T. Herrero

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.

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.

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.

Association between airborne pollen and epidemic asthma in Madrid, Spain: a case–control study

Background Despite the fact that airborne pollen is an important factor in precipitating asthma attacks, its implication in increases of epidemic asthma in usual meteorological conditions has not been reported. A study was undertaken to estimate the relationship between various types of aeroallergens and seasonal epidemic asthma in the region of Madrid, Spain. Methods A case–control study was carried out in individuals aged 4–79 years who received emergency healthcare for asthma during 2001 in a base hospital covering a population of 750 000 inhabitants of Madrid. A skin prick test was performed with grass pollen, plantain pollen, olive pollen, cypress pollen, plane tree pollen, dust mites and Alternaria and the prevalence of skin reactivity was compared between subjects with asthma requiring emergency care for asthma within (cases) and outside (controls) the seasonal epidemic period. Data were analysed using logistic regression adjusting for age and sex. Results The response rate was 61.7% for cases (n=95) and 51.6% for controls (n=146). The OR of sensitisation to grass pollen for cases compared with controls was 9.9 (95% CI 4.5 to 21.5); plantain pollen: 4.5 (95% CI 2.5 to 8.2); olive pollen: 7.3 (95% CI 3.5 to 15.2); plane tree pollen: 3.6 (95% CI 2.0 to 6.4); cypress pollen: 3.5 (95% CI 2.0 to 6.2); dust mites: 1.1 (95% CI 0.6 to 1.9); Alternaria: 0.9 (95% CI 0.5 to 1.9). The association with grasses was maintained after adjusting simultaneously for the remaining aeroallergens (OR 5.0 (95% CI 1.5 to 16.4)); this was the only one that retained statistical significance (p=0.007). Conclusions These results suggest that allergy to pollen, particularly grass pollen, is associated with the epidemic increase in asthma episodes during the months of May and June in the Madrid area of Spain.

Urticaria due to mepivacaine with tolerance to lidocaine and bupivacaine

tion) to which he had no reaction. Modified radioallergosorbent test (RAST) testing was performed with the patient’s serum to naproxen and no specific IgE was identified (Quest Diagnostics, Teterboro, NJ, USA). He was also skin-prick tested to 1/100, 1/10 and full-strength liquid naproxen (125 mg/5 ml), without wheal and flare reaction. This case demonstrated reproducible anaphylaxis to naproxen without cross reactivity to rofecoxib, aspirin or ibuprofen. Without this patient’s insistence and his professional and athletic performance requirements we would not have challenged him with naproxen, but would have challenged him with the later three drugs to provide his alternative NSAIDs. Anaphylaxis to naproxen is not rare. A recent study by van Puijenbroek (3), reported naproxen as the second leading cause of NSAID-induced anaphylaxis between 1985 and 2000 in the Netherlands. The mechanism of the reaction to naproxen is not well defined. A case report by Cisterno (4), in 1983, reported a positive intradermal skin test in a naproxen specific anaphylaxis case. This same report also demonstrated a positive basophil release assay to naproxen. To date, there have been rare reports of cross-reactions to NSAIDS in normal individuals who have anaphylaxis (1). Although we used liquid naproxen for challenge, we feel his reaction on challenge was consistent with his prior reaction and is specific for naproxen. We have been unable to demonstrate naproxenspecific IgE either by RAST or skin testing but this does not rule out the probability that an IgE-mediated reaction occurred.

Systemic allergic reaction by a human insulin analog

cribed. In Fradin et al. s seminal work, a 6-mg/kg dose was administered for a period of 3–9 weeks to three patients suffering from CU. Despite its beneficial effects, CsA was discontinued in all the three patients because of its undesirable side-effects (1). Barlow et al. reported the beneficial effect of 3 mg/kg CsA for a period of 1 month to 10 patients (2). This group described a modified protocol administration of CsA over a 3-month period, with the initial dose at 3 mg/kg which was gradually reduced (3). One-third of the CU patients were cured, with another third experiencing reduced symptom severity. Notably, in one-third of the patients in remission, urticaria relapsed 3–6 months after CsA discontinuation (4). Furthermore, those who relapsed developed CsA unresponsiveness (escape of therapy) following a second course of CsA, even when higher doses of CsA were administered (E. Toubi, personal observation). In the present study, the administration of CsA for prolonged periods to patients who experienced a severe urticarial relapse following the tapering of CsA has been studied. Case I. A 54-year-old male patient in whom severe CU could be controlled only with repeated courses of prednisolone administered over 2 years, was studied. CsA, at 3 mg/kg/day induced a full remission, yet each tapering attempt below 2.0 mg/kg/day was followed by a severe relapse, necessitating the return to the starting dose. This regimen was continued for 8 months, without any side-effects, and ultimately resulted in full cure during a 1-year follow-up. Case II. The patient was a 51-year-old steroid-dependent female with severe CU lasting 14 months. Gradual tapering of CsA dosage after 3 months resulted in a severe relapse. Despite diarrhea and mild peripheral neuropathy, she insisted on continuing a dosage of 2 mg/kg/day.After 6 months the CsA dose was gradually tapered and patient remained asymptomatic during a 5-month follow-up. Case III. The patient was a 51-year-old female with severe CU lasting 3 years that was successfully treated with CsA. As previously described in the aforementioned cases, we were unable to taper the dose below 2 mg/kg/day because of subsequent relapse. Moreover, corticosteroids were contraindicated because of the patient’s comorbidity to diabetes mellitus. Six months after the initiation of treatment (with six more months of treatment planned), the patient continues to be asymptomatic. As most reports on CsA treatment suggest this regimen for a limited period of time, and urticaria relapses follow CsA discontinuation in many, caregivers are urged to consider a more prolonged therapy with CsA. The notion of allowing an extended treatment period is especially attractive in those patients in whom escape of therapy may ensue with the discontinuation of CsA. We propose that, as is customary in the management of autoimmune diseases, CsA should be considered as a possible treatment option early in the course of severe CU. When prolonged treatment with prednisolone is inadvisable, the use of CsA may have added value. Further experience with prolonged CsA treatment is needed in order to determine the extent to which this regimen might reduce the incidence of relapse upon CsA discontinuation and thus provide enhanced treatment efficacy.

Sympathomimetic drug allergy: cross-reactivity study by patch test

AbstractIntroduction: Sympathomimetic (α-adrenergic) drugs are mainly used because of their vasoconstrictor properties, for nasal congestion, or as mydriatics. Although sympathomimetic drugs are used often, allergic reactions are rare, especially when the drugs are administered systemically. Cross-reactivity may exist among catecholamine derivatives, although reported data on this are contradictory. In this study, we investigate if there is cross-reactivity in patch tests among these drugs. Material and methods: Patch tests with 10% phenylephrine and 10% pseudoephedrine in petrolatum, and 10% and 20% ephedrine, 10% phenylpropanolamine, 5% fepradinol, 1% methoxamine, and 10% oxymetazoline, all administered in dimethyl sulfoxide (DMSO), were carried out in 14 patients with a history of allergy to any of these drugs. DMSO was used as the negative control. Results: All patients except one (patient number five) showed positive patch-test reactions to at least two different drugs. Nine patients (64.3%) were cross-sensitized to three or more different drugs, and 57.1% of patients were sensitized to four or more sympathomimetic drugs. Patients who experienced generalized rashes caused by orally administered pseudoephedrine had a stronger response and more cross-reactivity with other sympathomimetic drugs in patch tests than those who experienced local contact dermatitis. Conclusions: We conclude that there is cross-reactivity among the different sympathomimetic drugs tested, especially if the drug is administered systemically.

Allergy to calcitonin

. CALCITONIN is a polypeptidic hormone that regulates calcium metabolism. It is mainly used in severe osteoporosis treatment. A 65-year-old woman reported eye and nose congestion, itching nose, and sneezing minutes after application of a salmon calcitonin nasal spray. She had tolerated this calcitonin previously. Her doctor modi®ed the treatment to daily parenteral administration. Minutes after the ®rst dose of intramuscular (IM) salmon calcitonin, she developed an itching nose and generalized urticaria that wore off after parenteral administration of antihistamines and corticosteroids. After a second dose, she reported the same but milder symptoms, and she tolerated the third dose. She was able to ®nish the 15-day treatment cycle without further reactions. The patient ate salmon and other ®sh without problems. Skin prick tests with commercial salmon extract and salmon calcitonin (100 UI/ml) were negative. Skin prick tests with eel calcitonin (100 UI/ml) and the ID test with salmon calcitonin (1 UI/ml) were positive (both negative in 10 healthy control subjects). Skin prick (100 UI/ml) and ID tests with human calcitonin (1 UI/ml) were negative. We did not detect speci®c IgE antibodies to any calcitonin by the ELISA technique. The patient was diagnosed as having salmon calcitonin allergy. Because of the molecular differences and the negative skin tests to the human product, the patient, after giving informed consent, underwent a simple blind controlled IM challenge with human calcitonin with good tolerance. She could follow the subsequent calcitonin cycles without further reactions. Every calcitonin has 32 amino acids. All the calcitonins have a similar structure at both chain terminals. The amino acids in positions 1, 3, 4, 5, 6, 7, 9, 28, and 32 are the same in all calcitonins, while the amino acids in other positions vary among different species. Despite the phylogenetic factor, calcitonins are not more similar among mammals than between them and other animal groups. Calcitonins can be classi®ed by their structure into three groups: 1) pig, cow, and sheep (28 identical amino acids) 2) rat and human (30 equal amino acids) 3) salmon and eel (29 identical amino acids) (4). The more common calcitonin sideeffects are ̄ushing, nausea, vomiting, and tingling hands. These reactions improve, in most patients, with continued therapy (1). The positive skin tests in our patient and the negative results in 10 healthy controls strongly suggest the speci®city of these tests. Repetitive injections made the patient tolerant to salmon calcitonin, probably through a desensitization mechanism. During the refractory period of allergic reactions, patients may tolerate allergen reexposure. Allergic reactions to calcitonin are rare and are usually referred to nonhuman calcitonins (2). However, adverse effects are more frequent and severe with the human species. Subcutaneous administration is safer than IM injections (1, 3). Our skin tests suggest the existence of cross-reactivity between salmon and eel calcitonin, but not with the human one, probably because salmon and eel calcitonins are very similar. These two calcitonins differ in only three amino acids, while they both differ in 16 amino acids from the human one.