Skin test-positive immediate hypersensitivity reaction to iodinated contrast media: the role of controlled challenge testing.

BACKGROUND: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed. OBJECTIVE: We aimed to evaluate the role of controlled challenge testing in skin test-positive IHR to ICM. PATIENTS AND METHODS: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test-negative ICM; a further 2 patients underwent computed tomography with an alternative skin test-negative ICM. No premedication was administered. RESULTS: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test-negative ICM. The 2 patients who underwent computed tomography with an alternative skin test-negative ICM tolerated the medium. CONCLUSIONS: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test-positive reactions in order to identify an alternative non-cross-reactive ICM.

Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction.

Allergies to iron salts are seldom reported. We studied a patient with iron-deficiency anemia who had suffered anaphylactic reactions caused by oral iron salts. An allergy study was performed using single-blind, placebo-controlled oral challenge and skin tests with various iron salts as well as excipients in commercial formulations. Oral challenges were positive for 2 of the commercial formulations of iron salts. Intradermal tests with ferrous sulphate and ferrous lactate also showed positive results. All of the cutaneous tests using the excipients were negative. A desensitization protocol was designed which enabled us to readminister ferrous sulphate, although antihistamines were necessary to guarantee good tolerance to iron salts. We report a patient with allergy to iron salts, positive skin tests, and positive controlled challenge. We highlight the desensitization protocol designed to complete the therapeutic management of the anemia.

Unilateral conjunctival chemosis as a unique symptom of nonsteroidal anti-inflammatory drug intolerance.

Patients with nonsteroidal anti-inflammatory drug (NSAID) intolerance usually have cutanous-mucosal or/and respiratory symptoms. We report the case of a patient who developed several episodes of left-eye conjunctivitis, manifested as conjunctival chemosis, with no other symptoms, after taking metamizole and other unidentified NSAIDs. We performed both a single blind placebo-controlled oral challenge test and conjunctival challenge test with different NSAIDs. The single blind placebo-controlled oral challenge was positive to ketoprofen and diclofenac. The conjunctival challenge with diclofenac and flurbiprofen was negative. The patient tolerated celecoxib and nabumetone. We believe this to be an exceptional case of NSAID intolerance as conjunctival chemosis has not hitherto been included in any of the classic types of pseudoallergic reactions.

Allergy to chironomid larvae (red migde larvae) in non professional handlers of fish food.

UNLABELLED: Chironomids are insects which inhabit wetlands. In countries such as Sudan, The United States. Egypt and Japan they are the cause of serious environmental allergy. In Europe, and particularly in Spain, allergy to Chironomids is infrequent and has only been described in patients who handle Chironomid larvae which form part of certain fish foods. MATERIALS AND METHODS: We report a case of hypersensitivity to the Chironomid Midge (Chironomus thummi thummi) in a 23-year-old patient who on two occasions, after being in contact with fishfood, suffered rash, rhinoconjunctivitis, dyspnea and dysphagia. A Prick test was carried out with the habitual pneumoallergens, Chironomid Midge extract (PBS: 1.3 mg/ml), Common Mosquito (Culex pipiens), Squid, Mussel, Prawn and Anisakis. Conjunctival provocation was also carried out with Chironomid Midge extract; detection of specific IgE for Chironomid Midge, Common Mosquito (Aedes comunis), Mussel, Squid, Shrimp, Anisakis, house dust and house mites by means of the CAP technique; detection of IgE by means of ELISA in response to Chironomid Midge, Aedes mosquito, Squid, Prawn, Mussel and Anisakis; ELISA-inhibition and Immunoblott-inhibition. RESULTS: The positive results of the cutaneous tests, the detection of specific IgE and conjunctival provocation confirmed the existence of an IgE-mediated mechanism. In our patient, the in vitro techniques demonstrated cross reactivity with the Common Mosquito. CONCLUSIONS: We report on a patient with a case history of rhinoconjunctivitis, rash, dyspnea, and dysphagia after handling fish food. The etiological agent was the Chironomid larvae. The sensitization of our patient has been demonstrated by means of in vivo and in vitro techniques.

Diagnosis and management of hypersensitivity reactions caused by oxaliplatin.

Hypersensitivity reactions to oxaliplatin have been increasing since its introduction at the end of the 1990s, but allergy tests with antineoplastic drugs are rarely used to aid diagnosis. We describe 5 cases in which hypersensitivity reactions to oxaliplatin after several courses of chemotherapy were managed by allergy testing and desensitization. Skin prick tests were negative at 1 mg/mL in all patients, positive at 10 mg/mL in 2 tested patients, and negative in 10 control subjects. Intradermal tests were positive and not irritant at 0.01 to 0.001 mg/mL concentrations. A desensitization protocol with increasing concentrations and flow rates was successfully completed in all patients. We conclude that prick and intradermal skin tests are useful in the diagnosis of hypersensitivity reactions to oxaliplatin and that the desensitization protocol performed avoided discontinuation of chemotherapy in all patients.

Recurrent fixed drug eruption caused by citiolone.

Citiolone (N-acetylhomocysteinethiolactone) is a thiolic-derived medication frequently used in Spain and in other countries as a mucolytic agent for the treatment of certain hepatic disorders. Mucolytic drugs have rarely been implicated in the fixed drug eruption etiology. We report on a patient who presented several episodes of fixed exanthema related to citiolone intake. The patch test with citiolone (10% in dimethyl sulfoxide) was negative. The diagnosis was confirmed by a positive controlled oral challenge test. Other mucolytic thiolic-derivatives (N-acetylcysteine) were tolerated by the patient, thus crossreactivity between these drugs seems to be unlikely.

Fixed drug eruption induced by indapamide. Cross-reactivity with sulfonamides.

Indapamide is a nontiazidic sulfonamide diuretic which has not been previously reported as a cause of fixed drug eruption. We describe a patient who experienced several episodes of fixed drug eruption during treatment with indapamide. The diagnosis was confirmed by positive controlled oral challenge test. The possible existence of cross-reactivity with other sulfonamide derivatives was investigated by controlled oral challenge test with sulfamethoxazole, sulfadiazine and furosemide, with the tests with sulfamethoxazole and sulfadiazine resulting positive.

Bezafibrate-induced anaphylactic shock: unusual clinical presentation.

We report a case of a patient who suffered generalized urticaria, chest tightness, wheezing, nausea, vomiting, hypotension, and loss of consciousness. Two hours earlier she had taken Eulitop Retard following lunch. She had tolerated all the implicated food after the reaction. Allergy evaluation revealed intense positive responses to intradermal tests with bezafibrate active component and Eulitop Retard (skin tests in control subjects were negative). Specific IgE tests (RAST) to Eulitop Retard were negative. An IgE mechanism is suggested to be responsible for this adverse reaction on the basis of the positive skin tets. The delayed onset (two hours) of this anaphylactic shock is unusual. Although infrequent, it may be caused by the specific pharmacokinetic characteristics of this drug, which is a slow releasing agent, mainly absorbed in the gut. The drug was taken just after lunch, and this concomitant food ingestion could also have produced a delay in gastric drainage and a retarded drug absorption. An IgE-mediated accelerated type reaction could also explain this delay. Apparently the patient reacted after the first contact to the drug, and the absence of a sensitization period is not usual in this type of immune reponse. Finally, we recommend the performance of prick and intradermal skin tests prior to any systemic challenge when allergic reactions to fibric acid derivatives are suspected.

Cross-reactivity among p-amino group compounds in sulfonamide fixed drug eruption: diagnostic value of patch testing.

We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross-reactivity between sulfonamide derivatives and p-amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX-induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross-reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross-reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p-amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients.

Cross-sensitivity among oxicams in piroxicam-caused fixed drug eruption: two case reports.

Fixed drug eruption (FDE) caused by oxicams is very rare. There are few reports of FDE induced by piroxicam, and this explains why cross-sensitivity among oxicams (piroxicam, tenoxicam, and droxicam) has been studied in only one patient. The patch test on residual lesions has lately been used by some authors in FDE diagnosis with variable results. We describe two cases of piroxicam-caused FDE and demonstrate cross-sensitivity among piroxicam, tenoxicam, and droxicam in both of them. One patient had residual lesions and the patch test was useful for diagnosis and cross-sensitization studies. The second patient had no residual lesions, and the patch test was negative on normal but previously affected skin; therefore, the study was performed by single-blind controlled oral challenge.

Acute IgE-mediated generalized urticaria-angioedema after topical application of povidone-iodine.

Povidone is a synthetic polymer mainly used as a dispersing or suspending agent for many pharmaceutical products. It is also used as a carrier for iodine. In many countries it is not mandatory its inclusion in drug labels so many adverse effects may be under diagnosed. Povidone-iodine used as a topical antiseptic solution may produce allergic contact dermatitis and irritation. Povidone, when systemically administered may deposit in tissues causing local lesions and pain. Three cases of immediate hypersensitivity to this agent have been reported. We present a patient who developed generalized urticaria and angioedema immediately after the first topical use of Betadine (povidone-iodine) on a right arm wound. The positive skin prick test to Betadine and povidone extract and the demonstration of serum specific IgE to povidone, confirmed an IgE-mediated hypersensitivity.

Lupine-induced anaphylaxis.

BACKGROUND: Legumes are one of the most common foods causing allergic reactions in children and adults. Cross-reacting antibodies are frequently demonstrated in this family but the real clinical cross-reactivity is uncommon. OBJECTIVE: To report a case of lupine-induced anaphylaxis and to elucidate in vivo and in vitro cross-reactivity with some legumes. METHODS: Skin prick test (SPT) with some legumes were performed. Cap-IgE, ELISA-IgE, and immunoblotting were carried out. Open oral challenges with some legumes were performed. Cross-reactivity was studied by ELISA and immunoblotting inhibition. RESULTS: The results demonstrated type-I hypersensitivity reactions with lupine and some other legumes. Cap-IgE with peanut was positive but the SPT and ELISA-IgE were negative and the patient tolerated a peanut challenge. ELISA inhibition revealed a partial inhibition (62%) using lupine as the solid phase. Partial inhibition was demonstrated by immunoblotting inhibition. Open oral challenge with peanut and green bean were negative but positive with pea. CONCLUSION: We present a lupine sensitized patient with positive SPT and in vitro cross-reactivity with other legumes. Clinical cross-reactivity progressively developed over a 5-year period. Discrepancies were found between the clinical aspect and in vitro study of peanut allergy. Factors determining the wide variability in cross-reactivity among individuals are still obscure.

Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens.

BACKGROUND: Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole-body extracts of the larva are clearly insufficient. OBJECTIVES: To study the allergenicity of the proteins secreted by the parasite. Comparison with somatic antigens and determination of their clinical importance in allergic patients were also addressed. METHODS: An excretory/secretory (E/S) extract was produced by culturing third-stage A.s. larvae. It was used to perform immediate skin tests and to determine specific IgE in 10 patients diagnosed with allergy to A.s. Both tests were compared with the results obtained with the whole-body extract (somatic (S)). The molecular weight (MW) of their allergens was determined by immunoblotting, and a single-blind placebo-controlled oral challenge with E/S proteins was performed. Finally, allergens' resistance to gastric pepsin and acid pH was explored. RESULTS: A.s. larvae secreted allergens more potent than those present in the S extract. The skin prick test wheal area produced by E/S molecules and the absorbance obtained in the determination of specific IgE with these allergens (ELISA) were 5.8 times bigger than those obtained with S extract. MW allergens of 72 and 56 kDa in E/S extracts and those of 56, 48 and 43 kDa in S extract were recognized by more than 50% of the patients. Partial cross-reactivity between them was revealed by immunoblotting inhibition studies. Oral challenge with E/S extract (up to 479 microg) was negative in all the patients. Treatment of E/S proteins with gastric pepsin inhibited the binding of the E/S allergens for specific IgE. The acid pH did not affect the overall binding of IgE to E/S extract. It decreased by 15.23% and 19.96% at pH 4 and 2, but the difference was not statistically significant. CONCLUSION: A.s. secretes allergens more potent than somatic antigens and should be used in the diagnostic procedures. These allergens are inactivated by the pepsin, which supports the theory that live larva is necessary to induce an allergic reaction in most of the patients.

Piroxicam-induced photodermatitis. Cross-reactivity among oxicams. A case report.

BACKGROUND: there is a group of patients with contact allergy to thimerosal (thiosalicylic acid and ethylmercuric chloride), thiosalicylic acid sensitized, who develop photodermatitis to piroxicam. We present a case which we have investigated cross-reactivity among different oxicams. METHODS AND RESULTS: a 44-year-old man with contact allergy to thimerosal. A few hours after the intake of Feldene (piroxicam) while running outside, developed a papuloerithematosus exanthema in the neck, knees and forearms, and microvesicles on the finger webs, that became descamative a few days later. Oclusive patch tests with thiosalicylic acid, mercury, piroxicam, tenoxicam, droxicam and meloxicam and photopatch test with the oxicams were performed. Patch tests with thiosalicylic acid and piroxicam were positive and negative with the others. All the oxicams photopatch tests were positive. CONCLUSIONS: we present a case of photodermatitis and dermatitis to piroxicam, in a patient with contact allergy to the thiosalicylic moiety of thimerosal, in which cross-reactivity with the other oxicams have been demonstrated. In cases of oxicams-induced photodermatitis, all oxicams should be avoided, to elude posible cross-reactions.

Clinical tolerance, parasitological efficacy and environmental effects of dehumidifiers in stable asthmatics sensitized to house dust mites.

Dehumidifiers (DH) are potentially effective appliances as coadjuvant therapy in the treatment of bronchial asthma caused by sensitization to house dust mites. The aims of this study were to analyze DH tolerance in asthmatic patients, to assess the parasitological effects and to analyze the environmental effects produced by the use of these appliances in the bedrooms of asthmatic patients sensitized to house dust mites. 10 stable asthmatic patients sensitized to house dust mites were studied. DH appliances (CD-300) were installed in their bedrooms. Each patient was given symptom scoring tables and a portable peak expiratory flow (P.E.F.) during a period of 5 months, 1 month before installing the DH and 4 months afterwards. To study the parasitological efficacy of the DHs, we analyzed dust samples from the bedrooms and determined the Der p I, Der f I and Der II allergens by means of a modified ELISA based on monoclonal antibodies. Dust samples were collected before installing the DHs and after they had been working for 2 and 4 months. Dry temperature and relative humidity measurements at three time intervals (7-9, 15-17 and 22-24 h) were carried out. The 1st measurement was done prior to installation of the DHs in the patients' bedrooms and the 2nd and 3rd were achieved 2 and 4 months respectively after the installation. Statistical analysis was done by comparison of paired means. No significant differences were detected in the patients' symptoms nor in the P.E.F. measurements in the course of the study. Decreases in the house dust mite allergens were observed in 4 bedrooms. A significant decrease in relative humidity in the bedrooms of mite asthma patients after use of dehumidifier appliances was observed (p < 0.01). Significant differences between the measurements of the bedrooms with and without DH were detected (p < 0.01). In summary, DHs were well tolerated by stable asthmatic patients, produced a significant decrease in the relative humidity level and showed some parasitological efficacy.