Contact Allergic Reactions Research Articles

Hypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema, and T‐cell hyperresponsiveness in vitro: case report and review of the literature

There are very few reports on hypersensitivity reactions in association with titanium-based materials so that the existence of allergy to titanium is still put in question. We report on a patient in whom impaired fracture healing and eczema localized to the perioperative area developed upon titanium-based osteosynthesis. Patch testing gave no reactions to titanium nor to nickel, chromium, or cobalt. However, in the lymphocyte transformation test, the patient's lymphocytes showed markedly enhanced proliferation in vitro to titanium. After removal of the titanium material, fracture healing was achieved and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium disappeared. Although contact allergic reactions to titanium have been very rarely reported, these findings support a diagnosis of titanium allergy in our patient.

Allergic skin reactions in the tropics

Cutaneous allergic reactions are relatively common in tropical countries, with some caused by the tropical environment and others by changes in the traditional living conditions combined with poverty. HIV infection is a major contributory factor. A large number of reactions are eczematous. Atopic dermatitis is on the increase together with contact allergic reactions. Available products are often of inferior quality and contain irritants and allergens that may be forbidden elsewhere in the world. The extensive and uncontrolled use of drugs and indigenous medications together with an increase in HIV prevalence leads to drug eruptions such as the Stevens-Johnson syndrome and toxic epidermal necrolysis. Poverty plays an important role in the prevalence of insect bites and resulting papular urticaria and possibly in acropustulosis infantum. Many unexplained environmentally induced blistering diseases occur, ranging from phytophotodermatitis to fogo selvagem and from pemphigus foliaceus to chronic bullous dermatosis of childhood. This article describes the allergic conditions that occur in the tropics. Special attention is given to those cases of eczema and eruptions that are specific to tropical countries. Available treatments are also discussed.

Schwarze Hennatattoos: eine unterschätzte Ursache für Lawson- und Benzocainallergie

Background and aims: Paraphenylenediamine (PPD) was identified as the major allergen responsible for most contact reactions due to black henna tattoos. Lawsone, a naphthoquinone (2-hydroxy-1,4-naphtoquinon) and the allergenic compound in henna, seemed to have low sensitization potential. As a consequence, lawsone was not considered important in adverse reactions to henna tattoos. Methods: 12 Patients with adverse reactions to black henna tattoos were investigated. Epicutaneous tests were performed using a standard series. Furthermore, PPD at a concentration of 1% and lawsone at a concentration of 10% were used. The substances were applied to the upper back. Readings were made after 3 days. Reactions were scored as recommended by the ICDRG. Results: Patch test results revealed 11 allergic reactions to PPD 1%, 4 allergic reactions to lawsone 10%, 4 to benzocaine 5% and 2 to IPPD 0,1%. Conclusion: All patients with allergic reactions after black henna tattoos reacted as expected to PPD, but 4 of 11 also to lawsone. In this context, lawsone might have more relevance than previously assumed. Furthermore, 4 of 11 patients showed cross-sensitization to benzocaine which, in this circumstance, might be attributed more clinical value as well. Taken these observations and the rare occurrence of contact allergic reactions due to lawsone into consideration, it seems that the allergic reaction caused by the potent allergen PPD triggers sensitization to weak allergens.

Contact allergy in patients with chronic venous leg ulcers – possible role of chronic venous insufficiency

The purpose of this study was to evaluate frequency of contact allergy in patients with chronic venous leg ulcers (CVLU) and to estimate possible relationships between allergic contact reactions and characteristics of both chronic venous insufficiency (CVI) and CVLU. We performed patch tests with the European standard series, antibiotics, glucocorticosteroids and ointment vehicles in 50 patients with CVLU. Patients underwent detailed CVI diagnostics using colour flow duplex ultrasound examination, ankle brachial pressure index determination and leg ulcers area measurement. Positive patch tests results were found in 80% and polyvalent allergy in 56% of patients. Statistically significant correlations were recorded between CVI and CVLU duration, CVLU duration and CVLU area and between CVI duration and polyvalent allergy frequency. Statistically significant differences were observed between coexistence of superficial and deep system insufficiency and CVLU duration, characteristics of contact allergic reactions and CVI duration, frequency of allergic contact reaction and presence or absence of long saphenous vein insufficiency, incidences of vein thrombosis and characteristics of contact allergic reactions as well as between characteristics of contact allergic reactions and both CVLU duration and area. Complex pathophysiological processes, including inflammatory reactions, in course of CVI may influence development of allergic contact reaction in CVLU patients.

Upregulation of the Axonal Growth and the Expression of Substance P and its NK1 Receptor in Human Allergic Contact Dermatitis

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.

6. Contact allergic reactions in patients with atopic eczema

The controversy concerning the sensitizing potential of a common agent to which there is contact sensitivity, dinitrochlorobenzene, has been reassessed by Rees et al. (1). Dose-response relationships for contact sensitization and elicitation at three different concentrations of dinitrochlorobenzene were determined for 22 patients with minimal atopic eczema compared to 27 non-atopic healthy control subjects. Atopic patients were significantly less responsive, with smaller reactions at all challenge doses and exhibited flatter challenge doseresponse curves than did healthy controls. This is in keeping with the classic cytokine route of sensitization, which indicates that atopics should be less prone to sensitization under experimental conditions.

Colourants in transferable picture tattoos for the skin

Transferable picture tattoos for the skin are popular among children. There is however very little knowledge about the colourants that may be present in the picture tattoos and thus of the risk of contact allergic reactions. In the present investigation, 36 picture tattoos were analysed for the content of 129 organic colourants listed in the Cosmetic Directive, to which these products should comply as they are used on the skin. Only 11 of the cosmetic colourants could be identified in the analysed samples. Allergenic potential of 7 of these colourants (CI 15850, CI 11920, CI 45220, CI 75300, CI 13015, CI 45100 and CI 15525, maximum concentration 35-4479 p.p.m.) was evaluated on the basis of published scientific data. Only scarce information regarding contact allergy to these substances was found in the available literature. Most information in the literature regarding contact allergy has concerned CI 75300, curcumin, which is reported to have caused a few cases of contact allergy as a colourant in food or in disinfectants used prior to surgery. In no case, allergic reactions to any of the colourants have been verified from transferable picture tattoos. On the basis of this investigation, the risk of allergic reactions from the colourants in the transferable picture tattoos seems to be limited.

Contact and photocontact allergy to ketoprofen. The Belgian experience.

Topical ketoprofen (KP) is widely used because of its anti-inflammatory effect. However, photocontact dermatitis is a side-effect. Between May 2001 and June 2002, the Belgian Contact & Environmental Dermatitis Group conducted a prospective, open patch and photopatch test study in 20 patients suspected of KP dermatitis. Severe skin symptoms requiring systemic corticotherapy occurred in 47%. 5 patients were hospitalized. 1 patient showed prolonged photosensitivity. All patients were tested with KP and the other constituents of KP gel. Attribution to KP was demonstrated in all cases. Patch and photopatch tests with KP 2% in petrolatum showed contact photoallergy in 17 patients, contact allergy in 1 patient and photoaggravated contact allergy in 2 patients. 5 patients also reacted to the fragrance components lavender (Lavandula augustifolia) oil and/or neroli (Citrus aurantium dulcis) oil 5% in alcohol. However, in 4 of these, irritant reactions to the ethanolic dilutions could not be ruled out. Additional tests with 3 non-steroidal anti-inflammatory drugs without benzophenone structure ibuprofen, naproxen and diclofenac identified only 1 contact allergic reaction to diclofenac. Cross-reactivity to the substituted benzophenones, oxybenzone and sulisobenzone occurred only to the first in less than 30% of the patients. A high frequency (69%) of contact allergy to fragrance mix was found. Dermatologists should be aware of the severity of photoallergic reactions to KP and the risk of cross-sensitization.

FS06.4 Milia as sequelae to allergic contact dermatitis, a case report

Milia are small sub epidermal keratin cysts. They may be seen following bullous diseases disrupting the dermo‐epidermal junction. They may occur rarely as a complication to contact allergic reactions. An oak moss allergic patient participated in a dose response ROAT with chloratranol, shown to be a potent allergen in oak moss. The patient reacted to choratranol at patch testing down to 0.0063 ppm, and started a ROAT by application of 2 drops of a 5 ppm solution to an area of 3 × 3 centimetres on the volar aspect of one forearm. After 1 day severe oedematous dermatitis was observed and blistering was seen at day 2. The test was stopped and the patient treated with systemic prednisolone. At a 3 month control visit milia were seen at the application site on the forearm but not on the back where the patch tests were applied. The patient had no subjective symptoms and the milia were easily removed with a sterile needle. The presence of milia as sequelae seems to reflect the depth and severity of the allergic contact dermatitis developed months earlier. This observation underlines the potency of chloratranol as a very strong allergen.

FC04.1 Some new and unexpected allergens in cosmetics

Labels on cosmetics with statements such as ‘recommended by dermatologists’, ‘allergy‐tested’, ‘hypo‐allergenic’, and more recently ‘for use on intolerant’ or for ‘sensitive skin’ have become very popular. Indeed, many ingredients are used precisely because of their low irritancy potential. However, this does not preclude the occurrence of contact allergic reactions from such cosmetic products. During the last few months several of these substances have been identified as allergens. Examples are: – Alkylglucosides, e.g. coco‐, decyl‐, and laurylglucosides, which are condensation products of the corresponding fatty alcohols with glucose, are widely used as emulsifiers in skin‐care products, mild surfactants and cleansing agents, as well as in fragrance products, hair dyes, sunscreens and tanning products. – Ethylhexylglycerin (syn.: octoxyglycerin) is used as a skin conditioning agent (and for miscellaneous purposes). – Methoxy PEG‐17 and PEG‐22/dodecyl glycol copolymers, which are alkoxylated alcohols and synthetic polymers, are used as emulsion stabilizers and suspending and viscosity‐increasing agents, and also as skin‐conditioning agents. – Butylene glycol and pentylene glycol are aliphatic alcohols with applications similar to those of propylene glycol, which is considered to be more irritant and allergenic. These agents are widely used in a wide variety of cosmetic products because of their solvent, humectant and antibacterial effects. Butylene glycol is also usd as a fragrance ingredient and as a skin conditioner.

Contact dermatoconjunctivitis secondary to phenylephrine hydrochloride ophthalmic solution

The patient is an 81 year-old male evaluated by ophthalmology for cataract surgery. The patient's eyes were dilated with one drop each of the anticholinergic agent tropicamide ( Mydriacyl 0.5% ®), and the sympathomimetic agent, phenylephrine hydrochloride 2.5%. The combination solution, fluorescein sodium 0.25%/benoxinate hydrochloride 0.4% ( FluorBenox ®), was also instilled in both eyes prior to tanometry. After several hours, the patient developed ocular redness and swelling, lasting one week in duration. On examination 3+ conjunctival injection, 2+ chemosis, and corneal immune infiltrates were seen. A similar reaction occurred one year prior, after dilation with phenylephrine hydrochloride. Patch tests were performed with the above ophthalmic solutions and a standard panel (T.R.U.E. Test ®) and were read at 48 and 96 hours. Strong positive reactions were documented for the phenylephrine hydrochloride 2.5% ophthalmic solution and four non- contributory compounds at 96 hours. The preservative in the phenylephrine solution, benzalkonium chloride 0.01%, was also an ingredient in the tropicamide solution, and thus was not the cause of the reaction. Allergic contact reactions to phenylephrine hydrochloride have rarely been reported in the literature despite its wide use. This patient's history, clinical findings and positive patch test results suggest a delayed type cell-mediated hypersensitivity reaction to phenylephrine. Ophthalmologists and allergists need to be aware that such hypersensitivity exists and should patch test patients who present with a similar history.

Management with topical nitrogen mustard in mycosis fungoides.

Topical nitrogen mustard (mechlorethamine, NM) has been used as primary therapy for management of patients with mycosis fungoides (MF) since the 1950s. Many investigators have demonstrated the efficacy of topical NM in patch and/or plaque disease of MF. Updated results from Stanford also confirm the clinical efficacy. The complete response (CR) rates reported are 76-80% for patients with limited patch/plaque (stage IA), and 35-68% for those with generalized patch/plaque (stage IB) disease. Topical NM can be used as an aqueous (water) or ointment-based preparation. The efficacy results are similar in patients who were treated with aqueous versus ointment preparations. Maintenance regimens used are variable, but there is no data to suggest that a longer maintenance duration results in greater potential for long-term remission. Most patients who achieve initial CR with topical NM tend to require NM-only for disease management. Topical NM is equally effective when used as salvage therapy with disease relapse. The most common toxicity of topical NM therapy is contact irritant or allergic reaction. The potential for allergic reaction is significantly reduced (< 10%) when NM is used as an ointment preparation. The potential for secondary skin cancer development is increased in patients who have used multiple sequential topical skin-damaging therapies or NM in the genital skin, but not in patients who have used NM as monotherapy (avoiding genital skin application). Topical NM is used safely in pediatric patients and there is no evidence of any clinically significant systemic absorption of topically applied NM.

Contact orofacial granulomatosis caused by delayed hypersensitivity to gold and mercury

Orofacial granulomatosis, an entity with characteristic clinicopathologic features, is thought to be a reactive process. The authors describe orofacial granulomatosis associated with contact allergy to gold in dental crowns in one patient and a possible allergic contact reaction to mercury from dental fillings in another one. Thus allergic contact dermatitis to the metals gold and mercury should be considered as a possible etiologic agent of orofacial granulomatosis.

Temporary holiday “tattoos” may cause lifelong allergic contact dermatitis when henna is mixed with PPD

Temporary tattoos are becoming more popular especially among teenagers. For this purpose henna tattoos are usually used. Although pure henna is relatively safe, combining it with other colouring agents such as para-phenylenediamine (PPD), may cause skin sensitisation. Several cases of contact allergy from temporary tattoos have been reported, each with positive reactions to PPD. Six cases of allergic contact reaction to temporary tattoos are reported. In all cases, the responsible agent was PPD. Two were also allergic to black 'henna' hair dye which also contained PPD. They had been sensitised on earlier holidays by their temporary tattoos. Temporary holiday tattoos may cause lifelong contact allergy. Although the allergenicity of pure henna is low, the allergenicity of PPD is high. Holiday 'tattoo' reactions are going to be common until PPD is removed from the mixture.

Hydroxyisohexyl 3‐cyclohexene carboxaldehyde‐ known as Lyral®: quantitative aspects and risk assessment of an important fragrance allergen

Hydroxyisohexyl 3-cyclohexene carboxaldehyde, also known as Lyral, is a fragrance ingredient identified as the cause of contact allergic reactions in 2-3% of eczema patients undergoing patch testing. Lyral has been included in the standard patch test series in many clinics due to its importance as an allergen. It has been used without restrictions in cosmetic products, until now. In the present study, the dose-response relationship of Lyral contact allergy was studied with doses relevant for normal exposure in cosmetic products. 18 eczema patients, who previously had given a positive patch test to Lyral 5% petrolatum, were included along with 7 control subjects. All cases were tested with a serial dilution of Lyral in ethanol 6% to 6 p.p.m and subjected to a 2-week, repeated open application test with a low dose of Lyral in ethanol. In the case of no reaction, this was followed by another 2 weeks of testing with a higher dose. The test was performed at the volar aspect of the forearm. In 16 of 18 cases (89%), a positive use test developed, 11 reacting to the low and 5 to the high concentration. None reacted to the vehicle control of ethanol applied to the contralateral arm. All controls were negative to both the test solutions of Lyral and the ethanol control. The difference between the test and the control group was statistically significant (Fisher's test, P < 0.001). It is concluded that Lyral at the current usage levels is inducing sensitization in the community. The same levels were shown to elicit allergic contact dermatitis in almost all sensitized individuals. A significant reduction in usage concentrations is recommended to prevent contact allergic reactions.

Occupational contact dermatitis.

Skin reactions are common in the workplace. The skin, which constantly is exposed to chemicals and industrial processes, develops inflammatory reactions, most commonly dermatitis, which may have an allergic or irritant basis. The epidemiology, pathophysiology, and clinical features of common occupational dermatoses are discussed. Irritant, allergic, and urticarial contact reactions are compared, and their clinical features are outlined. Important occupational irritants and allergens, their sources, and the industries in which they most commonly are found are listed. The prognosis and therapy of these occupational reactions are examined.

Electrical impedance as a potential tool to distinguish between allergic and irritant contact dermatitis

Background and Objective: The allergic contact reaction is a model reaction for studying the cell-mediated immune system of the skin. In this study we use a noninvasive method, electrical impedance (IMP), to compare nickel (Ni) allergic contact reactions with an irritant contact reaction induced by sodium lauryl sulfate, which has already been carefully evaluated with this method. For this purpose, we included only Ni- and sodium lauryl sulfate-induced reactions of very similar appearance. Methods: Various concentrations of Ni sulfate in distilled water were applied on the volar aspect of the forearms of 33 adult women who were allergic to Ni. Assessments were made using visual scoring, a new IMP technique, and transepidermal water loss 3 and 7 days later. Results: In the 19 patients who completed the study, 3 of the 4 impedance indices were significantly lower at the sodium lauryl sulfate sites than at the Ni sites on day 3; ie, the mean magnitude (MIX) (P ≤ .001), imaginary part (IMAX) (P ≤ .001), and real part (RIX) indices (P ≤ .01). Unlike the irritant reactions, no significant increases in transepidermal water loss occurred in the allergic contact reactions. This may be because, in reactions of the studied magnitude, an allergic contact reaction does not significantly affect the epidermis because the inflammatory process is located deeper in the dermis than an irritant reaction. Conclusion: This study suggests that IMP, as used herein, is suitable for distinguishing between contact reactions of allergic and irritant nature. Although pathophysiologic events in the tissue studied significantly modify impedance patterns, little is known about how to interpret the structural and chemical changes underlying these patterns. Studies are needed to determine the relation between anatomic or pathophysiologic parameters, and the findings using IMP and other established methods, such as chemical extraction and histopathology. (J Am Acad Dermatol 2003;48:394-400.)

All that drains is not infectious otorrhea

It has been said that, ‘All that wheezes is not asthma.’ Thus, is also so of otorrhea. Bacterial infection most often causes otorrhea which, in turn, generally responds to treatment with ototopical antimicrobial therapy. When it persists, non-infectious etiologies must be considered. Although allergic causes of otorrhea have been described in the literature, inhalant environmental allergens (Type I Allergy) causing eustachian tube dysfunction or ototopical drops, most notoriously neomycin containing formulations, causing contact dermatitis are those usually mentioned. Further, most reports of contact allergic reactions of the ear have involved the external auditory canal skin or pinna and have been attributed to non-medicinal triggers like shampoos and metals used in ear rings. A search of the literature failed to reveal a reported case of recurrent or chronic otorrhea without cholesteatoma due to an allergic reaction to the components of a tympanotomy tube (TT). Such a case is presented here.

Fragrance contact allergy: a clinical review.

Most people in modern society are exposed daily to fragrance ingredients from one or more sources. Fragrance ingredients are also one of the most frequent causes of contact allergic reactions. The diagnosis is made by patch testing with a mixture of fragrance ingredients, the fragrance mix. This gives a positive patch-test reaction in about 10% of tested patients with eczema, and the most recent estimates show that 1.7-4.1% of the general population are sensitized to ingredients of the fragrance mix. Fragrance allergy occurs predominantly in women with facial or hand eczema. These women typically have a history of rash to a fine fragrance or scented deodorants. Chemical analysis has revealed that well known allergens from the fragrance mix are present in 15-100% of cosmetic products, including deodorants and fine fragrances, and most often in combinations of three to four allergens in the same products. This means that it is difficult to avoid exposure, as products labelled as 'fragrance free' have also been shown to contain fragrance ingredients, either because of the use of fragrance ingredients as preservatives or masking perfumes, or the use of botanicals. About 2500 different fragrance ingredients are currently used in the composition of perfumes and at least 100 of these are known contact allergens. Therefore, it is advisable to supplement standard patch testing with the patient's own stay-on cosmetic products, as well as the fragrance chemical hydroxyisohexyl-3-cyclohexane carboxaldehyde, which on its own gives responses in 1-3% of tested patients. The focus in recent years on the ingredients of the fragrance mix will probably result in the fragrance industry changing the composition of perfumes, and thus make the current diagnostic test less useful. New diagnostic tests are under development to identify contact allergy to new allergens, reflecting the continuous developments and trends in exposure.

Allergic contact dermatitis to epoxy resin in immersion oil for light microscopy

Allergic contact dermatitis caused by immersion oil used for microscopy is a recently recognized phenomenon. We report a case with characteristic findings of periorbital erythema and edema in a cytogenetics technician. Positive patch test responses to epoxy resin, epoxy acrylate, and the immersion oil were noted. This case represents yet another contact allergic reaction, possibly airborne, to epoxy resin present in immersion oil used for microscopy. (J Am Acad Dermatol 2002;47:954-5.)