Safety of meloxicam in patients with aspirin/non-steroidal anti-inflammatory drug-induced urticaria and angioedema

It has been proposed that aspirin (ASA) and other non-steroidal anti-inflammatory drug (NSAID)-induced urticaria (UR)/angioedema (AE) are mediated through inhibition of cyclooxygenase-1 (COX-1) enzymes. Therefore, drugs with COX-2 selectivity may be well tolerated in such patients. We investigated the safety of preferential COX-2 inhibitor meloxicam in subjects with UR or AE type intolerance reaction to classical ASA/NSAIDs. Subjects with reliable or documented history of UR/AE due to classical ASA/NSAIDs underwent a single-blinded, placebo-controlled oral challenge with a cumulative dose of 7.5 mg meloxicam on 2 separate days. One-quarter and three-quarter divided doses of placebo and the active drug were given at 1-h intervals. A total of 116 patients (86 women and 30 men, mean age 39.6 ± 12.7 years) were enrolled to the study. The rate of atopy was 25.9%. Mean duration of drug reaction was 87.4 ± 110.8 (1-720) months. Almost half of the patients were multi-reactors. The most comorbid disease was asthma and the two most frequent NSAIDs inducing UR/AE were paracetamol (19. 6%) and ASA (19%). No reaction to placebo was observed. Ten out of 116 patients (8.6%) developed mild UR/AE, or only erythema and pruritus at a one-quarter or cumulative dose of 7.5 mg of meloxicam. The remaining subjects (91.4%) tolerated perfectly meloxicam challenge. This study indicates that 7.5 mg meloxicam is a safe alternative for ASA/NSAID-intolerant UR/AE patients. Intolerance reactions to meloxicam are much milder forms of the patients' historical ASA/NSAID-induced cutaneous reactions.     

Intolerance reactions due to the selective cyclooxygenase type II inhibitors rofecoxib and celecoxib. Results of oral provocation tests in patients with NSAID hypersensitivity

Intolerance reactions due to the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) are frequent emergencies. It is thought that inhibition of the isoenzyme cyclooxygenase type I (COX-1) is responsible for the common NSAID-associated adverse effects, whereas inhibition of COX-2 is mainly responsible for the therapeutic effects. The goal of our study was to estimate the frequency of intolerance reactions due to ingestion of the two newly approved selective COX-2 inhibitors, rofecoxib or celecoxib. In a sample of 13 patients who had previously documented NSAID hypersensitivity reactions to non-selective COX inhibitors, 2 patients (15.3%) showed intolerance reactions (2 of 9 patients with rofecoxib, 1 of 5 patients with celecoxib). These drugs cannot therefore be administered uncritically to patients with known NSAID hypersensitivity. Selective COX-2 inhibitors can only be used as alternative drugs in these patients after assessing their specific tolerability in a properly performed provocation test.     

Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide

The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.     

Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966-2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966-2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous.     

Acetylsalicylic acid pseudoallergy: an anomaly of thrombocyte function?

After a short historical review, the clinical symptomatology of the pseudoallergic reactions (PAR) after intake of acetylsalicylic acid (ASS) is examined. An intolerance to ASS mostly becomes manifest as bronchial asthma--sometimes up to a status asthmaticus: it is frequently combined with vasomotoric rhinopathia and nasal polyps (so-called "aspirin triad") or as urticaria and angio-edema, seldom as a shock reaction. These symptoms can - in contrast to an allergy--appear at the first intake of the drug. Changes in the arachidonic acid metabolism are of pathogenetic importance, as all substances that inhibit the cyclooxygenase pathway [e.g., most of the nonsteroidal anti-inflammatory drugs (NSAIDs)] are not tolerated by ASS-sensitive patients. Generally, a typical clinical history is sufficient for the diagnosis. Due to the fact that the ASS and NSAID pseudoallergy so far cannot be proved by in vitro methods, oral or inhalative provocation tests are needed when the tolerance situation to the drugs is unknown. However, these tests present high risks. A research group working with Capron (Lille) has recently been able to prove that washed platelets from patients with an analgetic asthma syndrome show an abnormal in vitro response to ASS or NSAID - like indomethacin and fluriprufen - which is characterized by liberation of cytocydal supernatants against parasites, as well as of free O2 radicals, which can be detected by chemiluminescence. Therefore, a platelet anomaly of arachidonic acid metabolism seems to be pathognomonic for ASS asthma. It is not yet known whether or not this is also related to ASS urticaria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple NSAID intolerance in chronic idiopathic urticaria is correlated with delayed, pronounced and prolonged autoreactivity

Autologous serum skin test (ASST) reactivity is positive in up to 60% of patients with chronic idiopathic urticaria (CIU). About 21 to 30% of patients with CIU have intolerance to acetyl salicylic acid (ASA) and/or other chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs). To investigate the relationship between ASA/NSAID intolerance and ASST reactivity, a case-control study was performed in 110 patients with CIU and 60 healthy controls. A positive ASST was defined as an erythematous wheal with a diameter of > 5 mm more than the saline-induced response. Patients were assessed at 10-minute intervals for a minimum of three hours. ASA/NSAID intolerance was ascertained by a placebo controlled-provocation test with offending drug (s). Forty-two patients with CIU (38.2%) had autoreactivity whereas only two of the controls (3.3%) displayed early and weak skin responses (P<.0001). ASA/NSAID intolerance was demonstrated in 30 (27.3%) patients with CIU. The prevalences of autoreactivity were 93.3% (28/30) and 17.5% (14/80) in patients with and without ASA/NSAID intolerance, respectively (P<.001). Thirteen of the 25 ASST-positive patients (52%) who had single (n: 7) or multiple (n: 6) NSAID intolerance showed early (before or at 30 min) and mild autoreactivity of short duration, whereas 15 of the remaining 17 ASST-positive patients (88.2%) who all had multiple NSAID intolerance showed delayed (later than 30 min) and prolonged autoreactivity (P<.05). These findings suggest that a common mechanism may be responsible for the pathogeneses of both delayed autoreactivity and multiple NSAID intolerance in CIU. It might be further speculated that delayed, prolonged, and pronounced autoreactivity may be a possible predictor for multiple NSAID sensitivity in CIU.     

Positive patch test reactions to celecoxib may be due to irritation and do not correlate with the results of oral provocation

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among those therapeutics most frequently causing pseudoallergic and sometimes allergic cutaneous adverse reactions. Coxibs preferentially inhibiting cyclooxygenase-2 are increasingly propagated as alternatives in NSAID-sensitive patients. We evaluated the tolerability of celecoxib in NSAID-sensitive patients. In 14 consecutive patients (6 males, 8 females, age 18-72 years), scratch and patch tests with homogenized Celebrex were performed, followed by single-blind, placebo-controlled oral provocation (maximal single dose: 200 mg; cumulative dose: 350 mg). 8 of the first 10 patients showed erythematous reactions to celecoxib on patch testing after 2 days with decrescendo kinetics between then and day 3. 9 patients with no history of NSAID intolerance showed similar reactions. When the patch tests were repeated with homogenized Celebrex at final concentrations of 5% and 10% in petrolatum, no reaction was observed in any patient. Subsequent oral provocation was tolerated without adverse effects by all individuals. We conclude that patch tests with high concentrations of celecoxib cause irritant reactions and do not correlate with the outcome of oral provocation tests. Therefore, these tests should be performed with lower concentrations of celecoxib (Celebrex). Celecoxib itself seems to be a valuable alternative drug in NSAID-sensitive patients.     

Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases. OBJECTIVES: To assess safety of cyclooxygenase inhibitors in patients with chronic idiopathic urticaria (CIU) and NSAID sensitivity and to evaluate a role of cysteinyl leukotriene metabolism and mast cell activation in sensitivity to NSAIDs in CIU. DESIGN: Aspirin challenge test followed by randomized, prospective, double-blind, placebo-controlled crossover trial with cyclooxygenase 2 inhibitors. SETTING: Tertiary referral center of a university hospital. PATIENTS: Thirty-six patients with CIU. INTERVENTIONS: Aspirin challenge test (up to 500 mg); randomized trial with rofecoxib (up to 37.5 mg) and celecoxib (up to 300 mg) in aspirin-sensitive patients. After completion of the trial, 7 patients received naproxen sodium (500 mg) as a positive control. MAIN OUTCOME MEASURES: Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell tryptase. RESULTS: Aspirin induced skin eruption in 18 patients. Rofecoxib or celecoxib did not elicit skin eruption in any of the aspirin-sensitive patients. Patients with CIU had higher urinary excretion of LTE4 than healthy control subjects. Basal urinary levels of LTE4 and serum mast cell tryptase were increased in aspirin-sensitive compared with aspirin-tolerant patients. Severity and duration of aspirin-induced urticaria showed a positive correlation with urinary LTE4 excretion. Naproxen precipitated urticaria in 5 of 7 aspirin-sensitive patients and caused further increase in urinary LTE4. CONCLUSIONS: Cyclooxygenase 2 inhibitors do not induce urticaria in patients with CIU sensitive to NSAIDs. Sensitivity to NSAIDs in CIU is associated with overproduction of cysteinyl leukotrienes and mast cell activation and most likely depends on inhibition of cyclooxygenase 1.     

Delayed contact hypersensitivity to non-steroidal anti-inflammatory drugs

Several non-steroidal anti-inflammatory drugs (NSAIDs) are available for topical treatment of acute soft tissue trauma or degenerative musculoskeletal disorders; the NSAID bufexamac is mainly used for therapy of chronic inflammatory skin diseases. In order to assess the occurrence of contact allergy to NSAIDs in 371 consecutive patients presenting for diagnosis of presumed contact allergy, patch tests were performed with a standard series and additionally with a series of NSAIDs, comprising acetylsalicylic acid, bufexamac, diclofenac, etofenamate, felbinac, flufenamic acid, ibuprofen, indomethacin, and piroxicam. 17 individuals (4.6%) exhibited delayed hypersensitivity to one of the NSAID preparations: 12 patients (3.2%) had patch test reactions to bufexamac, 2 (0.5%) to etofenamate, 2 (0.5%) to indomethacin, and 1 patient (0.3%) to flufenamic acid. These patch test results corresponded well to the individual history in 11 individuals (including 10 patients with reactions to bufexamac), and in 2 patients the clinical relevance of the reactions was probable. In view of the high frequency of allergic contact reactions to bufexamac, we propose to test this drug particularly in patients with atopic eczema or other chronic eczematous diseases.     

Adverse cutaneous reactions to selective cyclooxygenase 2 inhibitors: experience of an Italian drug-surveillance center

BACKGROUND: Selective cyclooxygenase (COX) 2 nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with a general lower incidence of side effects compared with nonselective NSAIDs. Postmarketing information has highlighted the need to reassess the risk evaluation for specific organs, including the skin. OBJECTIVE: A prospective databank to record all cases of adverse cutaneous reactions associated with the use of COX inhibitors was conducted at the Centre for Drug Surveillance of the Dermatology Department of Cagliari University. MATERIAL AND METHODS: An intensive surveillance program from November 2000 to October 2004, adopting the World Health Organization Collaborating Centre for Drug Monitoring causality assessment criteria and algorithm. RESULTS: Seventeen cases, 4 male and 13 female, were studied. None had previously presented any drug intolerance or allergy. Clinical manifestations were mainly maculopapular exanthema followed by urticaria-angioedema. A severe case of leukocytoclastic vasculitis was also observed. Responsible drugs were celecoxib (13 cases; 76%), rofecoxib (3 cases; 18%), and etoricoxib (1 case; 6%). All cases recovered with drug withdrawal. Causality was probable for all eruptions, except for the fixed drug eruption, for which causality was certain. DISCUSSION: Although most cases were associated with celecoxib, the observation of severe eruptions owing to rofecoxib and etoricoxib in this prospective study is consistent with a class effect of COX inhibitors on the skin, which merits further studies to explain the fine underlying mechanisms.     

Meloxicam in acute UV dermatitis — a pilot study

The non-steroidal anti-inflammatory drug (NSAID) meloxicam is a preferential cyclooxygenase-2 (COX-2) antagonist. The UV protective potential of this drug was studied to compare it with the reported beneficial effects of such preferentially COX-1 specific NSAIDs as indomethacin and acetylsalicylic acid in the literature. In a pilot study (open-label, non-randomized, non-controlled, unblinded), 10 patients received UV irradiation with the minimal erythema dose (MED), first with meloxicam (7.5 mg/die) to reduce post-operative pain and second without ingestion of meloxicam. The factor of UV protection was evaluated. In six of ten patients meloxicam showed no benefit, whereas four of ten patients had a 1.3- up to 3-fold UV protection. In this study, the benefit in UV protection of meloxicam as a prefential COX-2 antagonist was not above the reported benefit of the "old" COX-1 inhibiting NSAIDS.     

Drug‐induced angioedema without urticaria: prevalence and clinical features

Background Angioedema without urticaria can be caused by drugs. The purpose of our study was to assess the prevalence and clinical features of patients with drug‐induced angioedema without urticaria. Methods This study retrospectively reviewed case records at Siriraj Hospital, between January 2007 and December 2008. Patients aged at least 15 years were included. Results The prevalence of drug‐induced angioedema without urticaria among patients with adverse drug reactions was 2.3%/year. Non‐steroidal anti‐inflammatory drugs (NSAID) were the most common cause (50%), followed by antibiotics (20%). The commonest NSAID which induced angioedema were ibuprofen and diclofenac. The common sites were periorbital area (67.3%) and lips (27.6%). The median duration of suspected drug therapy before the development of angioedema was 1 day with the range of 10 min to 23 days. Conclusions Non‐steroidal anti‐inflammatory drugs and antibiotics were the most common drugs causing angioedema without urticaria. The duration of onset ranged from minutes to days. After stopping the suspected drugs, symptoms disappeared within 2–5 days in most patients.     

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.     

The effectiveness of montelukast for the treatment of anti-histamine-resistant chronic urticaria

Many patients with chronic idiopathic urticaria are not sufficiently controlled with histamine H₁-receptor antagonists. Leukotriene receptor antagonists have been reported to be effective for certain cases of urticaria, although their proper application remains to be established. To study the effectiveness of montelukast, a leukotriene receptor antagonist, for the treatment of chronic urticaria that was not controlled by histamine H₁-receptor antagonists. Twenty-five patients with chronic idiopathic urticaria were treated with 10 mg of montelukast for one week or more, without changing any precedent treatment that they were using before the study including histamine H₁-receptor antagonists. The effectiveness of montelukast for each patient was evaluated and compared with clinical features and/or backgrounds of the patients. Twelve patients, including six who had been treated with corticosteroids, were evaluated as “markedly improved” or “improved” following treatment with montelukast. There was no statistically significant relation of the effectiveness to the complications with non-steroidal anti-inflammatory drugs (NSAIDs) intolerance, mechanical urticaria, or reactions to autologous serum skin test. However, the patients for whom montelukast was effective were younger (33.2±16.3 years, mean ± SD)(P<0.05, Mann-Whitney test) and their duration of illness shorter (15.9±18.3 months) (P<0.005, Mann-Whitney test) than those of patients for whom montelukast was ineffective (45.9±15.0 years, 89.6±71.7 months). Montelukast may be worth trying for patients with chronic idiopathic urticaria, when the condition is not sufficiently controlled with histamine H₁-receptor antagonists.     

Immediate hypersensitivity is rarely implicated in drug induced urticaria

INTRODUCTION: The unexpected appearance of acute urticaria during the course of drug treatment gives rise to the following question: is it an allergic urticaria (due to an immediate hypersensitivity: IgE mediated specific immunity) or is it pseudo-allergic? We report our findings in an immuno-allergological study of patients who were sent for drug intolerance which presented as immediate hypersensivity (urticaria, angiooedema, anaphylactic shock). METHODS: A prospective study was conducted including all the patients who were sent to the unit for urticaria or angiooedema type drug intolerance. Patients were questioned about previous chronic urticaria and also about urticaria after taking different medicines. The clinical examination looked for a dermographism. All the patients then took skin tests for immediate hypersensitivity, the molecule was contra-indicated and tests for cross-reactivity were conducted. PATIENTS: Three hundred fifty patients were sent to this unit between February 2000 and April 2001 for drug intolerance, mostly with urticaria/angiooedema but in 7 cases with anaphylactic shock. The incriminated drugs were varied: 50 p. 100 were due mainly to penicillins and cephalosporins. Other drug groups were also involved: non steroid anti-inflammatories, aspirin and paracetamol for the most part, along with local anesthetics, morphine-based products, contrast iodine products, corticosteroids. RESULTS: Of the 350 patients tested, only 22 were allergic and had positive tests for the incriminated drug. In these 22 patients, with the exception of 2 of them, the effects were severe (anaphylactic shock in 7 patients) and the urticaria was only a minor manifestation of the reaction. The drugs responsible were cephalosporin (10 patients), the penicillin (6 patients), insulin (2 patients), gonadorelin (1 patient), carboxymethylcellulose (1 patient), lidocain (1 patient), and sulfamethoxazole (1 patient). The 328 other patients had negative tests and were able to retake the tested molecule without incident. Most of them had antecedents of chronic urticaria or dermographism. DISCUSSION: Only 22 patients of the 350, i.e. 6 p. 100 were genuinely allergic. These patients were those who presented the most severe symptoms. The other patients, i.e. the majority, suffered from pseudo-allergic drug-induced urticaria, which made retaking the medicines possible.     

Aspirin-sensitive urticaria: provocation with a leukotriene receptor antagonist

The diagnosis of two patients with aspirin-induced urticaria (AIU) was confirmed by oral provocation with aspirin, other non-steroidal anti-inflammatory drugs, and food additives. Low doses of a novel leukotriene (LT) receptor antagonist, ONO-1078 (ONO, Japan) induced urticaria in these patients, while the same doses of ONO-1078 did not provoke any eruptions in 10 normal healthy volunteers or five patients with aspirin-unrelated chronic urticaria. This is the first report that a selective LTD4/LTE4 receptor antagonist that is effective as an antiasthmatic agent evoked urticaria in patients with AIU. Our observation suggests that the pathogenesis of AIU depends on the stimulation of LT receptors. The accumulation of results of anti-LT therapy may provide clues to resolve the pathogenetic mechanisms of this disorder.     

Hypersensitivity to cyclooxygenase inhibitory drugs in children: a study of 164 cases

Hypersensitivity to cyclooxygenase (COX) inhibitors is rare in children. We studied 164 children reporting 213 reactions to paracetamol, ibuprofen and/or acetylsalicylic acid (ASA). Most reactions were cutaneous, either isolated or associated with respiratory symptoms and/or anaphylaxis. Based on a convincing clinical history or positive responses in challenges with the drug(s), hypersensitivity to one or several drug(s) was diagnosed in 49.4% of the children (60, 76.5 and 23.2% of the children reporting reactions to ASA, ibuprofen and paracetamol respectively). Cross-reactivity between nonsteroidal anti-inflammatory drugs (NSAIDs) was frequent (69.1%), but only 10.6% of the NSAID-sensitive children reacted to paracetamol. In contrast, all paracetamol-sensitive children reacted to NSAIDs. Anaphylaxis, immediate and accelerated reactions, atopy, older age and chronic/recurrent urticaria were risk factors for hypersensitivity and/or cross-reactivity between ASA, ibuprofen and paracetamol. In conclusion, hypersensitivity to COX inhibitors was frequent, especially in children reporting severe and/or immediate and accelerated reactions, and in older and atopic children. Cross-reactivity was frequent, suggesting that most reactions resulted from a non allergic hypersensitivity linked to the pharmacological properties of the drugs. However, in a few children, the reactions may result from allergic hypersensitivity to selective (families of) drugs, with tolerance to other drugs.     

Patch testing in fixed drug eruptions--a 20-year review

Background. The fixed drug eruption is a common adverse drug reaction. Clear identification of the culprit drug is not always possible in the clinical setting, and oral rechallenge may induce new lesions or severe reactions. Objectives. The main purpose of this study was to evaluate the diagnostic value of patch testing in establishing an aetiological diagnosis in fixed drug eruptions. Method. A retrospective analysis was conducted evaluating 52 patients (17M/35F, mean age 53±17 years) with clinical diagnoses of fixed drug eruptions submitted to patch tests in a 20‐year period in a Dermatology Department. Nonsteroidal anti‐inflammatory drugs (NSAID) were clinically suspected in 90.4% of the cases, followed by antibiotics (28.9%) and paracetamol (15.4%). Results. Patch tests on pigmented lesions were reactive in 21 patients (40.4%), 20 of those to NSAID (nimesulide, piroxicam and etoricoxib) and 1 to an antihistamine (cetirizine). All patch tests using other drugs were negative, even under conditions of high clinical suspicion. Oral rechallenge allowed confirmation of drug imputability in 5 of 31 test‐negative cases. Cross reactivity was frequently observed between piroxicam and other oxicams, and between different antihistamines. Conclusions. Patch testing was shown to be a simple and safe method to confirm drug imputabililty in fixed drug eruption, mainly when NSAID or multiple drugs are suspected. Persistent lack of reactivity to drug classes such as antibiotics and allopurinol represent an important limitation.