Allergic skin disease: investigation of both immediate- and delayed-type hypersensitivity is essential

BACKGROUND: In our clinic we routinely patch test patients referred from occupational health for the investigation of latex contact urticaria. We also undertake both patch and prick testing (where indicated) in patients referred with persistent dermatitis/eczema. If investigation of allergic skin disease is undertaken by a non-dermatologist, it is unlikely that patch testing will be performed. OBJECTIVE: To carry out a retrospective analysis of patients who had been prick tested to establish whether an incomplete diagnosis would have been reached if patch testing had been omitted. METHODS: Details of patients who had attended for patch testing between July 2004 and December 2005 were analysed. Patients who had had prick tests and patch testing were identified. The outcomes of prick tests and patch testing were documented together with the clinical relevance. RESULTS: Three hundred and thirty out of 1060 patients referred to the clinic were prick tested. 54.2% patients were referred from dermatologists. 26.6% were referred from occupational health, 68 patients had positive reactions on prick testing of whom 36 had positive patch tests (52.9%), which were of current relevance in 27 patients (39.7%). Nine out of 106 health workers referred to exclude latex contact urticaria had positive prick tests to latex. Fifty of these patients demonstrated delayed-type hypersensitivity with nickel, cobalt, rubber and its additives being the most common allergens found. Of the 262 patients who had negative prick tests, 121 had positive patch tests (46.1%) of current relevance to patient history in 92 subjects (35.1%). While none of the six patients referred for investigation of reaction to local anaesthetics had a positive prick test, one was allergic to local anaesthetic on patch testing. CONCLUSION: Omission of patch testing from the investigation of allergic skin disease, even when contact urticaria may be the sole suspected diagnosis, would result in the frequent missed diagnosis of contact allergy. We recommend that patients with suspected allergic skin disease are investigated in an environment where investigation of both immediate- and delayed-type hypersensitivity can be undertaken. In particular, patients with atopic eczema, suspected latex rubber allergy, hand dermatitis (particularly occupational) and drug reactions should be targeted to receive both investigations.     

Occupational asthma,rhinitis, and contact urticaria caused by oxidative hair dyes in hairdressers

BackgroundOxidative hair dyes commonly contain paraphenylene diamine (PPD) and its derivatives, a well-known cause of delayed hypersensitivity among both consumers and hairdressers. They are also considered possible causes of occupational respiratory diseases. Despite the widespread use of hair dyes, there are only a few reports of asthma, rhinitis, and contact urticaria caused by PPD and related compounds.ObjectiveTo characterize patients with occupational asthma, rhinitis, or contact urticaria associated with oxidative hair dyes and to evaluate the diagnostic methods.MethodsWe reviewed the patient files of the Finnish Institute of Occupational Health for the period January 1, 2001, through May 31, 2011, to identify patients diagnosed as having asthma, rhinitis, or contact urticaria associated with oxidative hair dyes. The diagnoses of asthma and rhinitis were based on specific inhalation challenges with hair dye products. Skin prick tests were performed with hair dye ingredients as hapten conjugates of human serum albumin and with hair dye products and ingredients as is. Open skin tests confirmed the diagnosis of contact urticaria.ResultsWe describe 11 hairdressers with occupational asthma (5 cases), rhinitis (5 cases), and contact urticaria (3 cases) due to hair dyes. Of the 52 specific inhalation challenges performed, 9 (17%) had positive results. One patient who experienced an anaphylactic reaction when having her own hair dyed had positive skin prick test results to PPD and toluene-2,5-diamine sulfate.ConclusionHairdressers are at risk for occupational asthma, rhinitis, and contact urticaria due to oxidative hair dyes. Skin prick testing may be insensitive for detecting immediate hypersensitivity to PPD and related compounds.     

Hypersensitivity to natural latex

Rubber hypersensitivity is well described but usually as a contact dermatitis caused by chemicals added during the process of making natural latex or synthetic rubber. IgE-mediated reactions, mainly contact urticaria, have rarely been reported in Europe. We report a case of immediate hypersensitivity to latex. A 34-year-old female operating room nurse developed hand eczema to natural latex. On two occasions, while she was gloving for surgery, she had the following reactions: flushing, tachycardia, urticaria, angioedema, wheezing, and light-headedness. Prick and patch testing to thiuram mix, mercaptobenzothiazole, phenylenediamine mix, and carbamate mix (common rubber additives) were negative. Prick tests to natural latex elicited a 4+ reaction associated with immediate flushing, tachycardia, urticaria, and light-headedness. Five control subjects did not react. IgE antibodies to latex by RAST demonstrated 17.7% binding (control, 4%). This case demonstrates that natural latex can cause IgE-mediated symptoms. The route of exposure was cutaneous absorption of relevant latex allergens. As the use of latex rubber products continues to escalate, more cases are likely to occur.     

Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove-related skin symptoms

BACKGROUND: It has been established that there are type I and type IV allergens in latex gloves. OBJECTIVE: The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. METHODS: Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. RESULTS: Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P < 0.05). Subjects who exhibited positive patch test were significantly more likely to have a prior hand dermatitis (P < 0.001). Of the 295 cases, 275 (93.2%) were contact dermatitis (CD), 13 (4.4%) contact urticaria (CU) (including protein CD) and 7 (2.4%) CD associated with CU. CONCLUSIONS: Our results show a high prevalence of rubber glove-induced dermatoses among the employees in one Italian hospital. The majority of skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.     

Responsiveness to autologous sweat and serum in cholinergic urticaria classifies its clinical subtypes

BACKGROUND: It has been reported that patients with cholinergic urticaria have a type 1 allergy to autologous sweat; however, the pathogenesis of that disorder has not been fully elucidated. OBJECTIVE: We investigated the responsiveness to autologous sweat and serum in patients with cholinergic urticaria in relation to their clinical characteristics. We further classified the clinical subtypes that are clearly characterized by responsiveness to in vivo and in vitro tests as well as their clinical features. METHODS: Intradermal tests with autologous sweat and serum were performed in 18 patients with cholinergic urticaria. Histamine release from peripheral blood basophils induced by autologous sweat was measured. RESULTS: Eleven of 17 patients with cholinergic urticaria showed positive reactions in skin tests with their own diluted sweat. Substantial amounts of sweat-induced histamine release from autologous basophils were observed in 10 of 17 patients. Eight of 15 patients with cholinergic urticaria showed positive reactions in the autologous serum skin tests. All 6 patients who developed satellite wheals after the acetylcholine test showed hypersensitivity to sweat. Further, patients whose eruptions were coincident with hair follicles showed positive responses to the skin test with autologous serum, whereas patients whose eruptions were not coincident with hair follicles did not. CONCLUSION: On the basis of these findings, we propose that cholinergic urticaria should be classified into 2 distinct subtypes. The first (nonfollicular) subtype shows strong positive reactions to autologous sweat and negative reactions to autologous serum. The second (follicular) subtype shows weak reactions to autologous sweat and positive reactions to autologous serum.     

Hypersensitivity to trimethoprim

We present two patients who experienced life-threatening immediate reactions and one patient who developed generalized urticaria following oral administration of trimethoprim (TMP) and sulfamethoxazole (SMX) combination. Skin prick tests with TMP were positive in the three patients. No patients reacted to skin prick tests with SMX. No significant levels of IgE antibodies to TMP were found by RAST in the serum of the patients. Normal subjects used as controls did not react to any of these tests. Single-blind, placebo-controlled oral challenges were positive with TMP and negative with SMX in all patients. These results suggest that the three patients developed type I hypersensitivity reactions to TMP. In our patients skin prick tests with TMP were useful in TMP hypersensitivity diagnosis.     

The role of iodine in hypersensitivity reactions to radio contrast media

Introduction Hypersensitivity reactions to iodinated radio contrast media (RCM) are either immediate‐type (IT) or delayed reactions (DT). In IT, the pathomechanism is unclear. In DT, delayed positive patch (PT) and intradermal tests (IDT) and RCM‐specific T cells suggest a T cell‐mediated mechanism. In both, the role of iodine has not been clarified; however, patients are often labelled as ‘iodine allergic’. Occasionally, positive skin tests to iodine‐containing drugs are observed. Objective We investigated the presence of hypersensitivity to iodine in patients with a history of hypersensitivity reactions to RCM. Methods Nineteen patients with a history of IT (n=9) or DT (n=10) to RCM were investigated. Skin prick tests, IDT and PT with several RCM and iodine formulations were carried out. All underwent oral provocation with Lugol's solution (LS). Two patients each with iodine mumps, contact dermatitis to iodized antiseptics and chronic idiopathic urticaria served as control or proof of concept. Results In the IT group, skin tests were positive in three out of nine patients to one RCM. One patient with negative skin tests reacted twice to oral iodine with urticaria. In the DT group, sensitization to one or several RCM was identified in 10 out of 10 patients. In seven out of 10 patients, additional sensitizations to the iodine formulations were found. Two patients developed a mild exanthema after oral provocation with LS. Conclusion We have previously demonstrated in patients with iodine mumps that an oral challenge with LS is a valid means to elicit hypersensitivity reactions to iodine. In 19 patients, we showed that iodine is rarely the eliciting agent in hypersensitivity reactions to RCM. Only one patient with a late urticaria to an RCM with a late urticaria to LS and two patients with DT and broad sensitization to all RCM tested reacted to LS with an exanthema. In most cases, more likely the RCM molecules and not iodine are the eliciting compounds. Cite this as: K. Scherer, T. Harr, S. Bach and A. J. Bircher, Clinical & Experimental Allergy, 2010 (40) 468–475.     

Type I hypersensitivity to rubber

Seven patients with type I hypersensitivity reactions to rubber are reported. Radioallergosorbent testing with crude latex antigen was positive in 6/7 patients. Five patients had coexisting spina bifida, and all had undergone surgery before the development of rubber allergy. Rubber allergy is a new phenomenon that should be in the differential diagnosis of idiopathic anaphylaxis and urticaria.     

Occupational asthma due to latex surgical gloves

Since 1979 several reports of contact urticaria due to natural latex have been well documented. Recent case reports suggest that rhinitis and asthma may also be due to rubber exposure. We describe an operating room nurse who was exposed at work to natural rubber (latex) due to the use of latex surgical gloves. After 25 years, she developed contact urticaria, rhinoconjunctivitis and acute asthma following the handling of rubber gloves for surgical purposes. She was symptom-free when on vacation. Skin prick testing demonstrated an immediate skin reaction to latex. Rub testing with surgical gloves was positive. Specific IgE antibodies to latex were found by indirect ELISA. Specific bronchial challenge with latex extract elicited an isolated immediate asthmatic reaction that was inhibited with cromolyn sodium pretreatment. Patch testing to common rubber additives was negative. These results suggest that latex present in surgical rubber gloves and probably acting as inhalant allergen may produce occupational asthma in exposed subjects, probably by means of an IgE-mediated mechanism.     

A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance

Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.     

Anaphylaxis to intravenous furosemide

A patient with long-standing hypertension developed urticaria, angioedema, and hypotension within 5 minutes after the intravenous administration of furosemide. Immediate hypersensitivity was documented by positive skin tests to furosemide as well as to related sulfonamide-based drugs. This is the first finding of an anaphylactic reaction to furosemide and underscores the need to consider such adverse reactions when patients who are sensitive to other sulfonamide-containing drugs are being treated.     

Intraoperative anaphylaxis: an association with latex sensitivity

Latex products have recently been identified as the cause of severe intraoperative anaphylactic reactions. We have identified a group of pediatric patients who appear to be at increased risk for such reactions. Fifteen patients with either spina bifida or congenital urologic abnormalities experienced 19 intraoperative anaphylactic reactions. All patients had frequent previous exposures to rubber materials since infancy as part of their management and/or investigative procedures. Seven of 15 patients had a previous history of local skin reactions to rubber. Only four patients were atopic. All patients had undergone multiple (two of 26) operative procedures before their reactions, the onset of which ranged from 40 to 290 minutes after induction of anesthesia. The reactions varied in intensity from urticaria to severe cardiorespiratory collapse. All these patients subsequently had positive allergy skin tests and positive RAST to latex antigen. We conclude that this group is at risk when they are exposed to latex intraoperatively as a result of frequent past exposure to these materials. Allergic evaluation for latex allergy may assist in the preoperative evaluation of similar patients. In sensitized patients, appropriate prophylactic measures, particularly the avoidance of latex, is required.     

Delayed hypersensitivity reaction to paracetamol (acetaminophen)

We are reporting three patients who experienced delayed cutaneous reactions after treatment with paracetamol (acetaminophen). These reactions were confirmed in controlled challenge tests. Patch tests with paracetamol were positive in all patients. A biopsy performed of the case 1 patch test confirmed that the lesion was compatible with delayed hypersensitivity reaction-type allergic contact dermatitis.     

Anaphylaxis produced by rubber glove contact. Case reports and immunological identification of the antigens involved

A study was carried out on six subjects suffering from anaphylactic reactions including asthma, rhinoconjunctivitis, contact urticaria and hypotension following contact with rubber gloves. All of them showed skin sensitivity and serum specific IgE to various preparations of natural latex, and not to other chemicals used in glove manufacturing. Immunoblotting techniques demonstrated that at least four soluble polypeptides from natural latex had the ability to bind specific human IgE. The results suggested that natural latex proteins present in rubber gloves can cause severe specific hypersensitivity reactions.     

An anaphylactic reaction to intra-articular triamcinolone: a case report and review of the literature.

OBJECTIVE: The primary objective was to report a case of triamcinolone-induced anaphylaxis and review the proposed mechanisms of corticosteroid-associated hypersensitivity reactions. DATA SOURCES: Articles in French and English were identified from references in relevant articles and from articles retrieved from the PubMed web site. Indexing terms consisted of corticosteroids in conjunction with the terms anaphylaxis, hypersensitivity reactions, asthma, urticaria, and angioedema. STUDY SELECTION: We reviewed all articles that described a case or cases of allergic-type reaction in association with corticosteroid use and for which we could obtain the full text of the article (>95%). RESULTS: We report an anaphylactic reaction occurring after an intraarticular injection of triamcinolone in a 75-year-old man who had positive prick skin tests to triamcinolone and negative tests to lidocaine, methylprednisolone, and hydrocortisone. CONCLUSIONS: To date, there have been approximately 100 published reports of immediate hypersensitivity reactions occurring after oral and parenteral administration of corticosteroids. Both immunologic and nonimmunologic mechanisms are proposed, but there is no definitive evidence in favor of either hypothesis. Our patient demonstrated positive prick skin tests to triamcinolone in a dose-response manner, suggesting the likelihood that an immunoglobulin E-mediated hypersensitivity mechanism may play a role.     

Etoricoxib tolerability in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem in clinical practice. Our aim was to investigate the clinical tolerability of etoricoxib, a new selective cyclooxygenase-2 inhibitor, in a group of patients with well-established NSAID hypersensitivity. METHODS: We assessed 31 adults (21 women and 10 men) who reported one or more adverse reactions to NSAIDs, manifested as cutaneous, respiratory or anaphylactic symptoms. Sixteen of them reported reactions to a single NSAID (single reactors) and 15 to more than one NSAID (multiple reactors); the most frequently involved drug was acetylsalicylic acid. First, each patient underwent allergologic tests (skin and/or oral challenge tests) with culprit NSAIDs and then tolerability tests with increasing doses of etoricoxib up to 120 mg. All challenges were performed under single-blind, placebo-controlled conditions. RESULTS: NSAID hypersensitivity was diagnosed in all 31 patients: 3 displayed positive results to pyrazolone skin tests and the other 28 to challenges with culprit NSAIDs. None reacted to either placebos or etoricoxib. CONCLUSIONS: Etoricoxib seems to be a safe alternative for patients with well-demonstrated NSAID hypersensitivity.     

Contact urticaria caused by Obeche wood (Triplochiton scleroxylon). Report of eight patients

A variety of plant substances may induce contact urticaria and the list of substances responsible for such reactions is increasing. We report eight patients suffering from occupational asthma caused by Obeche wood sawdust. These patients also presented with urticaria when they worked with this wood. Studies revealed immediate positive skin test reactivity to Obeche wood extracts in all patients. The presence of specific IgE antibodies against Obeche wood could also be demonstrated by a reverse ELISA method. Finally, skin provocation tests (rubbing test) on the eight patients evoked a positive reaction within 20 minutes. These findings strongly suggest an IgE-mediated immunologic mechanism as responsible for the patients' urticaria. Obeche wood should be considered a health hazard capable of causing both bronchial asthma and contact urticaria. At the present time, this timber constitutes the most frequently commercially exported African wood. Many individuals, including carpenters and hobbyists, may come into contact with this wood due to the common use of Obeche wood in the "Do it yourself" type of shops.     

Serum IgE antibodies to Trichophyton in patients with urticaria, angioedema, asthma, and rhinitis: development of a radioallergosorbent test

A series of patients was identified who demonstrated immediate positive skin tests to intradermal Trichophyton extract. These skin responses did not correlate with other fungal skin tests and were present both in atopic and nonatopic patients. The individuals demonstrating positive immediate skin tests included patients with urticaria, angioedema, asthma, and/or rhinitis, as well as five of 34 normal control subjects. Most skin test positive individuals had a history of local fungal infection and clinical signs suggestive of fungal infection. By use of Trichophyton tonsurans extract linked to Sepharose as the immunosorbent, it was possible to measure IgE antibodies in 26/30 sera from skin test positive individuals. With strongly positive sera, RAST bound up to 30% of the radiolabeled anti-IgE added. The results confirm that most skin test positive individuals have IgE-mediated hypersensitivity to Trichophyton. These observations support the older view that absorption of dermatophyte allergen through the skin should be considered as a possible cause of allergic disease.     

Contact reactions to fragrances.

BACKGROUND: The most common reaction to fragrances is contact dermatitis, a delayed hypersensitivity reaction; however, other reactions include immediate contact reactions (contact urticaria) and photo-allergic reactions. Fragrance mix (FM) and balsam of Peru (BP) are used to screen for fragrance allergy. OBJECTIVE: To study the different types of allergic skin reactions to fragrance compounds. METHODS: Delayed hypersensitivity reactions to FM and BP were studied in 4,975 patients with suspected contact dermatitis by routine patch testing interpreted at 48 and 96 hours. In 664 of the patients, patch tests were read at 30 minutes to evaluate for immediate (wheal-and-flare) contact reactions and again at 48 and 96 hours. Photopatch tests to FM were performed in 111 patients with suspected photo-allergic dermatitis. RESULTS: Delayed contact reactions to FM occurred in 6.6% of females and 5.4% of males and to BP in 3.9% of females and 4.1% of males. Analysis of data over time (12 study years) showed an increased trend for reactions to fragrances, particularly in males. Sensitivity to other contact allergens (polysensitivity) was found in 62% of patients and polysensitivity presented more often with generalized contact dermatitis. The most sensitizing components of the fragrance mix that were tested in 38 patients were cinnamic alcohol, oak moss, and cinnamic aldehyde. There were 112 immediate patch test reactions to FM and 113 to BP in 664 patients. Immediate contact reactions were followed by delayed contact reactions in 13.4% of patients for FM and 8.8% for BP, representing a significant increase in the frequency of delayed contact reactions. Patients with immediate contact reactions to fragrances did not have a higher incidence of atopy (25.9%). No cases of positive photopatch test reactions to FM were seen. CONCLUSION: Fragrances commonly cause both delayed and immediate patch test reactions and patients with immediate contact reactions have an increase in delayed contact reactions to the same allergen.