Richard G. Van Dellen

Penicillin allergy: clinical experience with a battery of skin-test reagents

From 1971 through August 1978, 778 patients underwent penicillin skin testing. Each patient gave a history of previous penicillin allergy. The skin-test reagents consisted of (1) fresh solutions of commercially prepared penicillin G (PEN G), ampicillin (AMP), and methicillin (METH); (2) polylysine conjugates of the major antigenic determinants of each of the three drugs: and (3) alkaline hydrolysates of each drug. A total of 108 (14%) patients showed positive reactions to one or more of the reagents. Certain patients showed reactivity to many reagents, whereas others reacted selectively to only one or two reagents. Addition of reagents of AMP and METH resulted in a greater number of positive reactors than when reagents of PEN G alone were used. Of the group whose skin tests were negative, 290 (43%) were later treated with penicillin, twelve of these (4.1%) had allergic reactions. Eight of the group of whose skin tests were positive were subsequently treated, and four of these (50%) had allergic reactions again. A group 151 patients whose skin tests were negative and 27 patients whose skin tests were positive were treated with a cephalosporin. Only two patients had allergic reactions to the drug: both had had negative skin tests to penicillin. We conclude that the risk of subsequent allergic reactivity to penicillin is much lower if the skin tests are negative than if positive, that testing with semisynthetic penicillins increases the number of skin-test reactors, and that the incidence of allergic reactions is low in patients treated with cephalosporin.

Frequency of systematic reactions to penicillin skin tests

BACKGROUND Penicillin skin testing is generally considered to be safe when performed sequentially with puncture and intradermal testing although fatalities have been reported. OBJECTIVE We analyzed the rate of systemic reactions to penicillin skin tests for a period of seven and two-thirds years. METHOD This retrospective study used a computerized database at the Mayo Clinic. Altogether 1710 patients were skin-tested to penicillin from January 1992 to September 1999. All patients tested had a history of penicillin allergy. Patients were tested with benzylpenicilloyl polylysine (Pre-Pen) (6.0 X 10(-5) M), freshly prepared penicillin G (10,000 units/ml), and penicilloate (0.01 M). Prick tests were done first and if negative then intradermal tests. Systemic reactions were evaluated and treated by physicians. RESULTS Eighty-six patients had positive penicillin skin tests of which two had systemic reactions. Our systemic reaction rate for all patients tested was 0.12%; and 2.3% for the penicillin skin test-positive group, with no fatalities. CONCLUSION The incidence of systemic reaction to penicillin skin tests is low. Skin prick tests should always be done first. If there is a history of a previous serious reaction, the skin tests-if done-should be diluted to start with. Those doing penicillin skin tests should be prepared to treat a systemic reaction.

Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine : case report and review

BACKGROUND Hypersensitivity reactions to cyclosporine are rare. The mechanism of the reaction and guidelines for subsequent use of cyclosporine are not well defined. OBJECTIVE To investigate the mechanisms involved in hypersensitivity reactions to cyclosporine and determine the feasibility of future cyclosporine use. METHODS We report a patient who had an anaphylactic reaction during the intravenous infusion of cyclosporine. Skin-prick tests were performed for the antibiotics he received earlier in the day and the cyclosporine. A MEDLINE search identified all the reported cases of hypersensitivity reactions to cyclosporine. Each was analyzed to determine a mechanism of the hypersensitivity reaction and subsequent management outcomes. RESULTS Intradermal tests to intravenous cyclosporine formulation (1 mg/mL) were positive in the patient and negative in two controls. There was no reaction to the antibiotics. The literature search revealed 22 cases of hypersensitivity reaction to cyclosporine. The clinical setting and diagnostic evaluation suggest multiple mechanisms for the hypersensitivity response. All seven patients who were given an oral formulation of cyclosporine tolerated it well after a reaction to the intravenous infusion. Two patients who initially reacted to an oral solution formulation subsequently tolerated the corn oil-based soft gelatin capsule. CONCLUSIONS Hypersensitivity reactions to cyclosporine are due to Cremophor EL. There is direct and indirect evidence for various immunologic and nonimmunologic pathways precipitating the reaction. This case suggests a role for IgE in the hypersensitivity reaction. Fortunately, a hypersensitivity reaction to one formulation of cyclosporine does not preclude use of a different formulation. The corn oil-based soft gelatin capsule appears to be the safest formulation.

Asthma Caused by Topical Application of Ketorolac

BACKGROUND Ketorolac tromethamine 0.5 percent ophthalmic solution is a widely used nonsteroidal anti-inflammatory drug (NSAID) in ophthalmology. Ketorolac eye drops have not been implicated previously as a cause of NSAID-induced asthma. STUDY DESIGN A patient with severe asthma after topical application of ketorolac is described. The current ophthalmic indications for topical application of ketorolac and reported hypersensitivity reactions with systemic use of ketorolac are reviewed. RESULTS A 44-year-old woman with chronic asthma, rhinosinusitis, and nasal polyps inadvertently was given ketorolac to be applied topically. After applying the first dose of ketorolac, an exacerbation of her asthma developed, necessitating hospital admission. CONCLUSIONS Topical application of ketorolac is safe in the vast majority of ophthalmology patients. However, NSAID eye drops should not be prescribed for patients with aspirin or NSAID allergy or the combination of asthma and nasal polyps unless the patient is known to tolerate aspirin without trouble.

Oral Administration of Cromolyn in a Patient With Protein-Losing Enteropathy, Food Allergy, and Eosinophilic Gastroenteritis

OBJECTIVE To determine treatment for a woman with a 2 1/2-year history of edema and diarrhea. DESIGN We present a case report of a 47-year-old woman with protein-losing enteropathy and eosinophilic gastroenteritis who had positive results to allergy prick skin tests and increased allergen-specific IgE antibodies to numerous foods. MATERIAL AND METHODS Laboratory studies revealed low levels of serum total protein and albumin. Biopsy specimens showed widespread eosinophilia. A restricted diet was recommended. An elemental diet was poorly tolerated, and the patient wanted to avoid systemic administration of corticosteroids. Thus, we initiated oral cromolyn sodium therapy. RESULTS After oral administration of cromolyn, the patients condition improved dramatically; the diarrhea abated, and the edema resolved. Her serum albumin level returned to normal. CONCLUSION Oral cromolyn therapy should be considered in patients with eosinophilic gastroenteritis in whom food allergy has been implicated. No side effects associated with use of this drug were noted in our patient.

Genetic Test Indications and Interpretations in Patients With Hereditary Angioedema

Patients with hereditary angioedema (HAE) present with recurrent, circumscribed, and self-limiting episodes of tissue or mucous membrane swelling caused by C1-inhibitor (CI-INH) deficiency. The estimated frequency of HAE is 1:50,000 persons. Distinguishing HAE from acquired angioedema (AAE) facilitates therapeutic interventions and family planning or testing. Patients with HAE benefit from treatment with attenuated androgen, antifibrinolytic agents, and C1-INH concentrate replacement during acute attacks. HAE is currently recognized as a genetic disorder with autosomal dominant transmission. Other forms of inherited angioedema that are not associated with genetic mutations have also been identified. Readily available tests are complement studies, including C4 and C1-esterase inhibitor, both antigenic and functional C1-INH. These are the most commonly used tests in the diagnosis of HAE. Analysis of C1q can help differentiate between HAE and AAE caused by C1-INH deficiency. Genetic tests would be particularly helpful in patients with no family history of angioedema, which occurs in about half of affected patients, and in patients whose C1q level is borderline and does not differentiate between HAE and AAE. Measuring autoantibodies against C1-INH also would be helpful, but the test is available in research laboratories only. Simple complement determinations are appropriate for screening and diagnosis of the disorder.

Evaluation of IgE tests in an allergy practice

Abstract We measured serum IgE in 264 patients seen in the course of an allergy practice during the summer of 1970. IgE values were elevated in 21 per cent of patients who had idiopathic asthma and 10 per cent of patients who had idiopathic rhinitis. The elevated IgE was of no immediate clinical help in this idiopathic group because we were unable to detect hidden allergenic factors on further review of the history and skin tests. The finding of such an elevation, however, will prompt us to a continuing search for an allergic etiology or other condition associated with elevation of IgE. In patients who had hypersensitivity to stinging insects, IgE was elevated in 9 of 29 (31 per cent), and in patients with asthma and aspirin intolerance it was elevated in one of 5. Results in small numbers of patients with several other conditions including cold urticaria, chronic urticaria, and drug allergy are also presented.

Long-Term Treatment of C1 Inhibitor Deficiency With ɛ-Aminocaproic Acid in Two Patients

Most patients who have hereditary angioedema receive treatment with androgens or impeded androgens. ɛ-Aminocaproic acid (EACA) is another treatment for C1 inhibitor deficiency. In two patients with angioedema and attacks of abdominal pain due to C1 inhibitor deficiency, long-term treatment with EACA (for more than 2 decades in one of them) was associated with a substantial decrease in the frequency and severity of episodes. One patient had definite hereditary angioedema, and the other had probable hereditary angioedema but the family history was negative for the disease. The EACA therapy caused no major side effects.

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Acute Anaphylactic Reactions and Aspirin Allergy

The subject of anaphylaxis immediately brings to mind penicillin, and for good reasons. Still, any of a long list of diagnostic and therapeutic agents and foods can be the cause of this life-threatening event. Every physician and even some patients should be prepared to deal with this emergency. For some asthmatic patients, even taking aspirin can precipitate a severe attack of asthma. In particular, the combination of asthma and nasal polyps should raise suspicion of this type of aspirin allergy.