Nonsteroidal anti-inflammatory drug hypersensitivity: fable or reality?

In the medical community lectures and publications about nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity have led to an increasing awareness and diagnosis of this condition. Frequently, the diagnosis NSAID hypersensitivity is based only on history, which is a vague and unreliable indicator. A two-stage diagnostic procedure with skin tests (to exclude IgE-mediated allergy) followed by single-blinded, placebo-controlled oral challenges was carried out on patients attending our clinic from 1997 to 2003 with the diagnosis of a NSAID hypersensitivity. Out of 260 patients tested, 61.5% described their NSAID hypersensitivity as cutaneous (urticaria, angioedema), 24.2% had respiratory symptoms (asthma, rhinitis), 3.5% had anaphylactoid reactions, and 10.8% described uncertain signs. In fact 55.0% of all patients previously labelled as NSAID sensitive tolerated NSAID when assessed by oral challenge, whereas 13.8% were truly NSAID sensitive. In 31.2% of patients the challenge test with the suspicious drug was either not done or rejected by the patient; but all showed a proven tolerance of alternative NSAID. Our study demonstrates that oral challenge tests are safe, practical and useful in ruling out NSAID hypersensitivity in approximately 50% of the patients who have previously been labelled as such.

Radiocontrast media-associated exanthema: identification of cross-reactivity and tolerability by allergologic testing.

BACKGROUND: All iodinated radiocontrast media (RCM) may cause hypersensitivity reactions, either immediate-type within 5-10 min of RCM injection or delayed-type, which become apparent more than 1h after RCM exposure. Delayed-type hypersensitivity to RCM may pose a problem for future radiologic investigations because due to possible immunological cross-reactivity all iodinated RCM are usually avoided. OBJECTIVE: The aim of this study was not only to identify the causal RCM for the exanthema but also to demonstrate that patients may receive alternative iodinated RCM despite a history of RCM-induced allergic exanthema. METHODS: We evaluated 32 patients with a history of exanthema after RCM application using standardized patch, prick and intradermal skin testing. In case of positive skin tests intravenous challenges with skin-test-negative RCM were performed to identify non-ionic monomer RCM which are tolerated. RESULTS: In 6 out of 32 patients skin tests strongly suggested a delayed-type non-IgE-mediated allergic hypersensitivity to the RCM iomeprol (3x), iopromide (2x), and iopamidol. In 4 patients alternative non-ionic monomer RCM (2x iosarcol, iopromide, and iomeprol) were identified by controlled challenge tests. CONCLUSIONS: The evaluation of patients with RCM-associated exanthema should always include appropriate skin tests ensuring that patients with a delayed-type allergic RCM-induced exanthema are not missed. Moreover, allergologic testing may identify alternative RCM of the group of non-ionic monomers, which are tolerated in future radiologic investigations.

Food allergy in adults: an over- or underrated problem?

BACKGROUND: 10% to 20% of the population sees itself as suffering from food allergy, yet genuine, immune-mediated food allergy is suspected by patients and their physicians far more often than it is actually shown to be present. The unfounded suspicion of an IgE-mediated food allergy can substantially impair a patient's quality of life through needless dietary restriction and the accompanying anxiety. On the other hand, an IgE-mediated food allergy that has gone undiagnosed or that has not been taken seriously can manifest suddenly with anaphylaxis, which may be life-threatening. The present study, carried out on a large cohort of patients, underscores the importance of differentiating IgE-mediated food allergy from other, nonallergic types of food reaction. METHODS: 419 patients that had been referred to our outpatient allergy clinic for suspected food allergies underwent a standardized allergological diagnostic evaluation, including thorough allergologic history-taking, IgE serology, and challenge tests when indicated. RESULTS: 214 patients (51.1%) were found to have an IgE-mediated food allergy. Almost half of these patients (24.3% of the overall group) had previously experienced food-induced anaphylaxis. In 205 patients (48.9%), however, an IgE-mediated food allergy was ruled out as far as possible. CONCLUSION: Only a comprehensive allergological evaluation performed by an experienced allergologist in accordance with current guidelines can protect patients from the negative consequences of excessive concern about a nonexistent food allergy (e.g., needless dietary restriction) or, on the other hand, the negative consequences of inadequate attention to a genuine food allergy (anaphylaxis). A proper evaluation consists of detailed allergologic history-taking, skin tests, and challenge tests when indicated.

Anticonvulsant hypersensitivity syndrome: cross-reactivity with tricyclic antidepressant agents.

BACKGROUND: Aromatic anticonvulsant agents such as carbamazepine and phenytoin can induce anticonvulsant hypersensitivity syndrome (AHS) at a frequency of 1 in 10,000 to 1 in 1,000 treated patients. The hypersensitivity syndrome is a potentially life-threatening adverse drug reaction with multiorgan involvement, and incidental reexposure must be strictly avoided. Patients and treating physicians must be informed and educated about the causal drug and its potential immunologic or toxicologic cross-reactivity with other compounds. It has been well established that for future antiepileptic drug therapy, carboxamides (carbamazepine and oxcarbazepine), phenytoin, and barbiturates (phenobarbital and primidone) have to be avoided owing to their high degree of cross-reactivity. Other anticonvulsant agents, such as valproic acid, benzodiazepines, and gabapentin, may be prescribed. OBJECTIVES: To present the clinical data for and to describe the potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant agents in patients with carbamazepine- and phenytoin-induced AHS. METHODS: The knowledge of cross-reactivity among aromatic anticonvulsant agents mainly emerged from clinical experience and observations because diagnostic challenge tests are not advisable. Thirty-six patients with the diagnosis of AHS were instructed to contact our unit if the symptoms relapsed. RESULTS: Despite better knowledge of AHS, one third of the patients had avoidable recurrences after exposure to cross-reactive drugs. Besides the known cross-reactivity among aromatic anticonvulsant agents, we observed a recurrence of the hypersensitivity syndrome in 5 patients after the administration of tricyclic antidepressant agents. CONCLUSION: The important potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant drugs should be brought to the attention of treating physicians.

Tolerance to intravenous heparin in patients with delayed-type hypersensitivity to heparins: a prospective study.

Delayed-type hypersensitivity to subcutaneously injected heparin is relatively common. Particularly, extensive cross-reactivity between different heparins and heparinoids often occurs. Delayed-type hypersensitivity to heparin implies the risk of a generalized eczema when heparin is administered intravenously. However, case reports demonstrated a tolerance to intravenous heparin in patients with delayed-type hypersensitivity to subcutaneous heparin, but prospective studies have not been performed. Our study group, of 28 patients with a proven delayed-type hypersensitivity to subcutaneous heparin, was challenged with intravenous heparin, which was well tolerated in all 28 patients. Therefore, in case of therapeutic necessity, the shift from subcutaneous to intravenous heparin administration is justified.