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.

[1]  P. Roberson,et al.  Immunotherapy for Recalcitrant Warts in Children Using Intralesional Mumps or Candida Antigens , 2003, Pediatric dermatology.

[2]  T. Randall,et al.  CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Roberson,et al.  Intralesional injection of mumps or Candida skin test antigens: a novel immunotherapy for warts. , 2001, Archives of dermatology.

[4]  E. de Villiers,et al.  Degenerate and Nested PCR: a Highly Sensitive and Specific Method for Detection of Human Papillomavirus Infection in Cutaneous Warts , 1999, Journal of Clinical Microbiology.

[5]  W. Mcclements,et al.  Effect of vaccine delivery system on the induction of HPV16L1-specific humoral and cell-mediated immune responses in immunized rhesus macaques. , 2003, Vaccine.

[6]  H. Erlich,et al.  Rapid typing of DNA sequence polymorphism at the HLA-DRB1 locus using the polymerase chain reaction and nonradioactive oligonucleotide probes. , 1991, Human immunology.

[7]  G. Micali,et al.  An open label evaluation of the efficacy of imiquimod 5% cream in the treatment of recalcitrant subungual and periungual cutaneous warts , 2003, The Journal of dermatological treatment.

[8]  William T. Lee,et al.  Antigen-specific CD4 T cell clonal expansion and differentiation in the aged lymphoid microenvironment I. The primary T cell response is unaffected , 2004, Mechanisms of Ageing and Development.

[9]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .

[10]  J. Pfenninger,et al.  Treatment of warts with Candida antigen injection. , 2000, Archives of dermatology.

[11]  P. Romagnoli,et al.  Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro , 2001, Journal of the European Academy of Dermatology and Venereology : JEADV.

[12]  J. Berzofsky,et al.  Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. , 2003, The Journal of infectious diseases.

[13]  A. Moscicki,et al.  Cell-Mediated Immune Response to Human Papillomavirus Infection , 2001, Clinical Diagnostic Laboratory Immunology.

[14]  M. Stanley Progress in prophylactic and therapeutic vaccines for human papillomavirus infection , 2003, Expert review of vaccines.

[15]  D. Buckley,et al.  The therapeutic use of topical contact sensitizers in benign dermatoses , 2001, The British journal of dermatology.

[16]  Jun Yu,et al.  Enhanced immune response to DNA-based HPV16L1 vaccination by costimulatory molecule B7-2. , 2003, Antiviral research.

[17]  R. Stern,et al.  Utilization of physician services for dermatologic complaints. The United States, 1974. , 1977, Archives of dermatology.

[18]  A. Sette,et al.  Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of cervical cancer patients by in vitro stimulation with a synthetic human papillomavirus type 16 E7 epitope. , 1996, American journal of obstetrics and gynecology.

[19]  H. Fox,et al.  Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. , 1990, Journal of the National Cancer Institute.