Faculty Bibliography

Mycotoxins are toxic secondary metabolites produced by a variety of fungi including Aspergillus, Alternaria, and Penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to chronic rhinosinusitis (CRS) or other diseases of the head and neck have not been reported. The authors performed an exploratory study to determine the presence and levels of mycotoxins in the sinonasal tissue and secretions of 18 subjects undergoing endoscopic sinus surgery for CRS. Using commercial enzyme-linked immunosorbent assay kits, samples were analyzed for the following mycotoxins: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. Four (22%) of 18 specimens were positive for ochratoxin. The clinical significance of this finding remains to be determined

RATIONALE: Rhinosinusitis is one of the most common chronic conditions in the US. The etiology of chronic rhinosinusitis (CRS) remains unknown and controversial. Mycotoxins are toxic secondary metabolites produced by fungi including aspergillus, alternaria, and penicillium species. The presence of mycotoxins in sinonasal tissue and secretions and any possible link to CRS has not been reported. METHODS: Sinonasal tissue and mucus specimens, predominantly from the ethmoid sinuses, were collected from 18 subjects undergoing endoscopic sinus surgery for CRS. The specimens were pulverized and centrifuged, then the resultant supernatant fraction was collected. The following mycotoxins were analyzed using commercial ELISA test kits: aflatoxin, deoxynivalenol, zearalenone, ochratoxin, and fumonisin. Mycotoxin concentrations were quantified from a standard curve. All standards and samples were analyzed in duplicate. We considered a sample positive when the mean value of the sample was two standard deviations above the limit of detection for the test kit. RESULTS: Four (22%) of 18 specimens were positive for ochratoxin. All specimens were negative for aflatoxin, deoxynivalenol, zearalenone, and fumonisin. CONCLUSIONS: Ochratoxin was identified in the sinonasal tissue and/or mucus of some subjects with CRS. The clinical significance of this is not known

RATIONALE: Immediate hypersensitivity reactions (HSR) are commonly encountered during infusion of chemotherapy, especially with platinum agents suchas oxaliplatin. The literature contains reports of4 patients who developed reactions during, or up to 24 hours after oxaliplatin infusion, with fever being a predominant symptom. Since fever is not an expected feature of an immediate HSR, the term idiosyncratic has been used to describe these reactions. While rapid drug desensitization has been shown effective in allowing infusion of drugs despite a history of immediate HSR, there are no reports indicating whether rapid drug desensitization is helpful is the management of febrile idiosyncratic reactions to oxaliplatin. METHODS: We report two patients with a history of immediate HSR to oxaliplatin, referred for rapid drug desensitization. During or within 1 hour after rapid drug desensitization with oxaliplatin, both patients developed signs and symptoms similar to previously reported cases of febrile idiosyncratic reactions to oxaliplatin, with maximum temperatures of 101.8 and 103.0 respectively. Both patients were hospitalized for several days, during which infection was ruled out. RESULTS: Rapid drug desensitization did not prevent febrile idiosyncratic reactions to oxaliplatin. CONCLUSION: The optimal management of patients with febrile idiosyncratic reactions to oxaliplatin remains unclear

RATIONALE: Natalizumab is a monoclonal antibody (mAb) indicated for treatment of multiple sclerosis. Natalizumab has special attributes which must be addressed when planning rapid desensitization for immediate hypersensitivity reactions (HSR.) Immediate HSRs during rapid desensitization are common, with consequent need to hold the infusion, treat the HSR, and possibly maintain a slower infusion rate. Complete infusion could require more than 8 hours, however, per FDA approved instructions, each bag of natalizumab solution must be infused within 8 hours of preparation or be discarded. Natalizumab is only supplied as 300 mg singledose vials. One published 3-bag, 12-step rapid desensitization protocol wastes approximately 10% of the drug, by discarding most solution in the first 2 bags. Accordingly, one must open another vial of natalizumab, costing approximately $3,000, or the patient will only receive approximately 90% of the typical intended dose. METHODS: Report of two patients with history of immediate HSR to natalizumab, and adaptation of a 3-bag, 12-step, rapid desensitization protocol as follows: Bag #1-0.6 mg in 50ml; Bag #2-6 mg in 50ml; Bag #3 and Bag #4-each 146.7 mg in 122.25ml. Bag #4 was not prepared until Bag #2 was mostly infused. Bags #2, #3 and #4 were infused completely. RESULTS: 99.8% of the intended dose was infused, without immediate HSR. CONCLUSIONS: With adaptation of a published protocol, rapid desensitization to natalizumab 300 mg is possible, utilizing only one single-dose vial, and with minimal chance of exceeding the FDA-approved eight hour infusion window from the time of preparation of each bag

RATIONALE: Rituximab is a monoclonal antibody shown to be effective in treating pediatric chronic idiopathic thrombocytopenic purpura (ITP). Hypersensitivity reactions (HSR), both immediate HSR and systemic delayed HSR have been reported to rituximab, but not in the same patient. METHODS: We report a pediatric patient with immediate HSR to rituximab who underwent successful rapid drug desensitization and later developed serum sickness. RESULTS: On Day 0, this 4 YO male with chronic refractory ITP, developed urticaria and bronchospasm during initial rituximab infusion and the infusion was terminated. On Day 4, rituximab was infused without immediate HSR, utilizing a published 3-bag, 12-step, rapid desensitization protocol, with a maximum infusion rate of 40 ml/hour. On Day 11, rituximab was infused again without immediate HSR, utilizing the same protocol and infusion rates. On Day 14, he developed serum sickness. CONCLUSIONS: This 3-bag, 12-step rapid desensitization protocol, previously shown effective in adult subjects, was successful in a 4 YO. The patient later developed serum sickness, which rapid desensitization would not be expected to prevent. There are published reports of patients developing both immediate and delayed HSRs to a drug, however the delayed HSRs in those cases were cutaneous due to topical drug exposure, whereas in the present case, the delayed HSR was systemic from intravenous administration. We believe this is the first report of a pediatric patient receiving rituximab by rapid desensitization and first report of a pediatric patient developing both immediate HSR and systemic delayed HSR to the same drug, in this case, rituximab