Intralesional vitamin D3 versus Candida antigen immunotherapy in the treatment of multiple recalcitrant plantar warts: A comparative case–control study

Intralesional immunotherapy is one of the therapeutic tools of warts. Intralesional Candida antigen was reported as successful treatment of warts. Topical and intralesional vitamin D have been used recently for wart treatment. We aim to evaluate the efficacy and safety of intralesional injection of vitamin D3 in treatment of multiple recalcitrant plantar warts in comparison with intralesional Candida antigen. Sixty patients were divided into three groups: Group I received intralesional vitamin D3, Group II intralesional Candida antigen, and Group III intralesional saline (control group). Injection was done every 3 weeks until clearance of warts or a maximum of three treatments. There was a statistically significant more reduction of warts numbers after treatment in Group I than in the other groups (p < .05). Group I showed better clinical response than Group II (p = .021). In both Groups I and II, clinical response was less favorable in patients with longer disease duration (p = .026). There was also limitation as it is a small study population. Intralesional vitamin D3 injection in multiple recalcitrant plantar warts is a simple, safe, cost effective treatment modality with minimal side effects, and superior results compared with intralesional injection of Candida antigen.     

Intralesional immunotherapy of common warts: successful treatment with mumps,measles and rubella vaccine

Background Despite numerous therapeutic modalities reported in the literature, treatment of common warts remains a continuing challenge and there is no universal consensus about optimal treatment. Recently, intralesional immunotherapy by different antigens has proved efficacy in the treatment of different types of warts. Objective To evaluate the efficacy and safety of intralesional mumps, measles and rubella (MMR) vaccine in the treatment of common warts. Methods The study included 135 patients with single or multiple recalcitrant or non‐recalcitrant common warts. They were randomly assigned to two groups; the first group (85 patients) received intralesional MMR vaccine, and the second group (50 patients) received intralesional saline as a control group. Both treatments were injected into single lesions or largest wart in case of multiple lesions at 2‐week intervals until complete clearance or for a maximum of five treatments. Follow‐up was made every 2 months for 6 months to detect any recurrence. Results A highly significant difference was found between the therapeutic response of common warts to MMR vaccine and saline control group (P < 0.001). In the MMR group, complete response was achieved in 80% and 84.6% of patients presenting with recalcitrant and multiple warts respectively. No recurrence was observed in the MMR group and side effects included pain during injection and flu‐like symptoms. Conclusions Intralesional immunotherapy by MMR vaccine is a promising effective and safe treatment modality for common warts, particularly the multiple ones.     

Intralesional immunotherapy for pediatric warts: A review

Cutaneous warts are a common pediatric complaint with modest response to first-line treatments. Warts are a manifestation of human papillomavirus (HPV) infection and are cleared by cell-mediated immunity (CMI). Intralesional immunotherapy treatments have been studied as alternative therapies, particularly for recalcitrant or multiple warts, including Candida antigen, mumps antigen, the combined measles, mumps, and rubella (MMR) vaccine, tuberculin purified protein derivative (PPD), and bacille Calmette-Guerin (BCG) vaccine. These treatments are thought to increase HPV recognition by stimulating CMI. In this review, we evaluate and compare the efficacy and adverse effects of intralesional immunotherapy in the treatment of pediatric warts. Articles met inclusion criteria if they specifically evaluated the effects of intralesional immunotherapy (candida, MMR, tuberculin PPD, or BCG) as treatment for cutaneous warts in a pediatric population, and if they quantified treatment effect in a reproducible manner. Twenty-one studies met criteria. Many studies demonstrated complete clearance of injected common warts in pediatric patients with clearance rates ranging from 23.3% to 95.2%. Distant wart resolution was common. Intralesional immunotherapy is a promising treatment option for cutaneous warts in children.     

Intralesional injection of measles,mumps, and rubella vaccine versus cryotherapy in treatment of warts: A randomized controlled trial

Cutaneous warts are benign hyperkeratotic papillomas resulting from infection by human papillomavirus (HPV). Cryotherapy is a known method for warts treatment. Immunotherapy stimulates HPV recognition by the immune system; this helps resolution of warts. To determine the efficacy of intralesional immunotherapy with measles, mumps, and rubella (MMR) vaccine versus cryotherapy in the treatment of patients with multiple common and plantar warts. Forty‐eight patients with multiple common and plantar warts were divided into two groups: to undergo either intralesional injection of MMR vaccine (Group A), or cryotherapy (Group B). Forty patients completed the study. In the MMR group, 70% of the patients showed complete response, 5% partial response, and 25% showed no response to treatment. In the CRYO group, 45% of the patients showed complete response, 35% partial response, and 20% showed no response to treatment. The complete response was higher in the MMR group (70%) as compared to the CRYO group (45%), but the difference between the two groups was not statistically significant. Meanwhile, the partial response was significantly higher in the CRYO group. Intralesional MMR injection was a safe and effective treatment for multiple common and plantar warts as compared to cryotherapy.     

Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature

Warts are common epidermal growths caused by human papillomavirus that often cause significant discomfort and embarrassment. Current treatment options include topical therapies, cryotherapy, laser vaporization, and surgical excision. Many of these options are destructive and may result in scarring, while less aggressive approaches can lead to lesion recurrence. Additionally, these local modalities are not practical for patients with a large number of warts. Systemic approaches such as immunotherapy have demonstrated success in treating multiple lesions by combining a targeted approach with upregulation of the host immune system. An extensive literature review was performed to evaluate the various vaccine antigens that have been used intralesionally to treat cutaneous and anogenital warts. The specific intralesional immunotherapies that have been studied include: Candida albicans; measles, mumps, and rubella; Trichophyton; and tuberculin antigens such as purified protein derivative, Mycobacterium w vaccine, and Bacillus Calmette‐Guerin. Intralesional vaccine injection represents a safe, effective, and tolerable treatment for warts, including recalcitrant and anogenital warts. This approach has been somewhat overlooked in the past despite substantial evidence of high response rates with a low side effect profile. Large comparative trials are necessary to determine the most effective immunotherapy treatment option as well as the most appropriate dosing parameters.     

Intralesional injection of mumps or Candida skin test antigens: a novel immunotherapy for warts

BACKGROUND: Warts are common and induce physical and emotional discomfort. Numerous therapies exist, yet none is optimal. Despite theoretical advantages, immunotherapeutic modalities are often neglected as first-line wart therapies. OBJECTIVE: To compare treatment with intralesional skin test antigen injection of 1 wart vs cryotherapy of all warts. DESIGN: Pilot study. SETTING: University dermatology outpatient clinic. PATIENTS: A total of 115 consecutive patients with at least 1 nongenital wart. INTERVENTIONS: Patients with warts were tested for immunity to mumps and Candida using commercial antigens. Nonresponders received cryotherapy and immune individuals received cryotherapy or intralesional injection of 1 antiserum. RESULTS: Thirty-four (30%) of the 115 patients did not respond to the test injections and 81 (70%) had detectable immunity. Of the immune group, 26 (32%) received cryotherapy, 45 (56%) received intralesional mumps antiserum, and 10 (12%) received intralesional Candida antiserum. Of the anergic patients, 28 (82%) were treated with cryotherapy; 6 (18%) refused cryotherapy. Of the 39 patients who were treated with immunotherapy and completed the protocol, 29 (74%) had complete clearing of the treated wart. Fourteen (78%) of 18 patients with complete resolution of their immunotherapy-treated wart also had resolution of untreated, distant warts. CONCLUSIONS: Intralesional injection of mumps or Candida antigens into warts of immune individuals represents effective treatment. Observation of clearing of anatomically distinct and distant warts suggests acquisition of human papillomavirus-directed immunity in some patients. We conclude that this novel approach to immunotherapy may serve as first-line treatment in immune individuals with multiple or large warts and as second-line treatment in immune patients for whom cryotherapy fails.     

Comparative study of autoimplantation therapy and intralesional injection of MMR vaccine in warts treatment

Autoimplantation is a simple technique and considered as a novel method of immunotherapy in treating warts. Intralesional immunotherapy by mumps, measles, and rubella (MMR) vaccine is also a promising treatment modality for multiple warts. To compare the efficacy and safety of both the methods in treating multiple warts, the study included 80 patients divided into two groups (Group A and Group B), each containing 40 patients. Informed consent was taken from each patient before enrollment into the study. Group A patients were treated by autoimplantation technique every 2 weeks for a maximum of four treatments. Similarly, Group B patients received MMR intralesional injection at a dose of 0.5 ml every 2 weeks for a maximum of four treatments. Complete clearance of the donor wart was observed in 60% patients in Group A, whereas complete clearance in the Group B injected by MMR was 72.5%. On the other hand, a significant difference (p < .05) was found in the therapeutic response among nonmanipulated warts in both groups, where complete clearance was observed in 47.5% of Group A patients versus 20% of Group B patients. Autoimplantation is a suitable approach for patients with multiple warts associated with distant lesions, while MMR injection is ideal for a single or fewer number of warts.     

Intralesional measles,mumps, and rubella vaccine after failure of intralesional Candida antigen for the treatment of recalcitrant pediatric warts

Numerous studies have investigated the efficacy of intralesional immunotherapy for warts, but there are a lack of studies investigating the efficacy of alternative intralesional immunotherapies following failure of initial intralesional immunotherapy. In this retrospective study, we aimed to investigate the efficacy of intralesional measles, mumps, and rubella vaccine for the treatment of pediatric warts following failure of intralesional therapy with Candida antigen. Following intralesional measles, mumps, and rubella vaccine administration, 8/51 (15.5%) patients had complete resolution of their warts, 6/51 (12%) had near complete resolution, 19/51 (37%) had partial improvement, 12/51 (23.5%) had no change, and 6/51 (12%) had worsening. Although limited by retrospective nature and low sample size, our results demonstrate that intralesional immunotherapy with measles, mumps, and rubella vaccine provides an alternative therapeutic option for the treatment of recalcitrant pediatric warts in patients who fail to respond to intralesional Candida antigen.     

Immunotherapy with Intralesional Candida Albicans Antigen in Resistant or Recurrent Warts: A Study

Background:

Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases.

Aim:

The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy.

Materials and Methods:

A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented.

Results:

Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body. In addition, two patients (6%) showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38%) failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection.

Conclusions:

Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences.

Limitations:

The small sample size and lack of control group are the main limitations of the study.     

Immunotherapy for recalcitrant warts in children using intralesional mumps or Candida antigens

Intralesional injection of mumps and Candida skin test antigens has been shown to be effective in the treatment of warts. Warts are generally difficult to treat in children. To determine the efficacy of intralesional skin test antigen injection for the treatment of resistant warts in children, we treated 47 pediatric patients with one or more warts with intralesional injection of mumps or Candida skin test antigen into one wart. Twenty-two patients (47%) with resistant warts experienced complete resolution of treated warts. An average of 3.78 treatments were necessary. An additional 34% of children had a greater than 25% improvement in their warts. Sixty-eight percent of subjects with more than one wart also noted at least partial resolution (greater than 25% resolution) of untreated warts at distant sites, with 34% experiencing complete resolution. We concluded that intralesional injection of skin test antigens is an effective therapy for children who have recalcitrant, nongenital, cutaneous warts.     

Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a single-blinded, randomized, and controlled trial

BACKGROUND: Warts occur commonly in humans. Destructive modalities are generally the first physician-administered therapy. Other treatment options include immunotherapy. Intralesional immunotherapy using mumps, Candida, or Trichophyton skin test antigens has proved efficacy in the treatment of warts. OBJECTIVES: To determine rates of wart resolution in response to injection of antigen alone, antigen plus interferon alfa-2b, interferon alfa-2b alone, and normal saline; and to compare response according to viral type, major histocompatibility complex antigens, and peripheral blood mononuclear cell proliferation to autologous human papillomavirus antigen before and after injection. DESIGN: Randomized, single-blinded, placebo-controlled, clinical trial. SETTING: Medical school-based dermatology department. PATIENTS: Two hundred thirty-three patients clinically diagnosed as having 1 or more warts.Main Outcome Measure Clinical resolution of warts in response to intralesional immunotherapy. RESULTS: Responders were observed in all treatment arms, but were significantly more likely to have received antigen (P<.001). Resolution of distant untreated warts was observed, and was significantly more likely in subjects receiving antigen (P<.001). Interferon did not significantly enhance the response rate (P = .20) and did not differ from normal saline (P = .65). No viral type or major histocompatibility complex antigen correlated with response or lack of response (P>.99 and P = .86, respectively). A positive peripheral blood mononuclear cell proliferation assay result (2 times pretreatment levels) was significantly more likely among responders (P = .002). While there was no significant difference in response based on sex (P = .56), older subjects (>40 years) were less likely to respond (P = .01). CONCLUSIONS: Intralesional immunotherapy using injection of Candida, mumps, or Trichophyton skin test antigens is an effective treatment for warts, as indicated by significantly higher response rates and distant response rates in subjects receiving antigen. Viral type and major histocompatibility complex antigens did not seem to influence treatment response. Response is accompanied by proliferation of peripheral blood mononuclear cells to human papillomavirus antigens, suggesting that a human papillomavirus-directed cell-mediated immune response plays a role in wart resolution.     

Effect of varicella zoster vaccine vs candida antigen injection in treatment of warts

Treatment of warts is considered as a big challenge for patients as well as doctors. Immunotherapy represents a promising and successful method of warts treatment. A great attention has been paid for various types of immunotherapeutic agents. One of the immunotherapeutic approaches is intralesional immunotherapy that showed a successful result in treatment of warts. Complete resolution of warts was achieved in many of studied patients, while some of them showed partial response and only few patients showed no response. Our study was based on the previous observations and reports of regression of several types of warts after administration of candida antigen and other new immunotherapeutic antigens. Candida antigen group showed complete clearance in 16 patients (69.6%), partial response in seven patients (30.4%). In VZV vaccine group, complete clearance was observed in 15 patients (65.2%), partial response in eight patients (34.8%). These results showed that the therapeutic response in two groups had a close statistical result and more chances must be given to VZV vaccine specially after its promising and successful results. In conclusion, we presented a novel approach for the treatment of recalcitrant wart using intralesional immunotherapy with Candida antigen and VZV vaccine. VZV vaccine seems to be promising, safe and effective remedy for any type warts mainly plantar warts.     

Effectiveness of intralesional vitamin D3 injection in the treatment of common warts: Single‐blinded placebo‐controlled study

Warts are common viral infection of the skin, usually treated with destructive methods like electrocautery, cryotherapy or laser ablation. Topical vitamin D has been used to treat warts with variable success is to evaluate the efficacy of intralesional vitamin D₃ injection in the treatment of common warts. Fifty patients were divided into two groups: 30 patients as cases group who received intralesional injection of 0.2 mL of vitamin D₃ (300,000 IU) into the base of mother wart for two sessions and another 20 patients as a control group who were injected with normal saline solution. Standardized photographs were taken before the procedure, and 1 month and 3 months after the procedure. The degree of the response was classified into complete, partial, and no response. Complete clearance of the target injected warts occurred in 40% of patients in cases group while it occurred only in 5% of patients in control group (p ≤ .001) that was statistically significant. Intralesional injection of vitamin D₃ may be considered a good and safe modality for the treatment of common warts.     

OK-432 Therapy for Recalcitrant Warts

Twelve patients with warts recalcitrant to various treatments, including cryotherapy, were treated with OK-432 injection therapy. Six patients received only subcutaneous injection, three received only intralesional injection, and the other three received both subcutaneous and intralesional injections. Complete clearing of the warts occurred in nine (75%) of 12 patients, while the other three patients were not cured. Grouping the patients by the method of injection, the success rate of subcutaneous injection was 5/9 (55.6%), and that of intralesional injection was 4/6 (66.7%). Although five patients complained of mild fever and malaise, these side effects gradually disappeared during the repeated injections. OK-432 injection is considered as a hopeful therapy for recalcitrant warts.     

Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Background  Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART).
Objectives  To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions.
Methods  Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm⁻³ and plasma HIV RNA load < 10⁴ copies mL⁻¹) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA.
Results  Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied.
Conclusions  Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.     

Intralesional immunotherapy with Candida antigen for the treatment of molluscum contagiosum in children

Intralesional injection of Candida and other antigens is an established and useful therapy for warts; a cutaneous immune response can induce improvement and or clearance of warts, often with response in anatomically distinct lesions other than those injected. Molluscum contagiosum virus is a common cutaneous infection seen primarily in pediatric dermatology clinics. Treatment is often unsatisfactory, painful, and time consuming. A retrospective chart review was conducted to examine the efficacy of intralesional injection of Candida antigen into a maximum of three individual molluscum lesions. Twenty-nine patients were treated with this therapy; 55% had complete resolution. In addition, 37.9% experienced partial resolution, yielding an overall response rate of 93%. Only two patients failed to respond (6.9%). In addition, only four patients reported a single adverse effect of pain with injection. No other adverse effects were reported or noted clinically. Scarring was absent. No recurrences were reported at the time of publication. This report establishes the efficacy of intralesional injection of Candida for molluscum contagiosum.     

Cidofovir Intralesional Injection for Recalcitrant Common Warts: A Comparison with Sodium Tetradecyl Sulfate Intralesional Injection

BackgroundA novel treatment method is required for recalcitrant common warts.ObjectiveThis study aimed to compare the complete wart removal rate of cidofovir, a broad-spectrum antiviral agent, intralesional injection and sodium tetradecyl sulfate intralesional injection.MethodsThis retrospective study included 45 patients with recalcitrant common warts on the hands and/or feet, treated with cidofovir or sodium tetradecyl sulfate intralesional injection.ResultsThe treatment results were evaluated in three groups as follows: (1) failure - recalcitrant common warts remaining despite three or more injections, (2) success - free from warts for more than 6 months after the injection, and (3) recurrence. The cidofovir group (n=22) showed significantly higher treatment success rates than the sodium tetradecyl sulfate group (n=23) (90.91% vs. 26.09%, p<0.001). Two immunosuppressed patients in the cidofovir group had recurrent lesions after 2 months of being declared free from warts. Considering adverse effects, two patients in the cidofovir group complained of bulla formation with severe pain requiring narcotic painkillers.ConclusionAlthough this study has the limitations of a small sample size and retrospective design, patients with recalcitrant common warts showed a dramatic response to the treatment with cidofovir intralesional injection, with minimal complications.     

The diverse methods of bleomycin delivery in cutaneous warts: A literature review

Bleomycin is a useful treatment option for recalcitrant verrucae. Several different methods of bleomycin delivery have been described, including intralesional injection, intralesional injection combined with laser, microneedling, multiple puncture and adhesive tape. We reviewed the literature to evaluate the various methods of bleomycin administration to treat warts, including the different doses, instruments and procedures used. Intralesional injection (cure rate ranged from 67.8% to 99.23%) and topical bleomycin with multipuncture or microneedling methods (63.6% to 100%) were found to be effective in the treatment of warts. Overall, pain is significantly less with microneedling and multipuncture techniques compared with intralesional injection. Bleomycin injection combined with pulsed dye laser, electroporation, or by other methods, such as, microneedle patches or adhesive tape do not seem to be more beneficial than bleomycin administered by intralesional injection, multipuncture or microneedling techniques.     

Failure of Intralesional Propranolol in Infantile Hemangiomas

The purpose of this study was to evaluate the use of intralesional propranolol injection in the management of small, noncomplicated infantile hemangiomas (IHs) located in areas of cosmetic concern. A prospective study was performed in six female infants with small, non‐complicated IHs in areas of cosmetic concern. The parents had refused oral propranolol or the patients had no response to topical timolol or had relapsed after oral propranolol and the parents refused further systemic treatment. All six patients were treated with 1 mg/mL propranolol solution at a dose of 0.2 mL/cm². The size, color, and growth of the hemangiomas were monitored and recorded every 4 weeks. Treatment response was evaluated using a 5‐point scale: much better (+2), better (+1), same (0), worse (?1), and much worse (?2). Heart rate and blood pressure were measured before and 1 hour after each injection. Adverse effects after medication were evaluated and managed accordingly. All hemangiomas stopped growing during therapy, but no significant changes in size or color were observed, even after repeated injections, and all patients were evaluated as 0 (same). One patient whose hemangioma stopped growing during treatment presented rebound growth after therapy cessation. No changes in heart rate or blood pressure were observed after intralesional propranolol injection. Adverse effects observed were pain and redness after injection. Intralesional propranolol seems safe but is not effective for the treatment of IH.     

Bleomycin in the treatment of recalcitrant warts

Bleomycin is gaining increasing popularity in the treatment of warts, but its efficacy has not been examined in well-controlled studies. We evaluated bleomycin in a double-blind placebo-controlled crossover study in recalcitrant warts treated unsuccessfully by conventional methods. Patients were assigned alternately to placebo or bleomycin groups and treated by intralesional injections of bleomycin, 1 U/ml, or saline, at 2-week intervals. If warts persisted, patients were changed after two injections to the alternate group and retreated with up to two further injections. Forty patients entered the study. Of 151 warts treated with intralesional bleomycin, 123 were cured after one or two injections (81%). The cure rate for plantar warts (60%) was lower than that for periungual warts (94%) and warts elsewhere on the extremities (95%). Fifty-five warts were injected with normal saline; none was cured. Responding warts showed a hemorrhagic eschar and healed without scarring, atrophy, or pigmentary change. Pain was usually mild and patient acceptance superior to that with liquid nitrogen. There was no evidence of systemic toxicity. Bleomycin is highly efficacious in the treatment of recalcitrant warts, is convenient, and has high patient acceptance. Long-term safety requires further study.