Contact allergy to corticosteroids in patients using inhaled or intranasal corticosteroids for allergic rhinitis or asthma.

BACKGROUND: Patients using topically applied corticosteroids are at risk of developing allergic contact hypersensitivity. OBJECTIVE: To assess prevalence of allergic contact hypersensitivity reactions to inhaled or intranasal corticosteroids. METHODS: A prospective study of 30 adult patients using inhaled or intranasal corticosteroids for conditions such as allergic rhinitis was performed. We used epicutaneous patch testing to determine the prevalence of allergic contact hypersensitivity to corticosteroids and common additives (propylene glycol and benzalkonium chloride) in inhaled and nasal corticosteroid preparations in this population. RESULTS: Of 30 patients, 4 (13%) had positive patch test results. 3 (10%) were allergic reactions and 1 (3%) was an irritant reaction. Half of the reactions were to a corticosteroid (budesonide) and half were to a common preservative in nasal preparations (benzalkonium chloride). CONCLUSION: This study supports other clinical evidence that contact dermatitis/mucositis from inhaled or intranasal corticosteroid products can occur. The corticosteroids or added agents such as preservatives can be causative and may result in allergic or irritant reactions, which can be relevant to clinical symptoms.     

Type 1 and type IV hypersensitivity to nickel

We report a case of type 1 and type IV contact hypersensitivity to nickel. Very few cases of immediate contact urticaria to nickel have been reported. The mechanism behind this is not fully understood, although it has been postulated that nickel may act as a mast cell discharger on a non-immunological basis. Nickel is found in varying concentrations in stainless steels; its biological availability varies depending on the alloy composition. Our patient has adapted her lifestyle to minimize her contact with household appliances containing nickel. If medical or dental treatment using stainless steel equipment is required, we recommend a short course of oral corticosteroids and antihistamines.     

Immediate and delayed hypersensitivity to corticosteroids

Corticosteroids are therapeutic agents used in cases of allergy and intolerance. Due to the antiinflammatory effects of the corticosteroids, hypersensitivity reactions often are considered to be a paradox. However, delayed‐type reaction to corticosteroids is a frequent phenomenon in the daily routine. Non‐responding eczema, development of subacute contact eczema, systemic contact dermatitis or maculopapular exanthemas can be a clinical symptom of a delayed‐type hypersensitivity reaction to corticosteroids. Immediate‐type hypersensitivity reactions to corticosteroids remain uncommon. Nevertheless, they can take a severe clinical course. Patients react with anaphylaxis after systemic administration or with aggravation of an allergic reaction under therapy with corticosteroids. Allergologic testing is necessary for diagnosis and providing alternative corticosteroids in case of an emergency.     

Langerhans cells but not monocytes are capable of antigen presentation in vitro in corticosteroid contact hypersensitivity

Corticosteroids suppress delayed-type hypersensitivity (DTH) reactions in vivo and impair lymphoid cell functions in vitro. In contact hypersensitivity (CHS) to corticosteroids, however, the corticosteroids are capable of inducing DTH responses in vivo. The present study examined the capacity of corticosteroids to induce in vitro proliferation of T lymphocytes from patients with CHS to corticosteroids. With peripheral blood mononuclear adherent cells as antigen-presenting cells (APC) and hydrocortisone-17-butyrate (H-17-B) as hapten, no proliferation responses were detected of T lymphocytes from patients with CHS to H-17-B. However, when epidermal Langerhans cells (LC) were used as APC, weak proliferation responses were observed.     

Hypersensitivity to topical corticosteroids

Contact hypersensitivity from topical corticosteroids is becoming increasingly recognized; it is present in 2–5% of the patients attending contact dermatitis clinics. The use of a corticosteroid series containing tixocortal pivalate 1% (petrolatum), to detect hypersensitivity to hydrocortisone, and other steroids 1% (ethanol), depending on local corticosteroid usage, detects the majority of cases of corticosteroid hypersensitivity. In selected cases, the use of intradermal tests further improves the diagnosis of corticosteroid hypersensitivity. Corticosteroid hypersensitivity occurs most frequently among patients with stasis dermatitis. However, corticosteroid hypersensitivity is also common in other types of dermatitis, occurring as frequently as hypersensitivity to several allergens (e.g. wool alcohols and colophony) in the European standard battery. Although hypersensitivity has mainly been reported with corticosteroids applied to the skin, reactions may also occur on mucosal surfaces, following systemic administration and with sex steroids.     

The significance of previous allergic contact dermatitis for elicitation of delayed hypersensitivity to nickel

Several factors, such as amount of allergen, vehicle, anatomic site, immunologic status and previous eczema, may influence delayed hypersensitivity reactions. In an extended model, we have studied the significance of previous allergic contact dermatitis for elicitation of delayed hypersensitivity to nickel in 25 nickel-allergic females. On 3 occasions, 8, 4 and 1 months before the final challenge patch testing, an experimental allergic contact dermatitis from nickel was induced on the lower back. At the challenge patch testing, 4 identical dilution series of nickel were tested on 4 areas on the lower back 3 with previous but healed dermatitis and I control area. The tests were read in a blind way. A significantly higher test reactivity was found at the areas with a previous allergic contact dermatitis, the shorter the time interval between the previous provocation and the challenge, the stronger the reaction. These results may be of importance for the understanding of factors contributing to chronicity of allergic contact dermatitis.     

Flare-up reactions after oral challenge with nickel in relation to challenge dose and intensity and time of previous patch test reactions

BACKGROUND: In this study we have taken an interest in systemic exposure to nickel in patients with delayed hypersensitivity to nickel. OBJECTIVE: The aim of the study was to more closely investigate the importance of factors such as ingested nickel dose, time interval between nickel patch testing and oral nickel challenge as well as degree of nickel hypersensitivity in relation to flare-up reactions. METHODS: Thirty nickel-sensitive female subjects were patch tested with a serial dilution of nickel sulfate in water on 4 different test occasions during a period of 7 months. One month after the last patch test the patients were randomly divided into 3 different groups. The patients in the groups were challenged orally with a placebo capsule, 1.0 mg nickel, or 3.0 mg nickel. RESULTS: None of the patients challenged with placebo had flare-up reactions of earlier patch test sites, but 2 of the patients challenged with 1.0 mg nickel and all of the patients challenged with 3.0 mg nickel had flare-up reactions. There were significantly more flare-up reactions of the most recent patch test sites (1 month) compared with the most distant (8 months) test sites. There was also a statistically significant positive correlation between the intensity of previous positive patch tests and the flare-up reactions. CONCLUSION: In the assessment of the possibility of systemic allergic contact dermatitis from nickel, the dose as well as the intensity and time since previous nickel eczema have to be considered.     

Copper hypersensitivity

The world production of copper is steadily increasing. Although humans are widely exposed to copper‐containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.     

Detection of contact hypersensitivity to topical corticosteroids with hydrocortisone-17-butyrate

We showed earlier that most patients with contact dermatitis due to corticosteroids show cross-reactions when patch tested with hydrocortisone-17-butyrate (H-17-B). To test whether H-17-B could be used for detecting topical corticosteroid allergy, we screened patients undergoing routine patch testing with H-17-B. Patients with clearly allergic or doubtful/mildly irritant patch test reactions to H-17-B, and with a history suggesting topical corticosteroid allergy, were further tested with a large panel of steroid preparations. 20 out of 4039 patients (0.5%) showed definite allergic test reactions to corticosteroids. A further 165 patients with clinically suspected corticosteroid allergy were directly tested with a panel of steroid preparations; 14 patients showed positive patch test reactions. Altogether, 33 out of 34 patients with corticosteroid allergy had positive test reactions to H-17-B. Inclusion of 1.0% H-17-B in ethanol in the standard patch test series improves the diagnosis of topical corticosteroid hypersensitivity.     

Nickel dental alloys can induce laryngeal edema attacks: A case report

Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration.     

Polyvalent contact allergy to corticosteroids: A report of two cases

Two cases of positive allergic reactions to eight patch-tested corticosteroid substances are reported. The patients were middle-aged women with a long history of contact dermatitis who had used topical corticosteroids for years. Pure corticosteroid substances were tested in therapeutic and 1% concentrations in ethanol and petrolatum. The intensity of reactions was different depending on the vehicle and concentration. Patients with hypersensitivity to several corticosteroid substances represent an important therapeutic problem.     

Contact dermatitis following sustained exposure to pecans (Carya illinoensis): a case report

Type I hypersensitivity reactions following ingestion of peanuts and tree nuts are well characterized. Cutaneous hypersensitivity reactions are less well characterized, yet they remain the second most common reaction pattern to contact with or ingestion of such nuts. We present a case of a patient who experienced an acute vesicular cutaneous reaction after prolonged contact with pecans. This case illustrates the salient features of contact dermatitis and serves as a reminder that contact with allergenic foods can lead to hypersensitivity reactions.     

Connubial contact dermatitis to an inhaled corticosteroid

BACKGROUND: Inhaled corticosteroids are widely used in allergic asthma and rhinitis. They are most often used alone or sometimes in association. Allergic side-effects of inhaled corticosteroids are less frequent than those of topical corticosteroids. We report a case of a connubial dermatitis to a budesonide spray. OBSERVATION: A 3-year old boy was treated for asthma by budesonide (Pulmicort) and terbutaline (Bricanyl) aerosols with an inhalation chamber (Babyhaler). From the fourth day of treatment onwards, his mother had swollen and itchy lesions on the face with conjunctivitis several hours after the administration of the corticosteroids using the inhalation chamber. The last eruptions were marked by extensive lesions. The patient reported a worsening of her eruption when she was treated with a desonide cream (Tridesonit). Prick-tests conducted later on confirmed the contact allergy to budesonide and Pulmicort spray. They were also positive for Tridesonit cream and triamcinolone acetonide. Repeated open application tests with a 17-butyrate hydrocortisone cream (Locoid) for three weeks remainded negative. DISCUSSION: Our observation is original: allergic contact dermatitis to inhaled corticosteroids is rare, the clinical presentation mimicked angioedema although it was a delayed-type hypersensitivity, hypersensitivity was limited to group B corticosteroids and it was in fact a connubial contact dermatitis.     

Easter Egg Hunt Dermatitis: Systemic Allergic Contact Dermatitis Associated with Chocolate Ingestion

Pediatric systemic allergic contact dermatitis to nickel has previously been reported in association with cocoa. We present four clinical cases of hypersensitivity temporally associated with chocolate consumption at Easter. Clinicians should be aware of the potential for foods high in nickel to provoke patients with known nickel sensitivity and systemic dermatitis.     

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.     

Looking back,and forward to 2015

Nickel‐containing alloys are widely used in orthodontic appliances, even though nickel is by far the most common contact allergen. However, the scientific evidence concerning allergic reactions to nickel in orthodontic patients has not been evaluated systematically. The objective of this study was to investigate whether the prevalence of nickel hypersensitivity is affected by orthodontic treatment. Unrestricted electronic and manual searches were performed until July 2013 for human clinical studies assessing orthodontic treatment and nickel hypersensitivity. Methodological limitations were evaluated with the Downs and Black tool. Crude and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated from random‐effects meta‐analyses, followed by subgroup and sensitivity analyses. Thirty studies were included in the review, and 24 datasets with 10 184 patients in the meta‐analyses. Orthodontic treatment had no significant effect on nickel hypersensitivity (n = 11; crude OR 0.99; 95%CI: 0.78–1.25; p = 0.914). However, when confounding from factors such as sex and piercings was taken into account, orthodontic treatment was associated with a lower risk of hypersensitivity (n = 1; adjusted OR 0.60; 95%CI: 0.40–0.80; p < 0.001). This was even more pronounced when orthodontic treatment was performed prior to piercing (n = 7; crude OR 0.35; 95%CI: 0.24–0.50; p < 0.001). Orthodontic treatment seems to have a protective role against nickel hypersensitivity, especially when it precedes piercings.     

An overview of the efficacy of topical corticosteroids in experimental human nickel contact dermatitis

We review controlled trials of corticosteroid effect in experimentally elicited acute nickel contact dermatitis in man, in the hope of clarifying optimal efficacy for clinical use. To maximize discrimination and objectivity, we focus on data with 1 well-characterized allergen, nickel, in studies utilizing bioengineering documentation. Higher potency corticosteroids are effective (unlike in experimental irritant contact dermatitis), but optimum schedules still require definition.     

Predictive evaluation in animals of the contact allergenic potential of medically important substances

Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives {formalin, ethylenediamine and sorbic acid), drugs (penicillin G, benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p-phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as t in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.     

Immediate- and Delayed-Type Contact Hypersensitivity in Children Older than 5 Years With Atopic Dermatitis: A Pilot Study Comparing Different Tests

Abstract: We conducted a prospective open study of immediate- and delayed-type contact hypersensitivity to food and other allergens in 33 children with atoplc dermatitis (AD). The design of the study was exploratory and not randomized. Various methods for detecting immediate-type hypersensitivity were compared. Thirty-three children age 5 to 15 years with persistent AD were initially enrolled, but 3 dropped out. Nine patients had positive reactions to foods in the patch-scratch tests, four had positive reactions in the skin application food test, and five had positive reactions to foods in the prick tests. Positive reactions to foods were observed in only three patients on the delayed-type patch tests. In all tests, but especially the patch-scratch and prick tests, positive reactions to food allergens were observed without clinically related symptoms. None of these tests gave ideal results. Twenty (67%) of the 30 children had positive reactions to inhalants in prick testing. Fourteen showed positive patch-test reactions with the European standard series (True Test). The most positive reactions were to nickel (9 patients), cobalt, and balsam of Peru. Restrictive measures led to evident improvement of AD only in some children. The results of this study illustrate that food allergy plays only a limited rote in patients with AD age 5 to 15 years. We could not conclude which of the tests would predict which children might benefit from dietary manipulation.