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Anaphylaxis can be difficult to diagnose in the postmortem setting. Postmortem tryptase is a widely used ancillary test in aiding the diagnosis in which an elevation supports a death from anaphylaxis. Postmortem tryptase can be difficult to interpret, and the effects of postmortem kinetics are not fully understood. Clinically, mast cell tryptase returns to baseline 24 to 72 hours after an anaphylactic stimulus. We report another anaphylactic death from antibiotic administration in which 2 serial postmortem total tryptase measurements at 3 days (72 hours) and 6 days (144 hours) after death declined from 522 μg/L to 300 μg/L (baseline, 5.6 μg/L). The declination appears to be slower than what is expected in the clinical setting. This case highlights yet another example of the difficult and complex interaction of postmortem interval on postmortem tryptase, especially in an anaphylactic death. We suggest that early blood sampling and serial tests be performed if possible in suspected anaphylactic death.

Background: In some diseases penicillin is the treatment of choice. Case studies have shown a good response for the treatment of circumscribed scleroderma or scleroderma adultorum of Buschke. A suspected allergy to penicillin in a patient's history may limit this helpful therapy option. Allergy testing is often inconclusive. If indicated, tolerance induction leading to therapy with penicillin can be carried out., Patients and Methods: We present two patients with circumscribed sclerosis and scleredema Buschke, who had a suspected allergy to penicillin. Due to limited therapy options and in insufficient response to other therapeutics, the decision for a tolerance induction with penicillin was made. Penicillin was successfully administered by following a scheme of tolerance induction starting with oral doses and ending with high doses of intravenous penicillin G., Results: In both cases, penicillin G, administered over a period of three weeks, was well tolerated up to the high dose of 3 x 10 Mega IU/day. Substantial clinical improvement was achieved in all cases without any complications., Conclusion: This case study demonstrates that a suspected allergy to penicillin does not preclude an eventual treatment with this valuable drug. Allergy testing should routinely be carried out first. If suspicion of an allergy persists, tolerance induction can be attempted according to the new scheme described here. Starting with a careful, initial oral dose regimen, treatment can be continued with an increasing intravenous dose followed by maintenance therapy with high-dose penicillin G. It should be clear that this policy is only restricted for patients who are at risk for a hypersensitivity to penicillin, i.e., because of a clinical manifested incompatibility in the past.

Background: Immediate allergic reactions to beta-lactam antibiotics are mediated by specific IgE antibodies. The Phadia CAP System FEIA is a commercial method for quantification of specific IgE. We wished to determine anti-beta-lactam IgE antibodies in patients without penicillin allergy but with high levels of total IgE., Methods: Sera from 41 patients (31 with high total IgE, 10 with low total IgE) were analyzed for IgE antibodies specific to penicilloyl G, penicilloyl V, amoxicilloyl and ampicilloyl using the CAP FEIA((R)) method that was available up to 2006. Seven sera that tested positive were rechecked in a new improved system available after 2006., Results: In patients without a history of penicillin allergy, the specificities of commercial tests for anti-beta-lactam IgE antibodies were 100%, 60%, 27% and 20% at total IgE levels of 8-263 kU/l, 500-664 kU/l, 1000-2000 kU/l and > 2000 kU/l, respectively. In seven retested sera, only 2 (28%) were still positive for penicillin-specific IgE antibody., Conclusion: Before 2006, tests for anti-beta-lactam IgE antibody in patients with total IgE > 500 kU/l were probably often false positive. Patients who were diagnosed as penicillin allergic before 2006 solely on the basis of a positive CAP FEIA test for specific IgE should be considered for diagnostic reevaluation.

A 24 year-old man developed an anaphylactic reaction within thirty minutes of an oral administration of penicillin V. He suffered from recurrent streptococal pharyngitis that was usually treated with penicillin V with good tolerance. Skin prick and intradermal tests with penicilloyl-polylysine, minor determinant mixture, amoxicillin, ampicillin and cefuroxima were negative. However, a skin prick test with penicillin V was positive in the patient and negative in 10 controls. Determination of specific (Immunogloblulin (Ig) E to penicillin V was 0.64 kU/L. Specific IgE to penicillin G, amoxicillin and ampicillin were all negative. Single blind controlled oral challenge with amoxicillin and cefuroxime were both negative. This is an exceptional case of an anaphylactic reaction induced by phenoxymethylpenicillin with positive allergologic study in vivo and in vitro tests and with negative allergological study to other beta-lactams.

Background: Despite the widespread use of an acute oral desensitization procedure in patients with allergic reactions to a variety of antibiotics, the precise mechanism of this procedure is poorly understood., Objective: To investigate the mechanisms underlying acute oral desensitization to antibiotics., Methods: Using a murine model of active systemic anaphylaxis to penicillin V (Pen V), mice previously sensitized to Pen V were desensitized by oral feeding of Pen V. The dose was doubled every 15 min and five feedings were given. The achievement of acute oral desensitization was evaluated by induction of active systemic and active cutaneous anaphylaxis, and by measuring the plasma levels of platelet-activating factor and histamine. Antigen-specific serum IgE antibody (Ab) levels were determined by passive cutaneous anaphylaxis., Results: Mice fed more than 3 mg of cumulative dose of Pen V were completely protected from fatal systemic anaphylactic reaction and the desensitized state lasted approximately 1 h. Antigen-specific mast cell desensitization, but not hapten inhibition, consumption of IgE Abs, or depletion of mast cell mediators, occurred during acute oral desensitization., Conclusions: Acute oral desensitization to Pen V occurred in the mice, and antigen-specific mast cell desensitization was associated with the underlying mechanism for oral desensitization.

Clinical situations for which penicillin is indicated as the sole effective treatment are not infrequent, in these circumstances penicillin allergy complicates their medical management. No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women, it is not possible choosing an alternative non betalactam antibiotic. The management of the patient who has a history of penicillin allergy include skin testing to determine if penicillin-specific IgE antibodies exist, and desensitization if penicillin is the choice treatment. We report a case of successful desensitization to penicillin in a 30 year-old pregnant woman with latent syphilis and penicillin allergy, where the first penicillin study was not positive, but the repetition of diagnosis test (reassessment) with the same betalactam reagents than in the first study two weeks later the initial evaluation was positive, detecting allergic sensitization not detected at the previous examination.

Background: Literature reports dealing with cell-mediated allergy to betalactams have appeared with increasing frequency in the last years., Objective: To evaluate patients with such reactions and to identify cross-reactivities among betalactams in order to provide safe guidelines for their further clinical management., Methods: Thirty consecutive subjects with cell-mediated allergy to betalactams (history of adverse reactions to these antibiotics; serum total IgE within the normal range; absence of serum specific IgE antibodies to penicillin G and V, amoxicillin, and ampicillin; negative skin tests with a wide pattern of betalactam preparations; and positive patch-test to at least one betalactam antigenic determinant) were investigated. The subjects admitted to the study were patch tested with a wide variety of betalactam preparations in order to identify alternative molecules tolerated by the patient. To better evaluate the cross-reactivity pattern, tolerance challenges with patch-negative betalactams were also performed in each subject., Results: Both specific IgE and skin tests were negative in all patients. The skin biopsies performed on the positive patch-tested area in four patients showed a clear T-lymphocyte, CD4+-type infiltrate, thus definitely proving the occurrence of a cell-mediated response. A total of 44 adverse reactions (mean: 1.47 episodes for each patient) were reported in history, with a mean interval of 15 hours after betalactam administration. The reported symptoms were mainly cutaneous (maculo-papular rash and urticaria) and the responsible drugs were chiefly aminopenicillins (86.4% of cases) and penicillin G (9.1%). We were able to identify three separate groups of patients on the basis of clinical history, patch-test, and tolerance challenge pattern: allergy to the side chain of aminopenicillins in 16 patients (53.3%); allergy to the thiazolidine ring in 3 patients (10.0%); undetermined specificity in the remainder 11 patients (36.7%). Cross-reactivity among different betalactam molecules (revealed by positive tolerance tests performed with patch-negative betalactams) was found in 4.8% of cases only (23.3% of all investigated patients). This fact demonstrates a very high (95.2%) predictive value of a negative patch-test in excluding the occurrence of a cross-reactivity. The mis-match between patch and tolerance tests was observed in 3 out of 178 cases only (1.7% of cases, 10.5% of patients) in groups A and B, and in as much as 12.2% of cases (45.5% of subjects) in group C (P < .05)., Conclusions: Delayed allergy to betalactams (mainly to aminopenicillins) may be exerted by a cell-mediated response. Patch tests and tolerance challenges are extremely useful and safe for diagnosis and further clinical treatment of these patients, helping to identify safe alternative betalactam molecules that could be successfully tolerated by the allergic subjects.