An Alarming Complication of Candida albicans Antigen Treatment of Recalcitrant Warts

Response To the Editor: I thank Dr. Signore for his interest in our study and insightful comments related to our case report. In response, note the following comments: While I agree that it is important to consider the concentration of the Candida albicans antigen, it is, in my opinion, more important to consider the patient's immune response (delayed-type hypersensitivity [DTH]) with the associated inflammatory reaction) to this injected antigen. It is our standard of practice to administer a 0.1 mL intradermal injection of a 1:10 dilution of the stock solution of Candida albicans antigen solution on the volar forearm prior to the intralesional administration into the base of the wart, which was performed in the patient described in our case report.1 The size of the subsequent local inflammatory response to this test antigen dose will dictate whether this or a more dilute preparation is injected into patients' warts. Our patient exhibited a normal DTH response to the diluted antigen.1 Based on her normal DTH response to this dose of antigen, there was no reason to anticipate the type of response that she subsequently encountered. Our clinical experience with this working dilution of Candida albicans antigen has not resulted in any “rapid tissue sloughing” (presumably tissue necrosis) in any of the 10 patients we have treated, as has been cited by Dr. Signore.2 Even the patient we describe with the “painful purple digit” did not develop tissue necrosis although this was our initial concern. Additionally, we treated more than one subungual wart in this patient and observed the complication in only one of the two treated digits. Dr. Signore noted that he had encountered a patient with a painful reaction to a 1:1,000 dilution of Candida antigen into a subungual wart, which he no longer treats. The patient described in our case report experienced a painful reaction, also in the subungual area. This suggests that it is not the concentration of the antigen but the patient's reaction to the antigen, as well as the anatomic location, that presents a risk for this potential complication. The correspondent's reluctance to use this treatment modality in the subungual area raises an important point. If it is not feasible to use Candida albicans antigen in the treatment of warts located in difficult-to-treat areas (such as subungual warts and plantar warts), then what is the utility of such a treatment? First- and second-line therapies such as salicylic acid plasters and cryotherapy are likely to be as successful in common warts outside of these difficult-to-treat areas, without the use of injected materials. It also raises the question that the high reported success rates of intradermal injections of Candida albicans antigen into warts may be related to the exclusion of warts located in these problematic areas. In our case report, we utilized a 1:10 dilution of the stock solution and based this dose on the patient's immune response to a prior skin test reaction (see item 1, above), as we do with every patient. We titrate the dilution and antigen volume on the basis of the prior DTH response. Because some patients react very vigorously to this antigen, we indeed dilute the antigen well beyond the 1:10 initial working dilution. In this regard, I disagree with the author's recommendation to start with a dilute solution directly administered to the warts. It is essential to titrate the antigen dose injected into the warts in accordance with the patient's DTH skin test response; one size (ie, the 1:500 dilution recommended by Dr. Signore) does not fit all! It is more likely that the compartment-like syndrome that occurred in our patient was related more to the anatomic compartment (fingertip) than to the concentration of the antigen. Regarding the use of systemic corticosteroids, this is a reasonable consideration as a treatment to potentially avoid surgery. If systemic corticosteroids are utilized to treat such a syndrome, they should be given very early in the course of the evolution of signs and symptoms, and a rapidly acting preparation should be administered (by oral or intravenous route) because tissue necrosis can ensue rapidly in true compartment syndromes. Anthony Gaspari MD Department of Dermatology University of Maryland Baltimore, MD

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