Safety of parecoxib in patients with nonsteroidal anti-inflammatory drug-induced urticaria or angioedema.

BACKGROUND: Parecoxib is the first injectable cyclooxygenase 2 selective inhibitor indicated for the treatment of acute postoperative pain. OBJECTIVE: To describe the results of a challenge with parecoxib in patients with a history of urticaria or angioedema to 1 or more nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: The study was performed from October 1, 2006, through March 31, 2007, with 79 patients who historically had experienced urticaria or angioedema after use of NSAIDs. The patients underwent a single-blind challenge with parecoxib, 40 mg. RESULTS: No reaction to placebo was observed in any patient. Similarly, no reaction to parecoxib was observed in any patients in the single-class or multiple-class intolerance group. CONCLUSION: Our report demonstrates that parecoxib does not induce cross-reactivity in patients with a history of urticaria or angioedema. Hence, this finding suggests that this drug could be safely proposed as an alternative (but only after a prior challenge) in patients with previous hypersensitive reactions to NSAIDs, even if there are added risk factors such as atopy and antimicrobial allergy, who require an analgesic drug perioperatively.     

Safety of etoricoxib, a new cyclooxygenase 2 inhibitor, in patients with nonsteroidal anti-inflammatory drug-induced urticaria and angioedema.

BACKGROUND: The use of selective inhibitors of cyclooxygenase 2 (COX-2) has been shown to be safe in patients with aspirin-induced asthma. However, a few individuals with cutaneous reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) experience urticaria or angioedema when challenged with various coxibs. OBJECTIVE: To investigate the clinical tolerance of NSAID-sensitive individuals to the selective COX-2 inhibitors etoricoxib and celecoxib. METHODS: Patients with NSAID-induced urticaria or angioedema were challenged in a double-masked, placebo-controlled design protocol with etoricoxib (120 mg) and celecoxib (200 mg). Cutaneous, respiratory, and general symptoms; vital signs; and pulmonary function were monitored hourly for 3 hours. RESULTS: Fifty-eight patients (46 females and 12 males) with a mean +/- SD age of 31.7 +/- 14.1 years (range, 13-66 years) who showed urticaria or angioedema when challenged with NSAIDs were included in this study. A cutaneous clinical pattern was observed in 34 patients (59%), and a mixed pattern (cutaneous and respiratory) was seen in 24 (41%). Celecoxib provocation of 54 patients induced urticaria in 3, urticaria and angioedema in 2, and urticaria, rhinorrhea, and conjunctival erythema in 1 (reaction rate, 11.1%). Etoricoxib challenges performed in 56 patients induced urticaria in 3 and angioedema in 1 (reaction rate, 7.1%). CONCLUSIONS: These results confirm that most NSAID-sensitive individuals with cutaneous reactions to classic NSAIDs will tolerate specific COX-2 inhibitors, supporting the use of thesedrugs after careful oral provocation in such patients.     

Genetic mechanism of aspirin-induced urticaria/angioedema

PURPOSE OF REVIEW: Aspirin-induced urticaria/angioedema is a major aspirin-related hypersensitivity often associated with aspirin-intolerant asthma. Genetic studies on aspirin-intolerant asthma have shown chronic overproduction of cysteinyl leukotrienes. The genetic analysis of aspirin-induced urticaria/angioedema is limited, however. RECENT FINDINGS: A recent study on HLA genotypes has suggested that the HLA alleles DRB11302 and DQB10609 may be genetic markers for aspirin-induced urticaria/angioedema. A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway. A second polymorphism study, conducted on histamine-related genes, did not find any significant associations with aspirin-induced urticaria/angioedema for the genes HNMT (encoding histamine N-methyltransferase), HRH1 or HRH2 (encoding histamine receptor types 1 and 2 respectively), or the gene encoding high-affinity IgE receptor Ibeta (FcepsilonRIbeta); however, the FcepsilonRIalpha gene promoter polymorphism was significantly associated with aspirin-induced urticaria/angioedema. This finding has been supported by in vitro functional studies. SUMMARY: The HLA alleles DRB11302 and DQB10609, and the ALOX5 and FcepsilonRIalpha promoter polymorphisms, may contribute to the pathogenesis of aspirin-induced urticaria/angioedema. Further investigation to identify candidate genetic markers would help to elucidate the pathogenic mechanism of this condition.     

Chronic urticaria and angioedema

Of 231 patients evaluated for chronic urticaria and angioedema (CUA), 192 were diagnosed as having an idiopathic condition. The roles of serum IgE, complement (CH₅₀), and immune complexes (IC) were investigated in 112 patients with idiopathic CUA. Immediate skin tests were not helpful, but total IgE was elevated in 13%, equally divided between dermographic (D) and non-dermographic (ND) patients. Depressed haemolytic complement (CH₅₀) was noted in 10% of CUA, all of whom were D. Serum IC were elevated in 38%, equally divided between D and ND patients. There was no relationship between depressed CH₅₀ and elevated IC. Skin biopsies, evaluated by both light and immunofluorescent techniques, were negative for all specimens tested. The pathophysiology of idiopathic CUA is multifactorial, with a variety of immunological mechanisms involving serum IgE, CH₅₀, and IC. The relationship between depressed CH₅₀ and dermographism was noted but unexplained by serum or tissue studies.     

Allergic urticaria and hereditary angioedema

A patient presented with both allergic urticaria and hereditary angioedema. The two conditions occurred independently, the urticaria being associated with allergy to food (which could be managed by control of the diet), whereas the angioedema was associated with C₁ esterase inhibitor deficiency.     

Tolerance to etoricoxib in 37 patients with urticaria and angioedema induced by nonsteroidal anti-inflammatory drugs.

BACKGROUND: The use of cyclooxygenase-2 inhibitors, a new class of analgesic drugs, is suggested in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To evaluate tolerance to etoricoxib, a new cyclooxygenase-2 inhibitor, in NSAID-sensitive patients with urticaria-type adverse reactions. PATIENTS: Thirty-seven patients with adverse reactions to NSAIDs. METHODS: Single-blind, placebo-controlled oral challenge with increasing doses of etoricoxib. RESULTS: Thirty-four patients tolerated etoricoxib treatment without adverse reactions, but a generalized urticarial rash developed in 3 patients (8%). CONCLUSIONS: Etoricoxib, like other cyclooxygenase-2 inhibitors, is a well-tolerated drug in most NSAID-sensitive patients. However, according to our experience, a previous challenge test in a safe environment may be necessary before prescribing the drug to such patients.     

Masqueraders of angioedema and urticaria.

OBJECTIVES: Reading this article will remind the reader that some patients presenting with complaints of urticaria and angioedema may not have urticaria or angioedema at all, but may have other causes, often unusual, sometimes treatable. It will also increase the reader's ability to recognize masqueraders of angioedema, urticaria, and facial swelling thought to be angioedema. DATA SOURCES: Data for this article come mainly from the authors' personal experiences and selected references to illustrate points made in the article. STUDY SELECTION: The criteria used are patients and articles from the authors' experiences that illustrate the point of this article that patients presenting with urticaria and angioedema may have other diseases and some of these are treatable. RESULTS: The objectives will be met by patient presentations plus pertinent literature review. CONCLUSIONS: Some patients presenting as angioedema and urticaria have swelling and skin lesions attributable to other causes. Although they are uncommon, they are sometimes treatable. Not all patients referred to an allergist for angioedema have angioedema.     

Pathogenesis of nonsteroidal antiinflammatory drug-induced asthma

PURPOSE OF REVIEW: To summarize recent findings related to the pathogenic mechanisms of aspirin-induced asthma with emphasis on molecular genetic mechanisms. RECENT FINDINGS: The overproduction of cysteinyl leukotrienes with the increased expression of cysteinyl leukotriene receptor 1 (CYSLTR1) is a consistent finding in aspirin-induced asthma patients. Recent data have suggested a dysregulation of cyclooxygenase-2 and prostaglandin E2, increased levels of 15-hydroxyeicosatetranoic acid, and decreased lipoxin generation as characteristics of the condition. The HLA allele DPB10301 was documented as a strong genetic marker for susceptibility in an Asian population. Leukotriene C4 synthase has been established as a key genetic determinant of aspirin-induced asthma, but recent studies have demonstrated that several single nucleotide polymorphisms in the promoters of prostaglandin E2 receptor subtype 2, CYSLTR1 and CYSLTR2 and T-box expressed in T cells (TBX21) could increase risk for the condition. Although cyclooxygenase-2 and thromboxane A2 receptor polymorphisms were not associated with aspirin-induced asthma phenotype, they may exert functional effects. SUMMARY: The identification of genetic markers for aspirin-induced asthma susceptibility along with in-vitro functional studies would help to elucidate the pathogenesis of the condition. Further studies of the interactions among genes and between genes and the environment will be essential.     

Exercise-induced urticaria, angioedema, and anaphylactoid episodes

Six subjects with exercise-induced anaphylactoid symptoms were evaluated by exercise challenge. Five of the six patients developed symptoms during free running. One subject developed only periorbital angioedema; another developed giant urticaria, wheeze, and hypotension; and three subjects developed cholinergic urticaria. One of the subjects with cholinergic urticaria also became hypotensive. Both of the subjects who developed hypotension also exhibited elevations in plasma histamine (11.2 and 23.2 ng/ml). Subjects who exhibited only cutaneous or subcutaneous manifestations failed to develop elevated levels of plasma histamine. Serum complement determinations (C′3, C′4) remained normal in all subjects at all time intervals. Thus exercise-induced anaphylactoid reactions can appear with a variety of cutaneous manifestations, including angioedema only, giant urticaria, and cholinergic urticaria. Elevated levels of plasma histamine are found only when systemic symptoms such as hypotension occur concomitantly.     

Hyperthyroidism and polycythemia vera with chronic urticaria and angioedema

Of 154 patients with chronic urticaria, six manifested concomitant hyperthyroidism and four polycythemia vera. Investigations of serum IgE, immune complex quantitation, complement and skin biopsies failed to elucidate a causal relationship. Polycythemia vera and hyperthyroidism should be considered as possible associations in the evaluation of chronic urticaria.