches to and immunobiochemical studies of these arthropods are relatively sparse compared with those of mites and cockroaches, recent reports have shown that many species of household arthropods can elicit IgE-mediated reactions via inhalation, biting, or stinging. In this chapter, we review the other arthropods that can induce allergic reaction to human beings. Where the information exists, the frequency of sensitivity and clinical manifestation, and the characterization of the allergens are also reviewed. Virtually all species of arthropods may be sources of allergens that can sensitize and induce IgE-mediated allergic reactions in humans.     

Baculoviral infection reduces the expression of four allergen proteins of silkworm pupa

Silkworm (Bombyx mori) larvae are widely used to express exogenous proteins. Moreover, some silkworm pupal proteins can be used as drug‐loading materials for selfexpressed oral tolerance drugs. However, several proteins expressed in silkworm pupae cause severe allergic reactions in humans and animals. Interestingly, some baculovirus vectors have been shown to alter the host gene and its expression in insect cells, but this has not been confirmed in silkworm. Here, we analyzed the effects of infection with an empty B. mori baculovirus (BmNPV) vector on silkworm pupal protein expression. Using a proteomics approach, the allergens thiol peroxiredoxin (Jafrac1), 27‐kDa glycoprotein (p27k), arginine kinase, and paramyosin as well as 32 additional differentially expressed proteins were identified. Downregulation of the messenger RNA expression of the four known allergens was observed after BmNPV infection; subsequent changes in protein expression were confirmed by the western blot analysis using polyclonal antibodies prepared with recombinant proteins of the four allergens. Collectively, these data indicate that the four known allergens of silkworm pupae can be reduced by infection ith an empty BmNPV vector to increase the safety of silkworm pupa‐based exogenous protein expression and drug delivery of oral pharmaceuticals. In addition, the four recombinant allergen proteins may contribute to the diagnosis of allergic diseases of silkworm pupa.     

Cytokine fingerprinting: characterization of chemical allergens.

Chemical allergy is a common and important occupational health issue. Allergic sensitization induced by chemicals may take a variety of forms, including allergic contact dermatitis (skin sensitization) and allergic asthma and rhinitis (sensitization of the respiratory tract). There is a need to identify and characterize chemicals that have the potential to cause such sensitization reactions. Although a number of methods are available for the prospective analysis of skin sensitizing activity, there are currently no widely accepted tests for the identification of chemical respiratory allergens. We here describe a novel approach, cytokine fingerprinting, that has the potential to distinguish between chemical contact and respiratory allergens. The pattern of cytokine production by draining lymph node cells (LNCs) is evaluated following repeated topical exposure of mice to test chemicals. Experience to date reveals that contact allergens stimulate the selective development of type 1 immune responses associated with the secretion by draining LNCs of interferon gamma (IFN-gamma), but little interleukin-4 (IL-4) or interleukin-10 (IL-10). In contrast, chemical respiratory allergens are found to induce the appearance of preferential type 2 immune responses characterized by IL-4 and IL-10 production, but comparatively low levels of IFN-gamma. It is proposed that cytokine fingerprinting may permit the simultaneous identification and characterization of those chemicals that have the potential to cause allergic sensitization.     

House-dust-mite allergens: A review

The house-dust mites,Dermatophagoides farinae, D. pheronyssinus andEuroglyphus maynei are cosmopolitan inhabitants of the homes of humans worldwide. These mites are the sources of multiple potent allergens that trigger allergic reactions in house-dust-mite-sensitive individuals. Many laboratories using widely varied mite materials and allergic sera, and biochemical and immunological assays, have isolated and characterized, to varying degrees, some of the allergens produced by these mites. The resulting large body of literature is difficult to interpret and relate. This review briefly summarizes the progress made in isolating and characterizing mite-derived antigens and allergens, the relationship between antigens isolated in different laboratories, and the patients' reactivity to these allergens. A brief summary of the allergic reaction and the role of IgE are provided as background.     

Mosquito allergy and mosquito salivary allergens

Allergic reactions to mosquito bites are caused by allergens in mosquito saliva. In this review, allergic reactions to mosquito salivary allergens, and characteristics of salivary allergens and their recombinant forms are described. The use of the recombinant allergens in the diagnosis of mosquito allergy is discussed.     

Mammalian sensitivity to elemental gold (Au degrees)

There is increasing documentation of allergic contact dermatitis and other effects from gold jewelry, gold dental restorations, and gold implants. These effects were especially pronounced among females wearing body-piercing gold objects. One estimate of the prevalence of gold allergy worldwide is 13%, as judged by patch tests with monovalent organogold salts. Eczema of the head and neck was the most common response of individuals hypersensitive to gold, and sensitivity can last for at least several years. Ingestion of beverages containing flake gold can result in allergic-type reactions similar to those seen in gold-allergic individuals exposed to gold through dermal contact and other routes. Studies with small laboratory mammals and injected doses of colloidal gold showed increased body temperatures, accumulations in reticular cells, and dose enhancement in tumor therapy; gold implants were associated with tissue injuries. It is proposed that Au degrees toxicity to mammals is associated, in part, with formation of the more reactive Au+ and Au3+ species.     

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

Background

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction.

Methods and Findings

A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine.

Conclusion

This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens.

Trial Registration

www.ncbi.nlm.nih.gov/pubmed NTR3572     

Mechanism and epidemiology of laboratory animal allergy

Laboratory animal allergy (LAA) is a form of occupational allergic disease. The development of laboratory animal allergy is due to the presence of IgE antibodies directed against animal proteins. The process of sensitization (development of IgE antibodies) is a complex process which involves interaction of antigen presenting cells and lymphocytes of the Th-2 cell type. These cells generate a host of cytokines and other factors which lead to immediate hypersensitivity reactions and other factors which lead to immediate hypersensitivity reactions and the generation of allergic inflammation. Typical symptoms of laboratory animal allergy include nasal symptoms, such as sneezing, watery discharge, and congestion. Skin rashes are also common. Asthma, which produces symptoms of cough, wheezing, and shortness of breath, may affect 20-38% of workers who are sensitized to laboratory animal allergens. Rarely a generalized, life-threatening allergic reaction (anaphylaxis) may occur. The estimated prevalence of laboratory animal allergy is variable depending on the method used for diagnosis, but nonetheless may affect up to 46% of exposed workers. The presence of pre-existing allergies to non-work place allergens (e.g., dust mite, pollens, molds), exposure to laboratory animal allergens, and possibly tobacco smoking are risk factors for the development of laboratory animal allergy. Progress in the understanding of the mechanism and epidemiology of laboratory animal allergy will lead to improved methods for its prevention.     

Clinical significance of dust mite allergens

Dust mites are an important cause of allergic diseases worldwide. The traces of Dermatophagoides farinae and Dermatophagoides pteronyssinus can be found all over the world, while Blomia tropicalis are more common allergenic mites in tropical areas. A variety of allergenic components in dust mites have been found, apart from the different positive rates of IgE reactions in dust mite allergic patients, their biological characteristics, effects on the innate immune system, and especially their distribution characteristics in patients are different. Studying the relationship between dust mite allergens and clinical significance will help for diagnosis of patients and formulation of corresponding Allergen Specific Immunotherapy.