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Anaphylaxis After Cystoscopy
Ask the Expert : Phillip Lieberman, MD Anaphylaxis After Cystoscopy Phillip Lieberman, MD Each month we present highlights from the Ask the Expert section of the American Academy of Allergy, Asthma & Immunology (AAAAI) Web site written by Phil Lieberman, MD. For more questions and answers, visit www.aaaai.org/ask-the-expert.aspx.
Question: My patient is an 85-year-old man with bladder cancer who has been well for many years. He undergoes cystoscopy every 3 months. His last cystoscopy was uneventful, at least during the procedure, and he left the office in stable condition, with normal results. Approximately 10 minutes after leaving the office, he began to notice hives and then swelling of the tongue. He went to the emergency department, where he was treated with corticosteroids (exact drug and dose unknown) and diphenhydramine (dose unknown), but he is quite sure that he did not receive any injections, and so I do not think that epinephrine was given. Both he and his wife appear to be much younger than their stated ages and are quite on the ball, and she too confirms the lack of any injections having been given. Of note, there was no respiratory or cardiovascular compromise. He was kept in the emergency department for several hours and then sent home with prednisone, diphenhydramine, and famotidine. He was sent to see me for an evaluation of the situation to determine what the cause was because he will need more cystoscopies in the future. The procedure was performed with lidocaine gel in the urethra and no other medication. There was no intravenous treatment, and no antibiotics were given. I was initially told that there was no latex used, but, on further questioning of the urologist (the second time I spoke with him), he said that he could not be sure. So I ordered a serum-specific IgE to latex. It was negative. He had not eaten or had anything to drink before the procedure. He was cleansed with providone-iodine before his cystoscopy. He took his usual medications; however, he has taken these medications from the same vials since then uneventfully. IgE-mediated reactions to local anesthetics are said to be very, very rare, and I have actually not ever seen one in 18 years of practice. Although he is in good shape, I hesitate to start local anesthetics testing in an 85-year-old man unless it is absolutely necessary. He has had cystoscopies performed many times before without event. The urologist wants to perform the procedure again soon and are willing to do it in the hospital with intravenous sedation, no local anesthetics, and no latex. Is there anything else that you can think of that might have occurred here? Could it be related to the sterilization preparation used to clean the scope? Do you think it is latex because the urologist is unsure whether or not they actually used any? A serum-specific IgE antilatex latex test can be falsely negative. Your help would be much appreciated. Available online July 3, 2014. J Allergy Clin Immunol Pract 2015;3:469-70. 2213-2198/$36.00 Ó 2015 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2014.05.007
Response: There are several points that could be mentioned that are salient to the evaluation of your patient. These are the following: 1. Chlorhexidine should be considered as a possible causative agent.1,2 The patient described in Dyer et al2 is very similar to yours. Thus, if chlorhexidine was used as a sterilization agent during his previous cystoscopies, it should not be used in any future cystoscopies, and you should consider evaluating him for chlorhexidine allergy as described in the references cited. 2. Although perhaps not as likely as chlorhexidine in your particular case, povidone-iodine (Betadine) is another possibility as a cause. Betadine has caused anaphylactic reactions during surgery and should also be investigated as the possible culprit.3 3. He should be tested for lidocaine or an alternative local anesthetic. The point is that he may need a local anesthetic in the future, and it would be a disservice to him to allow him to think, incorrectly, that he might be allergic to lidocaine. In addition, it would be a disservice to have him undergo a procedure without anesthetic if he was not allergic to lidocaine. The testing and graded challenge procedure is extremely safe and well tolerated, even in the elderly. It is well described in the literature.4 4. You should also test him to lidocaine gel because it contains hypromellose, and there has been a rare case of anaphylaxis to hypromellose contained in the gel.5 5. You are correct in your statement regarding latex because the sensitivity of this test leaves a great deal to be desired. Although I think that latex is an unlikely candidate, he should have further surgical procedures done in a latex-safe environment unless you discern that chlorhexidine or even perhaps hypromellose was the responsible agent. In summary, based upon the information available to us in the literature, chlorhexidine is the most likely candidate. It would be very unusual for lidocaine itself, as you mentioned, to be responsible. But, because lidocaine may be needed in the future, and because a procedure without lidocaine might be painful to him, I would proceed with the testing and challenge procedure as described in Schatz.4 I would also test to lidocaine gel because hypromellose is (albeit very unlikely) a possible candidate. Thank you again for your inquiry, and we hope this response is helpful to you. REFERENCES 1. Sokol WN. Nine episodes of anaphylaxis following cystoscopy caused by Cidex OPA (ortho-phthalaldehyde) high-level disinfectant in 4 patients after cystoscopy. J Allergy Clin Immunol 2004;114:392-7.
469
470
ASK THE EXPERT
2. Dyer JE, Nafie S, Mellon JK, Khan MA. Anaphylactic reaction to intraurethral chlorhexidine: sensitization following previous repeated uneventful administration. Ann R Coll Surg Engl 2013;95:e105-6. 3. Gray PE, Katelaris CH, Lipson D. Recurrent anaphylaxis caused by topical povidone-iodine (Betadine). J Paediatr Child Health 2013;49:506-7.
J ALLERGY CLIN IMMUNOL PRACT MAY/JUNE 2015
4. Schatz M. Skin testing and incremental challenge in the evaluation of adverse reactions to local anesthetics. J Allergy Clin Immunol 1984;74(Pt 2):606-16. 5. Munk SJ, Heegaard S, Mosbech H, Garvey L. Two episodes of anaphylaxis following exposure to hydroxypropyl methylcellulose during cataract surgery. J Cataract Refract Surg 2013;39:948-51.
Question: My patient is an 85-year-old man with bladder cancer who has been well for many years. He undergoes cystoscopy every 3 months. His last cystoscopy was uneventful, at least during the procedure, and he left the office in stable condition, with normal results. Approximately 10 minutes after leaving the office, he began to notice hives and then swelling of the tongue. He went to the emergency department, where he was treated with corticosteroids (exact drug and dose unknown) and diphenhydramine (dose unknown), but he is quite sure that he did not receive any injections, and so I do not think that epinephrine was given. Both he and his wife appear to be much younger than their stated ages and are quite on the ball, and she too confirms the lack of any injections having been given. Of note, there was no respiratory or cardiovascular compromise. He was kept in the emergency department for several hours and then sent home with prednisone, diphenhydramine, and famotidine. He was sent to see me for an evaluation of the situation to determine what the cause was because he will need more cystoscopies in the future. The procedure was performed with lidocaine gel in the urethra and no other medication. There was no intravenous treatment, and no antibiotics were given. I was initially told that there was no latex used, but, on further questioning of the urologist (the second time I spoke with him), he said that he could not be sure. So I ordered a serum-specific IgE to latex. It was negative. He had not eaten or had anything to drink before the procedure. He was cleansed with providone-iodine before his cystoscopy. He took his usual medications; however, he has taken these medications from the same vials since then uneventfully. IgE-mediated reactions to local anesthetics are said to be very, very rare, and I have actually not ever seen one in 18 years of practice. Although he is in good shape, I hesitate to start local anesthetics testing in an 85-year-old man unless it is absolutely necessary. He has had cystoscopies performed many times before without event. The urologist wants to perform the procedure again soon and are willing to do it in the hospital with intravenous sedation, no local anesthetics, and no latex. Is there anything else that you can think of that might have occurred here? Could it be related to the sterilization preparation used to clean the scope? Do you think it is latex because the urologist is unsure whether or not they actually used any? A serum-specific IgE antilatex latex test can be falsely negative. Your help would be much appreciated. Available online July 3, 2014. J Allergy Clin Immunol Pract 2015;3:469-70. 2213-2198/$36.00 Ó 2015 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2014.05.007
Response: There are several points that could be mentioned that are salient to the evaluation of your patient. These are the following: 1. Chlorhexidine should be considered as a possible causative agent.1,2 The patient described in Dyer et al2 is very similar to yours. Thus, if chlorhexidine was used as a sterilization agent during his previous cystoscopies, it should not be used in any future cystoscopies, and you should consider evaluating him for chlorhexidine allergy as described in the references cited. 2. Although perhaps not as likely as chlorhexidine in your particular case, povidone-iodine (Betadine) is another possibility as a cause. Betadine has caused anaphylactic reactions during surgery and should also be investigated as the possible culprit.3 3. He should be tested for lidocaine or an alternative local anesthetic. The point is that he may need a local anesthetic in the future, and it would be a disservice to him to allow him to think, incorrectly, that he might be allergic to lidocaine. In addition, it would be a disservice to have him undergo a procedure without anesthetic if he was not allergic to lidocaine. The testing and graded challenge procedure is extremely safe and well tolerated, even in the elderly. It is well described in the literature.4 4. You should also test him to lidocaine gel because it contains hypromellose, and there has been a rare case of anaphylaxis to hypromellose contained in the gel.5 5. You are correct in your statement regarding latex because the sensitivity of this test leaves a great deal to be desired. Although I think that latex is an unlikely candidate, he should have further surgical procedures done in a latex-safe environment unless you discern that chlorhexidine or even perhaps hypromellose was the responsible agent. In summary, based upon the information available to us in the literature, chlorhexidine is the most likely candidate. It would be very unusual for lidocaine itself, as you mentioned, to be responsible. But, because lidocaine may be needed in the future, and because a procedure without lidocaine might be painful to him, I would proceed with the testing and challenge procedure as described in Schatz.4 I would also test to lidocaine gel because hypromellose is (albeit very unlikely) a possible candidate. Thank you again for your inquiry, and we hope this response is helpful to you. REFERENCES 1. Sokol WN. Nine episodes of anaphylaxis following cystoscopy caused by Cidex OPA (ortho-phthalaldehyde) high-level disinfectant in 4 patients after cystoscopy. J Allergy Clin Immunol 2004;114:392-7.
469
470
ASK THE EXPERT
2. Dyer JE, Nafie S, Mellon JK, Khan MA. Anaphylactic reaction to intraurethral chlorhexidine: sensitization following previous repeated uneventful administration. Ann R Coll Surg Engl 2013;95:e105-6. 3. Gray PE, Katelaris CH, Lipson D. Recurrent anaphylaxis caused by topical povidone-iodine (Betadine). J Paediatr Child Health 2013;49:506-7.
J ALLERGY CLIN IMMUNOL PRACT MAY/JUNE 2015
4. Schatz M. Skin testing and incremental challenge in the evaluation of adverse reactions to local anesthetics. J Allergy Clin Immunol 1984;74(Pt 2):606-16. 5. Munk SJ, Heegaard S, Mosbech H, Garvey L. Two episodes of anaphylaxis following exposure to hydroxypropyl methylcellulose during cataract surgery. J Cataract Refract Surg 2013;39:948-51.