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Yeast rising: Predicting the efficacy of candida antigen immunotherapy for warts

DII small banner By Warren R. Heymann, MD
Oct. 2, 2017

Numerous flat warts (verrucae plana) seen on upper extremities of patient with epidermodysplasia verruciformis.
Credit: JAAD

Perhaps I’m paranoid, but I always think that warts are laughing at me, or at least at whatever I throw at them — cryosurgery, curettage, electrosurgery, laser, salicylic acid, cantharadin, squaric acid dibutyl ester, 5 fluorouracil, imiquimod, podophylloltoxin, sinecatechins, or cidofovir. I think the wart has a grand time scheduling a follow-up appointment, thinking to itself: “How can I make Dr. Heymann look foolish the next time”?

Silently, I hope that spontaneous remission due to natural immunity transpires before the next visit. Should the wart(s) prove recalcitrant, I will likely initiate the following conversation:
“Why don’t we try immunotherapy with Candida antigen? It’s a series of injections into the largest wart that can boost the immune system and fight the human papilloma virus. In the best circumstances, all the warts resolve.”

“How good is it?” the parent inquires while the child shrieks “NO NEEDLES!!!”

“No treatment is perfect, and in my experience, it works more than half the time. It also hurts a lot less than cryosurgery, even with the needle.”

Intralesional immunotherapy for warts has been reported with multiple antigens: Candida albicans,; measles, mumps, and rubella (MMR); Trichophyton; and tuberculin antigens such as purified protein derivative (PPD) and Bacillus Calmette-Guerin (BCG). The presumed mechanism of action is the induction of a systemic T-cell mediated response. Cytokines released from Th1 cells such as interleukin-2 and interferon-gamma are increased in response to the injected antigen. (1)
Alikhan et al reported a retrospective study of adult and pediatric patients treated with Candida antigen for verruca vulgaris. Of the 100 patients treated, 80% responded to therapy: 39% demonstrated a complete response and 41% demonstrated a partial response. Additionally, 6 out of 7 immunocompromised patients who were treated demonstrated a partial or complete response. Injections were generally well tolerated and adverse events were minimal and short-lived. The authors concluded that intralesional Candida antigen therapy for cutaneous warts is an efficacious option, even for immunosuppressed patients. (2)

In a study 220 children (age 3-18 years) with recalcitrant or multiple warts, 156 (70.9%) had a complete response, 37 (16.8%) had a partial response, and 27 (12.2%) had no improvement. An average of 2.73 treatments was needed. Forty-seven of the patients with more than one wart (21.3%) also noted at least partial resolution of untreated warts at distant sites. Twenty-seven of the 47 patients (57.4%) had complete resolution. All treated patients experienced some discomfort at the time of the injection, but no serious side effects were reported. (3)
The most commonly reported side effects of intralesional Candida antigen injection include pruritus, pain (immediately and up to 24 hours following injections), local reactions (burning, blistering, peeling), erythema, edema, and immunologically-induced lymphangitis. (4) Vitiligo has been reported at the site of injection of Candida antigen, although this was in an 8 year-old girl with a history of lichen sclerosus and vulvar vitiligo. (5) If injecting into a small area, such as a digit, edema could result in a compartment syndrome; I have had two patients where this was a potential concern. They responded well to prednisone administration.

Nofal et al studied 54 patients with multiple common warts. A whole blood sample was collected from patients before therapy, cultured in 10% fetal calf serum and 2% penicillin-streptomyin, then incubated with Candida antigen. Following incubation, the supernatant was collected for evaluation of IFN-gamma by ELISA. Candida antigen was directly injected into the largest wart at 2-week intervals until complete clearance or for a maximum of five treatments. Follow-up was made for 6 months to detect any recurrence. Complete clearance of the lesions was seen in 61.1% of the studied patients. IFN-gamma was statistically higher in responded cases as compared to nonresponders. Adverse effects were insignificant, and no recurrence of warts was observed. The authors concluded that IFN-gamma may serve as a good predictor of its therapeutic response. (6)

One day there will be a cure for warts, either by vaccination or a novel anti-HPV drug. Until then, we will all muddle through the myriad treatments as previously listed. Predicting a response to therapy, however, would be most valuable. Should the work by Nofal et al be confirmed, it would be a significant advance in managing the scourge of verrucae.

1. Aldahan AS, et al. Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature. Dermatol Ther 2016; 197-207.
2. Alikhan A, et al. Use of Candida antigen injections for the treatment of verruca vulgaris: A two-year Mayo Clinic experience. J Dermatolog Treat 2016; 27: 355-8.
3. Muñoz Garza FZ, et al. Intralesional Candida antigen immunotherapy for the treatment of recalcitrant and multiple warts in children. Pediatr Dermatol 2015; 32: 797-801.
4. Zubritsky L, et al. Lymphangitis occurring after intralesional Candida antigen for verruca vulgaris. Dermatol Online J 2016; 22 (6): 18.
5. Wilmer EN, et al. Goodbye warts, hello vitiligo: Candida antigen injection-induced depigmentation. Pediatr Dermatol 2013; 30: e214-5.
6. Nofal A, et al. Significance of interferon gamma in the prediction of successful therapy of common warts by intralesional injection of Candida antigen. Int J Dermatol 2017; 56: 1003-9.

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