Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series.

BACKGROUND: Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published. OBJECTIVE: To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series. METHODS: We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series. RESULTS: Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid. CONCLUSIONS: This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.

Hereditary angioedema with F12 mutation: Clinical features and enzyme polymorphisms in 9 Southwestern Spanish families.

BACKGROUND: Information on F12 mutation hereditary angioedema (HAE) is still limited, but Spain is now recognized as having one of the highest concentrations of cases in Western Europe. OBJECTIVE: To describe unique features of HAE in Spanish carriers of the F12 mutation and investigate a potential role for angiotensin-converting enzyme (ACE) and aminopeptidase-P polymorphisms in disease expression. METHODS: This was a prospective observational cohort study of 35 individuals (80% females) from 9 unrelated families carrying the p.Thr309Lys mutation. We analyzed detailed medical records and complement activity (C4, C1q, C1 inhibitor) and screened for mutations in exon 9 of the F12 gene and 2 polymorphisms: XPNPEP2 c-2399A and the ACE insertion/deletion polymorphism. RESULTS: The p.Thr309Lys mutation was found in all individuals. Three of the 9 index patients had a clinically negative family history, and 72% of males and 29% of females were asymptomatic. Sixteen females (44% estrogen dependent, 56% estrogen sensitive) were clearly symptomatic. The most common locations of attacks were the abdomen (63%), face (25%), and peripheral structures (6%). Triggers other than hyperestrogenic states included stress and minor trauma or pressure. Short-term treatment with C1-inhibitor concentrate and icatibant and long-term prophylaxis with tranexamic acid were useful. The combination of the I allele and A allele was detected in 17% of patients. CONCLUSION: The polymorphisms analyzed were not a major determinant of disease expression in our population. We recommend searching for F12 mutations in women with edema attacks without associated wheals and with normal C1-inhibitor levels, particularly when they develop symptoms during hyperestrogenic states or are of Western European or African origin.

Safety of the new selective cyclooxygenase type 2 inhibitors rofecoxib and celecoxib in patients with anaphylactoid reactions to nonsteroidal anti-inflammatory drugs.

BACKGROUND: Controlled oral challenge with nonsteroidal anti-inflammatory drugs (NSAIDs) is the only definite way to detect safe NSAIDs in patients with NSAID-induced anaphylactoid reactions. OBJECTIVE: To evaluate the safety of the selective cyclooxygenase (COX) type 2 inhibitors rofecoxib and celecoxib in patients with single-reactive, NSAID-induced anaphylactoid reactions. METHODS: We prospectively conducted single-blind, placebo-controlled oral challenges (SBPCOCs) with rofecoxib and celecoxib in 33 patients with single-reactive, NSAID-induced anaphylactoid reactions. RESULTS: Nineteen women and 14 men (age range, 20-78 years; mean age, 44.8 years) exhibited anaphylactoid reactions on emergency department admission. Symptoms involved the skin (100%), laryngeal edema (73%), systolic hypotension (39%), and the gastrointestinal system (15%). The NSAIDs most frequently involved in the episodes were dipyrone (64%), propyphenazone (12%), and diclofenac (12%). In all patients, tolerance to a potent, nondiscriminatory COX inhibitor (except those reported as being responsible for the reaction) was noted. The SBPCOCs with the selective COX-2 inhibitors celecoxib and rofecoxib were well tolerated in all cases. Twenty-three patients who had an anaphylactoid reaction involving dipyrone and propyphenazone showed good tolerance to celecoxib (which contains a pyrazole group in its structure) on challenge. CONCLUSIONS: The SBPCOCs with highly selective COX-2 inhibitors were safe in patients with single-reactive, NSAID-induced anaphylactoid reactions, even in cases that involved pyrazole derivatives.

Boosted IgE response after anaphylaxis reaction to cefuroxime with cross-reactivity with cefotaxime.

BACKGROUND: Cefuroxime is a second-generation lactamase-stable cephalosporin. Its use is on the increase, and in recent years several reactions to this compound have been reported. OBJECTIVE: To describe a case of selective reaction to cefuroxime, showing a boosted immunoglobulin (Ig)E response after administration of this drug. METHODS: Specific serum IgE antibodies to several cephalosporins were monitored in a 52-year-old man after a selective systemic anaphylaxis attributable to cefuroxime, who showed a good tolerance to penicillin V during a single-blind, placebo-controlled challenge. RESULTS: Specific IgE levels to cefuroxime were not detected at the moment of the reaction but became positive 1 day after, increasing to peak at day 51, and still positive after 115 days. Through radioallergosorbent test inhibition, cross-reactivity between cefuroxime and cefotaxime was demonstrated. CONCLUSIONS: IgE-mediated reaction attributable to cefuroxime with cross-reactivity to cefotaxime was reported. A prompt evaluation undertaking skin tests and additional radioallergosorbent test studies with different betalactam derivatives improves the evaluation of subjects with allergic reactions to betalactams.

Safety of selective cyclooxygenase-2 inhibitor rofecoxib in patients with NSAID-induced cutaneous reactions.

BACKGROUND: Controlled oral challenge with nonsteroidal anti-inflammatory drugs (NSAIDs) is the only definite way to diagnose the different clinical manifestations of NSAID sensitivity. OBJECTIVE: To evaluate the safety of selective cyclooxygenase-2 inhibitor rofecoxib in a patient population with NSAID-induced skin reactions. METHODS: We prospectively conducted single-blind, placebo-controlled, oral challenges (SBPCOCs) with rofecoxib in 15 patients with challenge-proven NSAID-induced cutaneous reactions. RESULTS: Fifteen patients (9 men and 6 women, ranging in age from 14 to 60 years) had positive SBPCOC response to at least one of the following NSAIDs: aspirin (in 46.7% of cases), nimesulide (in 40% of cases), and diclofenac (in the remaining 13.3% of cases). During controlled challenges, 8 patients (53.3%) had urticaria (1 of them with associated angioedema); 6 (40%) had facial angioedema; and 1 (6.6%) had nonurticarial rash. Controlled oral challenge with rofecoxib were well tolerated in all patients. CONCLUSION: Rofecoxib did not cross-react with aspirin and other NSAIDs in patient with NSAID-induced skin reactions. A tolerance observed to this drug during SBPCOCs will indicate a safe alternative in this patient-group.