Utility of topic application of NSAIDs as diagnostic test of aspirin intolerance

Utility of topic application of NSAIDs as diagnostic test of aspirin intolerance

$170 05 Abstracts CD69for In Vitro Diagnosis of Delayed Drug Reactions M. Yazicioglu, K. Cresswell, G. Whalen, J. N. Baraniuk; Georgetown Universi...

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$170

05

Abstracts

CD69for In Vitro Diagnosis of Delayed Drug Reactions

M. Yazicioglu, K. Cresswell, G. Whalen, J. N. Baraniuk; Georgetown University, Washington, DC. RATIONALE: CD69 is a rapidly up-regulated lymphoid activation antigen. We evaluated flow cytometric detection of CD69 on T cells for the diagnosis of delayed immune-mediated drug reactions. CASE REPORT: A 26 yr Caucasian non-Hispanic male had a 6 month history of facial and neck eczema. He used intranasal dihydroergotamine for 7 yr and oral finasteride for 189 yr. The rash responded to tacrolimus but not to stopping dihydroergotamine for 3 months. METHODS: Liquid dihydroergotamine, chloroform-extracted finasteride tablets, nickel sulfate, positive and negative controls were used for immediate and skin patch tests, and whole blood culture. TrueTest patch tests were also applied. Whole blood was diluted 1/5 with RPMI media, and cultured with dilutions of each substance. CD69+ subsets of CD3+, lymphocyte-gated CD4+ and CD8+ cells were counted by fluorescence assisted cell sorting (FACS) after 4 and 8 days. RESULTS: Puncture and intradermal tests were positive to histamine only. The nickel patch test was positive. Nickel and flnasteride significantly increased the Day 8/Day 4 ratios of CD69+CD8+ cells by 8-fold (p<0.001, X2) and 4.9-fold (p<0.001), respectively. CD69+CD8+ responses were also significantly greater than the RPMI media negative control. There were no changes in CD4+ cells. CONCLUSIONS: Nickel sensitivity was detected by positive patch test and CD69+CD8+ responses. Finasteride was implicated as the cause of his eczema by the CD69+CD8+ proliferative response. These may represent drug-specific CD8+ cells.

Funding: Self-funded Ajr~J~' A Case of Local Anesthetic HypersensitivityCross-Reactiveto "MJlU Both PharmacologicEster and Amide Anesthetic Groups R. S. Botta, B. A. Muller; Internal Medicine, University of Iowa Healthcare, Iowa City, IA. RATIONALE: Bonafide IgE mediated hypersensitivity to a local anesthetic agent is an exceedingly rare occurrence. This case demonstrates sustained sensitivity over time by history, with positive skin testing to both pharmacologic local anesthetic groups, directing future care requirements to include general anesthesia as a sedative preference. METHODS: A 57 year-old Caucasian woman with multiple medical comorbidities requiring a surgically necessary procedure presents with a history of anaphylaxis to Bupivacaine, after a stellate ganglion block performed four years previously. She had experienced acute shortness of breath, stridor and generalized urticaria that subsided within minutes after subcutaneous epinephrine, intravenous diphenhydramine and corticosteroids. Skin testing to local anesthetic agents and RAST to latex was performed. RESULTS: Prick and intradermal testing to positive and negative controls showed appropriate responses. The prick test was positive at 1:1000 dilution of a 2% Procaine (ester) solution with preservative, as a 10 mm wheal response. Incremental intra-dermal testing for Lidocaine (amide) was positive with an 8 mm wheal at 1:10 dilution of a 2% solution without preservative. Latex Cap-RAST was negative. CONCLUSIONS: Patients with true lgE mediated hypersensitivity to local anesthetics are exceedingly rare. Moreover, cross-reactivity between the amide and ester groups defies current dogma in the Allergy literature. This case is the first report to our knowledge of an IgE mediated hypersensitivity, confirmed by skin testing to both pharmacologic local anesthetic groups.

Funding: Self-funded

407 Allergyance to tOprocaineLOCal Anaesthetics of the Amide Group with TolerM. Morais-Almeida, A. Gaspar, J. Rosado-Pinto; Immunoallergy Department, D. Estef~nia Hospital, Lisbon, PORTUGAL. Adverse drug reactions to local anaesthetic (LA) agents are frequently reported but IgE-mediated allergic reactions are rare. We report a case of a 46-year-old woman, nurse, referred to evaluate tolerance to LA before

J ALLERGY CLIN IMMUNOL FEBRUARY 2003

skin biopsies; in briefly, she had had anaphylactic reactions after the administration of an unknown local anaesthetic agent 20 years ago and after lidocaine administration 12 years ago. Five years ago the patient also referred urticaria after topical use of lidocaine (EMLA| After obtaining patient's consent, the diagnostic approach was carried out: we performed skin tests with other amide LA drugs: bupivacaine, positive prick test (6x4mm); mepivacaine, positive prick test (4• ropivacaine, negative prick test but positive intradermal test with 1:100 dilution (12xl0mm). Afterwards, we performed skin tests (prick and ID testing) with procaine (benzoates esters group), that were negative; the patient was admitted in an ICU for challenge procedures. The subcutaneous challenge with lml of procaine (2%) was negative, allowing it use (3 biopsies - lorearm and thigh), with no adverse reaction. Afterwards, to ensure that the positive skin test results were relevant, we carried out placebo-controlled, single blind subcutaneous challenge test with 0.1 ml of ropivacaine (0.2%), and it was positive (severe systemic reaction), confirming the diagnosis of allergy to LA of the amide group. The immunological IgEmediated reaction was proved in this case and, as far as we know, this is the first report of hypersensitivity to ropivacaine. The therapeutic alternative was procaine, ester anaesthetic, not anymore routinely used.

Funding: Self-funded 408

Allergy to Local Anaesthetic

A. Spinola Santos, A. Lopes Pregal, S. Lopes da Silva, A. Vinhas de Sousa, M. Branco Ferreira, E. Pedro, A. G. Palma-Carlos; Immunoallergology, HSM, Lisbon, PORTUGAL. RATIONALE: To evaluate the clinical profile of patients undergoing local anaesthetics (LA) challenge tests. METHODS: Retrospective analysis of the clinical records of 22 patients submitted to LA challenge tests during the last 2 years at our Immunoallergology Unit. After exclusion of latex allergy and CI- inhibitor deficit, challenge tests were perlbrmed, according to the method used by Vervloet et al (skin pricktests first and thereafter subcutaneous administration of 0.1, 0.5, 1, 2 ml of an undiluted LA solution every 15 minutes). The anaesthetic (lidocaine, carbocaine, procaine or bupivacaine) was chosen according to clinical history. RESULTS: The 22 patients (F=I4; M=8; mean age=49.7_+ 13.6 years) were sent to our Unit from Dentistry (77%), Surgery (14%) and Ophthalmology (9%). Urticaria/angioedema was the most frequent complaint (43% of patients) that led to the performance of the challenge, being facial angioedema (28%), bronchospasm (7%), hypotension (7%) and non-specific symptoms (21%) other clinical reasons. No patient had a history of laryngeal obstruction or anaphylaxis. Previous history of other drug allergies was present in 50% of patients and atopy in 27%. We performed 29 challenge tests: lidocaine - 12, carbocaine - 12, procaine - 4 and bupivacaine - 1. Two patients had positive challenge tests to both "ester" and "amide" LA. CONCLUSIONS: Challenge tests are an important diagnostic method in local anaesthetics allergic reactions, we have diagnosed 2 (9%) cases out of 22 in our population. These 2 patients have positive challenge tests in both LA groups, which is an unusual finding.

Funding: Self-funded

409 Aspirin Utility of Topic Application of NSAIDs as Diagnostic Test of Intolerance S. H. Cimbollek j , A. Jimenez 2, C. Lozoya 2, R. Merchan 2, C. Fernandez 2, R. Vives2; ~Allergy, Hospital Doce de Octubre, Madrid, SPAIN, 2Hospital Doce de Octubre, Madrid, SPAIN. BACKGROUND: Three types of provocation are being used for the diagnosis of NSAIDs intolerance (NI). Only few cases of adverse reaction due to topic application have been described. Could topic application be used as a diagnostic test for NI? OBJECTIVE: Validation of a topic cutaneous test as diagnostic alternative. Confirm N1 by transdermal absorption of Ketoprofen in patients with history of cutaneous or mixed reactions with NSAIDs. M A T E R I A L S : Case I reported several episodes after oral NSAIDs ingestion consisting in generalized urticaria, angioedema and bron-

J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2

chospasm. After topic application of Ketoprofen he presented two hours later generalized urticaria and angioedema and intense bronchospasm. Case 2: had past history of atopy and urticaria after ingestion of aspirin and topic application of Ketoprofen. Case 3 and 4: referred several episodes of generalized urticaria due to NSAIDs. METHODS: Oral and bronchial provocation test with aspirin for diagnostic confirmation of NI. Cutaneous test consisted in progressive dose application of Ketoprofen. Test was considered positive if cutaneous reaction appeared or Fev~ decreased >20%. RESULTS: In case 1, confirmation was realized with bronchial provocation test with immediate bronchial reaction and urticaria two hours later. The cutaneous test with Ketoprofen was positive (local apparition of hives). No fall of Fevl was observed. In the other three cases the confirmation was obtained by oral provocation with aspirin. The topic application of Ketoprofen did not give any reaction. CONCLUSIONS: Even though the topic application has confirmed NI in one of the patients further studies are necessary to know its utility.

Funding: Self-funded

410 ASA Desensitization Assisted by Monteleukast in Patients with Nasal Polyps, Asthma, and ASA Sensitivity A. S. Cheema ], J. Mendelsohn2; JClinical Research Group, Mississauga, ON, CANADA, 2Ent, Trillium Health Centre, Mississauga, ON, CANADA. RATIONALE: ASA desensitization is usually carried out in the hospital setting. We performed gradual ASA desensitization in the office and home setting in patients who were pretreated with Monteleukast and optimally treated for asthma. METHODS: For one week prior to administration of ASA the patients were on daily Singulair and their asthma was optimally controlled with Flovent and Serevent. Their rhinosinusitis symptoms were treated with nasal steroids. Asthma was stable and FEVI was greater than 70% in all patients, desensitization was begun at 20 mg of ASA on day one and gradually increased thereafter. The patients were maintained on 650 mg of ASA per day. RESULTS: Of the 12 patients, 11 were successfully desensitized. One had urticaria at the dose of 160 mg ASA but was able to complete the desensitization. The other patient had recurrent asthma for 2 to 3 weeks after the desensitization and therefore ASA was discontinued. CONCLUSIONS: With careful selection of patients and use of Singulair along with Flovent and Serevent, ASA desensitization can be carried out to benefit rhinosinusitis symtpoms.

Funding: Selffunded

411

Valdecoxib Is a Safe Alternative Drug for NSAlD-Sensitive Patients with Cutaneous Reactions

M. S~inchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca; AllergyImmunology, Centro Mrdico-Docente La Trinidad, Caracas, VENEZUELA. RATIONALE: COX-2 selective inhibitors are generally well tolerated by individuals who develop urticaria (U) and angioedema (AE) from NSAIDs that inhibit cyclooxygenase-l. Valdecoxib(4-(5-methyl-3phenyl-4-isoxazolil)benzenesulphonamide) is a new COX-2 specific inhibitor indicated for acute pain, dysmenorrhea, osteoarthritis and rheumatoid arthritis. The objective of this study was to evaluate the tolerance of NSAID-sensitive patients to Rofecoxib and Valdecoxib. PATIENTS AND METHODS: 20 patients (female 14, male 6), aged 29.5+_15 years (range 10-61) with challenge-proven NSAID sensitivity manifested as U or AE were submitted to single-blinded oral challenges with Rofecoxib 50 mg and Valdecoxib 40 mg. Ten subjects had allergic rhinitis, 3 rhinitis and asthma, I asthma alone and 13/16 (81.2%) positive prick tests to aeroallergens. An exclusive cutaneous pattern (U and/or AE) was present in 6 patients and a mixed clinical pattern of skin and respiratory symptoms was observed in 13 subjects, with one patient exhibiting anaphylactoid clinical picture. Half dose of the drug was given one hour apart and the patient was observed in the hospital for three hours. A test was regarded as positive if >20% of surface body area was involved by urticaria or angioedema after challenge. Patients with chronic urticaria were excluded from the study. RESULTS: None of the challenged patients had cutaneous or respiratory

Abstracts

$171

reactions to Valdecoxib. One patient reacted to Rofecoxib 25 mg with laryngeal edema. CONCLUSIONS: Rofecoxib and Valdecoxib are tolerated by the majority of NSAID-sensitive patients with cutaneous reactions. However, controlled challenges should be carried out before administration of highly specific COX-2 inhibitors to these patients.

Funding: Self-funded

412 Severe Delayed Local Reaction to Childhood Vaccina,ions Containing Adjuvants U. K. Reddy, G. Avshalomov, V. R. Bonagura; Allergy and Immunology, Long Island Jewish Medical Center, New Hyde Park, NY. RATIONALE: We report severe local delayed reactions to vaccines occurring in an infant under one year of age resulting in extensive cutaneous scarring to almost all of her childhood vaccinations received by eight months of age. She received diphtheria, pertussis and tetanus combined vaccination, combined Haemophilus influenza B and recombinant hepatitis B, and conjugated pneumococcal vaccine. METHODS: Specific immunoglobulin titers, patch testing, gram stain and culture of aspirated fluid were done. RESULTS: Specific immunoglobulin titers were unusually elevated indicating a vigorous immune response to these vaccines. Gram stain revealed numerous white blood cells, but no organisms. Culture was negative. Patch testing was positive at 48 and 72 hours for aluminum, but negative for thimerosal and formaldehyde. CONCLUSIONS: The etiology of the lesions in this patient are very likely to be secondary to a DTH reaction to the aluminum adjuvant contained the vaccinations received. Sterile abscess is unlikely given the multiplicity of lesions and the high vaccine-specific immunoglobulin titers, both of which are atypical features sterile abscess. Given the potential for permanent disfigurement, physicians should be cognizant of the possibility of local DTH reactions to adjuvants in vaccinations that enhance immunogenicity, but can cause severe cutaneous side effects. In patients showing signs of DTH like reactions to vaccines, preparations devoid of these components should be sought and administered in place of those containing the offending agents.

Funding: Division of Allergy Immunology l_zmgIsland Jewish Medical

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Degree of Systemic Allergic Reactions to Measles, Mumps, and Rubella Vaccines

M. Sakaguchi, K. Tanuguchi, S. Inouye; National Institute of Infectious Diseases, Tokyo, JAPAN. RATIONALE: To examine the relationship between sensitization to gelatin, onset time and degree of systemic allergic reactions to measles, mumps, and rubella vaccines, we analyzed the cases of systemic allergic reactions. METHODS: We collected 521 case reports and serum samples from patients who had experienced anaphylaxis or other allergic reactions to these vaccines and measured anti-gelatin lgE in the serum samples. RESULTS: The cases were classified into three groups according to the degree of symptoms. The first group consisted of 37 patients that had developed severe, life-threatening anaphylaxis and 92% of these patients were positive for anti-gelatin IgE. All 37 patients developed anaphylaxis within one hour after vaccination. The second group consisted of 56 patients showing mild anaphylaxis and 95% of these were positive for anti-gelatin lgE. Of the 56 patients, 55 showed mild anaphylaxis within one hour after vaccination and one patient developed symptoms 3 hours after vaccination. The third group consisted of 428 patients showing only systemic cutaneous reactions to the vaccines. Of the 428 patients, 86 developed allergic reactions within one hour after vaccination and 81% of the 86 patients were positive for anti-gelatin lgE. The other 342 patients developed allergic reactions more than one hour after vaccination but only 6% of these patients were positive for anti-gelatin IgE. CONCLUSIONS: Apparent life-threatening anaphylaxis to the vaccines containing gelatin occurred within one hour after vaccination. The onset time of the allergic reactions to these vaccines depended upon the severity of the reactions.

Funding: Self-funded