Laila Sabino Garro

Nonsteroidal Anti-Inflammatory Drugs are Major Causes of Drug-Induced Anaphylaxis

BACKGROUND Drugs are responsible for 40% to 60% of anaphylactic reactions treated in the emergency department. A global research agenda to address uncertainties in anaphylaxis includes studies that identify factors associated with morbidity and mortality. OBJECTIVE The present study investigated drug-induced anaphylaxis, etiologies, aggravating factors, and treatment. METHODS A total of 806 patients with adverse drug reactions were screened, and those who had a clinical diagnosis of anaphylaxis were included in the study. Clinical and demographic characteristics of anaphylaxis were described, including etiologies, pathophysiologic mechanisms involved in the reactions, and a personal history of atopy and asthma. Factors associated with disease severity also were identified. RESULTS Anaphylaxis was diagnosed in 117 patients (14.5%). The etiologies were defined in 76% of the cases, nonsteroidal anti-inflammatory drugs being the most frequent. Seventy-eight patients (66.7%) reported a previous reaction to the drug involved in the current reaction or to a drug from the same class and/or group. Epinephrine was used to treat 34.2% of patients who presented with anaphylaxis, and 40.8% of those with anaphylactic reactions with cardiovascular involvement. IgE-mediated reactions were associated with greater severity, manifested by the rates of cardiovascular dysfunction, hospitalization, and use of epinephrine. CONCLUSIONS The prevalence of anaphylaxis is high in patients who seek medical assistance for drug reactions, but its diagnosis is missed in emergency services, and adrenaline is underused. Drugs were prescribed to many patients despite a history of previous reaction. Nonsteroidal anti-inflammatory drugs were implicated in most cases of anaphylaxis induced by drugs, and IgE-mediated reactions were less frequent but more severe.

Outcomes and safety of drug provocation tests.

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs.

Specific questionnaire detects a high incidence of intra-operative hypersensitivity reactions

OBJECTIVE: To assess the incidence of intra-operative immediate hypersensitivity reactions and anaphylaxis. METHODS: A cross-sectional observational study was conducted at the Department of Anesthesiology, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil, from January to December 2010. We developed a specific questionnaire to be completed by anesthesiologists. This tool included questions about hypersensitivity reactions during anesthesia and provided treatments. We included patients with clinical signs compatible with immediate hypersensitivity reactions. Hhypersensitivity reactions were categorized according to severity (grades I-V). American Society of Anesthesiologists physical status classification (ASA 1-6) was analyzed and associated with the severity of hypersensitivity reactions. RESULTS: In 2010, 21,464 surgeries were performed under general anesthesia. Anesthesiologists answered questionnaires on 5,414 procedures (25.2%). Sixty cases of intra-operative hypersensitivity reactions were reported. The majority patients (45, 75%) had hypersensitivity reactions grade I reactions (incidence of 27.9:10,000). Fifteen patients (25%) had grade II, III or IV reactions (intra-operative anaphylaxis) (incidence of 7:10,000). No patients had grade V reactions. Thirty patients (50%) were classified as ASA 1. The frequency of cardiovascular shock was higher in patients classified as ASA 3 than in patients classified as ASA 1 or ASA 2. Epinephrine was administered in 20% of patients with grade III hypersensitivity reactions and in 50% of patients with grade II hypersensitivity reactions. CONCLUSIONS: The majority of patients had hypersensitivity reactions grade I reactions; however, the incidence of intra-operative anaphylaxis was higher than that previously reported in the literature. Patients with ASA 3 had more severe anaphylaxis; however, the use of epinephrine was not prescribed in all of these cases. Allergists and anesthesiologists should implement preventive measures to reduce the occurrence of anaphylaxis.

Occupational contact dermatitis due to captopril

Results We assessed a 36 years old female with a history of palpebral and lips oedema, flaking and pruritus, for two months, especially during her work. She worked in pharmaceutical industry and was referred to our outpatient because she had noticed worsening after contact with residues contained in captopril packaging during its manipulation. She had improved when had no contact with the packages. She was treated with topical corticosteroids and oral antihistamines. We performed contact delayed reading test (patch test) with captopril in the concentration of 10%, resulting papules, vesicles and swelling at the application site. In addition, there was a negative reaction standard test series. We told her to avoid new exposures to this drug and others with cross reaction.

Erythema multiforme induced by clindamycin diagnosed by patch test

Results A 17 years of age male was admitted in a University Hospital In Sao Paulo, Brazil, because he had been a victim of a car accident in May 2012. He suffered a tibia open fracture and was submitted to a surgical treatment. Three days after the procedure he developed face rash, cutaneous itching, target lesions in oropharynx and lower limbs peeling. He was being treated with Clindamycin, Ciprofloxacin, Dipyrone, Ketoprofen and Tramadol. The patient evolved with fever and leucocytosis, without eosinophilia. This reaction was diagnosed as EM major by Dermatology Unit and he was successfully treated with antihistamines and corticosteroids, besides suspected drugs substitution. After been discharged the patient was referred to the Allergy Unit to perform a drug hypersensitivity investigation. He was submitted to patch test with all the suspected drugs diluted in petrolatum 10%. Only the clindamycin patch test was positive, which was confirmed with a second patch test. The patient also presented reactivation of previous lesions. Conclusions As far as we know, this is the first patient who had developed erythema multiforme due to clindamycin. The patch test was essential to confirm the diagnosis and the use of all other drugs which were present at the time of the reaction could be released.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): two atypical case reports

Background The symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a delayed-type hypersensitivity drug reaction (HDR) that causes symmetrical erythematous lesions in flexural areas, including buttocks and groin, which arise following exposure to drugs, especially beta-lactams. The involvement of palms and soles is rare and, until now, it has only been described after exposure of amoxicillin. We hereby report a patient with SDRIFE and involvement of the palms and soles after taking cephalexin and another patient who developed SDRIFE after exposure to doxycyclin.

Persistence of positive skin test 25 years after a penicillin-induced anaphylaxis

Background Skin tests are important in the investigation of hypersensitivity drug reactions (HDR), particularly when betalactams are involved. However, the sensitivity decreases with time. It has been described that skin tests become negative about five years after a betalactam hypersensitivity reaction. We report a patient with persistence of a positive skin test twenty five years after an anaphylactic reaction due to penicillin.

Therapeutic trial in hereditary angioedema type III: Icatibant

Background Hereditary angioedema (HAE) is a disease transmitted by autosomal dominant inheritance, characterized by quantitative and / or functional deficiency of C1 inhibitor (C1-INH), which causes episodes of swelling, with involvement of many organs. HAE is currently divided into three groups. The HAE type III is a less frequent disorder that mainly affects women and is characterized by normal levels and activity of C1-INH.

Humoral biomarkers of latex allergy

Results The prevalence of sensitization and allergy to latex in patients presenting defects in neural tube closure was 33.2% and 12.2%, respectively. Cutaneous manifestations of latex allergy were the most common (79.6%), but anaphylaxis was observed in 4.75% of patients. Clinical and surgical factors associated with latex allergy were identified and a symptom score to screening patients was developed. Concentration of specific IgE to latex >0.77 kUA/l presented good accuracy in differentiating asymptomatic sensitization from allergy. Measurement of specific IgE to recombinant allergens also showed good accuracy in the diagnosis of allergy. The specific serum IgG4 concentration was negatively associated with allergy to latex, but this was not observed for specific IgA. Conclusion Higher concentration of specific IgE to latex and Hevb5, lower concentration of specific IgG4 to latex and symptom score iÝ 40% were associated with latex allergy.

518 Association between Clinical History and Specific IgE Recombinants Latex Allergens.

Background To identify the profile of sensitization to latex allergens in patients with spina bifida, with and without symptoms of latex allergy. Methods Cross-sectional study with 210 pacients aged 0 to 18 who have spina bifida and who have been followed in a Reference Hospital, in São Paulo, Brazil. Patients were submitted to a questionnaire for immediate symptoms related to latex allergy and they were classified as symptomatic (S) or asymptomatic (A), depending the presence of immediate symptoms on exposure to latex. Their blood were collected for the detection of serum total IgE, specific IgE to latex, and specific IgE to rHev b1, 3, 5, 6.01, 6.02, 8, 9, 11, through ImmunoCAP technique. Results Patients’ mean age were 7.9 years and 108 (51%) were female. S patients were 47 (22%). For these patients, 28 (60%) had at least one specific IgE positive test and 19 (40%) presented all tests negative. The A cases accounted for 163 (78%) patients. For these patients, 57 (35%) had at least one specific IgE test positive and 106 (65%) presented all tests negative. The prevalence of sensitization to recombinant latex allergens is not the same among patients S and A: rHev b 1 (S = 68%, A = 49%), rHev b3 (S = 39%, A = 28%), rHev b5 (S = 32%, A = 21%), rHev b6.01 (S = 43%, A = 23%), rHev b6.02 (S = 43%, A = 19%), rHev b8 (S = 0, A = 2%), rHev b9 (S = 4%, A = 5%), rHev b11 (S = 32%, A = 23%). Conclusions In this study, the prevalence of latex allergy in spina bifida patients is 22%. In symptomatic patients, the sensitivity of specific IgE tests is very poor. The profile for rHev b positivity is different in symptomatic and asymptomatic patients.