Failure to Develop Sensitization Despite Repeated Administration of Ovine Fab Snake Antivenom: Update of a Single-Patient, Multicenter Case Series

Abstract

We are writing to provide an update about a patient whose case was previously reported by Wilson.1Wilson L. Repeated administration of crotalid Fab antivenin in the same patient.Ann Emerg Med. 2002; 20: 572Scopus (5) Google Scholar The original report, published in October 2002, described a man who received Crotalidae polyvalent immune Fab (ovine) antivenom (CroFab; hereafter, FabAV; BTG, West Conshohocken, PA) on 6 separate occasions.This patient is now 42 years old. Since the initial report, we have been able to document 13 additional episodes in which he has received FabAV in New Mexico and Colorado.Despite serial exposures to ovine antigens, this patient has shown evidence of hypersensitivity reaction on only 2 occasions. The first, in 1994, was reported in the letter by Wilson1Wilson L. Repeated administration of crotalid Fab antivenin in the same patient.Ann Emerg Med. 2002; 20: 572Scopus (5) Google Scholar; the patient developed mild periorbital edema during the (then-experimental) FabAV infusion, followed 5 hours later by generalized urticaria. This was treated with diphenhydramine and methylprednisolone, and he received subsequent FabAV doses without incident. The other episode occurred in 2012, when he developed urticaria during the FabAV infusion. He was treated with diphenhydramine and famotidine and received additional FabAV without incident. No indication of acute or delayed hypersensitivity was documented on the other 17 known FabAV exposures, including 12 cases in which the lack of any antihistamine or corticosteroid pretreatment was documented. The patient has received at least 153 vials of FabAV during this 17-year period.In addition to the apparent lack of sensitization to sheep protein, this case is remarkable for the large number of snake envenomations experienced by a single person. In addition to the 19 episodes described above, we have been able to document at least 8 crotaline snake and 3 “spitting cobra” (Naja spp) envenomations managed without antivenom, an unknown number of native crotaline envenomations treated with whole immunoglobulin G equine antivenom (Antivenin [Crotalidae] Polyvalent; Wyeth-Ayerst, Marietta, PA) before the approval of FabAV, and a rattlesnake envenomation treated with an investigational equine F(ab′)2 antivenom. The patient claims to have had more than 100 venomous snakebites. He has also had at least 6 hospitalizations for gastrointestinal foreign body removal and ingestion of ethylene glycol and mercury. This constellation of self-inflicted injuries, habit of providing elaborate but factitious history, and repeated demands for surgical intervention establishes the diagnosis of Munchausen's syndrome, which has been confirmed by formal psychiatric evaluation. Multiple psychiatric interventions have thus far proven nontherapeutic.This case demonstrates that even with repeated administration of highly purified Fab antivenom, some patients will not develop sensitization. In addition, this case demonstrates the refractory nature of Munchausen's syndrome. We are writing to provide an update about a patient whose case was previously reported by Wilson.1Wilson L. Repeated administration of crotalid Fab antivenin in the same patient.Ann Emerg Med. 2002; 20: 572Scopus (5) Google Scholar The original report, published in October 2002, described a man who received Crotalidae polyvalent immune Fab (ovine) antivenom (CroFab; hereafter, FabAV; BTG, West Conshohocken, PA) on 6 separate occasions. This patient is now 42 years old. Since the initial report, we have been able to document 13 additional episodes in which he has received FabAV in New Mexico and Colorado. Despite serial exposures to ovine antigens, this patient has shown evidence of hypersensitivity reaction on only 2 occasions. The first, in 1994, was reported in the letter by Wilson1Wilson L. Repeated administration of crotalid Fab antivenin in the same patient.Ann Emerg Med. 2002; 20: 572Scopus (5) Google Scholar; the patient developed mild periorbital edema during the (then-experimental) FabAV infusion, followed 5 hours later by generalized urticaria. This was treated with diphenhydramine and methylprednisolone, and he received subsequent FabAV doses without incident. The other episode occurred in 2012, when he developed urticaria during the FabAV infusion. He was treated with diphenhydramine and famotidine and received additional FabAV without incident. No indication of acute or delayed hypersensitivity was documented on the other 17 known FabAV exposures, including 12 cases in which the lack of any antihistamine or corticosteroid pretreatment was documented. The patient has received at least 153 vials of FabAV during this 17-year period. In addition to the apparent lack of sensitization to sheep protein, this case is remarkable for the large number of snake envenomations experienced by a single person. In addition to the 19 episodes described above, we have been able to document at least 8 crotaline snake and 3 “spitting cobra” (Naja spp) envenomations managed without antivenom, an unknown number of native crotaline envenomations treated with whole immunoglobulin G equine antivenom (Antivenin [Crotalidae] Polyvalent; Wyeth-Ayerst, Marietta, PA) before the approval of FabAV, and a rattlesnake envenomation treated with an investigational equine F(ab′)2 antivenom. The patient claims to have had more than 100 venomous snakebites. He has also had at least 6 hospitalizations for gastrointestinal foreign body removal and ingestion of ethylene glycol and mercury. This constellation of self-inflicted injuries, habit of providing elaborate but factitious history, and repeated demands for surgical intervention establishes the diagnosis of Munchausen's syndrome, which has been confirmed by formal psychiatric evaluation. Multiple psychiatric interventions have thus far proven nontherapeutic. This case demonstrates that even with repeated administration of highly purified Fab antivenom, some patients will not develop sensitization. In addition, this case demonstrates the refractory nature of Munchausen's syndrome.